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Gestational hypertension | Gestational hypertension or pregnancy-induced hypertension (PIH) is the development of new hypertension in a pregnant woman after 20 weeks gestation without the presence of protein in the urine or other signs of pre-eclampsia. Gestational hypertension is defined as having a blood pressure
greater than 140/90 on two occasions at least 6 hours apart.
Signs and symptoms
No single diagnostic test currently exists to predict the likelihood of developing gestational hypertension. High blood pressure is the major sign in diagnosing gestational hypertension. Some women with gestational hypertension may present asymptomatic, but a number of symptoms are associated with the condition.[1]
Symptoms
Edema
Sudden weight gain
Blurred vision or sensitivity to light
Nausea and vomiting
Persistent headaches
Increased blood pressure
Risk factors
Maternal causes
Obesity
Mothers under 20 or over 40 years old
Past history of diabetes mellitus, hypertension (particularly gestational hypertension) and renal disease
Pre-existing hypertension
Thrombophilias (anti-phospholipid syndrome, protein C/S deficiency, factor V Leiden)
Having donated a kidneyPregnancy
Multiple gestation (twins or triplets, etc.)
Placental abnormalities:
Hyperplacentosis: Excessive exposure to chorionic villi
Placental ischemiaFamily history
Family history of pre-eclampsia
Diagnosis
Conditions
There exist several hypertensive states of pregnancy:
Gestational hypertension
Gestational hypertension is usually defined as having a blood pressure higher than 140/90 measured on two separate occasions, more than 6 hours apart, without the presence of protein in the urine and diagnosed after 20 weeks of gestation.
Pre-eclampsia
Pre-eclampsia is gestational hypertension plus proteinuria (>300 mg of protein in a 24-hour urine sample). Severe pre-eclampsia involves a blood pressure greater than 160/110, with additional medical signs and symptoms. HELLP syndrome is a type of pre-eclampsia. It is a combination of three medical conditions: hemolytic anemia, elevated liver enzymes and low platelet count.
Eclampsia
This is when tonic-clonic seizures appear in a pregnant woman with high blood pressure and proteinuria.Pre-eclampsia and eclampsia are sometimes treated as components of a common syndrome.
Treatment
There is no specific treatment, but is monitored closely to rapidly identify pre-eclampsia and its life-threatening complications (HELLP syndrome and eclampsia).Drug treatment options are limited, as many antihypertensives may negatively affect the fetus. Methyldopa, hydralazine, and labetalol are most commonly used for severe pregnancy hypertension.The fetus is at increased risk for a variety of life-threatening conditions, including pulmonary hypoplasia (immature lungs). If the dangerous complications appear after the fetus has reached a point of viability, even though still immature, then an early delivery may be warranted to save the lives of both mother and baby. An appropriate plan for labor and delivery includes selection of a hospital with provisions for advanced life support of newborn babies.
Evolutionary considerations
Humans
Gestational hypertension is one of the most common disorders seen in human pregnancies. Though relatively benign on its own, in roughly half of the cases of gestational hypertension the disorder progresses into pre-eclampsia, a dangerous condition that can prove fatal to expectant mothers. However, gestational hypertension is a condition that is fairly rare to see in other animals. For years, it has been the belief of the scientific community that gestational hypertension and pre-eclampsia were relatively unique to humans, although there has been some recent evidence that other primates can also develop similar conditions, albeit due to different underlying mechanisms. The underlying cause of gestational hypertension in humans is commonly believed to be an improperly implanted placenta. Humans have evolved to have a very invasive placenta to facilitate better oxygen transfer from the mother to the fetus, to support the growth of its large brain.
Origins of the placenta
The origins of gestational hypertension may lie with the development of humans hemochorial placenta. A hemochorial placenta optimizes the amount of oxygen and nutrients that can be absorbed into the fetal blood supply, while at the same time ensuring rapid diffusion of wastes away from the fetus. This hemochorial placenta differs from lower primates epitheliochorial placentae in the way that it allows the fetal tissues to interact directly with the mothers blood. The hemochorial placenta thereby promotes more rapid diffusion to and from the fetal blood supply.In animals with epitheliochorial placentae such as horses and pigs, the greatest resistance to maternal blood flow in the vascular system was found within the placenta. However, in animals with hemochorial placental structures such as rodents and primates, the vascular resistance in the placenta was low, leading scientists to the conclusion that the greatest resistance to maternal blood flow is found elsewhere in the maternal vascular system. The high vascular resistance outside of the placenta leads to higher maternal blood pressure throughout the body.The fetal cells that implant into the uterine wall are known as the trophoblast. The hemochorial placenta bathes the fetal trophoblast in maternal blood by forming lacunae, or lakes, of the mothers blood that surround fetal tissue. The lacunae are filled by the spiral arteries, which means that the mothers blood pressure is the driving force behind the introduction of new blood, which contains both oxygen and food for the fetus, to the system. It is thought that humans need the increased diffusion provided by the hemochorial placenta in order to grow the large brains compared to their body size that distinguish them from other primates.
Incorrect placental implantation
It is thought that "failings" in normal hemochorial placental structure lead to pre-eclampsia and gestational hypertension. The human placenta implants "earlier, deeper, and more extensively" into the uterine wall, which can potentially lead to many problems that are found in human pregnancies, but not as much in other animals. Miscarriage and pre-eclampsia are both very rare in other species, but are two of the most common pregnancy-related diseases in humans. The genetic roots of gestational hypertension and pre-eclampsia are certain, as women with a family history of the condition are three times more likely to develop it when they are pregnant.One of the potential causes of gestational hypertension and pre-eclampsia is when the trophoblast does not invade far enough into the uterine lining. When the fetuss trophoblast does not fully extend into the uterine wall, the spiral arteries do not become fully converted into low-resistance channels. It has been found that this incomplete conversion of spiral arteries increases the resistance to uterine blood flow during pregnancy, and that this occurrence was associated with gestational hypertension. One potential cause of this incomplete breach of the spiral arteries that leads to gestational hypertension is a mistaken immune response by the maternal tissue, reaction to the alien fetal tissue. Therefore, it is clear that the complication of gestational hypertension has roots in the early implantation of the fetus in the uterine wall, an implantation technique that is unique to humans.The highly invasive placenta that is found in humans is thought to be linked to humans high circulating levels of the hormones CG and hCG. It has been shown that the higher the levels of these hormones, the deeper the trophoblasts invasion into the uterine wall. Instances of gestational hypertension and pre-eclampsia have been shown to occur when the invasion of the uterine wall is not deep enough, because of lower CG and hCG levels in the mother.
Evolutionary tradeoff
Despite these risks for gestational hypertension, the hemochorial placenta has been favored because of its advantages in the way that it aids in diffusion from mother to fetus later in pregnancy. The bipedal posture that has allowed humans to walk upright has also led to a reduced cardiac output, and it has been suggested that this is what necessitated humans aggressive early placental structures. Increased maternal blood pressure can attempt to make up for lower cardiac output, ensuring that the fetuss growing brain receives enough oxygen and nutrients. The benefits of being able to walk upright and run on land have outweighed the disadvantages that come from bipedalism, including the placental diseases of pregnancy, such as gestational hypertension. Similarly, the advantages of having a large brain size have outweighed the deleterious effects of having a placenta that does not always convert the spiral arteries effectively, leaving humans vulnerable to contracting gestational hypertension. It is speculated that this was not the case with Neanderthals, and that they died out because their cranial capacity increased too much, and their placentae were not equipped to handle the fetal brain development, leading to widespread pre-eclampsia and maternal and fetal death.Gestational hypertension in the early stages of pregnancy (trimester 1) has been shown to improve the health of the child both in its first year of life, and its later life. However, when the disease develops later in the pregnancy (subsequent trimesters), or turns into pre-eclampsia, there begin to be detrimental health effects for the fetus, including low birth-weight. It has been proposed that fetal genes designed to increase the mothers blood pressure are so beneficial that they outweigh the potential negative effects that can come from pre-eclampsia. It has also been suggested that gestational hypertension and pre-eclampsia have remained active traits due to the cultural capacity of humans, and the tendency for midwives or helpers to aid in delivering babies.
Relevance of evolutionary history
It is the goal of evolutionary medicine to find treatments for diseases that are informed by the evolutionary history of a disease. It has been suggested that gestational hypertension is linked to insulin resistance during pregnancy. Both the increase in blood sugar that can lead to gestational diabetes and the increase in blood pressure that can lead to gestational hypertension are mechanisms that mean to optimize the amount of nutrients that can be passed from maternal tissue to fetal tissue. It has been suggested that techniques used to combat insulin insensitivity might also prove beneficial to those with gestational hypertension. Measures to avoid insulin resistance include avoiding obesity before pregnancy, minimizing weight gain during pregnancy, eating foods with low glycemic indices, and exercising.
References
== External links == |
Essential thrombocythemia | Essential thrombocythemia (ET) is a rare chronic blood cancer (myeloproliferative neoplasm) characterised by the overproduction of platelets (thrombocytes) by megakaryocytes in the bone marrow. It may, albeit rarely, develop into acute myeloid leukemia or myelofibrosis. It is a type of myeloproliferative neoplasm (blood cancers) wherein the body makes too many white or red blood cells, or platelets).
Signs and symptoms
Most people with essential thrombocythemia are without symptoms at the time of diagnosis, which is usually made after noting an elevated platelet level on a routine complete blood count (CBC). The most common symptoms are bleeding (due to dysfunctional platelets), blood clots (e.g., deep vein thrombosis or pulmonary embolism), fatigue, headache, nausea, vomiting, abdominal pain, visual disturbances, dizziness, fainting, and numbness in the extremities; the most common signs are increased white blood cell count, reduced red blood cell count, and an enlarged spleen.
Cause
In ET, megakaryocytes are more sensitive to growth factors. Platelets derived from the abnormal megakaryocytes are activated, which, along with the elevated platelet count, contributes to the likelihood of forming blood clots. The increased possibility of bleeding when the platelet count is over 1 million is due to von Willebrand factor (vWF) sequestration by the increased mass of platelets, leaving insufficient vWF for platelet adhesion. A mutation in the JAK2 kinase (V617F) is present in 40–50% of cases and is diagnostic if present. JAK2 is a member of the Janus kinase family.In 2013, two groups detected calreticulin mutations in a majority of JAK2-negative/MPL-negative patients with essential thrombocythemia and primary myelofibrosis, which makes CALR mutations the second most common in myeloproliferative neoplasms. All mutations (insertions or deletions) affected the last exon, generating a reading frame shift of the resulting protein, that creates a novel terminal peptide and causes a loss of endoplasmic reticulum KDEL retention signal.
Diagnosis
The following revised diagnostic criteria for essential thrombocythemia were proposed in 2005. The diagnosis requires the presence of both A criteria together with B3 to B6, or of criterion A1 together with B1 to B6. The criteria are as follows:
A1. Platelet count > 400 × 103/µL for at least 2 months.
A2. Acquired V617F JAK2 mutation present
B1. No cause for a reactive thrombocytosis
normal inflammatory indices
B2. No evidence of iron deficiency
stainable iron in the bone marrow or normal red cell mean corpuscular volume
B3. No evidence of polycythemia vera
hematocrit < midpoint of normal range or normal red cell mass in presence of normal iron stores
B4. No evidence of chronic myeloid leukemia
But the Philadelphia chromosome may be present in up to 10% of cases. Patients with the Philadelphia chromosome have a potential for the development of acute leukemia, especially acute lymphocytic leukemia.
B5. No evidence of myelofibrosis
no collagen fibrosis and ≤ grade 2 reticulin fibrosis (using 0–4 scale)
B6. No evidence of a myelodysplastic syndrome
no significant dysplasia
no cytogenetic abnormalities suggestive of myelodysplasia
Treatment
Indications
Not all those affected will require treatment at presentation. People are usually split up into low and high risk for bleeding/blood clotting groups (based on their age, their medical history, their blood counts and their lifestyles), low risk individuals are usually treated with aspirin, whereas those at high risk are given hydroxycarbamide and/or other treatments that reduce platelet count (such as interferon-α and anagrelide).
Agents
Hydroxycarbamide, interferon-α and anagrelide can lower the platelet count. Low-dose aspirin is used to reduce the risk of blood clot formation unless the platelet count is very high, where there is a risk of bleeding from the disease, and hence this measure would be counter-productive as aspirin-use increases the risk of bleeding.The PT1 study compared hydroxyurea plus aspirin to anagrelide plus aspirin as initial therapy for ET. Hydroxyurea treated patients had a lower incidence of arterial thrombosis, lower incidence of severe bleeding and lower incidence of transformation to myelofibrosis, but the risk of venous thrombosis was higher with hydroxycarbamide than with anagrelide. It is unknown whether the results are applicable to all ET patients. In people with symptomatic ET and extremely high platelet counts (exceeding 1 million), plateletpheresis can be used to remove platelets from the blood to reduce the risk of thrombosis.
Prognosis
Essential thrombocythemia is sometimes described as a slowly progressive disorder with long asymptomatic periods punctuated by thrombotic or hemorrhagic events. However, well-documented medical regimens can reduce and control the number of platelets, which reduces the risk of these thrombotic or hemorrhagic events. The lifespan of a well-controlled ET person is well within the expected range for a person of similar age but without ET. ET is the myeloproliferative neoplasm least likely to progress to acute myeloid leukemia.
Epidemiology
The incidence of ET is 0.6-2.5/100,000 per year, the median age at onset is 65–70 years and it is more frequent in females than in males. The incidence in children is 0.09/100,000 per year.
Pregnancy
Hydroxycarbamide and anagrelide are contraindicated during pregnancy and nursing. Essential thrombocythemia can be linked with a three-fold increase in risk of miscarriage. Throughout pregnancy, close monitoring of the mother and fetus is recommended. Low-dose low molecular weight heparin (e.g. enoxaparin) may be used. For life-threatening complications, the platelet count can be reduced rapidly using plateletpheresis, a procedure that removes platelets from the blood and returns the remainder to the patient.
References
== External links == |
Transient synovitis | Transient synovitis of hip (also called toxic synovitis; see below for more synonyms) is a self-limiting condition in which there is an inflammation of the inner lining (the synovium) of the capsule of the hip joint. The term irritable hip refers to the syndrome of acute hip pain, joint stiffness, limp or non-weightbearing, indicative of an underlying condition such as transient synovitis or orthopedic infections (like septic arthritis or osteomyelitis). In everyday clinical practice however, irritable hip is commonly used as a synonym for transient synovitis. It should not be confused with sciatica, a condition describing hip and lower back pain much more common to adults than transient synovitis but with similar signs and symptoms.
Transient synovitis usually affects children between three and ten years old (but it has been reported in a 3-month-old infant and in some adults). It is the most common cause of sudden hip pain and limp in young children. Boys are affected two to four times as often as girls. The exact cause is unknown. A recent viral infection (most commonly an upper respiratory tract infection) or a trauma have been postulated as precipitating events, although these are reported only in 30% and 5% of cases, respectively.Transient synovitis is a diagnosis of exclusion. The diagnosis can be made in the typical setting of pain or limp in a young child who is not generally unwell and has no recent trauma. There is a limited range of motion of the hip joint. Nevertheless, children with transient synovitis of the hip can usually weight bear. This is an important clinical differentiating sign from septic arthritis. Blood tests may show mild inflammation. An ultrasound scan of the hip joint can show a fluid collection (effusion). Treatment is with nonsteroidal anti-inflammatory drugs and limited weight-bearing. The condition usually clears by itself within seven to ten days, but a small group of patients will continue to have symptoms for several weeks. The recurrence rate is 4–17%, most of which is in the first six months.
Symptoms and signs
Transient synovitis causes pain in the hip, thigh, groin or knee on the affected side. However, children with transient synovitis of the hip can usually weight bear with varying degrees of limping. There may be a limp (or abnormal crawling in infants) with or without pain. In small infants, the presenting complaint can be unexplained crying (for example, when changing a diaper). The condition is nearly always limited to one side. The pain and limp can range from mild to severe.Some children may have a slightly raised temperature; high fever and general malaise point to other, more serious conditions. On clinical examination, the child typically holds the hip slightly bent, turned outwards and away from the middle line (flexion, external rotation and abduction). Active and passive movements may be limited because of pain, especially abduction and internal rotation. The hip can be tender to palpation. The log roll test involves gently rotating the entire lower limb inwards and outwards with the patient on his back, to check when muscle guarding occurs. The unaffected hip and the knees, ankles, feet and spine are found to be normal.
Complications
In the past, there have been speculations about possible complications after transient synovitis. The current consensus however is that there is no proof of an increased risk of complications after transient synovitis.One such previously suspected complication was coxa magna, which is an overgrowth of the femoral head and broadening of the femoral neck, accompanied by changes in the acetabulum, which may lead to subluxation of the femur. There was also some controversy about whether continuous high intra-articular pressure in transient synovitis could cause avascular necrosis of the femoral head (Legg-Calvé-Perthes disease), but further studies did not confirm any link between the two conditions.
Diagnosis
There are no set standards for the diagnosis of suspected transient synovitis, so the amount of investigations will depend on the need to exclude other, more serious diseases. It is of great importance to exclude the diagnosis of septic arthritis. This is because if septic arthritis is missed in children, grave complications can occur. The exclusion of septic arthritis is mainly built upon the physicians clinical expertise and is supplemented by basic laboratory test and relevant imaging modalities. Additionally, beware to exclude the diagnosis of acute osteomyelitis, because it not uncommonly cooccurs with septic arthritis of the hip in children.Inflammatory parameters in the blood may be slightly raised (these include erythrocyte sedimentation rate, C-reactive protein and white blood cell count), but raised inflammatory markers are strong predictors of other more serious conditions such as septic arthritis.X-ray imaging of the hip is most often unremarkable. Subtle radiographic signs include an accentuated pericapsular shadow, widening of the medial joint space, lateral displacement of the femoral epiphyses with surface flattening (Waldenström sign), prominent obturator shadow, diminution of soft tissue planes around the hip joint or slight demineralisation of the proximal femur. The main reason for radiographic examination is to exclude bony lesions such as occult fractures, slipped upper femoral epiphysis or bone tumours (such as osteoid osteoma). An anteroposterior and frog lateral (Lauenstein) view of the pelvis and both hips is advisable.An ultrasound scan of the hip can easily demonstrate fluid inside the joint capsule (Fabella sign), although this is not always present in transient synovitis. However, it cannot reliably distinguish between septic arthritis and transient synovitis. If septic arthritis needs to be ruled out, needle aspiration of the fluid can be performed under ultrasound guidance. In transient synovitis, the joint fluid will be clear. In septic arthritis, there will be pus in the joint, which can be sent for bacterial culture and antibiotic sensitivity testing.
More advanced imaging techniques can be used if the clinical picture is unclear; the exact role of different imaging modalities remains uncertain. Some studies have demonstrated findings on magnetic resonance imaging (MRI scan) that can differentiate between septic arthritis and transient synovitis (for example, signal intensity of adjacent bone marrow). Skeletal scintigraphy can be entirely normal in transient synovitis, and scintigraphic findings do not distinguish transient synovitis from other joint conditions in children. CT scanning does not appear helpful.
Differential diagnosis
Pain in or around the hip and/or limp in children can be due to a large number of conditions. Septic arthritis (a bacterial infection of the joint) is the most important differential diagnosis, because it can quickly cause irreversible damage to the hip joint. Fever, raised inflammatory markers on blood tests and severe symptoms (inability to bear weight, pronounced muscle guarding) all point to septic arthritis, but a high index of suspicion remains necessary even if these are not present. Osteomyelitis (infection of the bone tissue) can also cause pain and limp.Bone fractures, such as a toddlers fracture (spiral fracture of the shin bone), can also cause pain and limp, but are uncommon around the hip joint. Soft tissue injuries can be evident when bruises are present. Muscle or ligament injuries can be contracted during heavy physical activity —however, it is important not to miss a slipped upper femoral epiphysis. Avascular necrosis of the femoral head (Legg-Calvé-Perthes disease) typically occurs in children aged 4–8, and is also more common in boys. There may be an effusion on ultrasound, similar to transient synovitis.Neurological conditions can also present with a limp. If developmental dysplasia of the hip is missed early in life, it can come to attention later in this way. Pain in the groin can also be caused by diseases of the organs in the abdomen (such as a psoas abscess) or by testicular disease. Rarely, there is an underlying rheumatic condition (juvenile idiopathic arthritis, Lyme arthritis, gonococcal arthritis, ...) or bone tumour.
Treatment
Treatment consists of rest, non-weightbearing and painkillers when needed. A small study showed that the nonsteroidal anti-inflammatory drug ibuprofen could shorten the disease course (from 4.5 to 2 days) and provide pain control with minimal side effects (mainly gastrointestinal disturbances). If fever occurs or the symptoms persist, other diagnoses need to be considered.
References
Further reading
Leet AI, Skaggs DL (Feb 2000). "Evaluation of the acutely limping child". Am Fam Physician. 61 (4): 1011–8. PMID 10706154.: An illustrated, free full-text review with emphasis on clinical examination of the acutely limping child.
== External links == |
Intestinal malrotation | Intestinal malrotation is a congenital anomaly of rotation of the midgut. It occurs during the first trimester as the fetal gut undergoes a complex series of growth and development. Malrotation can lead to a dangerous complication called volvulus. Malrotation can refer to a spectrum of abnormal intestinal positioning, often including:
The small intestine found predominantly on the right side of the abdomen
The cecum displaced from its usual position in the right lower quadrant into the epigastrium or right hypochondrium
An absent or displaced ligament of Treitz
Fibrous peritoneal bands called bands of Ladd running across the vertical portion of the duodenum
An unusually narrow, stalk-like mesenteryThe position of the intestines, narrow mesentery and Ladds bands can contribute to several severe gastrointestinal conditions. The narrow mesentery predisposes some cases of malrotation to midgut volvulus, a twisting of the entire small bowel that can obstruct the mesenteric blood vessels leading to intestinal ischemia, necrosis, and death if not promptly treated. The fibrous Ladds bands can constrict the duodenum, leading to intestinal obstruction.
Signs and symptoms
Signs and symptoms of malrotation vary depending on if the patient is suffering from an acute volvulus or experiencing chronic symptoms.
If the patient, most often an infant, presents acutely with midgut volvulus, it is usually manifested by bilious vomiting, crampy abdominal pain, abdominal distention, and in late cases, the passage of blood and mucus in their stools.
Patients with chronic, uncorrected or undiagnosed malrotation can have recurrent abdominal pain and vomiting.
Malrotation may be asymptomatic.
Complications
Intestinal malrotation can lead to a number of disease manifestations and complications such as:
Acute midgut volvulus
Chronic midgut volvulus
Acute duodenal obstruction
Chronic duodenal obstruction
Short bowel syndrome, in cases of volvulus with intestinal necrosis
Death, in cases of volvulus with pan-necrosis of the bowel, severe septic shock or hypovolemic shock
Malabsorption
Chronic motility issues
Internal herniation
Superior mesenteric artery syndrome
Causes
The exact cause of intestinal malrotation is unknown. It is not definitively associated with a particular gene, but there is some evidence of recurrence in families.
Diagnosis
Malrotation is most often diagnosed during infancy, however, some cases are not discovered until later in childhood or even adulthood.With acutely ill patients, consider emergency surgery laparotomy if there is a high index of suspicion.In cases of volvulus, plain radiography may demonstrate signs of duodenal obstruction with dilatation of the proximal duodenum and stomach but it is often non-specific. Ultrasonography may be useful in some cases of volvulus, depicting a "whirlpool sign" where the superior mesenteric artery and superior mesenteric vein have twisted.Upper gastrointestinal series is the modality of choice for the evaluation of malrotation, as it will often show an abnormal position of the duodenum and duodeno-jejunal flexure (ligament of Treitz). In cases of malrotation complicated with volvulus, upper GI demonstrates a corkscrew appearance of the distal duodenum and jejunum. In cases of obstructing Ladds bands, upper GI may reveal a duodenal obstruction. Although upper GI series is regarded as the most reliable diagnostic test for intestinal malrotation, false negatives may occur in 5% of cases. False negatives are most frequently attributed to radiographer error, uncooperative pediatric patients, or variations in intestinal positioning. In equivocal cases physicians may wish to repeat the upper GI or consider additional diagnostic modalities. Lower gastrointestinal series, may be helpful in some patients by showing the caecum at an abnormal location. CT scan and magnetic resonance imaging may also aide in the diagnosis of equivocal cases.The incidence of intestinal malrotation in infants with omphalocoele is low. Therefore, there is little evidence to support the screening for intestinal malrotation in infants with omphalocoele.
Treatment
Prompt surgical treatment is necessary for intestinal malrotation when volvulus has occurred:
First, the patient is resuscitated with fluids to stabilize them for surgery
The volvulus is corrected (counterclockwise rotation of the bowel),
The fibrous Ladds bands over the duodenum are cut,
The mesenteric pedicle is widened by separation of the duodenum and cecum,
The small and large bowels are placed in a position that reduces their risk of future volvulusWith this condition the appendix is often on the wrong side of the body and therefore removed as a precautionary measure during the surgical procedure.
This surgical technique is known as the "Ladds procedure", after Dr. William Ladd. Long-term research on the Ladds procedure indicates that even after surgery, some patients are susceptible to GI issues and may need further surgery.
See also
Situs inversus, a congenital condition in which the major visceral organs are reversed or mirrored from their normal positions.
References
== External links == |
Iliotibial band syndrome | Iliotibial band syndrome (ITBS) is the second most common knee injury, and is caused by inflammation located on the lateral aspect of the knee due to friction between the iliotibial band and the lateral epicondyle of the femur. Pain is felt most commonly on the lateral aspect of the knee and is most intensive at 30 degrees of knee flexion. Risk factors in women include increased hip adduction, knee internal rotation. Risk factors seen in men are increased hip internal rotation and knee adduction. ITB syndrome is most associated with long-distance running, cycling, weight-lifting, and with military training.
Signs and symptoms
ITBS symptoms range from a stinging sensation just above the knee and outside of the knee (lateral side of the knee) joint, to swelling or thickening of the tissue in the area where the band moves over the femur. The stinging sensation just above the knee joint is felt on the outside of the knee or along the entire length of the iliotibial band. Pain may not occur immediately during activity, but may intensify over time. Pain is most commonly felt when the foot strikes the ground, and pain might persist after activity. Pain may also be present above and below the knee, where the ITB attaches to the tibia.
Causes
ITBS can result from one or more of the following: training habits, anatomical abnormalities, or muscular imbalances:
Anatomical mechanism
Iliotibial band syndrome is one of the leading causes of lateral knee pain in runners. The iliotibial band is a thick band of fascia on the lateral aspect of the knee, extending from the outside of the pelvis, over the hip and knee, and inserting just below the knee. The band is crucial to stabilizing the knee during running, as it moves from behind the femur to the front of the femur during activity. The continual rubbing of the band over the lateral femoral epicondyle, combined with the repeated flexion and extension of the knee during running may cause the area to become inflamed.
Diagnosis
Diagnosis of iliotibial band syndrome is based on history and physical exam findings, including tenderness at the lateral femoral epicondyle, where the iliotibial band passes over the bone.
Treatment
Conservative treatments
While ITBS pain can be acute, the iliotibial band can be rested, iced, compressed and elevated (RICE) to reduce pain and inflammation, followed by stretching. Utilization of corticosteroid injections and the use of anti-inflammatory medication on the painful area are possible treatments for ITB syndrome. Corticosteroid injections have been shown to decrease running pains significantly 7 days after the initial treatment. Similar results can be found with the use of anti-inflammatory medication, analgesic/anti-inflammatory medication, specifically. Other non-invasive treatments include things such as, flexibility and strength training, neuromuscular/gait training, manual therapy, training volume reduction, or changes in running shoe. Muscular training of the gluteus maximus and hip external rotators is stressed highly as those muscles are associated with many of the risk factors of ITBS. For runners specifically, neuromuscular/gait training may be needed for success in muscular training interventions to ensure that those trained muscles are used properly in the mechanics of running. Strength training alone will not result in decrease in pain due to ITBS, however, gait training, on its own can result in running form modification that reduces the prevalence of risk factors.
Surgical treatments
Treatments as intensive and invasive as surgery are utilized if several conservative approaches fail to produce results. 6 months should be given for conservative treatments to work before surgical intervention as used.
Epidemiology
Occupation
Significant association between the diagnosis of ITBS and occupational background of the patients has been thoroughly determined. Occupations that require extensive use of iliotibial band are more susceptible to develop ITBS due to continuum of their iliotibial band repeatedly abrading against lateral epicondyle prominence, thereby inducing inflammatory response. Professional or amateur runners are at high clinical risk of ITBS in which shows particularly greater risk in long-distance. Study suggests ITBS alone makes up 12% of all running-related injuries and 1.6% to 12% of runners are affected by ITBS.The relationship between ITBS and mortality/morbidity is claimed to be absent. A study showed that coordination variability did not vary significantly between runners with no injury and runners with ITBS. This result elucidates that the runners ability to coordinate themselves toward direction of their intention (motor coordination) is not, or very minorly affected by the pain of ITBS.Additionally, military trainee in marine boot camps displayed high incidence rate of ITBS. Varying incidence rate of 5.3–22% in basic training was reported in a case study. A report from the U.S. Marine Corps announces that running/overuse-related injuries accounted for >12% of all injuries.In contrast, studies suggested antithesis of conventional perception that racial, gender or age difference manifests in different incidence rate of ITBS diagnosis. No meaningful statistical data successfully provides significant correlation between ITBS and gender, age, or race. Although, there had been a claim that females are more prone to ITBS due to their anatomical difference in pelvis and lower extremity. Males with larger lateral epicondyle prominence may also be more susceptible to ITBS. Higher incidence rate of ITBS has been reported at age of 15–50, in which generally includes most of active athletes.Other professions that had noticeable association with ITBS include cyclists, heavy weightlifters, et cetera. One observational study discovered 24% of 254 cyclists were diagnosed with ITBS within 6 years. Another study provided data that shows more than half (50%) of professional cyclists complain of knee pain.
See also
Chondromalacia patellae
Patellofemoral pain syndrome
Plica syndrome
References
Further reading
van der Worp, Maarten P.; van der Horst, Nick; de Wijer, Anton; Backx, Frank J. G.; Nijhuis-van der Sanden, Maria W. G. (23 December 2012). "Iliotibial Band Syndrome in Runners". Sports Medicine. 42 (11): 969–992. doi:10.1007/BF03262306. S2CID 73959693.
== External links == |
Constipation in children | Constipation in children refers to the medical condition of constipation in children. It is a functional gastrointestinal disorder.
Presentation
Children have different bowel movement patterns than adults. In addition, there is a wide spectrum of normalcy when considering childrens bowel habits. On average, infants have 3-4 bowel movements/day, and toddlers have 2-3 bowel movements per day. At around age 4, children develop an adult-like pattern of bowel movements (1-2 stools/day). Children benefit from scheduled toilet breaks, once early in the morning and 30 minutes after meals. The Rome III Criteria for constipation in children helps to define constipation for various age groups.
Causes
While it is difficult to assess an exact age at which constipation most commonly arises, children frequently experience constipation in conjunction with life-changes. Examples include: toilet training, starting or transferring to a new school, and changes in diet. Especially in infants, changes in formula or transitioning from breast milk to formula can cause constipation. Fortunately, the majority of constipation cases are not tied to a medical disease, and treatment can be focused on simply relieving the symptoms.
Congenital causes
A number of diseases present at birth can result in constipation. They are as a group uncommon with Hirschsprungs disease (HD) being the most common. HD is more common in males than females, affecting 1 out of 5000 babies. In people with HD, specific types of cells called neural crest cells fail to migrate to parts of the colon. This causes the affected portion of the colon to be unable to contract and relax to help push out a bowel movement. The affected portion of the colon remains contracted, making it difficult for stool to pass through. Concern for HD should be raised in a child who has not passed stool during the first 48 hours of life. Milder forms of HD, in which only a small portion of the colon is affected, can present later in childhood as constipation, abdominal pain, and bloating. Similar disorders to HD include anal achalasia and hypoganglionosis. In hypoganglionosis, there is a low number of neural crest cells, so the colon remains contracted. In anal achalasia, the internal anal sphincter remains contracted, making it difficult for stool to pass. However, there is a normal number of neural crest cells present.There are also congenital structural anomalies that can lead to constipation, including anterior displacement of the anus, imperforate anus, strictures, and small left colon syndrome. Anterior displacement of the anus can be diagnosed on physical exam. The disease causes constipation because the inappropriate positioning of the anus which make it difficult to pass a bowel movement. Imperforate anus is an anus that ends in a blind pouch and does not connect to the rest of the persons intestines. Small left colon syndrome is a rare disease in which the left side of the babies colon has a small diameter, which makes it difficult for stool to pass. A risk factor for small left colon syndrome is having a mother with diabetes.Some symptoms that may indicate an underlying disease include:
Bowel movements that contain blood.
Severe abdominal bloating.
Peri-anal fistula
Absent anal wink reflex
Sacral dimple
Failure to thrive
Diagnosis
The Rome process suggests a diagnosis of constipation in children fewer than 4 years old when the child has 2 or more of the following complaints for at least 1 month. For children older than 4 years, there must be 2 of these complaints for at least 2 months.
2 or fewer bowel movements per week
Passing large bowel movements
On physical exam, a doctor may find large amounts of feces within the childs rectum.
A child who is already toilet trained has at least 1 accident per week involving a bowel movement.
Child demonstrates withholding behavior in which he or she actively tries not to pass a bowel movement.
Hard stools
Pain with defecation.For children, the degree of constipation may be scored by the Leech or the Barr systems:
The Leech system assigns a score of 0 to 5 based on the amount of feces:0: no visible feces
1: scanty feces visible
2: mild fecal loading
3: moderate fecal loading
4: severe fecal loading
5: severe fecal loading with bowel dilatation
These score are assigned separately for the right colon, the left colon and the rectosigmoid colon, resulting in a maximum score of 15. A Leech score of 9 or greater is regarded as positive for constipation.The Barr system rates both the amount and consistency of the faeces, and assigns a score separately for the ascending colon, transverse colon, descending colon and rectum. Its maximum score is 22, and a score of 10 or greater is regarded as positive for constipation.
Treatment
Lactulose and milk of magnesia have been compared with polyethylene glycol (PEG) in children. All had similar side effects, but PEG was more effective at treating constipation. Osmotic laxatives are recommended over stimulant laxatives.
Epidemiology
There is wide variation in the rates of constipation as reported by research in various countries. The variation in research data makes it challenging to describe the true global situation.Approximately 3% of children have constipation, with girls and boys being equally affected. With constipation accounting for approximately 5% of general pediatrician visits and 25% of pediatric gastroenterologist visits, the symptom carries a significant financial impact upon our healthcare system.
Society and culture
Constipation is often emotionally stressful for children and their caregivers. It is common for parents to bring their children to doctors for this condition. The experience of going to a doctor for this can be stressful.Too often, children at doctors receive unnecessary health care when they get medical imaging for constipation. Children should only get tests when there is an indication.
== References == |
Corneal abrasion | Corneal abrasion is a scratch to the surface of the cornea of the eye. Symptoms include pain, redness, light sensitivity, and a feeling like a foreign body is in the eye. Most people recover completely within three days.Most cases are due to minor trauma to the eye such as that which can occur with contact lens use or from fingernails. About 25% of cases occur at work. Diagnosis is often by slit lamp examination after fluorescein dye has been applied. More significant injuries like a corneal ulcer, globe rupture, recurrent erosion syndrome, and a foreign body within the eye should be ruled out.Prevention includes the use of eye protection. Treatment is typically with antibiotic ointment. In those who wear contact lenses a fluoroquinolone antibiotic is often recommended. Paracetamol (acetaminophen), NSAIDs, and eye drops such as cyclopentolate that paralyse the pupil can help with pain. Evidence does not support the usefulness of eye patching for those with simple abrasions.About 3 per 1,000 people are affected a year in the United States. Males are more often affected than females. The typical age group affected is those in their 20s and 30s. Complications can include bacterial keratitis, corneal ulcer, and iritis. Complications may occur in up to 8% of people.
Signs and symptoms
Signs and symptoms of corneal abrasion include pain, trouble with bright lights, a foreign-body sensation, excessive squinting, and reflex production of tears. Signs include epithelial defects and edema, and often redness of the eye. The vision may be blurred, both from any swelling of the cornea and from excess tears. Crusty buildup from excess tears may also be present.
Complications
Complications are the exception rather than the rule from simple corneal abrasions. It is important that any foreign body be identified and removed, especially if containing iron as rusting will occur.Occasionally the healed epithelium may be poorly adherent to the underlying basement membrane in which case it may detach at intervals giving rise to recurrent corneal erosions.
Causes
Corneal abrasions are generally a result of trauma to the surface of the eye. Common causes include being poked by a finger, walking into a tree branch, and wearing old contact lenses. A foreign body in the eye may also cause a scratch if the eye is rubbed.Injuries can also be incurred by "hard" or "soft" contact lenses that have been left in too long. Damage may result when the lenses are removed, rather than when the lens is still in contact with the eye. In addition, if the cornea becomes excessively dry, it may become more brittle and easily damaged by movement across the surface. Soft contact lens wear overnight has been extensively linked to gram negative keratitis (infection of the cornea) particularly by a bacterium known as Pseudomonas aeruginosa which forms in the eyes biofilm as a result of extended soft contact lens wear. When a corneal abrasion occurs either from the contact lens itself or another source, the injured cornea is much more susceptible to this type of bacterial infection than a non-contact lens users would be. This is an optical emergency as it is sight- (in some cases eye-) threatening. Contact lens wearers who present with corneal abrasions should never be pressure patched because it has been shown through clinical studies that patching creates a warm, moist dark environment that can cause the cornea to become infected or cause an existing infection to be greatly accelerated on its destructive path.Corneal abrasions are also a common and recurrent feature in people with specific types of corneal dystrophy, such as lattice corneal dystrophy. Lattice dystrophy gets its name from an accumulation of amyloid deposits, or abnormal protein fibers, throughout the middle and anterior stroma. During an eye examination, the doctor sees these deposits in the stroma as clear, comma-shaped overlapping dots and branching filaments, creating a lattice effect. Over time, the lattice lines will grow opaque and involve more of the stroma. They will also gradually converge, giving the cornea a cloudiness that may also reduce vision. In some people, these abnormal protein fibers can accumulate under the corneas outer layer—the epithelium. This can cause erosion of the epithelium. This condition is known as recurrent epithelial erosion. These erosions: (1) Alter the corneas normal curvature, resulting in temporary vision problems; and (2) Expose the nerves that line the cornea, causing severe pain. Even the involuntary act of blinking can be painful.
Diagnosis
Although corneal abrasions may be seen with ophthalmoscopes, slit lamp microscopes provide higher magnification which allow for a more thorough evaluation. To aid in viewing, a fluorescein stain that fills in the corneal defect and glows with a cobalt blue-light is generally instilled first.A careful search should be made for any foreign body, in particular looking under the eyelids. Injury following use of hammers or power-tools should always raise the possibility of a penetrating foreign body into the eye, for which urgent ophthalmology opinion should be sought.
Prevention
Prevention is the best method to avoid recurrence of corneal abrasions. Protective eyewear should be worn by people who work with hazardous machinery, metal, wood, or chemicals, as well as those who perform yard work or participate in certain contact sports. The appropriate type of protective eyewear depends on the specific circumstances, but all should provide shielding, good visibility, and a comfortable fit. Some examples include polycarbonate glasses or goggles, plastic safety glasses, face shields, and welding helmets. Specifically, welders should use a helmet with a lens that blocks UV light to avoid UV keratitis. It is important to notice that people with one eye are especially vulnerable to potentially blinding injuries, and should pay special attention to protecting their eyes. In these cases, protective eyewear can ensure some degree of safety while also allowing people to participate in their normal day-to-day activities.Ensuring both a proper contact lens fit and the compliance of the person with care measures can prevent contact lens-related complications. As it has been stated previously, these can cause both mechanic damage to the cornea and be a risk factor for the development of microbial keratitis. Thus, an emphasis should be placed on reducing lens contamination by using effective disinfecting solutions, as well as antimicrobial contact lenses and cases. It is important to avoid swimming with contact lenses, because this increases the frequency of bacterial infections, primarily from Staphylococcus epidermidis and other organisms found in contaminated water. Finally, people who use contact lenses can also avoid both mechanical and infectious trauma by not using contacts beyond the length of their intended use.
Treatment
The treatment of corneal abrasions aims to prevent bacterial superinfection, speed healing, and provide symptomatic relief. If a foreign body is found, it needs to be removed.
Foreign body
Positioning: The person is laid in a comfortable position with the affected eye closest to the physician. Loupes can be used if available and the eye can be illuminated with a medical light or, alternatively, with an ophtalmoscope held in the non-dominant hand. The person is then asked to focus on a particular point on the ceiling so that the foreign body sits as centrally between the eyelids as possible. This accounts for a more sterile procedure by keeping the eyelashes as far as possible, and reduces the chance of eliciting a blink reflex. If necessary, the eyelids can be kept open using an eyelid speculum, the examiners fingertips, a cotton tip or an assistant.
Anaesthetic and pupil dilator: Local anaesthetic is instilled into both eyes in order to reduce blepharospasm. Topical oxybuprocaine 0.4% is the preferred choice as it has an onset of action of 20 seconds and a half-life of 20 minutes. A drop of topical pupil dilator such a cyclopentolate 1%, if available, can be helpful to reduce ciliary spasm after removal of the foreign body. Atropine is generally avoided due to its long-lasting mydriatic effects.
Removal techniques: There are mainly two types of techniques, the choice of which will depend on the nature of the foreign body. The first technique is the cotton tip removal, which is indicated in superficial foreign bodies with no surrounding corneal reaction, and the second is the hypodermic needle or nº15 blade removal with which the complete foreign body and any surrounding rust ring can be removed.
Irrigation of the ocular surface and upper and lower fornices can be performed after the procedure to wash out any residual loose foreign body material. A 10 mL ampoule of sterile saline is usually sufficient.
Medications
Current recommendations stress the need to use topical and/or oral analgesia and topical antibiotics. One review has found that eye drops to numb the surface of the eye such as tetracaine improve pain; however, their safety is unclear. Another review did not find evidence of benefit and concluded there was not enough data on safety. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are useful to reduce the pain caused by corneal abrasions. Diclofenac and ketorolac are the most used, one drop four times a day. It is worth noting, however, that diclofenac may delay wound healing and ketorolac should be avoided in people who wear contact lenses. Some studies do not recommend using topical NSAIDs due to the risk of corneal toxicity. There is no direct evidence regarding the use of oral analgesics, but because pain relief is the main concern for people with corneal abrasions, these are prescribed according to individuals characteristics.
Topical antibiotics are used to prevent concomitant infections, which result in slower healing of corneal abrasions. Ointments are considered the first-line treatment, as they are more lubricating than drops. If the person uses contact lenses, an antibiotic with anti-pseudomonal activity is preferred (ciprofloxacin, gentamicin or ofloxacin), and the use of contact lenses should be discontinued until the abrasion has healed and the antibiotic treatment has ended. This is because contact lens wearers are often colonized with Pseudomonas aeruginosa, which may cause corneal perforations and subsequent permanent vision loss.
If the mechanism of injury involves contact lenses, fingernails or organic/ plant matter, antibiotic prophylaxis should be provided with topical fluoroquinolone drops 4 times a day, and a fluoroquinolone ointment, typically ciprofloxacin, at night. If the abrasion was caused by another mechanism, the recommended treatment includes antibiotic ointments (erythromycin, bacitracin or bacitracin/polymyxin B every 2 or 4 hours) or antibiotic drops, usually polymyxin B and trimethoprim 4 times a day.
Patching
Eye patching is not generally recommended as they do not help with healing or pain. Furthermore, it can result in decreased oxygen delivery, increased moisture and a higher chance of an infection. Another measure that is no longer recommended is the use of mydriatics, formerly used to relieve the pain caused by ciliary muscle spasm.
Animals
References
== External links == |
Pneumoconiosis | Pneumoconiosis is the general term for a class of interstitial lung diseases where inhalation of dust has caused interstitial fibrosis. The three most common types are asbestosis, silicosis, and coal miners lung. Pneumoconiosis often causes restrictive impairment, although diagnosable pneumoconiosis can occur without measurable impairment of lung function. Depending on extent and severity, it may cause death within months or years, or it may never produce symptoms. It is usually an occupational lung disease, typically from years of dust exposure during work in mining; textile milling; shipbuilding, ship repairing, and/or shipbreaking; sandblasting; industrial tasks; rock drilling (subways or building pilings); or agriculture. It is one of the most common occupational diseases in the world.
Types
Depending upon the type of dust, the disease is given different names:
Coalworkers pneumoconiosis (also known as coal miners lung, black lung or anthracosis) – coal, carbon
Aluminosis – Aluminium
Asbestosis – asbestos
Silicosis (also known as "grinders disease" or Potters rot) – crystalline silica dust
Bauxite fibrosis – bauxite
Berylliosis – beryllium
Siderosis – iron
Byssinosis – Byssinosis is caused by cotton dust inhalation and typically demonstrates a different pattern of lung abnormalities than most other pneumoconiosis.
Chalicosis – fine dust from stonecutting
Silicosiderosis (also sometimes called iron miners lung) – mixed dust containing silica and iron
Labrador lung (found in miners in Labrador, Canada) – mixed dust containing iron, silica and anthophyllite, a type of asbestos
Stannosis – tin oxide
Talcosis – talc
Baritosis - a benign type of pneumoconiosis caused by barium inhalation; it typically causes little or no overgrowth, hardening, and/or fibrosis.
Mixed-dust pneumoconiosis
Pathogenesis
The reaction of the lung to mineral dusts depends on many variables, including size, shape, solubility, and reactivity of the particles. For example, particles greater than 5 to 10 μm are unlikely to reach distal airways, whereas particles smaller than 0.5 μm move into and out of alveoli, often without substantial deposition and injury. Particles that are 1 to 5 μm in diameter are the most dangerous, because they get lodged at the bifurcation of the distal airways. Coal dust is relatively inert, and large amounts must be deposited in the lungs before lung disease is clinically detectable. Silica, asbestos, and beryllium are more reactive than coal dust, resulting in fibrotic reactions at lower concentrations. Most inhaled dust is entrapped in the mucus blanket and rapidly removed from the lung by ciliary movement. However, some of the particles become impacted at alveolar duct bifurcations, where macrophages accumulate and engulf the trapped particulates. The pulmonary alveolar macrophage is a key cellular element in the initiation and perpetuation of lung injury and fibrosis. Many particles activate the inflammasome and induce IL-1 production. The more reactive particles trigger the macrophages to release a number of products that mediate an inflammatory response and initiate fibroblast proliferation and collagen deposition. Some of the inhaled particles may reach the lymphatics either by direct drainage or within migrating macrophages and thereby initiate an immune response to components of the particulates and/or to self-proteins that are modified by the particles. This then leads to an amplification and extension of the local reaction. Tobacco smoking worsens the effects of all inhaled mineral dusts, more so with asbestos than with any other particle.
Diagnosis
Typical indications on patient assessment include:
Cough
Shortness of breath
Chest tightness
Chest X-ray may show a characteristic patchy, subpleural, bibasilar interstitial infiltrates or small cystic radiolucencies called honeycombing, particularly in advanced disease.Pneumoconiosis in combination with multiple pulmonary rheumatoid nodules in rheumatoid arthritis patients is known as Caplans syndrome.
Epidemiology
The prevalence as of 2021 of pneumoconiosis is around 527,500 cases, with over 60,000 new patients reported globally in 2017. Prevalence has trended somewhat downward since 2015. The mortality of pneumoconiosis patients remained at a high level in recent years, with over 21,000 deaths each year since 2015. It is likely that pneumoconiosis is under-diagnosed and under-reported, especially in countries without highly developed healthcare systems.
Treatment and Prognosis
Lung damage due to pneumoconiosis cannot be reversed. However, some steps can slow down disease progression and relieve symptoms. These include the prescription of medications and breathing treatments to open airways and reduce inflammation. Pulmonary rehabilitation and supplemental oxygen may also be recommended. A lung transplant may be needed in cases of serious diseases. If the patient smokes, smoking cessation is also important. Regular testing, such as X-rays or lung function tests, may be indicated to monitor disease progression.
Prevention
To reduce the likelihood of developing pneumoconiosis, individuals working in affected industries should wear a mask, wash skin that comes in contact with dust, remove dust from clothing and wash the face and hands before eating or drinking. In addition, governments often regulate industry, especially mines, to limit how much dust is in the air. In the United States, coal miners injured by pneumoconiosis and their families may receive monthly payments and medical benefits under the Black Lung Benefits Act.
See also
Aluminosis
Black Lung Benefits Act of 1972
Chalicosis
Philip DArcy Hart
Pneumonoultramicroscopicsilicovolcanoconiosis
Popcorn workers lung disease — diacetyl emissions and airborne dust from butter flavorings used in microwave popcorn production
References
Further reading
Cochrane, A.L.; Blythe, M. (1989). One Mans Medicine, an autobiography of Professor Archie Cochrane. London: BMJ Books. ISBN 0727902776. (Paperback ed. (2009) Cardiff University ISBN 0954088433.
External links
"Pneumoconioses". NIOSH Safety and Health Topic. Center for Disease Control. 30 March 2022.
"Black Lung Benefits Act". U.S. Department of Labor. Archived from the original on 2010-05-27. Retrieved 2007-03-02.
Coal Workers Pneumoconiosis at Merck Manual of Diagnosis and Therapy Professional Edition
Black Lung — United Mine Workers of America
"Black Lung" (PDF). U.S. Department of Labor Mine Safety and Health Administration. Archived from the original (PDF) on 2010-05-30.
A Conversation about Mining and Black Lung Disease
Flavorings-Related Lung Disease
The Institute of Occupational Medicine and its research into pneumocomiosis
Miller, B.G.; Kinnear, A.G. Pneumoconiosis in coalminers and exposure to dust of variable quartz content (PDF) (Technical report). Institute of Occupational Medicine. TM/88/17. |
Bartholins cyst | A Bartholins cyst occurs when a Bartholins gland within the labia becomes blocked. Small cysts may result in minimal or no symptoms. Larger cysts may result in swelling on one side of the vagina, as well as pain during sex or walking. If the cyst becomes infected, an abscess can occur, which is typically red and very painful. If there are no symptoms, no treatment is needed. Bartholins cysts affect about 2% of women at some point in their life. They most commonly occur during childbearing years.When the cyst becomes uncomfortable or painful, drainage is recommended. The preferred method is the insertion of a Word catheter for four weeks, as recurrence following simple incision and drainage is common. A surgical procedure known as marsupialization may be used or, if the problems persist, the entire gland may be removed. Removal is sometimes recommended in those older than 40 to ensure cancer is not present. Antibiotics are not generally needed to treat a Bartholins cyst.The cause of a Bartholins cyst is unknown. An abscess results from a bacterial infection, but it is not usually a sexually transmitted infection (STI). Rarely, gonorrhea may be involved. Diagnosis is typically based on symptoms and examination. In women over the age of 40, a tissue biopsy is often recommended to rule out cancer.The cyst is named after Caspar Bartholin who accurately described the glands in 1677. The underlying mechanism of the cyst was determined in 1967 by 20th Century obstetrician Samuel Buford Word.
Signs and symptoms
Most Bartholins cysts do not cause any symptoms, although some may cause pain during walking, sitting, or sexual intercourse (dyspareunia). They are usually between 1 and 4 cm, and are located just medial to the labia minora. Most Bartholins cysts only affect the left or the right side (unilateral). While small cysts are usually not painful, larger cysts can cause significant pain.
Pathophysiology
A Bartholins gland cyst develops when the duct that drains the gland becomes blocked. Blockage may be caused by an infection or a mucus plug. The secretions from the Bartholins gland are retained, forming a cyst.
Diagnosis
Other conditions that may present similarly include hidradenoma papilliferum, lipomas, epidermoid cysts and Skenes duct cysts, among others conditions. In women who are more than 40 years, a biopsy may be recommended to rule out cancer.
Treatment
If the Bartholins cysts is not painful or uncomfortable, treatment may not be necessary. Small, asymptomatic cysts can be observed over time to assess their development. In cases that require intervention, a catheter may be placed to drain the cyst, or the cyst may be surgically opened to create a permanent pouch (marsupialization). Intervention has a success rate of 85%, regardless of the method used, to alleviate swelling and discomfort.Catheterization is a minor procedure that can be performed locally as an outpatient procedure. A small tube with a balloon on the end (known as a Word catheter) may be inserted into the cyst. The balloon is then inflated to keep it in place. The catheter stays in place for 2 to 4 weeks, draining the fluid and causing a normal gland opening to form, after which the catheter is removed. The catheters do not generally impede normal activity, but sexual intercourse is generally abstained from while the catheter is in place.Cysts may also be opened permanently, a procedure called marsupialization, which involves opening the gland through an incision to ensure that the secretion channel remains open. If a cyst is infected, it may break open and start to heal on its own after 3 to 4 days. Nonprescription pain medication such as ibuprofen relieves pain, and a sitz bath may increase comfort and reduce pain. Warm compresses can also speed up healing. If a Bartholin gland abscess comes back several times, the gland and duct can be surgically removed.
Prognosis
While Bartholin cysts can be quite painful, they are not life-threatening. New cysts cannot absolutely be prevented from forming, but surgical or laser removal of a cyst makes it less likely that a new one will form at the same site. Those with a cyst are more likely than those without a cyst to get one in the future. They can recur every few years or more frequently. Many women who have marsupialization done find that the recurrences may slow, but do not actually stop.
Epidemiology
Two percent of women will have a Bartholins gland cyst at some point in their lives. They occur at a rate of 0.55 per 1000 person-years and in women aged 35–50 years at a rate of 1.21 per 1000 person-years. The incidence of Bartholin duct cysts increases with age until menopause, and decreases thereafter. Hispanic women may be more often affected than white women and black women. The risk of developing a Bartholins gland cyst increases with the number of childbirths.
References
== External links == |
Pagets disease of bone | Pagets disease of bone (commonly known as Pagets disease or, historically, osteitis deformans) is a condition involving cellular remodeling and deformity of one or more bones. The affected bones show signs of dysregulated bone remodeling at the microscopic level, specifically excessive bone breakdown and subsequent disorganized new bone formation. These structural changes cause the bone to weaken, which may result in deformity, pain, fracture or arthritis of associated joints.The exact cause is unknown, although leading theories indicate both genetic and acquired factors (see Causes). Pagets disease may affect any one or several bones of the body (most commonly pelvis, tibia, femur, lumbar vertebrae, and skull), but never the entire skeleton, and does not spread from bone to bone. Rarely, a bone affected by Pagets disease can transform into a malignant bone cancer.
As the disease often affects people differently, treatments of Pagets disease can vary. Although there is no cure for Pagets disease, medications (bisphosphonates and calcitonin) can help control the disorder and lessen pain and other symptoms. Medications are often successful in controlling the disorder, especially when started before complications begin.
Pagets disease affects from 1.5 to 8.0 percent of the population, and is most common in those of British descent. It is primarily diagnosed in older people and is rare in people less than 55 years of age. Men are more commonly affected than women (3:2). The disease is named after English surgeon Sir James Paget, who described it in 1877.
Signs and symptoms
Mild or early cases of Pagets are asymptomatic, and so most people are diagnosed with Pagets disease incidentally during medical evaluation for another problem. Approximately 35% of patients with Pagets have symptoms related to the disease when they are first diagnosed. Overall, the most common symptom is bone pain. When symptoms do occur, they may be confused with those of arthritis or other disorders, and so diagnosis may be delayed. Pagets may first be noticed as an increasing deformity of a persons bones.Pagets disease affecting the skull may cause frontal bossing, increased hat size, and headaches. Often patients may develop loss of hearing in one or both ears due to auditory foramen narrowing and resultant compression of the nerves in the inner ear. Rarely, skull involvement may lead to compression of the nerves that supply the eye, leading to vision loss.
Associated conditions
Pagets disease is a frequent component of multisystem proteinopathy.
Advanced Pagets disease may lead to other medical conditions, including:
Osteoarthritis may result from changes in bone shape that alter normal skeletal mechanics. For example, bowing of a femur affected by Pagets may distort overall leg alignment, subjecting the knee to abnormal mechanical forces and accelerating degenerative wear.
Heart failure is a rare, reported consequence of severe Pagets disease (i.e. more than 40% skeletal involvement). The abnormal bone formation is associated with recruitment of abnormal blood vessels, forcing the cardiovascular system to work harder (pump more blood) to ensure adequate circulation.
Kidney stones are somewhat more common in patients with Pagets disease.
Nervous system problems may occur in Pagets disease, resulting from increased pressure on the brain, spinal cord, or nerves, and reduced blood flow to the brain and spinal cord.
When Pagets disease affects the facial bones, the teeth may become loose. Disturbance in chewing may occur. Chronic dental problems may lead to infection of the jaw bone.
Angioid streaks may develop, possibly as a result of calcification of collagen or other pathological deposition.Pagets disease is not associated with osteoporosis. Although Pagets disease and osteoporosis can occur in the same patient, they are different disorders. Despite their marked differences, several treatments for Pagets disease are also used to treat osteoporosis.
Causes
Viral
Pagets disease may be caused by a slow virus infection (i.e., paramyxoviridae) present for many years before symptoms appear. Associated viral infections include respiratory syncytial virus, canine distemper virus, and the measles virus. However, recent evidence has cast some doubt upon the measles association. Laboratory contamination may have played a role in past studies linking paramyxovirus (e.g. measles) to Pagets disease.
Genetic
There is a hereditary factor in the development of Pagets disease of bone. Two genes, SQSTM1 and RANK, and specific regions of chromosome 5 and 6 are associated with Pagets disease of bone. Genetic causes may or may not involve a family history of Pagets disease.About 40–50% of people with the inherited version of Pagets disease have a mutation in the gene SQSTM1, which encodes a protein, called p62, that is involved in regulating the function of osteoclasts (bone cells). However, about 10-15 percent of people that develop the disease without any family history also have a mutation in the SQSTM1 gene.Pagets disease of bone is associated with mutations in RANK. Receptor Activator of Nuclear Factor κ B (RANK), which is a type I membrane protein that is expressed on the surface of osteoclasts and is involved in their activation upon ligand binding. Additional genetic associations include:
Pathogenesis
The pathogenesis of Pagets disease is described in four stages:
Osteoclastic activity
Mixed osteoclastic – osteoblastic activity
Osteoblastic activity
Malignant degenerationInitially, there is a marked increase in the rate of bone resorption in localized areas, caused by large and numerous osteoclasts. These localized areas of pathological destruction of bone tissue (osteolysis) are seen radiologically as an advancing lytic wedge in long bones or the skull. When this occurs in the skull, it is called osteoporosis circumscripta. The osteolysis is followed by a compensatory increase in bone formation induced by the bone-forming cells, called osteoblasts, that are recruited to the area. This is associated with accelerated deposition of lamellar bone in a disorganized fashion. This intense cellular activity produces a chaotic picture of trabecular bone ("mosaic" pattern), rather than the normal linear lamellar pattern. The resorbed bone is replaced and the marrow spaces are filled by an excess of fibrous connective tissue with a marked increase in blood vessels, causing the bone to become hypervascular. The bone hypercellularity may then diminish, leaving a dense "pagetic bone," also known as burned-out Pagets disease. A later phase of the disease is characterized by the replacement of normal bone marrow with highly vascular fibrous tissue.Sir James Paget first suggested the disease was due to an inflammatory process. Some evidence suggests that a paramyxovirus infection is the underlying cause of Pagets disease, which may support the possible role of inflammation in the pathogenesis. However, no infectious virus has yet been isolated as a causative agent, and other evidence suggests an intrinsic hyperresponsive reaction to vitamin D and RANK ligand is the cause. Further research is therefore necessary.
Diagnosis
The first clinical manifestation of Pagets disease is usually an elevated alkaline phosphatase in the blood.
Pagets disease may be diagnosed using one or more of the following tests:
Pagetic bone has a characteristic appearance on X-rays. A skeletal survey is therefore indicated.
An elevated level of alkaline phosphatase in the blood in combination with normal calcium, phosphate, and aminotransferase levels in an elderly patient are suggestive of Pagets disease.
Markers of bone turnover in urine eg. Pyridinoline
Elevated levels of serum and urinary hydroxyproline are also found.
Bone scans are useful in determining the extent and activity of the condition. If a bone scan suggests Pagets disease, the affected bone(s) should be X-rayed to confirm the diagnosis.
Differential diagnosis
Treatment
Although initially diagnosed by a primary care physician, endocrinologists (internal medicine physicians who specialize in hormonal and metabolic disorders), rheumatologists (internal medicine physicians who specialize in joint and muscle disorders), orthopedic surgeons, neurosurgeons, neurologists, oral and maxillofacial surgeons, and otolaryngologists are generally knowledgeable about treating Pagets disease and may be called upon to evaluate specialized symptoms. It can sometimes be difficult to predict whether a person with Pagets disease, who otherwise has no signs or symptoms of the disorder, will develop symptoms or complications (such as a bone fracture) in the future.
Medication
The goal of treatment is to relieve bone pain and prevent the progression of the disease. These medications are usually recommended for people with Pagets disease who:
have bone pain, headache, back pain, or a nerve-related symptom (such as "shooting" pains in the leg) that is directly associated with the disease;
have elevated levels of serum alkaline phosphatase (ALP) in their blood;
display evidence that a bone fracture will occur;
require pretreatment therapy for affected bones that require surgery;
have active symptoms in the skull, long bones, or vertebrae (spine);
have the disease in bones located next to major joints, placing them at risk of developing osteoarthritis;
develop hypercalcemia that occurs when a person, with several bones affected by Pagets disease and a high serum alkaline phosphatase level, is immobilized.
Bisphosphonates
Five bisphosphonates are currently available. In general, the most commonly prescribed are risedronic acid, alendronic acid, and pamidronic acid. Etidronic acid and other bisphosphonates may be appropriate therapies for selected patients but are less commonly used. In one study it was reported that people experienced side effects when taking bisphosphonates for six months, however the quality of evidence was low. None of these drugs should be used by people with severe kidney disease.
Neridronate
Etidronate disodium The approved regimen is once daily for six months; a higher dose is more commonly used. No food, beverage, or medications should be consumed for two hours before and after taking. The course should not exceed six months, but repeat courses can be given after rest periods, preferably of three to six months duration.
Pamidronate disodium in intravenous form: the approved regimen uses an infusion over four hours on each of three consecutive days, but a more commonly used regimen is over two to four hours for two or more consecutive or nonconsecutive days.
Alendronate sodium is given as tablets once daily for six months; patients should wait at least 30 minutes after taking before eating any food, drinking anything other than tap water, taking any medication, or lying down (patient may sit).
Tiludronate disodium is taken once daily for three months; they may be taken any time of day, as long as there is a period of two hours before and after resuming food, beverages, and medications.
Risedronate sodium tablet taken once daily for 2 months is the prescribed regimen; patients should wait at least 30 minutes after taking before eating any food, drinking anything other than tap water, taking any medication, or lying down (patient may sit).
Zoledronic acid is given as an intravenous infusion; a single dose is effective for two years. This is recommended for most people at high risk with active disease.
Calcitonin
Salcatonin, also called calcitonin-salmon is a synthetic copy of a polypeptide hormone secreted by the ultimobranchial gland of salmon. Miacalcin is administered by injection, three times per week or daily, for 6–18 months. Repeat courses can be given after brief rest periods. Miacalcin may be appropriate for certain patients but is seldom used. Calcitonin was putatively linked to increased chance of cancer. The European Medicines Agency (EMA) recommended that calcitonin be used only on a short-term basis for 3 conditions for which it had previously been approved in the European Union: Pagets disease, acute bone loss resulting from sudden immobilization, and hypercalcemia caused by cancer. As a solution for injection or infusion, calcitonin should be administered for no more than 4 weeks to prevent acute bone loss resulting from sudden immobilization, and normally for no more than 3 months to treat Pagets disease, the EMA said. The agency did not specify a time frame for the short-term use of calcitonin for treating hypercalcemia caused by cancer. The EMA based its recommendations on a review of the benefits and risks of calcitonin-containing medicines. Conducted by the agencys Committee for Medicinal Products for Human Use (CHMP), the review encompassed available data from the companies that market these drugs, postmarketing safety data, randomized controlled studies, 2 studies of unlicensed oral calcitonin drugs, and experimental cancer studies, among other sources.In 2014, the FDA noted the risk imbalances in the prescribing information for Miacalcin but declined to label this product with a boxed warning as a causal association was not identified.A more recent meta-analysis determined that a causal link between calcitonin and cancer is both unlikely and antithetical to known biology, although a weak association was not definitively excluded. The available studies for analysis were inconsistent and nonspecific, with one study noting an increased risk of liver cancer and decreased risk of breast cancer. This was not replicated in any other study.Additionally, there is question of the overall efficacy of calcitonin-containing nasal sprays. A phase III trial found no difference between placebo and nasal calcitonin sprays on lumbar bone mineral density in osteoporosis. It did find a significant increase in bone mineral density with oral calcitonin. This result was replicated in another study, but this study found that the bone mineral density increase did not significantly impact fracture risk. However, these studies were only inclusive of osteoporosis.
Surgery
Medical therapy prior to surgery helps to decrease bleeding and other complications. Patients who are having surgery should discuss treatment with their physician. There are generally three major complications of Pagets disease for which surgery may be recommended.
Fractures — Surgery may allow fractures to heal in a better position.
Severe degenerative arthritis — If disability is severe and medication and physical therapy are no longer helpful, joint replacement of the hips and knees may be considered.
Bone deformity — Cutting and realignment of pagetic bone (osteotomy) may help painful weight bearing joints, especially the knees.Complications resulting from enlargement of the skull or spine may injure the nervous system. However, most neurologic symptoms, even those that are moderately severe, can be treated with medication and do not require neurosurgery.
Diet and exercise
In general, patients with Pagets disease should receive 1000–1500 mg of calcium, adequate sunshine, and at least 400 units of vitamin D daily. This is especially important in patients being treated with bisphosphonates; however, taking oral bisphosphonates should be separated from taking calcium by at least two hours, because the calcium can inhibit the absorption of the bisphosphonate. Patients with a history of kidney stones should discuss calcium and vitamin D intake with their physicians.Exercise is very important in maintaining skeletal health, avoiding weight gain, and maintaining joint mobility. Since undue stress on affected bones should be avoided, people with Pagets disease of bone should discuss any exercise program with their physicians or physical therapists before beginning.
Prognosis
The disease is progressive and slowly worsens with time, although people may remain minimally symptomatic. Treatment is aimed at controlling symptoms, but there is no cure. Any bone or bones can be affected, but Pagets disease occurs most frequently in the spine, skull, pelvis, femur, and lower legs. Osteogenic sarcoma, a form of bone cancer, is a rare complication of Pagets disease occurring in less than one percent of those affected. The development of osteosarcoma may be suggested by the sudden onset or worsening pain.
Epidemiology
Pagets disease of bone is the second most common metabolic bone disorder, after osteoporosis. The overall prevalence and severity of Pagets disease are decreasing; the cause for these changes is unclear. Pagets disease is rare in people less than 55 years of age, and the prevalence increases with age. Evidence from studies of autopsy results have demonstrated Pagets disease in about 3 percent of people older than 40 years of age. Pagets disease is more common in males than females. Rates of Pagets disease are about 50 percent higher in men than in women.
About 15 percent of people with Pagets disease also have a family member with the disease. In cases where the disease is familial, it is inherited in an autosomal dominant fashion, although not all people that inherit the affected version of the genes will express the disease (incomplete penetrance).The incidence of Pagets disease varies considerably with geographic location. Pagets predominantly affects people of European descent, whereas people of African, Asian, or Indian descent are less commonly affected. Pagets disease is less common in Switzerland and Scandinavia than in the rest of Western Europe. Pagets disease is uncommon in the native populations of North and South America, Africa, Asia, and the Middle East. When an individual from these regions does develop Pagets disease, there is typically some European ancestry present.
History
The condition was initially described by Dr. James Paget. In a paper published in 1877, Paget told of five patients with "a rare disease of bones" which presented with slowly progressive bone deformities in the 4th and 5th decades of age. Strikingly, the first patient was described to have many of the classic complications of the disease, including arthritis related to abnormal bone mechanics, cranial nerve palsies associated with an enlarging skull, and malignant transformation of a tumor of the radius which ultimately proved fatal. Pagets post-mortem autopsy evaluation showed "bones of the vault of this skull were in every part increased to about four times the normal thickness," and microscopic evaluation showed evidence of both bone erosion and abnormal remodeling. Although he incorrectly attributed the findings to a process of chronic inflammation, having ruled out tumor and hypertrophy as alternative etiologies, these prescient observations of a mixed destructive/regenerative process correspond to the modern understanding of the disease.
Holding, then, the disease to be an inflammation of bones, I would suggest that, for brief reference, and for the present, it may be called, after its most striking character, Osteitis deformans. A better name may be given when more is known of it.
Pagets disease of bone was originally termed osteitis deformans, because it was thought to involve an inflammatory process, which is implied by the suffix -itis. Now, that term is considered technically incorrect, and the preferred term is osteodystrophia deformans.
Society and culture
Ludwig van Beethoven is speculated to have had Pagets disease based on autopsy description, and which may have contributed to his well-known deafness.
Retired Boston Red Sox center fielder Dom DiMaggio had Pagets disease and served as a member of the board of directors of the Paget Foundation.
References
External links
Pagets Disease of Bone Overview - NIH Osteoporosis and Related Bone Diseases ~ National Resource Center |
Focal seizure | Focal seizures (also called partial seizures and localized seizures) are seizures which affect initially only one hemisphere of the brain. The brain is divided into two hemispheres, each consisting of four lobes – the frontal, temporal, parietal and occipital lobes. A focal seizure is generated in and affects just one part of the brain – a whole hemisphere or part of a lobe. Symptoms will vary according to where the seizure occurs. When seizures occur in the frontal lobe the patient may experience a wave-like sensation in the head. When seizures occur in the temporal lobe, a feeling of déjà vu may be experienced. When seizures are localized to the parietal lobe, a numbness or tingling may occur. With seizures occurring in the occipital lobe, visual disturbances or hallucinations have been reported.
Types
As of 2017, focal seizures are split into two main categories, focal onset aware, and focal onset impaired awareness. What was previously termed a secondary generalised seizure is now termed a focal to bilateral seizure.In focal onset aware seizures, a small part of one of the lobes may be affected and the person remains conscious. This can often be a precursor to a larger focal onset impaired awareness seizure. When this is the case, the focal aware seizure is usually called an aura.
A focal impaired awareness seizure affects a larger part of the hemisphere and the person may lose consciousness.
If a focal seizure spreads from one hemisphere to the other side of the brain, this will give rise to a focal to bilateral seizure. The person will become unconscious and may experience a tonic clonic seizure. When people have multiple focal seizures they generally have a condition known as temporal lobe epilepsy. (A generalized seizure is one that involves both sides of the brain from the onset.)
Simple partial seizures
Simple partial seizures are seizures which affect only a small region of the brain, often the temporal lobes or structures found there, such as the hippocampi. People who have focal aware seizures remain conscious. Focal aware seizures often precede larger focal impaired awareness seizures, where the abnormal electrical activity spreads to a larger area of the brain. This can result in a tonic-clonic seizure.
Presentation
Simple partial seizures are a very subjective experience, and the symptoms vary greatly between people. Since symptoms can be subtle, diagnosis can be delayed by months or years. The symptoms of these seizures can also be misconstrued as auras, especially for epilepsy patients with multiple types of seizure diagnosis. This is due to the varying locations of the brain in which the seizures originate (e.g., Rolandic). A Simple partial seizure may go unnoticed by others or shrugged off by the patient as merely a "funny turn." Focal aware seizures usually start suddenly and are very brief, typically lasting 60 to 120 seconds.Some common symptoms of a simple partial seizure, when the person is awake, are:
preserved consciousness
sudden and inexplicable feelings of fear, anger, sadness, happiness or nausea
sensations of falling or movement
experiencing of unusual feelings or sensations
altered sense of hearing, smelling, tasting, seeing, and tactile perception (sensory illusions or hallucinations), or feeling as though the environment is not real (derealization) or dissociation from the environment or self (depersonalization)
a sense of spatial distortion—things close by may appear to be at a distance
déjà vu (familiarity) or jamais vu (unfamiliarity)
laboured speech or inability to speak at all
usually the event is remembered in detailWhen a seizure occurs during sleep, the person will often become semi-conscious and act out a dream they were having while engaging with the real environment as normal. Objects and people usually appear normal or only slightly distorted to them, and will be able to communicate with them on an otherwise normal level. However, since the person is still acting in a dream-like state, they will assimilate any hallucinations or delusions into their communication, often speaking to a hallucinatory person or speaking of events or thoughts pertaining to their dream or a hallucination.
While-asleep symptoms include:
onset usually in REM sleep
dream-like state
appearance of full consciousness
hallucinations or delusions
behavior or visions typical in dreams
ability to engage with the environment and other people as in full consciousness, though often behaving abnormally, erratically, or failing to be coherent
complete amnesia or assimilating the memory as though it was a normal dream on regaining full consciousness
dreams of daily life that appear as if they happened in reality, and can cause disorientation upon awakeningAlthough hallucinations may occur during focal aware seizures they are differentiated from psychotic symptoms by the fact that the person is usually aware that the hallucinations are not real.
Jacksonian march
Jacksonian march or Jacksonian seizure is a phenomenon where a simple partial seizure spreads from the distal part of the limb toward the ipsilateral face (on same side of body). They involve a progression of the location of the seizure in the brain, which leads to a "march" of the motor presentation of symptoms.Jacksonian seizures are initiated with abnormal electrical activity within the primary motor cortex. They are unique in that they travel through the primary motor cortex in succession, affecting the corresponding muscles, often beginning with the fingers. This is felt as a tingling sensation, or a feeling of waves through the fingers when touched together. It then affects the hand and moves on to more proximal areas on the same side of body. Symptoms often associated with a Jacksonian seizure are sudden head and eye movements, tingling, numbness, smacking of the lips, and sudden muscle contractions. Most of the time any one of these actions can be seen as normal movements, without being associated with the seizure occurring. They occur at no particular moment and last only briefly. They may result in secondary generalized seizure involving both hemispheres. They can also start at the feet, manifesting as tingling or pins and needles, and there are painful cramps in the foot muscles, due to the signals from the brain. Because it is a partial seizure, the postictal state is of normal consciousness.
Jacksonian seizures are named after their discoverer, John Hughlings Jackson, an English neurologist, whose studies led to the discovery of the seizures initiation point (in the primary motor cortex) in 1863.
Complex partial seizures
A complex partial seizure is a seizure that is associated with unilateral cerebral hemisphere involvement and causes impairment of awareness or responsiveness, i.e. alteration of consciousness.
Presentation
Complex partial seizures are often preceded by an aura. The seizure aura is a focal aware seizure. The aura may manifest itself as a feeling of déjà vu, jamais vu, fear, euphoria or depersonalization. The aura might also occur as a visual disturbance, such as tunnel vision or a change in the perceived size of objects. Once consciousness is impaired, the person may display automatisms, such as lip smacking, chewing or swallowing. There may also be loss of memory (amnesia) surrounding the seizural event. The person may still be able to perform routine tasks such as walking, although such movements are not purposeful or planned. Witnesses may not recognize that anything is wrong. The person may or may not even realize that they experienced a seizure.
Complex partial seizures might arise from any lobe of the brain. They most commonly arise from the mesial temporal lobe, particularly the amygdala, hippocampus, and neocortical regions. A common associated brain abnormality is mesial temporal sclerosis. Mesial temporal sclerosis is a specific pattern of hippocampal neuronal loss accompanied by hippocampal gliosis and atrophy. Complex partial seizures occur when excessive and synchronous electrical brain activity causes the impaired awareness and responsiveness. The abnormal electrical activity might spread to the rest of the brain and cause a focal to bilateral seizure or a generalized tonic–clonic seizure. The newer classification of 2017 groups only focal and generalized seizures, and generalized seizures are those that involve both sides of the brain from the onset.
References
== External links == |
Bipolar disorder in children | Bipolar disorder in children, or pediatric bipolar disorder (PBD), is a controversial mental disorder in children and adolescents that is mainly diagnosed in the United States, and is hypothesized to be like bipolar disorder (BD) in adults, thus is proposed as an explanation for extreme changes in mood and behavior accompanying periods of depressed or irritable moods and periods of elevated moods so called manic or hypomanic episodes. These shifts are sometimes quick, but usually are gradual. The average age of onset of pediatric bipolar disorder is unclear, but the risk increases with the onset of puberty. Bipolar disorder is rare in childhood. Pediatric bipolar disorder is typically more severe and has a poorer prognosis than bipolar disorder with onset in late-adolescence or adulthood.The DSM has specified that the criteria for bipolar disorder can be applied to children since 1980. However, the exact criteria for diagnosing pediatric bipolar disorder remains controversial and heavily debated. There are big differences in how commonly it is diagnosed across clinics and in different countries. There has been a rapid increase in research on the topic, but training and clinical practice lag behind.
Identifying bipolar disorder in youth is challenging. Children often exhibit chronic rather than episodic mania periods. Almost always, these chronic problems have causes other than bipolar disorder. The criteria for pediatric bipolar disorder can also often be masked by developmental differences. Comorbid disorders make determining what symptoms are signs of bipolar disorder and which are due to other disorders (e.g., OCD, ADHD, disruptive behavior problems) difficult, leading to complications in treatment. For example, a common treatment for OCD are serotonin re-uptake inhibitors (SRIs), however, SRIs can lead to mood instability and worsening bipolar disorder. The most common misdiagnosis for ADHD in the USA is pediatric bipolar disorder due to hyperactivity being described as prolonged periods of mania. Empirical research conducted in 2004 found that "bipolar disorder (in preadolescence) was initially misdiagnosed in 12 out of 24 youths" (Mahoney, 2004). This is a dangerous misdiagnosis due to the vastly different treatment forms. Firstly, ADHD does not require mood stabilizers like pediatric bipolar disorder. Secondly, the stimulants given to treat ADHD have been shown to cause psychosis and exacerbate mania in pediatric bipolar disorder (Wendling, 2009). This misuse of medication can lead to mood episodes, suicidality, and hospitalization.
Diagnosis
Diagnosis is made based on a clinical interview by a psychiatrist or other licensed mental health practitioner. There are no blood tests or brain scans to diagnose bipolar disorder. Obtaining information on family history and the use of questionnaires and checklists are helpful in making an accurate diagnosis. Commonly used assessment tools include the K-SADS (Kiddie Schedule for Affective Disorders and Schizophrenia), the Diagnostic Interview Schedule for Children (DISC), and the Child Mania Rating Scale (CMRS).
Signs and symptoms
In both the American Psychiatric Associations DSM-5 and the World Health Organizations ICD-10, the same criteria used to diagnose bipolar disorder in adults are used to make the diagnosis in children with some adjustments to account for differences in age and developmental stage. For example, the DSM-5 specifies that in children, depressive episodes can manifest as persistently irritable moods.In diagnosing manic episodes, it is important to compare the changes in mood and behavior to the childs normal mood and behaviors at baseline instead of to other children or adults. For example, grandiosity (i.e., unrealistic overestimation of ones intelligence, talent, or abilities) is normal at varying degrees during childhood and adolescence. Therefore, grandiosity is only considered symptomatic of mania in children when the beliefs are held despite being presented with concrete evidence otherwise or when they lead to a child attempting activities that are clearly dangerous, and most importantly, when the grandiose beliefs are an obvious change from that particular childs normal self-view in between episodes.
Controversy
The diagnosis of childhood bipolar disorder is controversial, although it is recognized that bipolar disorder typical symptoms are dysfunctional and have negative consequences for minors with the condition. Main discussion is centered on whether what is called bipolar disorder in children refers to the same disorder than when diagnosing adults, and the related question on whether adults criteria for diagnosis are useful and accurate when applied to children. More specifically, main discussion over diagnosis in children circles around mania symptomatology and its differences between children and adults.Diagnostic criteria may not correctly separate children with bipolar disorder from other problems such as ADHD, and emphasize fast mood cycles.
Treatment
Medications can produce important side effects, so interventions have been recommended to be closely monitored and families of patients to be informed of the different possible problems that can arise. Atypical antipsychotics are more effective than mood stabilizers, but have more side effects Typical antipsychotics may produce weight gains as well as other metabolic problems, including diabetes mellitus type 2 and hyperlipidemia. Extrapyramidal secondary effects may appear with these medications. These include tardive dyskinesia, a difficult-to-treat movement disorder (dyskinesia) that can appear after long-term use of anti-psychotics. Liver and kidney damage are a possibility with mood stabilizers.Psychological treatment usually includes some combination of education on the disease, group therapy and cognitive behavioral therapy. Children with bipolar disorder and their families are informed, in ways accordingly to their age and family role, about the different aspects of bipolar disorder and its management including causes, signs and symptoms and treatments. Group therapy aims to improve social skills and manage group conflicts, with role-playing as a critical tool. Finally, cognitive-behavioral training is directed towards the participants having a better understanding and control over their emotions and behaviors.BPD I, manic or mixed, without psychosis
Stage 1: Monotherapy with a mood stabilizer (lithium, Divalproex, or carbamazepine), or atypical antipsychotic (olanzapine, quetiapine, or risperidone). Lithium or Divalproex is recommended for first-line treatment. Partial (minimal to moderate) improvement with monotherapy, augment with another of the first-line recommendations.
Stage 2: Monotherapy with an alternative drug, then augmentation.
Stage 3: Possible medication combinations—lithium plus Divalproex, lithium plus atypical, or Divalproex plus atypical.
Stage 4: Combination of 2-3 mood stabilizers
Stage 5: Alternate monotherapy with oxcarbazepine, ziprasidone, or aripiprazole (all Level D).
Stage 6: For nonresponse or intolerable side effects—clozapine for children or adolescents, or electroconvulsive therapy (ECT) for adolescents only.
BPD II, manic or mixed, with psychosis
Stage 1: Same as BPD I without psychosis except for first-line treatment warrants a combination of mood stabilizer and an atypical antipsychotic.
Stages 2–4: Varying combinations and augmentations.
Stage 5: Alternate monotherapy (oxcarbazepine) plus an atypical antipsychotic. (Bipolar Disorder in Children and Adolescents, 2005).
Prognosis
Chronic medication is often needed, with relapses of individuals reaching rates over 90% in those not following medication indications and almost to 40% in those complying with medication regimens in some studies. Compared to adults, a juvenile onset has in general a similar or worse course, although age of onset predicts the duration of the episodes more than the prognosis. A risk factor for a worse outcome is the existence of additional (comorbid) pathologies.Children with bipolar disorder are more likely to commit suicide than other children.
Epidemiology
The prevalence of bipolar in youth is estimated at 2%.
History
Descriptions of children with symptoms similar to contemporary concepts of mania date back to the 18th century. In 1898, a detailed psychiatric case history was published about a 13-year-old that met Jean-Pierre Falret and Jules Baillargers criteria for folie circulaire, which is congruent to the modern conception of bipolar I disorder.In Emil Kraepelins descriptions of bipolar disorder in the 1920s, which he called "manic depressive insanity", he noted the rare possibility that it could occur in children. In addition to Kraepelin, Adolf Meyer, Karl Abraham, and Melanie Klein were some of the first to document bipolar disorder symptoms in children in the first half of the 20th century. It was not mentioned much in English literature until the 1970s when interest in researching the subject increased. It became more accepted as a diagnosis in children in the 1980s after the DSM-III (1980) specified that the same criteria for diagnosing bipolar disorder in adults could also be applied to children.Recognition came twenty years after, with epidemiological studies showing that approximately 20% of adults with bipolar disorder already had symptoms in childhood or adolescence. Nevertheless, onset before age 10 was thought to be rare, below 0.5% of the cases. During the second half of the century misdiagnosis with schizophrenia was not rare in the non-adult population due to common co-occurrence of psychosis and mania, this issue diminishing with an increased following of the DSM criteria in the last part of the 20th century.
References
Bipolar disorder in children and adolescents: treatment and diagnosis: new treatment guidelines available. (2005). The Brown University Psychopharmacology Update, 16(4), 1+. https://link.gale.com/apps/doc/A130389603/AONE?u=mcc_main&sid=AONE&xid=5c0b7c9e
Mahoney, D. (2004). More studies on bipolar disorder sorely needed. Clinical Psychiatry News, 32(3), 50. https://link.gale.com/apps/doc/A115228271/AONE?u=mcc_main&sid=AONE&xid=44d846bd
Wendling, P. (2009). Stimulant use in ADHD, bipolar discouraged: expert in mood disorders cites evidence showing that amphetamines might worsen both illnesses. Clinical Psychiatry News, 37(8), 16. https://link.gale.com/apps/doc/A207123442/AONE?u=mcc_main&sid=AONE&xid=c58b5005
External links
International Society for Bipolar Disorders Task Force report on current knowledge in pediatric bipolar disorder and future directions |
Mycoplasma | Mycoplasma is a genus of bacteria that, like the other members of the class Mollicutes, lack a cell wall around their cell membranes. Peptidoglycan (murein) is absent. This characteristic makes them naturally resistant to antibiotics that target cell wall synthesis (like the beta-lactam antibiotics). They can be parasitic or saprotrophic. Several species are pathogenic in humans, including M. pneumoniae, which is an important cause of "walking" pneumonia and other respiratory disorders, and M. genitalium, which is believed to be involved in pelvic inflammatory diseases. Mycoplasma species (like the other species of the class Mollicutes) are among the smallest organisms yet discovered, can survive without oxygen, and come in various shapes. For example, M. genitalium is flask-shaped (about 300 x 600 nm), while M. pneumoniae is more elongated (about 100 x 1000 nm), many Mycoplasma species are coccoid. Hundreds of Mycoplasma species infect animals.The trivial name “mycoplasma” (plural mycoplasmas or mycoplasms) is commonly used for all members of the class Mollicutes. In scientific classification, the designation Mycoplasma refers exclusively to the genus, a member of the Mycoplasmataceae, the only family of the order Mycoplasmatales (see “scientific classification”).
Etymology
The term "mycoplasma", from the Greek μύκης, mykes (fungus) and πλάσμα, plasma (formed), was first used by Albert Bernhard Frank in 1889 to describe an altered state of plant cell cytoplasm resulting from infiltration by fungus-like microorganisms. Julian Nowak later proposed the name mycoplasma for certain filamentous microorganisms imagined to have both cellular and acellular stages in their lifecycles, which could explain how they were visible with a microscope, but passed through filters impermeable to other bacteria. Later, the name for these mycoplasmas was pleuropneumonia-like organisms (PPLO), broadly referring to organisms similar in colonial morphology and filterability to the causative agent (a Mycoplasma species) of contagious bovine pleuropneumonia. At present, all these organisms are classified as Mollicutes and the term Mycoplasma refers solely to the genus.
Species that infect humans
Species of Mycoplasma, other than those listed below, have been recovered from humans, but are assumed to have been contracted from a non-human host. The following species use humans as the primary host:
Pathophysiology
Mycoplasma species have been isolated from women with bacterial vaginosis. M. genitalium is found in women with pelvic inflammatory disease. In addition, infection is associated with increased risk of cervicitis, infertility, preterm birth and spontaneous abortion. Mycoplasma genitalium has developed resistance to some antibiotics. Mycoplasma species are associated with infant respiratory distress syndrome, bronchopulmonary dysplasia, and intraventricular hemorrhage in preterm infants.
Characteristics
Over 100 species have been included in the genus Mycoplasma, a member of the class Mollicutes. They are parasites or commensals of humans, animals, and plants. The genus Mycoplasma uses vertebrate and arthropod hosts.
Dietary nitrogen availability has been shown to alter codon bias and genome evolution in Mycoplasma and Phytoplasma.Mycoplasma species are among the smallest free-living organisms (about 0.2 - 0.3 µm in diameter). They have been found in the pleural cavities of cattle suffering from pleuropneumonia. These organisms are often called MLO (mycoplasma-like organisms) or, formerly, PPLO (pleuropneumonia-like organisms).
Important characteristics of Mycoplasma species
Cell wall is absent and plasma membrane forms the outer boundary of the cell.
Due to the absence of cell walls these organisms can change their shape and are pleomorphic.
Lack of nucleus and other membrane-bound organelles.
Genetic material is a single DNA duplex and is naked.
Ribosomes are 70S type.
Possess a replicating disc at one end which assists replication process and also the separation of the genetic materials.
Heterotrophic nutrition. Some live as saprophytes but the majority are parasites of plants and animals. The parasitic nature is due to the inability of mycoplasmal bacteria to synthesise the required growth factor.
Cell and colony morphology
Due to the lack of a rigid cell wall, Mycoplasma species (like all Mollicutes) can contort into a broad range of shapes, from round to oblong. They are pleomorphic and therefore cannot be identified as rods, cocci or spirochetes.Colonies show the typical „fried egg” appearance (about 0.5 mm in diameter).
Reproduction
In 1954, using phase-contrast microscopy, continual observations of live cells have shown that Mycoplasma species ("mycoplasmas", formerly called pleuropneumonia-like organisms, PPLO, now classified as Mollicutes) and L-form bacteria (previously also called L-phase bacteria) do not proliferate by binary fission, but by a uni- or multi-polar budding mechanism. Microphotograph series of growing microcultures of different strains of PPLOs, L-form bacteria and, as a control, a Micrococcus species (dividing by binary fission) have been presented. Additionally, electron microscopic studies have been performed.
Phylogeny
Previously, Mycoplasma species (often commonly called "mycoplasmas", now classified as Mollicutes) were sometimes considered stable L-form bacteria or even viruses, but phylogenetic analysis has identified them as bacteria that have lost their cell walls in the course of evolution.The genus Mycoplasma as originally described is highly paraphyletic, as such it was redescibed by Gupta et al. 2018 and its emendation was accompanied by the removal of 78 species. The currently accepted taxonomy is based on the List of Prokaryotic names with Standing in Nomenclature (LPSN) and National Center for Biotechnology Information (NCBI)
Unassigned species:
Laboratory contaminant
Mycoplasma species are often found in research laboratories as contaminants in cell culture. Mycoplasmal cell culture contamination occurs due to contamination from individuals or contaminated cell culture medium ingredients. Mycoplasma cells are physically small – less than 1 µm, so are difficult to detect with a conventional microscope.Mycoplasmae may induce cellular changes, including chromosome aberrations, changes in metabolism and cell growth. Severe Mycoplasma infections may destroy a cell line. Detection techniques include DNA probe, enzyme immunoassays, PCR, plating on sensitive agar and staining with a DNA stain including DAPI or Hoechst.An estimated 11 to 15% of U.S. laboratory cell cultures are contaminated with mycoplasma.
A Corning study showed that half of U.S. scientists did not test for Mycoplasma contamination in their cell cultures. The study also stated that, in former Czechoslovakia, 100% of cell cultures that were not routinely tested were contaminated while only 2% of those routinely tested were contaminated (study p. 6). Since the U.S. contamination rate was based on a study of companies that routinely checked for Mycoplasma, the actual contamination rate may be higher. European contamination rates are higher and that of other countries are higher still (up to 80% of Japanese cell cultures).
About 1% of published Gene Expression Omnibus data may have been compromised. Several antibiotic-containing formulations of antimycoplasmal reagents have been developed over the years.
Synthetic mycoplasma genome
A chemically synthesized genome of a mycoplasmal cell based entirely on synthetic DNA which can self-replicate has been referred to as Mycoplasma laboratorium.
Pathogenicity
The P1 antigen is the primary virulence factor of mycoplasma. P1 is a membrane associated protein that allows adhesion to epithelial cells. The P1 receptor is also expressed on erythrocytes which can lead to autoantibody agglutination from mycobacteria infection. Several Mycoplasma species can cause disease, including M. pneumoniae, which is an important cause of atypical pneumonia (formerly known as "walking pneumonia"), and M. genitalium, which has been associated with pelvic inflammatory diseases. Mycoplasma infections in humans are associated with skin eruptions in 17% of cases.: 293
Sexually transmitted infections
Mycoplasma and Ureaplasma species are not part of the normal vaginal flora. Some Mycoplasma species are spread through sexual contact.
Infertility
Some Mycoplasma species have a negative effect on fertility. M. hominis causes male sterility/Genitals inflammation in humans.
Infant mortality
Low birth-weight, preterm infants are susceptible to Mycoplasma infections.
Links to cancer
Several species of Mycoplasma are frequently detected in different types of cancer cells. These species are:
M. fermentans
M. genitalium
M. hyorhinis
M. penetrans
U. urealyticumThe majority of these Mycoplasma species have shown a strong correlation to malignant transformation in mammalian cells in vitro.
Mycoplasma infection and host cell transformation
The presence of Mycoplasma was first reported in samples of cancer tissue in the 1960s. Since then, several studies tried to find and prove the connection between Mycoplasma and cancer, as well as how the bacterium might be involved in the formation of cancer. Several studies have shown that cells that are chronically infected with the bacteria go through a multistep transformation. The changes caused by chronic mycoplasmal infections occur gradually and are both morphological and genetic. The first visual sign of infection is when the cells gradually shift from their normal form to sickle-shaped. They also become hyperchromatic due to an increase of DNA in the nucleus of the cells. In later stages, the cells lose the need for solid support to grow and proliferate, as well as the normal contact-dependent inhibition cells.
Possible intracellular mechanisms of mycoplasmal malignant transformation
Karyotypic changes related to mycoplasma infections
Cells infected with Mycoplasma for an extended period of time show significant chromosomal abnormalities. These include the addition of chromosomes, the loss of entire chromosomes, partial loss of chromosomes, and chromosomal translocation. All of these genetic abnormalities may contribute to the process of malignant transformation. Chromosomal translocation and extra chromosomes help create abnormally high activity of certain proto-oncogenes, which caused by these genetic abnormalities and include those encoding c-myc, HRAS, and vav. The activity of proto-oncogenes is not the only cellular function that is affected; tumour suppressor genes are affected by the chromosomal changes induced by mycoplasma, as well. Partial or complete loss of chromosomes causes the loss of important genes involved in the regulation of cell proliferation. Two genes whose activities are markedly decreased during chronic infections with mycoplasma are the Rb and the p53 tumour suppressor genes. Another possible mechanism of carcinogenesis is RAC1 activation by a small GTPase-like protein fragment of Mycoplasma. A major feature that differentiates mycoplasmas from other carcinogenic pathogens is that the mycoplasmas do not cause the cellular changes by insertion of their own genetic material into the host cell. The exact mechanism by which the bacterium causes the changes is not yet known.
Partial reversibility of malignant transformationsThe malignant transformation induced by Mycoplasma species is also different from that caused by other pathogens in that the process is reversible. The state of reversal is, however, only possible up to a certain point during the infection. The window of time when reversibility is possible varies greatly; it depends primarily on the Mycoplasma involved. In the case of M. fermentans, the transformation is reversible until around week 11 of infection and starts to become irreversible between weeks 11 and 18. If the bacteria are killed using antibiotics (i.e. ciprofloxacin or Clarithromycin) before the irreversible stage, the infected cells should return to normal.
Connections to cancer in vivo and future research
Epidemiologic, genetic, and molecular studies suggest infection and inflammation initiate certain cancers, including those of the prostate. M. genitalium and M. hyorhinis induce malignant phenotype in benign human prostate cells (BPH-1) that were not tumorigenic after 19 weeks of exposure.
Types of cancer associated with Mycoplasma
Colon cancer: In a study to understand the effects of Mycoplasma contamination on the quality of cultured human colon cancer cells, a positive correlation was found between the number of M. hyorhinis cells present in the sample and the percentage of CD133-positive cells (a glycoprotein with an unknown function).Gastric cancer: Strong evidence indicates the infection of M. hyorhinis contributes to the development of cancer within the stomach and increases the likelihood of malignant cancer cell development.Lung cancer: Studies on lung cancer have supported the belief that more than a coincidental positive correlation exists between the appearance of Mycoplasma strains in patients and the infection with tumorigenesis.Prostate cancer: p37, a protein encoded for by M. hyorhinis, has been found to promote the invasiveness of prostate cancer cells. The protein also causes the growth, morphology, and gene expression of the cells to change, causing them to become a more aggressive phenotype.Renal cancer: Patients with renal cell carcinoma (RCC) exhibited a significantly high amount of Mycoplasma sp. compared with the healthy control group. This suggests Mycoplasma may play a role in the development of RCC.
See also
International Organization for Mycoplasmology (IOM)
Sexually transmitted disease
Vaginal flora
Vaginal infection
Vaginal disease
Vaginal health
Phytoplasma
List of bacterial orders
List of bacteria genera
References
== External links == |
Pulmonary insufficiency | Pulmonary (or pulmonic) insufficiency (or incompetence, or regurgitation) is a condition in which the pulmonary valve is incompetent and allows backflow from the pulmonary artery to the right ventricle of the heart during diastole. While a small amount of backflow may occur ordinarily, it is usually only shown on an echocardiogram and is harmless. More pronounced regurgitation that is noticed through a routine physical examination is a medical sign of disease and warrants further investigation. If it is secondary to pulmonary hypertension it is referred to as a Graham Steell murmur.
Signs and symptoms
Because pulmonic regurgitation is the result of other factors in the body, any noticeable symptoms are ultimately caused by an underlying medical condition rather than the regurgitation itself. However, more severe regurgitation may contribute to right ventricular enlargement by dilation, and in later stages, right heart failure. A diastolic decrescendo murmur can sometimes be identified,( heard best) over the left lower sternal border.
Causes
Among the causes of pulmonary insufficiency are:
Pathophysiology
The pathophysiology is due to diastolic pressure variations between the pulmonary artery and right ventricle, differences are often very small, but increase regurgitation. An elevation in pulmonary insufficiency due to elevated intrathoracic pressure is relevant in ventilated patients (having acute restrictive right ventricular physiology). The reasons for changes in stiffness of the right ventricles walls are not well understood, but such stiffness is thought to increase with hypertrophy of the ventricle.
Diagnosis
In the diagnosis of pulmonary insufficiency both echocardiograms and ECG is used to ascertain if the individual has this condition, as well as, the use of a chest x-ray to expose enlargement of the right atrium or ventricle.
Treatment
In treating pulmonary insufficiency, it should be determined if pulmonary hypertension is causing the problem to therefore begin the most appropriate therapy as soon as possible (primary pulmonary hypertension or secondary pulmonary hypertension due to thromboembolism). Furthermore, pulmonary insufficiency is generally treated by addressing the underlying condition, in certain cases, the pulmonary valve may be surgically replaced.
See also
Pulmonary valve stenosis
References
Further reading
Lake, Carol L.; Booker, Peter D. (2005-01-01). Pediatric Cardiac Anesthesia. Lippincott Williams & Wilkins. ISBN 9780781751759.
Bruce, Charles J.; Connolly, Heidi M. (2009-05-26). "Right-Sided Valve Disease Deserves a Little More Respect". Circulation. 119 (20): 2726–2734. doi:10.1161/CIRCULATIONAHA.108.776021. ISSN 0009-7322. PMID 19470901.
M.D, Steven Lehrer (2011-12-27). Understanding Pediatric Heart Sounds. Steven Lehrer. ISBN 9781468138030.
External links
"Problem: Pulmonary Valve Regurgitation". www.heart.org. Retrieved 2015-08-29. |
Stomach cancer | Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lymphomas and mesenchymal tumors may also develop in the stomach. Early symptoms may include heartburn, upper abdominal pain, nausea, and loss of appetite. Later signs and symptoms may include weight loss, yellowing of the skin and whites of the eyes, vomiting, difficulty swallowing, and blood in the stool, among others. The cancer may spread from the stomach to other parts of the body, particularly the liver, lungs, bones, lining of the abdomen, and lymph nodes.The most common cause is infection by the bacterium Helicobacter pylori, which accounts for more than 60% of cases. Certain types of H. pylori have greater risks than others. Smoking, dietary factors such as pickled vegetables and obesity are other risk factors. About 10% of cases run in families, and between 1% and 3% of cases are due to genetic syndromes inherited from a persons parents such as hereditary diffuse gastric cancer. Most of the time, stomach cancer develops in stages over years. Diagnosis is usually by biopsy done during endoscopy. This is followed by medical imaging to determine if the disease has spread to other parts of the body. Japan and South Korea, two countries that have high rates of the disease, screen for stomach cancer.A Mediterranean diet lowers the risk of stomach cancer, as does the stopping of smoking. Tentative evidence indicates that treating H. pylori decreases the future risk. If stomach cancer is treated early, it can be cured. Treatments may include some combination of surgery, chemotherapy, radiation therapy, and targeted therapy. For certain subtypes of gastric cancer, cancer immunotherapy is an option as well. If treated late, palliative care may be advised. Some types of lymphoma can be cured by eliminating H. pylori. Outcomes are often poor, with a less than 10% five-year survival rate in the Western world for advanced cases. This is largely because most people with the condition present with advanced disease. In the United States, five-year survival is 31.5%, while in South Korea it is over 65% and Japan over 70%, partly due to screening efforts.Globally, stomach cancer is the fifth-leading type of cancer and the third-leading cause of death from cancer, making up 7% of cases and 9% of deaths. In 2018, it newly occurred in 1.03 million people and caused 783,000 deaths. Before the 1930s, in much of the world, including most Western developed countries, it was the most common cause of death from cancer. Rates of death have been decreasing in many areas of the world since then. This is believed to be due to the eating of less salted and pickled foods as a result of the development of refrigeration as a method of storing food. Stomach cancer occurs most commonly in East Asia and Eastern Europe. It occurs twice as often in males as in females.
Signs and symptoms
Stomach cancer is often either asymptomatic (producing no noticeable symptoms) or it may cause only nonspecific symptoms (which may also be present in other related or unrelated disorders) in its early stages. By the time symptoms are recognized, the cancer has often reached an advanced stage (see below) and may have metastasized (spread to other, perhaps distant, parts of the body), which is one of the main reasons for its relatively poor prognosis. Stomach cancer can cause the following signs and symptoms: Unexplained nausea, vomiting, diarrhoea and constipation. Patients also can experience unexplained weight loss.Early cancers may be associated with indigestion or a burning sensation (heartburn). However, fewer than one in every 50 people referred for endoscopy due to indigestion has cancer. Abdominal discomfort and loss of appetite, especially for meat, can occur.Gastric cancers that have enlarged and invaded normal tissue can cause weakness, fatigue, bloating of the stomach after meals, abdominal pain in the upper abdomen, nausea and occasional vomiting. Further enlargement may cause weight loss or bleeding with vomiting blood or having blood in the stool, the latter apparent as black discolouration (melena) and sometimes leading to anemia. Dysphagia suggests a tumour in the cardia or extension of the gastric tumour into the esophagus.These can be symptoms of other problems such as a stomach virus, gastric ulcer, or tropical sprue.
Risk factors
Gastric cancer can occur as a result of many factors. It occurs twice as commonly in males as females. Estrogen may protect women against the development of this form of cancer.
Infections
Helicobacter pylori infection is an essential risk factor in 65–80% of gastric cancers, but only 2% of people with H. pylori infections develop stomach cancer. The mechanism by which H. pylori induces stomach cancer potentially involves chronic inflammation, or the action of H. pylori virulence factors such as CagA. It was estimated that Epstein–Barr virus is responsible for 84,000 cases per year. AIDS is also associated with elevated risk.
Smoking
Smoking increases the risk of developing gastric cancer significantly, from 40% increased risk for current smokers to 82% increase for heavy smokers. Gastric cancers due to smoking mostly occur in the upper part of the stomach near the esophagus. Some studies show increased risk with alcohol consumption as well.
Diet
Dietary factors are not proven causes, and the association between stomach cancer and various foods and beverages is weak. Some foods including smoked foods, salt and salt-rich foods, red meat, processed meat, pickled vegetables, and brackens are associated with a higher risk of stomach cancer. Nitrates and nitrites in cured meats can be converted by certain bacteria, including H. pylori, into compounds that have been found to cause stomach cancer in animals.Fresh fruit and vegetable intake, citrus fruit intake, and antioxidant intake are associated with a lower risk of stomach cancer. A Mediterranean diet is associated with lower rates of stomach cancer, as is regular aspirin use.Obesity is a physical risk factor that has been found to increase the risk of gastric adenocarcinoma by contributing to the development of gastroesophageal reflux disease (GERD). The exact mechanism by which obesity causes GERD is not completely known. Studies hypothesize that increased dietary fat leading to increased pressure on the stomach and the lower esophageal sphincter, due to excess adipose tissue, could play a role, yet no statistically significant data have been collected. However, the risk of gastric cardia adenocarcinoma, with GERD present, has been found to increase more than 2 times for an obese person. There is a correlation between iodine deficiency and gastric cancer.
Genetics
About 10% of cases run in families, and between 1 and 3% of cases are due to genetic syndromes inherited from a persons parents such as hereditary diffuse gastric cancer.A genetic risk factor for gastric cancer is a genetic defect of the CDH1 gene known as hereditary diffuse gastric cancer (HDGC). The CDH1 gene, which codes for E-cadherin, lies on the 16th chromosome. When the gene experiences a particular mutation, gastric cancer develops through a mechanism that is not fully understood. This mutation is considered autosomal dominant, meaning that half of a carriers children will likely experience the same mutation. Diagnosis of hereditary diffuse gastric cancer usually takes place when at least two cases involving a family member, such as a parent or grandparent, are diagnosed, with at least one diagnosed before the age of 50. The diagnosis can also be made if at least three cases occur in the family, in which case age is not considered.The International Cancer Genome Consortium is leading efforts to identify genomic changes involved in stomach cancer. A very small percentage of diffuse-type gastric cancers (see Histopathology below) arise from an inherited abnormal CDH1 gene. Genetic testing and treatment options are available for families at risk.
Other
Other risk factors include diabetes, pernicious anemia, chronic atrophic gastritis, Menetriers disease (hyperplastic, hypersecretory gastropathy), and intestinal metaplasia.In addition, Foxp3 polymorphism (rs3761548) might contribute to gastric cancer development through influencing Treg cell activity.
Diagnosis
To find the cause of symptoms, the doctor asks about the patients medical history, does a physical examination, and may order laboratory studies.
The patient may also have one or all of these exams:
Gastroscopic exam is the diagnostic method of choice. This involves insertion of a fibre optic camera into the stomach to visualise it.
Upper GI series (may be called barium roentgenogram)
Computed tomography or CT scanning of the abdomen may reveal gastric cancer. It is more useful to determine invasion into adjacent tissues or the presence of spread to local lymph nodes. Wall thickening of more than 1 cm that is focal, eccentric, and enhancing favours malignancy.In 2013, Chinese and Israeli scientists reported a successful pilot study of a breathalyzer-style breath test intended to diagnose stomach cancer by analyzing exhaled chemicals without the need for an intrusive endoscopy. A larger-scale clinical trial of this technology was completed in 2014.Abnormal tissue seen in a gastroscope examination is biopsied by the surgeon or gastroenterologist. This tissue is then sent to a pathologist for histological examination under a microscope to check for the presence of cancerous cells. A biopsy, with subsequent histological analysis, is the only sure way to confirm the presence of cancer cells.Various gastroscopic modalities have been developed to increase yield of detected mucosa with a dye that accentuates the cell structure and can identify areas of dysplasia. Endocytoscopy involves ultra-high magnification to visualise cellular structure to better determine areas of dysplasia. Other gastroscopic modalities such as optical coherence tomography are being tested investigationally for similar applications.A number of cutaneous conditions are associated with gastric cancer. A condition of darkened hyperplasia of the skin, frequently of the axilla and groin, known as acanthosis nigricans, is associated with intra-abdominal cancers such as gastric cancer. Other cutaneous manifestations of gastric cancer include "tripe palms" (a similar darkening hyperplasia of the skin of the palms) and the Leser-Trelat sign, which is the rapid development of skin lesions known as seborrheic keratoses.Various blood tests may be done, including a complete blood count to check for anaemia, and a fecal occult blood test to check for blood in the stool.
Histopathology
Gastric adenocarcinoma is a malignant epithelial tumour, originating from glandular epithelium of the gastric mucosa. Stomach cancers are about 90% adenocarcinomas. Histologically, there are two major types of gastric adenocarcinoma (Lauren classification): intestinal type or diffuse type. Adenocarcinomas tend to aggressively invade the gastric wall, infiltrating the muscularis mucosae, the submucosa and then the muscularis propria. Intestinal type adenocarcinoma tumour cells describe irregular tubular structures, harbouring pluristratification, multiple lumens, reduced stroma ("back to back" aspect). Often, it associates intestinal metaplasia in neighbouring mucosa. Depending on glandular architecture, cellular pleomorphism and mucosecretion, adenocarcinoma may present 3 degrees of differentiation: well, moderate and poorly differentiated. Diffuse type adenocarcinoma (mucinous, colloid, linitis plastica or leather-bottle stomach) tumour cells are discohesive and secrete mucus, which is delivered in the interstitium, producing large pools of mucus/colloid (optically "empty" spaces). It is poorly differentiated. In signet-ring cell carcinomas, the mucus remains inside the tumour cell and pushes the nucleus to the periphery, giving rise to signet-ring cells.
Around 5% of gastric cancers are lymphomas. These may include extranodal marginal zone B-cell lymphomas (MALT type) and to a lesser extent diffuse large B-cell lymphomas. MALT type make up about half of stomach lymphomas.
Carcinoid and stromal tumors may occur.
Staging
If cancer cells are found in the tissue sample, the next step is to stage, or find out the extent of the disease. Various tests determine whether the cancer has spread, and if so, what parts of the body are affected. Because stomach cancer can spread to the liver, pancreas, and other organs near the stomach, as well as to the lungs, the doctor may order a CT scan, a PET scan, an endoscopic ultrasound exam, or other tests to check these areas. Blood tests for tumor markers, such as carcinoembryonic antigen and carbohydrate antigen may be ordered, as their levels correlate to extent of metastasis, especially to the liver, and the cure rate.Staging may not be complete until after surgery. The surgeon removes nearby lymph nodes and possibly samples of tissue from other areas in the abdomen for examination by a pathologist.The clinical stages of stomach cancer are:
Stage 0 – Limited to the inner lining of the stomach, it is treatable by endoscopic mucosal resection when found very early (in routine screenings), or otherwise by gastrectomy and lymphadenectomy without need for chemotherapy or radiation.
Stage I – Penetration to the second or third layers of the stomach (stage 1A) or to the second layer and nearby lymph nodes (stage 1B): Stage 1A is treated by surgery, including removal of the omentum. Stage 1B may be treated with chemotherapy (5-fluorouracil) and radiation therapy.
Stage II – Penetration to the second layer and more distant lymph nodes, or the third layer and only nearby lymph nodes, or all four layers but not the lymph nodes, it is treated as for stage I, sometimes with additional neoadjuvant chemotherapy.
Stage III – Penetration to the third layer and more distant lymph nodes, or penetration to the fourth layer and either nearby tissues or nearby or more distant lymph nodes, it is treated as for stage II; a cure is still possible in some cases.
Stage IV – Cancer has spread to nearby tissues and more distant lymph nodes, or has metastasized to other organs. A cure is very rarely possible at this stage. Some other techniques to prolong life or improve symptoms are used, including laser treatment, surgery, and/or stents to keep the digestive tract open, and chemotherapy by drugs such as 5-fluorouracil, cisplatin, epirubicin, etoposide, docetaxel, oxaliplatin, capecitabine, or irinotecan.
The TNM staging system is also used.In a study of open-access endoscopy in Scotland, patients were diagnosed 7% in stage I, 17% in stage II, and 28% in stage III. A Minnesota population was diagnosed 10% in stage I, 13% in stage II, and 18% in stage III. However, in a high-risk population in the Valdivia Province of southern Chile, only 5% of patients were diagnosed in the first two stages and 10% in stage III.
Prevention
Getting rid of H. pylori in those who are infected decreases the risk of stomach cancer, at least in those who are Asian. A 2014 meta-analysis of observational studies found that a diet high in fruits, mushrooms, garlic, soybeans, and green onions was associated with a lower risk of stomach cancer in the Korean population. Low doses of vitamins, especially from a healthy diet, decrease the risk of stomach cancer. A previous review of antioxidant supplementation did not find supporting evidence and possibly worse outcomes.
Management
Cancer of the stomach is difficult to cure unless it is found at an early stage (before it has begun to spread). Unfortunately, because early stomach cancer causes few symptoms, the disease is usually advanced when the diagnosis is made.Treatment for stomach cancer may include surgery, chemotherapy, or radiation therapy. New treatment approaches such as immunotherapy or gene therapy and improved ways of using current methods are being studied in clinical trials.
Surgery
Surgery remains the only curative therapy for stomach cancer. Of the different surgical techniques, endoscopic mucosal resection (EMR) is a treatment for early gastric cancer (tumor only involves the mucosa) that was pioneered in Japan and is available in the United States at some centers. In EMR, the tumor, together with the inner lining of stomach (mucosa), is removed from the wall of the stomach using an electrical wire loop through the endoscope. The advantage is that it is a much smaller operation than removing the stomach. Endoscopic submucosal dissection is a similar technique pioneered in Japan, used to resect a large area of mucosa in one piece. If the pathologic examination of the resected specimen shows incomplete resection or deep invasion by tumor, the patient would need a formal stomach resection. A 2016 Cochrane review found low-quality evidence of no difference in short-term mortality between laparoscopic and open gastrectomy (removal of stomach), and that benefits or harms of laparoscopic gastrectomy cannot be ruled out. Post-operatively, up to 70% of people undergoing total gastrectomy develop complications such as dumping syndrome and reflux esophagitis. Construction of a "pouch", which serves as a "stomach substitute", reduced the incidence of dumping syndrome and reflux esophagitis by 73% and 63% respectively, and led to improvements in quality-of-life, nutritional outcomes, and body mass index.Those with metastatic disease at the time of presentation may receive palliative surgery, and while it remains controversial, due to the possibility of complications from the surgery itself and because it may delay chemotherapy, the data so far are mostly positive, with improved survival rates being seen in those treated with this approach.
Chemotherapy
The use of chemotherapy to treat stomach cancer has no firmly established standard of care. Unfortunately, stomach cancer has not been particularly sensitive to these drugs, and chemotherapy, if used, has usually served to palliatively reduce the size of the tumor, relieve symptoms of the disease, and increase survival time. Some drugs used in stomach cancer treatment have included: fluorouracil or its analog capecitabine, BCNU (carmustine), methyl-CCNU (semustine) and doxorubicin (Adriamycin), as well as mitomycin C, and more recently cisplatin and taxotere, often using drugs in various combinations. The relative benefits of these different drugs, alone and in combination, are unclear. Clinical researchers are exploring the benefits of giving chemotherapy before surgery to shrink the tumor, or as adjuvant therapy after surgery to destroy remaining cancer cells.
Targeted therapy
Recently, treatment with human epidermal growth factor receptor 2 (HER2) inhibitor, trastuzumab, has been demonstrated to increase overall survival in inoperable locally advanced or metastatic gastric carcinoma over-expressing the HER2/neu gene. In particular, HER2 is overexpressed in 13–22% of patients with gastric cancer. Of note, HER2 overexpression in gastric neoplasia is heterogeneous and comprises a minority of tumor cells (less than 10% of gastric cancers overexpress HER2 in more than 5% of tumor cells). Hence, this heterogeneous expression should be taken into account for HER2 testing, particularly in small samples such as biopsies, requiring the evaluation of more than one bioptic sample.
Radiation
Radiation therapy (also called radiotherapy) may be used to treat stomach cancer, often as an adjuvant to chemotherapy and/or surgery.
Lymphoma
MALT lymphomas can often be fully treated by treating an underlying H. pylori infection. This results in remission in about 80% of cases.
Prognosis
The prognosis of stomach cancer is generally poor, because the tumor has often metastasized by the time of discovery, and most people with the condition are elderly (median age is between 70 and 75 years) at presentation. The average life expectancy after being diagnosed is around 24 months, and the five-year survival rate for stomach cancer is less than 10%.Almost 300 genes are related to outcomes in stomach cancer, with both unfavorable genes where high expression is related to poor survival and favorable genes where high expression is associated with longer survival times. Examples of poor prognosis genes include ITGAV, DUSP1 and P2RX7.
Epidemiology
Worldwide, stomach cancer is the fifth most-common cancer with 952,000 cases diagnosed in 2012. It is more common both in men and in developing countries. In 2012, it represented 8.5% of cancer cases in men, making it the fourth-most common cancer in men. Also in 2012, the number of deaths was 700,000, having decreased slightly from 774,000 in 1990, making it the third-leading cause of cancer-related death (after lung cancer and liver cancer).Less than 5% of stomach cancers occur in people under 40 years of age, with 81.1% of that 5% in the age-group of 30 to 39 and 18.9% in the age-group of 20 to 29.In 2014, stomach cancer resulted in 0.61% of deaths (13,303 cases) in the U.S. In China, stomach cancer accounted for 3.56% of all deaths (324,439 cases). The highest rate of stomach cancer was in Mongolia, at 28 cases per 100,000 people.In the United Kingdom, stomach cancer is the 15th-most common cancer (around 7,100 people were diagnosed with stomach cancer in 2011), and it is the 10th-most common cause of cancer-related deaths (around 4,800 people died in 2012).Incidence and mortality rates of gastric cancer vary greatly in Africa. The GLOBOCAN system is currently the most widely used method to compare these rates between countries, but African incidence and mortality rates are seen to differ among countries, possibly due to the lack of universal access to a registry system for all countries. Variation as drastic as estimated rates from 0.3/100000 in Botswana to 20.3/100000 in Mali have been observed. In Uganda, the incidence of gastric cancer has increased from the 1960s measurement of 0.8/100000 to 5.6/100000. Gastric cancer, though present, is relatively low when compared to countries with high incidence like Japan and China. One suspected cause of the variation within Africa and between other countries is due to different strains of the H. pylori bacteria. The trend commonly seen is that H. pylori infection increases the risk for gastric cancer, but this is not the case in Africa, giving this phenomenon the name the "African enigma". Although this bacterial species is found in Africa, evidence has supported that different strains with mutations in the bacterial genotype may contribute to the difference in cancer development between African countries and others outside the continent. Increasing access to health care and treatment measures have been commonly associated with the rising incidence, though, particularly in Uganda.
Other animals
The stomach is a muscular organ of the gastrointestinal tract that holds food and begins the digestive process by secreting gastric juice. The most common cancers of the stomach are adenocarcinomas, but other histological types have been reported. Signs vary, but may include vomiting (especially if blood is present), weight loss, anemia, and lack of appetite. Bowel movements may be dark and tarry in nature. To determine whether cancer is present in the stomach, special X-rays and/or abdominal ultrasounds may be performed. Gastroscopy, a test using an endoscope to examine the stomach, is a useful diagnostic tool that can also take samples of the suspected mass for histopathological analysis to confirm or rule out cancer. The most definitive method of cancer diagnosis is through open surgical biopsy. Most stomach tumors are malignant with evidence of spread to lymph nodes or liver, making treatment difficult. Except for lymphoma, surgery is the most frequent treatment option for stomach cancers but it is associated with significant risks.
References
External links
National Cancer Institute Gastric cancer treatment guidelines |
Snoring | Snoring is the vibration of respiratory structures and the resulting sound due to obstructed air movement during breathing while sleeping. The sound may be soft or loud and unpleasant. Snoring during sleep may be a sign, or first alarm, of obstructive sleep apnea (OSA). Research suggests that snoring is one of the factors of sleep deprivation.
Causes
Snoring is the result of the relaxation of the uvula and soft palate. These tissues can relax enough to partially block the airway, resulting in irregular airflow and vibrations. Snoring can be attributed to one or more of the following:
Genetic predisposition, a proportion of which may be mediated through other heritable lifestyle factors such as body mass index, smoking and alcohol consumption.
Throat weakness, causing the throat to close during sleep.
Mispositioned jaw, often caused by tension in the muscles.
Obesity that has caused fat to gather in and around the throat.
Obstruction in the nasal passageway.
Obstructive sleep apnea.
Sleep deprivation.
Relaxants such as alcohol or other drugs relaxing throat muscles.
Sleeping on ones back, which may result in the tongue dropping to the back of the mouth.
Mouth breathing
Possible consequences
Snoring is known to cause sleep deprivation to snorers and those around them, as well as daytime drowsiness, irritability, lack of focus and decreased libido. It has also been suggested that it can cause significant psychological and social damage to those affected. Multiple studies reveal a positive correlation between loud snoring and risk of heart attack (about +34% chance) and stroke (about +67% chance).Though snoring is often considered a minor condition, snorers can sometimes experience severe impairment of lifestyle. The between-subjects trial by Armstrong et al. discovered a statistically significant improvement in marital relations after snoring was surgically corrected. This was confirmed by evidence from Gall et al., Cartwright and Knight and Fitzpatrick et al.Studies have associated loud snoring with the development of carotid artery atherosclerosis. Amatoury et al. demonstrated that snoring vibrations are transmitted to the carotid artery, identifying a possible mechanism for snoring-associated carotid artery damage and atherosclerotic plaque development. These researchers also found amplification of the snoring energy within the carotid lumen at certain frequencies, adding to this scenario. Vibration of the carotid artery with snoring also lends itself as a potential mechanism for atherosclerotic plaque rupture and consequently ischemic stroke. Researchers also hypothesize that loud snoring could create turbulence in carotid artery blood flow. Generally speaking, increased turbulence irritates blood cells and has previously been implicated as a cause of atherosclerosis. While there is plausibility and initial evidence to support snoring as an independent source of carotid artery/cardiovascular disease, additional research is required to further clarify this hypothesis.
Treatment
So far, there is no certain treatment that can completely stop snoring. Almost all treatments for snoring revolve around lessening the breathing discomfort by clearing the blockage in the air passage. Medications are usually not helpful in treating snoring symptoms, though they can help control some of the underlying causes such as nasal congestion and allergic reactions. Doctors, therefore, often recommend lifestyle changes as a first line treatment to stop snoring. This is the reason snorers are advised to lose weight (to stop fat from pressing on the throat), stop smoking (smoking weakens and clogs the throat), avoid alcohol and sedative medications before bedtime (they relax the throat and tongue muscles, which in turn narrow the airways) and sleep on their side (to prevent the tongue from blocking the throat).
A number of other treatment options are also used to stop snoring. These range from over-the-counter aids such as nasal sprays, nasal strips or nose clips, lubricating sprays, oral appliances and "anti-snore" clothing and pillows, to unusual activities such as playing the didgeridoo. However, one needs to be wary of over-the-counter snore treatments that have no scientific evidence to support their claims, such as stop-snore rings or wrist worn electrical stimulation bands.
Tongue exercises
Myofunctional therapy, which incorporates oropharyngeal and tongue exercises, reduces snoring in adults based on both subjective questionnaires and objective sleep studies. Snoring intensity was reduced by 51%.
Orthopedic pillows
Orthopedic pillows are the least intrusive option for reducing snoring. These pillows are designed to support the head and neck in a way that ensures the jaw stays open and slightly forward. This helps keep the airways unrestricted as possible and in turn leads to a small reduction in snoring.
Dental appliances
Specially made dental appliances called mandibular advancement splints, which advance the lower jaw slightly and thereby pull the tongue forward, are a common mode of treatment for snoring. Such appliances have been proven to be effective in reducing snoring and sleep apnea in cases where the apnea is mild to moderate. Mandibular advancement splints are often tolerated much better than CPAP machines.
Positive airway pressure
A continuous positive airway pressure (CPAP) machine is often used to control sleep apnea and the snoring associated with it. It is a relatively safe medical treatment. To keep the airway open, a device pumps a controlled stream of air through a flexible hose to a mask worn over the nose, mouth, or both. A CPAP is usually applied through a CPAP mask which is placed over the nose and/or mouth. The air pressure required to keep the airway open is delivered through this and it is attached to a CPAP machine which is like an air compressor.
The air that CPAP delivers is generally "normal air" – not concentrated oxygen. The machine utilizes the air pressure as an "air splint" to keep the airway open. In obstructive sleep apnea, the airway at the rear of the throat is prone to closure.
Surgery
Surgery is also available as a method of correcting social snoring. Some procedures, such as uvulopalatopharyngoplasty, attempt to widen the airway by removing tissues in the back of the throat, including the uvula and pharynx. These surgeries are quite invasive, however, and there are risks of adverse side effects. The most dangerous risk is that enough scar tissue could form within the throat as a result of the incisions to make the airway more narrow than it was prior to surgery, diminishing the airspace in the velopharynx. Scarring is an individual trait, so it is difficult for a surgeon to predict how much a person might be predisposed to scarring. Currently, the American Medical Association does not approve of the use of lasers to perform operations on the pharynx or uvula.
Radiofrequency ablation (RFA) is a relatively new surgical treatment for snoring. This treatment applies radiofrequency energy and heat (between 77 °C and 85 °C) to the soft tissue at the back of the throat, such as the soft palate and uvula, causing scarring of the tissue beneath the skin. After healing, this results in stiffening of the treated area. The procedure takes less than one hour, is usually performed on an outpatient basis, and usually requires several treatment sessions. Radiofrequency ablation is frequently effective in reducing the severity of snoring, but often does not eliminate it.Bipolar radiofrequency ablation, a technique used for coblation tonsillectomy, is also used for the treatment of snoring.
Pillar procedure
The pillar procedure is a minimally invasive treatment for snoring and obstructive sleep apnea. In the United States, this procedure was FDA indicated in 2004. During this procedure, three to six+ Dacron (the material used in permanent sutures) strips are inserted into the soft palate, using a modified syringe and local anesthetic. While the procedure was initially approved for the insertion of three "pillars" into the soft palate, it was found that there was a significant dosage response to more pillars, with appropriate candidates. As a result of this outpatient operation, which typically lasts no more than 30 minutes, the soft palate is more rigid, possibly reducing instances of sleep apnea and snoring. This procedure addresses one of the most common causes of snoring and sleep apnea — vibration or collapse of the soft palate (the soft part of the roof of the mouth). If there are other factors contributing to snoring or sleep apnea, such as conditions of the nasal airway or an enlarged tongue, it will likely need to be combined with other treatments to be more effective.
Alternative medicine
Among the natural remedies are exercises to increase the muscle tone of the upper airway, and one medical practitioner noting anecdotally that professional singers seldom snore, but there have been no medical studies to fully link the two.
Epidemiology
Statistics on snoring are often contradictory, but at least 30% of adults and perhaps as many as 50% of people in some demographics snore. One survey of 5,713 American residents identified habitual snoring in 24% of men and 13.8% of women, rising to 60% of men and 40% of women aged 60 to 65 years; this suggests an increased susceptibility to snoring with age.An observational study in the UK Biobank estimated that ~37% of 408,317 participants were habitual snorers, and confirmed positive associations with larger body-mass index, lower socio-economic status and more frequent smoking and alcohol consumption.
Further reading
Nestor, James (2020). Breath: The New Science of a Lost Art. Riverhead Books. ISBN 978-0735213616.
== References == |
Breech birth | A breech birth is when a baby is born bottom first instead of head first, as is normal. Around 3–5% of pregnant women at term (37–40 weeks pregnant) have a breech baby. Due to their higher than average rate of possible complications for the baby, breech births are generally considered higher risk. Breech births also occur in many other mammals such as dogs and horses, see veterinary obstetrics.
Most babies in the breech position are delivered via caesarean section because it is seen as safer than being born vaginally. Doctors and midwives in the developing world often lack many of the skills required to safely assist women giving birth to a breech baby vaginally. Also, delivering all breech babies by caesarean section in developing countries is difficult to implement as there are not always resources available to provide this service. OB-GYNs do not recommend home births if a breech birth is expected, even when attended by a medical professional.
Cause
With regard to the fetal presentation during pregnancy, three periods have been distinguished.During the first period, which lasts until the 24th gestational week, the incidence of a longitudinal lie increases, with equal proportions of breech or cephalic presentations from this lie. This period is characterized by frequent changes of presentations. The fetuses in breech presentation during this period have the same probability for breech and cephalic presentation at delivery.
During the second period, lasting from the 25th to the 35th gestational week, the incidence of cephalic presentation increases, with a proportional decrease of breech presentation. The second period is characterized by a higher than random probability that the fetal presentation during this period will also be present at the time of delivery. The increase of this probability is gradual and identical for breech and cephalic presentations during this period.
In the third period, from the 36th gestational week onward, the incidence of cephalic and breech presentations remain stable, i.e. breech presentation around 3–4% and cephalic presentation approximately 95%. In the general population, incidence of breech presentation at preterm corresponds to the incidence of breech presentation when birth occurs.A breech presentation at delivery occurs when the fetus does not turn to a cephalic presentation. This failure to change presentation can result from endogenous and exogenous factors. Endogenous factors involve fetal inability to adequately move, whereas exogenous factors refer to insufficient intrauterine space available for fetal movements.The incidence of breech presentation is affected by both maternal and fetal diseases and medical conditions. When these factors are present, the probability of breech presentation is between 4% and 50%.
Rates in various medical conditions
Fetal entities:
First twin 17–30%
Second twin 28–39%
Stillborn 26%
Prader–Willi syndrome 50%, Werdnig–Hoffman syndrome 10%
Smith–Lemli–Opitz syndrome 40%
Fetal alcohol syndrome 40%
Potter anomaly 36%
Zellweger syndrome 27%
Myotonic dystrophy 21%, 13 trisomy syndrome 12%
18 trisomy syndrome 43%
21 trisomy syndrome 5%
de Lange syndrome 10%
Anencephalus 6–18%, Spina bifida 20–30%
Congenital hydrocephalus 24–37%
Osteogenesis imperfecta 33.3%
Amyoplasia 33.3%
Achondrogenesis 33.3%
Amelia 50%
Craniosynostosis 8%
Sacral agenesis 30.4%
Arthrogriposis multiplex congenita 33.3
Congenital dislocation of the hip 33.3%
Hereditary sensory neuropathy type III 25%
Centronuclear myopathy 16.7%
Multiple pituitary hormone deficiency 50%
Isolated pituitary hormone deficiency 20%
Ectopic posterior pituitary gland 33.3%
Congenital bilateral perisilvian syndrome 33.3
Symmetric fetal growth restriction 40%
Asymmetric fetal growth restriction 40%
Nonimmune hydrops fetalis 15%
Atresia ani 18.2%
Microcephalus 15.4%
Omphalocele 12.5%
Prematurity 40%
Placental and amniotic fluid entities:
Amniotic sheet perpendicular to the placenta 50%
Cornual–fundal implantation of the placenta 30%
Placenta previa 12.5%
Oligohydramnios 17%
Polyhydramnios 15.8%
Maternal entities:
Uterus arcuatus 22.6%
Uterus unicornuatus 33.3%
Uterus bicornuatus 34.8%
Uterus didelphys 30–41%
Uterus septus 45.8%
Leiomyoma uteri 9–20%
Spinal cord injury 10%
Carriers of Duchenne muscular dystrophy 17%
Combination of two medical entities:
First twin in uterus with two bodies 14.29%
Second twin in uterus with two bodies 18.52%.Also, women with previous Caesarean deliveries have a risk of breech presentation at term twice that of women with previous vaginal deliveries.The highest possible probability of breech presentation of 50% indicates that breech presentation is a consequence of random filling of the intrauterine space, with the same probability of breech and cephalic presentation in a longitudinally elongated uterus.
Types
Types of breech depend on how the babys legs are lying.
A frank breech (otherwise known as an extended breech) is where the babys legs are up next to its abdomen, with its knees straight and its feet next to its ears. This is the most common type of breech.
A complete breech (or flexed breech) is when the baby appears as though it is sitting crossed-legged with its legs bent at the hips and knees.
A footling breech is when one or both of the babys feet are born first instead of the pelvis. This is more common in babies born prematurely or before their due date.
A kneeling breech is when the baby is born knees first.In addition to the above, breech births in which the sacrum is the fetal denominator can be classified by the position of a fetus. Thus sacro-anterior, sacro-transverse and sacro-posterior positions all exist, but left sacro-anterior is the most common presentation. Sacro-anterior indicates an easier delivery compared to other forms.
Complications
Umbilical cord prolapse may occur, particularly in the complete, footling, or kneeling breech. This is caused by the lowermost parts of the baby not completely filling the space of the dilated cervix. When the waters break the amniotic sac, it is possible for the umbilical cord to drop down and become compressed. This complication severely diminishes oxygen flow to the baby, so the baby must be delivered immediately (usually by Caesarean section) so that he or she can breathe. If there is a delay in delivery, the brain can be damaged. Among full-term, head-down babies, cord prolapse is quite rare, occurring in 0.4 percent. Among frank breech babies the incidence is 0.5 percent, among complete breeches 5 percent, and among footling breeches 15 percent.Head entrapment is caused by the failure of the fetal head to negotiate the maternal midpelvis. At full term, the fetal bitrochanteric diameter (the distance between the outer points of the hips) is about the same as the biparietal diameter (the transverse diameter of the skull)—simply put the size of the hips are the same as the size of the head. The relatively larger buttocks dilate the cervix as effectively as the head does in the typical head-down presentation. In contrast, the relative head size of a preterm baby is greater than the fetal buttocks. If the baby is preterm, it may be possible for the babys body to emerge while the cervix has not dilated enough for the head to emerge.
Because the umbilical cord—the babys oxygen supply—is significantly compressed while the head is in the pelvis during a breech birth, it is important that the delivery of the aftercoming fetal head not be delayed. If the arm is extended alongside the head, delivery will not occur. If this occurs, the Løvset manoeuvre may be employed, or the arm may be manually brought to a position in front of the chest. The Løvset manoeuvre involves rotating the fetal body by holding the fetal pelvis. Twisting the body such that an arm trails behind the shoulder, it will tend to cross down over the face to a position where it can be reached by the obstetricians finger, and brought to a position below the head. A similar rotation in the opposite direction is made to deliver the other arm. In order to present the smallest diameter (9.5 cm) to the pelvis, the babys head must be flexed (chin to chest). If the head is in a deflexed position, the risk of entrapment is increased. Uterine contractions and maternal muscle tone encourage the head to flex.
Oxygen deprivation may occur from either cord prolapse or prolonged compression of the cord during birth, as in head entrapment. If oxygen deprivation is prolonged, it may cause permanent neurological damage (for instance, cerebral palsy) or death. It has been suggested that a fast vaginal delivery would mean the risk of stopping babys oxygen supply is reduced. However, there is not enough research to show this and a quick delivery might cause more harm to the baby than a conservative approach to the birth.Injury to the brain and skull may occur due to the rapid passage of the babys head through the mothers pelvis. This causes rapid decompression of the babys head. In contrast, a baby going through labor in the head-down position usually experiences gradual molding (temporary reshaping of the skull) over the course of a few hours. This sudden compression and decompression in breech birth may cause no problems at all, but it can injure the brain. This injury is more likely in preterm babies. The fetal head may be controlled by a special two-handed grip call the Mauriceau–Smellie–Veit maneuver or the elective application of forceps. This will be of value in controlling the rate of delivery of the head and reduce decompression. Related to potential head trauma, researchers have identified a relationship between breech birth and autism.Squeezing the babys abdomen can damage internal organs. Positioning the baby incorrectly while using forceps to deliver the after coming head can damage the spine or spinal cord. It is important for the birth attendant to be knowledgeable, skilled, and experienced with all variations of breech birth.
Factors influencing safety
Birth attendants skill (and experience with breech birth) – The skill of the doctor or midwife and the number of breech births previously assisted is of crucial importance. Many of the dangers in vaginal birth for breech babies come from mistakes made by birth attendants. With the majority of breech babies being delivered by cesarean section there is more risk that birth attendants will lose their skills in delivering breech babies and therefore increase the risk of harm to the baby during a vaginal delivery.
Type of breech presentation – the frank breech has the most favorable outcomes in vaginal birth, with many studies suggesting no difference in outcome compared to head down babies. (Some studies, however, find that planned caesarean sections for all breech babies improve outcome. The difference may rest in part on the skill of the doctors who delivered babies in different studies.) Complete breech presentation is the next most favorable position, but these babies sometimes shift and become footling breeches during labour. Footling and kneeling breeches have a higher risk of cord prolapse and head entrapment.
Parity – Parity refers to the number of times a woman has given birth before. If a woman has given birth vaginally, her pelvis has "proven" it is big enough to allow a baby of that babys size to pass through it. However, a head-down babys head often molds (shifts its shape to fit the maternal pelvis) and so may present a smaller diameter than the same-size baby born breech.
Fetal size in relation to maternal pelvic size – If the mothers pelvis is roomy and the baby is not large, this is favorable for vaginal breech delivery. However, prenatal estimates of the size of the baby and the size of the pelvis are unreliable.
Hyperextension of the fetal head – this can be evaluated with ultrasound. Less than 5% of breech babies have their heads in the "star-gazing" position, face looking straight upwards and the back of the head resting against the back of the neck. Caesarean delivery is absolutely necessary, because vaginal birth with the babys head in this position confers a high risk of spinal cord trauma and death.
Maturity of the baby – Premature babies appear to be at higher risk of complications if delivered vaginally than if delivered by caesarean section.
Progress of labor – A spontaneous, normally progressing, straightforward labor requiring no intervention is a favorable sign.
Second twins – If a first twin is born head down and the second twin is breech, the chances are good that the second twin can have a safe breech birth.
Management
As in labour with a baby in a normal head-down position, uterine contractions typically occur at regular intervals and gradually the cervix begins to thin and open. In the more common breech presentations, the babys bottom (rather than feet or knees) is what is first to descend through the maternal pelvis and emerge from the vagina.At the beginning of labour, the baby is generally in an oblique position, facing either the right or left side. The babys bottom is the same size in the term baby as the babys head. Descent is thus as for the presenting fetal head and delay in descent is a cardinal sign of possible problems with the delivery of the head.
In order to begin the birth, descent of podalic pole along with compaction and internal rotation needs to occur. This happens when the mothers pelvic floor muscles cause the baby to turn so that it can be born with one hip directly in front of the other. At this point the baby is facing one of the mothers inner thighs. Then, the shoulders follow the same path as the hips did. At this time the baby usually turns to face the mothers back. Next occurs external rotation, which is when the shoulders emerge as the babys head enters the maternal pelvis. The combination of maternal muscle tone and uterine contractions cause the babys head to flex, chin to chest. Then the back of the babys head emerges and finally the face.
Due to the increased pressure during labour and birth, it is normal for the babys leading hip to be bruised and genitalia to be swollen. Babies who assumed the frank breech position in utero may continue to hold their legs in this position for some days after birth.
Cesarean or vaginal delivery
When a baby is born bottom first there is more risk that the birth will not be straight forward and that the baby could be harmed. For example, when the babys head passes through the mothers pelvis the umbilical cord can be compressed which prevents delivery of oxygenated blood to the baby. Due to this and other risks, babies in breech position are often born by a planned caesarean section in developed countries.Caesarean section reduces the risk of harm or death for the baby but does increase risk of harm to the mother compared with a vaginal delivery. It is best if the baby is in a head down position so that they can be born vaginally with less risk of harm to both mother and baby. The next section is looking at External cephalic version or ECV which is a method that can help the baby turn from a breech position to a head down position.
Vaginal birth of a breech baby has its risks but caesarean sections are not always available or possible, a mother might arrive in hospital at a late stage of her labour or may choose not to have a caesarean section. In these cases, it is important that the clinical skills needed to deliver breech babies are not lost so that mothers and babies are as safe as possible. Compared with developed countries, planned caesarean sections have not produced as good results in developing countries – it is suggested that this is due to more breech vaginal deliveries being performed by experienced, skilled practitioners in these settings.
Twin breech
In twin pregnancies, it is very common for one or both babies to be in the breech position. Most often twin babies do not have the chance to turn around because they are born prematurely. If both babies are in the breech position and the mother has gone into labour early, a cesarean section may be the best option. About 30–40% of twin pregnancies result in only one baby being in the breech position. If this is the case, the babies can be born vaginally. After the first baby who is not in the breech position is delivered, the baby who is presented in the breech position may turn itself around, if this does not happen another procedure may performed called the breech extraction. The breech extraction is the procedure that involves the obstetrician grabbing the second twins feet and pulling him/her into the birth canal. This will help with delivering the second twin vaginally. However, if the second twin is larger than the first, complications with delivering the second twin vaginally may arise and a cesarean section should be performed. At times, the first twin (the twin closest to the birth canal) can be in the breech position with the second twin being in the cephalic position (vertical). When this occurs, risks of complications are higher than normal. In particular, a serious complication known as Locked twins. This is when both babies interlock their chins during labour. When this happens a cesarean section should be performed immediately.
Turning the baby
Turning the baby, technically known as external cephalic version (ECV), is when the baby is turned by gently pressing the mothers abdomen to push the baby from a bottom first position, to a head first position. ECV does not always work, but it does improve the mothers chances of giving birth to her baby vaginally and avoiding a cesarean section. The World Health Organisation recommends that women should have a planned cesarean section only if an ECV has been tried and did not work.Women who have an ECV when they are 36–40 weeks pregnant are more likely to have a vaginal delivery and less likely to have a cesarean section than those who do not have an ECV. Turning the baby before this time makes a head first birth more likely but ECV before the due date can increase the risk of early or premature birth which can cause problems to the baby.There are treatments that can be used which might affect the success of an ECV. Drugs called beta-stimulant tocolytics help the womans muscles to relax so that the pressure during the ECV does not have to be so great. Giving the woman these drugs before the ECV improves the chances of her having a vaginal delivery because the baby is more likely to turn and stay head down. Other treatments such as using sound, pain relief drugs such as epidural, increasing the fluid around the baby and increasing the amount of fluids to the woman before the ECV could all effect its success but there is not enough research to make this clear.Turning techniques mothers can do at home are referred to as "spontaneous cephalic version" (SCV), this is when the baby can turn without any medical assistance. Some of these techniques include: a knee-to-chest position, the breech tilt, and moxibustion, these can be performed after the mother is 34 weeks pregnant. There is limited evidence that these techniques have any effect.
Notable cases
See also
Asynclitic birth, another abnormal birth position
References
External links
Breech birth controversies in Great Britain
GLOWM video demonstrating vaginal breech delivery techniques |
Eye injury | Physical or chemical injuries of the eye can be a serious threat to vision if not treated appropriately and in a timely fashion. The most obvious presentation of ocular (eye) injuries is redness and pain of the affected eyes. This is not, however, universally true, as tiny metallic projectiles may cause neither symptom. Tiny metallic projectiles should be suspected when a patient reports metal on metal contact, such as with hammering a metal surface. Corneal foreign body is one of the most common preventable occupational hazard. Intraocular foreign bodies do not cause pain because of the lack of nerve endings in the vitreous humour and retina that can transmit pain sensations. As such, general or emergency department doctors should refer cases involving the posterior segment of the eye or intraocular foreign bodies to an ophthalmologist. Ideally, ointment would not be used when referring to an ophthalmologist, since it diminishes the ability to carry out a thorough eye examination.
Flicking sand, flying pieces of wood, metal, glass and stone are notorious for causing much of the eye trauma. Sporting balls such as cricket ball, lawn tennis ball, squash ball, shuttlecock, and other high speed flying objects can strike the eye. The eye is also susceptible to blunt trauma in a fistfight. Children’s games such as bow-and-arrows, bb guns and firecrackers can lead to eye trauma. Road traffic accidents (RTAs) with head and facial trauma may also have an eye injury - these are usually severe in nature with multiple lacerations, shards of glasses embedded in tissues, orbital fractures, severe hematoma and penetrating open-globe injuries with prolapse of eye contents. Other causes of intraocular trauma may arise from workplace tools or even common household implements, including bottle-caps suddenly propelling at great force.About 5.3 million cases of foreign bodies in the eyes occurred in 2013.
Presentation
Complications
Multiple complications are known to occur following eye injury: corneal scarring, hyphema, iridodialysis, post-traumatic glaucoma, uveitis cataract, vitreous hemorrhage and retinal detachment. The complications risk is high with retinal tears, penetrating injuries and severe blunt trauma.
Diagnosis
The goal of investigation is the assessment of the severity of the ocular injury with an eye to implementing a management plan as soon as is required. The usual eye examination should be attempted, and may require a topical anesthetic in order to be tolerable. Many topical agents cause burning upon instillation. Proxymetacaine has been found to have the best tolerance.Depending on the medical history and preliminary examination, the primary care physician should designate the eye injury as a true emergency, urgent or semi-urgent.
Classification
Based on the injury to the eyewall (outer fibrous coat of the eye consisting of cornea and sclera)
Closed globe injury: the eye globe is intact, but the seven rings of the eye have been classically described as affected by blunt trauma. Types include contusion and lamellar laceration
Open globe injury: there is a full thickness injury of the eye wall (cornea and sclera)It includes
A) Globe rupture: caused by blunt trauma and is an inside-out injury.
B) Globe laceration: a full-thickness wound caused by sharp objects. It includes
1)Penetrating trauma: the globe integrity is disrupted by a full-thickness entry wound and may be associated with prolapse of the internal contents of the eye. Such injuries are often referred to as a Globe fracture or a Globe rupture, although these can be incurred by blunt trauma as well.
2) Perforating trauma: the globe integrity is disrupted in two places due to an entrance and exit wound (through and through injury). This is a quite severe type of eye injury.
Other types include
Blowout fracture of the orbit is caused by blunt trauma, classically described for fist or ball injury, leading to fracture of the floor or medial wall of the orbit due to sudden increased pressure on the orbital contents.
Muscular Entrapment Fracture of the orbital bones can lead to muscular entrapment limiting gaze in one direction.
Emergency
An emergency must be treated within minutes. This includes chemical burns of both the conjunctiva and cornea.
Urgent
An urgent case must be treated within hours. This includes penetrating globe injuries; corneal abrasions or corneal foreign bodies; hyphema (must be referred); eyelid lacerations that are deep, involve the lid margin or involve the lacrimal canaliculi; radiant energy burns such as arc eye (welders burn) or snow blindness; or, rarely, traumatic optic neuropathy.
Semi-urgent
Semi-urgent cases must be managed within 1–2 days. They include orbital fractures and subconjunctival hemorrhages.
Management
Irrigation
The first line of management for chemical injuries is usually copious irrigation of the eye with an isotonic saline or sterile water. In the cases of chemical burns, one should not try to buffer the solution, but instead dilute it with copious flushing.
Patching
Depending on the type of ocular injury, either a pressure patch or shield patch should be applied. Up until circa 1987, pressure patches were the preferred method of treatment for corneal abrasions in non-contact lens wearers; multiple controlled studies conducted by accredited organizations such as the American Academy of Ophthalmology have shown that pressure patching is of little or no value in healing corneal abrasions and is actually detrimental to healing in some cases. A Cochrane review found that patching simple corneal abrasions may not improve healing or reduce pain. Pressure patching should never be used on an individual presenting with a corneal abrasion who has a history of contact lens wear. In this circumstance, a virulent infection caused by the bacterium Pseudomonas aeruginosa is at a clearly delineated increased risk for occurrence. These infections can cause blindness within 24 – 48 hours and there is a possibility that the infection can move into the peri-orbital socket, resulting in the need for evisceration of the eyeball. In rare cases, the infection can enter the brain and cause death to the patient.
In cases of globe penetration, pressure patches should never be applied, and instead a shield patch should be applied that protects the eye without applying any pressure. If a shield patch is applied to one eye, the other eye should also be patched due to eye movement. If the uninjured eye moves, the injured eye will also move involuntarily possibly causing more damage.
Suturing
In cases of eyelid laceration, sutures may be a part of appropriate management by the primary care physician so long as the laceration does not threaten the canaliculi, is not deep, and does not affect the lid margins.
Epidemiology
A recent study estimated that from 2002–2003 there were 27,152 injuries in the United States related to the wearing of eyeglasses. The same study concluded that sports-related injuries due to eyeglasses wear were more common in those under the age of 18 and that fall-related injuries due to wearing eyeglasses were more common in those aged 65 and over. Although eyeglasses-related injuries do occur, prescription eyeglasses and non-prescription sunglasses have been found to "offer measurable protection which results in a lower incidence of severe eye injuries to those wearing [them]".
See also
Black eye
Chemical eye injury
United States Eye Injury Registry
Wilderness medical emergencies
== References == |
Alcoholic liver disease | Alcoholic liver disease (ALD), also called alcohol-related liver disease (ARLD), is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis.It is the major cause of liver disease in Western countries. Although steatosis (fatty liver disease) will develop in any individual who consumes a large quantity of alcoholic beverages over a long period of time, this process is transient and reversible. More than 90% of all heavy drinkers develop fatty liver whilst about 25% develop the more severe alcoholic hepatitis, and 15% liver cirrhosis.
Risk factors
Risk factors known as of 2010 are:
Quantity of alcohol taken: Consumption of 60–80 g per day (14 g is considered one standard drink in the US, i.e., 1.5 fl oz hard liquor, 5 fl oz wine, 12 fl oz beer; drinking a six-pack of 5% ABV beer daily would be 84 g and just over the upper limit) for 20 years or more in men, or 20 g/day for women significantly increases the risk of hepatitis and fibrosis by 6% to 41%.
Pattern of drinking: Drinking outside of meal times increases up to 3 times the risk of alcoholic liver disease.
Sex: Women are twice as susceptible to alcohol-related liver disease, and may develop alcoholic liver disease with shorter durations and doses of chronic consumption. The lesser amount of alcohol dehydrogenase secreted in the gut, higher proportion of body fat in women, and changes in alcohol absorption due to the menstrual cycle may explain this phenomenon.
Ethnicity: Higher rates of alcohol-related liver disease, unrelated to differences in amounts of alcohol consumed, are seen in African-American and Hispanic males compared to Caucasian males.
Hepatitis C infection: A concomitant hepatitis C infection significantly accelerates the process of liver injury.
Genetic factors: Genetic factors predispose both to alcoholism and to alcoholic liver disease. Both monozygotic twins are more likely to be alcoholics and to develop liver cirrhosis than both dizygotic twins. Polymorphisms in the enzymes involved in the metabolism of alcohol, such as ADH, ALDH, CYP4502E1, mitochondrial dysfunction, and cytokine polymorphism may partly explain this genetic component. However, no specific polymorphisms have currently been firmly linked to alcoholic liver disease.
Iron overload (hemochromatosis).
Diet: Malnutrition, particularly vitamin A and E deficiencies, can worsen alcohol-induced liver damage by preventing regeneration of hepatocytes. This is particularly a concern as alcoholics are usually malnourished because of a poor diet, anorexia, and encephalopathy.
Pathophysiology
The mechanism of ALD is not completely understood. 80% of alcohol passes through the liver to be detoxified. Chronic consumption of alcohol results in the secretion of pro-inflammatory cytokines (TNF-alpha, interleukin 6 and interleukin 8), oxidative stress, lipid peroxidation, and acetaldehyde toxicity. These factors cause inflammation, apoptosis and eventually fibrosis of liver cells. Why this occurs in only a few individuals is still unclear. Additionally, the liver has tremendous capacity to regenerate and even when 75% of hepatocytes are dead, it continues to function as normal.
Fatty change
Fatty change, or steatosis, is the accumulation of fatty acids in liver cells. These can be seen as fatty globules under the microscope. Alcoholism causes development of large fatty globules (macro-vesicular steatosis) throughout the liver and can begin to occur after a few days of heavy drinking. Alcohol is metabolized by alcohol dehydrogenase (ADH) into acetaldehyde, then further metabolized by aldehyde dehydrogenase (ALDH) into acetic acid, which is finally oxidized into carbon dioxide (CO2) and water (H2O). This process generates NADH, and increases the NADH/NAD+ ratio. A higher NADH concentration induces fatty acid synthesis while a decreased NAD level results in decreased fatty acid oxidation. Subsequently, the higher levels of fatty acids signal the liver cells to compound it to glycerol to form triglycerides. These triglycerides accumulate, resulting in fatty liver.
Alcoholic hepatitis
Alcoholic hepatitis is characterized by the inflammation of hepatocytes. Between 10% and 35% of heavy drinkers develop alcoholic hepatitis (NIAAA, 1993). While development of hepatitis is not directly related to the dose of alcohol, some people seem more prone to this reaction than others. This is called alcoholic steato-necrosis and the inflammation appears to predispose to liver fibrosis. Inflammatory cytokines (TNF-alpha, IL-6 and IL-8) are thought to be essential in the initiation and perpetuation of liver injury and cytotoxic hepatomegaly by inducing apoptosis and severe hepatotoxicity. One possible mechanism for the increased activity of TNF-α is the increased intestinal permeability due to liver disease. This facilitates the absorption of the gut-produced endotoxin into the portal circulation. The Kupffer cells of the liver then phagocytose endotoxin, stimulating the release of TNF-α. TNF-α then triggers apoptotic pathways through the activation of caspases, resulting in cell death.
Cirrhosis
Cirrhosis is a late stage of serious liver disease marked by inflammation (swelling), fibrosis (cellular hardening) and damaged membranes preventing detoxification of chemicals in the body, ending in scarring and necrosis (cell death). Between 10% to 20% of heavy drinkers will develop cirrhosis of the liver (NIAAA, 1993). Acetaldehyde may be responsible for alcohol-induced fibrosis by stimulating collagen deposition by hepatic stellate cells. The production of oxidants derived from NADPH oxi- dase and/or cytochrome P-450 2E1 and the formation of acetaldehyde-protein adducts damage the cell membrane.Symptoms include jaundice (yellowing), liver enlargement, and pain and tenderness from the structural changes in damaged liver architecture. Without total abstinence from alcohol use, cirrhosis will eventually lead to liver failure. Late complications of cirrhosis or liver failure include portal hypertension (high blood pressure in the portal vein due to the increased flow resistance through the damaged liver), coagulation disorders (due to impaired production of coagulation factors), ascites (heavy abdominal swelling due to buildup of fluids in the tissues) and other complications, including hepatic encephalopathy and the hepatorenal syndrome.
Cirrhosis can also result from other causes than hazardous alcohol use, such as viral hepatitis and heavy exposure to toxins other than alcohol. The late stages of cirrhosis may look similar medically, regardless of cause. This phenomenon is termed the "final common pathway" for the disease.
Fatty change and alcoholic hepatitis with abstinence can be reversible. The later stages of fibrosis and cirrhosis tend to be irreversible, but can usually be contained with abstinence for long periods of time.
Diagnosis
In the early stages, patients with ALD exhibit subtle and often no abnormal physical findings. It is usually not until development of advanced liver disease that stigmata of chronic liver disease become apparent. Early ALD is usually discovered during routine health examinations when liver enzyme levels are found to be elevated. These usually reflect alcoholic hepatic steatosis. Microvesicular and macrovesicular steatosis with inflammation are seen in liver biopsy specimens. These histologic features of ALD are indistinguishable from those of nonalcoholic fatty liver disease. Steatosis usually resolves after discontinuation of alcohol use. Continuation of alcohol use will result in a higher risk of progression of liver disease and cirrhosis. In patients with acute alcoholic hepatitis, clinical manifestations include fever, jaundice, hepatomegaly, and possible hepatic decompensation with hepatic encephalopathy, variceal bleeding, and ascites accumulation. Tender hepatomegaly may be present, but abdominal pain is unusual. Occasionally, the patient may be asymptomatic.
Laboratory findings
In people with alcoholic hepatitis, the serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio is greater than 2:1. AST and ALT levels are almost always less than 500. The elevated AST to ALT ratio is due to deficiency of pyridoxal phosphate, which is required in the ALT enzyme synthetic pathway. Furthermore, alcohol metabolite–induced injury of hepatic mitochondria results in AST isoenzyme release. Other laboratory findings include red blood cell macrocytosis (mean corpuscular volume > 100) and elevations of serum gamma-glutamyl transferase (GGT), alkaline phosphatase, and bilirubin levels. Folate level is reduced in alcoholic patients due to decreased intestinal absorption, increased bone marrow requirement for folate in the presence of alcohol, and increased urinary loss. The magnitude of leukocytosis (white blood cell depletion) reflects severity of liver injury. Histologic features include Mallory bodies, giant mitochondria, hepatocyte necrosis, and neutrophil infiltration in the area around the veins. Mallory bodies, which are also present in other liver diseases, are condensations of cytokeratin components in the hepatocyte cytoplasm and do not contribute to liver injury. Up to 70% of patients with moderate to severe alcoholic hepatitis already have cirrhosis identifiable on biopsy examination at the time of diagnosis.
Treatment
Not drinking further alcohol is the most important part of treatment. People with chronic HCV infection should abstain from any alcohol intake, due to the risk for rapid acceleration of liver disease.
Medications
A 2006 Cochrane review did not find evidence sufficient for the use of androgenic anabolic steroids. Corticosteroids are sometimes used; however, this is recommended only when severe liver inflammation is present.Silymarin has been investigated as a possible treatment, with ambiguous results. One review claimed benefit for S-adenosyl methionine in disease models.The effects of anti-tumor necrosis factor medications such as infliximab and etanercept are unclear and possibly harmful. Evidence is unclear for pentoxifylline. Propylthiouracil may result in harm.Evidence does not support supplemental nutrition in liver disease.
Transplantation
Although in rare cases liver cirrhosis is reversible, the disease process remains mostly irreversible. Liver transplantation remains the only definitive therapy. Today, survival after liver transplantation is similar for people with ALD and non-ALD. The requirements for transplant listing are the same as those for other types of liver disease, except for a 6-month sobriety prerequisite along with psychiatric evaluation and rehabilitation assistance. Specific requirements vary among the transplant centers. Relapse to alcohol use after transplant listing results in delisting. Re-listing is possible in many institutions, but only after 3–6 months of sobriety. There are limited data on transplant survival in patients transplanted for acute alcoholic hepatitis, but it is believed to be similar to that in nonacute ALD, non-ALD, and alcoholic hepatitis with MDF less than 32.
Prognosis
The prognosis for people with ALD depends on the liver histology as well as cofactors, such as concomitant chronic viral hepatitis. Among patients with alcoholic hepatitis, progression to liver cirrhosis occurs at 10–20% per year, and 70% will eventually develop cirrhosis. Despite cessation of alcohol use, only 10% will have normalization of histology and serum liver enzyme levels. As previously noted, the MDF has been used to predict short-term mortality (i.e., MDF ≥ 32 associated with spontaneous survival of 50–65% without corticosteroid therapy, and MDF < 32 associated with spontaneous survival of 90%). The Model for End-Stage Liver Disease (MELD) score has also been found to have similar predictive accuracy in 30-day (MELD > 11) and 90-day (MELD > 21) mortality. Liver cirrhosis develops in 6–14% of those who consume more than 60–80 g of alcohol daily for men and more than 20 g daily for women. Even in those who drink more than 120 g daily, only 13.5% will experience a serious alcohol-related liver injury. Nevertheless, alcohol-related mortality was the third leading cause of death in 2003 in the United States. Worldwide mortality is estimated to be 150,000 per year.
References
== External links == |
Mycobacterium avium complex | Mycobacterium avium complex is a group of mycobacteria comprising Mycobacterium intracellulare and Mycobacterium avium that are commonly grouped because they infect humans together; this group, in turn, is part of the group of nontuberculous mycobacteria. These bacteria cause Mycobacterium avium-intracellulare infections or Mycobacterium avium complex infections in humans. These bacteria are common and are found in fresh and salt water, in household dust and in soil. MAC bacteria usually cause infection in those who are immunocompromised or those with severe lung disease.
Description
In the Runyon classification, both bacteria are nonchromogens. They can be differentiated from M. tuberculosis and each other by commercially available DNA probes.: 245 They are characterized as Gram-positive, nonmotile, acid-fast, short to long rods.
Colony characteristics
Usually, colonies are smooth, rarely rough, and not pigmented colonies. Older colonies may become yellow.Physiology
Growth on Löwenstein-Jensen medium and Middlebrook 7H10 agar occurs at 37°C after seven or more days.
The complex can be (but is not often) resistant to isoniazid, ethambutol, rifampin, and streptomycin.Differential characteristics
M. intracellulare and M. avium form the M. avium complex (MAC).
Remarkable ITS heterogeneity is seen within different M. intracellulare isolates.
Type strains
M. intracellulare type strains include ATCC 13950, CCUG 28005, CIP 104243, DSM 43223, JCM 6384, and NCTC 13025.M. avium type strains include ATCC 25291, DSM 44156, and TMC 724.
Human health
MAC bacteria enter most peoples body when inhaled into the lungs or swallowed, but only cause infection in those who are immunocompromised or who have severe lung disease such as those with cystic fibrosis or chronic obstructive lung disease (COPD). MAC infection can cause COPD and lymphadenitis, and can cause disseminated disease, especially in people with immunodeficiency.: 245
History
In 2004, Tortoli et al. proposed the name M. chimaera for strains that a reverse hybridization–based line probe assay suggested belonged to MAIS (M. avium–M. intracellulare–M. scrofulaceum group), but were different from M. avium, M. intracellulare, or M. scrofulaceum. The new species name comes from the Chimera, a mythological being made up of parts of three different animals.
References
External links
Mycobacterium avium Complex at the US National Library of Medicine Medical Subject Headings (MeSH) |
SARS | Severe acute respiratory syndrome (SARS) is a viral respiratory disease of zoonotic origin caused by severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1), the first identified strain of the SARS coronavirus species severe acute respiratory syndrome–related coronavirus (SARSr-CoV). The first known cases occurred in November 2002, and the syndrome caused the 2002–2004 SARS outbreak. In the 2010s, Chinese scientists traced the virus through the intermediary of Asian palm civets to cave-dwelling horseshoe bats in Xiyang Yi Ethnic Township, Yunnan.SARS was a relatively rare disease; at the end of the epidemic in June 2003, the incidence was 8,469 cases with a case fatality rate (CFR) of 11%. No cases of SARS-CoV-1 have been reported worldwide since 2004.In December 2019, another strain of SARS-CoV was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This new strain causes coronavirus disease 2019 (COVID-19), a disease which brought about the COVID-19 pandemic.
Signs and symptoms
SARS produces flu-like symptoms which may include fever, muscle pain, lethargy, cough, sore throat, and other nonspecific symptoms. The only symptom common to all patients appears to be a fever above 38 °C (100 °F). SARS often leads to shortness of breath and pneumonia, which may be direct viral pneumonia or secondary bacterial pneumonia.The average incubation period for SARS is 4–6 days, although it is rarely as short as 1 day or as long as 14 days.
Transmission
The primary route of transmission for SARS-CoV is contact of the mucous membranes with respiratory droplets or fomites. While diarrhea is common in people with SARS, the fecal–oral route does not appear to be a common mode of transmission. The basic reproduction number of SARS-CoV, R0, ranges from 2 to 4 depending on different analyses. Control measures introduced in April 2003 reduced the R to 0.4.
Diagnosis
SARS-CoV may be suspected in a patient who has:
Any of the symptoms, including a fever of 38 °C (100 °F) or higher, and
Either a history of:
Contact (sexual or casual) with someone with a diagnosis of SARS within the last 10 days or
Travel to any of the regions identified by the World Health Organization (WHO) as areas with recent local transmission of SARS.
Clinical criteria of Sars-CoV diagnosisEarly illness: equal to or more than 2 of the following: chills, rigors, myalgia, diarrhea, sore throat (self-reported or observed)
Mild-to-moderate illness: temperature of >38 °C (100 °F) plus indications of lower respiratory tract infection (cough, dyspnea)
Severe illness: ≥1 of radiographic evidence, presence of ARDS, autopsy findings in late patients.For a case to be considered probable, a chest X-ray must be indicative for atypical pneumonia or acute respiratory distress syndrome.
The WHO has added the category of "laboratory confirmed SARS" which means patients who would otherwise be considered "probable" and have tested positive for SARS based on one of the approved tests (ELISA, immunofluorescence or PCR) but whose chest X-ray findings do not show SARS-CoV infection (e.g. ground glass opacities, patchy consolidations unilateral).The appearance of SARS-CoV in chest X-rays is not always uniform but generally appears as an abnormality with patchy infiltrates.
Prevention
There is no vaccine for SARS, although immunologist Anthony Fauci mentioned that the CDC developed one and placed it in the US national stockpile. That vaccine, however, is a prototype and not field-ready as of March 2020. Clinical isolation and quarantine remain the most effective means to prevent the spread of SARS. Other preventive measures include:
Hand-washing with soap and water, or use of alcohol-based hand sanitizer
Disinfection of surfaces of fomites to remove viruses
Avoiding contact with bodily fluids
Washing the personal items of someone with SARS in hot, soapy water (eating utensils, dishes, bedding, etc.)
Avoiding travel to affected areas
Wearing masks and gloves
Keeping people with symptoms home from school
Simple hygiene measures
Isolating oneself as much as possible to minimize the chances of transmission of the virusMany public health interventions were made to try to control the spread of the disease, which is mainly spread through respiratory droplets in the air, either inhaled or deposited on surfaces and subsequently transferred to a bodys mucous membranes. These interventions included earlier detection of the disease; isolation of people who are infected; droplet and contact precautions; and the use of personal protective equipment (PPE), including masks and isolation gowns. A 2017 meta-analysis found that for medical professionals wearing N-95 masks could reduce the chances of getting sick up to 80% compared to no mask. A screening process was also put in place at airports to monitor air travel to and from affected countries.SARS-CoV is most infectious in severely ill patients, which usually occurs during the second week of illness. This delayed infectious period meant that quarantine was highly effective; people who were isolated before day five of their illness rarely transmitted the disease to others.As of 2017, the CDC was still working to make federal and local rapid-response guidelines and recommendations in the event of a reappearance of the virus.It has been found that those with a Vitamin D deficiency were at a 19.61-fold higher risk of having a critical result from Covid-19 disease versus those with an adequate amount of vitamin D. Patients with low vitamin D levels had worse symptoms, were more likely to be hospitalized, and had a greater risk of death. It is believed the reason vitamin D supplementation helps with the prevention of Covid-19 is due to the fact that vitamin D combats cytokine storms that are brought on because of Covid-19. Vitamin D supplementation is only effective in preventing Covid-19 but has been shown to have no effect after Covid-19 is contracted.
Treatment
As SARS is a viral disease, antibiotics do not have direct effect but may be used against bacterial secondary infection. Treatment of SARS is mainly supportive with antipyretics, supplemental oxygen and mechanical ventilation as needed. While ribavirin is commonly used to treat SARS, there seems to have little to no effect on SARS-CoV, and no impact on patients outcomes. There is currently no proven antiviral therapy. Tested substances, include ribavirin, lopinavir, ritonavir, type I interferon, that have thus far shown no conclusive contribution to the diseases course. Administration of corticosteroids, is recommended by the British Thoracic Society/British Infection Society/Health Protection Agency in patients with severe disease and O2 saturation of <90%.People with SARS-CoV must be isolated, preferably in negative-pressure rooms, with complete barrier nursing precautions taken for any necessary contact with these patients, to limit the chances of medical personnel becoming infected. In certain cases, natural ventilation by opening doors and windows is documented to help decreasing indoor concentration of virus particles.Some of the more serious damage caused by SARS may be due to the bodys own immune system reacting in what is known as cytokine storm.
Vaccine
Vaccines can help immune system to create enough antibodies and also it can help to decrease a risk of side effects like arm pain, fever, headache etc. According to research papers published in 2005 and 2006, the identification and development of novel vaccines and medicines to treat SARS was a priority for governments and public health agencies around the world. In early 2004, an early clinical trial on volunteers was planned. A major researchers 2016 request, however, demonstrated that no field-ready SARS vaccine had been completed because likely market-driven priorities had ended funding.
Prognosis
Several consequent reports from China on some recovered SARS patients showed severe long-time sequelae. The most typical diseases include, among other things, pulmonary fibrosis, osteoporosis, and femoral necrosis, which have led in some cases to the complete loss of working ability or even self-care ability of people who have recovered from SARS. As a result of quarantine procedures, some of the post-SARS patients have been diagnosed with post-traumatic stress disorder (PTSD) and major depressive disorder.
Epidemiology
SARS was a relatively rare disease; at the end of the epidemic in June 2003, the incidence was 8,422 cases with a case fatality rate (CFR) of 11%.The case fatality rate (CFR) ranges from 0% to 50% depending on the age group of the patient. Patients under 24 were least likely to die (less than 1%); those 65 and older were most likely to die (over 55%).As with MERS and COVID-19, SARS resulted in significantly more deaths of males than females.
Outbreak in South China
The SARS epidemic began in the Guangdong province of China in November 2002. The earliest case developed symptoms on 16 November 2002. The index patient, a farmer from Shunde, Foshan, Guangdong, was treated in the First Peoples Hospital of Foshan. The patient died soon after, and no definite diagnosis was made on his cause of death. Despite taking some action to control it, Chinese government officials did not inform the World Health Organization of the outbreak until February 2003. This lack of openness caused delays in efforts to control the epidemic, resulting in criticism of the Peoples Republic of China from the international community. China officially apologized for early slowness in dealing with the SARS epidemic.The viral outbreak was subsequently genetically traced to a colony of cave-dwelling horseshoe bats in Xiyang Yi Ethnic Township, Yunnan.The outbreak first came to the attention of the international medical community on 27 November 2002, when Canadas Global Public Health Intelligence Network (GPHIN), an electronic warning system that is part of the World Health Organizations Global Outbreak Alert and Response Network (GOARN), picked up reports of a "flu outbreak" in China through Internet media monitoring and analysis and sent them to the WHO. While GPHINs capability had recently been upgraded to enable Arabic, Chinese, English, French, Russian, and Spanish translation, the system was limited to English or French in presenting this information. Thus, while the first reports of an unusual outbreak were in Chinese, an English report was not generated until 21 January 2003. The first super-spreader was admitted to the Sun Yat-sen Memorial Hospital in Guangzhou on 31 January, which soon spread the disease to nearby hospitals.In early April 2003, after a prominent physician, Jiang Yanyong, pushed to report the danger to China, there appeared to be a change in official policy when SARS began to receive a much greater prominence in the official media. Some have directly attributed this to the death of an American teacher, James Earl Salisbury, in Hong Kong. It was around this same time that Jiang Yanyong made accusations regarding the undercounting of cases in Beijing military hospitals. After intense pressure, Chinese officials allowed international officials to investigate the situation there. This revealed problems plaguing the aging mainland Chinese healthcare system, including increasing decentralization, red tape, and inadequate communication.Many healthcare workers in the affected nations risked their lives and died by treating patients, and trying to contain the infection before ways to prevent infection were known.
Spread to other regions
The epidemic reached the public spotlight in February 2003, when an American businessman traveling from China, Johnny Chen, became affected by pneumonia-like symptoms while on a flight to Singapore. The plane stopped in Hanoi, Vietnam, where the patient died in Hanoi French Hospital. Several of the medical staff who treated him soon developed the same disease despite basic hospital procedures. Italian doctor Carlo Urbani identified the threat and communicated it to WHO and the Vietnamese government; he later died from the disease.The severity of the symptoms and the infection among hospital staff alarmed global health authorities, who were fearful of another emergent pneumonia epidemic. On 12 March 2003, the WHO issued a global alert, followed by a health alert by the United States Centers for Disease Control and Prevention (CDC). Local transmission of SARS took place in Toronto, Ottawa, San Francisco, Ulaanbaatar, Manila, Singapore, Taiwan, Hanoi and Hong Kong whereas within China it spread to Guangdong, Jilin, Hebei, Hubei, Shaanxi, Jiangsu, Shanxi, Tianjin, and Inner Mongolia.
Hong Kong
The disease spread in Hong Kong from Liu Jianlun, a Guangdong doctor who was treating patients at Sun Yat-Sen Memorial Hospital. He arrived in February and stayed on the ninth floor of the Metropole Hotel in Kowloon, infecting 16 of the hotel visitors. Those visitors traveled to Canada, Singapore, Taiwan, and Vietnam, spreading SARS to those locations.Another larger cluster of cases in Hong Kong centred on the Amoy Gardens housing estate. Its spread is suspected to have been facilitated by defects in its bathroom drainage system that allowed sewer gases including virus particles to vent into the room. Bathroom fans exhausted the gases and wind carried the contagion to adjacent downwind complexes. Concerned citizens in Hong Kong worried that information was not reaching people quickly enough and created a website called sosick.org, which eventually forced the Hong Kong government to provide information related to SARS in a timely manner. The first cohort of affected people were discharged from hospital on 29 March 2003.
Canada
The first case of SARS in Toronto was identified on 23 February 2003. Beginning with an elderly woman, Kwan Sui-Chu, who had returned from a trip to Hong Kong and died on 5 March, the virus eventually infected 257 individuals in the province of Ontario. The trajectory of this outbreak is typically divided into two phases, the first centring around her son Tse Chi Kwai, who infected other patients at the Scarborough Grace Hospital and died on 13 March. The second major wave of cases was clustered around accidental exposure among patients, visitors, and staff within the North York General Hospital. The WHO officially removed Toronto from its list of infected areas by the end of June 2003.The official response by the Ontario provincial government and Canadian federal government has been widely criticized in the years following the outbreak. Brian Schwartz, vice-chair of Ontarios SARS Scientific Advisory Committee, described public health officials preparedness and emergency response at the time of the outbreak as "very, very basic and minimal at best". Critics of the response often cite poorly outlined and enforced protocol for protecting healthcare workers and identifying infected patients as a major contributing factor to the continued spread of the virus. The atmosphere of fear and uncertainty surrounding the outbreak resulted in staffing issues in area hospitals when healthcare workers elected to resign rather than risk exposure to SARS.
Identification of virus
In late February 2003, Italian doctor Carlo Urbani was called into The French Hospital of Hanoi to look at Johnny Chen, an American businessman who had fallen ill with what doctors thought was a bad case of influenza. Urbani realized that Chens ailment was probably a new and highly contagious disease. He immediately notified the WHO. He also persuaded the Vietnamese Health Ministry to begin isolating patients and screening travelers, thus slowing the early pace of the epidemic. He subsequently contracted the disease himself, and died in March 2003.The CDC and Canadas National Microbiology Laboratory identified the SARS genome in April 2003. Scientists at Erasmus University in Rotterdam, the Netherlands demonstrated that the SARS coronavirus fulfilled Kochs postulates thereby suggesting it as the causative agent. In the experiments, macaques infected with the virus developed the same symptoms as human SARS patients.
Origin and animal vectors
In late May 2003, a study was conducted using samples of wild animals sold as food in the local market in Guangdong, China. The study found that "SARS-like" coronaviruses could be isolated from masked palm civets (Paguma sp.). Genomic sequencing determined that these animal viruses were very similar to human SARS viruses, however they were phylogenetically distinct, and so the study concluded that it was unclear whether they were the natural reservoir in the wild. Still, more than 10,000 masked palm civets were killed in Guangdong Province since they were a "potential infectious source." The virus was also later found in raccoon dogs (Nyctereuteus sp.), ferret badgers (Melogale spp.), and domestic cats.In 2005, two studies identified a number of SARS-like coronaviruses in Chinese bats. Phylogenetic analysis of these viruses indicated a high probability that SARS coronavirus originated in bats and spread to humans either directly or through animals held in Chinese markets. The bats did not show any visible signs of disease, but are the likely natural reservoirs of SARS-like coronaviruses. In late 2006, scientists from the Chinese Centre for Disease Control and Prevention of Hong Kong University and the Guangzhou Centre for Disease Control and Prevention established a genetic link between the SARS coronavirus appearing in civets and in the second, 2004 human outbreak, bearing out claims that the disease had jumped across species.It took 14 years to find the original bat population likely responsible for the SARS pandemic. In December 2017, "after years of searching across China, where the disease first emerged, researchers reported ... that they had found a remote cave in Xiyang Yi Ethnic Township, Yunnan province, which is home to horseshoe bats that carry a strain of a particular virus known as a coronavirus. This strain has all the genetic building blocks of the type that triggered the global outbreak of SARS in 2002." The research was performed by Shi Zhengli, Cui Jie, and co-workers at the Wuhan Institute of Virology, China, and published in PLOS Pathogens. The authors are quoted as stating that "another deadly outbreak of SARS could emerge at any time. The cave where they discovered their strain is only a kilometre from the nearest village." The virus was ephemeral and seasonal in bats. In 2019, a similar virus to SARS caused a cluster of infections in Wuhan, eventually leading to the COVID-19 pandemic.
A small number of cats and dogs tested positive for the virus during the outbreak. However, these animals did not transmit the virus to other animals of the same species or to humans.
Containment
The World Health Organization declared severe acute respiratory syndrome contained on 5 July 2003. The containment was achieved through successful public health measures. In the following months, four SARS cases were reported in China between December 2003 and January 2004.While SARS-CoV-1 probably persists as a potential zoonotic threat in its original animal reservoir, human-to-human transmission of this virus may be considered eradicated because no human case has been documented since four minor, brief, subsequent outbreaks in 2004.
Laboratory accidents
After containment, there were four laboratory accidents that resulted in infections.
One postdoctoral student at the National University of Singapore in Singapore in August 2003
A 44-year-old senior scientist at the National Defense University in Taipei in December 2003. He was confirmed to have the SARS virus after working on a SARS study in Taiwans only BSL-4 lab. The Taiwan CDC later stated the infection occurred due to laboratory misconduct.
Two researchers at the Chinese Institute of Virology in Beijing, China around April 2004, who spread it to around six other people. The two researchers contracted it 2 weeks apart.Study of live SARS specimens requires a biosafety level 3 (BSL-3) facility; some studies of inactivated SARS specimens can be done at biosafety level 2 facilities.
Society and culture
Fear of contracting the virus from consuming infected wild animals resulted in public bans and reduced business for meat markets in southern China and Hong Kong.
See also
2009 swine flu pandemic
Avian influenza
Bat-borne virus
Coronavirus disease 2019 – a disease caused by Severe acute respiratory syndrome coronavirus 2
Health crisis
Health in China
List of medical professionals who died during the SARS outbreak
Middle East respiratory syndrome – a coronavirus discovered in June 2012 in Saudi Arabia
SARS conspiracy theory
Zhong Nanshan
References
Further reading
External links
MedlinePlus: Severe Acute Respiratory Syndrome News, links and information from The United States National Library of Medicine
Severe Acute Respiratory Syndrome (SARS) Symptoms and treatment guidelines, travel advisory, and daily outbreak updates, from the World Health Organization (WHO)
Severe Acute Respiratory Syndrome (SARS): information on the international outbreak of the illness known as a severe acute respiratory syndrome (SARS), provided by the US Centers for Disease Control |
CREST syndrome | CREST syndrome, also known as the limited cutaneous form of systemic sclerosis (lcSSc), is a multisystem connective tissue disorder. The acronym "CREST" refers to the five main features: calcinosis, Raynauds phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia.CREST syndrome is associated with detectable antibodies against centromeres (a component of the cell nucleus), and usually spares the kidneys (a feature more common in the related condition systemic scleroderma). If the lungs are involved, it is usually in the form of pulmonary arterial hypertension.
Signs and symptoms
Calcinosis
CREST causes thickening and tightening of the skin with deposition of calcific nodules ("calcinosis").
Raynauds phenomenon
Raynauds phenomenon is frequently the first manifestation of CREST/lcSSc, preceding other symptoms by years. Stress and cold temperature induce an exaggerated vasoconstriction of the small arteries, arterioles, and thermoregulatory vessels of the skin of the digits. Clinically this manifests as a white-blue-red transition in skin color. Underlying this transition is pallor and cyanosis of the digits, followed by a reactive hyperemia as they rewarm. When extreme and frequent, this phenomenon can lead to digital ulcerations, gangrene, or amputation.
Ulceration can predispose to chronic infections of the involved site.
Esophageal dysmotility
Presents as a sensation of food getting stuck (dysphagia) in the mid- or lower esophagus, atypical chest pain, or cough. People often state they must drink liquids to swallow solid food. This motility problem results from atrophy of the gastrointestinal tract wall smooth muscle. This change may occur with or without pathologic evidence of significant tissue fibrosis.
Sclerodactyly
Though it is the most easily recognizable manifestation, it is not prominent in all patients. Thickening generally only involves the skin of the fingers distal to the metacarpophalangeal joints in CREST. Early in the course of the disease, the skin may appear edematous and inflamed. Eventually, dermal fibroblasts overproduce extracellular matrix leading to increased tissue collagen deposition in the skin. Collagen cross-linking then causes a progressive skin tightening. Digital ischemic ulcers commonly form on the distal fingers in 30–50% of patients.
Telangiectasias
Marked telangiectasias (dilated capillaries) occur on the skin of the face, the palmar surface of the hands, and the mucous membranes. Telangiectasias tend to be more numerous in people with other scleroderma related vascular disease (i.e., pulmonary arterial hypertension). The number of telangiectasias and the sites involved tend to increase over time....
Other
Other symptoms of CREST syndrome can be exhaustion, weakness, difficulties with breathing, pain in hands and feet, dizziness and badly healing wounds.
Patients with lcSSc commonly induce pulmonary artery hypertension which may result in cor pulmonale (heart failure due to increased pulmonary artery pressure).
Cause
CREST syndrome involves the production of autoimmune anti-nuclear and anti-centromere antibodies, though their cause is not currently understood. There is no known infectious cause.
Diagnosis
CREST is not easily diagnosed as it closely mimics symptoms of other connective tissue and autoimmune diseases. Diagnoses are usually given when a patient presents two or more of the five major clinical symptoms. Additionally, blood exams can be given to test for a positive ANAs and ACAs or skin biopsies can be given to help confirm a diagnosis.
Treatment
Disease progression may be slowed with immunosuppressives and other medications, and esophageal reflux, pulmonary hypertension and Raynaud phenomenon may benefit from symptomatic treatment. However, there is no cure for this disease as there is no cure for scleroderma in general.
Epidemiology
CREST syndrome can be noted in up to 10% of patients with primary biliary cholangitis.
History
The combination of symptoms was first reported in 1964 by R.H. Winterbauer, at that point a medical student at Johns Hopkins School of Medicine.
See also
Scleroderma
References
== External links == |
Chikungunya | Chikungunya is an infection caused by the Chikungunya virus (CHIKV). Symptoms include fever and joint pains. These typically occur two to twelve days after exposure. Other symptoms may include headache, muscle pain, joint swelling, and a rash. Symptoms usually improve within a week; however, occasionally the joint pain may last for months or years. The risk of death is around 1 in 1,000. The very young, old, and those with other health problems are at risk of more severe disease.The virus is spread between people by two types of mosquitos: Aedes albopictus and Aedes aegypti. They mainly bite during the day. The virus may circulate within a number of animals including birds and rodents. Diagnosis is by either testing the blood for the viruss RNA or antibodies to the virus. The symptoms can be mistaken for those of dengue fever and Zika fever. It is believed most people become immune after a single infection.The best means of prevention is overall mosquito control and the avoidance of bites in areas where the disease is common. This may be partly achieved by decreasing mosquito access to water and with the use of insect repellent and mosquito nets. There is no vaccine and no specific treatment as of 2016. Recommendations include rest, fluids, and medications to help with fever and joint pain.While the disease typically occurs in Africa and Asia, outbreaks have been reported in Europe and the Americas since the 2000s. In 2014 more than a million suspected cases occurred. In 2014 it was occurring in Florida in the continental United States but as of 2016 there were no further locally acquired cases. The disease was first identified in 1952 in Tanzania. The term is from the Kimakonde language and means "to become contorted".
Signs and symptoms
Around 85% of people infected with Chikungunya virus experience symptoms, typically beginning with a sudden high fever above 39 °C (102 °F). The fever is soon followed by severe muscle and joint pain. Pain usually affects multiple joints in the arms and legs, and is symmetric – i.e. if one elbow is affected, the other is as well. People with Chikungunya also frequently experience headache, back pain, nausea, and fatigue. Around half of those affected develop a rash, with reddening and sometimes small bumps on the palms, foot soles, torso, and face. For some, the rash remains constrained to a small part of the body; for others, the rash can be extensive, covering more than 90% of the skin. Some people experience gastrointestinal issues, with abdominal pain and vomiting. Others experience eye problems, namely sensitivity to light, conjunctivitis, and pain behind the eye. This first set of symptoms – called the "acute phase" of Chikungunya – lasts around a week, after which most symptoms resolve on their own.Many people continue to have symptoms after the "acute phase" resolves, termed the "post-acute phase" for symptoms lasting three weeks to three months, and the "chronic stage" for symptoms lasting longer than three months. In both cases, the lasting symptoms tend to be joint pains: arthritis, tenosynovitis, and/or bursitis. If the affected person had pre-existing joint issues, these tend to worsen. Overuse of a joint can result in painful swelling, stiffness, nerve damage, and neuropathic pain. Typically the joint pain improves with time; however, the chronic stage can last anywhere from a few months to several years.Joint pain is reported in 87–98% of cases, and nearly always occurs in more than one joint, though joint swelling is uncommon. Typically the affected joints are located in both arms and legs. Joints are more likely to be affected if they have previously been damaged by disorders such as arthritis. Pain most commonly occurs in peripheral joints, such as the wrists, ankles, and joints of the hands and feet as well as some of the larger joints, typically the shoulders, elbows and knees. Pain may also occur in the muscles or ligaments. In more than half of cases, normal activity is limited by significant fatigue and pain. Infrequently, inflammation of the eyes may occur in the form of iridocyclitis, or uveitis, and retinal lesions may occur. Temporary damage to the liver may occur.People with Chikungunya occasionally develop neurologic disorders, most frequently swelling or degeneration of the brain, inflammation or degneration of the myelin sheaths around neurons, Guillain–Barré syndrome, acute disseminated encephalomyelitis, hypotonia (in newborns), and issues with visual processing. In particularly rare cases, people may develop behavioral changes, seizures, irritation of the cerebellum or meninges, oculomotor nerve palsy, or paralysis of the eye muscles.Newborns are susceptible to particularly severe effects of Chikungunya infection. Signs of infection typically begin with fever, rash, and swelling at the extremities. Around half of newborns have a mild case of the disease that resolves on its own; the other half have severe disease with inflammation of the brain and seizures. In severe cases, affected newborns may also have issues with bleeding and bloodflow, and problems with heart function.In addition to newborns, the elderly, and those with diabetes, heart disease, liver and kidney diseases, and human immunodeficiency virus infection tend to have more severe cases of Chikungunya. Around 1 to 5 in 1,000 people with symptomatic Chikungunya die of the disease.
Cause
Virology
Chikungunya virus (CHIKV), is a member of the genus Alphavirus, and family Togaviridae. It was first isolated in 1953 in Tanzania and is an RNA virus with a positive-sense single-stranded genome of about 11.6kb. It is a member of the Semliki Forest virus complex and is closely related to Ross River virus, Onyongnyong virus, and Semliki Forest virus. Because it is transmitted by arthropods, namely mosquitoes, it can also be referred to as an arbovirus (arthropod-borne virus). In the United States, it is classified as a category B priority pathogen, and work requires biosafety level III precautions.
Transmission
Chikungunya is generally transmitted from mosquitoes to humans. Less common modes of transmission include vertical transmission, which is transmission from mother to child during pregnancy or at birth. Transmission via infected blood products and through organ donation is also theoretically possible during times of outbreak, though no cases have yet been documented. The incubation period ranges from one to twelve days, and is most typically three to seven.Chikungunya is related to mosquitoes, their environments, and human behavior. The adaptation of mosquitoes to the changing climate of North Africa around 5,000 years ago made them seek out environments where humans stored water. Human habitation and the mosquitoes environments were then very closely connected. During periods of epidemics humans are the reservoir of the virus. Because high amounts of virus are present in the blood in the beginning of acute infection, the virus can be spread from a viremic human to a mosquito, and back to a human. During other times, monkeys, birds and other vertebrates have served as reservoirs. Three genotypes of this virus have been described, each with a distinct genotype and antigenic character: West African, East/Central/South African, and Asian genotypes. The Asian lineage originated in 1952 and has subsequently split into two lineages – India (Indian Ocean Lineage) and South East Asian clades. This virus was first reported in the Americas in 2014. Phylogenetic investigations have shown that there are two strains in Brazil – the Asian and East/Central/South African types – and that the Asian strain arrived in the Caribbean (most likely from Oceania) in about March 2013. The rate of molecular evolution was estimated to have a mean rate of 5 × 10−4 substitutions per site per year (95% higher probability density 2.9–7.9 × 10−4).Chikungunya is spread through bites from Aedes mosquitoes, and the species A. aegypti was identified as the most common vector, though the virus has recently been associated with many other species, including A. albopictus. Research by the Pasteur Institute in Paris has suggested Chikungunya virus strains in the 2005-2006 Reunion Island outbreak incurred a mutation that facilitated transmission by the Asian tiger mosquito (A. albopictus). Other species potentially able to transmit Chikungunya virus include Ae. furcifer-taylori, Ae. africanus, and Ae. luteocephalus.
Mechanism
Chikungunya virus is passed to humans when a bite from an infected mosquito breaks the skin and introduces the virus into the body. The pathogenesis of chikungunya infection in humans is still poorly understood, despite recent outbreaks. It appears that in vitro, Chikungunya virus is able to replicate in human epithelial and endothelial cells, primary fibroblasts, and monocyte-derived macrophages. Viral replication is highly cytopathic, but susceptible to type-I and -II interferon. In vivo, in studies using living cells, chikungunya virus appears to replicate in fibroblasts, skeletal muscle progenitor cells, and myofibers.The type-1 interferon response seems to play an important role in the hosts response to chikungunya infection. Upon infection with chikungunya, the hosts fibroblasts produce type-1 alpha and beta interferon (IFN-α and IFN-β). In mouse studies, deficiencies in INF-1 in mice exposed to the virus cause increased morbidity and mortality. The chikungunya-specific upstream components of the type-1 interferon pathway involved in the hosts response to chikungunya infection are still unknown. Nonetheless, mouse studies suggest that IPS-1 is an important factor, and that IRF3 and IRF7 are important in an age-dependent manner. Mouse studies also suggest that chikungunya evades host defenses and counters the type-I interferon response by producing NS2, a nonstructural protein that degrades RBP1 and turns off the host cells ability to transcribe DNA. NS2 interferes with the JAK-STAT signaling pathway and prevents STAT from becoming phosphorylated.In the acute phase of chikungunya, the virus is typically present in the areas where symptoms present, specifically skeletal muscles, and joints. In the chronic phase, it is suggested that viral persistence (the inability of the body to entirely rid itself of the virus), lack of clearance of the antigen, or both, contribute to joint pain. The inflammation response during both the acute and chronic phase of the disease results in part from interactions between the virus and monocytes and macrophages. Chikungunya virus disease in humans is associated with elevated serum levels of specific cytokines and chemokines. High levels of specific cytokines have been linked to more severe acute disease: interleukin-6 (IL-6), IL-1β, RANTES, monocyte chemoattractant protein 1 (MCP-1), monokine induced by gamma interferon (MIG), and interferon gamma-induced protein 10 (IP-10). Cytokines may also contribute to chronic Chikungunya virus disease, as persistent joint pain has been associated with elevated levels of IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF). In those with chronic symptoms, a mild elevation of C-reactive protein (CRP) has been observed, suggesting ongoing chronic inflammation. However, there is little evidence linking chronic Chikungunya virus disease and the development of autoimmunity.
Viral replication
The virus consists of four nonstructural proteins and three structural proteins. The structural proteins are the capsid and two envelope glycoproteins: E1 and E2, which form heterodimeric spikes on the viron surface. E2 binds to cellular receptors in order to enter the host cell through receptor-mediated endocytosis. E1 contains a fusion peptide which, when exposed to the acidity of the endosome in eukaryotic cells, dissociates from E2 and initiates membrane fusion that allows the release of nucleocapsids into the host cytoplasm, promoting infection. The mature virion contains 240 heterodimeric spikes of E2/E1, which after release, bud on the surface of the infected cell, where they are released by exocytosis to infect other cells.
Diagnosis
Chikungunya is diagnosed on the basis of clinical, epidemiological, and laboratory criteria. Clinically, acute onset of high fever and severe joint pain would lead to suspicion of chikungunya. Epidemiological criteria consist of whether the individual has traveled to or spent time in an area in which chikungunya is present within the last twelve days (i.e.) the potential incubation period). Laboratory criteria include a decreased lymphocyte count consistent with viremia. However a definitive laboratory diagnosis can be accomplished through viral isolation, RT-PCR, or serological diagnosis.The differential diagnosis may include other mosquito-borne diseases, such as dengue or malaria, or other infections such as influenza. Chronic recurrent polyarthralgia occurs in at least 20% of chikungunya patients one year after infection, whereas such symptoms are uncommon in dengue.Virus isolation provides the most definitive diagnosis, but takes one to two weeks for completion and must be carried out in biosafety level III laboratories. The technique involves exposing specific cell lines to samples from whole blood and identifying Chikungunya virus-specific responses. RT-PCR using nested primer pairs is used to amplify several chikungunya-specific genes from whole blood, generating thousands to millions of copies of the genes in order to identify them. RT-PCR can also be used to quantify the viral load in the blood. Using RT-PCR, diagnostic results can be available in one to two days. Serological diagnosis requires a larger amount of blood than the other methods, and uses an ELISA assay to measure chikungunya-specific IgM levels in the blood serum. One advantage offered by serological diagnosis is that serum IgM is detectable from 5 days to months after the onset of symptoms, but drawbacks are that results may require two to three days, and false positives can occur with infection due to other related viruses, such as onyongnyong virus and Semliki Forest virus.Presently, there is no specific way to test for chronic signs and symptoms associated with Chikungunya fever although nonspecific laboratory findings such as C reactive protein and elevated cytokines can correlate with disease activity.
Prevention
Because no approved vaccine exists, the most effective means of prevention are protection against contact with the disease-carrying mosquitoes and controlling mosquito populations by limiting their habitat. Mosquito control focuses on eliminating the standing water where mosquitos lay eggs and develop as larva; if elimination of the standing water is not possible, insecticides or biological control agents can be added. Methods of protection against contact with mosquitos include using insect repellents with substances such as DEET, icaridin, PMD (p-menthane-3,8-diol, a substance derived from the lemon eucalyptus tree), or ethyl butylacetylaminopropionate (IR3535). However, increasing insecticide resistance presents a challenge to chemical control methods.Wearing bite-proof long sleeves and trousers also offers protection, and garments can be treated with pyrethroids, a class of insecticides that often has repellent properties. Vaporized pyrethroids (for example in mosquito coils) are also insect repellents. As infected mosquitoes often feed and rest inside homes, securing screens on windows and doors will help to keep mosquitoes out of the house. In the case of the day-active A. aegypti and A. albopictus, however, this will have only a limited effect, since many contacts between the mosquitoes and humans occur outdoors.
Vaccine
As of 2021, no approved vaccines are available. A phase-II vaccine trial used a live, attenuated virus, to develop viral resistance in 98% of those tested after 28 days and 85% still showed resistance after one year. However, 8% of people reported transient joint pain, and attenuation was found to be due to only two mutations in the E2 glycoprotein. Alternative vaccine strategies have been developed, and show efficacy in mouse models. In August 2014 researchers at the National Institute of Allergy and Infectious Diseases in the USA were testing an experimental vaccine which uses virus-like particles (VLPs) instead of attenuated virus. All the 25 people participated in this phase 1 trial developed strong immune responses. As of 2015, a phase 2 trial was planned, using 400 adults aged 18 to 60 and to take place at 6 locations in the Caribbean. Even with a vaccine, mosquito population control and bite prevention will be necessary to control chikungunya disease. In 2021, two vaccine manufacturers, one in France, the other in the United States, reported successful completion of Phase II clinical trials.
Treatment
Currently, no specific treatment for chikungunya is available. Supportive care is recommended, and symptomatic treatment of fever and joint swelling includes the use of nonsteroidal anti-inflammatory drugs such as naproxen, non-aspirin analgesics such as paracetamol (acetaminophen) and fluids. Aspirin is not recommended due to the increased risk of bleeding. Despite anti-inflammatory effects, corticosteroids are not recommended during the acute phase of disease, as they may cause immunosuppression and worsen infection.Passive immunotherapy has potential benefit in treatment of chikungunya. Studies in animals using passive immunotherapy have been effective, and clinical studies using passive immunotherapy in those particularly vulnerable to severe infection are currently in progress. Passive immunotherapy involves administration of anti-CHIKV hyperimmune human intravenous antibodies (immunoglobulins) to those exposed to a high risk of chikungunya infection. No antiviral treatment for Chikungunya virus is currently available, though testing has shown several medications to be effective in vitro.
Chronic arthritis
In those who have more than two weeks of arthritis, ribavirin may be useful. The effect of chloroquine is not clear. It does not appear to help acute disease, but tentative evidence indicates it might help those with chronic arthritis. Steroids do not appear to be an effective treatment. NSAIDs and simple analgesics can be used to provide partial symptom relief in most cases. Methotrexate, a drug used in the treatment of rheumatoid arthritis, has been shown to have benefit in treating inflammatory polyarthritis resulting from chikungunya, though the drug mechanism for improving viral arthritis is unclear.
Prognosis
The mortality rate of chikungunya is slightly less than 1 in 1000. Those over the age of 65, neonates, and those with underlying chronic medical problems are most likely to have severe complications. Neonates are vulnerable as it is possible to vertically transmit chikungunya from mother to infant during delivery, which results in high rates of morbidity, as infants lack fully developed immune systems. The likelihood of prolonged symptoms or chronic joint pain is increased with increased age and prior rheumatological disease.
Epidemiology
Historically, chikungunya has been present mostly in the developing world. The disease causes an estimated 3 million infections each year. Epidemics in the Indian Ocean, Pacific Islands, and in the Americas, continue to change the distribution of the disease.
In Africa, chikungunya is spread by a sylvatic cycle in which the virus largely cycles between other non-human primates, small mammals, and mosquitos between human outbreaks. During outbreaks, due to the high concentration of virus in the blood of those in the acute phase of infection, the virus can circulate from humans to mosquitoes and back to humans. The transmission of the pathogen between humans and mosquitoes that exist in urban environments was established on multiple occasions from strains occurring on the eastern half of Africa in non-human primate hosts. This emergence and spread beyond Africa may have started as early as the 18th century. Currently, available data does not indicate whether the introduction of chikungunya into Asia occurred in the 19th century or more recently, but this epidemic Asian strain causes outbreaks in India and continues to circulate in Southeast Asia. In Africa, outbreaks were typically tied to heavy rainfall causing increased mosquito population. In recent outbreaks in urban centers, the virus has spread by circulating between humans and mosquitoes.Global rates of chikungunya infection are variable, depending on outbreaks. When chikungunya was first identified in 1952, it had a low-level circulation in West Africa, with infection rates linked to rainfall. Beginning in the 1960s, periodic outbreaks were documented in Asia and Africa. However, since 2005, following several decades of relative inactivity, chikungunya has re-emerged and caused large outbreaks in Africa, Asia, and the Americas. In India, for instance, chikungunya re-appeared following 32 years of absence of viral activity. Outbreaks have occurred in Europe, the Caribbean, and South America, areas in which chikungunya was not previously transmitted. Local transmission has also occurred in the United States and Australia, countries in which the virus was previously unknown. In 2005, an outbreak on the island of Réunion was the largest then documented, with an estimated 266,000 cases on an island with a population of approximately 770,000. In a 2006 outbreak, India reported 1.25 million suspected cases. Chikungunya was recently introduced to the Americas, and from 2013 to 2014 in the Americas, 1,118,763 suspected cases and 24,682 confirmed cases were reported by the PAHO.An analysis of the genetic code of Chikungunya virus suggests that the increased severity of the 2005–present outbreak may be due to a change in the genetic sequence which altered the E1 segment of the virus viral coat protein, a variant called E1-A226V. This mutation potentially allows the virus to multiply more easily in mosquito cells. The change allows the virus to use the Asian tiger mosquito (an invasive species) as a vector in addition to the more strictly tropical main vector, Aedes aegypti. Enhanced transmission of Chikungunya virus by A. albopictus could mean an increased risk for outbreaks in other areas where the Asian tiger mosquito is present. A albopictus is an invasive species which has spread through Europe, the Americas, the Caribbean, Africa and the Middle East.After the detection of zika virus in Brazil in April 2015, the first ever in the Western Hemisphere, it is now thought some chikungunya and dengue cases could in fact be zika virus cases or coinfections.
History
The word chikungunya is believed to have been derived from a description in the Makonde language, meaning "that which bends up", of the contorted posture of people affected with the severe joint pain and arthritic symptoms associated with this disease. The disease was first described by Marion Robinson and W.H.R. Lumsden in 1955, following an outbreak in 1952 on the Makonde Plateau, along the border between Mozambique and Tanganyika (the mainland part of modern-day Tanzania).According to the initial 1955 report about the epidemiology of the disease, the term chikungunya is derived from the Makonde root verb kungunyala, meaning to dry up or become contorted. In concurrent research, Robinson glossed the Makonde term more specifically as "that which bends up". Subsequent authors apparently overlooked the references to the Makonde language and assumed the term to have been derived from Swahili, the lingua franca of the region. The erroneous attribution to Swahili has been repeated in numerous print sources. Many erroneous spellings of the name of the disease are also in common use.
Since its discovery in Tanganyika, Africa, in 1952, Chikungunya virus outbreaks have occurred occasionally in Africa, South Asia, and Southeast Asia, but recent outbreaks have spread the disease over a wider range.The first recorded outbreak of this disease may have been in 1779. This is in agreement with the molecular genetics evidence that suggests it evolved around the year 1700.
Research
Chikungunya is one of more than a dozen agents researched as a potential biological weapon.This disease is part of the group of neglected tropical diseases.
See also
Coalition for Epidemic Preparedness Innovations
Epidemiology of chikungunya
References
Works cited
Burt FJ, Chen W, Miner JJ, Lenschow DJ, Merits A, Schnettler E, Kohl A, Rudd PA, Taylor A, Herrero LJ, Zaid A, Ng LF, Mahalingam S (April 2017). "Chikungunya virus: an update on the biology and pathogenesis of this emerging pathogen". Lancet Infect Dis. 17 (4): e107–e117. doi:10.1016/S1473-3099(16)30385-1. PMID 28159534.
Vairo F, Haider N, Kock R, Ntoumi F, Ippolito G, Zumla A (December 2019). "Chikungunya: Epidemiology, Pathogenesis, Clinical Features, Management, and Prevention" (PDF). Infect Dis Clin North Am. 33 (4): 1003–1025. doi:10.1016/j.idc.2019.08.006. PMID 31668189. S2CID 241044156.
External links
Chikungunya fact sheet—from the World Health Organization (WHO)
Chikungunya outbreaks—from the World Health Organization (WHO)
Togaviridae—from the Virus Pathogen Database and Analysis Resource (ViPR)
"Chikungunya". European Centre for Disease Prevention and Control. 23 January 2008. Archived from the original on 5 August 2009. Retrieved 20 May 2013.
Chikungunya in Cuba Archived 18 July 2014 at the Wayback Machine
Chikungunya: The key role of "innate immunity" |
Anterior cruciate ligament injury | An anterior cruciate ligament injury occurs when the anterior cruciate ligament (ACL) is either stretched, partially torn, or completely torn. The most common injury is a complete tear. Symptoms include pain, an audible cracking sound during injury, instability of the knee, and joint swelling. Swelling generally appears within a couple of hours. In approximately 50% of cases, other structures of the knee such as surrounding ligaments, cartilage, or meniscus are damaged.The underlying mechanism often involves a rapid change in direction, sudden stop, landing after a jump, or direct contact to the knee. It is more common in athletes, particularly those who participate in alpine skiing, football (soccer), netball, American football, or basketball. Diagnosis is typically made by physical examination and is sometimes supported by magnetic resonance imaging (MRI). Physical examination will often show tenderness around the knee joint, reduced range of motion of the knee, and increased looseness of the joint.Prevention is by neuromuscular training and core strengthening. Treatment recommendations depend on desired level of activity. In those with low levels of future activity, nonsurgical management including bracing and physiotherapy may be sufficient. In those with high activity levels, surgical repair via arthroscopic anterior cruciate ligament reconstruction is often recommended. This involves replacement with a tendon taken from another area of the body or from a cadaver. Following surgery rehabilitation involves slowly expanding the range of motion of the joint, and strengthening the muscles around the knee. Surgery, if recommended, is generally not performed until the initial inflammation from the injury has resolved.About 200,000 people are affected per year in the United States. In some sports, females have a higher risk of ACL injury, while in others, both sexes are equally affected. While adults with a complete tear have a higher rate of knee osteoarthritis, treatment strategy does not appear to change this risk. ACL tears can also occur in some animals, such as dogs. The most common knee injury in dogs is ACL or CCL rupture; in fact, till proven otherwise, unexpected hind limb lameness is usually due to a ruptured cruciate.
Signs and symptoms
When an individual has an ACL injury, they are likely to hear a "pop" in their knee followed by pain and swelling. They may also experience instability in the knee once they resume walking and other activities, as the ligament can no longer stabilize the knee joint and keep the tibia from sliding forward.Reduced range of motion of the knee and tenderness along the joint line are also common signs of an acute ACL injury. The pain and swelling may resolve on its own; however, the knee will remain unstable and returning to sport without treatment may result in further damage to the knee.
Causes
Causes may include:
Changing direction rapidly (also known as "cutting")
Landing from a jump awkwardly
Coming to a sudden stop when running
A direct contact or collision to the knee (e.g. during a football tackle or a motor vehicle collision)These movements cause the tibia to shift away from the femur rapidly, placing strain on the knee joint and potentially leading to rupture of the ACL. About 80% of ACL injuries occur without direct trauma. Risk factors include female anatomy, specific sports, poor conditioning, fatigue, and playing on a turf field.
Female predominance
Female athletes are two to eight times more likely to strain their ACL in sports that involve cutting and jumping as compared to men who play the same particular sports. NCAA data has found relative rates of injury per 1000 athlete exposures as follows:
Mens basketball 0.07, womens basketball 0.23
Mens lacrosse 0.12, womens lacrosse 0.17
Mens football 0.09, womens football 0.28The highest rate of ACL injury in women occurred in gymnastics, with a rate of injury per 1000 athlete exposures of 0.33.
Of the four sports with the highest ACL injury rates, three were womens – gymnastics, basketball and soccer.Differences between males and females identified as potential causes are the active muscular protection of the knee joint, differences in leg/pelvis alignment, and relative ligament laxity caused by differences in hormonal activity from estrogen and relaxin. Birth control pills also appear to decrease the risk of ACL injury.
Dominance theories
Some studies have suggested that there are four neuromuscular imbalances that predispose women to higher incidence of ACL injury. Female athletes are more likely to jump and land with their knees relatively straight and collapsing in towards each other, while most of their bodyweight falls on a single foot and their upper body tilts to one side. Several theories have been described to further explain these imbalances. These include the ligament dominance, quadriceps dominance, leg dominance, and trunk dominance theories.The ligament dominance theory suggests that when females athletes land after a jump, their muscles do not sufficiently absorb the impact of the ground. As a result, the ligaments of the knee must absorb the force, leading to a higher risk of injury. Quadriceps dominance refers to a tendency of female athletes to preferentially use the quadriceps muscles to stabilize the knee joint. Given that the quadriceps muscles work to pull the tibia forward, an overpowering contraction of the quadriceps can place strain on the ACL, increasing risk of injury.Leg dominance describes the observation that women tend to place more weight on one leg than another. Finally, trunk dominance suggests that males typically exhibit greater control of the trunk in performance situations as evidenced by greater activation of the internal oblique muscle. Female athletes are more likely to land with their upper body tilted to one side and more weight on one leg than the other, therefore placing greater rotational force on their knees.
Hormonal and anatomic differences
Before puberty, there is no observed difference in frequency of ACL tears between the sexes. Changes in sex hormone levels, specifically elevated levels of estrogen and relaxin in females during the menstrual cycle, have been hypothesized as causing predisposition of ACL ruptures. This is because they may increase joint laxity and extensibility of the soft tissues surrounding the knee joint. Ongoing research has observed a greater occurrence of ACL injuries in females during ovulation and fewer injuries during the follicular and luteal phases of the menstrual cycle.Study results have shown that female collegiate athletes with concentration levels of relaxin that are greater than 6.0 pg/mL are at four times higher risk of an ACL tear than those with lower concentrations.Additionally, female pelvises widen during puberty through the influence of sex hormones. This wider pelvis requires the femur to angle toward the knees. This angle towards the knee is referred to as the Q angle. The average Q angle for men is 14 degrees and the average for women is 17 degrees. Steps can be taken to reduce this Q angle, such as using orthotics. The relatively wider female hip and widened Q angle may lead to an increased likelihood of ACL tears in women.
ACL, muscular stiffness, and strength
During puberty, sex hormones also affect the remodeled shape of soft tissues throughout the body. The tissue remodeling results in female ACLs that are smaller and will fail (i.e. tear) at lower loading forces, and differences in ligament and muscular stiffness between men and women. Womens knees are less stiff than mens during muscle activation. Force applied to a less stiff knee is more likely to result in ACL tears.In addition, the quadriceps femoris muscle is an antagonist to the ACL. According to a study done on female athletes at the University of Michigan, 31% of female athletes recruited the quadriceps femoris muscle first as compared to 17% in males. Because of the elevated contraction of the quadriceps femoris muscle during physical activity, an increased strain is placed onto the ACL due to the "tibial translation anteriorly".
Pathophysiology
The knee joint is formed by three bones: the femur (thighbone), the tibia (shinbone), and the patella (kneecap). These bones are held together by ligaments, which are strong bands of tissue that keep the joint stable while an individual is walking, running, jumping, etc. There are two types of ligaments in the knee: the collateral ligaments and the cruciate ligaments.The collateral ligaments include the medial collateral ligament (along the inside of the knee) and the lateral or fibular collateral ligament (along the outside of the knee). These two ligaments function to limit sideways movement of the knee.The cruciate ligaments form an "X" inside the knee joint with the anterior cruciate ligament running from the front of the tibia to the back of the femur, and the posterior cruciate ligament running from the back of the tibia to the front of the femur. The anterior cruciate ligament prevents the tibia from sliding out in front of the femur and provides rotational stability.There are also two C-shaped structures made of cartilage called the medial meniscus and lateral meniscus that sit on top of the tibia in the knee joint and serve as cushion for the bones.
Diagnosis
Manual tests
Most ACL injuries can be diagnosed by examining the knee and comparing it to the other, non-injured knee. When a doctor suspects ACL injury in a person who reports a popping sound in the knee followed by swelling, pain, and instability of the knee joint, they can perform several tests to evaluate the damage to the knee. These tests include the pivot-shift test, anterior drawer test, and Lachman test. The pivot-shift test involves flexing the knee while holding onto the ankle and slightly rotating the tibia inwards. In the anterior drawer test, the examiner flexes the knees to 90 degrees, sits on the persons feet, and gently pulls the tibia towards themself. The Lachman test is performed by placing one hand on the persons thigh and the other on the tibia and pulling the tibia forward. These tests are meant to test whether the ACL is intact and therefore able to limit the forward motion of the tibia. The Lachman test is recognized by most authorities as the most reliable and sensitive of the three.
Medical imaging
Though clinical examination in experienced hands can be accurate, the diagnosis is usually confirmed by magnetic resonance imaging, which provides images of the soft tissues like ligaments and cartilage around the knee. It may also permit visualization of other structures which may have been coincidentally involved, such as the menisci or collateral ligaments. An x-ray may be performed in addition to evaluate whether one of the bones in the knee joint was broken during the injury.MRI is perhaps the most used technique for diagnosing the state of the ACL, but it is not always the most reliable technique as the ACL can be obscured by blood that fills the joint after an injury.
Arthrometers/Laximeters
Another form of evaluation that may be used in case physical examination and MRI are inconclusive is laximetry testing (i.e. arthrometry and stress imaging), which involve applying a force to the leg and quantifying the resulting displacement of the knee. These medical devices basically replicate manual tests but offer objective assessments. The GNRB arthrometer, for example, is a knee arthrometer that is considered more effective than the Lachman test.
Classification
An injury to a ligament is called a sprain. The American Academy of Orthopedic Surgeons defines ACL injury in terms of severity and classifies them as Grade 1, 2, or 3 sprains. Grade 1 sprains occur when the ligament is stretched slightly but the stability of the knee joint is not affected. Grade 2 sprains occur when the ligament is stretched to the point that it becomes loose; this is also referred to as a partial tear. Grade 3 sprains occur when the ligament is completely torn into two pieces, and the knee joint is no longer stable. This is the most common type of ACL injury.Around half of ACL injuries occur in conjunction with injury to other structures in the knee, including the other ligaments, menisci, or cartilage on the surface of the bones. A specific pattern of injury called the "unhappy triad" (also known as the "terrible triad," or "ODonoghues triad") involves injury to the ACL, MCL, and medial meniscus, and occurs when a lateral force is applied to the knee while the foot is fixed on the ground.
Prevention
Interest in reducing non-contact ACL injury has been intense. The International Olympic Committee, after a comprehensive review of preventive strategies, has stated that injury prevention programs have a measurable effect on reducing injuries. These programs are especially important in female athletes who bear higher incidence of ACL injury than male athletes, and also in children and adolescents who are at high risk for a second ACL tear.Researchers have found that female athletes often land with the knees relatively straight and collapsing inwards towards each other, with most of their bodyweight on a single foot and their upper body tilting to one side; these four factors put excessive strain on the ligaments on the knee and thus increase the likelihood of ACL tear. There is evidence that engaging in neuromuscular training (NMT), which focus on hamstring strengthening, balance, and overall stability to reduce risk of injury by enhancing movement patterns during high risk movements. Such programs are beneficial for all athletes, particularly adolescent female athletes.Injury prevention programs (IPPs), are reliable in reducing the risk factors of ACL inquiries, referring to dominance theories. The ligament dominance theory reduced peak knee abduction moment but should be more focused on prioritizing individualized, task-specific exercises focusing on an athletes risk profile. It is more beneficial than a generic program. There is an increase in hip and knee flexion angles, such as plyometrics and jump-landing tasks, which reduces the risk of quadriceps dominance. However, there were no changes found for peak vGRF, which measures for "softer" landings. Unfortunately, there was no conclusive data on how IPPs reduces the risk associated with leg dominance theory.
Treatment
Treatment for ACL tears is important to:
Reduce abnormal knee movements and improve knee function
Build trust and confidence to use the knee normally again
Prevent further injury to the knee and reduce the risk of osteoarthritis
Optimise long-term quality of life following the injury
Nonsurgical
Nonsurgical treatment for ACL rupture involves progressive, structured rehabilitation that aims to restore muscle strength, dynamic knee control and psychological confidence. For some, the ACL may heal without surgery during the rehabilitation process (i.e. the torn pieces re-unite to form a functional ligament).The purpose of exercise treatment is to restore the normal functioning of the muscular and balance system around the knee. Research has demonstrated that by training the muscles around the knee appropriately through exercise treatment, the body can learn to control the knee again, and despite extra movement inside the knee, the knee can feel strong and able to withstand force.Typically, this approach involves visiting a physical therapist or sports medicine professional soon after injury to oversee an intensive, structured program of exercises. Other treatments may be used initially such as hands-on therapies in order to reduce pain. The physiotherapist will act as a coach through rehabilitation, usually by setting goals for recovery and giving feedback on progress.
Estimated non-surgical recovery timeframe is 3–6 months and depends on the extent of the original injury, pre-existing fitness and commitment to the rehabilitation and sporting goals. Some may not be satisfied with the outcome of non-surgical management and may opt for surgery later.
Surgery
ACL reconstruction surgery involves replacing the torn ACL with a "graft," which is a tendon taken from another source. Grafts can be taken from the patellar tendon, hamstring tendon, quadriceps tendon from either the person undergoing the procedure ("autograft") or a cadaver ("allograft"). The graft serves as scaffolding upon which new ligament tissue will grow.The surgery is done with an arthroscope or tiny camera inserted inside the knee, with additional small incisions made around the knee to insert surgical instruments. This method is less invasive and is proven to result in less pain from surgery, less time in the hospital, and quicker recovery times than "open" surgery (in which a long incision is made down the front of the knee and the joint is opened and exposed).The timing of ACL reconstruction has been controversial, with some studies showing worse outcomes when surgery is done immediately after injury, and others showing no difference in outcomes when surgery is done immediately compared to when surgery is delayed. The American Academy of Orthopedic Surgeons has stated that there is moderate evidence to support the guideline that ACL reconstruction should occur within five months of injury in order to improve a persons function and protect the knee from further injury; however, additional studies need to be done to determine the best time for surgery and to better understand the effect of timing on clinical outcomes.Young athletes who have early surgical reconstruction are more likely to return to their previous level of athletic ability when compared to those who underwent delayed surgery or nonoperative treatment. They are also less likely to experience instability in their knee if they undergo early surgery.
There are over 100,000 ACL reconstruction surgeries per year in the United States. Over 95% of ACL reconstructions are performed in the outpatient setting. The most common procedures performed during ACL reconstruction are partial meniscectomy and chondroplasty. Asymmetry in the repaired knee is a possibility and has been found to have a large effect between limbs for peak vertical ground reaction force, peak knee-extension moment, and loading rate during double-limb landings, as well as mean knee-extension moment and knee energy absorption during both double- and single-limb landings. Analysis of joint symmetry along with movement patterns should be a part of return to sports criteria.
Rehabilitation
The goals of rehabilitation following an ACL injury are to regain knee strength and motion. If an individual with an ACL injury undergoes surgery, the rehabilitation process will first focus on slowly increasing the range of motion of the joint, then on strengthening the surrounding muscles to protect the new ligament and stabilize the knee. Finally, functional training specific to the activities required for certain sports is begun. It may take six or more months before an athlete can return to sport after surgery, as it is vital to regain a sense of balance and control over the knee in order to prevent a second injury.
Prognosis
The prognosis of ACL injury is generally good, with many people regaining function of the injured leg within months. ACL injury used to be a career-ending injury for competitive athletes; however, in recent years ACL reconstruction surgery followed by physical therapy has allowed many athletes to return to their pre-injury level of performance.Long term complications of ACL injury include early onset arthritis of the knee and/or re-tearing the ligament. Factors that increase risk of arthritis include severity of the initial injury, injury to other structures in the knee, and level of activity following treatment. Not repairing tears to the ACL can sometimes cause damage to the cartilage inside the knee because with the torn ACL, the tibia and femur bone are more likely to rub against each other.Unfortunately, young female athletes have a significant risk of re-tearing an ACL graft, or tearing the ACL on the other knee after their recovery. This risk has been recorded as being nearly 1 out of every 4 young athletes. Therefore, athletes should be screened for any neuromuscular deficit (i.e. weakness greater in one leg than another, or incorrect landing form) before returning to sport.
Epidemiology
There are around 200,000 ACL tears each year in the United States. ACL tears newly occur in about 69 per 100,000 per year with rates in males of 82 per 100,000 and females of 59 per 100,000. When breaking down rates based on age and sex, females between the ages of 14-18 had the highest rates of injury with 227.6 per 100,000. Males between the ages of 19-24 had the highest rates of injury with 241 per 100,000.
Sports
Rates of re-rupture among college athletes were highest in male football players with 15 per 10,000, followed by female gymnasts with 8 per 10,000 and female soccer players with 5.2 per 10,000.High school athletes are at increased risk for ACL tears when compared to non-athletes. Among high school girls in the US, the sport with the highest risk of ACL tear is soccer, followed by basketball and lacrosse. In the US womens basketball and soccer experience the most ACL tears then all other sports. The highest risk sport for high school boys in the US was basketball, followed by lacrosse and soccer. In basketball, women are 5-8 times more likely to experience an ACL tear then men.
Dogs
Cruciate ligament rupture is a common orthopedic disorder in dogs. A study of insurance data showed the majority of the breeds with increased risk of cruciate ligament rupture were large or giant.
References
== External links == |
Rotor syndrome | Rotor syndrome (also known as Rotor type hyperbilirubinemia) is a rare cause of mixed direct (conjugated) and indirect (unconjugated) hyperbilirubinemia, relatively benign, autosomal recessive bilirubin disorder characterized by non-hemolytic jaundice due to the chronic elevation of predominantly conjugated bilirubin.Rotor type hyperbilirubinemia is a distinct yet similar disorder to Dubin–Johnson syndrome – both diseases cause an increase in conjugated bilirubin. Whereas rotor syndrome differs in that it is a result of impaired hepatocellular storage of conjugated bilirubin that leaks into plasma causing hyperbilirubinemia.
Signs and symptoms
Rotor syndrome has many features in common with Dubin–Johnson syndrome, an exception being that the liver cells are not pigmented. The main symptom is a non-itching jaundice. There is a rise in bilirubin in the patients serum, mainly of the conjugated type.
It can be differentiated from Dubin–Johnson syndrome in the following ways:
Rotor syndrome may exacerbate toxic side effects of the medication irinotecan.
Pathophysiology
Rotor syndrome is caused by mutations in two proteins responsible for transporting bilirubin and other compounds from the blood to the liver to be metabolized and cleared from the body.Coproporphyrin I, a major coproporphyrin isomer in bile, is transported from the hepatocyte back into the circulation and is excreted in the urine. Thus, urine coproporphyrin is elevated in Rotor syndrome.Cholescintigraphy using sulfobromophthalein (BSP) have shown that the transport capacity of dye into bile is reduced by less than 50%, and the storage capacity in the hepatocytes is decreased more than 5-fold compared with normal values in this disease.
Genetics
Rotor syndrome is inherited in an autosomal recessive manner. The SLCO1B1 and SLCO1B3 genes are involved in Rotor syndrome. Mutations in both genes are required for the condition to occur. The SLCO1B1 and SLCO1B3 genes provide instructions for making similar proteins, called organic anion transporting polypeptide 1B1 (OATP1B1) and organic anion transporting polypeptide 1B3 (OATP1B3), respectively. Both proteins are found in liver cells; they transport bilirubin and other compounds from the blood into the liver so that they can be cleared from the body. In the liver, bilirubin is dissolved in a digestive fluid called bile and then excreted from the body. The SLCO1B1 and SLCO1B3 gene mutations that cause Rotor syndrome lead to abnormally short, nonfunctional OATP1B1 and OATP1B3 proteins or an absence of these proteins. Without the function of either transport protein, bilirubin is less efficiently taken up by the liver and removed from the body. The buildup of this substance leads to jaundice in people with Rotor syndrome.
Diagnosis
Increased conjugated hyperbilirubinemia is the hallmark for diagnosing Rotor syndrome. There is no distinct black pigmentation of the liver as seen in a similar, Dubin-Johnson Syndrome. Genes, SLCO1B1 and SLCO1B3 that result in complete functional deficiencies of both protein products (OATP1B1 and OATP1B3, respectively), are also present.Rotor syndrome is largely a diagnosis of exclusion. Serological abnormalities in Rotor syndrome only include elevated total serum bilirubin (typically elevated between 2 to 5 mg/dL but may be as high as 20 mg/dL).Most of the time, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase levels are normal, but mild elevations can be seen. If any of these lab values are markedly elevated, investigation for other, more serious conditions is warranted.Imaging studies cannot diagnose Rotor syndrome but can help rule out other diseases that cause hyperbilirubinemia. For example, ultrasound of the liver and the biliary tree can help investigate the causes of extra-hepatic biliary obstruction. The gallbladder is visualized on oral cholecystography in Rotor syndrome while it is not visualized in Dubin Johnson syndrome. Ultimately, the best method of diagnosing the disease is the analysis of urine coproporphyrin excretion. The total urine coproporphyrin excretion in Rotor syndrome has a 2- to 5-fold elevation, with 65% constituting coproporphyrin I.
Treatment
Rotor syndrome is a benign disease requiring no treatment. Jaundice is a lifelong finding, but the disease is not associated with morbidity or mortality, and life expectancy is not affected. Most individuals with Rotor syndrome are born to consanguineous couples and its diagnosis may coincidently identify consanguinity. Distinguishing Rotor syndrome from other more serious disorders is important to avoid unnecessary workup and interventions. It is also critical to reassure and calm patients or family members of patients with Rotors syndrome that the condition is benign.
History
Rotor syndrome is named after the Filipino internist Arturo Belleza Rotor (1907–1988).
See also
Jaundice
Bilirubin metabolism
Gilberts syndrome
Crigler–Najjar syndrome
References
External links
Hyperbilirubinemia, Conjugated at eMedicine
Rotor syndrome at NIHs Office of Rare Diseases
Mentioned in MedlinePlus Encyclopedia: Jaundice – yellow skin |
Erbs palsy | Erbs palsy is a paralysis of the arm caused by injury to the upper group of the arms main nerves, specifically the severing of the upper trunk C5–C6 nerves. These form part of the brachial plexus, comprising the ventral rami of spinal nerves C5–C8 and thoracic nerve T1. These injuries arise most commonly, but not exclusively, from shoulder dystocia during a difficult birth. Depending on the nature of the damage, the paralysis can either resolve on its own over a period of months, necessitate rehabilitative therapy, or require surgery.
Presentation
The paralysis can be partial or complete; the damage to each nerve can range from bruising to tearing. The most commonly involved root is C5 (aka Erbs point: the union of C5 & C6 roots) as this is mechanically the furthest point from the force of traction, therefore, the first/most affected. Erb–Duchenne palsy presents as a lower motor neuron syndrome associated with sensibility disturbance and vegetative phenomena.The most commonly involved nerves are the suprascapular nerve, musculocutaneous nerve, and the axillary nerve.The signs of Erbs palsy include loss of sensation in the arm and paralysis and atrophy of the deltoid, biceps, and brachialis muscles. "The position of the limb, under such conditions, is characteristic: the arm hangs by the side and is rotated medially; the forearm is extended and pronated. The arm cannot be raised from the side; all power of flexion of the elbow is lost, as is also supination of the forearm". The resulting biceps damage is the main cause of this classic physical position commonly called "waiters tip".If the injury occurs at age early enough to affect development (e.g. as a neonate or infant), it often leaves the patient with stunted growth in the affected arm with everything from the shoulder through to the fingertips smaller than the unaffected arm. This also leaves the patient with impaired muscular, nervous and circulatory development. The lack of muscular development leads to the arm being much weaker than the unaffected one, and less articulate, with many patients unable to lift the arm above shoulder height unaided, as well as leaving many with an elbow contracture.The lack of development to the circulatory system can leave the arm with almost no ability to regulate its temperature, which often proves problematic during winter months when it would need to be closely monitored to ensure that the temperature of the arm was not dropping too far below that of the rest of the body. However the damage to the circulatory system also leaves the arm with another problem. It reduces the healing ability of the skin, so that skin damage takes far longer than usual to heal, and infections in the arm can be quite common if cuts are not sterilized as soon as possible.The neurological damage is often the most problematic aspect of Erbs palsy, but it is also the most varying. There have been cases of patients who have lost complete sensory perception within the arm after procedures whereas they had full sensory perception before. The most common area for a loss of sensory perception (except where the arm faces a total loss) is between the shoulder and the elbow, since the nerves which provide information from that area to the brain are also those first damaged in the initial causative trauma.
Cause
The most common cause of Erbs palsy is dystocia, an abnormal or difficult childbirth or labor. For example, it can occur if the infants head and neck are pulled toward the side at the same time as the shoulders pass through the birth canal. The condition can also be caused by excessive pulling on the shoulders during a cephalic presentation (head first delivery), or by pressure on the raised arms during a breech (feet first) delivery. Erbs palsy can also affect neonates affected by a clavicle fracture unrelated to dystocia.A similar injury may be observed at any age following trauma to the head and shoulder, which cause the nerves of the plexus to violently stretch, with the upper trunk of the plexus sustaining the greatest injury. Injury may also occur as the result of direct violence, including gunshot wounds and traction on the arm, or attempting to diminish shoulder joint dislocation. The level of damage to the constituent nerves is related to the amount of paralysis.
Diagnosis
The appearance of the affected arm (or arms) depends on the individual case. In some cases the arm may lack the ability to straighten or rotate but otherwise function normally giving the overall appearance of the arm to be stiff and crooked. Whereas in other circumstances the arm has little to no control and has a "loose" appearance. Treatment such as physiotherapy, massage and electrical stimulation can help to prevent this early on (or throughout) the patients life by strengthening the arm.In some cases, again, individuals may experience a great deal of discomfort. For example, they may experience a severe cramping pain that lasts for some time and is particularly painful after they have slept, running from the shoulder all the way down to the wrist. Although pain does not affect everyone with Erbs palsy, it can be extremely uncomfortable to those that it does and can even cause patients to be physically sick or faint. This extreme nerve pain is mostly common during the final stages of growth and almost always eases off in time. Other pains that people with Erbs palsy might endure include strained muscle, stiffness, circulatory problems and cramp. Different factors are dependent on the severity of the condition and can vary, so whilst some patient experience a lot of pain, some patients may experience no pain at all and for their affected arm to simply be visually crooked.Discomfort with the shoulder blade is also extremely common in Erbs palsy as the shoulder is often at risk of dislocation. This can result, again, in sickness or lack of sleep.
Treatment
Some babies recover on their own; however, some may require specialist intervention.Neonatal/pediatric neurosurgery is often required for avulsion fracture repair. Lesions may heal over time and function return. Physiotherapeutic care is often required to regain muscle usage.
Although range of motion is recovered in many children under one year in age, individuals who have not yet healed after this point will rarely gain full function in their arm and may develop arthritis.The three most common treatments for Erbs palsy are nerve transfers (usually from the opposite arm or limb), subscapularis releases and latissimus dorsi tendon transfers.Nerve transfers are usually performed on babies under the age of 9 months since the fast development of younger babies increases the effectiveness of the procedure. They are not usually carried out on patients older than this because when the procedure is done on older infants, more harm than good is done, and it can result in nerve damage in the area from which the nerves were taken. Scarring can vary from faint scars along the lines of the neck to full "T" shapes across the whole shoulder depending on the training of the surgeon and the nature of the transplant.Subscapularis releases, however, are not time limited. Since it is merely cutting a "Z" shape into the subscapularis muscle to provide stretch within the arm, it can be carried out at almost any age and can be carried out repeatedly on the same arm; however, this will compromise the integrity of the muscle.Latissimus dorsi tendon transfers involve cutting the latissimus dorsi in half horizontally in order to pull part of the muscle around and attach it to the outside of the biceps. This procedure provides external rotation with varying degrees of success. A side effect may be increased sensitivity of the part of the biceps where the muscle will now lie, since the latissimus dorsi has roughly twice the number of nerve endings per square inch of other muscles.
History
The renowned British obstetrician William Smellie is credited with the first medical description of an obstetric brachial plexus palsy. In his 1768 treatise on midwifery, he reported a case of transient bilateral arm paralysis in a newborn after difficult labour.
In 1861, Guillaume Benjamin Amand Duchenne coined the term "obstetric palsy of the brachial plexus" after analyzing four infants with paralysis of identical muscles in the arm and shoulder, after publishing his initial findings in 1855. In 1874, Wilhelm Heinrich Erb concluded in his thesis on adult brachial plexus injuries that associated palsies of the deltoid, biceps and subscapularis are derived from a radicular lesion at the level of C5 and C6 rather than isolated peripheral nerve lesions.
Notable people with Erbs palsy
Notable individuals with Erbs palsy include Emperor Wilhelm II of Germany, King of Prussia, the Palestinian psychiatrist Samah Jabr, and the Canadian journalist Barbara Frum. Martin Sheen was injured during birth and developed the condition in his left arm. His difference in arm length and range of motion can be seen in his work, especially Apocalypse Now and the jacket flip during The West Wing.
Professional wrestler Traci Brooks has Erbs palsy and has achieved a successful career. Another is former Iowa Hawkeyes standout defensive lineman Adrian Clayborn. Gangster rapper and Academy Award winner DJ Paul of Three Six Mafia also has the condition in his arm, which he often hides by wearing a cast during public appearances. Teenage archery champion Faith Oakley, who has Erbs palsy affecting her right arm, uses her teeth to pull back the bow string to shoot the arrow.Military brace has also caused Erbs palsy in military school cadets.
See also
Klumpkes paralysis
References
Further reading
Brachial-Plexus-Injuries at NINDS
Watt AJ, Niederbichler AD, Yang LJ, Chung KC (2007). "Wilhelm Heinrich Erb, M.D. (1840 to 1921): a historical perspective on Erbs palsy". Plast. Reconstr. Surg. 119 (7): 2161–6. doi:10.1097/01.prs.0000260726.74745.b8. PMID 17519716. S2CID 25575613.
== External links == |
Cutaneous larva migrans | Cutaneous larva migrans (abbreviated CLM) is a skin disease in humans, caused by the larvae of various nematode parasites of the hookworm family (Ancylostomatidae). These parasites live in the intestines of dogs, cats, and wild animals and should not be confused with other members of the hookworm family for which humans are definitive hosts, namely Ancylostoma duodenale and Necator americanus.
Colloquially called creeping eruption due to its presentation, the disease is also somewhat ambiguously known as "ground itch" or (in some parts of the southern United States) "sandworms", as the larvae like to live in sandy soil. Another vernacular name is plumbers itch. The medical term CLM literally means "wandering larvae in the skin".
Symptoms and signs
The infection causes a red, intensely pruritic (itchy) eruption, and may look like twirling lesions. The itching can become very painful and if scratched may allow a secondary bacterial infection to develop. Cutaneous larva migrans usually heals spontaneously over weeks to months and has been known to last as long as one year. However, the severity of the symptoms usually causes those infected to seek medical treatment before spontaneous resolution occurs. Following proper treatment, migration of the larvae within the skin is halted and relief of the associated itching can occur in less than 48 hours (reported for thiabendazole).This is separate from the similar cutaneous larva currens which is caused by Strongyloides. Larva currens is also a cause of migratory pruritic eruptions but is marked by 1) migratory speed on the order of inches per hour 2) perianal involvement due to autoinfection from stool and 3) a wide band of urticaria.
Cause
Hookworm eggs are shed in the infected dog (or other animal) feces to the ground and beach sand, where they then develop over a period of 1–2 weeks into the infectious larval form (filariform larvae). The filariform larvae can burrow through intact skin that comes into contact with soil or sand that is contaminated with feces. Although they are able to infect the deeper tissues of animals (through to the lungs and then the intestinal tract), humans are incidental hosts and the larvae are only able to penetrate the epidermis of the skin and thus create the typical wormlike burrows visible underneath the skin. These parasites apparently lack the collagenase enzymes required to penetrate through the basement membrane deeper into the dermal layers of the skin.
Treatment
CLM can be treated in a number of different ways:
Systemic (oral) agents include albendazole (trade name Albenza) and ivermectin (trade name Stromectol).
Another agent which can be applied either topically or taken by mouth is thiabendazole (trade name Mintezol), an anti-helminthic.
Topical freezing agents, such as ethylene chloride or liquid nitrogen, applied locally can freeze and kill the larvae, but this method has a high failure rate because the larvae are usually located away from the site of the visible skin trails. Additionally, this is a painful method which can cause blistering and/or ulceration of the skin and it is therefore not recommended.
It is recommended to use Benadryl or some anti-itch cream (i.e. Cortizone or Calamine lotion). This will help relieve some of the itch.
Wearing shoes in areas where these parasites are known to be endemic offers protection from infection. In general, avoiding exposure of skin to contaminated soil or sand offers the best protection. In some areas dogs have been prohibited from beaches in an attempt to control human infection.
Additional images
See also
Dermatology
Intestinal parasite
Visceral larva migrans
List of migrating cutaneous conditions
References
External links
DermAtlas -1921851750 |
Hypertensive emergency | A hypertensive emergency is very high blood pressure with potentially life-threatening symptoms and signs of acute damage to one or more organ systems (especially brain, eyes, heart, aorta, or kidneys). It is different from a hypertensive urgency by this additional evidence for impending irreversible hypertension-mediated organ damage (HMOD). Blood pressure is often above 200/120 mmHg, however there are no universally accepted cutoff values. Signs of organ damage will be discussed below.
Signs and symptoms
Symptoms may include headache, nausea, or vomiting. Chest pain may occur due to increased workload on the heart resulting in inadequate delivery of oxygen to meet the heart muscles metabolic needs. The kidneys may be affected, resulting in blood or protein in the urine, and acute kidney failure. People can have decreased urine production, fluid retention, and confusion.Other signs and symptoms can include:
Chest pain
Abnormal heart rhythms
Headache
Nosebleeds that are difficult to stop
Dyspnea
Fainting or the sensation of the world spinning around them (vertigo)
Severe anxiety
Agitation
Altered mental status
Abnormal sensationsThe most common presentations of hypertensive emergencies are cerebral infarction (24.5%), pulmonary edema (22.5%), hypertensive encephalopathy (16.3%), and congestive heart failure (12%). Less common presentations include intracranial bleeding, aortic dissection, and pre-eclampsia or eclampsia.Massive, rapid elevations in blood pressure can trigger any of these symptoms, and warrant further work-up by physicians. Physical exam would include measurement of blood pressure in both arms. Laboratory tests to be conducted include urine toxicology, blood glucose, a basic metabolic panel evaluating kidney function, or a complete metabolic panel evaluating liver function, EKG, chest x-rays, and pregnancy screening.The eyes may show bleeding in the retina, an exudate, cotton-wool spots, scattered splinter hemorrhages, or swelling of the optic disc called papilledema.
Causes
Many factors and causes are contributory in hypertensive crises. The most common cause is patients with diagnosed, chronic hypertension who have discontinued anti hypertensive medications.Other common causes of hypertensive crises are autonomic hyperactivity such as pheochromocytoma, collagen-vascular diseases, drug use particularly stimulants, cocaine and amphetamines and their substituted analogues, monoamine oxidase inhibitors or food-drug interactions, spinal cord disorders, glomerulonephritis, head trauma, neoplasias, preeclampsia and eclampsia, hyperthyroidism and renovascular hypertension. People withdrawing from medications such as clonidine or beta-blockers have been frequently found to develop hypertensive crises. It is important to note that these conditions exist outside of hypertensive emergency, in that patients diagnosed with these conditions are at increased risk of hypertensive emergencies or end organ failure.
Pathophysiology
The pathophysiology of hypertensive emergency is not well understood. Failure of normal autoregulation and an abrupt rise in systemic vascular resistance are typical initial components of the disease process.Hypertensive emergency pathophysiology includes:
Abrupt increase in systemic vascular resistance, likely related to humoral vasoconstrictors
Endothelial injury and dysfunction
Fibrinoid necrosis of the arterioles
Deposition of platelets and fibrin
Breakdown of normal autoregulatory functionThe resulting ischemia prompts further release of vasoactive substances including prostaglandins, free radicals, and thrombotic/mitotic growth factors, completing a vicious cycle of inflammatory changes. If the process is not stopped, homeostatic failure begins, leading to loss of cerebral and local autoregulation, organ system ischemia and dysfunction, and myocardial infarction. Single-organ involvement is found in approximately 83% of hypertensive emergency patients, two-organ involvement in about 14% of patients, and multi-organ failure (failure of at least 3 organ systems) in about 3% of patients.In the brain, hypertensive encephalopathy - characterized by hypertension, altered mental status, and swelling of the optic disc - is a manifestation of the dysfunction of cerebral autoregulation. Cerebral autoregulation is the ability of the blood vessels in the brain to maintain a constant blood flow. People with chronic hypertension can tolerate higher arterial pressure before their autoregulation system is disrupted. Hypertensives also have an increased cerebrovascular resistance which puts them at greater risk of developing cerebral ischemia if the blood flow decreases into a normotensive range. On the other hand, sudden or rapid rises in blood pressure may cause hyperperfusion and increased cerebral blood flow, causing increased intracranial pressure and cerebral edema, with increased risk of intracranial bleeding.In the heart, increased arterial stiffness, increased systolic blood pressure, and widened pulse pressures, all resulting from chronic hypertension, can cause significant damage. Coronary perfusion pressures are decreased by these factors, which also increase myocardial oxygen consumption, possibly leading to left ventricular hypertrophy. As the left ventricle becomes unable to compensate for an acute rise in systemic vascular resistance, left ventricular failure and pulmonary edema or myocardial ischemia may occur.In the kidneys, chronic hypertension has a great impact on the kidney vasculature, leading to pathologic changes in the small arteries of the kidney. Affected arteries develop endothelial dysfunction and impairment of normal vasodilation, which alter kidney autoregulation. When the kidneys autoregulatory system is disrupted, the intraglomerular pressure starts to vary directly with the systemic arterial pressure, thus offering no protection to the kidney during blood pressure fluctuations. The renin-aldosterone-angiotensin system can be activated, leading to further vasoconstriction and damage. During a hypertensive crisis, this can lead to acute kidney ischemia, with hypoperfusion, involvement of other organs, and subsequent dysfunction. After an acute event, this endothelial dysfunction has persisted for years.
Diagnosis
The term hypertensive emergency is primarily used as a specific term for a hypertensive crisis with a diastolic blood pressure greater than or equal to 120 mmHg or systolic blood pressure greater than or equal to 180 mmHg. Hypertensive emergency differs from hypertensive urgency in that, in the former, there is evidence of acute organ damage. Both of these definitions had collectively been known as malignant hypertension, although this medical term is replaced.In the pregnant patient, the definition of hypertensive emergency (likely secondary to pre-eclampsia or eclampsia) is only a blood pressure exceeding 160 mmHg systolic blood pressure or 110 mmHg diastolic blood pressure.
Treatment
In a hypertensive emergency, treatment should first be to stabilize the patients airway, breathing, and circulation per ACLS guidelines. Patients should have their blood pressure slowly lowered over a period of minutes to hours with an antihypertensive agent. Documented goals for blood pressure include a reduction in the mean arterial pressure by less than or equal to 25% within the first 8 hours of emergency. If blood pressure is lowered aggressively, patients are at increased risk of complications including stroke, blindness, or kidney failure. Several classes of anti hypertensive agents are recommended, with the choice depending on the cause of the hypertensive crisis, the severity of the elevation in blood pressure, and the patients baseline blood pressure prior to a hypertensive emergency. Physicians will attempt to identify a cause of the patients hypertension, including chest radiograph, serum laboratory studies evaluating kidney function, urinalysis, as that will alter the treatment approach for a more patient-directed regimen.Hypertensive emergencies differ from hypertensive urgency in that they are treated parenterally, whereas in urgency it is recommended to use oral anti hypertensives to reduce the risk of hypotensive complications or ischemia. Parenteral agents are classified into beta-blockers, calcium channel blockers, systemic vasodilators, or other (fenoldopam, phentolamine, clonidine). Medications include labetalol, nicardipine, hydralazine, sodium nitroprusside, esmolol, nifedipine, minoxidil, isradipine, clonidine, and chlorpromazine. These medications work through a variety of mechanisms. Labetalol is a beta-blocker with mild alpha antagonism, decreasing the ability of catecholamine activity to increase systemic vascular resistance, while also decreasing heart rate and myocardial oxygen demand. Nicardipine, Nifedipine, and Isradipine are calcium channel blockers that work to decrease systemic vascular resistance and subsequently lower blood pressure. Hydralazine and Sodium nitroprusside are systemic vasodilators, thereby reducing afterload, however can be found to have reflex tachycardia, making them likely second or third line choices. Sodium nitroprusside was previously the first-line choice due to its rapid onset, although now it is less commonly used due to side effects, drastic drops in blood pressure, and cyanide toxicity. Sodium nitroprusside is also contraindicated in patients with myocardial infarction, due to coronary steal. It is again important that the blood pressure is lowered slowly. The initial goal in hypertensive emergencies is to reduce the pressure by no more than 25% the mean arterial pressure. Excessive reduction in blood pressure can precipitate coronary, cerebral, or kidney ischemia and, possibly, infarction.A hypertensive emergency is not based solely on an absolute level of blood pressure, but also on a patients baseline blood pressure before the hypertensive crisis occurs. Individuals with a history of chronic hypertension may not tolerate a "normal" blood pressure, and can therefore present symptomatically with hypotension, including fatigue, light-headedness, nausea, vomiting, or syncope.
Prognosis
Severe hypertension is a serious and potentially life-threatening medical condition. It is estimated that people who do not receive appropriate treatment only live an average of about three years after the event.The morbidity and mortality of hypertensive emergencies depend on the extent of end-organ dysfunction at the time of presentation and the degree to which blood pressure is controlled afterward. With good blood pressure control and medication compliance, the 5-year survival rate of patients with hypertensive crises approaches 55%.The risks of developing a life-threatening disease affecting the heart or brain increase as the blood flow increases. Commonly, ischemic heart attack and stroke are the causes that lead to death in patients with severe hypertension. It is estimated that for every 20 mm Hg systolic or 10 mm Hg diastolic increase in blood pressures above 115/75 mm Hg, the mortality rate for both ischemic heart disease and stroke doubles.Consequences of hypertensive emergency result after prolonged elevations in blood pressure and associated end-organ dysfunction. Acute end-organ damage may occur, affecting the neurological, cardiovascular, kidney, or other organ systems. Some examples of neurological damage include hypertensive encephalopathy, cerebral vascular accident/cerebral infarction, subarachnoid hemorrhage, and intracranial bleeding. Cardiovascular system damage can include myocardial ischemia/infarction, acute left ventricular dysfunction, acute pulmonary edema, and aortic dissection. Other end-organ damage can include acute kidney failure or insufficiency, retinopathy, eclampsia, and microangiopathic hemolytic anemia.
Epidemiology
In 2000, it was estimated that 1 billion people worldwide have hypertension, making it the most prevalent condition in the world. Approximately 60 million Americans have chronic hypertension, with 1% of these individuals having an episode of hypertensive urgency. In emergency departments and clinics around the U.S., the prevalence of hypertensive urgency is suspected to be between 3-5%. 25% of hypertensive crises have been found to be hypertensive emergency versus urgency when presenting to the ER.Risk factors for hypertensive emergency include age, obesity, noncompliance to anti hypertensive medications, female sex, Caucasian race, preexisting diabetes or coronary artery disease, mental illness, and sedentary lifestyle. Several studies have concluded that African Americans have a greater incidence of hypertension and a greater morbidity and mortality from hypertensive disease than non-Hispanic whites, however hypertensive crises have a greater incidence in Caucasians. Although severe hypertension is more common in the elderly, it may occur in children (though very rarely), likely due to metabolic or hormonal dysfunction. In 2014, a systematic review identified women as having slightly higher increased risks of developing hypertensive crises than do men.With the usage of anti hypertensives, the rates of hypertensive emergencies has declined from 7% to 1% of patients with hypertensive urgency.16% of patients presenting with hypertensive emergency can have no known history of hypertension.
See also
Hypertensive retinopathy
Hypertensive encephalopathy
Preeclampsia
Eclampsia
Aortic dissection
Intracranial hemorrhage
References
== External links == |
Overlap syndrome | An overlap syndrome is a medical condition which shares features of at least two more widely recognised disorders. Examples of overlap syndromes can be found in many medical specialties such as overlapping connective tissue disorders in rheumatology, and overlapping genetic disorders in cardiology.
Rheumatology
Examples of overlap syndromes in rheumatology include mixed connective tissue disease and scleromyositis. Diagnosis depends on which diseases the patient shows symptoms and has positive antibodies for in their lab serology.
In overlap syndrome, features of the following diseases are found (most common listed):
Systemic lupus erythematosus (SLE)
Systemic sclerosis
Polymyositis
Dermatomyositis
Rheumatoid arthritis (RA)
Sjögrens syndrome
Eosinophilic granulomatosis with polyangiitis (EGPA)
Autoimmune thyroiditis
Antiphospholipid antibody syndromeThe treatment of overlapping connective tissue disorders is mainly based on the use of corticosteroids and immunosuppressants. Biologic drugs, i.e. anti-TNFα or anti-CD20 monoclonal antibodies, have been recently introduced as alternative treatments in refractory cases. There are some concerns with the use of anti-TNF agents in patients with systemic autoimmune diseases due to the risk of triggering disease exacerbations.The term polyangiitis overlap syndrome refers to a systemic vasculitis that shares features with two or more distinct vasculitis syndromes. The most common type of polyangiitis overlap syndrome is microscopic polyangiitis (MPA), which shares features with EGPA, granulomatosis with polyangiitis and panarteritis nodosa. Sometimes polyangiitis overlap syndrome is used as a synonym for MPA.
Gastroenterology
In gastroenterology, the term overlap syndrome may be used to describe autoimmune liver diseases that combine characteristic features of autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis.
Cardiology
In cardiology, genetic conditions such as Brugada syndrome can share features with related disorders caused by mutations in the same gene. An overlap syndrome can be seen whereby a mutation in the SCN5A gene encoding the cardiac sodium channel causes a reduction in the peak sodium current leading to the typical ECG features of Brugada syndrome, but which simultaneously increases the sustained late sodium current leading to the ECG features of Long QT syndrome type 3. Brugada syndrome can also overlap with arrhythmogenic cardiomyopathy due to certain mutations in the plakophilin gene.
See also
Autoimmune
Mixed connective tissue disease
References
Further reading
The Myositis Association Overlap Syndrome 2011 Conference Presentation
== External links == |
Fifth disease | Erythema infectiosum, fifth disease, or slapped cheek syndrome is one of several possible manifestations of infection by parvovirus B19. Fifth disease typically presents as a rash and is more common in children. While parvovirus B19 can affect humans of all ages, only two out of ten individuals will present with physical symptoms.The name "fifth disease" comes from its place on the standard list of rash-causing childhood diseases, which also includes measles (first), scarlet fever (second), rubella (third), Dukes disease (fourth, but is no longer widely accepted as distinct from scarlet fever), and roseola (sixth). Treatment is mostly supportive.
Signs and symptoms
Fifth disease starts with a low-grade fever, headache, rash, and cold-like symptoms, such as a runny or stuffy nose. These symptoms pass, then a few days later, the rash appears. The bright red rash most commonly appears in the face, particularly the cheeks. This is a defining symptom of the infection in children (hence the name "slapped cheek disease"). Occasionally, the rash will extend over the bridge of the nose or around the mouth. In addition to red cheeks, children often develop a red, lacy rash on the rest of the body, with the upper arms, torso, and legs being the most common locations. The rash typically lasts a few days and may itch; some cases have been known to last for several weeks. Patients are usually no longer infectious once the rash has appeared.Teenagers and adults may present with a self-limited arthritis. It manifests in painful swelling of the joints that feels similar to arthritis. Older children and adults with fifth disease may have difficulty in walking and in bending joints such as wrists, knees, ankles, fingers, and shoulders.The disease is usually mild, but in certain risk groups and rare circumstances, it can have serious consequences:
In pregnant women, infection in the first trimester has been linked to hydrops fetalis, causing spontaneous miscarriage.
In people with sickle-cell disease or other forms of chronic hemolytic anemia such as hereditary spherocytosis, infection can precipitate an aplastic crisis.
Those who are immunocompromised (HIV/AIDS, chemotherapy) may be at risk for complications if exposed.
In less than 5% of women with parvovirus B19 infection, a baby may develop severe anemia leading to miscarriage. This occurs most often during the first half of pregnancy.
Causes
Fifth disease, also known as erythema infectiosum, is caused by parvovirus B19, which only infects humans. Infection by parvovirus B19 can lead to multiple clinical manifestations, but the most common is fifth disease.Parvovirus B19 (B19V) is a small, single-stranded, non-enveloped DNA virus. Binding of B19V capsid to the cellular receptor globoside (Gb4Cer) results in a cascade of structural changes and subsequent signal transduction processes facilitating the entry of parvovirus B19 into the host cell. After gaining access to the host cell, BV19 binds to glycosphingolipid globoside (blood group P antigen) targeting erythroid lineage in the bone marrow. Replication of viral genome and release of virus from infected cells lead to various complex effects on hosts cellular environment such as induction of DNA damage, hijack of cell cycle and apoptosis (killing of infected cells).B19V DNA has been found in a wide range of tissues in healthy and diseased individuals indicates the persistence of B19V infection. According to a clinical microbiology review published by Jianming Qiu "Persistence of viral DNA has been detected in up to 50% of biopsy specimens of the spleen, lymph nodes, tonsils, liver, heart, synovial tissues, skin, brain, and testes, for decades after infection."Recovery from parvovirus B19 infection is achieved by production of IgM antibodies which are specific for virus and are generated 10–12 days after infection. After day 16, when signs of fifth disease (red rashes) and arthralgia (pain in joints) becomes apparent, specific anti B19 IgG is produced by immune cells. Production of serum anti B19 IgG keeps infection under control and facilitates the recovery of erythroid cell production in erythroid lineage cells that were targeted by parvovirus B19.
Diagnosis
The "slapped cheek" appearance of the rash can be suggestive of fifth disease, however, the rash can be mistaken with other skin related disease or infections. Blood samples testing can be definitive in confirming diagnosis. Anti-parvovirus B19 IgM antibody serum assay is the preferred method to detect previous infection. An antibody assay uses antibodies designed to detect parvovirus antigen or protein in blood circulation. The assay can result positive one week after initial infection. Negative results may prompt retesting in the future to rule out early sampling of blood serum. A positive result can also be indicative of an infection within the past two to six months. People acquire lifetime immunity if IgG antibodies are produced in response to parvovirus B19 exposure. Infection by parvovirus B19 can also be confirmed by isolation of viral DNA detected by PCR or direct hybridization. PCR Is considered significantly more sensitive to detecting viral antigen compared direct DNA hybridization. DNA hybridization assay can better detect variants of the parvovirus B19. There exists 3 biological similar genotypes of parvovirus B19, numbered one through three. The most common genotype circulating is genotype one. Laboratory tests can indicate complications of infection, including anemia, liver damage, and low platelet count.
Transmission
Fifth disease is transmitted primarily by respiratory secretions (saliva, mucus, etc.), but can also be spread by contact with infected blood. The incubation period (the time between the initial infection and the onset of symptoms) is usually between 4 and 21 days. Individuals with fifth disease are most infectious before the onset of symptoms. Typically, school children, day-care workers, teachers, and parents are most likely to be exposed to the virus. When symptoms are evident, the risk of transmission is small; therefore, symptomatic individuals do not need to be isolated. Vertical transmission from maternal infection may also occur, which can lead to hydrops fetalis due to the infections detrimental effects on red blood cell production.
Treatment
Treatment is supportive, as the infection is frequently self-limiting. No specific therapy is recommended. Antipyretics are commonly used to reduce fevers. In cases of arthropathy, such as those with arthritis or arthralgia, non-steroidal anti-inflammatories (NSAIDs) or other ant-inflammatories can be used. The rash usually does not itch, but can be mildly painful. The rash itself is not considered contagious. The infection generally lasts about 5 to 10 days. Stress, hot temperatures, exercise, and exposure to sunlight can contribute to reoccurrence within months of the initial infection. Upon resolution, immunity is considered life-long. Populations at greater risk of complications (see below) may need referral to a specialist. Anemia is a more severe complication that could result from parvovirus B19 infection and requires a blood transfusion as part of therapy.
Epidemiology
Fifth Disease is a viral illness caused by Parvovirus B19. The illness is very common and self-limiting. The modes of transmission include respiratory droplets, blood, or mother to fetus. Fifth Disease is most prevalent in children aged 5 to 15 years old. Fifth disease occurs at lower rates in adults. The virus spreads easily and once contracted, the body will begin developing lasting immunity to reinfection. The prevalence of antibodies is 50% in children and 70% to 85% in adults. The virus affects both men and women equally. During the spring and winter, epidemic outbreaks are most likely to occur. In the summer and fall, sporadic cases and outbreaks occur. The outbreaks most commonly occur in daycares and schools. The periodicity of the outbreak cycle is three-to-seven years. The risk of acquiring the viral illness increases when exposed to an infected person or contaminated blood. Individuals who have an occupation that requires close contact with infected people such as healthcare workers and teachers are at an increased risk of acquiring the viral illness. Another risk factor of fifth disease are immunocompromised individuals, those with anemia are at a higher risk of developing complications. Pregnant women are at risk for acquiring viral illness, especially during the first half of pregnancy. Though, complications are very rare and less than 5% of these cases will experience serious complications. The most common complication among pregnant women is anemia. In rare cases, severe anemia can occur, and a buildup of fluid can develop. A buildup of fluid can cause congestive heart failure or death. A blood infusion or induction may be necessary. No vaccine is available for human parvovirus B19, though attempts have been made to develop one.
History
Parvovirus, the virus causing the fifth disease, was first discovered in 1975 by Yvonne Cossart. It, or a disease presenting similarly, was first described by Robert Willan in his book called On Cutaneous Diseases in 1808 as "rubeola, sine catarrho". It was better defined by Anton Tschamer in 1889 as a rubella variant (Ortliche Rotheln) and described it as abortive rubella, identified as a distinct condition in 1896 by Theodor Escherich, and given the name "erythema infectiosum" in 1899. The term "Fifth disease" was coined in 1905 by the Russian-French physician Léon Cheinisse (1871-1924), who proposed a numbered classification of the six most common childhood exanthems. The virus was first described in 1957 at the University of Pennsylvania by Werner, Brachman et al.
Vulnerable populations
A 2019 systematic review examined the rates of parvovirus B19 infection among daycare workers. Since transmission typically occurs through respiratory secretions, it was thought that daycare workers would be at an increased risk of infection because young children can spread saliva through drool. The systematic review indicates that daycare workers are at an increased risk for infection. Another review also supports the finding that daycare workers have an increased risk of contracting parvovirus B19 infection. A 2019 meta-analysis examined rates of parvovirus B19 infection among those with Sickle Cell Disease (SCD) using IgG and IgM antibody detection. Pooled data from Africa, Asia, and the Americas revealed a 48.8% parvovirus B19 infection prevalence among persons with SCD. Prevalence of infection was also determined by geographic location, where areas with reduced access to adequate housing had higher prevalence (Africa was 55.5%). A 2020 literature review also supports the finding that persons with SCD, as well as those with the blood disorder beta-thalassemia, are at a higher risk of parvovirus B19 infection.
Complications
There are some known complications associated with Fifth Disease relating to pregnancy. While parvovirus B19 is typically transmitted via respiratory secretions or hand to mouth contact, it has also been known to be passed from pregnant mothers to fetuses. Roughly 50-75% of all pregnant women are immune to parvovirus B19 while the remainder of women are susceptible to mild illness. A majority of fetuses who do contract parvovirus B19 show either no significant symptoms or complete resolution of the virus. However, the following serious complications are rare but possible: miscarriage, stillbirth, fetal anemia, hepatic failure, and abnormal neurodevelopment outcome. In some cases, fetuses would develop hydrops fetalis due to congenital parvovirus B19. This condition was studied as a determinant of later fetal outcomes, such as miscarriage or perinatal death, in 2016 systematic review. The review showed that those born with parvovirus B19 that caused hydrops fetalis did have an association with higher mortality risk and higher risk of complications. While the potential consequences of erythema infectiosum can be quite serious in pregnancy, mothers can be tested for immunity via the presence of IgG and IgM antibodies.In addition to fetuses, parvovirus B19 infection and its effects has been studied in adults as well. The virus has also been associated with the development of neurological complications, as identified in a systematic review in 2014. This analysis included a total of 89 studies covering complications in both the central and nervous system such as encephalitis, meningitis, and peripheral neuropathy. However, the specific pathophysiology of these complications has yet to be discovered but the review does encourage the use of antibody testing to determine a patients risk. Infection of this virus is not limited to the nervous system. Parvovirus B19 has also been linked to cases of cardiac inflammation that can cause structural damage to the heart over time. If the damage progresses and is significant, cardiac cell death may occur.Individuals that are living with HIV are also susceptible to complications if infected due to being immunocompromised. While relatively rare, those who live with both HIV and parvovirus B19 infection will be unable to fight off the B19 virus. This can result in substantial loss of red blood cells and cause anemia.
See also
List of cutaneous conditions
Roseola
Virals
References
External links
Parvovirus B19 at the Centers for Disease Control and Prevention |
Marfan syndrome | Marfan syndrome (MFS) is a multi-systemic genetic disorder that affects the connective tissue. Those with the condition tend to be tall and thin, with long arms, legs, fingers, and toes. They also typically have overly-flexible joints and scoliosis. The most serious complications involve the heart and aorta, with an increased risk of mitral valve prolapse and aortic aneurysm. The lungs, eyes, bones, and the covering of the spinal cord are also commonly affected. The severity of the symptoms is variable.MFS is caused by a mutation in FBN1, one of the genes that makes fibrillin, which results in abnormal connective tissue. It is an autosomal dominant disorder. In about 75% of cases, it is inherited from a parent with the condition, while in about 25% it is a new mutation. Diagnosis is often based on the Ghent criteria.There is no known cure for MFS. Many of those with the disorder have a normal life expectancy with proper treatment. Management often includes the use of beta blockers such as propranolol or atenolol or, if they are not tolerated, calcium channel blockers or ACE inhibitors. Surgery may be required to repair the aorta or replace a heart valve. Avoiding strenuous exercise is recommended for those with the condition.About 1 in 5,000 to 1 in 10,000 people have MFS. Rates of the condition are similar in different regions of the world. It is named after French pediatrician Antoine Marfan, who first described it in 1896.
Signs and symptoms
More than 30 signs and symptoms are variably associated with Marfan syndrome. The most prominent of these affect the skeletal, cardiovascular, and ocular systems, but all fibrous connective tissue throughout the body can be affected.
Skeletal system
Most of the readily visible signs are associated with the skeletal system. Many individuals with Marfan syndrome grow to above-average height, and some have disproportionately long, slender limbs with thin, weak wrists and long fingers and toes.
The Steinberg sign, also known as the thumb sign, is one of the clinical examination tests for Marfan disease in the hands. It is a clinical test in which the tip of the thumb extends beyond the palm when the thumb is clasped in the clenched hand.Besides affecting height and limb proportions, people with Marfan syndrome may have abnormal lateral curvature of the spine scoliosis, thoracic lordosis, abnormal indentation (pectus excavatum) or protrusion (pectus carinatum) of the sternum, abnormal joint flexibility, a high-arched palate with crowded teeth and an overbite, flat feet, hammer toes, stooped shoulders, and unexplained stretch marks on the skin. It can also cause pain in the joints, bones, and muscles. Some people with Marfan have speech disorders resulting from symptomatic high palates and small jaws. Early osteoarthritis may occur. Other signs include limited range of motion in the hips due to the femoral head protruding into abnormally deep hip sockets.
Eyes
In Marfan syndrome, the health of the eye can be affected in many ways, but the principal change is partial lens dislocation, where the lens is shifted out of its normal position. This occurs because of weakness in the ciliary zonules, the connective tissue strands which suspend the lens within the eye. The mutations responsible for Marfan syndrome weaken the zonules and cause them to stretch. The inferior zonules are most frequently stretched resulting in the lens shifting upwards and outwards, but it can shift in other directions as well. Nearsightedness (myopia), and blurred vision are common due to connective tissue defects in the eye. Farsightedness can also result particularly if the lens is highly subluxated. Subluxation (partial dislocation) of the lens can be detected clinically in about 60% of people with Marfan syndrome by the use of a slit-lamp biomicroscope. If the lens subluxation is subtle, then imaging with high-resolution ultrasound biomicroscopy might be used.Other signs and symptoms affecting the eye include increased length along an axis of the globe, myopia, corneal flatness, strabismus, exotropia, and esotropia. Those with MFS are also at a high risk for early glaucoma and early cataracts.
Cardiovascular system
The most serious signs and symptoms associated with Marfan syndrome involve the cardiovascular system: undue fatigue, shortness of breath, heart palpitations, racing heartbeats, or chest pain radiating to the back, shoulder, or arm. Cold arms, hands, and feet can also be linked to MFS because of inadequate circulation. A heart murmur, abnormal reading on an ECG, or symptoms of angina can indicate further investigation. The signs of regurgitation from prolapse of the mitral or aortic valves (which control the flow of blood through the heart) result from cystic medial degeneration of the valves, which is commonly associated with MFS (see mitral valve prolapse, aortic regurgitation). However, the major sign that would lead a doctor to consider an underlying condition is a dilated aorta or an aortic aneurysm. Sometimes, no heart problems are apparent until the weakening of the connective tissue (cystic medial degeneration) in the ascending aorta causes an aortic aneurysm or aortic dissection, a surgical emergency. An aortic dissection is most often fatal and presents with pain radiating down the back, giving a tearing sensation.Because underlying connective tissue abnormalities cause MFS, the incidence of dehiscence of prosthetic mitral valve is increased. Care should be taken to attempt repair of damaged heart valves rather than replacement.
Lungs
Individuals with Marfan Syndrome may be affected by various lung-related problems. One study found that only 37% of the patient sample studied (mean age 32±14 years; M 45%) had normal lung function. Spontaneous pneumothorax is common. In spontaneous unilateral pneumothorax, air escapes from a lung and occupies the pleural space between the chest wall and a lung. The lung becomes partially compressed or collapsed. This can cause pain, shortness of breath, cyanosis, and, if not treated, death. Other possible pulmonary manifestations of MFS include sleep apnea and idiopathic obstructive lung disease. Pathologic changes in the lungs have been described such as cystic changes, emphysema, pneumonia, bronchiectasis, bullae, apical fibrosis and congenital malformations such as middle lobe hypoplasia.
Nervous system
Dural ectasia, the weakening of the connective tissue of the dural sac encasing the spinal cord, can result in a loss of quality of life. It can be present for a long time without producing any noticeable symptoms. Symptoms that can occur are lower back pain, leg pain, abdominal pain, other neurological symptoms in the lower extremities, or headaches – symptoms which usually diminish when lying flat. On X-ray, however, dural ectasia is not often visible in the early stages. A worsening of symptoms might warrant an MRI of the lower spine. Dural ectasia that has progressed to this stage would appear in an MRI as a dilated pouch wearing away at the lumbar vertebrae. Other spinal issues associated with MFS include degenerative disc disease, spinal cysts, and dysfunction of the autonomic nervous system.
Genetics
Each parent with the condition has a 50% risk of passing the genetic defect on to any child due to its autosomal dominant nature. Most individuals with MFS have another affected family member. About 75% of cases are inherited. On the other hand, about 15–30% of all cases are due to de novo genetic mutations; such spontaneous mutations occur in about one in 20,000 births. Marfan syndrome is also an example of dominant negative mutation and haploinsufficiency. It is associated with variable expressivity; incomplete penetrance has not been definitively documented.
Pathogenesis
Marfan syndrome is caused by mutations in the FBN1 gene on chromosome 15, which encodes fibrillin 1, a glycoprotein component of the extracellular matrix. Fibrillin-1 is essential for the proper formation of the extracellular matrix, including the biogenesis and maintenance of elastic fibers. The extracellular matrix is critical for both the structural integrity of connective tissue, but also serves as a reservoir for growth factors. Elastic fibers are found throughout the body, but are particularly abundant in the aorta, ligaments and the ciliary zonules of the eye; consequently, these areas are among the worst affected. It can also be caused by a range of intravenous crystal treatments in those susceptible to the disorder.A transgenic mouse has been created carrying a single copy of a mutant fibrillin-1, a mutation similar to that found in the human gene known to cause MFS. This mouse strain recapitulates many of the features of the human disease and promises to provide insights into the pathogenesis of the disease. Reducing the level of normal fibrillin 1 causes a Marfan-related disease in mice.Transforming growth factor beta (TGF-β) plays an important role in MFS. Fibrillin-1 directly binds a latent form of TGF-β, keeping it sequestered and unable to exert its biological activity. The simplest model suggests reduced levels of fibrillin-1 allow TGF-β levels to rise due to inadequate sequestration. Although how elevated TGF-β levels are responsible for the specific pathology seen with the disease is not proven, an inflammatory reaction releasing proteases that slowly degrade the elastic fibers and other components of the extracellular matrix is known to occur. The importance of the TGF-β pathway was confirmed with the discovery of the similar Loeys–Dietz syndrome involving the TGFβR2 gene on chromosome 3, a receptor protein of TGF-β. Marfan syndrome has often been confused with Loeys–Dietz syndrome, because of the considerable clinical overlap between the two pathologies.
Marfanoid–progeroid–lipodystrophy syndrome
Marfanoid–progeroid–lipodystrophy syndrome (MPL), also referred to as Marfan lipodystrophy syndrome (MFLS), is a variant of MFS in which Marfan symptoms are accompanied by features usually associated with neonatal progeroid syndrome (also referred to as Wiedemann–Rautenstrauch syndrome) in which the levels of white adipose tissue are reduced. Since 2010, evidence has been accumulating that MPL is caused by mutations near the 3-terminus of the FBN1 gene. It has been shown that these people are also deficient in asprosin, a gluco-regulatory protein hormone which is the C-terminal cleavage product of profibrillin. The levels of asprosin seen in these people were lower than expected for a heterozygous genotype, consistent with a dominant negative effect.
Diagnosis
Diagnostic criteria of MFS were agreed upon internationally in 1996. However, Marfan syndrome is often difficult to diagnose in children, as they typically do not show symptoms until reaching pubescence. A diagnosis is based on family history and a combination of major and minor indicators of the disorder, rare in the general population, that occur in one individual – for example: four skeletal signs with one or more signs in another body system such as ocular and cardiovascular in one individual. The following conditions may result from MFS, but may also occur in people without any known underlying disorder.
Revised Ghent nosology
In 2010, the Ghent nosology was revised, and new diagnostic criteria superseded the previous agreement made in 1996. The seven new criteria can lead to a diagnosis:In the absence of a family history of MFS:
Aortic root Z-score ≥ 2 AND ectopia lentis
Aortic root Z-score ≥ 2 AND an FBN1 mutation
Aortic root Z-score ≥ 2 AND a systemic score* > 7 points
Ectopia lentis AND an FBN1 mutation with known aortic pathologyIn the presence of a family history of MFS (as defined above):
Ectopia lentis
Systemic score* ≥ 7
Aortic root Z-score ≥ 2Points for systemic score:
Wrist AND thumb sign = 3 (wrist OR thumb sign = 1)
Pectus carinatum deformity = 2 (pectus excavatum or chest asymmetry = 1)
Hindfoot deformity = 2 (plain pes planus = 1)
Dural ectasia = 2
Protrusio acetabuli = 2
pneumothorax = 2
Reduced upper segment/lower segment ratio AND increased arm/height AND no severe scoliosis = 1
Scoliosis or thoracolumbar kyphosis = 1
Reduced elbow extension = 1
Facial features (3/5) = 1 (dolichocephaly, enophthalmos, downslanting palpebral fissures, malar hypoplasia, retrognathia)
Skin striae (stretch marks) = 1
Myopia > 3 diopters = 1
Mitral valve prolapse = 1The thumb sign (Steinbergs sign) is elicited by asking the person to flex the thumb as far as possible and then close the fingers over it. A positive thumb sign is where the entire distal phalanx is visible beyond the ulnar border of the hand, caused by a combination of hypermobility of the thumb as well as a thumb which is longer than usual.The wrist sign (Walker-Murdoch sign) is elicited by asking the person to curl the thumb and fingers of one hand around the other wrist. A positive wrist sign is where the little finger and the thumb overlap, caused by a combination of thin wrists and long fingers.
Differential diagnosis
Many other disorders can produce the same type of body characteristics as Marfan syndrome. Genetic testing and evaluating other signs and symptoms can help to differentiate these. The following are some of the disorders that can manifest as "marfanoid":
Congenital contractural arachnodactyly, also known as Beals-Hecht syndrome
Ehlers–Danlos syndrome
Homocystinuria
Loeys–Dietz syndrome
MASS phenotype
Multiple endocrine neoplasia, type 2B
Shprintzen–Goldberg syndrome
Stickler syndrome
Management
There is no cure for Marfan syndrome, but life expectancy has increased significantly over the last few decades and is now similar to that of the average person.Regular checkups are recommended to monitor the health of the heart valves and the aorta. Marfan syndrome is treated by addressing each issue as it arises and, in particular, preventive medication even for young children to slow progression of aortic dilation. The goal of this treatment strategy is to slow the progression of aortic dilation and prevent any damage to heart valves by eliminating heart arrythmias, minimizing the heart rate, and lowering the persons blood pressure.
Physical activity
The American Heart Association made the following recommendations for people with Marfan syndrome with no or mild aortic dilation:
Probably permissible activities: bowling, golf, skating (but not ice hockey), snorkeling, brisk walking, treadmill, stationary biking, modest hiking, and tennis (doubles and singles).
Intermediate risk: basketball (both full- and half-court), racquetball, squash, running (sprinting and jogging), skiing (downhill and cross-country), soccer, touch (flag) football, baseball, softball, biking, lap swimming, motorcycling, and horseback riding.
High risk: bodybuilding, weightlifting (non-free and free weights), ice hockey, rock climbing, windsurfing, surfing, and scuba diving.
Medication
Management often includes the use of beta blockers such as propranolol or if not tolerated calcium channel blockers or ACE inhibitors. Beta blockers are used to reduce the stress exerted on the aorta and to decrease aortic dilation.
Surgery
If the dilation of the aorta progresses to a significant-diameter aneurysm, causes a dissection or a rupture, or leads to failure of the aortic or other valve, then surgery (possibly a composite aortic valve graft or valve-sparing aortic root replacement) becomes necessary. Although aortic graft surgery (or any vascular surgery) is a serious undertaking it is generally successful if undertaken on an elective basis. Surgery in the setting of acute aortic dissection or rupture is considerably more problematic. Elective aortic valve/graft surgery is usually considered when aortic root diameter reaches 50 millimeters (2.0 inches), but each case needs to be specifically evaluated by a qualified cardiologist. New valve-sparing surgical techniques are becoming more common. As people with Marfan syndrome live longer, other vascular repairs are becoming more common, e.g., repairs of descending thoracic aortic aneurysms and aneurysms of vessels other than the aorta.The skeletal and ocular manifestations of Marfan syndrome can also be serious, although not life-threatening. These symptoms are usually treated in an appropriate manner for the condition, such as with pain medications or muscle relaxants. Because Marfan syndrome may cause asymptomatic spinal abnormalities, any spinal surgery contemplated on a person Marfan should only follow detailed imaging and careful surgical planning, regardless of the indication for surgery. The ocular complications of MFS can often be treated with surgery. Ectopia lentis can be treated, as artificial lenses can be surgically implanted. In addition, surgery can address glaucoma and cataracts.Treatment of a spontaneous pneumothorax is dependent on the volume of air in the pleural space and the natural progression of the individuals condition. A small pneumothorax might resolve without active treatment in one to two weeks. Recurrent pneumothoraces might require chest surgery. Moderately sized pneumothoraces might need chest drain management for several days in a hospital. Large pneumothoraces are likely to be medical emergencies requiring emergency decompression.As an alternative approach, custom-built supports for the aortic root are also being used. As of 2020 this procedure has been used in over 300 people with the first case occurring in 2004.
Pregnancy
During pregnancy, even in the absence of preconception cardiovascular abnormality, women with Marfan syndrome are at significant risk of aortic dissection, which is often fatal even when rapidly treated. Women with Marfan syndrome, then, should receive a thorough assessment prior to conception, and echocardiography should be performed every six to 10 weeks during pregnancy, to assess the aortic root diameter. For most women, safe vaginal delivery is possible.Prenatal testing can be performed in females with Marfan syndrome to determine if the condition has been inherited in their child. At 10 to 12 weeks of pregnancy, examining a piece of placental tissue through a test called chorionic villus sampling can be performed to make a diagnosis. Another prenatal test can be performed called amniocentesis at 16 to 18 weeks of pregnancy.Marfan syndrome is expressed dominantly. This means a child with one parent a bearer of the gene has a 50% probability of getting the syndrome. In 1996, the first preimplantation genetic testing (PGT) therapy for Marfan was conducted; in essence PGT means conducting a genetic test on early-stage IVF embryo cells and discarding those embryos affected by the Marfan mutation.
Prognosis
Prior to modern cardiovascular surgical techniques and medications such as losartan, and metoprolol, the prognosis of those with Marfan syndrome was not good: a range of untreatable cardiovascular issues was common. Lifespan was reduced by at least a third, and many died in their teens and twenties due to cardiovascular problems. Today, cardiovascular symptoms of Marfan syndrome are still the most significant issues in diagnosis and management of the disease, but adequate prophylactic monitoring and prophylactic therapy offers something approaching a normal lifespan, and more manifestations of the disease are being discovered as more patients live longer. Women with Marfan syndrome live longer than men.
Epidemiology
Marfan syndrome affects males and females equally, and the mutation shows no ethnic or geographical bias. Estimates indicate about 1 in 5,000 to 10,000 individuals have Marfan syndrome.
History
Marfan syndrome is named after Antoine Marfan, the French pediatrician who first described the condition in 1896 after noticing striking features in a five-year-old girl. The gene linked to the disease was first identified by Francesco Ramirez at the Mount Sinai Medical Center in New York City in 1991.
Famous patients
Famous people who have had Marfan syndrome include:
Isaiah Austin
Javier Botet
Austin Carlile
Bradford Cox
Euell Gibbons
Flo Hyman
Jonathan Jeanne
Vincent Schiavelli
Troye Sivan
John TavenerIn addition the following historical figures and celebrities often appear on lists of people with Marfan syndrome, but from case to case the evidence is speculative, questionable, or even refuted.
See also
Ehlers–Danlos syndrome
Kashin–Beck disease
Loeys–Dietz syndrome
Nail-Patella syndrome
Mitral valve prolapse
Bibliography
Lorenz, Megaera. "Lorenz, Maegara "The Mystery of Akhenaton: Genetics or Aesthetics"". Heptune.com. Archived from the original on February 8, 2010. Retrieved March 21, 2010.
Montserrat, Dominic (2003) [2000]. Akhenaten: History, Fantasy and Ancient Egypt (1st paperback ed.). London; New York: Routledge. ISBN 0415301866.
Reeves, Nicholas (2019) [2001]. Akhenaten: Egypts False Prophet (Electronic ed.). London; New York: Thames & Hudson. ISBN 978-0-500-29469-7. LCCN 00108868.
References
External links
Marfan syndrome at Curlie
Orphanets disease page on Marfan syndrome |
Coccydynia | Coccydynia is a medical term meaning pain in the coccyx or tailbone area, often brought on by a fall onto the coccyx or by persistent irritation usually from sitting.
Synonyms
Coccydynia is also known as coccygodynia, coccygeal pain, coccyx pain, or coccalgia.
Anatomy
Structure
Coccydynia occurs in the lowest part of the spine, the coccyx, which is believed to be a vestigial tail, or in other words the “tail bone”. The name coccyx is derived from the Greek word for cuckoo due to its beak like appearance. The coccyx itself is made up of 3 to 5 vertebrae, some of which may be fused together. The ventral side of the coccyx is slightly concave whereas the dorsal aspect is slightly convex. Both of these sides have transverse grooves that show where the vestigial coccygeal units had previously fused. The coccyx attaches to the sacrum from the dorsal grooves, with the attachment being either a symphysis or as a true synovial joint, and also to the gluteus maximus muscle, the coccygeal muscle, and the anococcygeal ligament.
Orientations of the coccyx
There are four different orientations for the coccyx, as described by Postacchini and Massobrio. In type I the coccyx is curved anteriorly with its apex facing downward and caudally. In type II this forward curvature is more dramatic and the apex extends forward. Type III is where the coccyx angles forward sharply. Lastly, type IV is characterized by the coccyx being subluxated at the sacrococcygeal joint.
Pathophysiology
There are common pathophysiological ways that a person may develop coccydynia. The two main causes for this condition are sudden impact due to fall, and coccydynia caused by childbirth pressure in women. Other ways that coccydynia develops are partial dislocation of the sacrococcygeal synchondrosis that can possibly result in abnormal movement of the coccyx from excessive sitting, and repetitive trauma of the surrounding ligaments and muscles, resulting in inflammation of tissues and pain.
Diagnosis
A number of different conditions can cause pain in the general area of the coccyx, but not all involve the coccyx and the muscles attached to it. The first task of diagnosis is to determine whether the pain is related to the coccyx. Physical rectal examination, high resolution x-rays and MRI scans can rule out various causes unrelated to the coccyx, such as Tarlov cysts and pain referred from higher up the spine. Note that, contrary to most anatomical textbooks, most coccyxes consist of several segments: fractured coccyx is often diagnosed when the coccyx is in fact normal or just dislocated at an intercoccygeal joint.A simple test to determine whether the coccyx is involved is injection of local anesthetic into the area. If the pain relates to the coccyx, this should produce immediate relief.If the anesthetic test proves positive, then a dynamic (sit/stand) x-ray or MRI scan may show whether the coccyx dislocates when the patient sits.Use of dynamic x-rays on 208 patients who gave positive results with the anesthetic test showed:
31% Not possible to identify the cause of pain
27% Hypermobility (excessive flexing of the coccyx forwards and upwards when sitting)
22% Posterior luxation (partial dislocation of the coccyx backwards when sitting)
14% Spicule (bony spur) on the coccyx
5% Anterior luxation (partial dislocation of the coccyx forwards when sitting)This study found that the pattern of lesions was different depending on the obesity of the patients: obese patients were most likely to have posterior luxation of the coccyx, while thin patients were most likely to have coccygeal spicules.
Angle of incidence
Sagittal coccygeal movement is measured using the angle of incidence—or the angle at which the coccyx strikes the seat when an individual sits down. A smaller angle indicates the coccyx being more parallel to the seat, resulting in flexion (or “normal” movement) of the coccyx. A larger angle indicates the coccyx being more perpendicular to the seat, causing posterior subluxation (or “backward” movement) of the coccyx.
Causes
One way of classifying coccydynia is whether the onset was traumatic versus non-traumatic. In many cases the exact cause is unknown and is referred to as idiopathic coccydynia.
Coccydynia is a fairly common injury which can often result from falls, particularly in leisure activities such as cycling and skateboarding.
Coccydynia is often reported following a fall or after childbirth. In some cases, persistent pressure from activities like bicycling may cause the onset of coccyx pain. Coccydynia due to these causes usually is not permanent, but it may become very persistent and chronic if not controlled. Coccydynia may also be caused by sitting improperly thereby straining the coccyx.
Rarely, coccydynia is due to the undiagnosed presence of a sacrococcygeal teratoma or other tumor in the vicinity of the coccyx.
Prevalence
A study of 2000 cases of back pain referred to hospital found that 2.7% were diagnosed as coccydynia. This type of pain occurs five times more frequently in women than in men. It can occur at any age, the mean age of onset being around 40. There are no ethnicity or race associations with coccydynia.
Clinical features
Activities that put pressure on the affected area are bicycling, horseback riding, and other activities such as increased sitting that put direct stress on the coccyx. The medical condition is often characterized by pain that worsens with constipation and may be relieved with bowel movement. Rarely, even sexual intercourse can aggravate symptoms.
Non-surgical treatment
Since sitting on the affected area may aggravate the condition, a cushion with a cutout at the back under the coccyx is recommended. If there is tailbone pain with bowel movements, then stool softeners and increased fiber in the diet may help. Anti-inflammatory medications such as NSAIDS may be prescribed.If the pain persists, other treatments may be applied. Manual treatment is carried out by repeated massage of the muscles attached to the coccyx, via the anus. Such treatment is usually given by an intimate partner, chiropractor, osteopath or physical therapist. Thiele applied this treatment to a series of 169 coccydynia patients, and reported 63% cured.Orthopaedic surgeons commonly inject corticosteroids into the painful joint. Maigne and Tamalet applied this treatment to 86 patients under fluoroscopic guidance. Two months after the injection, 50% of the patients with luxation or hypermobility were improved or healed, but only 27% of the patients with no visible abnormality improved. Where an abnormality had been found, and injection relieved the pain, the abnormality remained but ceased to be painful.
Temporary or permanent nerve blocks are sometimes applied in cases of coccydynia. Foye et al reported that repeated temporary nerve blocks by injection at the ganglion impar could give relief in a number of cases, and occasionally a single injection was sufficient.
Surgical treatment
If non-surgical treatments fail to relieve the pain, or in cases of cancer, surgery to remove the coccyx (coccygectomy) may be required. In cases where pain persists after surgery, standard drugs for chronic pain, such as tri-cyclic anti-depressants, may help alleviate the pain.
Prevention or to ease coccyx pain
Body positioning and alignment is significant for producing less stress in the coccyx region. Bad posture can influence coccyx pain. People may not realize that they are over stressing their coccyx while doing daily activities. Pain in the coccyx can be caused from many incidents like falling, horseback riding, or even sitting on hard surfaces for a long period of time. The main focus is to prevent coccyx pain from occurring, by correcting everyday activities that contribute to tailbone pain. You can take hot or cold water baths. Have a stream of hot or cold water run down your back continuously if pain becomes unbearable. Use cold water if pain persists. Repeat the procedure in intervals of 5-6 minutes.
Proper equipment used to preventing coccyx pain
There is no definite way to fully prevent coccyx pain because an accident can occur at any given time. However, people who are obese are at a higher risk for developing coccyx pain. Carrying excessive weight contributes to more stress on the coccyx while sitting down causing increased chances of pain.
Prevention of carrying excessive weight gain can help reduce the tension and pressure on the coccyx. In other words, the coccyx for obese people may be more posteriorly outward when they are sitting down. Avoidance of contact sports like basketball, football, and or hockey can decrease the risks of coccyx pain, because it can help reduce the chances of falling.
Another method is proper safety equipment for sports is to prevent coccyx pain. For example, there are hockey pants that provide extra cushion that protect the thigh, coccyx, and buttocks. These results will lead to less falls that can cause trauma to the coccyx.
Stretches and strengthening exercises for prevention
A kneeling groin stretch can help prevent coccyx pain from occurring after long periods of sitting. The adductor magnus is involved in the kneeling groin stretch, and when it is tight it can contribute to tailbone pain, so stretching can help prevent tailbone pain. Other stretches like piriformis stretch, and hands to feet stretch, can relieve stress off the muscles around the coccyx, after sitting for a long time. These release tension built up around the muscles in the coccyx.
See also
Coccyx (tailbone)
Ganglion impar
References
External links
www.coccyx.org, website about coccydynia causes, treatments and coping with the condition
Coccyx pain, tailbone pain, coccydynia review article at eMedicine via Medscape |
Zika fever | Zika fever, also known as Zika virus disease or simply Zika, is an infectious disease caused by the Zika virus. Most cases have no symptoms, but when present they are usually mild and can resemble dengue fever. Symptoms may include fever, red eyes, joint pain, headache, and a maculopapular rash. Symptoms generally last less than seven days. It has not caused any reported deaths during the initial infection. Mother-to-child transmission during pregnancy can cause microcephaly and other brain malformations in some babies. Infections in adults have been linked to Guillain–Barré syndrome (GBS).Zika fever is mainly spread via the bite of mosquitoes of the Aedes type. It can also be sexually transmitted and potentially spread by blood transfusions. Infections in pregnant women can spread to the baby. Diagnosis is by testing the blood, urine, or saliva for the presence of the viruss RNA when the person is sick, or the blood for antibodies after symptoms are present more than a week.Prevention involves decreasing mosquito bites in areas where the disease occurs and proper use of condoms. Efforts to prevent bites include the use of insect repellent, covering much of the body with clothing, mosquito nets, and getting rid of standing water where mosquitoes reproduce. There is no effective vaccine. Health officials recommended that women in areas affected by the 2015–16 Zika outbreak consider putting off pregnancy and that pregnant women not travel to these areas. While there is no specific treatment, paracetamol (acetaminophen) may help with the symptoms. Admission to hospital is rarely necessary.The virus that causes the disease was first isolated in Africa in 1947. The first documented outbreak among people occurred in 2007 in the Federated States of Micronesia. An outbreak started in Brazil in 2015, and spread to the Americas, Pacific, Asia, and Africa. This led the World Health Organization to declare it a Public Health Emergency of International Concern in February 2016. The emergency was lifted in November 2016, but 84 countries still reported cases as of March 2017. The last proven case of Zika spread in the Continental United States was in 2017.
Signs and symptoms
Most people who are infected have no or few symptoms. Otherwise the most common signs and symptoms of Zika fever are fever, rash, conjunctivitis (red eyes), muscle and joint pain, and headache, which are similar to signs and symptoms of dengue and chikungunya fever. The time from a mosquito bite to developing symptoms is not yet known, but is probably a few days to a week. The disease lasts for several days to a week and is usually mild enough that people do not have to go to a hospital.Due to being in the same family as dengue, there has been concern that it could cause similar bleeding disorders. However that has only been documented in one case, with blood seen in semen, also known as hematospermia.
Guillain–Barré syndrome
Zika virus infections have been strongly associated with Guillain–Barré syndrome (GBS), which is a rapid onset of muscle weakness caused by the immune system damaging the peripheral nervous system, and which can progress to paralysis. While both GBS and Zika infection can simultaneously occur in the same individual, it is difficult to definitively identify Zika virus as the cause of GBS. Though Zika virus has been shown to infect human Schwann cells. Several countries affected by Zika outbreaks have reported increases in the rate of new cases of GBS. During the 2013–2014 outbreak in French Polynesia there were 42 reported cases of GBS over a 3-month period, compared to between 3 and 10 annually prior to the outbreak.
Pregnancy
The disease spreads from mother to child in the womb and can cause multiple problems, most notably microcephaly, in the baby. The full range of birth defects caused by infection during pregnancy is not known, but they appear to be common, with large scale abnormalities seen in up to 42% of live births. The most common observed associations have been abnormalities with brain and eye development such as microcephaly and chorioretinal scarring. Less commonly there have been systemic abnormalities such as hydrops fetalis, where there is abnormal accumulation of fluid in the fetus. These abnormalities can lead to intellectual problems, seizures, vision problems, hearing problems, problems feeding and slow development.Whether the stage of pregnancy at which the mother becomes infected affects the risk to the fetus is not well understood, nor is whether other risk factors affect outcomes. One group has estimated the risk of a baby developing microcephaly at about 1% when the mother is infected during the first trimester, with the risk of developing microcephaly becoming uncertain beyond the first trimester. Affected babies might appear normal but actually have brain abnormalities; infection in newborns could also lead to brain damage.
Cause
Reservoir
Zika virus is a mosquito-borne flavivirus closely related to the dengue and yellow fever viruses. While mosquitoes are the vector, the main reservoir species remains unknown, though serological evidence has been found in both West African monkeys and rodents.
Transmission
Transmission is via the bite of mosquitoes from the genus Aedes, primarily Aedes aegypti in tropical regions. It has also been isolated from Ae. africanus, Ae. apicoargenteus, Ae. luteocephalus, Ae. albopictus, Ae. vittatus and Ae. furcifer. During the 2007 outbreak on Yap Island in the South Pacific, Aedes hensilli was the vector, while Aedes polynesiensis spread the virus in French Polynesia in 2013.Zika virus can also spread by sexual transmission from infected men to their partners. Zika virus has been isolated from semen samples, with one person having 100,000 times more virus in semen than blood or urine, two weeks after being infected. It is unclear why levels in semen can be higher than other body fluids, and it is also unclear how long infectious virus can remain in semen. There have also been cases of men with no symptoms of Zika virus infection transmitting the disease. The CDC has recommended that all men who have travelled to affected areas should wait at least 6 months before trying to attempt conception, regardless of whether they were ill. To date there have been no reported sexual transmissions from women to their sexual partners. Oral, anal or vaginal sex can spread the disease.Cases of vertical perinatal transmission have been reported. The CDC recommends that women with Zika fever should wait at least 8 weeks after they start having symptoms of disease before attempting to conceive. There have been no reported cases of transmission from breastfeeding, but infectious virus has been found in breast milk.Like other flaviviruses it could potentially be transmitted by blood transfusion and several affected countries have developed strategies to screen blood donors. The U.S. FDA has recommended universal screening of blood products for Zika. The virus is detected in 3% of asymptomatic blood donors in French Polynesia.
Pathophysiology
In fruit flies microcephaly appears to be caused by the flavivirid virus protein NS4A, which can disrupt brain growth by hijacking a pathway which regulates growth of new neurons.
Diagnosis
It is difficult to diagnose Zika virus infection based on clinical signs and symptoms alone due to overlaps with other arboviruses that are endemic to similar areas. The US Centers for Disease Control and Prevention (CDC) advises that "based on the typical clinical features, the differential diagnosis for Zika virus infection is broad. In addition to dengue, other considerations include leptospirosis, malaria, rickettsia, group A streptococcus, rubella, measles, and parvovirus, enterovirus, adenovirus, and alphavirus infections (e.g., chikungunya, Mayaro, Ross River, Barmah Forest, Onyongnyong, and Sindbis viruses)."In small case series, routine chemistry and complete blood counts have been normal in most patients. A few have been reported to have mild leukopenia, thrombocytopenia, and elevated liver transaminases.Zika virus can be identified by reverse transcriptase PCR (RT-PCR) in acutely ill patients. However, the period of viremia can be short and the World Health Organization (WHO) recommends RT-PCR testing be done on serum collected within 1 to 3 days of symptom onset or on saliva samples collected during the first 3 to 5 days. When evaluating paired samples, Zika virus was detected more frequently in saliva than serum. Urine samples can be collected and tested up to 14 days after the onset of symptoms, as the virus has been seen to survive longer in the urine than either saliva or serum. The longest period of detectable virus has been 11 days and Zika virus does not appear to establish latency.Later on, serology for the detection of specific IgM and IgG antibodies to Zika virus can be used. IgM antibodies can be detectable within 3 days of the onset of illness. Serological cross-reactions with closely related flaviviruses such as dengue and West Nile virus as well as vaccines to flaviviruses are possible. As of 2019, the FDA has authorized two tests to detect Zika virus antibodies.
Screening in pregnancy
The CDC recommends screening some pregnant women even if they do not have symptoms of infection. Pregnant women who have traveled to affected areas should be tested between two and twelve weeks after their return from travel. Due to the difficulties with ordering and interpreting tests for Zika virus, the CDC also recommends that healthcare providers contact their local health department for assistance. For women living in affected areas, the CDC has recommended testing at the first prenatal visit with a doctor as well as in the mid-second trimester, though this may be adjusted based on local resources and the local burden of Zika virus. Additional testing should be done if there are any signs of Zika virus disease. Women with positive test results for Zika virus infection should have their fetus monitored by ultrasound every three to four weeks to monitor fetal anatomy and growth.
Infant testing
For infants with suspected congenital Zika virus disease, the CDC recommends testing with both serologic and molecular assays such as RT-PCR, IgM ELISA and plaque reduction neutralization test (PRNT). RT-PCR of the infants serum and urine should be performed in the first two days of life. Newborns with a mother who was potentially exposed and who have positive blood tests, microcephaly or intracranial calcifications should have further testing including a thorough physical investigation for neurologic abnormalities, dysmorphic features, splenomegaly, hepatomegaly, and rash or other skin lesions. Other recommended tests are cranial ultrasound, hearing evaluation, and eye examination. Testing should be done for any abnormalities encountered as well as for other congenital infections such as syphilis, toxoplasmosis, rubella, cytomegalovirus infection, lymphocytic choriomeningitis virus infection, and herpes simplex virus. Some tests should be repeated up to 6 months later as there can be delayed effects, particularly with hearing.
Infant feeding in areas of Zika virus transmission
In response to the widespread transmission of Zika virus during the 2016 outbreak and concerns of viral genetic material detected in breast milk the World Health Organization (WHO) released a Guideline of infant feeding in areas of Zika virus transmission, first in 2016 and updated in 2021, where the evidence showed that despite the detection of Zika virus in breast milk, there is unclear evidence of transmission to the infant, and considering that Zika virus infection among infants is mild, the balance between desirable and undesirable effects favours breastfeeding versus not breastfeeding. According to the 2021WHO guidelines:
Infants born to mothers with suspected, probable or confirmed Zika virus infection or who reside in or have travelled to areas of ongoing Zika virus transmission should be fed according to normal infant feeding guidelines. They should start breastfeeding within one hour of birth, be exclusively breastfed for six months and have timely introduction of adequate, safe and properly fed complementary foods, while continuing breastfeeding up to two years of age or beyond.
Infants fed with expressed breast-milk from mothers with suspected, probable or confirmed Zika virus infection or who reside in or have travelled to areas of ongoing Zika virus transmission should be fed according to normal infant feeding guidelines (strong recommendation, very-low certainty of evidence).
Among infants (0–12 months) affected by complications associated with Zika virus infection, infant feeding practices should be modified (such as adjusting the environment, postural correction or thickening feeds) to achieve and maintain optimal possible infant growth and development (strong recommendation, very- low certainty of evidence).
Mothers and caregivers of infants affected by complications associated with Zika virus (such as feeding difficulties) should receive skilled support from health-care workers to initiate and sustain optimal infant feeding practices
Prevention
The virus is spread by mosquitoes, making mosquito avoidance an important element to disease control. The CDC recommends that individuals:
Cover exposed skin by wearing long-sleeved shirts and long pants treated with permethrin.
Use an insect repellent containing DEET, picaridin, oil of lemon eucalyptus (OLE), or ethyl butylacetylaminopropionate (IR3535)
Always follow product directions and reapply as directed
If you are also using sunscreen, apply sunscreen first, let it dry, then apply insect repellent
Follow package directions when applying repellent on children. Avoid applying repellent to their hands, eyes, or mouth
Stay and sleep in screened-in or air-conditioned rooms
Use a bed net if the area where you are sleeping is exposed to the outdoors
Cover cribs, strollers and carriers with mosquito netting for babies under 2 months old.The CDC also recommends strategies for controlling mosquitoes such as eliminating standing water, repairing septic tanks and using screens on doors and windows. Spraying insecticide is used to kill flying mosquitoes and larvicide can be used in water containers.Because Zika virus can be sexually transmitted, men who have gone to an area where Zika fever is occurring should be counseled to either abstain from sex or use condoms for 6 months after travel if their partner is pregnant or could potentially become pregnant. Breastfeeding is still recommended by the WHO, even by women who have had Zika fever. There have been no recorded cases of Zika transmission to infants through breastfeeding, though the replicative virus has been detected in breast milk.When returning from travel, with or without symptoms, it is suggested that prevention of mosquito bites continue for 3 weeks in order reduce the risk of virus transmission to uninfected mosquitos.
CDC travel alert
Because of the "growing evidence of a link between Zika and microcephaly", in January 2016, the CDC issued a travel alert advising pregnant women to consider postponing travel to countries and territories with ongoing local transmission of Zika virus. Later, the advice was updated to caution pregnant women to avoid these areas entirely if possible and, if travel is unavoidable, to protect themselves from mosquito bites. Male partners of pregnant women and couples contemplating pregnancy who must travel to areas where Zika is active are advised to use condoms or abstain from sex. The agency also suggested that women thinking about becoming pregnant should consult with their physicians before traveling.In September 2016, the CDC travel advisories included:
Cape Verde
Many parts of the Caribbean: Anguilla, Antigua and Barbuda, Aruba, The Bahamas, Barbados, Bonaire, British Virgin Islands, Cayman Islands, Cuba, Curaçao, Dominica, Dominican Republic, Grenada, Guadeloupe, Haiti, Jamaica, Martinique, Puerto Rico, Saba, Saint Saint Barthélemy, Saint Lucia, Saint Martin, Saint Vincent and the Grenadines, Sint Eustatius, Sint Maarten, Trinidad and Tobago, and the U.S. Virgin Islands
Central America: Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, and Panama
Mexico
Most of South America: Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Paraguay, Peru, Suriname, and Venezuela
Several Pacific Islands: American Samoa, Fiji, Marshall Islands, Micronesia, New Caledonia, Papua New Guinea, Samoa, and Tonga
In Asia: Singapore, Malaysia, BruneiIn December 2020, no active Zika outbreaks were reported by the CDC.
WHO response
Both the regional Pan American Health Organization (PAHO) as well as the WHO have issued statements of concern about the widespread public health impact of the Zika virus and its links to GBS and microcephaly. The WHO Director-General, Margaret Chan, issued a statement in February 2016 "declaring that the recent cluster of microcephaly cases and other neurological disorders reported in Brazil, following a similar cluster in French Polynesia in 2014, constitutes a Public Health Emergency of International Concern." The declaration allowed the WHO to coordinate international response to the virus as well as gave its guidance the force of international law under the International Health Regulations. The declaration was ended in November 2016.
Vaccine
As of 2016 there was no available vaccine. Development was a priority of the US National Institutes of Health (NIH), but officials stated that development of a vaccine could take years. To speed new drug development regulatory strategies were proposed by the WHO and NIH. Animal and early human studies were underway as of September 2016. As of December 2019, there were several vaccine candidates in various stages of development.
Mosquito control
Disease control in the affected countries currently centres around mosquito control. Several approaches are available for the management of Aedes aegypti mosquito populations, including the destruction of larval breeding sites (the aquatic pools in which eggs are laid and larvae hatch prior to mosquito development into flying adults); and, insecticides targeting either the larval stages, adult mosquitoes or both. Additionally, a whole host of novel technologies are under current development for mosquito control and the World Health Organization has recently lent its support for the accelerated development of modern methods for mosquito control such as the use of Wolbachia bacteria to render mosquitoes resistant to the virus, and, the release of sterilized male mosquitoes that breed with wild female mosquitoes to give rise to non-viable offspring (offspring that do not survive to the biting, adult stage).Oxitec’s genetically modified OX513A mosquito was approved by Brazils National Biosecurity Technical Commission (CTNBio) in April 2014 and it was being used to try to combat mosquitoes carrying the Zika virus in the town of Piracicaba, São Paulo in 2016.In the 1940s and 1950s, the Aedes aegypti mosquito was eradicated on some Caribbean islands and in at least eighteen Latin American countries. Decreasing political will and presumably available money, mosquito resistance to insecticide, and a pace of urbanization which exceeded eradication efforts led to this mosquitos comeback.
Treatment
There is currently no specific treatment for Zika virus infection. Care is supportive with treatment of pain, fever, and itching. Some authorities have recommended against using aspirin and other NSAIDs as these have been associated with hemorrhagic syndrome when used for other flaviviruses. Additionally, aspirin use is generally avoided in children when possible due to the risk of Reye syndrome.Zika virus had been relatively little studied until the major outbreak in 2015, and no specific antiviral treatments are available as yet. Advice to pregnant women is to avoid any risk of infection so far as possible, as once infected there is little that can be done beyond supportive treatment.
Outcomes
Most of the time, Zika fever resolves on its own in two to seven days, but rarely, some people develop Guillain–Barré syndrome. The fetus of a pregnant woman who has Zika fever may die or be born with congenital central nervous system malformations, like microcephaly.
Epidemiology
In April 1947, as part of studies sponsored by the Rockefeller Foundation into yellow fever, 6 caged rhesus monkeys were placed in the canopy of the Zika Forest of Uganda. On April 18 one of the monkeys (no. 776) developed a fever and blood samples revealed the first known case of Zika fever. Population surveys at the time in Uganda found 6.1% of individuals to be seropositive for Zika. The first human cases were reported in Nigeria in 1954. A few outbreaks have been reported in tropical Africa and in some areas in Southeast Asia. Until recently there were no documented cases of Zika virus in the Indian subcontinent, however, the first cases were reported in 2017 from Gujarat state and Tamil Nadu, more cases were reported in Rajasthan state involving an outbreak of 153 reported cases and in a pregnant women living in Kerala state. A 1954 study assessing blood samples from several people from different states found antibodies to Zika in healthy people in India which could indicate past exposure, though it could also be due to cross-reaction with other flaviviruses.By using phylogenetic analysis of Asian strains, it was estimated that Zika virus had moved to Southeast Asia by 1945. In 1977–1978, Zika virus infection was described as a cause of fever in Indonesia. Before 2007, there were only 13 reported natural infections with Zika virus, all with a mild, self-limited febrile illness. As of July 2019, evidence of local transmission from mosquitoes to humans has been reported in a total of 87 countries from four of six WHO Regions; African, Americas, South-East Asia and Western Pacific.
Yap Islands
The first major outbreak, with 185 confirmed cases, was reported in 2007 in the Yap Islands of the Federated States of Micronesia. A total of 108 cases were confirmed by PCR or serology and 72 additional cases were suspected. The most common symptoms were rash, fever, arthralgia, and conjunctivitis, and no deaths were reported. The mosquito Aedes hensilli, which was the predominant species identified in Yap during the outbreak, was probably the main vector of transmission. While the way of introduction of the virus on Yap Island remains uncertain, it is likely to have happened through introduction of infected mosquitoes or a human infected with a strain related to those in Southeast Asia. This was also the first time Zika fever had been reported outside Africa and Asia. Before the Yap Island outbreak, only 14 human cases had ever been reported.
Oceania
In 2013–2014, several outbreaks of Zika were reported in French Polynesia, New Caledonia, Easter Island and the Cook Islands. The source of the virus was thought to be an independent introduction of the virus from Southeast Asia, unrelated to the Yap Islands outbreak.
Americas
Genetic analyses of Zika virus strains suggest that Zika first entered the Americas between May and December 2013. It was first detected in the Western Hemisphere in February 2014, and rapidly spread throughout South and Central America, reaching Mexico in November 2015. In 2016 it established local transmission in Florida and Texas. The first death in the United States due to Zika occurred in February 2016.In May 2015, Brazil officially reported its first 16 cases of the illness. Although, a case of illness was reported in March 2015 in a returning traveller. According to the Brazilian Health Ministry, as of November 2015 there was no official count of the number of people infected with the virus in Brazil, since the disease is not subject to compulsory notification. Even so, cases were reported in 14 states of the country. Mosquito-borne Zika virus is suspected to be the cause of 2,400 possible cases of microcephaly and 29 infant deaths in Brazil in 2015 (of the 2400 or so notified cases in 2015, 2165 were under investigation in December 2015, 134 were confirmed and 102 were ruled out for microcephaly).The Brazilian Health Ministry has reported at least 2,400 suspected cases of microcephaly in the country in 2015 as of 12 December, and 29 fatalities. Before the Zika outbreak, only an average of 150 to 200 cases per year were reported in Brazil. In the state of Pernambuco the reported rates of microcephaly in 2015 are 77 times higher than in the previous 5 years. A model using data from a Zika outbreak in French Polynesia estimated the risk of microcephaly in children born to mothers who acquired Zika virus in the first trimester to be 1%.On 24 January 2016, the WHO warned that the virus is likely to spread to nearly all countries of the Americas, since its vector, the mosquito Aedes aegypti, is found in all countries in the region, except for Canada and continental Chile. The mosquito and dengue fever have been detected in Chiles Easter Island, some 3,500 km (2,200 mi) away from its closest point in mainland Chile, since 2002.In February 2016, WHO declared the outbreak a Public Health Emergency of International Concern as evidence grew that Zika is a cause of birth defects and neurological problems. In April 2016, WHO stated there is a scientific consensus, based on preliminary evidence, that Zika is a cause of microcephaly in infants and Guillain–Barré syndrome in adults. Studies of this and prior outbreaks have found Zika infection during pregnancy to be associated with early pregnancy loss and other pregnancy problems. In the Americas the number of cases peaked during the first half of 2016 and declined through 2017–2018, with a total of 31,587 suspected, probable, and confirmed cases of ZIKV disease were reported in the Region of the Americas. Of these, 3,473 (11%) were laboratory confirmed. In general, transmission persists at low levels in some areas and is not uniformly distributed within countries.
Asia
In 2016 imported or locally transmitted Zika was reported in all the countries of Asia except Brunei, Hong Kong, Myanmar and Nepal. Serological surveys have indicated that Zika virus is endemic in most areas of Asia, though at a low level. While there was a sharp rise in the number of cases of Zika detected in Singapore after the 2016 Summer Olympics in Brazil, genetic analysis revealed that the strains were more closely related to strains from Thailand than from those causing the epidemic in the Americas.
History
Origin of the name
It is named after the Zika Forest near Entebbe, Uganda, where the Zika virus was first identified.
Microcephaly and other infant disorders
Zika virus was first identified in the late 1940s in Kampala, Uganda, Africa but was first confirmed in Brazil. Since it was first identified, Zika has been found in more than 27 countries and territories. Following the initial Zika outbreak in Northeastern Brazil in May 2015, physicians observed a very large surge of reports of infants born with microcephaly, with 20 times the number of expected cases. Many of these cases have since been confirmed, leading WHO officials to project that approximately 2,500 infants will be found to have born in Brazil with Zika-related microcephaly.Proving that Zika causes these effects was difficult and complex for several reasons. For example, the effects on an infant might not be seen until months after the mothers initial infection, long after the time when Zika is easily detected in the body. In addition, research was needed to determine the mechanism by which Zika produced these effects.Since the initial outbreak, studies that use several different methods found evidence of a link, leading public health officials to conclude that it appears increasingly likely the virus is linked to microcephaly and miscarriage. On 1 February 2016, the World Health Organization declared recently reported clusters of microcephaly and other neurological disorders a Public Health Emergency of International Concern (PHEIC). On 8 March 2016, the WHO Committee reconfirmed that the association between Zika and neurological disorders is of global concern.The Zika virus was first linked with newborn microcephaly during the Brazil Zika virus outbreak. In 2015, there were 2,782 suspected cases of microcephaly compared with 147 in 2014 and 167 in 2013. Confirmation of many of the recent cases is pending, and it is difficult to estimate how many cases went unreported before the recent awareness of the risk of virus infections.
In November 2015, the Zika virus was isolated in a newborn baby from the northeastern state of Ceará, Brazil, with microcephaly and other congenital disorders. The Lancet medical journal reported in January 2016 that the Brazilian Ministry of Health had confirmed 134 cases of microcephaly "believed to be associated with Zika virus infection" with an additional 2,165 cases in 549 counties |
Zika fever | in 20 states remaining under investigation. An analysis of 574 cases of microcephaly in Brazil during 2015 and the first week of 2016, reported in March 2016, found an association with maternal illness involving rash and fever during the first trimester of pregnancy. During this period, 12 Brazilian states reported increases of at least 3 standard deviations (SDs) in cases of microcephaly compared with 2000–14, with the northeastern states of Bahia, Paraíba and Pernambuco reporting increases of more than 20 SDs.In January 2016, a baby in Oahu, Hawaii, was born with microcephaly, the first case in the United States of brain damage linked to the virus. The baby and mother tested positive for a past Zika virus infection. The mother, who had probably acquired the virus while traveling in Brazil in May 2015 during the early stages of her pregnancy, had reported her bout of Zika. She recovered before relocating to Hawaii. Her pregnancy had progressed normally, and the babys condition was not known until birth.In February 2016, ocular disorders in newborns have been linked to Zika virus infection. In one study in Pernambuco state in Brazil, about 40 percent of babies with Zika-related microcephaly also had scarring of the retina with spots, or pigment alteration. On 20 February 2016, Brazilian scientists announced that they had successfully sequenced the Zika virus genome and expressed hope that this would help in both developing a vaccine and in determining the nature of any link to birth defects.Also in February 2016, rumors that microcephaly is caused by the use of the larvicide pyriproxyfen in drinking water were refuted by scientists. "Its important to state that some localities that do not use pyriproxyfen also had reported cases of microcephaly", read a Brazilian government statement. The Brazilian government also refuted conspiracy theories that chickenpox and rubella vaccinations or genetically modified mosquitoes were causing increases in microcephaly.Researchers also suspected that Zika virus could be transmitted by a pregnant woman to her babies ("vertical transmission"). This remained unproven until February 2016, when a paper by Calvet et al. was published, showing not only was the Zika virus genome found in the amniotic fluid but also IgM antibodies against the virus. This means that not only can the virus cross the placental barrier, but also the antibodies produced by the mother can reach the fetus, which suggests that vertical transmission is plausible in these cases. One other study published in March 2016 by Mlakar and colleagues analyzed autopsy tissues from a fetus with microcephaly that was probably related to Zika virus; researchers found ZIKV in the brain tissue and suggested that the brain injuries were probably associated with the virus, which also shed a light on the vertical transmission theory. Also in March 2016, first solid evidence was reported on how the virus affects the development of the brain, indicating that it appears to preferentially kill developing brain cells.The first cases of birth defects linked to Zika in Colombia and in Panama were reported in March 2016. In the same month, researchers published a prospective cohort study that found profound impacts in 29 percent of infants of mothers infected with Zika, some of whom were infected late in pregnancy. This study did not suffer from some of the difficulties of studying Zika: the study followed women who presented to a Rio de Janeiro clinic with fever and rash within the last five days. The women were then tested for Zika using PCR, then the progress of the pregnancies were followed using ultrasound.
Guillain–Barré syndrome
A high rate of the autoimmune disease Guillain–Barré syndrome (GBS), noted in the French Polynesia outbreak, has also been found in the outbreak that began in Brazil. Laboratory analysis found Zika infections in some patients with GBS in Brazil, El Salvador, Suriname and Venezuela, and the WHO declared on 22 March 2016 that Zika appeared to be "implicated" in GBS infection and that if the pattern was confirmed it would represent a global public health crisis.
Research
Mechanism
Research has been ongoing to better understand how Zika virus causes microcephaly and other neurological disorders.It may involve infection of the primary neural stem cells of the fetal brain, known as neural progenitor cells. The main roles of brain stem cells are to proliferate until the correct number is achieved, and then to produce neurons through the process of neurogenesis. Zika proteins NS4A and NS4B have also been shown to directly suppress neurogenesis. Infection of brain stem cells can cause cell death, which reduces the production of future neurons and leads to a smaller brain. Zika also appears to have an equal tropism for cells of the developing eye, leading to high rates of eye abnormalities as well.In addition to inducing cell death, infection of neural progenitor cells may alter the process of cell proliferation, causing a depletion in the pool of progenitor cells. A large number of cases of microcephaly have been associated with inherited gene mutations, and specifically with mutations that lead to dysfunction of the mitotic spindle. There is some evidence that Zika virus may directly or indirectly interfere with mitotic function, this may play a role in altering cell proliferation.Another line of research considers that Zika, unlike other flaviviruses, may target developing brain cells after it crosses the placenta, and considers the resulting damage likely to be the result of inflammation as a byproduct of the immune response to the infection of those cells.
Mosquito control
Some experimental methods of prevention include breeding and releasing mosquitoes that have been genetically modified to prevent them from transmitting pathogens, or have been infected with the Wolbachia bacterium, believed to inhibit the spread of viruses. A strain of Wolbachia helped to reduce the vector competence of the Zika virus in infected Aedes aegypti released in Medellin, Colombia.Gene drive is a technique for changing wild populations, for instance to combat insects so they cannot transmit diseases (in particular mosquitoes in the cases of malaria and Zika). Another method which been researched aims to render male mosquitoes infertile by nuclear radiation in the hope to reduce populations; this is done with a cobalt-60 gamma cell irradiator. In 2016 the World Health Organization encouraged field trials of transgenic male Aedes aegypti mosquitoes developed by Oxitec to try to halt the spread of the Zika virus.
References
External links
Managing Zika in babies (CDC)
Species Profile – Zika Virus Disease, National Invasive Species Information Center, United States National Agricultural Library. Lists general information and resources for White-Nose Syndrome. |
Sjögren syndrome | Sjögren syndrome or Sjögrens syndrome (SjS, SS) is a long-term autoimmune disease that affects the bodys moisture-producing (lacrimal and salivary) glands, and often seriously affects other organ systems, such as the lungs, kidneys, and nervous system. Primary symptoms are dryness (dry mouth and dry eyes), pain and fatigue. Other symptoms can include dry skin, vaginal dryness, a chronic cough, numbness in the arms and legs, feeling tired, muscle and joint pains, and thyroid problems. Those affected are also at an increased risk (15%) of lymphoma.While the exact cause is unclear, it is believed to involve a combination of genetics and an environmental trigger such as exposure to a virus or bacterium. It can occur independently of other health problems (primary Sjögrens syndrome) or as a result of another connective tissue disorder (secondary Sjögrens syndrome). Sjögrens syndrome may be associated with other autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or systemic sclerosis. The inflammation that results progressively damages the glands. Diagnosis is by biopsy of moisture-producing glands and blood tests for specific antibodies. On biopsy there are typically lymphocytes within the glands.While Sjögrens syndrome is one of the most common auto-immune diseases, it has no specific and non-invasive diagnostic tests and treatment is directed at managing the persons symptoms. For dry eyes, artificial tears, medications to reduce inflammation, punctal plugs, or surgery to shut the tear ducts may be tried. For a dry mouth, chewing gum (preferably sugar-free), sipping water, or a saliva substitute may be used. In those with joint or muscle pain, ibuprofen may be used. Medications that can cause dryness, such as antihistamines, may also be stopped. The most specific extant diagnostic test requires lip biopsy.
The disease was described in 1933 by Henrik Sjögren, after whom it is named; however, a number of earlier descriptions of people with the symptoms exist. Between 0.2 and 1.2% of the population is affected, with half having the primary form and half the secondary form. Females are affected about 10 times as often as are males. Though the disease commonly begins in middle age, anyone can be affected. Among those without other autoimmune disorders, life expectancy is unchanged.
Signs and symptoms
The hallmark symptom of Sjögren syndrome is dry mouth and keratoconjunctivitis sicca (dry eyes). Vaginal dryness, dry skin, and dry nose may also occur. Other organs of the body may also be affected, including the kidneys, blood vessels, lungs, liver, pancreas, and brain.Skin dryness in some people with SS may be the result of lymphocytic infiltration into skin glands. The symptoms may develop insidiously, with the diagnosis often not considered for several years because sicca may be attributed to medications, a dry environment, or aging, or may be regarded as not of a severity warranting the level of investigation necessary to establish the presence of the underlying autoimmune disorder.Sjögrens syndrome can damage vital organs, with symptoms that may plateau or worsen, or go into remission, as with other autoimmune diseases. Some people may experience only the mild symptoms of dry eyes and mouth, while others have symptoms of severe disease. Many patients can treat problems symptomatically. Others experience blurred vision, constant eye discomfort, recurrent mouth infections, swollen parotid glands, dysphonia (vocal disorders including hoarseness), and difficulty in swallowing and eating. Debilitating fatigue and joint pain can seriously impair quality of life. Some patients can develop kidney involvement (autoimmune tubulointerstitial nephritis) leading to proteinuria (excess protein in urine), urinary concentrating defect, and distal renal tubular acidosis.Hypokalemic paralysis due to primary Sjögren syndrome was rarely reported in the literature.
Complications
Among the complications discussed above, women with anti-Ro/SS-A and anti-La/SS-B antibodies who become pregnant have an increased rate of neonatal lupus erythematosus with congenital heart block requiring a pacemaker. Type I cryoglobulinemia is a known complication of Sjögrens syndrome.Sjögrens syndrome can affect such organs as the liver, pancreas, kidneys, lungs, and central nervous system.
Associated conditions
Sjögrens syndrome is associated with a number of other medical conditions, many of which are autoimmune or rheumatic disorders, such as celiac disease, fibromyalgia, SLE (lupus), autoimmune thyroiditis, multiple sclerosis and spondyloarthropathy, and several malignancies, principally non-Hodgkin lymphoma.
Causes
The cause of Sjögrens syndrome is unknown, but it may be the influence of a combination of genetic, environmental, and other factors, as is the case with many other autoimmune disorders. Around 20 autoantibodies could be involved.
Genetics
The observation of high rates of autoimmune disorders in families with a history of Sjögrens syndrome is linked with a genetic predisposition to the syndrome. Studies on the polymorphisms of human leukocyte antigen (HLA)-DR and HLA-DQ gene regions in Sjögrens patients show differential susceptibility to the syndrome as the result of different types of the resulting autoantibody production.
Hormones
Since Sjögrens syndrome is associated with a high prevalence in women, sex hormones, especially estrogen, are believed to affect humoral and cell-mediated immune responses affecting susceptibility to the syndrome. Androgens are generally considered to prevent autoimmunity. Studies on mice models suggest estrogen deficiency stimulates presentation of autoantigens, inducing Sjögrens-like symptoms.
Microchimerism
Microchimerism of fetal cells (offspring lymphoid cells in maternal circulation) may generate autoimmunity in women who have previously been pregnant. Generation of an autoimmune potential via microchimerism may lead to a switch from a silent form of autoimmunity with age-dependent decrease in self-tolerance.
Environment
Viral proteins, engulfed molecules, or degraded self-structures may initiate autoimmunity by molecular mimicry and increase the chances of Sjögrens syndrome development. Epstein–Barr virus, hepatitis C, and human T-cell leukemia virus-1 are among the most studied infectious agents in Sjögrens syndrome. To date, no direct causes and effect relationship has been identified between these pathogens and the development of Sjögrens syndrome. Damaged self-structures targeted for apoptosis may be mistakenly exposed to the immune system, triggering autoimmunity in exocrine glands, which are often prone to autoimmune responses.
Pathogenesis
The pathogenetic mechanisms of Sjögrens syndrome have not been fully elucidated, resulting in the lack of pathophysiology knowledge of the management of this autoimmune exocrinopathy. Although the numerous factors contributing to the progression of this disease have made discovering the exact origin and cause difficult, major advances over the past decade have contributed to a proposed set of pathogenic events that occur prior to the diagnosis of Sjögrens syndrome.Sjögrens syndrome was originally proposed as a specific, self-perpetuating, immune system-mediated loss of exocrine glands, specifically acinar and ductal cells. Although this explains the more obvious symptoms (such as the lack of saliva and lacrimal fluid), it does not explain the more widespread systemic effects seen in the progression of the disease.In the presence of a susceptible genetic background, both environmental and hormonal factors are thought capable of triggering the infiltration of lymphocytes, specifically CD4+ T cells, B cells, and plasma cells, causing glandular dysfunction in the salivary and lacrimal glands.Sjögrens syndrome is associated with increased levels in cerebrospinal fluid (CSF) of IL-1RA, an interleukin 1 antagonist. This suggests that the disease begins with increased activity in the interleukin 1 system, followed by an autoregulatory upregulation of IL-1RA to reduce the successful binding of interleukin 1 to its receptors. Interleukin 1 likely is the marker for fatigue, but increased IL-1RA is observed in the CSF and is associated with increased fatigue through cytokine-induced sickness behavior. However, Sjögrens syndrome is characterized by decreased levels of IL-1ra in saliva, which could be responsible for mouth inflammation and dryness. Patients with secondary Sjögrens syndrome also often exhibit signs and symptoms of their primary rheumatic disorders, such as systemic lupus erythematosus, rheumatoid arthritis, or systemic sclerosis.
Genetic predisposition
The genetic locus most significantly associated with primary SS is the major histocompatibility complex/human leukocyte antigen (MHC/HLA) region, as demonstrated by the preliminary results of the first genome-wide association study. This study included data from a discovery cohort of 395 patients of European ancestry with primary Sjögrens syndrome, and 1,975 healthy control individuals, and from a replication study that comprised 1,234 cases and 4,779 healthy controls. Associations with polymorphisms located at six independent loci were also detected; IRF5, STAT4, BLK, IL12A, TNIP1, and CXCR5. This also suggested the activation of the innate immune system, notably through the IFN system, B-cell activation through CXCR5-directed recruitment to lymphoid follicles and B-cell receptor (BCR) activation involving BLK, and T-cell activation owing to HLA susceptibility and the IL-12-IFN-γ-axis.Patients of different ethnic origin carry different HLA-susceptibility alleles, of which HLA-DR and HLA-DQ are involved in the pathogenesis of Sjögrens syndrome. For example, patients from Northern and Western Europe and from North America show a high prevalence of B8, DRw52, and DR3 genes. HLA class II alleles are associated with the presence of specific subsets of autoantibodies, rather than with the disease itself. Autoantibodies refer to the loss of B-cell tolerance leading to production of antibodies directed against diverse organ-specific and organ nonspecific antigens. Association between HLA and SS is restricted to patients with anti-SSA/Ro or anti-SSB/La antibodies. Seropositivity for anti-Ro and anti-La is associated with greater severity and longer duration of disease, and findings of their high abundance from the salivary glands of Sjögrens patients suggests their imperative role in the pathogenesis of SS.Beyond genetics, epigenetic abnormality related to DNA methylation, histone acetylation, or microRNA expression probably has a key role in the pathogenesis of autoimmune diseases, including Sjögrens syndrome, though research in this area is very limited.
Environmental triggers
Environmental factors, such as glandular viral infection, could prompt epithelial cells to activate the HLA-independent innate immune system through toll-like receptors. Although a number of infectious, exogenous agents have been implicated in the pathogenesis of Sjögrens syndrome, such as Epstein-Barr virus (EBV), human T-lymphotropic virus 1, and hepatitis C virus, their association with Sjögrens syndrome appears weak. While EBV is present in the salivary glands of normal individuals, a high incidence of EBV reactivation in Sjögrens patients has been reported with increased levels of EBV DNA. This indicates viral reactivation and inability of lymphoid infiltrates to control EBV replication in Sjögrens syndrome, leading to the initiation or perpetuation of an immune response in target organs. Nonetheless, exactly how reactivation of EBV is induced in lesions of patients with Sjögrens syndrome, and which specific molecular mechanisms are involved in the process of viral reactivation, remain to be clarified.
Inflammation
Epithelial cells in Sjögrens syndrome lesions are active participants in the induction and perpetuation of the inflammatory process. Environmental and hormonal factors, in concert with an appropriate genetic background, are believed to trigger Sjögrens syndrome, which dysregulates epithelial cells and allows aberrant homing and activation of dendritic cells (DCs), T cells, and B cells. Dendritic cells are antigen-presenting cells that process antigen material and present it to other T cells. Following the migration of lymphocytes into the glands in response to chemokines and specific adhesion molecules, T cells interact with epithelial cells. Epithelial cells are further activated by proinflammatory cytokines (IL-1β, IFN-γ, and TNF), which are produced by adjacent T cells. The early accumulation of plasmacytoid dendritic cells in the target tissues, which produce high levels of type 1 IFNs, seems important, as these cells can further dysregulate the immune response through abnormal retention of lymphocytes in the tissues and their subsequent activation. IFN-α stimulates the production of B-cell activating factor (BAFF) by epithelial cells, DCs, and T cells. BAFF stimulates aberrant B-cell maturation, leading to the emergence of self-reactive B cells, which locally produce autoantibodies, in a germinal centre-like structure (GC-like), which is also the location of lymphomagenesis (origin of lymphoma).
Programmed cell death
Dysregulation of apoptosis (programmed cell death) is believed to play a role in the pathogenesis of a variety of autoimmune diseases, though its role in Sjögrens syndrome is controversial. Both the Fas and Fas ligand proteins are overexpressed in primary Sjögrens patients, while expression of BCL-1, which is known to downregulate apoptosis, was found significantly reduced in acinar and ductal epithelial cells of Sjögrens patients compared to healthy people. In situ studies did not show increased apoptosis among glandular epithelial cells, but did show reduced apoptosis among infiltrating mononuclear cells. Reduced apoptosis was also implicated in the accumulation of autoreactive B-cells found in the glands. The relationship of autoantibodies expressed in Sjögrens syndrome with apoptosis is still being researched.
Hormonal factors
Sex hormones seem to influence humoral and cell-mediated immune response, with estrogen being considered one of the biggest factors responsible for sex-immunologic dimorphism. Estrogen deficiency appears to play a role in development of Sjögrens syndrome. It has been hypothesized that androgen administration to the ocular surface may serve as an effective therapy for dry eyes.
Diagnosis
Diagnosing Sjögrens syndrome (SS) is complicated by the range of symptoms that a patient may manifest, and the similarity between symptoms of Sjögrens syndrome and those of other conditions. Also, patients with SS symptoms approach different specialities for treatment, which can make diagnosis difficult. Since dry eyes and dry mouth are very common symptoms, and frequently occur in people over 40, affected people may believe that the symptoms are age-related, so ignore them. Some medications can cause symptoms similar to those of Sjögrens syndrome. The combination of several tests, which can be done in a series, can eventually diagnose Sjögrens syndrome.Blood tests can be done to determine if a patient has high levels of antibodies that are indicative of the condition, such as antinuclear antibody (ANA) and rheumatoid factor (because Sjögrens syndrome frequently occurs secondary to rheumatoid arthritis), which are associated with autoimmune diseases. Typical SS ANA patterns are SSA/Ro and SSB/La, of which anti-SSB/La is far more specific; anti-SSA/Ro is associated with numerous other autoimmune conditions, but is often present in SS, but aAnti-SSA and anti-SSB tests are frequently not positive in SS.The rose bengal test uses a stain that measures state and function of the lacrimal glands. This test involves placing the nontoxic dye rose bengal on the eyes. The dyes distinctive colour helps in determining the state and functioning of tear film and the rate of tear evaporation. Any distinctive colour change can indicate SS, but confirming the condition requires many related diagnostic tools.Schirmers test measures the production of tears: a strip of filter paper is held inside the lower eyelid for five minutes, and its wetness is then measured with a ruler. Producing less than 5 mm (0.20 in) of liquid is usually indicative of SS. This measurement analysis varies among people depending on other eye-related conditions and medications in use when the test is taken. A slit-lamp examination can reveal dryness on the surface of the eye.Symptoms of dry mouth and dryness in the oral cavity are caused by the reduced production of saliva from the salivary glands (parotid gland, submandibular gland, and sublingual gland). To check the status of salivary glands and the production of saliva, a salivary flow-rate test is performed, in which the person is asked to spit as much as they can into a cup, and the resulting saliva sample is collected and weighed. This tests results can determine whether the salivary glands are functioning adequately. Not enough saliva produced could mean the person has SS. An alternative test is nonstimulated whole saliva flow collection, in which the person spits into a test tube every minute for 15 minutes. A resultant collection of less than 1.5 ml (0.053 imp fl oz; 0.051 US fl oz) is considered a positive result.
A lip/salivary gland biopsy takes a tissue sample that can reveal lymphocytes clustered around salivary glands, and damage to these glands from inflammation. This test involves removing a sample of tissue from a persons inner lip/salivary gland and examining it under a microscope. On such biopsies, the single most important test result in the diagnosis of the oral component of Sjögren syndrome is likely the focus score, which is the number of mononuclear cell infiltrates containing at least 50 inflammatory cells in a 4 mm2 glandular section. The Chisholm-Mason grades are also widely used for salivary gland biopsies (see table).A radiological procedure is available as a reliable and accurate test for Sjögrens syndrome, in the form of a sialogram. A contrast agent is injected into the parotid duct, which opens from the cheek into the vestibule of the mouth opposite the neck of the upper second molar tooth. The test is intended to detect any blockage in the salivary gland ducts (i.e. parotid duct) and the amount of saliva that flows into the mouth.For Sjögrens syndrome, sudomotor function through electrochemical skin conductance may help in the diagnosis process.Sjögrens syndrome can be excluded from people with past head and neck radiation therapy, acquired immunodeficiency syndrome, pre-existing lymphoma, sarcoidosis, graft-versus-host disease, and use of anticholinergic drugs.
Prevention
No prevention mechanism exists for Sjögrens syndrome (SS) because of its complexity as an autoimmune disorder, but lifestyle changes can reduce the risk factors related to developing SS or reduce the severity of the condition for patients who have already been diagnosed. Diet is strongly associated with the inflammation seen in many autoimmune related diseases, including SS. An experimental study concluded that SS patients often show high sensitivity to gluten that directly relates to inflammation. Moderate exercise is also helpful in SS patients, mainly reducing the effect of lung inflammation.
Treatment
Neither a cure nor a specific treatment for Sjögrens syndrome is known to permanently restore gland secretion. Instead, treatment is generally symptomatic and supportive.
Eye care
Moisture replacement therapies such as artificial tears may ease the symptoms of dry eyes. Some patients with more severe problems use goggles to increase local humidity or have punctal plugs inserted to help retain tears on the ocular surface for a longer time.Additionally, cyclosporine (Restasis) is available by prescription to treat chronic dry eye by suppressing the inflammation that disrupts tear secretion. Prescription drugs are also available that help to stimulate salivary flow, such as cevimeline (Evoxac) and pilocarpine. Salagen, a manufactured form of pilocarpine, can be used to help produce tears, as well as saliva in the mouth and intestines. It is derived from the jaborandi plant.
Vaginal dryness
In women with Sjögrens syndrome, vaginal dryness, vulvodynia and dyspareunia (painful sexual intercourse) are often reported; personal lubricants are recommended to help lessen irritation or pain that may result from dryness in the vaginal and vulval areas.
Musculoskeletal
Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used to treat musculoskeletal symptoms. For individuals with severe complications, corticosteroids or immunosuppressive drugs may be prescribed, and sometimes intravenous immunoglobulins. Also, disease-modifying antirheumatic drugs such as methotrexate may be helpful. Hydroxychloroquine (Plaquenil) is another option and is generally considered safer than methotrexate. However, these prescribed drugs have a range of side effects such as nausea, loss of appetite, dizziness, hair loss, stomach aches/cramps, headache, liver toxicity and increased risk of infections. Also, those who take drugs to suppress the immune system are more likely to develop cancer later.
Systemic
For systemic symptoms, including fatigue, joint pain, myositis and neuropathy, biologic immunosuppressant drugs such as rituximab and belimumab that work via B-cell pathology are often used and have less toxic profiles than traditional immunosuppressive regimens.
Dental care
Preventive dental treatment is also necessary (and often overlooked by the patient), as the lack of saliva associated with xerostomia creates an ideal environment for the proliferation of bacteria that cause cavities. Treatments include at-home topical fluoride application to strengthen tooth enamel and frequent teeth cleanings by a dental hygienist. Existing cavities must also be treated, as cavities that extend into the tooth cannot be effectively treated by teeth cleaning alone, and are at a high risk of spreading into the pulp of the tooth, leading to the loss of vitality and need for extraction or root canal therapy. This treatment regimen is the same as for all xerostomia patients, such as for those undergoing head and neck radiation therapy, which often damages the salivary glands; these glands are more susceptible to radiation than are other body tissues.
Prognosis
Published studies on the survival of Sjögrens syndrome patients are limited in varied respects, perhaps owing to the relatively small sample sizes, and the fact that secondary Sjögrens syndrome is associated with other autoimmune diseases. Results from a number of studies indicate that, compared to other autoimmune diseases, Sjögrens syndrome is associated with a notably high incidence of malignant non-Hodgkin lymphoma, a cancer of white blood cells. About 5% of patients with SS develop some form of lymphoid malignancy. Patients with severe cases are much more likely to develop lymphomas than patients with mild or moderate cases. The most common lymphomas are salivary extranodal marginal zone B cell lymphomas (MALT lymphomas in the salivary glands) and diffuse large B-cell lymphoma.Lymphomagenesis in primary Sjögrens syndrome patients is considered as a multistep process, with the first step being chronic stimulation of autoimmune B cells, especially B cells that produce rheumatoid factor at sites targeted by the disease. This increases the frequency of oncogenic mutation, leading to any dysfunction at checkpoints of autoimmune B-cell activation to transform into malignancy. A studys finding has concluded the continuous stimulation of autoimmune B cells, leading to subtle germinal abnormalities in genes having specific consequences in B cells, which underlies the susceptibility to lymphoma.Apart from this notably higher incidence of malignant NHL, Sjögrens patients show only modest or clinically insignificant deterioration in specific organ-related function, which explains the only slight increases in mortality rates of Sjögrens patients in comparison with the remainder of the population.Sjögrens syndrome is associated with a high burden of illness, and has been shown to markedly reduce quality of life (QoL), with a significant impact on ability to work resulting from increased rates of disability. The reduction in QoL is similar to that seen in other chronic conditions such as rheumatoid arthritis, lupus and fibromyalgia.
Epidemiology
Sjögrens syndrome (SS) is the second-most common rheumatic autoimmune disorder, behind rheumatoid arthritis and systemic lupus erythematosus. There are no geographical differences in the rates of SS. Sjögrens syndrome has been reported in all areas of the world, although regional rates have not been well studied. Depending on the criteria for determining prevalence, studies estimate the prevalence of SS at between 500,000 and two million people in the United States. Broader studies of SS prevalence range widely, with some reports of up to a prevalence of 3% of the population. A few studies have reported that the incidence of the syndrome varies between three and six per 100,000 per year.Nine out of 10 SS patients are women. In addition to prevalence in women, having a first-degree relative with an autoimmune disease and previous pregnancies have been identified as epidemiological risk factors. Despite the lower risk for men, primary SS in men tends to represent a more severe form of the disease. The role of race and ethnicity in the prevalence of the disease is unknown.Although Sjögrens syndrome occurs in all age groups, the average age of onset is between ages 40 and 60, although as many as half of all cases may be left undiagnosed or unreported. The prevalence of SS generally increases with age.Sjögrens syndrome is reported in 30-50% of people with rheumatoid arthritis and in 10-25% with systemic lupus erythematosus.
History
Jan Mikulicz-Radecki (1850–1905) is generally credited with the first description of SS. In 1892, he described a 42-year-old man with enlargement of the parotid and lacrimal glands associated with a round-cell infiltrate and acinar atrophy. However, the criteria that Mikulicz established for diagnosis often led to misdiagnosis of Mikuliczs syndrome. Many conditions, such as tuberculosis, infections, sarcoidosis and lymphoma present with similar conditions to those ascribed to Mikuliczs syndrome. Nevertheless, the term "Mikulicz’s syndrome" is still used occasionally to describe the appearance of lymphocytic infiltrates on salivary-gland biopsies.In 1930, Henrik Sjögren (1899–1986), an ophthalmologist in Jönköping, Sweden, observed a patient with low secretions from the lacrimal and salivary glands. Sjögren introduced the term keratoconjunctivitis sicca for the symptom of dry eyes (keratoconjunctivitis). In 1933, he published his doctoral thesis describing 19 females, most of whom were postmenopausal and had arthritis, showing clinical and pathological manifestations of the syndrome. Sjögren clarified that keratoconjunctivitis sicca, resulting from water deficiency, had no relation to xerophthalmia, resulting from vitamin A deficiency. Sjögrens thesis was not well received as the Board of Examiners criticized some clinical aspects.After extensive research and data collection, Sjögren published an essential paper in 1951, describing 80 patients with keratoconjunctivitis sicca, 50 of whom also had arthritis. His subsequent follow-up conference trips pertaining to his paper led to an international interest in Sjögrens syndrome. The term "keratoconjunctivitis sicca" was coined by Sjögren himself and began to be identified as Sjögrens syndrome in literature, although it can now have more general usage.
Research
Research into multifactorial autoimmune diseases such as SS focuses on expanding the knowledge surrounding the disorder, improving diagnostic tools and finding ways to prevent, manage and cure the disorder. The United Kingdom Primary Sjögrens Syndrome Registry, a tissue biobank of samples taken for research, supported by the Medical Research Council, UK, was established in 2010. It supports clinical trials and genetic studies of Sjögrens syndrome and is open to those wishing to participate in research studies and to researchers studying the disease.As with other autoimmune diseases, susceptibility to Sjögrens syndrome is greatly influenced by the human leukocyte antigen. DQA1* |
Sjögren syndrome | 05:01, DQB1*02:01, and DRB1*03:01 alleles were identified as risk factors, while DQA1*02:01, DQA1*03:01 and DQB1*05:01 alleles were found to be protective factors for the disease. The relationship between alleles and specific race was also established. HLA-DQ2 and HLA-B8 are generally found in Caucasian patients, while HLA-DR5 is related to Greek and Israeli patients. Multiple genome-wide association scans may be conducted in the future to identify key risk variants.Viruses that have been associated with Sjögrens syndrome include human T-lymphotropic virus type 1 (HTLV-1), Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), hepatitis delta virus (HDV) and hepatitis C virus (HCV).Some research has showed that the lack of vitamin A and vitamin D are associated with the disease. Vitamin D deficiency was found to be related to neurological manifestations and the presence of lymphoma among patients, but vitamin A levels were inversely associated with extraglandular manifestations of the disease.Saliva is a potential diagnostic tool for Sjögrens syndrome because the salivary component is changed after onset of the disease. With the new miniaturization technology, called lab on a chip, the diagnosis can be more convenient.With regard to therapeutics, multiple monoclonal antibodies were under investigation in 2007. The most promising seemed to be the anti-CD20 rituximab and the anti-CD22 epratuzumab, while the anti-TNF-α and IFN-α seemed less effective.In 2014, the Sjögrens Syndrome Foundation announced a five-year goal to halve the diseases average time to diagnosis.
Notable cases
Shannon Boxx (U.S. Olympic soccer player) has both Sjögrens syndrome and lupus.
Carrie Ann Inaba (singer-actress) is the national awareness ambassador and spokesperson for the Sjögrens Syndrome Foundation.
Venus Williams (world-champion tennis player) has been diagnosed with Sjögrens syndrome and said she had struggled with fatigue for years.
Stephen McPhail (professional soccer player for Ireland, Leeds and Cardiff City) was diagnosed with lymphoma and Sjögrens syndrome at age 29.
Halsey (singer) diagnosed with Sjorgens, Ehlers-Danlos syndrome, Mast Cell Activation Syndrome, and Postural Orthostatic Tachycardia Syndrome
References
Some of the original text for this article was obtained from a public domain resource at NIH
External links
Sjögren syndrome at NHS Choices
Sjögren syndrome – US National Institute of Arthritis and Musculoskeletal and Skin Diseases
US Sjögren‘s Foundation
Price, EJ; Rauz, S; Tappuni, AR; Sutcliffe, N; Hackett, KL; Barone, F; Granata, G; Ng, WF; Fisher, BA; Bombardieri, M; Astorri, E; Empson, B; Larkin, G; Crampton, B; Bowman, SJ; British Society for Rheumatology Standards, Guideline and Audit Working, Group. (1 October 2017). "The British Society for Rheumatology guideline for the management of adults with primary Sjögrens Syndrome". Rheumatology. 56 (10): e24–e48. doi:10.1093/rheumatology/kex166. PMID 28957550. |
Inflammatory myopathy | Inflammatory myopathy is disease featuring weakness and inflammation of muscles and (in some types) muscle pain. The cause of much inflammatory myopathy is unknown (idiopathic), and such cases are classified according to their symptoms and signs and electromyography, MRI and laboratory findings. It can also be associated with underlying cancer. The main classes of idiopathic inflammatory myopathy are polymyositis (PM), dermatomyositis (DM), and inclusion-body myositis (IBM).
Diagnosis
There are a number of known causes of myopathy, and it is only once these have been ruled out that a clinician will assign an idiopathic inflammatory myopathy (IIM) syndrome to a case. The usual criteria for a diagnosis of PM are weakness in muscles of the head, neck, trunk, upper arms or upper legs; raised blood serum concentrations of some muscle enzymes such as creatine kinase; unhealthy muscle changes on electromyography; and biopsy findings of (i) muscle cell degeneration and regeneration and (ii) chronic inflammatory infiltrates in muscle cells. If heliotrope (purple) rash or Gottrons papules are also present, then the diagnosis is DM. In DM, myositis may not be clinically apparent but detectable via biopsy or MRI. If the criteria for PM are met but muscle weakness also affects the hands and feet or is not accompanied by pain IBM should be suspected, and confirmed when muscle cell biopsy reveals (i) cytoplasmic vacuoles fringed by basophilic granules and (ii) inflammatory infiltrate comprising mostly CD8 T lymphocytes and macrophages; and electron microscopy reveals filamentous inclusions in both cytoplasm and nucleus.
Treatment
There have been few randomized treatment trials, due to the relative rarity of inflammatory myopathies. The goal of treatment is improvement in activities of daily living and muscle strength. Suppression of immune system activity (immunosuppression) is the treatment strategy. Patients with PM or DM almost always improve to some degree in response to treatment, at least initially, and many recover fully with maintenance therapy. (If there is no initial improvement from treatment of PM or DM, the diagnosis should be carefully re-examined.) There is no proven effective therapy for IBM, and most IBM patients will need assistive devices such as a cane, a walking frame or a wheelchair. The later in life IBM arises, the more aggressive it appears to be.
Polymyositis and dermatomyositis
In severe cases of PM and DM with systemic signs, an initial three to five days on intravenous corticosteroid (methylprednisolone) may be used; but normally treatment begins with a single daily (after breakfast) high dose of oral corticosteroid (prednisone). After a month or so the strength of every second days dose is very gradually reduced over three to four months, to minimize the negative effects of the prednisone. When a high dose of prednisone cannot be reduced without losing muscle strength, or when prednisone is effective but it is producing significant complications, "steroid sparing" oral immunosuppressants such as azathioprine, mycophenolate mofetil, methotrexate and cyclosporine, may be used in combination with reduced prednisone. Some of these steroid sparing drugs can take several months to demonstrate an effect.To minimize side effects, patients on corticosteroids should follow a strict high-protein, low-carbohydrate, low-salt diet; and with long-term corticosteroid use a daily calcium supplement and weekly vitamin D supplement (and a weekly dose of Fosamax for postmenopausal women) should be considered.For patients not responding to this approach there is weak evidence supporting the use of intravenous immunoglobulin, ciclosporin, tacrolimus, mycophenolate mofetil and other agents; and trials of rituximab have indicated a potential therapeutic effect.
Inclusion-body myositis
Despite its very similar clinical presentation to PM, IBM does not respond to the drugs that effectively treat PM, and there is no proven effective therapy for IBM. Alemtuzumab is being studied but as of May 2013 it had not demonstrated clinical effectiveness in IBM. Dysphagia (difficulty swallowing) may be improved by intravenous immunoglobulin, though more trials are needed. Non-fatiguing, systematic strength-building exercise has demonstrated benefit. Occupational and rehabilitation therapists can offer good advice on walking without falling and performing fine motor tasks, and can provide appropriate canes, braces and wheelchairs. Speech pathologists can provide advice on preventing choking episodes and reducing the anxiety of an immanent aspiration for both patients and carers.
Epidemiology
Every year between 2.18 and 7.7 people per million receive a diagnosis of PM or DM. Around 3.2 children per million per year are diagnosed with DM (termed juvenile dermatomyositis), with an average age of onset of seven years. Diagnosis of adult DM commonly occurs between 30 and 50 years of age. PM is an adult disease, usually emerging after the age of twenty. PM and DM are more common in females, more common in Caucasians, and least common in Asians. At any given time, about 35.5 people per million have IBM; it emerges after the age of 30 (usually after 50), and may be more common in males.
References
== External links == |
Hemolytic disease of the newborn | Hemolytic disease of the newborn, also known as hemolytic disease of the fetus and newborn, HDN, HDFN, or erythroblastosis foetalis, is an alloimmune condition that develops in a fetus at or around birth, when the IgG molecules (one of the five main types of antibodies) produced by the mother pass through the placenta. Among these antibodies are some which attack antigens on the red blood cells in the fetal circulation, breaking down and destroying the cells. The fetus can develop reticulocytosis and anemia. The intensity of this fetal disease ranges from mild to very severe, and fetal death from heart failure (hydrops fetalis) can occur. When the disease is moderate or severe, many erythroblasts (immature red blood cells) are present in the fetal blood, earning these forms of the disease the name erythroblastosis fetalis (British English: erythroblastosis foetalis).
HDFN represents a breach of immune privilege for the fetus or some other form of impairment of the immune tolerance in pregnancy. Various types of HDFN are classified by which alloantigen provokes the response. The types include ABO, anti-RhD, anti-RhE, anti-Rhc, anti-Rhe, anti-RhC, multiantigen combinations, and anti-Kell. Although global prevalence studies of the differential contribution of those types are lacking, regional population studies have shown the anti-RhD type to be the most common cause of HDFN, followed by anti-RhE, anti-RhC, and anti-Rhc.
Signs and symptoms
Signs of hemolytic disease of the newborn include a positive direct Coombs test (also called direct agglutination test), elevated cord bilirubin levels, and hemolytic anemia. It is possible for a newborn with this disease to have neutropenia and neonatal alloimmune thrombocytopenia as well. Hemolysis leads to elevated bilirubin levels. After delivery, bilirubin is no longer cleared (via the placenta) from the neonates blood and the symptoms of jaundice (yellowish skin and yellow discoloration of the whites of the eyes, or icterus) increase within 24 hours after birth. Like other forms of severe neonatal jaundice, there is the possibility of the neonate developing acute or chronic kernicterus, however the risk of kernicterus in HDN is higher because of the rapid and massive destruction of blood cells. It is important to note that isoimmunization is a risk factor for neurotoxicity and lowers the level at which kernicterus can occur. Untreated profound anemia can cause high-output heart failure, with pallor, enlarged liver and/or spleen, generalized swelling, and respiratory distress.HDN can be the cause of hydrops fetalis, an often-severe form of prenatal heart failure that causes fetal edema.
Complications
Complications of HDN could include kernicterus, hepatosplenomegaly, inspissated (thickened or dried) bile syndrome and/or greenish staining of the teeth, hemolytic anemia and damage to the liver due to excess bilirubin. Conditions that may cause similar symptoms in the newborn period include: acquired hemolytic anemia, congenital toxoplasma, congenital syphilis infection, congenital obstruction of the bile duct, and cytomegalovirus (CMV) infection.
High at birth or rapidly rising bilirubin
Prolonged hyperbilirubinemia
Bilirubin Induced Neurological Dysfunction
Cerebral Palsy
Kernicterus
Neutropenia
Thrombocytopenia
Hemolytic anemia – must not be treated with iron
Late onset anemia – must not be treated with iron. Can persist up to 12 weeks after birth.
Pathophysiology
Antibodies are produced when the body is exposed to an antigen foreign to the make-up of the body. If a mother is exposed to a foreign antigen and produces IgG (as opposed to IgM which does not cross the placenta), the IgG will target the antigen, if present in the fetus, and may affect it in utero and persist after delivery. The three most common models in which a woman becomes sensitized toward (i.e., produces IgG antibodies against) a particular antigen are hemorrhage, blood transfusion, and ABO incompatibility.Fetal-maternal hemorrhage, which is the movement of fetal blood cells across the placenta, can occur during abortion, ectopic pregnancy, childbirth, ruptures in the placenta during pregnancy (often caused by trauma), or medical procedures carried out during pregnancy that breach the uterine wall. In subsequent pregnancies, if there is a similar incompatibility in the fetus, these antibodies are then able to cross the placenta into the fetal bloodstream to attach to the red blood cells and cause their destruction (hemolysis). This is a major cause of HDN, because 75% of pregnancies result in some contact between fetal and maternal blood, and 15–50% of pregnancies have hemorrhages with the potential for immune sensitization. The amount of fetal blood needed to cause maternal sensitization depends on the individuals immune system and ranges from 0.1 mL to 30 mL.The woman may have received a therapeutic blood transfusion. ABO blood group system and the D antigen of the Rhesus (Rh) blood group system typing are routine prior to transfusion. Suggestions have been made that women of child-bearing age or young girls should not be given a transfusion with Rhc-positive blood or Kell1-positive blood to avoid possible sensitization, but this would strain the resources of blood transfusion services, and it is currently considered uneconomical to screen for these blood groups. HDFN can also be caused by antibodies to a variety of other blood group system antigens, but Kell and Rh are the most frequently encountered.The third sensitization model can occur in women of blood type O. The immune response to A and B antigens, which are widespread in the environment, usually leads to the production of IgM or IgG anti-A and anti-B antibodies early in life. Women of blood type O are more prone than women of types A and B to making IgG anti-A and anti-B antibodies, and these IgG antibodies are able to cross the placenta. For unknown reasons, the incidence of maternal antibodies against type A and B antigens of the IgG type that could potentially cause hemolytic disease of the newborn is greater than the observed incidence of "ABO disease." About 15% of pregnancies involve a type O mother and a type A or type B child; only 3% of these pregnancies result in hemolytic disease due to A/B/O incompatibility. In contrast to antibodies to A and B antigens, production of Rhesus antibodies upon exposure to environmental antigens seems to vary significantly across individuals. In cases where there is ABO incompatibility and Rh incompatibility, the risk of alloimmunization is decreased because fetal red blood cells are removed from maternal circulation due to anti-ABO antibodies before they can trigger an anti-Rh response.
Serological types
HDN is classified by the type of antigens involved. The main types are ABO HDN, Rhesus HDN, Kell HDN, and other antibodies. Combinations of antibodies (for example, anti-Rhc and anti-RhE occurring together) can be especially severe.ABO hemolytic disease of the newborn can range from mild to severe, but generally, it is a mild disease. It can be caused by anti-A and anti-B antibodies.Rhesus D hemolytic disease of the newborn (often called Rh disease) is the most common and only preventable form of severe HDN. Since the introduction of Rho-D immunoglobulin, (Rhogam, at 1968, which prevents the production of maternal Rho-D antibodies, the incidence of anti-D HDN has decreased dramatically.Rhesus c HDFN can range from a mild to severe disease and is the third most common form of severe HDN. Rhesus e and rhesus C hemolytic disease of the newborn are rare. Anti-C and anti-c can both show a negative DAT but still have a severely affected infant. An indirect Coombs must also be run.
Anti-Kell hemolytic disease of the newborn is most commonly caused by anti-K1 antibodies, the second most common form of severe HDN. Over half of the cases of anti-K1 related HDN are caused by multiple blood transfusions. Antibodies to the other Kell antigens are rare. Anti-Kell can cause severe anemia regardless of titer. It suppresses the bone marrow by inhibiting the erythroid progenitor cells.Anti-M also recommends antigen testing to rule out the presence of HDN as the direct coombs can come back negative in a severely affected infant.Kidd antigens are also present on the endothelial cells of the kidneys.One study states that it would be unwise to routinely dismiss anti-E as being of little clinical consequence. It also found that the most severe case of anti-E HDFN occurred with titers 1:2, concluding that titers are not reliable for the diagnosis of the anti-E type.
Diagnosis
The diagnosis of HDN is based on history and laboratory findings:Blood tests done on the newborn baby
Biochemistry tests for jaundice including total and direct bilirubin levels.
Complete blood count (CBC) which may show a decreased hemoglobin and hematocrit due to red blood cell destruction
Reticulocyte count which will usually be increased as the bone marrow makes new red blood cells to replace the ones that are being destroyed, and a peripheral blood smear to look at cell morphology. In the presence of significant hemolysis the smear will show schistocytes (fragmented red blood cells), reticulocytosis, and in severe cases Erythroblasts (also known as nucleated red blood cells).
Positive direct Coombs test (might be negative after fetal interuterine blood transfusion)Blood tests done on the mother
Positive indirect Coombs testBlood tests done on the father (rarely needed)
Erythrocyte antigen status
Prevention
In cases of Rho(D) incompatibility, Rho(D) immunoglobulin is given to prevent sensitization. However, there is no comparable immunotherapy available for other blood group incompatibilities.Early pregnancy
IVIG – IVIG stands for Intravenous Immunoglobulin. It is used in cases of previous loss, high maternal titers, known aggressive antibodies, and in cases where religion prevents blood transfusion. IVIG can be more effective than IUT alone. Fetal mortality was reduced by 36% in the IVIG and IUT group than in the IUT alone group. IVIG and plasmapheresis together can reduce or eliminate the need for an IUT.
Plasmapheresis – Plasmapheresis aims to decrease the maternal titer by direct plasma replacement and physical removal of antibody. Plasmapheresis and IVIG together can even be used on women with previously hydropic fetuses and fetal losses.Mid- to late- pregnancy
IUT – Intrauterine Transfusion (IUT) is done either by intraperitoneal transfusion (IPT) or intravenous transfusion (IVT). IVT is preferred over IPT. IUTs are only done until 35 weeks. After that, the risk of an IUT is greater than the risk from post birth transfusion.
Steroids – Steroids are sometimes given to the mother before IUTs and early delivery to mature the fetal lungs.
Phenobarbital – Phenobarbital is sometimes given to the mother to help mature the fetal liver and reduce hyperbilirubinemia.
Early Delivery – Delivery can occur anytime after the age of viability. Emergency delivery due to failed IUT is possible, along with induction of labor at 35–38 weeks.Rhesus-negative mothers who are pregnant with a rhesus-positive infant are offered Rho(D) immune globulin (RhIG, or RhoGam) at 28 weeks during pregnancy, at 34 weeks, and within 48 hours after delivery to prevent sensitization to the D antigen. It works by binding any fetal red blood cells with the D antigen before the mother is able to produce an immune response and form anti-D IgG. A drawback to pre-partum administration of RhIG is that it causes a positive antibody screen when the mother is tested, which can be difficult to distinguish from natural immunological responses that result in antibody production. Without Rho(D) immunoglobulin, the risk of isoimmunization is approximately 17%; with proper administration, the risk is reduced to less than 0.1–0.2%.
After birth testing
Coombs – in certain instances (when there is concern for blood group incompatibility between mother and baby for example), after birth a baby will have a direct Coombs test run to confirm the antibodies attached to the infants red blood cells. This test is run on the infants cord blood.In some cases, the direct Coombs will be negative but severe, even fatal HDN can occur. An indirect Coombs needs to be run in cases of anti-C, anti-c, and anti-M. Infants with Anti-M are also recommended to receive antigen testing to rule out the presence of HDN. The below tests are often useful in cases of hemolytic disease of the newborn but are not required for treatment of all newborns.
Hgb – the infants hemoglobin should be tested from cord blood.
Reticulocyte count – Reticulocytes are elevated when the infant is producing more red blood cells in response to anemia. A rise in the retic count can mean that an infant may not need additional transfusions. Low retic is observed in infants treated with IUT and in those with HDN from anti-Kell.
Neutrophils – as neutropenia is one of the complications of HDN, the neutrophil count should be checked.
Thrombocytes - as thrombocytopenia is one of the complications of HDN, the thrombocyte count should be checked.
Bilirubin should be tested from cord blood.
Ferritin – because most infants affected by HDN have iron overload, a ferritin must be run before giving the infant any additional iron.
Newborn Screening Tests – Transfusion with donor blood during pregnancy or shortly after birth can affect the results of the Newborn Screening Tests. It is recommended to wait and retest 10–12 months after last transfusion. In some cases, DNA testing from saliva can be used to rule out certain conditions.
Treatment
After birth, treatment depends on the severity of the condition, but could include temperature stabilization and monitoring, phototherapy, transfusion with compatible packed red blood, exchange transfusion, sodium bicarbonate for correction of acidosis and/or assisted ventilation.
Phototherapy – Exposure to ultraviolet light (phototherapy) is recommended when the cord bilirubin is 3 or higher. Some doctors use it at lower levels while awaiting lab results. This converts unconjugated bilirubin to an conjugated form that is easier for the infant to clear.
IVIG - IVIG has been used to successfully treat many cases of HDN. It has been used not only on anti-D, but on anti-E as well. IVIG can be used to reduce the need for exchange transfusion and to shorten the length of phototherapy. The AAP recommends "In isoimmune hemolytic disease, administration of intravenousγ-globulin (0.5-1 g/kg over 2 hours) is recommended if the TSB (total serum bilirubin) is rising despite intensive phototherapy or the TSB level is within 2 to 3 mg/dL (34–51 μmol/L) of the exchange level. If necessary, this dose can be repeated in 12 hours (evidence quality B: benefits exceed harms). Intravenous γ-globulin has been shown to reduce the need for exchange transfusions in Rh and ABO hemolytic disease."
Exchange transfusion – Exchange transfusion is used when bilirubin reaches either the high or medium risk lines on the nonogram provided by the American Academy of Pediatrics (Figure 4). Cord bilirubin >4 is also indicative of the need for exchange transfusion.
Transfusion reactions
Once a woman has antibodies, she is at high risk for a future transfusion reaction if she is in need of a blood transfusion. For this reason, she must carry a medical alert card at all times and inform all doctors and emergency personnel of her antibody status. The absence of antibodies however does not preclude a woman from having a transfusion reaction:
"Acute hemolytic transfusion reactions may be either immune-mediated or nonimmune-mediated. Immune-mediated hemolytic transfusion reactions caused by immunoglobulin M (IgM) anti-A, anti-B, or anti-A, B typically result in severe, potentially fatal complement-mediated intravascular hemolysis. Immune-mediated hemolytic reactions caused by IgG, Rh, Kell, Duffy, or other non-ABO antibodies typically result in extravascular sequestration, shortened survival of transfused red cells, and relatively mild clinical reactions. Acute hemolytic transfusion reactions due to immune hemolysis may occur in patients who have no antibodies detectable by routine laboratory procedures."For a summary of transfusion reactions in the US, see reference.
Epidemiology
In 2003, the incidence of Rh(D) sensitization in the United States was 6.8 per 1000 live births; 0.27% of women with an Rh incompatible fetus experience alloimmunization.
Other animals
Hemolytic disease of the newborn is most commonly seen in kittens (where it is known as "fading kitten syndrome") and foals. It has also been reported in puppies.
See also
Exchange transfusion
Rh disease
Alloimmunization
Hemolytic disease of the newborn (anti-Kell)
Hemolytic disease of the newborn (anti-Rhc)
Hemolytic disease of the newborn (anti-RhE)
Hemolytic disease of the newborn (ABO)
Neonatal red cell transfusion
References
Further reading
== External links == |
Hand, foot, and mouth disease | Hand, foot, and mouth disease (HFMD) is a common infection caused by a group of enteroviruses. It typically begins with a fever and feeling generally unwell. This is followed a day or two later by flat discolored spots or bumps that may blister, on the hands, feet and mouth and occasionally buttocks and groin. Signs and symptoms normally appear 3–6 days after exposure to the virus. The rash generally resolves on its own in about a week. Fingernail and toenail loss may occur a few weeks later, but they will regrow with time.The viruses that cause HFMD are spread through close personal contact, through the air from coughing and the feces of an infected person. Contaminated objects can also spread the disease. Coxsackievirus A16 is the most common cause, and enterovirus 71 is the second-most common cause. Other strains of coxsackievirus and enterovirus can also be responsible. Some people may carry and pass on the virus despite having no symptoms of disease. Other animals are not involved. Diagnosis can often be made based on symptoms. Occasionally, a throat or stool sample may be tested for the virus.Handwashing may prevent spread, and those infected should not go to work, daycare or school. No antiviral medication or vaccine is available, but development efforts are underway. Most cases require no specific treatment. Simple pain medication such as ibuprofen or numbing mouth gel may be used. Occasionally, intravenous fluids are given to children who are unable to drink enough. Rarely, viral meningitis or encephalitis may complicate the disease.HFMD occurs in all areas of the world. It often occurs in small outbreaks in nursery schools or kindergartens. Large outbreaks have been occurring in Asia since 1997. It usually occurs during the spring, summer and fall months. Typically it occurs in children less than five years old but can occasionally occur in adults. HFMD should not be confused with foot-and-mouth disease (also known as hoof-and-mouth disease), which mostly affects livestock.
Signs and symptoms
Common constitutional signs and symptoms of the HFMD include fever, nausea, vomiting, feeling tired, generalized discomfort, loss of appetite, and irritability in infants and toddlers. Skin lesions frequently develop in the form of a rash of flat discolored spots and bumps which may be followed by vesicular sores with blisters on palms of the hands, soles of the feet, buttocks, and sometimes on the lips. The rash is rarely itchy for children, but can be extremely itchy for adults. Painful facial ulcers, blisters, or lesions may also develop in or around the nose or mouth. HFMD usually resolves on its own after 7–10 days. Most cases of the disease are relatively harmless, but complications including encephalitis, meningitis, and paralysis that mimics the neurological symptoms of polio can occur.
Cause
The viruses that cause the disease are of the Picornaviridae family. Coxsackievirus A16 is the most common cause of HFMD. Enterovirus 71 (EV-71) is the second-most common cause. Many other strains of coxsackievirus and enterovirus can also be responsible.
Transmission
HFMD is highly contagious and is transmitted by nasopharyngeal secretions such as saliva or nasal mucus, by direct contact, or by fecal-oral transmission. It is possible to be infectious for days to weeks after the symptoms have resolved.Child care settings are the most common places for HFMD to be contracted because of toilet training, diaper changes, and the fact that children often put their hands into their mouths. HFMD is contracted through nose and throat secretions such as saliva, sputum, nasal mucus and as well as fluid in blisters, and stool.
Diagnosis
A diagnosis usually can be made by the presenting signs and symptoms alone. If the diagnosis is unclear, a throat swab or stool specimen may be taken to identify the virus by culture. The common incubation period (the time between infection and onset of symptoms) ranges from three to six days. Early detection of HFMD is important in preventing an outbreak in the pediatric population.
Prevention
Preventive measures include avoiding direct contact with infected individuals (including keeping infected children home from school), proper cleaning of shared utensils, disinfecting contaminated surfaces, and proper hand hygiene. These measures have been shown to be effective in decreasing the transmission of the viruses responsible for HFMD.Protective habits include hand washing and disinfecting surfaces in play areas. Breast-feeding has also shown to decrease rates of severe HFMD, though does not reduce the risk for the infection of the disease.
Vaccine
A vaccine known as the EV71 vaccine is available to prevent HFMD in China as of December 2015. No vaccine is currently available in the United States.
Treatment
Medications are usually not needed as hand, foot, and mouth disease is a viral disease that typically resolves on its own. Currently, there is no specific curative treatment for hand, foot and mouth disease. Disease management typically focuses on achieving symptomatic relief. Pain from the sores may be eased with the use of analgesic medications. Infection in older children, adolescents, and adults is typically mild and lasts approximately 1 week, but may occasionally run a longer course. Fever reducers can help decrease body temperature.In 2018, National Health Commission of China assembled a panel of experts to revise their guidelines for the diagnosis and treatment of hand, foot and mouth disease. Consumption of Traditional Chinese medicine, prescribed by certified physicians, are recommended to clear the symptoms.A minority of individuals with hand, foot and mouth disease may require hospital admission due to complications such as inflammation of the brain, inflammation of the meninges, or acute flaccid paralysis. Non-neurologic complications such as inflammation of the heart, fluid in the lungs, or bleeding into the lungs may also occur.
Complications
Complications from the viral infections that cause HFMD are rare, but require immediate medical treatment if present. HFMD infections caused by Enterovirus 71 tend to be more severe and are more likely to have neurologic or cardiac complications including death than infections caused by Coxsackievirus A16. Viral or aseptic meningitis can occur with HFMD in rare cases and is characterized by fever, headache, stiff neck, or back pain. The condition is usually mild and clears without treatment; however, hospitalization for a short time may be needed. Other serious complications of HFMD include encephalitis (inflammation of the brain), or flaccid paralysis in rare circumstances.Fingernail and toenail loss have been reported in children 4–8 weeks after having HFMD. The relationship between HFMD and the reported nail loss is unclear; however, it is temporary and nail growth resumes without treatment.Minor complications due to symptoms can occur such as dehydration, due to mouth sores causing discomfort with intake of foods and fluid.
Epidemiology
Hand, foot and mouth disease most commonly occurs in children under the age of 10 and more often under the age of 5, but it can also affect adults with varying symptoms. It tends to occur in outbreaks during the spring, summer, and autumn seasons. This is believed to be due to heat and humidity improving spread. HFMD is more common in rural areas than urban areas; however, socioeconomic status and hygiene levels need to be considered. Poor hygiene is a risk factor for HFMD.
Outbreaks
In 1997, an outbreak occurred in Sarawak of Malaysia with 600 cases and over 30 children died.
In 1998, there was an outbreak in Taiwan, affecting mainly children. There were 405 severe complications, and 78 children died. The total number of cases in that epidemic is estimated to have been 1.5 million.
In 2008 an outbreak in China, beginning in March in Fuyang, Anhui, led to 25,000 infections, and 42 deaths, by May 13. Similar outbreaks were reported in Singapore (more than 2,600 cases as of April 20, 2008), Vietnam (2,300 cases, 11 deaths), Mongolia (1,600 cases), and Brunei (1053 cases from June–August 2008)
In 2009 17 children died in an outbreak during March and April 2009 in Chinas eastern Shandong Province, and 18 children died in the neighboring Henan Province. Out of 115,000 reported cases in China from January to April, 773 were severe and 50 were fatal.
In 2010 in China, an outbreak occurred in southern Chinas Guangxi Autonomous Region as well as Guangdong, Henan, Hebei and Shandong provinces. Until March, 70,756 children were infected and 40 died from the disease. By June, the peak season for the disease, 537 had died.
The World Health Organization reporting between January to October 2011 (1,340,259) states the number of cases in China had dropped by approx 300,000 from 2010 (1,654,866) cases, with new cases peaking in June. There were 437 deaths, down from 2010 (537 deaths).
In December 2011, the California Department of Public Health identified a strong form of the virus, coxsackievirus A6 (CVA6), where nail loss in children is common.
In 2012 in Alabama, United States there was an outbreak of an unusual type of the disease. It occurred in a season when it is not usually seen and affected teenagers and older adults. There were some hospitalizations due to the disease but no reported deaths.
In 2012 in Cambodia, 52 of 59 reviewed cases of children reportedly dead (as of July 9, 2012) due to a mysterious disease were diagnosed to be caused by a virulent form of HFMD. Although a significant degree of uncertainty exists with reference to the diagnosis, the WHO report states, "Based on the latest laboratory results, a significant proportion of the samples tested positive for enterovirus 71 (EV-71), which causes hand foot and mouth disease (HFMD). The EV-71 virus has been known to generally cause severe complications amongst some patients."
HFMD infected 1,520,274 people with up to 431 deaths reported at the end of July in 2012 in China.
In 2018, more than 50,000 cases have occurred through a nationwide outbreak in Malaysia with two deaths also reported.
India 2022
An outbreak of an illness referred to as tomato fever or tomato flu was identified in the Kollam district on May 6, 2022. The illness is endemic to Kerala, India and gets its name because of the red and round blisters it causes, which look like tomatoes. The disease may be a new variant of the viral HFMD or an effect of chikungunya or dengue fever. Flu may be a misnomer.The condition mainly affects children under the age of five. An article in The Lancet states that the appearance of the blisters is similar to that seen in monkey pox, and the illness is not thought to be related to SARS-CoV-2. Symptoms, treatment and prevention are similar to HFMD.
History
HFMD cases were first described clinically in Canada and New Zealand in 1957. The disease was termed "Hand Foot and Mouth Disease", by Thomas Henry Flewett, after a similar outbreak in 1960.
Research
Novel antiviral agents to prevent and treat infection with the viruses responsible for HFMD are currently under development. Preliminary studies have shown inhibitors of the EV-71 viral capsid to have potent antiviral activity.
References
External links
Media related to Hand, foot and mouth disease at Wikimedia Commons
Highly contagious Hand, foot and mouth disease killing Chinas children at Wikinews |
Sialadenitis | Sialadenitis (sialoadenitis) is inflammation of salivary glands, usually the major ones, the most common being the parotid gland, followed by submandibular and sublingual glands. It should not be confused with sialadenosis (sialosis) which is a non-inflammatory enlargement of the major salivary glands.Sialadenitis can be further classed as acute or chronic. Acute sialadenitis is an acute inflammation of a salivary gland which may present itself as a red, painful swelling that is tender to touch. Chronic sialadenitis is typically less painful but presents as recurrent swellings, usually after meals, without redness.Causes of sialadenitis are varied, including bacterial (most commonly Staphylococcus aureus), viral and autoimmune conditions.
Types
Acute
Predisposing factorssialolithiasis
decreased flow (dehydration, post-operative, drugs)
poor oral hygiene
exacerbation of low grade chronic sialoadenitisClinical featurespainful swelling
reddened skin
edema of the cheek, periorbital region and neck
low grade fever
malaise
raised ESR, CRP, leucocytosis
purulent exudate from duct punctum
Chronic
Clinical featuresunilateral
mild pain / swelling
common after meals
duct orifice is reddened and flow decreases
may or may not have visible/palpable stone.
Parotid gland
recurrent painful swellings
Submandibular gland
usually secondary to sialolithiasis or stricture
Signs and Symptoms
Sialadenitis is swelling and inflammation of the parotid, submandibular, or sublingual major salivary glands. It may be acute or chronic, infective or autoimmune.
Acute
Acute sialadenitis secondary to obstruction (sialolithiasis) is characterised by increasingly, painful swelling of 24–72 hours, purulent discharge and systemic manifestations.
Chronic
Chronic sialadenitis causes intermittent, recurrent periods of tender swellings. Chronic sclerosing sialadenitis is commonly unilateral and can mimic a tumour.
Autoimmune
Autoimmune sialadenitis (i.e Sjogren’s syndrome) causes unilateral or bilateral painless swellings unless there is a secondary infection.
Infection
The most common salivary gland infection is mumps. It is characterised by bilateral swelling of the parotid glands, however other major salivary glands may also be affected in around 10% of cases. The swelling persists for about a week, along with low grade fever and general malaise.
Recurrent parotitis of childhood is characterised by periods of pain and swelling in the parotid gland accompanied by a fever
Complications
Causes
Sialadenitis can be caused by cancer, autoimmune conditions, viral and bacterial infections, idiopathic causes or stones formed mainly from calculus. It was thought that morphological characteristics of the salivary ducts could also be a contributing factor, as stagnation of saliva due to these could perhaps cause an increased incidence of sialadenitis. However, one study found no statistically significant difference between the length of ducts or the angles they incorporate within them and the likelihood of developing sialadenitis, although this study only had a small sample size of 106. The study also confirmed that age, gender, side of face and degree of sialadenitis had no impact on the length of the ducts or the angles formed within the ducts.Viral pathogens more commonly cause sialadenitis in comparison to bacterial pathogens. Mumps is the most common virus that affects the parotid and submandibular glands, with the parotid gland affected most often out of these two. Other viruses that have been shown to cause sialadenitis in both these glands include HIV, coxsackie, and parainfluenza. Classically, HIV parotitis is either asymptomatic or a non-painful swelling, which is not characteristic of sialadenitis. Some common bacterial causes are S. aureus, S. pyogenes, viridans streptococci and H. influenzae.Autoimmune conditions that can cause sialadenitis include Sjögren’s syndrome, sarcoidosis, and granulomatosis with polyangiitis. Sjögren’s syndrome and Sarcoidosis are the most common causes of chronic sialadenitis and are often closely associated with it, and in many cases are believed to be the primary cause, although often with other contributing factors present also. One well known form of sarcoidosis is known as Heerfordt’s syndrome which is characterized by facial nerve palsy, enlargement of the parotid and anterior uveitis. One study came to the conclusion that the presence of salivary calculi is the main indicator for the removal of the submandibular gland, in patients where neoplasia is absent. This was because 82% of glands removed in an ENT department in Stockholm were found to have salivary calculi within them and all of these cases but one had chronic sialadenitis. A mucous retention cyst was found in one patient, but this was not considered to have contributed to the sialadenitis in this case.The duration of the sialadenitis was found to be closely linked to atrophy, fibrosis and the degree of the inflammation in another study, which looked primarily at microliths found in the ducts and glands. Liths were also found to be related to the duration that the individual had symptoms of sialadenitis, whereas microliths were found in normal glands and varied with age. Microliths could possibly form reservoirs, thus allowing infection to ascend further towards the glands but this could not be confirmed due to the liths and microliths being distinct in this study. However, many glands did show only very minimal variations, which could allow the opportunity for more conservative treatment instead of the surgical removal of the affected gland in the future.
Histopathology
Initial stage of acute bacterial sialadenitis involves the accumulation of bacteria, neutrophils and inspissated fluid in lumen of ductal structures. Damage to ductal epithelium results in sialodochitis (periductal inflammation), accumulation of neutrophils in glandular stroma, followed by acini necrosis with microabscesses formation. Recurrent episodes results in chronic stage, which involves the establishment of periductal lymph follicles and further destruction of salivary acini.
Infective sialadenitis
Generally, in acute bacterial and viral sialadenitis cases, the lobular architecture of the gland is maintained or may be slightly expanded. Areas of liquefaction, indicating presence of abscess, may also be seen microscopically.
In Acute bacterial sialadenitis, acinar destruction with interstitial neutrophil infiltrates is observed. Small abscesses with necrosis are common.
In Viral sialadenitis, vacuolar changes are seen in the acini with lymphocytic and monocytic infiltrate found in the interstitium
Cytomegalovirus (CMV) sialadenitis may show no gross symptoms
Chronic sialadenitis (also known as lymphoepithelial sialadenitis (LESA)) presents with 50% of which are monoclonal by PCR while mucosa-associated lymphoid tissue (MALT) lymphoma has ducts surrounded by broad coronas of monocytoid cells, infiltration of interfollicular region by monocytoid cells or atypical plasma cells containing Dutcher bodies, monoclonality by immunohistochemistry or flow cytometry, and monocytoid infiltrates in regional lymph nodes.Histologically, chronic sialadenitis can appear from unremarkable to a firm tan with expansion or atrophy of the lobular structure depending on the degree of inflammation and chronicity. Salivary stones (Sialolith) may be evident with cystic dilation of the salivary ducts and periductal fibrosis. Mucus extravasation may also be observed.
Common observations of chronic sialadenitis include chronic inflammatory infiltrate (lymphocytes, plasma cells and macrophages), fibrosis, acinar atrophy, mucous cell metaplasia of the ductal system is observed.
In Sialoithiasis, concomitant squamous metaplasia may be observed in the salivary ducts with dark calcific stone fragments.
Chronic sialadenitis
Chronic sclerosing sialadenitis has various degrees of inflammation which can include focal lymphocytic sialadenitis to widespread salivary gland cirrhosis with obliteration of acini. This can be a result of obstruction of salivary ducts by microliths (due to associated intercurrent infections), or a result of immune reaction with the formation of secondary lymph follicles. Chronic sclerosing sialadenitis is characterised by presence of three major criteria of dense lymphoplasmacytic infiltrate, storiform pattern of fibrosis and obliterative phlebitis. Minor criteria include phlebitis without obliteration of the lumen and increased numbers of eosinophils. There are two features relatively inconsistent with diagnosis of IgG4-related disease which are the presence of epithelioid cell granulomas and a prominent neutrophilic infiltrate.Sclerosing polycystic sialadenitis histologically resembles sclerosing adenosis/fibrocystic change of breast tissue. It composes of acini and ductal elements embedded in dense sclerotic stroma, and has a characteristic finding of large acinar cells present with abundant eosinophilic cytoplasmic granules. In addition, it may also present ductal epithelial proliferation which could range from hyperplasia, atypia to DCIS-like. Its stroma may show focal adipose tissue with myxoid change and variable radial scar. At present, there are immunohistochemical studies of limited value only. It is cytologically difficult to diagnose this type of sialadenitis due to the rarity of this condition and the presence of variable cell types in a cystic background.In autoimmune sialadenitis, activation of T and B cells that infiltrate the interstitium occurs due to a response to an unidentified antigen present in the salivary gland parenchyma. This response then results in acini destruction and the formation of epimyoepithelial islands.
Autoimmune sialadenitis
Most histological appearance of autoimmune sialadenitis are similar to that of Myoepithelial sialadenitis. In general, a diffuse to multinodular expansion is observed in myoepithelial sialadenitis. A distinguishing feature is the presence of epithelial-myoepithelial islands infiltrated by lymphocytes. Germinal centers may form with the progression of lymphoid infiltrate resulting in acinar atrophy. Proliferation of ductal epithelium-myoepithelium arises causing the obliteration of ductal lumina causing the formation of the epithelial-myoepithelial islands.
Granulomatosis with polyangiitis may have areas of liquefaction necrosis caused by vasculitis. A triad of vasculitis, necrosis and granulomatous inflammation may be observed.
In secondary Sjogren’s syndrome, periglandular fibrosis with the absence of inflammation may also be observed in addition to that of Myoepithelial sialadenitis from the progressive systemic sclerosis.
Sarcoid has tight epithelioid granulomas and lymphoid infiltrate.
Chronic Sclerosing Sialadenitis has peridutcal fibrosis with a dense lymphoplasmacytic infiltrate with lymphoid follicles. Eosinophils may be seen.
Diagnosis
According to the British Medical Journal (The BMJ) Best Practice on Sialadenitis, there are multiple factors to consider during the diagnosis of sialadenitis, including history, presenting signs and symptoms, followed by appropriate investigations in relation to the presenting case. Other factors to also consider include the type of gland affected as well as underlying conditions such as an autoimmune disease or ductal stones.
Acute bacterial sialadenitis
May present with a history of recent surgical intervention or use of medications such as antihistamines, antidepressants, or anticholinergic agents. These medications may lead to objective hypofunction or subjective feeling of a dry mouth without hypofunction. There may also be a history of decrease in salivary volume secondary to a systemic disease.
A unilateral or bilateral painful swelling of the parotid or submandibular regions may be present upon a physical examination. This could be accompanied by an external displacement of the earlobe usually adjacent to an inflamed parotid gland. Pus suppuration from major salivary gland duct openings may occur spontaneously or after manipulation of the affected gland. Mandibular trismus is a rare finding but may be present with larger swellings. Dysphagia may also be present in some cases. Fever may also be noted, whilst spiking temperatures may be suggestive of an abscess formation.
Chronic recurrent sialadenitis
The occurrence of chronic recurrent episodes may be due to underlying Sjogrens syndrome or ductal abnormalities. Prodrome of tingling in the gland preceding pain and swelling may be reported in such cases.
Chronic sclerosing sialadenitis
Typically presents unilaterally in submandibular gland that cannot be differentiated clinically from a neoplasm, with pain an inconsistent finding.
Obstructive sialadenitis
Formation of stones in glandular ducts (sialoliths) can result in the development of obstructive sialadenitis. There may be a history of abrupt episodic swelling of the parotid or submandibular gland which is usually painful. These episodes typically occur around meal times, lasting 2 – 3 hours and gradually subsides.
Autoimmune sialadenitis
Characterised by persistent, asymptomatic bilateral swelling of parotid glands, and may represent as a manifestation of more widespread systemic disease. Dry eyes and dry mouth are commonly present and may be indicative of concomitant connective tissue disease (e.g. SLE, RA, or scleroderma). Oral candidiasis may also be present.
Common key diagnostic factors
1. Fever – may present with an acute infective sialadenitis or autoimmune aetiology suggestive of an infection or inflammation.
2. Pain and dysphagia (ie. difficulty swallowing) – usually unilateral affecting the parotid or submandibular regions, with worse pain during eating and swallowing.
3. Facial swelling – usually unilaterally and affecting parotid region, under the tongue, or below the jaw. May have acute onset and may have a history of repeated episodes.
4. Recurrent painful swellings – indicative of chronic recurrent sialadenitis, may have similar signs and symptoms to an acute episode.
5. Pus exudation from salivary gland openings – indicative of bacterial infection, may occur on manipulation of the affected gland or spontaneously.
Other common diagnostic factors to consider
1. Episodic swelling during meal times – may present as an acute salivary gland swelling without visible salivary flow from ductal openings. While palpation of affected glad may reveal an indurated salivary gland and presence of a sialolith.
2. Use of xerostomic medications – these medications will result in a decreased salivary flow rate which can predispose to infections of glands. Examples of medications that may contribute to this include antihistamines, antidepressant, and anticholinergic agents.
3. Recent surgical intervention under general anaesthetic – this could predispose to sialadenitis due to direct effects of anaesthetic agents used and volume depletion from surgery.
4. Dry eyes and mouth – dryness affecting the eyes and oral cavity are key symptoms of Sjogren’s syndrome and may be seen in combination with a connective tissue disease such as rheumatoid arthritis, scleroderma, or dermatomyositis.
5. Oral candidiasis – may be present in cases of Sjogren’s syndrome or in associate with a connective tissue disorder.
Key factors to also consider which are less common
1. Mandibular trismus – restricted mouth opening to its full extent (of approximately 40mm) may be present with large swellings typically due to acute bacterial infection of affected gland.
2. Respiratory distress – this could present in the form of stridor, use or reliance on accessory muscles of respiratory, nasal flaring, or wheeze. These signs may develop if glandular swelling is significant enough, resulting in airway obstruction.
3. Cranial nerve palsy – swelling increases the risk of compression of cranial nerves VII, IX and XII.
Other diagnostic factors which are less common
1. Connective tissue disorder or Sjogren’s syndrome – history of Sjogren’s syndrome, or a concomitant connect tissue disorder such as systemic lupus erythematosus, rheumatoid arthritis, or scleroderma.
2. Recurrent painless swellings – indicative of underlying autoimmune aetiology.
3. Displacement of earlobe – may be present when swelling of the parotid gland is present.
4. Prodrome of tingling in the affected gland
5. Swelling on hard palate
Diagnostic tests
Tests available as part of diagnosing sialadenitis include:
Culture and sensitivity testing of exudate from salivary duct. Culturing of purulent discharge is advisable in acute presentations of sialadenitis to allow targeted antibiotic therapy.
Full blood count if infection is suspected.
Facial radiographs such as dental radiographic views should be taken to exclude an obstructive element due to presence of sialolith or evolving abscess. However, sialoliths with low calcium phosphate content may not be visible.
Treatment
In chronic recurrent sialadenitis or chronic sclerosing sialadenitis, acute attacks are managed with conservative therapies such as hydration, analgesics (mainly NSAIDs), sialogogues to stimulate salivary secretion, and regular, gentle gland massage. If infection is present, appropriate cultures should be obtained, followed by empirical antibiotic therapy initially, for example amoxicillin/clavulanate or clindamycin which cover oral flora.
If there are attacks more than approximately 3 times per year or severe attacks, surgical excision of the affected gland should be considered.
Epidemiology
Sialadenitis of the parotid gland accounts for a much larger percentage of hospital admissions than sialadenitis of the submandibular gland. Submandibular sialadenitis has been said to only account for 10% of all cases diagnosed as sialadenitis. Chronic sialadenitis has been classified as a relatively common presentation, whereas bacterial sialadenitis and sclerosing polycystic sialadenitis are defined as rare. Chronic sclerosing sialadenitis has been shown to affect predominantly males who are over the age of 50, with 40% of cases having an allergic disease, such as chronic sinusitis or bronchial asthma.One study found that 112 patients from England and Wales ranging from 12 to 81 years of age complained of symptoms from their diagnosed sialadenitis, with the group having a mean age of 39 and a standard deviation of 16 years. The study also found that more patients underwent surgery to treat their sialadenitis between the ages of 20 and 69 years but that there were many more patients who complained of symptoms between the ages of 20 and 49, and then went on to be diagnosed with sialadenitis. In each group studied, most patients suffered from sialadenitis in their twenties but there was also found to be a significant number of females whose symptoms started in their thirties and forties. More women reported symptoms that were confirmed to be sialadenitis than men in this study, which may suggest that females are more likely to be affected but more research would need to be done to be sure of this.A study done on the epidemiology of sialadenitis in the United States of America found that acute suppurative parotitis is responsible for 0.01-0.02% of hospital admissions, with the submandibular gland accounting for 10% of cases of sialadenitis in the major salivary glands in this population. This study found that there was no predilection to any race, sex or age, although it was noted that sialadenitis in general tended to occur in people who are debilitated, dehydrated or older.Bacterial sialadenitis is uncommon nowadays and is usually associated with sialoliths. A study involving hospitals in the United Kingdom found that the incidence of admissions for sialadenitis is 27.5 per million of the population, with the most common cause being mumps which causes a viral infection in the salivary gland. Ascending acute bacterial parotitis used to be a common perimortal event but today this is no longer the case due to antibiotics and basic modern care which means that patients will be much less likely to become dehydrated.
See also
Sialoendoscopy
References
== External links == |
Molluscum contagiosum | Molluscum contagiosum (MC), sometimes called water warts, is a viral infection of the skin that results in small raised pink lesions with a dimple in the center. They may become itchy or sore, and occur singularly or in groups. Any area of the skin may be affected, with abdomen, legs, arms, neck, genital area, and face being the most common. Onset of the lesions is around seven weeks after infection. They usually go away within a year without scarring.The infection is caused by a poxvirus called the molluscum contagiosum virus (MCV). The virus is spread either by direct contact, including sexual activity, or via contaminated objects such as towels. The condition can also be spread to other areas of the body by the person themselves. Risk factors include a weak immune system, atopic dermatitis, and crowded living conditions. Following one infection, it is possible to get re-infected. Diagnosis is typically based on the appearance of the lesions.Prevention includes hand washing and not sharing personal items. While treatment is not necessary, some may wish to have the lesions removed for cosmetic reasons or to prevent spread. Removal may occur with freezing, laser therapy, or opening up the lesion and scraping the inside. Scraping the lesion can, however, result in scarring. The oral medication cimetidine, or podophyllotoxin cream applied to the skin, may also be used for treatment.Approximately 122 million people globally were affected by molluscum contagiosum as of 2010 (1.8% of the population). It is more common in children between the ages of one and ten years old. The condition has become more common in the United States since 1966. But having an infection is not a reason to keep a child out of school or daycare.
Signs and symptoms
Molluscum contagiosum lesions are flesh-colored, dome-shaped, and pearly in appearance. They are often 1–5 mm in diameter, with a dimpled center. Molluscum lesions are most commonly found on the face, arms, legs, torso, and armpits in children. Adults typically have molluscum lesions in the genital region and this is considered to be a sexually transmitted infection; because of this, if genital lesions are found on a child, sexual abuse should be suspected. These lesions are generally not painful, but they may itch or become irritated. Picking or scratching the bumps may lead to a spread of the viral infection responsible for molluscum contagiosum, an additional bacterial infection, and scarring. In some cases, eczema develops around the lesions.Individual molluscum lesions may go away on their own within two months and generally clear completely without treatment or scarring in six to twelve months. Mean durations for an outbreak are variously reported from eight to about 18 months, but durations are reported as widely as six months to five years, lasting longer in immunosuppressed individuals.
Transmission
As the name implies, molluscum contagiosum is extremely contagious. Transmission of the molluscum contagiosum virus can occur many different ways including direct skin contact (e.g., contact sports or sexual activity), contact with an infected surface (fomite), or autoinoculation (self-infection) by scratching or picking molluscum lesions and then touching other parts of the skin not previously affected by the virus. Children are particularly susceptible to autoinoculation and may have widespread clusters of lesions.The viral infection is limited to a localized area on the topmost layer of the superficial layer of the skin. Once the virus-containing head of the lesion has been destroyed, the infection is gone. The central waxy core contains the virus.
Diagnosis
Diagnosis is made on the appearance; the virus cannot routinely be cultured. The diagnosis can be confirmed by excisional biopsy.Histologically, molluscum contagiosum is characterized by molluscum bodies (also known as Henderson-Patersen bodies) in the epidermis, above the stratum basale, which consist of cells with abundant large granular eosinophilic cytoplasmic inclusion bodies (accumulated virions) and a small nucleus that has been pushed to the periphery.
Management
Because molluscum contagiosum usually resolves without treatment and treatment options can cause discomfort to children, initial recommendations are often to simply wait for the lesions to resolve on their own. Of the treatments available, a meta-analysis of randomized controlled trials suggested that there is no difference between treatments in short term improvement, and no single treatment is significantly better than natural resolution of the condition.Bumps located in the genital area may be treated in an effort to prevent them from spreading. When treatment has resulted in the elimination of all bumps, the infection has been effectively cured and will not reappear unless the person is reinfected.
Medications
For mild cases, over-the-counter wart medicines, such as salicylic acid may shorten infection duration. Daily topical application of tretinoin cream may also trigger resolution.Studies have found cantharidin to be an effective and safe treatment for removing molluscum contagiosum. This medication is usually well tolerated though mild side effects such as pain or blistering are common.
There is no high-quality evidence for cimetidine. However, oral cimetidine has been used as an alternative treatment for the pediatric population as it is generally well tolerated and less invasive.
Imiquimod
Imiquimod is a form of immunotherapy initially proposed as a treatment for molluscum based on promising results in small case series and clinical trials. However, two large randomized controlled trials, specifically requested by the U.S. Food and Drug Administration under the Best Pharmaceuticals for Children Act both demonstrated that imiquimod cream applied three times per week was no more effective than placebo cream for treating molluscum after 18 weeks of treatment in a total of 702 children aged 2–12 years. In 2007, results from those trials—which remain unpublished—were incorporated into FDA-approved prescribing information for imiquimod, which states: "Limitations of Use: Efficacy was not demonstrated for molluscum contagiosum in children aged 2–12." In 2007, the FDA also updated imiquimods label concerning safety issues raised in the two large trials and an FDA-requested pharmacokinetic study (the latter of which was published). The updated safety label reads as follows:
Potential adverse effects of imiquimod use: "Similar to the studies conducted in adults, the most frequently reported adverse reaction from 2 studies in children with molluscum contagiosum was application site reaction. Adverse events which occurred more frequently in Aldara-treated subjects compared with vehicle-treated subjects generally resembled those seen in studies in indications approved for adults and also included otitis media (5% Aldara vs. 3% vehicle) and conjunctivitis (3% Aldara vs. 2% vehicle). Erythema was the most frequently reported local skin reaction. Severe local skin reactions reported by Aldara-treated subjects in the pediatric studies included erythema (28%), edema (8%), scabbing/crusting (5%), flaking/scaling (5%), erosion (2%) and weeping/exudate (2%)."
Potential systemic absorption of imiquimod, with negative effects on white blood cell counts overall, and specifically neutrophil counts: "Among the 20 subjects with evaluable laboratory assessments, the median WBC count decreased by 1.4*109/L and the median absolute neutrophil count decreased by 1.42×109 L−1."
Surgery
Surgical treatments include cryosurgery, in which liquid nitrogen is used to freeze and destroy lesions, as well as scraping them off with a curette. Application of liquid nitrogen may cause burning or stinging at the treated site, which may persist for a few minutes after the treatment. With liquid nitrogen, a blister may form at the treatment site, but it will slough off in two to four weeks. Cryosurgery and curette scraping can be painful procedures and can result in residual scarring.
Laser
A 2014 systematic review of case reports and case series concluded that the limited available data suggest pulsed dye laser therapy is a safe and effective treatment for molluscum contagiosum and is generally well tolerated by children. Side effects seen with pulsed dye laser therapy included mild temporary pain at the site of therapy, bruising (lasting up to 2–3 weeks), and temporary discoloration of the treated skin (as long as 1–6 months). No cases of permanent scarring have been reported. As of 2009, however, there is no evidence for genital lesions.
Prognosis
Most cases of molluscum contagiosum will clear up naturally within two years (usually within nine months). So long as the skin growths are present, there is a possibility of transmitting the infection to another person. When the growths are gone, the possibility of spreading the infection is ended.Unlike herpesviruses, which can remain inactive in the body for months or years before reappearing, molluscum contagiosum does not remain in the body when the growths are gone from the skin and will not reappear on their own.
Epidemiology
As of 2010, approximately 122 million people were affected worldwide by molluscum contagiosum (1.8% of the population).
See also
Acrochordons (also called skin tags—similar in appearance and grow in similar areas)
Basal-cell carcinoma
Wart (caused by the human papillomavirus; also similar in appearance to molluscum)
References
External links
Molluscum—Center for Disease Control
Virus Pathogen Database and Analysis Resource (ViPR): Poxviridae |
Drowning | Drowning is a type of suffocation induced by the submersion of the mouth and nose in a liquid. Most instances of fatal drowning occur alone or in situations where others present are either unaware of the victims situation or unable to offer assistance. After successful resuscitation, drowning victims may experience breathing problems, vomiting, confusion, or unconsciousness. Occasionally, victims may not begin experiencing these symptoms until several hours after they are rescued. An incident of drowning can also cause further complications for victims due to low body temperature, aspiration of vomit, or acute respiratory distress syndrome (respiratory failure from lung inflammation).
Drowning is more likely to happen when spending extended periods of time near large bodies of water. Risk factors for drowning include alcohol use, drug use, epilepsy, low socioeconomic status (which is often accompanied by diminished or non-existent swimming skills), lack of training and, in the case of children, a lack of supervision. Common drowning locations include natural and man-made bodies of water, bathtubs, and swimming pools.Drowning occurs when an individual spends too much time with their nose and mouth submerged in a liquid to the point of being unable to breathe. If this is not followed by an exit to the surface, low oxygen levels and excess carbon dioxide in the blood trigger a neurological state of breathing emergency, which results in increased physical distress and occasional contractions of the vocal folds. Significant amounts of water usually only enter the lungs later in the process.While the word "drowning" is commonly associated with fatal results, drowning may be classified into three different types: drowning that results in death, drowning that results in long-lasting health problems, and drowning that results in no health complications. Sometimes the term "near-drowning" is used in the latter cases. Among children who survive, health problems occur in about 7.5% of cases.Steps to prevent drowning include teaching children and adults to swim and to recognise unsafe water conditions; never swimming alone; use of personal flotation devices on boats and when swimming in unfavourable conditions; limiting or removing access to water, such as with fencing of swimming pools; and exercising appropriate supervision. Treatment of victims who are not breathing should begin with opening the airway and providing five breaths of mouth-to-mouth resuscitation. Cardiopulmonary resuscitation (CPR) is recommended for a person whose heart has stopped beating and has been underwater for less than an hour.
Causes
A major contributor to drowning is the inability to swim. Other contributing factors include the state of the water itself, distance from a solid footing, physical impairment, or prior loss of consciousness. Anxiety brought on by fear of drowning or water itself can lead to exhaustion, thus increasing the chances of drowning.
Approximately 90% of drownings take place in freshwater (rivers, lakes, and a relatively small number of swimming pools); the remaining 10% take place in seawater. Drownings in other fluids are rare, and often related to industrial accidents. In New Zealands early colonial history, so many settlers died while trying to cross the rivers that drowning was called "the New Zealand death."People have drowned in as little as 30 mm (1.2 in) of water while lying face down. Children have drowned in baths, buckets, and toilets. People who are inebriated or otherwise intoxicated can drown in puddles.
Death can occur due to complications following an initial drowning. Inhaled fluid can act as an irritant inside the lungs. Even small quantities can cause the extrusion of liquid into the lungs (pulmonary edema) over the following hours; this reduces the ability to exchange the air and can lead to a person "drowning in their own body fluid." Vomit and certain poisonous vapors or gases (as in chemical warfare) can have a similar effect. The reaction can take place up to 72 hours after the initial incident and may lead to a serious injury or death.
Risk factors
Many behavioral and physical factors are related to drowning:
Drowning is the most common cause of death for people with seizure disorders, largely in bathtubs. Epileptics are more likely to die due to accidents such as drowning. However, this risk is especially elevated in low- and middle-income countries compared to high-income countries.
The use of alcohol increases the risk of drowning across developed and developing nations. Alcohol is involved in approximately 50% of fatal drownings, and 35% of non-fatal drownings.
Inability to swim can lead to drowning. Participation in formal swimming lessons can reduce this risk. The optimal age to start the lessons is childhood, between one and four years of age.
Feeling overly tired reduces swimming performance. This exhaustion can be rapidly aggravated by anxious movements motivated by fear during or in anticipation of drowning. An overconfident appraisal of ones own physical capabilities can lead to "swimming out too far" and exhaustion before returning to solid footing.
Free access to water can be hazardous, especially to young children. Barriers can prevent young children from gaining access to the water.
Ineffective supervision. Drowning can occur anywhere there is water, even in the presence of lifeguards.
Risk can vary with location depending on age. Children between one and four more commonly drown in home swimming pools than elsewhere. Drownings in natural water settings increase with age. More than half of drownings occur among those fifteen years and older and occurred in natural water environments.
Familial or genetic history of sudden cardiac arrest (SCA) or sudden cardiac death (SCD) can predispose children to drown. Extensive genetic testing and/or consultation with a cardiologist should be done especially when there is a high suspicion of familial history and/or clinical evidence of sudden cardiac arrest or sudden cardiac death.
Individuals with undetected primary cardiac arrhythmias, as cold water immersion or aquatic exercise can induce these arrhythmias to occur.Population groups at risk in the US are generally the old and young.
Youth: drowning rates are highest for children under five years of age and people fifteen to twenty-four years of age.
Males: nearly 80% of drowning victims are male.
Minorities: the fatal unintentional drowning rate for African Americans above the age of 29 between 1999 and 2010 was significantly higher than that of whites above the age of 29. The fatal drowning rate of African American children of ages from five to fourteen is almost three times that of white children in the same age range, and 5.5 times higher in swimming pools. These disparities might be associated with a lack of basic swimming skills in some minority populations.
Free-diving
Some additional causes of drowning can also happen during freediving activities:
Ascent blackout, also called deep water blackout, is caused by hypoxia during ascent from depth. The partial pressure of oxygen in the lungs under pressure at the bottom of a deep free dive is adequate to support consciousness but drops below the blackout threshold as the water pressure decreases on the ascent. It usually strikes upon arriving near the surface as the pressure approaches normal atmospheric pressure.
Shallow water blackout – caused by hyperventilation prior to swimming or diving. The primary urge to breathe is triggered by rising carbon dioxide (CO2) levels in the bloodstream. The body detects CO2 levels very accurately and relies on this to control breathing. Hyperventilation reduces the carbon dioxide content of the blood but leaves the diver susceptible to a sudden loss of consciousness without warning from hypoxia. There is no bodily sensation that warns a diver of an impending blackout, and people (often capable swimmers swimming under the surface in shallow water) become unconscious and drown quietly without alerting anyone to the fact that there is a problem; they are typically found at the bottom.
Pathophysiology
Drowning can be considered as going through four stages:
Breath-hold under voluntary control until the urge to breathe due to hypercapnia becomes overwhelming
Fluid is swallowed and/or aspirated into the airways
Cerebral anoxia stops breathing and aspiration
Cerebral injury due to anoxia becomes irreversibleGenerally, in the early stages of drowning, a person holds their breath to prevent water from entering their lungs. When this is no longer possible, a small amount of water entering the trachea causes a muscular spasm that seals the airway and prevents further passage of water. If the process is not interrupted, loss of consciousness due to hypoxia is followed rapidly by cardiac arrest.
Oxygen deprivation
A conscious person will hold their breath (see Apnea) and will try to access air, often resulting in panic, including rapid body movement. This uses up more oxygen in the bloodstream and reduces the time until unconsciousness. The person can voluntarily hold his or her breath for some time, but the breathing reflex will increase until the person tries to breathe, even when submerged.The breathing reflex in the human body is weakly related to the amount of oxygen in the blood but strongly related to the amount of carbon dioxide (see Hypercapnia). During an apnea, the oxygen in the body is used by the cells and excreted as carbon dioxide. Thus, the level of oxygen in the blood decreases, and the level of carbon dioxide increases. Increasing carbon dioxide levels lead to a stronger and stronger breathing reflex, up to the breath-hold breakpoint, at which the person can no longer voluntarily hold his or her breath. This typically occurs at an arterial partial pressure of carbon dioxide of 55 mm Hg but may differ significantly between people.
The breath-hold breakpoint can be suppressed or delayed, either intentionally or unintentionally. Hyperventilation before any dive, deep or shallow, flushes out carbon dioxide in the blood resulting in a dive commencing with an abnormally low carbon dioxide level; a potentially dangerous condition known as hypocapnia. The level of carbon dioxide in the blood after hyperventilation may then be insufficient to trigger the breathing reflex later in the dive.
Following this, a blackout may occur before the diver feels an urgent need to breathe. This can occur at any depth and is common in distance breath-hold divers in swimming pools. Both deep and distance free divers often use hyperventilation to flush out carbon dioxide from the lungs to suppress the breathing reflex for longer. It is important not to mistake this for an attempt to increase the bodys oxygen store. The body at rest is fully oxygenated by normal breathing and cannot take on any more. Breath-holding in water should always be supervised by a second person, as by hyperventilating, one increases the risk of shallow water blackout because insufficient carbon dioxide levels in the blood fail to trigger the breathing reflex.A continued lack of oxygen in the brain, hypoxia, will quickly render a person unconscious, usually around a blood partial pressure of oxygen of 25–30 mmHg. An unconscious person rescued with an airway still sealed from laryngospasm stands a good chance of a full recovery. Artificial respiration is also much more effective without water in the lungs. At this point, the person stands a good chance of recovery if attended to within minutes. More than 10% of drownings may involve laryngospasm, but the evidence suggests that it is not usually effective at preventing water from entering the trachea. The lack of water found in the lungs during autopsy does not necessarily mean there was no water at the time of drowning, as small amounts of freshwater are readily absorbed into the bloodstream. Hypercapnia and hypoxia both contribute to laryngeal relaxation, after which the airway is effectively open through the trachea. There is also bronchospasm and mucous production in the bronchi associated with laryngospasm, and these may prevent water entry at terminal relaxation.The hypoxemia and acidosis caused by asphyxia in drowning affect various organs. There can be central nervous system damage, cardiac arrhythmia, pulmonary injury, reperfusion injury, and multiple-organ secondary injury with prolonged tissue hypoxia.A lack of oxygen or chemical changes in the lungs may cause the heart to stop beating. This cardiac arrest stops the flow of blood and thus stops the transport of oxygen to the brain. Cardiac arrest used to be the traditional point of death, but at this point, there is still a chance of recovery. The brain cannot survive long without oxygen, and the continued lack of oxygen in the blood, combined with the cardiac arrest, will lead to the deterioration of brain cells, causing first brain damage and eventually brain death from which recovery is generally considered impossible. The brain will die after approximately six minutes without oxygen at normal body temperature, but hypothermia of the central nervous system may prolong this.The extent of central nervous system injury to a large extent determines the survival and long term consequences of drowning, In the case of children, most survivors are found within 2 minutes of immersion, and most fatalities are found after 10 minutes or more.
Water aspiration
If water enters the airways of a conscious person, the person will try to cough up the water or swallow it, often inhaling more water involuntarily. When water enters the larynx or trachea, both conscious and unconscious people experience laryngospasm, in which the vocal cords constrict, sealing the airway. This prevents water from entering the lungs. Because of this laryngospasm, in the initial phase of drowning, water generally enters the stomach, and very little water enters the lungs. Though laryngospasm prevents water from entering the lungs, it also interferes with breathing. In most people, the laryngospasm relaxes sometime after unconsciousness, and water can then enter the lungs, causing a "wet drowning." However, about 7–10% of people maintain this seal until cardiac arrest. This has been called "dry drowning", as no water enters the lungs. In forensic pathology, water in the lungs indicates that the person was still alive at the point of submersion. An absence of water in the lungs may be either a dry drowning or indicates a death before submersion.Aspirated water that reaches the alveoli destroys the pulmonary surfactant, which causes pulmonary edema and decreased lung compliance, compromising oxygenation in affected parts of the lungs. This is associated with metabolic acidosis, secondary fluid, and electrolyte shifts. During alveolar fluid exchange, diatoms present in the water may pass through the alveolar wall into the capillaries to be carried to internal organs. The presence of these diatoms may be diagnostic of drowning.
Of people who have survived drowning, almost one-third will experience complications such as acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). ALI/ARDS can be triggered by pneumonia, sepsis, and water aspiration. These conditions are life-threatening disorders that can result in death if not treated promptly. During drowning, aspirated water enters the lung tissues, causes a reduction in alveolar surfactant, obstructs ventilation, and triggers a release of inflammatory mediators which ultimately results in hypoxia. Specifically, upon reaching the alveoli, hypotonic liquid found in freshwater dilutes pulmonary surfactant, destroying the substance. Comparatively, aspiration of hypertonic seawater draws liquid from the plasma into the alveoli and similarly causes damage to surfactant by disrupting the alveolar-capillary membrane. Still, there is no clinical difference between salt and freshwater drowning. Once someone has reached definitive care, supportive care strategies such as mechanical ventilation can help to reduce the complications of ALI/ARDS.Whether a person drowns in freshwater or salt water makes no difference in respiratory management or its outcome. People who drown in freshwater may experience worse hypoxemia early in their treatment, however, this initial difference is short-lived and the management of both fresh water and salt water drowning is essentially the same.
Cold-water immersion
Submerging the face in water cooler than about 21 °C (70 °F) triggers the diving reflex, common to air-breathing vertebrates, especially marine mammals such as whales and seals. This reflex protects the body by putting it into energy-saving mode to maximise the time it can stay underwater. The strength of this reflex is greater in colder water and has three principal effects:
Bradycardia, a slowing of the heart rate to less than 60 beats per minute.
Peripheral vasoconstriction, the restriction of the blood flow to the extremities to increase the blood and oxygen supply to the vital organs, especially the brain.
Blood shift, the shifting of blood to the thoracic cavity, the region of the chest between the diaphragm and the neck, to avoid the collapse of the lungs under higher pressure during deeper dives.The reflex action is automatic and allows both a conscious and an unconscious person to survive longer without oxygen underwater than in a comparable situation on dry land. The exact mechanism for this effect has been debated and may be a result of brain cooling similar to the protective effects seen in people who are treated with deep hypothermia.The actual cause of death in cold or very cold water is usually lethal bodily reactions to increased heat loss and to freezing water, rather than any loss of core body temperature. Of those who die after plunging into freezing seas, around 20% die within 2 minutes from cold shock (uncontrolled rapid breathing and gasping causing water inhalation, a massive increase in blood pressure and cardiac strain leading to cardiac arrest, and panic), another 50% die within 15 – 30 minutes from cold incapacitation (loss of use and control of limbs and hands for swimming or gripping, as the body protectively shuts down the peripheral muscles of the limbs to protect its core), and exhaustion and unconsciousness cause drowning, claiming the rest within a similar time. A notable example of this occurred during the sinking of the Titanic, in which most people who entered the −2 °C (28 °F) water died within 15–30 minutes.
[S]omething that almost no one in the maritime industry understands. That includes mariners [and] even many (most) rescue professionals: It is impossible to die from hypothermia in cold water unless you are wearing flotation, because without flotation – you won’t live long enough to become hypothermic.
Submersion into cold water can induce cardiac arrhythmias (abnormal heart rates) in healthy people, sometimes causing strong swimmers to drown. The physiological effects caused by the diving reflex conflict with the bodys cold shock response, which includes a gasp and uncontrollable hyperventilation leading to aspiration of water. While breath-holding triggers a slower heart rate, cold shock activates tachycardia, an increase in heart rate. It is thought that this conflict of these nervous system responses may account for the arrhythmias of cold water submersion.Heat transfers very well into water, and body heat is therefore lost extremely quickly in water compared to air, even in merely cool swimming waters around 70 °F (~20 °C). A water temperature of 10 °C (50 °F) can lead to death in as little as one hour, and water temperatures hovering at freezing can lead to death in as little as 15 minutes. This is because cold water can have other lethal effects on the body. Hence, hypothermia is not usually a reason for drowning or the clinical cause of death for those who drown in cold water.
Upon submersion into cold water, remaining calm and preventing loss of body heat is paramount. While awaiting rescue, swimming or treading water should be limited to conserve energy, and the person should attempt to remove as much of the body from the water as possible; attaching oneself to a buoyant object can improve the chance of survival should unconsciousness occur.Hypothermia (and cardiac arrest) presents a risk for survivors of immersion. This risk increases if the survivor—feeling well again—tries to get up and move, not realizing their core body temperature is still very low and will take a long time to recover.Most people who experience cold-water drowning do not develop hypothermia quickly enough to decrease cerebral metabolism before ischemia and irreversible hypoxia occur. The neuroprotective effects appear to require water temperatures below about 5 °C (41 °F).
Diagnosis
The World Health Organization in 2005 defined drowning as "the process of experiencing respiratory impairment from submersion/immersion in liquid." This definition does not imply death or even the necessity for medical treatment after removing the cause, nor that any fluid enters the lungs. The WHO further recommended that outcomes should be classified as death, morbidity, and no morbidity. There was also consensus that the terms wet, dry, active, passive, silent, and secondary drowning should no longer be used.Experts differentiate between distress and drowning.
Distress – people in trouble, but who can still float, signal for help, and take action.
Drowning – people suffocating and in imminent danger of death within seconds.
Forensics
Forensic diagnosis of drowning is considered one of the most difficult in forensic medicine. External examination and autopsy findings are often non-specific, and the available laboratory tests are often inconclusive or controversial. The purpose of an investigation is generally to distinguish whether the death was due to immersion or whether the body was immersed postmortem. The mechanism in acute drowning is hypoxemia and irreversible cerebral anoxia due to submersion in liquid.Drowning would be considered a possible cause of death if the body was recovered from a body of water, near a fluid that could plausibly have caused drowning, or found with the head immersed in a fluid. A medical diagnosis of death by drowning is generally made after other possible causes of death have been excluded by a complete autopsy and toxicology tests. Indications of drowning are seldom completely unambiguous and may include bloody froth in the airway, water in the stomach, cerebral edema and petrous or mastoid hemorrhage. Some evidence of immersion may be unrelated to the cause of death, and lacerations and abrasions may have occurred before or after immersion or death.Diatoms should normally never be present in human tissue unless water was aspirated. Their presence in tissues such as bone marrow suggests drowning; however, they are present in soil and the atmosphere, and samples may easily be contaminated. An absence of diatoms does not rule out drowning, as they are not always present in water. A match of diatom shells to those found in the water may provide supporting evidence of the place of death. Drowning in saltwater can leave significantly different concentrations of sodium and chloride ions in the left and right chambers of the heart, but they will dissipate if the person survived for some time after the aspiration, or if CPR was attempted, and have been described in other causes of death.Most autopsy findings relate to asphyxia and are not specific to drowning. The signs of drowning are degraded by decomposition. Large amounts of froth will be present around the mouth and nostrils and in the upper and lower airways in freshly drowned bodies. The volume of froth is generally much greater in drowning than from other origins. Lung density may be higher than normal, but normal weights are possible after cardiac arrest or vasovagal reflex. The lungs may be overinflated and waterlogged, filling the thoracic cavity. The surface may have a marbled appearance, with darker areas associated with collapsed alveoli interspersed with paler aerated areas. Fluid trapped in the lower airways may block the passive collapse that is normal after death. Hemorrhagic bullae of emphysema may be found. These are related to the rupture of alveolar walls. These signs, while suggestive of drowning, are not conclusive.
Prevention
It is estimated that more than 85% of drownings could be prevented by supervision, training in water skills, technology, and public education.
Surveillance: Watching the swimmers is a basic task, because drownings can be silent and unnoticed: a person drowning may not always be able to attract attention, often because they have become unconscious. Surveillance of children is especially important. The highest rates of drowning globally are among children under five, and young children should be supervised, regardless of whether they can already swim. The danger increases when they are alone. A baby can drown in the bathtub, in the toilet, and even in a small bucket filled with less than an inch of water. It only takes around 2 minutes underwater for an adult to lose consciousness, and only between 30 seconds and 2 minutes for a small child to die. Choosing supervised swimming places is safer. Many pools and bathing areas either have lifeguards or a pool safety camera system for local or remote monitoring, and some have computer-aided drowning detection. Bystanders are also important in detection of drownings and in notifying them (personally or by phone, alarm, etc.) to lifeguards, who may be unaware if distracted or busy. Evidence shows that alarms in pools are poor for any utility. The World Health Organization recommends analyzing when the most crowded hours in the swimming zones are, and to increase the number of lifeguards at those moments.
Learning to swim: Being able to swim is one of the best defenses against drowning. It is recommended that children learn to swim in a safe and supervised environment when they are between 1 and 4 years old. Learning to swim is also possible in adults by using the same methods as children. Its still possible to drown even after learning to swim (because of the state of the water and other circumstances), so its recommended to choose swimming places that are safe and kept under surveillance.
Additional education: The WHO recommends training the general public in first-aid for the drowned, cardiopulmonary resuscitation (CPR), and to behave safely when in the water. It is recommended to teach those who cannot swim to keep themselves away from deep waters.
Pool fencing: Every private and public swimming pool should be fenced and enclosed on every side, so no person can access the water unsupervised. The "Raffarin law", applied in France in 2003, forced the fencing of pools.
Pool drains: Swimming pools often have drainage systems to cycle the water. Drains without covers can injure swimmers by trapping hair or other parts of the body, leading to immobilization and drowning. Drains should not suction too strongly. It is recommended for a pool to have many small drainage holes instead of a single large one. Periodic revisions are required to certify that the system is working well.
Caution with certain conditions: Some conditions require one to be cautious when near water. For example, epilepsy and other seizure disorders may increase the possibility of drowning during a convulsion, making it more dangerous to swim, dive, and bathe. It is recommended that people with these conditions take showers rather than baths and are taught about the dangers of drowning.
Alcohol or drugs: Alcohol and drugs increase the probability of drowning. This danger is greater in bars near the water and parties on boats where alcohol is consumed. For example, Finland sees several drownings every year at Midsummer weekend as Finnish people spend more time in and around the lakes and beaches, often after having consumed alcohol.
Lifejacket use: Children that cannot swim and other people at risk of drowning should wear a fastened and well-fitting lifejacket when near or in the water. Other flotation devices (inflatable inner tubes, water wings, foam tubes, etc.) may be useful, although they are usually considered toys. Other flotation instruments are considered safe, like the professional circle-shaped lifebuoy (hoop-buoy, ring-buoy, life-ring, life-donut, lifesaver, or life preserver), which is mainly designed to be thrown, and some other professional variants that are used by lifeguards in their rescues.
Depth awareness: Diving accidents in pools can cause serious injury. Up to 21% of shallow-water diving accidents can cause spinal injury, occasionally leading to death. Between 1.2% and 22% of all spinal injuries are from diving accidents. If the person does not die, the injury could cause permanent paralysis.
Avoid dangerous waters: Avoid swimming in waters that are too turbulent, where waves are large, with dangerous animals, or are too cold. Also avoid dragging currents, which are currents that are turbulent, foamy, and that can drag people or debris. If caught by one of these currents, swim out from it (it is possible to move out gradually, in a diagonal direction until you arrive at the shore).
Navigating safely: Many people who die by drowning die in navigation accidents. Safe navigation practices include being informed of the state of the sea and equipping the boat with regulatory instruments to keep people afloat. These instruments are lifejackets (see lifejacket use above) and professional lifebuoys with the shape of a circle (ring-buoy, hoop-buoy, life-ring, life-donut, lifesaver, or life preserver).
Use the "buddy system": Dont swim alone, but with another person who can help in case of a problem.
Rescue robots and drones: Nowadays, there exist some remote-controlled modern devices that can accomplish a water rescue. Floating rescue robots can move across the water, |
Drowning | allowing the victim to hold on to the drone and be moved out of the water. Flying drones are very fast and can drop life jackets from air, and may help to locate the victim’s position.
Follow the rules: Many people who drown fail follow the safety guidelines of the area. It is important to pay attention to the signage that indicates whether swimming is allowed or if a lifeguard is on duty. (lifeguards, coastguards, etc.)
Water safety
The concept of water safety involves the procedures and policies that are directed to prevent people from drowning or from becoming injured in water.
Time limits
The time a person can safely stay underwater depends on many factors, including energy consumption, number of prior breaths, physical condition and age. An average person can last between one and three minutes before falling unconscious, and around ten minutes before dying. In an unusual case, a person was resuscitated after 65 minutes underwater.
Management
Rescue
When a person is drowning or a swimmer becomes missing, a fast water rescue may become necessary to take that person out of the water as soon as possible. Drowning is not necessarily violent or loud, with splashing and cries; it can be silent.Rescuers should avoid endangering themselves unnecessarily; whenever it is possible, they should assist from a safe ground position, such as a boat, a pier, or any patch of land near the victim. The fastest way to assist is to throw a buoyant object (such as a lifebuoy). It is very important to avoid aiming directly at the victim, since even the lightest lifebuoys weight over 2 kilograms, and can stun, injure or even render a person unconscious if they impact on the head. Alternatively, one could try to pull the victim out of the water by holding out an object to grasp. Some examples include: ropes, oars, poles, ones own arm, a hand, etc. This carries the risk of the rescuer being pulled into the water by the victim, so the rescuer must take a firm stand, lying down, as well as securing to some stable point. Alternatively, there are modern flying drones that drop life jackets.
Bystanders should immediately call for help. A lifeguard should be called, if present. If not, emergency medical services and paramedics should be contacted as soon as possible. Less than 6% of people rescued by lifeguards need medical attention, and only 0.5% need CPR. The statistics worsen when rescues are made by bystanders.
If lifeguards or paramedics are unable to be called, bystanders must rescue the drowning person. Alternatively, there are small floating robots that can reach the victim, as human rescue carries a risk for the rescuer, who could be drowned. Death of the would-be rescuer can happen because of the water conditions, the instinctive drowning response of the victim, the physical effort, and other problems.
After reaching the victim, first contact made by the rescuer is important. A drowning person in distress is likely to cling to the rescuer in an attempt to stay above the water surface, which could submerge the rescuer in the process. To avoid this, it is recommended that the rescuer approaches the panicking person with a buoyant object or extending a hand, so the victim has something to grasp. It can even be appropriate to approach from behind, taking one of the victims arms, and pressing it against the victims back to restrict unnecessary movement. Communication is also important.
If the victim clings to the rescuer, and the rescuer cannot control the situation, a possibility is to dive underwater (as drowning people tend to move in the opposite direction, seeking the water surface) and consider a different approach to help the drowning victim.
It is possible that the victim has already sunk beneath the water surface. If this has happened, the rescue requires caution, as the victim could be conscious and cling to the rescuer underwater. The rescuer must bring the victim to the surface by grabbing either (or both) of the victims arms and swimming upward, which may entice the victim to travel in the same direction, thus making the task easier, especially in the case of an unconscious victim. Should the victim be located in deeper waters (or simply complicates matters too much) the rescuer should dive, take the victim from behind, and ascend vertically to the water surface holding the victim.
After a successful contact with the victim, any ballast (such as weight belt) should be discarded.
Finally, the victim must be taken out of the water, which is achieved by a towing maneuver. This is commonly done placing the victim body in a face-up horizontal position, passing one hand under the victims armpit to then grab the jaw with it, and towing by swimming backwards. The victims mouth and nose must be kept above the water surface.
If the person is cooperative, the towing may be done in a similar fashion with the hands going under the victims armpits. Other styles of towing are possible, but all of them keeping the victims mouth and nose above the water.
Unconscious people may be pulled in an easier way: pulling on a wrist or on the shirt while they are in a face-up horizontal position. Victims with suspected spinal injuries can require a more specific grip and special care, and a backboard (spinal board) may be needed for their rescue.For unconscious people, an in-water resuscitation could increase the chances of survival by a factor of about three, but this procedure requires both medical and swimming skills, and it becomes impractical to send anyone besides the rescuer to execute that task. Chest compressions require a suitable platform, so an in-water assessment of circulation is pointless. If the person does not respond after a few breaths, cardiac arrest may be assumed, and getting them out of the water becomes a priority.
First aid
The checks for responsiveness and breathing are carried out with the person horizontally supine. If unconscious but breathing, the recovery position is appropriate.If not breathing, rescue ventilation is necessary. Drowning can produce a gasping pattern of apnea while the heart is still beating, and ventilation alone may be sufficient. The airway-breathing-circulation (ABC) sequence should be followed, rather than starting with compressions as is typical in cardiac arrest, because the basic problem is lack of oxygen.
If the victim is not a baby, it is recommended to start with 5 normal rescue breaths, as the initial ventilation may be difficult because of water in the airways, which can interfere with effective alveolar inflation. Thereafter, a continual sequence of 2 rescue breaths and 30 chest compressions is applied. This alternation is repeated until vital signs are re-established, the rescuers are unable to continue, or advanced life support is available.For babies (very small sized infants), the procedure is slightly modified. In each sequence of rescue breaths (the 5 initial breaths, and the further series of 2 breaths), the rescuers mouth covers the babys mouth and nose simultaneously (because a babys face is too small). Besides, the intercalated series of 30 chest compressions are applied by pressing with only two fingers (due to the body of the babies is more fragile) on the chest bone (approximately on the lower part).
Attempts to actively expel water from the airway by abdominal thrusts, Heimlich maneuver or positioning head downwards should be avoided as there is no obstruction by solids, and they delay the start of ventilation and increase the risk of vomiting, with a significantly increased risk of death, as the aspiration of stomach contents is a common complication of resuscitation efforts.Treatment for hypothermia may also be necessary. However, in those who are unconscious, it is recommended their temperature not be increased above 34 degrees C. Because of the diving reflex, people submerged in cold water and apparently drowned may revive after a relatively long period of immersion. Rescuers retrieving a child from water significantly below body temperature should attempt resuscitation even after protracted immersion.
Medical care
People with a near-drowning experience who have normal oxygen levels and no respiratory symptoms should be observed in a hospital environment for a period of time to ensure there are no delayed complications. The target of ventilation is to achieve 92% to 96% arterial saturation and adequate chest rise. Positive end-expiratory pressure will generally improve oxygenation. Drug administration via peripheral veins is preferred over endotracheal administration. Hypotension remaining after oxygenation may be treated by rapid crystalloid infusion. Cardiac arrest in drowning usually presents as asystole or pulseless electrical activity. Ventricular fibrillation is more likely to be associated with complications of pre-existing coronary artery disease, severe hypothermia, or the use of epinephrine or norepinephrine.While surfactant may be used, no high-quality evidence exist that looks at this practice. Extracorporeal membrane oxygenation may be used in those who cannot be oxygenated otherwise. Steroids are not recommended.
Prognosis
People who have drowned who arrive at a hospital with spontaneous circulation and breathing usually recover with good outcomes. Early provision of basic and advanced life support improve the probability of a positive outcome.A longer duration of submersion is associated with a lower probability of survival and a higher probability of permanent neurological damage.Contaminants in the water can cause bronchospasm and impaired gas exchange and can cause secondary infection with delayed severe respiratory compromise.Low water temperature can cause ventricular fibrillation, but hypothermia during immersion can also slow the metabolism, allowing longer hypoxia before severe damage occurs. Hypothermia that reduces brain temperature significantly can improve the outcome. A reduction of brain temperature by 10 °C decreases ATP consumption by approximately 50%, which can double the time the brain can survive.The younger the person, the better the chances of survival. In one case, a child submerged in cold (37 °F (3 °C)) water for 66 minutes was resuscitated without apparent neurological damage. However, over the long term significant deficits were noted, including a range of cognitive difficulties, particularly general memory impairment, although recent magnetic resonance imaging (MRI) and magnetoencephalography (MEG) were within normal range.
Children
Drowning is a major worldwide cause of death and injury in children. An estimate of about 20% of non-fatal drowning victims may result in varying degrees of ischemic and/or hypoxic brain injury. Hypoxic injuries refers to a lack or absence of oxygen in certain organs or tissues. Ischemic injuries on the other hand refers inadequate blood supply to certain organs or part of the body. These injuries can lead to an increased risk of long-term morbidity. Prolonged hypothermia and hypoxemia from nonfatal submersion drowning can result in cardiac dysrhythmias such as ventricular fibrillation, sinus bradycardia, or atrial fibrillation. Long-term neurological outcomes of drowning cannot be predicted accurately during the early stages of treatment. Although survival after long submersion times, mostly by young children, has been reported, many survivors will remain severely and permanently neurologically compromised after much shorter submersion times. Factors affecting the probability of long-term recovery with mild deficits or full function in young children include the duration of submersion, whether advanced life support was needed at the accident site, the duration of cardiopulmonary resuscitation, and whether spontaneous breathing and circulation are present on arrival at the emergency room. Prolonged submersion in water for more than 5–10 minutes usually leads to poorer prognosis.Data on the long-term outcome are scarce and unreliable. Neurological examination at the time of discharge from the hospital does not accurately predict long-term outcomes. Some people with severe brain injury who were transferred to other institutions died months or years after the drowning and are recorded as survivors. Nonfatal drownings have been estimated as two to four times more frequent than fatal drownings.
Long-Term Effects of Drowning in Children
Long-term effects of nonfatal drowning mainly include damage to major organs such as the brain, lungs, and kidneys. Prolonged submersion time is highly attributed to hypoxic ischemic brain injury in susceptible areas of the brain such as the hippocampus, insular cortex, and/or basal ganglia. Severity in hypoxic ischemic damage of these brain structures corresponds to the severity in global damage to areas of the cerebral cortex. The cerebral cortex is a brain structure that is responsible for language, memory, learning, emotion, intelligence, and personality. Global damage to the cerebral cortex can affect one or more of its primary function, Treatment of pulmonary complication from drowning is highly dependent on the amount of lung injury that occurred during the incident. These lung injuries can be contributed by water aspiration and also irritants present in the water such as microbial pathogens leading to complications such as lung infection that can develop in adult respiratory disease syndrome later on in life. Some literature suggests that occurrences of drowning can lead to acute kidney injury from lack of blood flow and oxygenation due to shock and global hypoxia. These kidney injury can cause irreversible damage to the kidneys and may require long-term treatment such as renal replacement therapy.
Infant Risk
Children are overrepresented in drowning statistics, with children aged 0–4 years old having the highest number of deaths due to unintentional downing. In 2019 alone 32,070 children between the ages 1–4 years old died as a result of unintentional drowning, equating to an age-adjusted fatality of 6.04 per 100,000 children. Infants are particularly vulnerable because while their mobility develops quickly, their perception concerning their ability for locomotion between surfaces develops slower. An infant can have full control of their movements, but simply wont recognize that water does not provide the same support for crawling as hardwood floors would. An infant’s capacity for movement needs to be met with an appropriate perception of surfaces of support (and avoidance of surfaces that do not support locomotion) to avoid drowning. By crawling and interacting with their environment, infants learn to distinguish surfaces offering support for locomotion from those that do not, and their perception of surface characteristics will improve, as well as their perception of falls risk, over several weeks.
Epidemiology
In 2019 alone, roughly 236,000 people died from drowning, thereby causing it to be the third leading cause of unintentional death globally trailing only traffic injuries and falls.In many countries, drowning is one of the main causes of preventable death for children under 12 years old. In the United States in 2006, 1100 people under 20 years of age died from drowning. The United Kingdom has 450 drownings per year, or 1 per 150,000, whereas in the United States, there are about 6,500 drownings yearly, around 1 per 50,000. In Asia suffocation and drowning were the leading causes of preventable death for children under five years of age; a 2008 report by UNICEF found that in Bangladesh, for instance, 46 children drown each day.Due to a generally increased likelihood for risk-taking, males are four times more likely to have submersion injuries.In the fishing industry, the largest group of drownings is associated with vessel disasters in bad weather, followed by man-overboard incidents and boarding accidents at night, either in foreign ports or under the influence of alcohol. Scuba diving deaths are estimated at 700 to 800 per year, associated with inadequate training and experience, exhaustion, panic, carelessness and barotrauma.
South Asia
Deaths due to drowning is high in the South Asian region with India, China, Pakistan and Bangladesh accounting for up to 52% of the global deaths. Death due to drowning is known to be high in the Sundarbans region in West Bengal and in Bihar.According to Daily Times in rural Pakistan while boats are preferred mode of transport where available same time, due to influence of female modesty culture in Pakistan generally women are not encouraged in swimming; in a 2022 July tragedy at Sadiqabad when a boat carrying 100 people capsized in Indus river, many could rescue themselves but 19 women were confirmed dead by drowning since they could not save themselves by swimming.
Africa
In lower income countries, cases of drowning and deaths caused by drowning are under reported and data collection is limited. In spite of this, many low-income countries in Africa still exhibit some of the highest rates of drowning, with incidence rates calculated from population based studies across 15 different countries (Egypt, Ethiopia, Kenya, Uganda, Tanzania, Malawi, Zimbabwe, South Africa, Nigeria, Ghana, Burkina Faso, Ghana, Guinea, Cote dIvoire, and the Gambia) ranging from 0.33 per 100,000 population to 502 per 100,000 population. Potential risk factors include young age, male gender, having to commute across or work on the water (e.g. Fishermen), quality and carrying capacity of the boat, and poor weather.
United States
In the United States, drowning is the second leading cause of death (after motor vehicle accidents) in children 12 and younger.People who drown are more likely to be male, young, or adolescent. There is a racial disparity found in drowning incidents. According to CDC data collected from 1999 to 2019, drowning rates among Native Americans was 2 times higher than non-Hispanic whites while the rate among African-Americans was 1.5 times higher. Surveys indicate that 10% of children under 5 have experienced a situation with a high risk of drowning. Worldwide, about 175,000 children die through drowning every year. The causes of drowning cases in the US from 1999 to 2006 were as follows:
According to the US National Safety Council, 353 people ages 5 to 24 drowned in 2017.
Society and culture
Old terminology
The word "drowning"—like "electrocution"—was previously used to describe fatal events only. Occasionally, that usage is still insisted upon, though the medical communitys consensus supports the definition used in this article. Several terms related to drowning which have been used in the past are also no longer recommended. These include:
Active drowning: People, such as non-swimmers and the exhausted or hypothermic at the surface, who are unable to hold their mouth above water and are suffocating due to lack of air. Instinctively, people in such cases perform well-known behaviors in the last 20–60 seconds before being submerged, representing the bodys last efforts to obtain air. Notably, such people are unable to call for help, talk, reach for rescue equipment, or alert swimmers even feet away, and they may drown quickly and silently close to other swimmers or safety.
Dry drowning: Drowning in which no water enters the lungs.
Near drowning: Drowning which is not fatal.
Wet drowning: Drowning in which water enters the lungs.
Passive drowning: People who suddenly sink or have sunk due to a change in their circumstances. Examples include people who drown in an accident due to sudden loss of consciousness or sudden medical condition.
Secondary drowning: Physiological response to foreign matter in the lungs due to drowning causing extrusion of liquid into the lungs (pulmonary edema) which adversely affects breathing.
Silent drowning: Drowning without a noticeable external display of distress.
Dry drowning
Dry drowning is a term that has never had an accepted medical definition, and that is currently medically discredited. Following the 2002 World Congress on Drowning in Amsterdam, a consensus definition of drowning was established: it is the "process of experiencing respiratory impairment from submersion/immersion in liquid." This definition resulted in only three legitimate drowning subsets: fatal drowning, non-fatal drowning with illness/injury, and non-fatal drowning without illness/injury. In response, major medical consensus organizations have adopted this definition worldwide and have officially discouraged any medical or publication use of the term "dry drowning". Such organizations include the International Liaison Committee on Resuscitation, the Wilderness Medical Society, the American Heart Association, the Utstein Style system, the International Lifesaving Federation, the International Conference on Drowning, Starfish Aquatics Institute, the American Red Cross, the Centers for Disease Control and Prevention (CDC), the World Health Organization and the American College of Emergency Physicians.Drowning experts have recognized that the resulting pathophysiology of hypoxemia, acidemia, and eventual death is the same whether water entered the lung or not. As this distinction does not change management or prognosis but causes significant confusion due to alternate definitions and misunderstandings, it is generally established that pathophysiological discussions of "dry" versus "wet" drowning are not relevant to drowning care."Dry drowning" is frequently cited in the news with a wide variety of definitions. and is often confused with the equally inappropriate and discredited term "secondary drowning" or "delayed drowning". Various conditions including spontaneous pneumothorax, chemical pneumonitis, bacterial or viral pneumonia, head injury, asthma, heart attack, and chest trauma have been misattributed to the erroneous terms "delayed drowning," "secondary drowning," and "dry drowning." Currently, there has never been a case identified in the medical literature where a person was observed to be without symptoms and who died hours or days later as a direct result of drowning alone.
Capital punishment
In Europe, drowning was used as capital punishment. During the Middle Ages, a sentence of death was read using the words cum fossa et furca, or "with pit and gallows".Drowning survived as a method of execution in Europe until the 17th and 18th centuries. England had abolished the practice by 1623, Scotland by 1685, Switzerland in 1652, Austria in 1776, Iceland in 1777, and Russia by the beginning of the 1800s. France revived the practice during the French Revolution (1789–1799) and it was carried out by Jean-Baptiste Carrier at Nantes.
References
External links
Canadian Red Cross: Drowning Research: Drownings in Canada, 10 Years of Research Module 2 – Ice & Cold Water Immersion |
Cardiac myxoma | A myxoma is a rare benign tumor of the heart. Myxomata are the most common primary cardiac tumor in adults, and are most commonly found within the left atrium near the valve of the fossa ovalis. Myxomata may also develop in the other heart chambers. The tumor is derived from multipotent mesenchymal cells. Cardiac myxoma can affect adults between 30 and 60 years of age.
Signs and symptoms
Symptoms may occur at any time, but most often they accompany a change of body position. Pedunculated myxomata can have a "wrecking ball effect", as they lead to stasis and may eventually embolize themselves. Symptoms may include:
Shortness of breath with activity
Platypnea – Difficulty breathing in the upright position with relief in the supine position
Paroxysmal nocturnal dyspnea – Breathing difficulty when asleep
Dizziness
Fainting
Palpitations – Sensation of feeling your heart beat
Chest pain or tightness
Sudden Death (In which case the disease is an autopsy finding)The symptoms and signs of left atrial myxomata often mimic mitral stenosis.
General symptoms may also be present, such as:
Cough
Pulmonary edema – as blood backs up into the pulmonary artery, after increased pressures in the left atrium and atrial dilation
Hemoptysis
Fever
Cachexia – Involuntary weight loss
General discomfort (malaise)
Joint pain
Blue discoloration of the skin, especially the fingers change color upon pressure, cold, or stress (Raynauds phenomenon)
Clubbing – Curvature of nails accompanied with soft tissue enlargement of the fingers
Swelling – any part of the body
Presystolic heart murmurThese general symptoms may also mimic those of infective endocarditis.
Complications
Arrhythmias
Pulmonary edema
Peripheral emboli
Spread (metastasis) of the tumor
Blockage of the mitral heart valve
Stroke
Fusiform cerebral aneurysms
Causes
Myxomata are the most common type of adult primary heart tumor. Most myxomata arise sporadically (90%), and only about 10% are thought to arise due to inheritance.About 10% of myxomata are inherited, as in Carney syndrome. Such tumors are called familial myxomata. They tend to occur in more than one part of the heart at a time, and often cause symptoms at a younger age than other myxomata. Other abnormalities are observed in people with Carney syndrome include skin myxomata, pigmentation, endocrine hyperactivity, schwannomas and epithelioid blue nevi. Myxomata are more common in women than men.
Diagnosis
A doctor will listen to the heart with a stethoscope. A "tumor plop" (a sound related to movement of the tumor), abnormal heart sounds, or a murmur similar to the mid-diastolic rumble of mitral stenosis may be heard. These sounds may change when the patient changes position.Right atrial myxomata rarely produce symptoms until they have grown to be at least 13 cm (about 5 inches) wide.Tests may include:
Echocardiogram and Doppler study
Chest x-ray
CT scan of chest
Heart MRI
Left heart angiography
Right heart angiography
ECG—may show atrial fibrillationBlood tests:
Blood tests: An FBC may show anemia and increased WBCs (white blood cells). The erythrocyte sedimentation rate (ESR) is usually increased.
Blood tests: An FBC may show anemia and increased WBCs (white blood cells). The erythrocyte sedimentation rate (ESR) is usually increased.
Treatment
The surgery is treatment of choice, tumor must be surgically removed. Some patients will also need their mitral valve replaced. This can be done during the same surgery. Usually, inadequate excision of the tumor, development from a secondary focus, or intracardiac implantation from the primary tumor are the attributable explanation for recurrence, and it is more likely to occur in the first 10 postoperative years, especially in younger patients.
Prognosis
Although a myxoma is not malignant with risk of metastasis, complications are common. Untreated, a myxoma can lead to an embolism (tumor cells breaking off and traveling with the bloodstream). Myxoma fragments can move to the brain, eye, or limbs.If the tumor continues to enlarge inside the heart, it can block blood flow through the mitral valve and cause symptoms of mitral stenosis or mitral regurgitation. This may require emergency surgery to prevent sudden death.
See also
Myxoma
Interleukin 6
Papillary fibroelastoma
Rhabdomyomas
Cardiac sarcomas
References
== External links == |
Coarctation of the aorta | Coarctation of the aorta (CoA or CoAo), also called aortic narrowing, is a congenital condition whereby the aorta is narrow, usually in the area where the ductus arteriosus (ligamentum arteriosum after regression) inserts. The word coarctation means "pressing or drawing together; narrowing". Coarctations are most common in the aortic arch. The arch may be small in babies with coarctations. Other heart defects may also occur when coarctation is present, typically occurring on the left side of the heart. When a patient has a coarctation, the left ventricle has to work harder. Since the aorta is narrowed, the left ventricle must generate a much higher pressure than normal in order to force enough blood through the aorta to deliver blood to the lower part of the body. If the narrowing is severe enough, the left ventricle may not be strong enough to push blood through the coarctation, thus resulting in a lack of blood to the lower half of the body. Physiologically its complete form is manifested as interrupted aortic arch.
Classification
There are three types of aortic coarctations:
Preductal coarctation: The narrowing is proximal to the ductus arteriosus. Blood flow to the aorta that is distal to the narrowing is dependent on the ductus arteriosus; therefore severe coarctation can be life-threatening. Preductal coarctation results when an intracardiac anomaly during fetal life decreases blood flow through the left side of the heart, leading to hypoplastic development of the aorta. This is the type seen in approximately 5% of infants with Turner syndrome.
Ductal coarctation: The narrowing occurs at the insertion of the ductus arteriosus. This kind usually appears when the ductus arteriosus closes.
Postductal coarctation: The narrowing is distal to the insertion of the ductus arteriosus. Even with an open ductus arteriosus, blood flow to the lower body can be impaired. This type is most common in adults. It is associated with notching of the ribs (because of collateral circulation), hypertension in the upper extremities, and weak pulses in the lower extremities. Postductal coarctation is most likely the result of the extension of a muscular artery (ductus arteriosus) into an elastic artery (aorta) during fetal life, where the contraction and fibrosis of the ductus arteriosus upon birth subsequently narrows the aortic lumen.Aortic coarctation and aortic stenosis are both forms of aortic narrowing. In terms of word root meanings, the names are not different, but a conventional distinction in their usage allows differentiation of clinical aspects. This spectrum is dichotomized by the idea that aortic coarctation occurs in the aortic arch, at or near the ductus arteriosus, whereas aortic stenosis occurs in the aortic root, at or near the aortic valve. This naturally could present the question of the dividing line between a post valvular stenosis and a preductal coarctation; nonetheless, the dichotomy has a practical use, as most defects are either one or the other.
Signs and symptoms
In mild cases, children may show no signs or symptoms at first and their condition may not be diagnosed until later in life. Some children born with coarctation of the aorta have additional heart defects, such as aortic stenosis, ventricular septal defect, patent ductus arteriosus or mitral valve abnormalities.Coarctation is about twice as common in boys as it is in girls. It is frequently found in girls who have Turner syndrome.Symptoms may be absent with mild narrowings (coarctation). When present, they include breathing difficulties, poor appetite or trouble feeding, and failure to thrive. Later on, children may develop symptoms related to problems with blood flow and an enlarged heart. They may experience dizziness or shortness of breath, fainting or near-fainting episodes, chest pain, abnormal tiredness or fatigue, headaches, or nosebleeds. They have cold legs and feet or have pain in their legs with exercise (intermittent claudication).In cases of more severe coarctations, babies may develop serious problems soon after birth because not enough blood can get through the aorta to the rest of their body.
Arterial hypertension in the arms with low blood pressure in the lower extremities is classic. In the lower extremities, weak pulses in the femoral arteries and arteries of the feet are found.The coarctation typically occurs after the left subclavian artery. However, if situated before it, blood flow to the left arm is compromised and asynchronous or radial pulses of different "strength" may be detected (normal on the right arm, weak or delayed on the left), termed radio-radial delay. In these cases, a difference between the normal radial pulse in the right arm and the delayed femoral pulse in the legs (either side) may be apparent, whilst no such delay would be appreciated with palpation of both delayed left arm and either femoral pulses. On the other hand, a coarctation occurring after the left subclavian artery will produce synchronous radial pulses, but radio-femoral delay will be present under palpation in either arm (both arm pulses are normal compared to the delayed leg pulses).
Diagnosis
With imaging, resorption of the lower part of the ribs may be seen, due to increased blood flow over the neurovascular bundle that runs there. Prestenotic dilatation of the aortic arch and left subclavian artery, as well as indentation at the site of coarctation results in a classic figure 3 sign on x-ray. The characteristic bulging of the sign is caused by dilatation of the aorta due to an indrawing of the aortic wall at the site of cervical rib obstruction, with consequent poststenotic dilatation. This physiology results in the 3 image for which the sign is named. When the esophagus is filled with barium, a reverse 3 or E sign is often seen and represents a mirror image of the areas of prestenotic and poststenotic dilatation.Coarctation of the aorta can be accurately diagnosed with magnetic resonance angiography. In teenagers and adults echocardiograms may not be conclusive.The severity of coarctation of the aorta can be rated by a combination of the smallest aortic cross-sectional area of the aorta (adjusted for body surface area) as measured by 3D-rendered contrast MRI, as well as mean heart rate–corrected flow deceleration in the descending aorta as measured by phase contrast magnetic resonance imaging.
Prevention
Unfortunately, coarctations can not be prevented because they are usually present at birth. The best thing for patients who are affected by coarctations is early detection. Some signs that can lead to a coarctation have been linked to pathologies such as Turner syndrome, bicuspid aortic valve, and other family heart conditions.
Treatment
In adults and children found to have coarctation, treatment is conservative if asymptomatic, but may require surgical resection of the narrow segment if there is arterial hypertension. The first operations to treat coarctation were carried out by Clarence Crafoord in Sweden in 1944. In some cases angioplasty can be performed to dilate the narrowed artery, with or without the placement of a stent graft.For fetuses at high risk for developing coarctation, a novel experimental treatment approach is being investigated, wherein the mother inhales 45% oxygen three times a day (3 x 3–4 hours) beyond 34 weeks of gestation. The oxygen is transferred via the placenta to the fetus and results in dilatation of the fetal lung vessels. As a consequence, the flow of blood through the fetal circulatory system increases, including that through the underdeveloped arch. In suitable fetuses, marked increases in aortic arch dimensions have been observed over treatment periods of about two to three weeks.The long-term outcome is very good. Some patients may, however, develop a narrowing (stenosis) or dilatation at the previous coarctation site. All patients with unrepaired or repaired aortic coarctation require follow-up in specialized Congenital Heart Disease centers.
Gallery
Complications of surgery
Surgical treatment involves resection of the stenosed segment and re-anastomosis. Two complications specific to this surgery are left recurrent nerve palsy and chylothorax, as the recurrent laryngeal nerve and thoracic duct are in the vicinity. Chylothorax is a troublesome complication and is usually managed conservatively by adjusting the diet to eliminate long-chain fatty acids and supplementing medium-chain triglycerides. When conservative management fails surgical intervention is then most often required. Fluorescein dye can aid in the localisation of chyle leak.
Prognosis
Side effects
Previously, hypertension was defined as a blood pressure of 140/90 mm Hg but has since been revised by the American College of Cardiology/American Heart Association Task Force to a blood pressure of 130/80 mm Hg or higher in adults. This is a severe problem for the heart and can cause many other complications. In a study of 120 coarctation repair recipients done in Groningen, The Netherlands, twenty-nine patients (25%) experienced hypertension in the later years of life due to the repair. While hypertension has many different factors that lead to this stage of blood pressure, people who have had a coarctation repair — regardless of the age at which the operation was performed — are at much higher risk than the general public of hypertension later in life. Undetected chronic hypertension may result earlier atherosclerosis in the arterial area and can lead to earlier death among coarctation repair patients, at higher rates as time progresses.Angioplasty is a procedure done to dilate an abnormally narrow section of a blood vessel to allow better blood flow. This is done in a cardiac catheterization laboratory. Typically taking two to three hours, the procedure may take longer but usually patients are able to leave the hospital the same day. After a coarctation repair 20-60% of infant patients may experience reoccurring stenosis at the site of the original operation. This can be fixed by either another coarctectomy.Coronary artery disease (CAD) is a major issue for patients who have undergone a coarctation repair. Many years after the procedure is done, heart disease not only has an increased chance of affecting coarctation patients, but also progresses through the levels of severity at an alarmingly increased rate. In one study, one fourth of the patients who experienced a coarctation later died of heart disease, some at a relatively young age.Clinical criteria are used in most studies when defining recurrence of coarctation (recoarctation) when blood pressure is at a difference of >20 mmHg between the lower and upper limbs. This procedure is most common in infant patients and is uncommon in adult patients. 10.8% of infant patients underwent recoarctations at less than two years of age while another 3.1% of older children received a recoarctation.People who have had a coarctation of the aorta are likely to have bicuspid aortic valve disease. Between 20% and 85% of patients are affected by this disease. Bicuspid aortic valve disease is a big contributor to cardiac failure, which in turn makes up roughly 20% of late deaths to coarctation patients.
Follow-up
Because of the risk of recoarctation and late hypertension, check-ups are needed once a year or less frequently depending on the individual case. It is important to visit the cardiologist on a regular basis. Depending on the severity of the patients condition, which is evaluated on a case-by-case level, visiting a cardiologist can be a once a year or less frequent surveillance check-up. Keeping a regular schedule of appointments with a cardiologist after a coarctation procedure is complete helps increase the chances of optimal health for the patients. Nowadays, life expectancy is considered normal given the repair was successfully done in early childhood. Treatment of recoarctation is usually successfully done without the need for open-heart surgery. Recoarctation is increasingly less common in the modern era. Late hypertension does also seem to be much less of a problem if the coarctation repair was performed within the first 5 years of life. Life expectancy and quality of life are therefore the same or very close to that of the normal population, but check ups are recommended so that those few percent who need further treatment get it in time.
History
The condition was largely unidentified until the mid-20th century. History of the condition prior to 1945 has been understood via post-mortem records, the first series of which was published in 1928, which examined cases as far back as 1791. The first surgery for coarctation of the aorta was performed by Clarence Crafoord and G. Nylin on October 19, 1944 in Stockholm, Sweden on a 12-year old boy.An anecdotal history statement describes the first diagnosed case of the coarctation of the aorta in Julia the daughter of the French poet Alphonse de Lamartine after the autopsy in 1832 in Beirut, the referenced manuscript still exists in one of the Maronite monasteries in Mount Lebanon.
References
Further reading
Toro-Salazar, Olga H; Steinberger, Julia; Thomas, William; Rocchini, Albert P; Carpenter, Becky; Moller, James H (2002). "Long-term follow-up of patients after coarctation of the aorta repair". The American Journal of Cardiology. 89 (5): 541–7. doi:10.1016/S0002-9149(01)02293-7. PMID 11867038.
Brouwer, Rene M.H.J.; Erasmus, Michiel E.; Ebels, Tjark; Eijgelaar, Anton (1994). "Influence of age on survival, late hypertension, and recoarctation in elective aortic coarctation repair. Including long-term results after elective aortic coarctation repair with a follow-up from 25 to 44 years". The Journal of Thoracic and Cardiovascular Surgery. 108 (3): 525–31. doi:10.1016/S0022-5223(94)70264-0. PMID 8078345.
Jenkins, N.P. (1999). "Coarctation of the aorta: natural history and outcome after surgical treatment". QJM. 92 (7): 365–71. doi:10.1093/qjmed/92.7.365. PMID 10627885.
External links
"Coarctation of the aorta". Mayo Clinic. April 20, 2012.
"Cardiac Catheterization". Cleveland Clinic. September 2013. |
Concussion | A concussion, also known as a mild traumatic brain injury (mTBI), is a head injury that temporarily affects brain functioning. Symptoms may include loss of consciousness (LOC); memory loss; headaches; difficulty with thinking, concentration, or balance; nausea; blurred vision; sleep disturbances; and mood changes. Any of these symptoms may begin immediately, or appear days after the injury. Concussion should be suspected if a person indirectly or directly hits their head and experiences any of the symptoms of concussion. It is not unusual for symptoms to last 2 weeks in adults and 4 weeks in children. Fewer than 10% of sports-related concussions among children are associated with loss of consciousness.Common causes include motor vehicle collisions, falls, sports injuries, and bicycle accidents. Risk factors include drinking alcohol and a prior history of concussion. The mechanism of injury involves either a direct blow to the head or forces elsewhere on the body that are transmitted to the head. This is believed to result in neuron dysfunction, as there are increased glucose requirements, but not enough blood supply. A thorough evaluation by a qualified medical provider (such as a physician, physician assistant, or nurse practitioner) is required to rule out life-threatening head injuries, injuries to the cervical spine, and neurological conditions. Glasgow coma scale score 13 to 15, loss of consciousness for less than 30 minutes, and memory loss for less than 24 hours may be used to rule out moderate or severe traumatic brain injuries. Diagnostic imaging such as a CT scan or an MRI may also be required to rule out severe head injuries. Routine imaging is not required to diagnose concussion.Prevention of concussions includes the use of a helmet when bicycling or motorbiking. Treatment includes physical and cognitive rest for 1–2 days, with a gradual step-wise return to activities, school, and work. Prolonged periods of rest may slow recovery and result in greater depression and anxiety. Paracetamol (acetaminophen) or NSAIDs may be recommended to help with a headache. Physiotherapy may be useful for persistent balance problems; cognitive behavioral therapy may be useful for mood changes. Evidence to support the use of hyperbaric oxygen therapy and chiropractic therapy is lacking.Worldwide, concussions are estimated to affect more than 3.5 per 1,000 people a year. Concussions are classified as mild traumatic brain injuries and are the most common type of TBIs. Males and young adults are most commonly affected. Outcomes are generally good. Another concussion before the symptoms of a prior concussion have resolved is associated with worse outcomes. Repeated concussions may also increase the risk in later life of chronic traumatic encephalopathy, Parkinsons disease and depression.
Signs and symptoms
Concussions symptoms vary between people and include physical, cognitive, and emotional symptoms. Symptoms may appear immediately or be delayed. Up to one-third of people with concussion experience prolonged or persistent concussion symptoms, also known as post concussion syndrome, which is defined as concussion symptoms lasting for 4-weeks or longer in children/adolescents and symptoms lasting for more than 14 days in an adult. The severity of the initial symptoms is the strongest predictor of recovery time in adults.
Physical
Headaches are the most common mTBI symptom. Others include dizziness, vomiting, nausea, lack of motor coordination, difficulty balancing, or other problems with movement or sensation. Visual symptoms include light sensitivity, seeing bright lights, blurred vision, and double vision. Tinnitus, or a ringing in the ears, is also commonly reported. In one in about seventy concussions, concussive convulsions occur, but seizures that take place during or immediately after a concussion are not "post-traumatic seizures", and, unlike post-traumatic seizures, are not predictive of post-traumatic epilepsy, which requires some form of structural brain damage, not just a momentary disruption in normal brain functioning. Concussive convulsions are thought to result from temporary loss or inhibition of motor function and are not associated either with epilepsy or with more serious structural damage. They are not associated with any particular sequelae and have the same high rate of favorable outcomes as concussions without convulsions.
Cognitive and emotional
Cognitive symptoms include confusion, disorientation, and difficulty focusing attention. Loss of consciousness may occur, but is not necessarily correlated with the severity of the concussion if it is brief. Post-traumatic amnesia, in which events following the injury cannot be recalled, is a hallmark of concussions. Confusion, another concussion hallmark, may be present immediately or may develop over several minutes. A person may repeat the same questions, be slow to respond to questions or directions, have a vacant stare, or have slurred or incoherent speech. Other mTBI symptoms include changes in sleeping patterns and difficulty with reasoning, concentrating, and performing everyday activities.A concussion can result in changes in mood including crankiness, loss of interest in favorite activities or items, tearfulness, and displays of emotion that are inappropriate to the situation. Common symptoms in concussed children include restlessness, lethargy, and irritability.
Mechanism
Forces
The brain is surrounded by cerebrospinal fluid, which protects it from light trauma. More severe impacts, or the forces associated with rapid acceleration, may not be absorbed by this cushion. Concussions, and other head-related injuries, occur when external forces acting on the head are transferred to the brain. Such forces can occur when the head is struck by an object or surface (a direct impact), or when the torso rapidly changes position (i.e. from a body check) and force is transmitted to the head (an indirect impact).Forces may cause linear, rotational, or angular movement of the brain or a combination of them. In rotational movement, the head turns around its center of gravity and in angular movement, it turns on an axis, not through its center of gravity. The amount of rotational force is thought to be the major component in concussion and its severity.
As of 2007, studies with athletes have shown that the amount of force and the location of the impact are not necessarily correlated with the severity of the concussion or its symptoms, and have called into question the threshold for concussion previously thought to exist at around 70–75 g.The parts of the brain most affected by rotational forces are the midbrain and diencephalon. It is thought that the forces from the injury disrupt the normal cellular activities in the reticular activating system located in these areas and that this disruption produces the loss of consciousness often seen in concussion. Other areas of the brain that may be affected include the upper part of the brain stem, the fornix, the corpus callosum, the temporal lobe, and the frontal lobe. Angular accelerations of 4600, 5900, or 7900 rad/s2 are estimated to have 25, 50, or 80% risk of mTBI respectively.
Pathophysiology
In both animals and humans, mTBI can alter the brains physiology for hours to years, setting into motion a variety of pathological events. As one example, in animal models, after an initial increase in glucose metabolism, there is a subsequent reduced metabolic state which may persist for up to four weeks after injury. Though these events are thought to interfere with neuronal and brain function, the metabolic processes that follow concussion are reversible in a large majority of affected brain cells; however, a few cells may die after the injury.Included in the cascade of events unleashed in the brain by concussion is impaired neurotransmission, loss of regulation of ions, deregulation of energy use and cellular metabolism, and a reduction in cerebral blood flow. Excitatory neurotransmitters, chemicals such as glutamate that serve to stimulate nerve cells, are released in excessive amounts. The resulting cellular excitation causes neurons to fire excessively. This creates an imbalance of ions such as potassium and calcium across the cell membranes of neurons (a process like excitotoxicity).At the same time, cerebral blood flow is relatively reduced for unknown reasons, though the reduction in blood flow is not as severe as it is in ischemia. Thus cells get less glucose than they normally do, which causes an "energy crisis".Concurrently with these processes, the activity of mitochondria may be reduced, which causes cells to rely on anaerobic metabolism to produce energy, increasing levels of the byproduct lactate.For a period of minutes to days after a concussion, the brain is especially vulnerable to changes in intracranial pressure, blood flow, and anoxia. According to studies performed on animals (which are not always applicable to humans), large numbers of neurons can die during this period in response to slight, normally innocuous changes in blood flow.Concussion involves diffuse (as opposed to focal) brain injury, meaning that the dysfunction occurs over a widespread area of the brain rather than in a particular spot. It is thought to be a milder type of diffuse axonal injury, because axons may be injured to a minor extent due to stretching. Animal studies in which rodents were concussed have revealed lifelong neuropathological consequences such as ongoing axonal degeneration and neuroinflammation in subcortical white matter tracts. Axonal damage has been found in the brains of concussion patients who died from other causes, but inadequate blood flow to the brain due to other injuries may have contributed. Findings from a study of the brains of deceased NFL athletes who received concussions suggest that lasting damage is done by such injuries. This damage, the severity of which increases with the cumulative number of concussions sustained, can lead to a variety of other health issues.The debate over whether concussion is a functional or structural phenomenon is ongoing. Structural damage has been found in the mildly traumatically injured brains of animals, but it is not clear whether these findings would apply to humans. Such changes in brain structure could be responsible for certain symptoms such as visual disturbances, but other sets of symptoms, especially those of a psychological nature, are more likely to be caused by reversible pathophysiological changes in cellular function that occur after concussion, such as alterations in neurons biochemistry. These reversible changes could also explain why dysfunction is frequently temporary. A task force of head injury experts called the Concussion In Sport Group met in 2001 and decided that "concussion may result in neuropathological changes but the acute clinical symptoms largely reflect a functional disturbance rather than structural injury."Using animal studies, the pathology of a concussion seems to start with mechanical shearing and stretching forces disrupting the cell membrane of nerve cells through "mechanoporation". This results in potassium outflow from within the cell into the extracellular space with the subsequent release of excitatory neurotransmitters including glutamate which leads to enhanced potassium extrusion, in turn resulting in sustained depolarization, impaired nerve activity and potential nerve damage. Human studies have failed to identify changes in glutamate concentration immediately post-mTBI, though disruptions have been seen 3 days to 2 weeks post-injury. In an effort to restore ion balance, the sodium-potassium ion pumps increase activity, which results in excessive ATP (adenosine triphosphate) consumption and glucose utilization, quickly depleting glucose stores within the cells. Simultaneously, inefficient oxidative metabolism leads to anaerobic metabolism of glucose and increased lactate accumulation. There is a resultant local acidosis in the brain and increased cell membrane permeability, leading to local swelling. After this increase in glucose metabolism, there is a subsequent lower metabolic state which may persist for up to 4 weeks after injury. A completely separate pathway involves a large amount of calcium accumulating in cells, which may impair oxidative metabolism and begin further biochemical pathways that result in cell death. Again, both of these main pathways have been established from animal studies and the extent to which they apply to humans is still somewhat unclear.
Diagnosis
Head trauma recipients are initially assessed to exclude a more severe emergency such as an intracranial hemorrhage. This includes the "ABCs" (airway, breathing, circulation) and stabilization of the cervical spine which is assumed to be injured in any athlete who is found to be unconscious after head or neck injury. Indications that screening for more serious injury is needed include worsening of symptoms such as headaches, persistent vomiting, increasing disorientation or a deteriorating level of consciousness, seizures, and unequal pupil size. Those with such symptoms, or those who are at higher risk of a more serious brain injury, may undergo brain imaging to detect lesions and are frequently observed for 24–48 hours. A brain CT or brain MRI should be avoided unless there are progressive neurological symptoms, focal neurological findings or concern of skull fracture on exam.Diagnosis of concussion requires an assessment performed by a physician or nurse practitioner to rule out severe injuries to the brain and cervical spine, mental health conditions, or other medical conditions. Diagnosis is based on physical and neurological examination findings, duration of unconsciousness (usually less than 30 minutes) and post-traumatic amnesia (PTA; usually less than 24 hours), and the Glasgow Coma Scale (people with mTBI have scores of 13 to 15). A CT scan or MRI is not required to diagnose concussion. Neuropsychological tests such as the SCAT5/child SCAT5 may be suggested measure cognitive function. Such tests may be administered hours, days, or weeks after the injury, or at different times to demonstrate any trend. Some athletes are also being tested pre-season (pre-season baseline testing) to provide a baseline for comparison in the event of an injury, though this may not reduce risk or affect return to play and baseline testing is not required or suggested for most children and adults.If the Glasgow coma scale is less than 15 at two hours or less than 14 at any time, a CT is recommended. In addition, a CT scan is more likely to be performed if observation after discharge is not assured or intoxication is present, there is suspected increased risk for bleeding, age greater than 60, or less than 16. Most concussions, without complication, cannot be detected with MRI or CT scans. However, changes have been reported on MRI and SPECT imaging in those with concussion and normal CT scans, and post-concussion syndrome may be associated with abnormalities visible on SPECT and PET scans. Mild head injury may or may not produce abnormal EEG readings. A blood test known as the Brain Trauma Indicator was approved in the United States in 2018 and may be able to rule out the risk of intracranial bleeding and thus the need for a CT scan for adults.Concussion may be under-diagnosed because of the lack of the highly noticeable signs and symptoms while athletes may minimize their injuries to remain in the competition. Direct impact to the head is not required for a concussion diagnosis, as other bodily impacts with a subsequent force transmission to the head are also causes. A retrospective survey in 2005 suggested that more than 88% of concussions are unrecognized. Particularly, many younger athletes struggle with identifying their concussions, which often result in the non-disclosure of concussions and consequently under-representing the incidence of concussions in the context of sport.Diagnosis can be complex because concussion shares symptoms with other conditions. For example, post-concussion symptoms such as cognitive problems may be misattributed to brain injury when, in fact, due to post-traumatic stress disorder (PTSD).There are no fluid biomarkers (i.e., blood or urine tests) that are validated for diagnosing concussion in children or adolescents.
Classification
No single definition of concussion, minor head injury, or mild traumatic brain injury is universally accepted. In 2001, the expert Concussion in Sport Group of the first International Symposium on Concussion in Sport defined concussion as "a complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces." It was agreed that concussion typically involves temporary impairment of neurological function that heals by itself within time, and that neuroimaging normally shows no gross structural changes to the brain as the result of the condition.However, although no structural brain damage occurs according to the classic definition, some researchers have included injuries in which structural damage has occurred and the National Institute for Health and Clinical Excellence definition includes physiological or physical disruption in the brains synapses. Also, by definition, concussion has historically involved a loss of consciousness. However, the definition has evolved over time to include a change in consciousness, such as amnesia, although controversy continues about whether the definition should include only those injuries in which loss of consciousness occurs.
This debate resurfaces in some of the best-known concussion grading scales, in which those episodes involving loss of consciousness are graded as being more severe than those without.Definitions of mild traumatic brain injury (mTBI) were inconsistent until the World Health Organizations International Statistical Classification of Diseases and Related Health Problems (ICD-10) provided a consistent, authoritative definition across specialties in 1992.
Since then, various organizations such as the American Congress of Rehabilitation Medicine and the American Psychiatric Association in its Diagnostic and Statistical Manual of Mental Disorders have defined mTBI using some combination of loss of consciousness (LOC), post-traumatic amnesia (PTA), and the Glasgow Coma Scale (GCS).
Concussion falls under the classification of mild TBI, but it is not clear whether concussion is implied in mild brain injury or mild head injury. "mTBI" and "concussion" are often treated as synonyms in medical literature but other injuries such as intracranial hemorrhages (e.g. intra-axial hematoma, epidural hematoma, and subdural hematoma) are not necessarily precluded in mTBI or mild head injury, as they are in concussion. mTBI associated with abnormal neuroimaging may be considered "complicated mTBI". "Concussion" can be considered to imply a state in which brain function is temporarily impaired and "mTBI" to imply a pathophysiological state, but in practice, few researchers and clinicians distinguish between the terms. Descriptions of the condition, including the severity and the area of the brain affected, are now used more often than "concussion" in clinical neurology.
Prevention
Prevention of mTBI involves general measures such as wearing seat belts, using airbags in cars, and protective equipment such as helmets for high-risk sports. Older people are encouraged to reduce fall risk by keeping floors free of clutter and wearing thin, flat, shoes with hard soles that do not interfere with balance.Protective equipment such as helmets and other headgear and policy changes such as the banning of body checking in youth hockey leagues have been found to reduce the number and severity of concussions in athletes. Secondary prevention such as a Return to Play Protocol for an athlete may reduce the risk of repeat concussions. New "Head Impact Telemetry System" technology is being placed in helmets to study injury mechanisms and may generate knowledge that will potentially help reduce the risk of concussions among American Football players.Educational interventions, such as handouts, videos, workshops, and lectures, can improve concussion knowledge of diverse groups, particularly youth athletes and coaches. Strong concussion knowledge may be associated with greater recognition of concussion symptoms, higher rates of concussion reporting behaviors, and reduced body checking-related penalties and injuries, thereby lowering risk of mTBI.Due to the incidence of concussion in sport, younger athletes often do not disclose concussions and their symptoms. Common reasons for non-disclosure include a lack of awareness of the concussion, the belief that the concussion was not serious enough, and not wanting to leave the game or team due to their injury. Self-reported concussion rates among U-20 and elite rugby union players in Ireland are 45–48%, indicating that many concussions go unreported. Changes to the rules or enforcing existing rules in sports, such as those against "head-down tackling", or "spearing", which is associated with a high injury rate, may also prevent concussions.
Treatment
Adults and children with a suspected concussion require a medical assessment to confirm the diagnosis of concussion and rule out more serious head injuries. After life-threatening head injuries, injuries to the cervical spine, and neurological conditions are ruled out, exclusion of neck or head injury, observation should be continued for several hours. If repeated vomiting, worsening headache, dizziness, seizure activity, excessive drowsiness, double vision, slurred speech, unsteady walk, or weakness or numbness in arms or legs, or signs of basilar skull fracture develop, immediate assessment in an emergency department is needed. Observation to monitor for worsening condition is an important part of treatment. People may be released after assessment from their primary care medical clinic, hospital, or emergency room to the care of a trusted person with instructions to return if they display worsening symptoms or those that might indicate an emergent condition ("red flag symptoms") such as change in consciousness, convulsions, severe headache, extremity weakness, vomiting, new bleeding or deafness in either or both ears. Education about symptoms, their management, and their normal time course, may lead to an improved outcome.
Rest and return to physical and cognitive activity
Physical and cognitive rest is recommended for the first 24–48 hours following a concussion after which injured persons should gradually start gentle low-risk physical and cognitive activities that do not make current symptoms worse or bring on new symptoms. Any activity for which there is a risk of contact, falling, or bumping the head should be avoided. Low-risk activities can be started even while a person has symptoms, as long as the activity does not worsen existing symptoms or bring on new concussion symptoms. Resting for longer than 24–48 hours follow concussion has been shown to be associated with longer recovery.
Return-to-school
The resumption of low-risk school activities should begin as soon as the student feels ready and has completed an initial period of cognitive rest of no more than 24–48 hours following the acute injury. Long absences from school are not suggested, however, the return to school should be gradual and step-wise. Prolonged complete mental or physical rest (beyond 24–48 hours after the accident that lead to the concussion) may worsen outcomes, however, rushing back to school before the person is ready, has also been associated with longer-lasting symptoms and an extended recovery time. Students with a suspected concussion are required to see a doctor for an initial medical assessment and for suggestions on recovery, however, medical clearance is not required for a student to return to school. Since students may appear normal, continuing education of relevant school personnel may be needed to ensure appropriate accommodations are made such as part-days and extended deadlines. Accommodations should be based on the monitoring of symptoms that are present during the return-to-school transition including headaches, dizziness, vision problems, memory loss, difficulty concentrating, and abnormal behavior. Students must have completely resumed their school activities (without requiring concussion-related academic supports) before returning to full-contact sports.
Return-to-sport
For persons participating in athletics, it is suggested that participants progress through a series of graded steps. These steps include:
Immediately after injury: 24–48 hours (maximum) of relative physical and cognitive rest.
Stage 1: Gentle daily activities such as walking in the house, gentle housework, and light school work that do not make symptoms worse. No sports activities.
Stage 2: Light aerobic activity such as walking or stationary cycling
Stage 3: Sport-specific activities such as running drills and skating drills
Stage 4: Non-contact training drills (exercise, coordination, and cognitive load)
Stage 5: Full-contact practice (requires medical clearance)
Stage 6: Return to full-contact sport or high-risk activities (requires medical clearance)At each step, the person should not have worsening or new symptoms for at least 24 hours before progressing to the next. If symptoms worsen or new symptoms begin, athletes should drop back to the previous level for at least another 24 hours.Intercollegiate or professional athletes, are typically followed closely by team athletic trainers during this period but others may not have access to this level of health care and may be sent home with minimal monitoring.
Medications
Medications may be prescribed to treat headaches, sleep problems and depression. Analgesics such as ibuprofen can be taken for headaches, but paracetamol (acetaminophen) is preferred to minimize the risk of intracranial hemorrhage. Concussed individuals are advised not to use alcohol or other drugs that have not been approved by a doctor as they can impede healing. Activation database-guided EEG biofeedback has been shown to return the memory abilities of the concussed individual to levels better than the control group.About one percent of people who receive treatment for mTBI need surgery for a brain injury.
Return to work
Determining the ideal time for a person to return to work will depend on personal factors and job-related factors including the intensity of the job and the risk of falling or hitting ones head at work during recovery. After the required initial recovery period of complete rest (24–48 hours after the concussion began), gradually and safely returning to the workplace with accommodations and support in place, should be prioritized over staying home and resting for long periods of time, to promote physical recovery and reduce the risk of people becoming socially isolated. The person should work with their employer to design a step-wise "return-to-work" plan. For those with a high-risk job, medical clearance may be required before resuming an activity that could lead to another head injury. Students should have completed the full return-to-school progression with no academic accommodations related to the concussion required before starting to return to part-time work.
Prognosis
The majority of children and adults fully recover from a concussion, however some may experience a prolonged recovery. There is no single physical test, blood test (or fluid biomarkers), or imaging test that can be used to determine when a person has fully recovered from concussion.A persons recovery may be influenced by a variety of factors that include age at the time of injury, intellectual abilities, family environment, social support system, occupational status, coping strategies, and financial circumstances. Factors such as a previous head injury or a coexisting medical condition have been found to predict longer-lasting post-concussion symptoms. Other factors that may lengthen recovery time after mTBI include psychological problems such as substance abuse or clinical depression, poor health before the injury or additional injuries sustained during it, and life stress. Longer periods of amnesia or loss of consciousness immediately after the injury may indicate longer recovery times from residual symptoms. Other strong factors include participation in a contact sport and body mass size.
Pediatric concussion
Most children recovery completely from concussion in less than four weeks, however 15–30% of youth may experience symptoms that last longer than a month.
People aged 65+ with concussion
Mild traumatic brain injury recovery time in people over age 65 may have increased complications due to elevated health concerns, or comorbidities. This often results in longer hospitalization duration, poorer cognitive outcomes, and higher mortality rates.
Repeat concussion
For unknown reasons, having had one concussion significantly increases a persons risk of having another. Having previously sustained a sports concussion has been found to be a strong factor increasing the likelihood of a concussion in the future. People who have had a concussion seem more susceptible to another one, particularly if the new injury occurs before symptoms from the previous concussion have completely gone away. It is also a negative process if smaller impacts cause the same symptom severity. Repeated concussions may increase a persons risk in later life for dementia, Parkinsons disease, and depression.
Post-concussion syndrome
In post-concussion syndrome, symptoms do not resolve for weeks, months, or years after a concussion, and may occasionally be permanent. About 10% to 20% of people have post-concussion syndrome for more than a month. Symptoms may include headaches, dizziness, fatigue, anxiety, memory and attention problems, sleep problems, and irritability. Rest, a previously recommended recovery technique, has limited effectiveness. A recommended treatment in both children and adults with symptoms beyond 4 weeks involves an active rehabilitation program with reintroduction of non-contact aerobic activity. Progressive physical exercise has been shown to reduce long-term post-concussive symptoms. Symptoms usually go away on their own within months but may last for years. The question of whether the syndrome is due to structural damage or other factors such as psychological ones, or a combination of these, has long been the subject of debate.
Cumulative effects
As of 1999, cumulative effects of concussions were poorly understood, especially the effects on children. The severity of concussions and their symptoms may worsen with successive injuries, even if a subsequent injury occurs months or years after an initial one. Symptoms may be more severe and changes in neurophysiology can occur with the third and subsequent concussions. As of 2006, studies had conflicting findings on whether athletes have longer recovery times after repeat concussions and whether cumulative effects such as impairment in cognition and memory occur.Cumulative effects may include chronic traumatic encephalopathy, psychiatric disorders and loss of long-term memory. For example, the risk of developing clinical depression has been found to be significantly greater for retired American football players with a history of three or more concussions than for those with no concussion history. An experience of three or more concussions is associated with a fivefold greater |
Concussion | chance of developing Alzheimers disease earlier and a threefold greater chance of developing memory deficits.Chronic traumatic encephalopathy, or "CTE", is an example of the cumulative damage that can occur as the result of multiple concussions or less severe blows to the head. The condition was previously referred to as "dementia pugilistica", or "punch drunk" syndrome, as it was first noted in boxers. The disease can lead to cognitive and physical disablities such as parkinsonism, speech and memory problems, slowed mental processing, tremor, depression, and inappropriate behavior. It shares features with Alzheimers disease.
Second-impact syndrome
Second-impact syndrome, in which the brain swells dangerously after a minor blow, may occur in very rare cases. The condition may develop in people who receive a second blow days or weeks after an initial concussion before its symptoms have gone away. No one is certain of the cause of this often fatal complication, but it is commonly thought that the swelling occurs because the brains arterioles lose the ability to regulate their diameter, causing a loss of control over cerebral blood flow. As the brain swells, intracranial pressure rapidly rises. The brain can herniate, and the brain stem can fail within five minutes. Except in boxing, all cases have occurred in athletes under age 20. Due to the very small number of documented cases, the diagnosis is controversial, and doubt exists about its validity. A 2010 Pediatrics review article stated that there is debate whether the brain swelling is due to two separate hits or to just one hit, but in either case, catastrophic football head injuries are three times more likely in high school athletes than in college athletes.
Epidemiology
Most cases of traumatic brain injury are concussions. A World Health Organization (WHO) study estimated that between 70 and 90% of head injuries that receive treatment are mild. However, due to under reporting and to the widely varying definitions of concussion and mTBI, it is difficult to estimate how common the condition is. Estimates of the incidence of concussion may be artificially low, for example, due to under reporting. At least 25% of people with mTBI fail to get assessed by a medical professional. The WHO group reviewed studies on the epidemiology of mTBI and found a hospital treatment rate of 1–3 per 1000 people, but since not all concussions are treated in hospitals, they estimated that the rate per year in the general population is over 6 per 1000 people.
Age
Young children have the highest concussion rate among all age groups. However, most people with a concussion are young adults. A Canadian study found that the yearly incidence of mTBI is lower in older age groups (graph at right). Studies suggest males develop mTBI at about twice the rate of their female counterparts. However, female athletes may be at a higher risk of sustaining a concussion than their male counterparts.
Sports
Up to five percent of sports injuries are concussions. The U.S. Centers for Disease Control and Prevention estimates that 300,000 sports-related concussions occur yearly in the U.S., but that number includes only athletes who lost consciousness. Since loss of consciousness is thought to occur in less than 10% of concussions, the CDC estimate is likely lower than the real number. Sports in which concussion is particularly common include American football, the rugby codes, MMA and boxing (a boxer aims to "knock out", i.e. give a mild traumatic brain injury to, the opponent). The injury is so common in the latter that several medical groups have called for a ban on the sport, including the American Academy of Neurology, the World Medical Association, and the medical associations of the UK, the US, Australia, and Canada.
Workplace
Concussions may also be common and occur in the workplace. According to the US Bureau of Labour Statistics, the most common causes of mTBI-related hospitalizations and deaths from the workplace are falls, force of heavy objects, and vehicular collisions. As a consequence, jobs in the construction, transportation, and natural resource industries (e.g. agriculture, fishing, mining) have more elevated mTBI incidence rates ranging from 10 to 20 cases per 100 000 workers. In particular, as vehicular collisions are the leading cause of workplace mTBI-related injuries, workers from the transportation sector often carry the most risk. Despite these findings, there still remain important gaps in data compilation on workplace-related mTBIs, which has raised questions about increased concussion surveillance and preventive measures in private industry.
History
The Hippocratic Corpus, a collection of medical works from ancient Greece, mentions concussion, later translated to commotio cerebri, and discusses loss of speech, hearing and sight that can result from "commotion of the brain". This idea of disruption of mental function by "shaking of the brain" remained the widely accepted understanding of concussion until the 19th century. In the 10th century, the Persian physician Muhammad ibn Zakarīya Rāzi was the first to write about concussion as distinct from other types of head injury. He may have been the first to use the term "cerebral concussion", and his definition of the condition, a transient loss of function with no physical damage, set the stage for the medical understanding of the condition for centuries.In the 13th century, the physician Lanfranc of Milans Chiurgia Magna described concussion as brain "commotion", also recognizing a difference between concussion and other types of traumatic brain injury (though many of his contemporaries did not), and discussing the transience of post-concussion symptoms as a result of temporary loss of function from the injury. In the 14th century, the surgeon Guy de Chauliac pointed out the relatively good prognosis of concussion as compared to more severe types of head trauma such as skull fractures and penetrating head trauma. In the 16th-century, the term "concussion" came into use, and symptoms such as confusion, lethargy, and memory problems were described. The 16th century physician Ambroise Paré used the term commotio cerebri, as well as "shaking of the brain", "commotion", and "concussion".
Until the 17th century, a concussion was usually described by its clinical features, but after the invention of the microscope, more physicians began exploring underlying physical and structural mechanisms. However, the prevailing view in the 17th century was that the injury did not result from physical damage, and this view continued to be widely held throughout the 18th century. The word "concussion" was used at the time to describe the state of unconsciousness and other functional problems that resulted from the impact, rather than a physiological condition. In 1839, Guillaume Dupuytren described brain contusions, which involve many small hemorrhages, as contusio cerebri and showed the difference between unconsciousness associated with damage to the brain parenchyma and that due to concussion, without such injury. In 1941, animal experiments showed that no macroscopic damage occurs in concussion.
Society and culture
Costs
Due to the lack of a consistent definition, the economic costs of mTBI are not known, but they are estimated to be very high. These high costs are due in part to the large percentage of hospital admissions for head injury that is due to mild head trauma, but indirect costs such as lost work time and early retirement account for the bulk of the costs. These direct and indirect costs cause the expense of mild brain trauma to rival that of moderate and severe head injuries.
Terminology
The terms mild brain injury, mild traumatic brain injury (mTBI), mild head injury (MHI), and concussion may be used interchangeably; although the term "concussion" is still used in sports literature as interchangeable with "MHI" or "mTBI", the general clinical medical literature uses "mTBI" instead, since a 2003 CDC report outlined it as an important strategy. In this article, "concussion" and "mTBI" are used interchangeably.
The term "concussion" is from Latin concutere, "to shake violently" or concussus, "action of striking together".
Research
Minocycline, lithium, and N-acetylcysteine show tentative success in animal models.Measurement of predictive visual tracking is being studied as a screening technique to identify mild traumatic brain injury. A head-mounted display unit with eye-tracking capability shows a moving object in a predictive pattern for the person to follow with their eyes. People without brain injury will be able to track the moving object with smooth pursuit eye movements and correct trajectory while it is hypothesized that those with mild traumatic brain injury cannot.
Grading systems
At least 41 systems measure the severity, or grade, of a mild head injury, and there is little agreement about which is best. In an effort to simplify, the 2nd International Conference on Concussion in Sport, meeting in Prague in 2004, decided that these systems should be abandoned in favor of a simple or complex classification. However, the 2008 meeting in Zurich abandoned the simple versus complex terminology, although the participants did agree to keep the concept that most (80–90%) concussions resolve in a short period (7–10 days) and although the recovery time frame may be longer in children and adolescents.In the past, the decision to allow athletes to return to participation was frequently based on the grade of concussion. However, current research and recommendations by professional organizations including the National Athletic Trainers Association recommend against such use of these grading systems. Currently, injured athletes are prohibited from returning to play before they are symptom-free during both rest and exertion and until results of the neuropsychological tests have returned to pre-injury levels.Three grading systems have been most widely followed: by Robert Cantu, the Colorado Medical Society, and the American Academy of Neurology. Each employs three grades, as summarized in the following table:
See also
Concussions in American football
Concussion in Rugby Union
Head injury criterion
Helmet removal (sports)
References
External links
"Facts about Concussion and Brain Injury and Where to Get Help" US Centers for Disease Control and Prevention
"Concussion in High School Sports" US Centers for Disease Control and Prevention
2018 CDC Guideline on MTBI in children |
Costochondritis | Costochondritis, also known as chest wall pain syndrome or costosternal syndrome, is a benign inflammation of the upper costochondral (rib to cartilage) and sternocostal (cartilage to sternum) joints. 90% of patients are affected in multiple ribs on a single side, typically at the 2nd to 5th ribs. Chest pain, the primary symptom of costochondritis, is considered a symptom of a medical emergency, making costochondritis a common presentation in the emergency department. One study found costochondritis was responsible for 30% of patients with chest pain in an emergency department setting.The exact cause of costochondritis is not known; however, it is believed to be due to repetitive minor trauma, called microtrauma. In rarer cases, costochondritis may develop as a result of an infectious factor. Diagnosis is predominantly clinical and based on physical examination, medical history, and ruling other conditions out. Costochondritis is often confused with Tietze syndrome, due to the similarity in location and symptoms, but with Tietze syndrome being differentiated by swelling of the costal cartilage.
Costochondritis is considered a self-limited condition that will resolve on its own. Treatment options usually involve rest, pain medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), ice, heat, and manual therapy. Cases with persistent discomfort may be managed with an intercostal nerve blocking injection utilizing a combination of corticosteroids and local anesthetic. The condition predominantly affects women over the age of 40, though some studies have found costochondritis to still be common among adolescents presenting with chest pain.: 388
Presentation
Costochondritis typically presents unilaterally (one side), which is typically the left side. It affects primarily the 2nd to 5th ribs at the sternocostal and costochondral joints. The most commonly reported symptom of costochondritis is chest pain that is often exacerbated by movement and deep breathing. Pain is typically widespread and reproducible with palpation of the anterior (front) chest at the affected joints.: 171 Pain from costochondritis can vary between individuals, and is typically described as a sharp, aching, dull, or pressure-like pain. It may also be accompanied by a radiating pain to the shoulder, arm, front neck, or scapula (shoulder blade).: 550 The condition usually onsets gradually following repetitive coughing, strenuous physical activity, or trauma to the chest.: 171 Symptoms of costochondritis may be recurrent and last weeks to months; however, refractory cases of the condition can persist to over a year.Costochondritis does not present with heat, erythema, or swelling of the affected area, the presence of which would indicate Tietze syndrome.: 171 Additionally, symptoms such as tachycardia, hypotension, radiating pain, shortness of breath, fever, nausea, or a productive cough are unrelated to costochondritis. These signs warrant further investigation for other, more serious causes of chest pain.
Cause
The exact etiology of costochondritis is unknown. Repetitive minor trauma is proposed to be a likely cause, with risk factors such as strenuous coughing, exercise, and lifting identified.Infection of the costosternal joint may cause costochondritis in rare cases. Most cases of infectious costochondritis are caused by Actinomyces, Staphylococcus aureus, Candida albicans, and Salmonella. In rare cases, Escherichia coli can be a cause of infectious costochondritis.
Pathogenesis
The pathogenesis underlying the development of costochondritis remains unclear. Proposed mechanisms of pain include neurogenic inflammation, muscular imbalances, neuropathy of the intercostal nerves, myofascial pain, or mechanical dysfunction.
Diagnosis
Costochondritis is predominately a clinical diagnosis only after life-threatening conditions have been ruled out, with physical examination and medical history being considered. Before a costochondritis diagnosis is made, other serious causes of chest pain are investigated. Further evaluation for cardiopulmonary or neoplastic causes is typically based on history, age, and risk factors, with diagnostic imaging and tests, completed to assess for life-threatening emergencies. If there is a suspicion of infection or a rheumatoid condition, laboratory work may be conducted.A physical exam will assess for tenderness or pain upon palpation, with an absence of heat, erythema, or swelling. The physical exam may assess if the pain is worsened with movements of the upper body or breathing, and may be reproduced upon using the crowing rooster maneuver, the hooking maneuver, or the horizontal flexion maneuver. Medical history is considered in diagnosing costochondritis, such as inquiry regarding any recent trauma, coughing, exercise, or activity involving the upper body that may have caused the symptoms.
Differential diagnosis
Cardiopulmonary
Life-threatening medical emergencies that may be associated with chest wall pain include acute coronary syndrome, aortic dissection, pneumothorax, or pulmonary embolism. Other cardiopulmonary causes of chest pain similar to that produced by costochondritis may include but are not limited to myocardial infarction, angina, and pericarditis. With costochondritis, the pain is typically worse with respiration, with movement, or within certain positions. Typically with other causes of chest pain, individuals will likely have radiating pain, shortness of breath, fever, a productive cough, nausea, dizziness, tachycardia, or hypotension.These conditions will be ruled out using tests such as X-rays, which will help assess for pneumonia, pneumothorax, lung mass, and other concerns. Other tests such as an electrocardiogram (ECG) can be performed to exclude infection, ischemia, and other conditions. A laboratory workup can rule out acute coronary syndrome, pulmonary embolism, and pneumonia. Costochondritis will yield normal results for these tests.
Musculoskeletal
There are several musculoskeletal conditions similar to costochondritis that are often confused. One such condition includes Tietze syndrome, which is often confused with costochondritis due to the similarity in location and symptomatology. Typically, costochondritis is a more common condition that is not associated with any swelling, affects multiple joints (usually of the 2nd to 5th ribs), and is usually seen in individuals older than 40 years of age. Tietze syndrome is a rarer condition that usually has visible swelling, commonly affecting a single joint (usually of the 2nd or 3rd rib), and typically seen in individuals younger than 40 years of age.A similar condition known as slipping rib syndrome is also associated with chest pain and inflammation of the costal cartilage. Unlike costochondritis, the pain associated with slipping rib syndrome is often felt in the lower ribs, abdomen, and back, commonly affecting the interchondral junctions of the false 8th to 10th ribs. Costochondritis is typically experienced within the sternocostal junctions of the true 2nd to 5th ribs.
Other musculoskeletal conditions that may cause chest pain similar to costochondritis includes but are not limited to, painful xiphoid syndrome, muscle strain, myofascial pain syndrome, thoracic disk herniation, and rib fracture.
Other
Rheumatologic conditions such as fibromyalgia, SAPHO syndrome, ankylosing spondylitis, rheumatoid arthritis, and psoriatic arthritis can cause symptoms similar to costochondritis.
Oncology-related conditions, namely neoplasms and myelomatous pleural effusion have been associated with chest pain.
Chest pain is occasionally experienced with respiratory-related conditions such as pleuritis, precordial catch syndrome, and pneumonia.
Psychogenic conditions such as anxiety disorders, panic disorders, and hyperventilation syndrome may cause chest pain.
Some gastroenterology conditions may be associated with costochondritis-like chest pain such as gastroesophageal reflux disease, and esophagitis.
Viral infections such as herpes zoster and Bornholm disease are seen as differential diagnoses for costochondritis due to chest pain being a reported symptom.
Vitamin D deficiency can be a differential diagnosis for costochondritis as it may cause chest pain.
Chest pain has also been reported following the use of cocaine, which can increase the risk of various cardiovascular conditions.
Treatment
Costochondritis is referred to as being self-limited, which is a condition in which will typically resolve on its own without treatment. Conservative methods are often the first method to treat the condition. If the condition is a result of trauma or over-use of the upper extremity, individuals will be told to rest and avoid activities. Pain relief medications (analgesics) such as acetaminophen, or the use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, or meloxicam may be suggested to relieve discomfort. If the pain is localized, occasionally creams and patches containing compounds such as capsaicin, NSAIDs, or lidocaine may be used. Heat or ice compresses may also be used for treatment.Outpatient follow-up may also be a form of treatment for costochondritis. Manual therapy methods such as myofascial release, muscle energy techniques, balanced ligamentous tension (BLT), rib mobilization techniques, and stretching exercises may be used. Additionally, educating the individual with costochondritis about their body mechanics, posture, and activity modification can be beneficial.In severe cases where symptoms do not resolve and last up to a year or longer, corticosteroids or local anesthetic injections may be considered.
Epidemiology
Costochondritis is a common condition that is responsible for approximately 13-36% of acute chest pain-related concerns from adults depending on the setting, with 14-39% for adolescents. It is most often seen in individuals who are older than 40 years of age and occurs more often in women than in men.
References
== External links == |
Temporomandibular joint dysfunction | Temporomandibular joint dysfunction (TMD, TMJD) is an umbrella term covering pain and dysfunction of the muscles of mastication (the muscles that move the jaw) and the temporomandibular joints (the joints which connect the mandible to the skull). The most important feature is pain, followed by restricted mandibular movement, and noises from the temporomandibular joints (TMJ) during jaw movement. Although TMD is not life-threatening, it can be detrimental to quality of life; this is because the symptoms can become chronic and difficult to manage.
In this article, the term temporomandibular disorder is taken to mean any disorder that affects the temporomandibular joint, and temporomandibular joint dysfunction (here also abbreviated to TMD) is taken to mean symptomatic (e.g. pain, limitation of movement, clicking) dysfunction of the temporomandibular joint. However, there is no single, globally accepted term or definition concerning this topic.
TMDs have a range of causes and often co-occur with a number of overlapping medical conditions, including headaches, fibromyalgia, back pain, and irritable bowel. However, these factors are poorly understood, and there is disagreement as to their relative importance. There are many treatments available, although there is a general lack of evidence for any treatment in TMD, and no widely accepted treatment protocol. Common treatments include provision of occlusal splints, psychosocial interventions like cognitive behavioral therapy, physical therapy, and pain medication or others. Most sources agree that no irreversible treatment should be carried out for TMD.About 20% to 30% of the adult population are affected to some degree. Usually people affected by TMD are between 20 and 40 years of age, and it is more common in females than males. TMD is the second most frequent cause of orofacial pain after dental pain (i.e. toothache).
Classification
TMD is considered by some to be one of the 4 major symptom complexes in chronic orofacial pain, along with burning mouth syndrome, atypical facial pain and atypical odontalgia. TMD has been considered as a type of musculoskeletal, neuromuscular, or rheumatological disorder. It has also been called a functional pain syndrome, and a psychogenic disorder. Others consider TMD a "central sensitivity syndrome", in reference to evidence that TMD might be caused by a centrally mediated sensitivity to pain. It is hypothesized that there is a great deal of similarity between TMD and other pain syndromes like fibromyalgia, irritable bowel syndrome, interstitial cystitis, headache, chronic lower back pain and chronic neck pain. These disorders have also been theorized to be caused by centrally mediated sensitivity to pain, and furthermore they often occur together.
Definitions and terminology
Frequently, TMD has been treated as a single syndrome, but the prevailing modern view is that TMD is a cluster of related disorders with many common features. Indeed, some have suggested that, in the future, the term TMD may be discarded as the different causes are fully identified and separated into different conditions. Sometimes, "temporomandibular joint dysfunction" is described as the most common form of temporomandibular disorder, whereas many other sources use the term temporomandibular disorder synonymously, or instead of the term temporomandibular joint dysfunction. In turn, the term temporomandibular disorder is defined as "musculoskeletal disorders affecting the temporomandibular joints and their associated musculature. It is a collective term which represents a diverse group of pathologies involving the temporomandibular joint, the muscles of mastication, or both". Another definition of temporomandibular disorders is "a group of conditions with similar signs and symptoms that affect the temporomandibular joints, the muscles of mastication, or both." Temporomandibular disorder is a term that creates confusion since it refers to a group of similarly symptomatic conditions, whilst many sources use the term temporomandibular disorders as a vague description, rather than a specific syndrome, and refer to any condition which may affect the temporomandibular joints (see table). The temporomandibular joint is susceptible to a huge range of diseases, some rarer than others, and there is no implication that all of these will cause any symptoms or limitation in function at all.The preferred terms in medical publications is to an extent influenced by geographic location. For example, in the United Kingdom, the term pain dysfunction syndrome is in common use. In the United States, the term temporomandibular disorder is generally favored. The American Academy of Orofacial Pain uses temporomandibular disorder, whilst the National Institute of Dental and Craniofacial Research uses temporomandibular joint disorder. A more complete list of synonyms for this topic is extensive, with some being more commonly used than others. In addition to those already mentioned, examples include temporomandibular joint pain dysfunction syndrome, temporomandibular pain dysfunction syndrome, temporomandibular joint syndrome, temporomandibular dysfunction syndrome, temporomandibular dysfunction, temporomandibular disorder, temporomandibular syndrome, facial arthromyalgia, myofacial pain dysfunction syndrome, craniomandibular dysfunction (CMD), myofacial pain dysfunction, masticatory myalgia, mandibular dysfunction, and Costens syndrome.
The lack of standardization in terms is not restricted to medical papers. Notable internationally recognized sources vary in both their preferred term, and their offered definition. For example:
"Temporomandibular Pain and Dysfunction Syndrome – Aching in the muscles of mastication, sometimes with an occasional brief severe pain on chewing, often associated with restricted jaw movement and clicking or popping sounds." (Classification of Chronic Pain, International Association for the Study of Pain).
"Headache or facial pain attributed to temporomandibular joint disorder." (International Classification of Headache Disorders 2nd edition (ICHD-2), International Headache Society).
"Temporomandibular joint-pain-dysfunction syndrome" listed in turn under "Temporomandibular joint disorders" (International Classification of Diseases 10th revision, World Health Organization).
By cause and symptoms
It has been suggested that TMD may develop following physical trauma, particularly whiplash injury, although the evidence for this is not conclusive. This type of TMD is sometimes termed "posttraumatic TMD" (pTMD) to distinguish it from TMD of unknown cause, sometimes termed "idiopathic TMD" (iTMD). Sometimes muscle-related (myogenous) TMD (also termed myogenous TMD, or TMD secondary to myofascial pain and dysfunction) is distinguished from joint-related TMD (also termed arthogenous TMD, or TMD secondary to true articular disease), based upon whether the muscles of mastication or the TMJs themselves are predominantly involved. This classification, which effectively divides TMD into 2 syndromes, is followed by the American Academy of Orofacial Pain. However, since most people with TMD could be placed into both of these groups, which makes a single diagnosis difficult when this classification is used. The Research Diagnostic Criteria (RDC/TMD) allows for multiple diagnoses in an attempt to overcome the problems with other classifications. RDC/TMD considers temporomandibular disorders in 2 axes; axis I is the physical aspects, and axis II involves assessment of psychological status, mandibular function and TMD-related psychosocial disability. Axis I is further divided into 3 general groups. Group I are muscle disorders, group II are disc displacements and group III are joint disorders, although it is common for people with TMD to fit into more than one of these groups.
By duration
Sometimes distinction is made between acute TMD, where symptoms last for less than 3 months, and chronic TMD, where symptoms last for more than 3 months. Not much is known about acute TMD since these individuals do not typically attend in secondary care (hospital).
Signs and symptoms
Signs and symptoms of temporomandibular joint disorder vary in their presentation. The symptoms will usually involve more than one of the various components of the masticatory system, muscles, nerves, tendons, ligaments, bones, connective tissue, or the teeth.The three classically described, cardinal signs and symptoms of TMD are:
Pain and tenderness on palpation in the muscles of mastication, or of the joint itself (preauricular pain – pain felt just in front of the ear). Pain is the defining feature of TMD and is usually aggravated by manipulation or function, such as when chewing, clenching, or yawning, and is often worse upon waking. The character of the pain is usually dull or aching, poorly localized, and intermittent, although it can sometimes be constant. The pain is more usually unilateral (located on one side) rather than bilateral. It is rarely severe.
Limited range of mandibular movement, which may cause difficulty eating or even talking. There may be locking of the jaw, or stiffness in the jaw muscles and the joints, especially present upon waking. There may also be incoordination, asymmetry or deviation of mandibular movement.
Noises from the joint during mandibular movement, which may be intermittent. Joint noises may be described as clicking, popping, or crepitus (grating).TMJ dysfunction is commonly associated with symptoms affecting cervical spine dysfunction and altered head and cervical spine posture.Other signs and symptoms have also been described, although these are less common and less significant than the cardinal signs and symptoms listed above. Examples include:
Headache (possibly), e.g. pain in the occipital region (the back of the head), or the forehead; or other types of facial pain including migraine, tension headache. or myofascial pain.
Pain elsewhere, such as the teeth or neck.
Diminished auditory acuity (hearing loss).
Tinnitus (occasionally).
Dizziness.
Sensation of malocclusion (feeling that the teeth do not meet together properly).
Causes
TMD is a symptom complex (i.e. a group of symptoms occurring together and characterizing a particular disease), which is thought to be caused by multiple, poorly understood factors, but the exact etiology is unknown. There are factors which appear to predispose to TMD (genetic, hormonal, anatomical), factors which may precipitate it (trauma, occlusal changes, parafunction), and also factors which may prolong it (stress and again parafunction). Overall, two hypotheses have dominated research into the causes of TMD, namely a psychosocial model and a theory of occlusal dysharmony. Interest in occlusal factors as a causative factor in TMD was especially widespread in the past, and the theory has since fallen out of favor and become controversial due to lack of evidence.
Disc displacement
In people with TMD, it has been shown that the lower head of lateral pterygoid contracts during mouth closing (when it should relax), and is often tender to palpation. To theorize upon this observation, some have suggested that due to a tear in the back of the joint capsule, the articular disc may be displaced forwards (anterior disc displacement), stopping the upper head of lateral pterygoid from acting to stabilize the disc as it would do normally. As a biologic compensatory mechanism, the lower head tries to fill this role, hence the abnormal muscle activity during mouth closure. There is some evidence that anterior disc displacement is present in a proportion of TMD cases. Anterior disc displacement with reduction refers to abnormal forward movement of the disc during opening which reduces upon closing. Anterior disc displacement without reduction refers to an abnormal forward, bunched-up position of the articular disc which does not reduce. In this latter scenario, the disc is not intermediary between the condyle and the articular fossa as it should be, and hence the articular surfaces of the bones themselves are exposed to a greater degree of wear (which may predispose to osteoarthritis in later life).
Degenerative joint disease
The general term "degenerative joint disease" refers to arthritis (both osteoarthritis and rheumatoid arthritis) and arthrosis. The term arthrosis may cause confusion since in the specialized TMD literature it means something slightly different from in the wider medical literature. In medicine generally, arthrosis can be a nonspecific term for a joint, any disease of a joint (or specifically degenerative joint disease), and is also used as a synonym for osteoarthritis. In the specialized literature that has evolved around TMD research, arthrosis is differentiated from arthritis by the presence of low and no inflammation respectively. Both are however equally degenerative. The TMJs are sometimes described as one of the most used joints in the body. Over time, either with normal use or with parafunctional use of the joint, wear and degeneration can occur, termed osteoarthritis. Rheumatoid arthritis, an autoimmune joint disease, can also affect the TMJs. Degenerative joint diseases may lead to defects in the shape of the tissues of the joint, limitation of function (e.g. restricted mandibular movements), and joint pain.
Psychosocial factors
Emotional stress (anxiety, depression, anger) may increase pain by causing autonomic, visceral and skeletal activity and by reduced inhibition via the descending pathways of the limbic system. The interactions of these biological systems have been described as a vicious "anxiety-pain-tension" cycle which is thought to be frequently involved in TMD. Put simply, stress and anxiety cause grinding of teeth and sustained muscular contraction in the face. This produces pain which causes further anxiety which in turn causes prolonged muscular spasm at trigger points, vasoconstriction, ischemia and release of pain mediators. The pain discourages use of the masticatory system (a similar phenomenon in other chronic pain conditions is termed "fear avoidance" behavior), which leads to reduced muscle flexibility, tone, strength and endurance. This manifests as limited mouth opening and a sensation that the teeth are not fitting properly.Persons with TMD have a higher prevalence of psychological disorders than people without TMD. People with TMD have been shown to have higher levels of anxiety, depression, somatization and sleep deprivation, and these could be considered important risk factors for the development of TMD. In the 6 months before the onset, 50–70% of people with TMD report experiencing stressful life events (e.g. involving work, money, health or relationship loss). It has been postulated that such events induce anxiety and cause increased jaw muscle activity. Muscular hyperactivity has also been shown in people with TMD whilst taking examinations or watching horror films.Others argue that a link between muscular hyperactivity and TMD has not been convincingly demonstrated, and that emotional distress may be more of a consequence of pain rather than a cause.
Bruxism
Bruxism is an oral parafunctional activity where there is excessive clenching and grinding of the teeth. It can occur during sleep or whilst awake. The cause of bruxism itself is not completely understood, but psychosocial factors appear to be implicated in awake bruxism and dopaminergic dysfunction and other central nervous system mechanisms may be involved in sleep bruxism. If TMD pain and limitation of mandibular movement are greatest upon waking, and then slowly resolve throughout the day, this may indicate sleep bruxism. Conversely, awake bruxism tends to cause symptoms that slowly get worse throughout the day, and there may be no pain at all upon waking.
The relationship of bruxism with TMD is debated. Many suggest that sleep bruxism can be a causative or contributory factor to pain symptoms in TMD. Indeed, the symptoms of TMD overlap with those of bruxism. Others suggest that there is no strong association between TMD and bruxism. A systematic review investigating the possible relationship concluded that when self-reported bruxism is used to diagnose bruxism, there is a positive association with TMD pain, and when more strict diagnostic criteria for bruxism are used, the association with TMD symptoms is much lower. Self-reported bruxism is probably a poor method of identifying bruxism. There are also very many people who grind their teeth and who do not develop TMD. Bruxism and other parafunctional activities may play a role in perpetuating symptoms in some cases.Other parafunctional habits such as pen chewing, lip and cheek biting (which may manifest as morsicatio buccarum or linea alba), are also suggested to contribute to the development of TMD. Other parafunctional activities might include jaw thrusting, excessive gum chewing, nail biting and eating very hard foods.
Trauma
Trauma, both micro and macrotrauma, is sometimes identified as a possible cause of TMD; however, the evidence for this is not strong. Prolonged mouth opening (hyper-extension) is also suggested as a possible cause. It is thought that this leads to microtrauma and subsequent muscular hyperactivity. This may occur during dental treatment, with oral intubation whilst under a general anesthetic, during singing or wind instrument practice (really these can be thought of as parafunctional activities). Damage may be incurred during violent yawning, laughing, road traffic accidents, sports injuries, interpersonal violence, or during dental treatment, (such as tooth extraction).It has been proposed that a link exists between whiplash injuries (sudden neck hyper-extension usually occurring in road traffic accidents), and the development of TMD. This has been termed "post-traumatic TMD", to separate it from "idiopathic TMD". Despite multiple studies having been performed over the years, the cumulative evidence has been described as conflicting, with moderate evidence that TMD can occasionally follow whiplash injury. The research that suggests a link appears to demonstrate a low to moderate incidence of TMD following whiplash injury, and that pTMD has a poorer response to treatment than TMD which has not developed in relation to trauma.
Occlusal factors
Occlusal factors as an etiologic factor in TMD is a controversial topic. Abnormalities of occlusion (problems with the bite) are often blamed for TMD but there is no evidence that these factors are involved. Occlusal abnormalities are incredibly common, and most people with occlusal abnormalities do not have TMD. Although occlusal features may affect observed electrical activity in masticatory muscles, there are no statistically significant differences in the number of occlusal abnormalities in people with TMD and in people without TMD. There is also no evidence for a causal link between orthodontic treatment and TMD. The modern, mainstream view is that the vast majority of people with TMD, occlusal factors are not related. Theories of occlusal factors in TMD are largely of historical interest. A causal relationship between occlusal factors and TMD was championed by Ramfjord in the 1960s. A small minority of dentists continue to prescribe occlusal adjustments in the belief that this will prevent or treat TMD despite the existence of systematic reviews of the subject which state that there is no evidence for such practices, and the vast majority of opinion being that no irreversible treatment should be carried out in TMD (see Occlusal adjustment).
Genetic factors
TMD does not obviously run in families like a genetic disease. It has been suggested that a genetic predisposition for developing TMD (and chronic pain syndromes generally) could exist. This has been postulated to be explained by variations of the gene which codes for the enzyme catechol-O-methyl transferase (COMT) which may produce 3 different phenotypes with regards pain sensitivity. COMT (together with monoamine oxidase) is involved in breaking down catecholamines (e.g. dopamine, epinephrine, and norepinephrine). The variation of the COMT gene which produces less of this enzyme is associated with a high sensitivity to pain. Females with this variation, are at 2–3 times greater risk of developing TMD than females without this variant. However this theory is controversial since there is conflicting evidence.
Hormonal factors
Since females are more often affected by TMD than males, the female sex hormone estrogen has been suggested to be involved. The results of one study suggested that the periods of highest pain in TMD can be correlated with rapid periods of change in the circulating estrogen level. Low estrogen was also correlated to higher pain. In the menstrual cycle, estrogen levels fluctuate rapidly during ovulation, and also rapidly increases just before menstruation and rapidly decreases during menstruation. Post-menopausal females who are treated with hormone replacement therapy are more likely to develop TMD, or may experience an exacerbation if they already had TMD. Several possible mechanisms by which estrogen might be involved in TMD symptoms have been proposed. Estrogen may play a role in modulating joint inflammation, nociceptive neurons in the trigeminal nerve, muscle reflexes to pain and μ-opioid receptors.
Possible associations
TMD has been suggested to be associated with other conditions or factors, with varying degrees of evidence and some more commonly than others. E.g. It has been shown that 75% of people with TMD could also be diagnosed with fibromyalgia, since they met the diagnostic criteria, and that conversely, 18% of people with fibromyalgia met diagnostic criteria for TMD. A possible link between many of these chronic pain conditions has been hypothesized to be due to shared pathophysiological mechanisms, and they have been collectively termed "central sensitivity syndromes", although other apparent associations cannot be explained in this manner. Recently a plethora of research has substantiated a causal relationship between TMD and Obstructive Sleep Apnea (OSA). Severe TMD restricts oral airway opening, and can result in a retrognathic posture that results in glossal blockage of the oropharynx as the tongue relaxes in sleep. This mechanism is exacerbated by alcohol consumption, as well as other chemicals that result in reduced myotonic status of the oropharynx.
Obstructive sleep apnea.
Headache.
Chronic neck pain.
Chronic back pain.
Systemic joint laxity.
Rheumatoid arthritis.
Irritable bowel syndrome.
Interstitial cystitis.
Regular scuba diving.
Pathophysiology
Anatomy and physiology
Temporomandibular joints
The temporomandibular joints are the dual articulation of the mandible with the skull. Each TMJ is classed as a "ginglymoarthrodial" joint since it is both a ginglymus (hinging joint) and an arthrodial (sliding) joint, and involves the condylar process of the mandible below, and the articular fossa (or glenoid fossa) of the temporal bone above. Between these articular surfaces is the articular disc (or meniscus), which is a biconcave, transversely oval disc composed of dense fibrous connective tissue. Each TMJ is covered by a fibrous capsule. There are tight fibers connecting the mandible to the disc, and loose fibers which connect the disc to the temporal bone, meaning there are in effect 2 joint capsules, creating an upper joint space and a lower joint space, with the articular disc in between. The synovial membrane of the TMJ lines the inside of the fibrous capsule apart from the articular surfaces and the disc. This membrane secretes synovial fluid, which is both a lubricant to fill the joint spaces, and a means to convey nutrients to the tissues inside the joint. Behind the disc is loose vascular tissue termed the "bilaminar region" which serves as a posterior attachment for the disc and also fills with blood to fill the space created when the head of the condyle translates down the articular eminence. Due to its concave shape, sometimes the articular disc is described as having an anterior band, intermediate zone and a posterior band. When the mouth is opened, the initial movement of the mandibular condyle is rotational, and this involves mainly the lower joint space, and when the mouth is opened further, the movement of the condyle is translational, involving mainly the upper joint space. This translation movement is achieved by the condylar head sliding down the articular eminence, which constitutes the front border of the articular fossa. The function of the articular eminence is to limit the forwards movement of the condyle. The ligament directly associated with the TMJ is the temporomandibular ligament, also termed the lateral ligament, which really is a thickening of the lateral aspect of the fibrous capsule. The stylomandibular ligament and the sphenomandibular ligament are not directly associated with the joint capsule. Together, these ligaments act to restrict the extreme movements of the joint.
Muscles of mastication
The muscles of mastication are paired on each side and work together to produce the movements of the mandible. The main muscles involved are the masseter, temporalis and medial and lateral pterygoid muscles.
They can be thought of in terms of the directions they move the mandible, with most being involved in more than one type of movement due to the variation in the orientation of muscle fibers within some of these muscles.
Protrusion – Lateral and medial pterygoid.
Retraction – Posterior fibers of temporalis (and the digastric and geniohyoid muscles to a lesser extent).
Elevation – Anterior and middle fibers of temporalis, the superficial and deep fibers of masseter and the medial pterygoid.
Lateral movements – Medial and lateral pterygoid (the ipsilateral temporalis and the pterygoid muscles of the contralateral side pull the mandible to the ipsilateral side).Each lateral pterygoid muscle is composed of 2 heads, the upper or superior head and the lower or inferior head. The lower head originates from the lateral surface of the lateral pterygoid plate and inserts at a depression on the neck of mandibular condyle, just below the articular surface, termed the pterygoid fovea. The upper head originates from the infratemporal surface and the infratemporal crest of the greater wing of the sphenoid bone. The upper head also inserts at the fovea, but a part may be attached directly to the joint capsule and to the anterior and medial borders of the articular disc. The 2 parts of lateral pterygoid have different actions. The lower head contracts during mouth opening, and the upper head contracts during mouth closing. The function of the lower head is to steady the articular disc as it moves back with the condyle into the articular fossa. It is relaxed during mouth closure.
Mechanisms of symptoms
Joint noises
Noises from the TMJs are a symptom of dysfunction of these joints. The sounds commonly produced by TMD are usually described as a "click" or a "pop" when a single sound is heard and as "crepitation" or "crepitus" when there are multiple, grating, rough sounds. Most joint sounds are due to internal derangement of the joint, which is instability or abnormal position of the articular disc. Clicking often accompanies either jaw opening or closing, and usually occurs towards the end of the movement. The noise indicates that the articular disc has suddenly moved to and from a temporarily displaced position (disk displacement with reduction) to allow completion of a phase of movement of the mandible. If the disc displaces and does not reduce (move back into position) this may be associated with locking. Clicking alone is not diagnostic of TMD since it is present in high proportion of the general population, mostly in people who have no pain. Crepitus often indicates arthritic changes in the joint, and may occur at any time during mandibular movement, especially lateral movements. Perforation of the disc may also cause crepitus. Due to the proximity of the TMJ to the ear canal, joint noises are perceived to be much louder to the individual than to others. Often people with TMD are surprised that what sounds to them like very loud noises cannot be heard at all by others next to them. However, it is occasionally possible for loud joint noises to be easily heard by others in some cases and this can be a source of embarrassment e.g. when eating in company.
Pain
Pain symptoms in TMD can be thought of as originating |
Temporomandibular joint dysfunction | from the joint (arthralgia), or from the muscles (myofascial), or both. There is a poor correlation between TMD pain severity and evidence of tissue pathology.Generally, degenerative joint changes are associated with greater pain.
Myofascial pain
Pain originating from the muscles of mastication as a result of abnormal muscular function or hyperactivity. The muscular pain is frequently, but not always, associated with daytime clenching or nocturnal bruxism.
Limitation of mandibular movement
The jaw deviates to the affected side during opening, and restricted mouth opening usually signifies that both TMJs are involved, but severe trismus rarely occurs. If the greatest reduction in movement occurs upon waking then this may indicate that there is concomitant sleep bruxism. In other cases the limitation in movement gets worse throughout the day.The jaw may lock entirely.Limitation of mandibular movement itself may lead to further problems involving the TMJs and the muscles of mastication. Changes in the synovial membrane may lead to a reduction in lubrication of the joint and contribute to degenerative joint changes. The muscles become weak, and fibrosis may occur. All these factors may lead to a further limitation of jaw movement and increase in pain.Degenerative joint disease, such as osteoarthritis or organic degeneration of the articular surfaces, recurrent fibrous or bony ankylosis, developmental abnormality, or pathologic lesions within the TMJ. Myofascial pain syndrome.
Referred TMD pain
Sometimes TMD pain can radiate or be referred from its cause (i.e. the TMJ or the muscles of mastication) and be felt as headaches, earache or toothache.Due to the proximity of the ear to the temporomandibular joint, TMJ pain can often be confused with ear pain. The pain may be referred in around half of all patients and experienced as otalgia (earache). Conversely, TMD is an important possible cause of secondary otalgia. Treatment of TMD may then significantly reduce symptoms of otalgia and tinnitus, as well as atypical facial pain. Despite some of these findings, some researchers question whether TMJD therapy can reduce symptoms in the ear, and there is currently an ongoing debate to settle the controversy.
Diagnosis
Pain is the most common reason for people with TMD to seek medical advice.
Joint noises may require auscultation with a stethoscope to detect. Clicks of the joint may also be palpated, over the joint itself in the preauricular region, or via a finger inserted in the external acoustic meatus, which lies directly behind the TMJ.
The differential diagnosis is with degenerative joint disease (e.g. osteoarthritis), rheumatoid arthritis, temporal arteritis, otitis media, parotitis, mandibular osteomyelitis, Eagle syndrome, trigeminal neuralgia, oromandibular dystonia, deafferentation pains, and psychogenic pain.
Diagnostic criteria
Various diagnostic systems have been described. Some consider the Research Diagnostic Criteria method the gold standard. Abbreviated to "RDC/TMD", this was first introduced in 1992 by Dworkin and LeResche in an attempt to classify temporomandibular disorders by etiology and apply universal standards for research into TMD. This method involves 2 diagnostic axes, namely axis I, the physical diagnosis, and axis II, the psychologic diagnosis. Axis I contains 3 different groups which can occur in combinations of 2 or all 3 groups, (see table).
McNeill 1997 described TMD diagnostic criteria as follows:
Pain in muscles of mastication, the TMJ, or the periauricular area (around the ear), which is usually made worse by manipulation or function.
Asymmetric mandibular movement with or without clicking.
Limitation of mandibular movements.
Pain present for a minimum of 3 months.The International Headache Societys diagnostic criteria for "headache or facial pain attributed to temporomandibular joint disorder" is similar to the above:
A. Recurrent pain in one or more regions of the head or face fulfilling criteria C and D
B. X-ray, MRI or bone scintigraphy demonstrate TMJ disorder
C. Evidence that pain can be attributed to the TMJ disorder, based on at least one of the following:
pain is precipitated by jaw movements or chewing of hard or tough food
reduced range of or irregular jaw opening
noise from one or both TMJs during jaw movements
tenderness of the joint capsule(s) of one or both TMJs
D. Headache resolves within 3 months, and does not recur, after successful treatment of the TMJ disorder
Medical imaging
The advantages brought about by diagnostic imaging mainly lie within diagnosing TMD of articular origin. Additional benefits of imaging the TMJ are as follows:
Assess the integrity of anatomical structures in suspicion of disorders
Staging the extent of any pathology
Monitoring and staging the progress of disease
Determining the effects of treatmentWhen clinical examination alone is unable to bring sufficient detail to ascertain the state of the TMJ, imaging methods can act as an adjuvant to clinical examination in the diagnosis of TMD.
Plain radiography
This method of imaging allows the visualisation of the joints mineralised areas, therefore excluding the cartilage and soft tissues. A disadvantage of plain radiography is that images are prone to superimposition from surrounding anatomical structures, thereby complicating radiographic interpretation. It was concluded that there is no evidence to support the use of plain radiography in the diagnosis of joint erosions and osteophytes. It is reasonable to conclude that plain film can only be used to diagnose extensive lesions.
Panoramic tomography
The distortion brought about by panoramic imaging decreases its overall reliability. Data concluded from a systematic review showed that only extensive erosions and large osteophytes can be detected by panoramic imaging.
Computerised tomography (CT)
Studies have shown that tomography of the TMJ provided supplementary information that supersedes what is obtainable from clinical examination alone. However, the issues lies in the fact that it is impossible to determine whether certain patient groups would benefit more or less from a radiographic examination.The main indications of CT and CBCT examinations are to assess the bony components of the TMJ, specifically the location and extent of any abnormalities present.The introduction of cone beam computed tomography (CBCT) imaging allowed a lower radiation dose to patients, in comparison to conventional CT. Hintze et al. compared CBCT and CT techniques and their ability to detect morphological TMJ changes. No significant difference was concluded in terms of their diagnostic accuracy.
Magnetic resonance imaging (MRI)
MRI is the optimal choice for the imaging of soft tissues surrounding the TMJ. It allows three-dimensional evaluation of the axial, coronal and sagittal plane. It is the gold standard method for assessing disc position and is sensitive for intra-articular degenerative alterations.Indications for MRI are pre-auricular pain, detection of joint clicking and crepitus, frequent incidents of subluxation and jaw dislocation, limited mouth opening with terminal stiffness, suspicion of neoplastic growth, and osteoarthritic symptoms. It is also useful for assessing the integrity of neural tissues, which may produce orofacial pain when compressed.MRI provides evaluation of pathology such as necrosis and oedema all without any exposure to ionizing radiation. However, there is a high cost associated with this method of imaging, due to the need for sophisticated facilities. Caution should be taken in patient selection, as MRI is contraindicated in those with claustrophobic tendencies, pacemakers and metallic heart valves, ferromagnetic foreign bodies and pregnant women.
Ultrasound
Where internal TMJ disorders are concerned, ultrasound (US) imaging can be a useful alternative in assessing the position of the disc While having significant diagnostic sensitivity, US has inadequate specificity when identifying osteoarthrosis. Moreover, it is not accurate enough for the diagnosis of cortical and articular disc morphology based on the findings done related to morphological alterations. However, with US, identification of effusion in individuals with inflammatory conditions associated with pain is possible and confirmed by MRIUS can be a useful alternative in initial investigation of internal TMJ dysfunctions especially in MRI contraindicated individuals despite its limitations. in addition to being less costly, US provides a quick and comfortable real-time imaging without exposing the individual to ionizing radiationUS is commonly assessed in the differential diagnosis of alterations of glandular and neighbouring structures, such as the TMJ and the masseter muscle. Symptoms of sialendenitis and sialothiasis cases can be confused with Eagle syndrome, TMD, myofascial and nerve pain, and other pain of the orofacial region.US assessment is also indicated where there is need to identify the correct position of the joint spaces for infiltrative procedures, arthrocentesis, and viscosupplementation. This is due to the fact that US provides a dynamic and real-time location of the component of the joints, while providing adequate lubrication and washing, which can be confirmed by the joint space increase post-treatment.
Management
TMD can be difficult to manage, and since the disorder transcends the boundaries between several health-care disciplines – in particular, dentistry and neurology, the treatment may often involve multiple approaches and be multidisciplinary. Most who are involved in treating and researching TMD now agree that any treatment carried out should not permanently alter the jaw or teeth, and should be reversible. To avoid permanent change, over-the-counter or prescription pain medications may be prescribed.
Psychosocial and behavioral interventions
Given the important role that psychosocial factors appear to play in TMD, psychosocial interventions could be viewed to be central to management of the condition. There is a suggestion that treatment of factors that modulate pain sensitivity such as mood disorders, anxiety and fatigue, may be important in the treatment of TMD, which often tends to attempt to address the pain directly.Cognitive Behavioral Therapy (CBT) has been used in TMD and has been shown to be efficacious by meta analyses.Hypnosis is suggested by some to be appropriate for TMD. Studies have suggested that it may even be more beneficial than occlusal splint therapy, and has comparable effects to relaxation techniques.Relaxation techniques include progressive muscle relaxation, yoga, and meditation. It has been suggested that TMD involves increased sensitivity to external stimuli leading to an increased sympathetic ("fight or flight") response with cardiovascular and respiratory alterations. Relaxation techniques cause reduced sympathetic activity, including muscle relaxation and reducing sensitivity to external stimuli, and provoke a general sense of well-being and reduced anxiety.
Devices
Occlusal splints (also termed bite plates or intra-oral appliances) are often used by dentists to treat TMD. They are usually made of acrylic and can be hard or soft. They can be designed to fit onto the upper teeth or the lower teeth. They may cover all the teeth in one arch (full coverage splint) or only some (partial coverage splint). Splints are also termed according to their intended mechanism, such as the anterior positioning splint or the stabilization splint. Although occlusal splints are generally considered a reversible treatment, sometimes partial coverage splints lead to pathologic tooth migration (changes in the position of teeth). Normally splints are only worn during sleep, and therefore probably do nothing for people who engage in parafunctional activities during wakefulness rather than during sleep. There is slightly more evidence for the use of occlusal splints in sleep bruxism than in TMD. A splint can also have a diagnostic role if it demonstrates excessive occlusal wear after a period of wearing it each night. This may confirm the presence of sleep bruxism if it was in doubt. Soft splints are occasionally reported to worsen discomfort related to TMD. Specific types of occlusal splint are discussed below.
A stabilization splint is a hard acrylic splint that forces the teeth to meet in an "ideal" relationship for the muscles of mastication and the TMJs. It is claimed that this technique reduces abnormal muscular activity and promotes "neuromuscular balance". A stabilization splint is only intended to be used for about 2–3 months. It is more complicated to construct than other types of splint since a face bow record is required and significantly more skill on the part of the dental technician. This kind of splint should be properly fitted to avoid exacerbating the problem and used for brief periods of time. The use of the splint should be discontinued if it is painful or increases existing pain. A systematic review of all the scientific studies investigating the efficacy of stabilization splints concluded the following:
"On the basis of our analysis we conclude that the literature seems to suggest that there is insufficient evidence either for or against the use of stabilization splint therapy over other active interventions for the treatment of TMD. However, there is weak evidence to suggest that the use of stabilization splints for the treatment of TMD may be beneficial for reducing pain severity, at rest and on palpation, when compared to no treatment".
Partial coverage splints are recommended by some experts, but they have the potential to cause unwanted tooth movements, which can occasionally be severe. The mechanism of this tooth movement is that the splint effectively holds some teeth out of contact and puts all the force of the bite onto the teeth which the splint covers. This can cause the covered teeth to be intruded, and those that are not covered to over-erupted. I.e. a partial coverage splint can act as a Dahl appliance. Examples of partial coverage splints include the NTI-TSS ("nociceptive trigeminal inhibitor tension suppression system"), which covers the upper front teeth only. Due to the risks involved with long term use, some discourage the use of any type of partial coverage splint.An anterior positioning splint is a splint that designed to promote an anteriorly displaced disc. It is rarely used. A 2010 review of all the scientific studies carried out to investigate the use of occlusal splints in TMD concluded:
"Hard stabilization appliances, when adjusted properly, have good evidence of modest efficacy in the treatment of TMD pain compared to non-occluding appliances and no treatment. Other types of appliances, including soft stabilization appliances, anterior positioning appliances, and anterior bite appliances, have some RCT evidence of efficacy in reducing TMD pain. However, the potential for adverse events with these appliances is higher and suggests the need for close monitoring in their use."
Ear canal inserts are also available, but no published peer-reviewed clinical trials have shown them to be useful.
Medication
Medication is the main method of managing pain in TMD, mostly because there is little if any evidence of the effectiveness of surgical or dental interventions. Many drugs have been used to treat TMD pain, such as analgesics (pain killers), benzodiazepines (e.g. clonazepam, prazepam, diazepam), anticonvulsants (e.g. gabapentin), muscle relaxants (e.g. cyclobenzaprine), and others. Analgesics that have been studied in TMD include non-steroidal anti-inflammatory drugs (e.g. piroxicam, diclofenac, naproxen) and cyclo-oxygenase-2 inhibitors (e.g. celecoxib).
Topical methyl salicylate and topical capsaicin have also been used.
Other drugs that have been described for use in TMD include glucosamine hydrochloride/chondroitin sulphate and propranolol. Low-doses of anti-muscarinic tricyclic antidepressants such as amitriptyline, or nortriptyline have also been described.Despite many randomized control trials being conducted on these commonly used medications for TMD a systematic review carried out in 2010 concluded that there was insufficient evidence to support or not to support the use of these drugs in TMD.In a subset of people with TMD who are not helped by either noninvasive and invasive treatments, long term use of opiate analgesics has been suggested, although these drugs carry a risk of drug dependence and other side effects. Examples include morphine, fentanyl, oxycodone, tramadol, hydrocodone, and methadone.Injections of local anesthetic, sometimes combined with steroids, into the muscles (e.g. the temoralis muscle or its tendon) are also sometimes used. Local anesthetics may provide temporary pain relief, and steroids inhibit pro-inflammatory cytokines. Steroids and other medications are sometimes injected directly into the joint (See Intra-articular injections).
Botulinum toxin solution ("Botox") is sometimes used to treat TMD. Injection of botox into the lateral pterygoid muscle has been investigated in multiple randomized control trials, and there is evidence that it is of benefit in TMD. It is theorized that spasm of lateral pterygoid causes anterior disc displacement. Botulinum toxin causes temporary muscular paralysis by inhibiting acetylcholine release at the neuromuscular junction. The effects usually last for a period of months before they wear off. Complications include the creation of a "fixed" expression due to diffusion of the solution and subsequent involvement of the muscles of facial expression, which lasts until the effects of the botox wear off.
Physiotherapy
Physiotherapy (physical therapy) is sometimes used as an adjuvant to other methods of treatment in TMD. There are many different approaches described, but exercises aiming to increase the range of mandibular movements are commonly involved. Jaw exercises aim to directly oppose the negative effects of disuse that may occur in TMD, due to pain discouraging people from moving their jaw. After initial instruction, people are able to perform a physical therapy regimen at home. The most simple method is by regular stretching within pain tolerance, using the thumb and a finger in a "scissor" maneuver. Gentle force is applied until pain of resistance is felt, and then the position is held for several seconds. Commercial devices have been developed to carry out this stretching exercise (e.g. the "Therabite" appliance). Over time, the amount of mouth opening possible without pain can be gradually increased. A baseline record of the distance at the start of physical therapy (e.g. the number of fingers that can be placed vertically between the upper and lower incisors), can chart any improvement over time.It has been suggested that massage therapy for TMD improves both the subjective and objective health status. "Friction massage" uses surface pressure to causes temporary ischemia and subsequent hyperemia in the muscles, and this is hypothesized to inactivate trigger points and disrupt small fibrous adhesions within the muscle that have formed following surgery or muscular shortening due to restricted movement.Occasionally physiotherapy for TMD may include the use of transcutaneous electrical nerve stimulation (TENS), which may override pain by stimulation of superficial nerve fibers and lead to pain reduction which extends after the time where the TENS is being actually being applied, possibly due to release of endorphins. Others recommend the use of ultrasound, theorized to produce tissue heating, alter blood flow and metabolic activity at a level that is deeper than possible with surface heat applications. There is tentative evidence that low level laser therapy may help with pain.The goals of a PT in reference to treatment of TMD should be to decrease pain, enable muscle relaxation, reduce muscular hyperactivity, and reestablish muscle function and joint mobility. PT treatment is non-invasive and includes self-care management in an environment to create patient responsibility for their own health.Therapeutic exercise and Manual Therapy (MT) are used to improve strength, coordination and mobility and to reduce pain. Treatment may focus on poor posture, cervical muscle spasms and treatment for referred cervical origin (pain referred from upper levels of the cervical spine) or orofacial pain. MT has been used to restore normal range of motion, promoting circulation, stimulate proprioception, break fibrous adhesions, stimulate synovial fluid production and reduce pain. Exercises and MT are safe and simple interventions that could potentially be beneficial for patients with TMD. No adverse events regarding exercise therapy and manual therapy have been reported.There have been positive results when using postural exercises and jaw exercises to treat both myogenous (muscular) and arthrogenous (articular) TMJ dysfunction. MT alone or in combination with exercises shows promising effects.It is necessary that trials be performed isolating the type of exercise and manual techniques to allow a better understanding of the effectiveness of this treatment. Additionally, details of exercise, dosage, and frequency as well as details on manual techniques should be reported to create reproducible results. High quality trails with larger sample sizes are needed.There is some evidence that some people who use nighttime biofeedback to reduce nighttime clenching experience a reduction in TMD.
Occlusal adjustment
This is the adjustment or reorganizing of the existing occlusion, carried out in the belief that this will redistribute forces evenly across the dental arches or achieve a more favorable position of the condyles in the fossae, which is purported to lessen tooth wear, bruxism and TMD, but this is controversial. These techniques are sometimes termed "occlusal rehabilitation" or "occlusal equilibration". At its simplest, an occlusal adjustment involves selective grinding (with a dental drill) of the enamel of the occlusal surfaces of teeth, with the aim of allowing the upper teeth to fit with the lower teeth in a more harmonious way. However, there is much disagreement between proponents of these techniques on most of the aspects involved, including the indications and the exact goals. Occlusal adjustment can also be very complex, involving orthodontics, restorative dentistry or even orthognathic surgery. Some have criticized these occlusal reorganizations as having no evidence base, and irreversibly damaging the dentition on top of the damage already caused by bruxism. A "middle ground" view of these techniques is that occlusal adjustment in most cases of TMD is neither desirable nor helpful as a first-line treatment, and furthermore, with few exceptions, any adjustments should be reversible. However, most dentists consider this unnecessary overtreatment, with no evidence of benefit. Specifically, orthodontics and orthognathic surgery are not considered by most to be appropriate treatments for TMD. A systematic review investigating all the scientific studies carried out on occlusal adjustments in TMD concluded the following:
"There is an absence of evidence of effectiveness for occlusal adjustment. Based on these data occlusal adjustment cannot be recommended for the treatment or prevention of TMD.
These conclusions were based largely on the fact that, despite many different scientific studies investigating this measure as a therapy, overall no statistically significant differences can be demonstrated between treatment with occlusal adjustment and treatment with placebo. The reviewers also stated that there are ethical implications if occlusal adjustment was found to be ineffective in preventing TMD.Orthodontic treatment, as described earlier, is sometimes listed as a possible predisposing factor in the development of TMD. On the other hand, orthodontic treatment is also often carried out in the belief that it may treat or prevent TMD. Another systematic review investigating the relationship between orthodontics and TMD concluded the following:
"There is no evidence to support or refute the use of orthodontic treatment for the treatment of TMD. In addition, there are no data which identify a link between active orthodontic intervention and the causation of TMD. Based on the lack of data, orthodontic treatment cannot be recommended for the treatment or prevention of TMD."
A common scenario where a newly placed dental restoration (e.g. a crown or a filling) is incorrectly contoured, and creates a premature contact in the bite. This may localize all the force of the bite onto one tooth, and cause inflammation of the periodontal ligament and reversible increase in tooth mobility. The tooth may become tender to bite on. Here, the "occlusal adjustment" has already taken place inadvertently, and the adjustment aims to return to the pre-existing occlusion. This should be distinguished from attempts to deliberately reorganize the native occlusion.
Surgery
Attempts in the last decade to develop surgical treatments based on MRI and CAT scans now receive less attention. These techniques are reserved for the most difficult cases where other therapeutic modalities have failed. The American Society of Maxillofacial Surgeons recommends a conservative/non-surgical approach first. Only 20% of patients need to proceed to surgery.
Examples of surgical procedures that are used in TMD, some more commonly than others, include arthrocentesis arthroscopy, meniscectomy, disc repositioning, condylotomy or joint replacement. Invasive surgical procedures in TMD may cause symptoms to worsen. Meniscectomy, also termed discectomy refers to surgical removal of the articular disc. This is rarely carried out in TMD, it may have some benefits for pain, but dysfunction may persist and overall it leads to degeneration or remodeling of the TMJ.
Alternative medicine
Acupuncture
Acupuncture is sometimes used for TMD. There is limited evidence that acupuncture is an effective symptomatic treatment for TMD. A short-term reduction in muscular pain of muscular origin can usually be observed after acupuncture in TMD, and this is more than is seen with placebo. There are no reported adverse events of acupuncture when used for TMD, and some suggest that acupuncture is best employed as an adjuvant to other treatments in TMD. However, some suggest that acupuncture may be no more effective than sham acupuncture, that many of the studies investigating acupuncture and TMD have significant risk of bias, and that the long term efficacy of acupuncture for TMD is unknown.
Chiropractic
Chiropractic adjustments (also termed manipulations or mobilizations) are sometimes used in the belief that this will treat TMD. Related conditions that are also claimed to be treatable by chiropractic include tension headaches and neck pain. Some sources suggest that there is some evidence of efficacy of chiropractic treatment in TMD, but the sources cited for these statements were case reports and a case series of only 9 participants. One review concluded "inconclusive evidence in a favorable direction regarding mobilization and massage for TMD". Overall, although there is general agreement that chiropractic may be of comparable benefit to other manual therapies for lower back pain, there is no credible evidence of efficacy in other conditions, including TMD. However, there is some evidence of possible adverse effects from cervical (neck) vertebral manipulation, which sometimes may be serious.
Prognosis
It has been suggested that the natural history of TMD is benign and self-limiting, with symptoms slowly improving and resolving over time. The prognosis is therefore good. However, the persistent pain symptoms, psychological discomfort, physical disability and functional limitations may detriment quality of life. It has been suggested that TMD does not cause permanent damage and does not progress to arthritis in later life,: 174–175 however degenerative disorders of the TMJ such as osteoarthritis are included within the spectrum of TMDs in some classifications.
Epidemiology
TMD mostly affects people in the 20 – 40 age group, and the average age is 33.9 years. People with TMD tend to be younger adults, who are otherwise healthy. Within the catchall umbrella of TMD, there are peaks for disc displacements at age 30, and for inflammatory-degenerative joint disorders at age 50.About 75% of the general population may have at least one abnormal sign associated with the TMJ (e.g. clicking), and about 33% have at least one symptom of TMD. However, only in 3.6–7% will this be of sufficient severity to trigger the individual to seek medical advice.For unknown reasons, females are more likely to be affected than males, in a ratio of about 2:1, although others report this ratio to be as high as 9:1. Females are more likely to request treatment for TMD, and their symptoms are less likely to resolve. Females with TMD are more likely to be nulliparous than females without TMD. It has also been reported that female caucasians are more likely to be affected by TMD, and at an earlier age, than female African Americans.According to the most recent analyses of epidemiologic data using the RDC/TMD diagnostic criteria, of all TMD cases, group I (muscle disorders) accounts for 45.3%, group II (disc displacements) 41.1%, and group III (joint disorders) 30.1% (individuals may have diagnoses from more than one group). Using the RDC/TMD criteria, TMD has a prevalence in the general population of 9.7% for group I, 11.4% for group |
Temporomandibular joint dysfunction | IIa, and 2.6% for group IIIa.
History
Temporomandibular disorders were described as early as ancient Egypt. An older name for the condition is "Costens syndrome", eponymously referring to James B. Costen. Costen was an otolaryngologist, and although he was not the first physician to describe TMD, he wrote extensively on the topic, starting in 1934, and was the first to approach the disorder in an integrated and systematic way. Costen hypothesized that malocclusion caused TMD, and placed emphasis on ear symptoms, such as tinnitus, otaglia, impaired hearing, and even dizziness. Specifically, Costen believed that the cause of TMD was mandibular over-closure, recommending a treatment revolving around building up the bite. The eponym "Costen syndrome" became commonly used shortly after his initial work, but in modern times it has been dropped, partially because occlusal factors are now thought to play little, if any, role in the development of TMD, and also because ear problems are now thought to be less associated with TMD. Other historically important terms that were used for TMD include "TMJ disease" or "TMJ syndrome", which are now rarely used.
== References == |
VIPoma | A VIPoma or vipoma () is a rare endocrine tumor that overproduces vasoactive intestinal peptide (thus VIP + -oma). The incidence is about 1 per 10,000,000 per year. VIPomas usually (about 90%) originate from the non-β islet cells of the pancreas. They are sometimes associated with multiple endocrine neoplasia type 1. Roughly 50–75% of VIPomas are malignant, but even when they are benign, they are problematic because they tend to cause a specific syndrome: the massive amounts of VIP cause a syndrome of profound and chronic watery diarrhea and resultant dehydration, hypokalemia, achlorhydria, acidosis, flushing and hypotension (from vasodilation), hypercalcemia, and hyperglycemia. This syndrome is called Verner–Morrison syndrome (VMS), WDHA syndrome (from watery diarrhea–hypokalemia–achlorhydria), or pancreatic cholera syndrome (PCS). The eponym reflects the physicians who first described the syndrome.
Symptoms and signs
The major clinical features are prolonged watery diarrhea (fasting stool volume > 750 to 1000 mL/day) and symptoms of hypokalemia and dehydration.
Half of the patients have relatively constant diarrhea while the rest have alternating periods of severe and moderate diarrhea.
One third have diarrhea < 1yr before diagnosis, but in 25%, diarrhea is present for 5 yr or more before diagnosis.
Lethargy, muscle weakness, nausea, vomiting and crampy abdominal pain are frequent symptoms.
Hypokalemia and impaired glucose tolerance occur in < 50% of patients. Achlorhydria is also a feature.
During attacks of diarrhea, flushing similar to the carcinoid syndrome occur rarely.
Diagnosis
Besides the clinical picture, fasting VIP plasma level may confirm the diagnosis, and CT scan and somatostatin receptor scintigraphy are used to localise the tumor, which is usually metastatic at presentation.Tests include:
Blood chemistry tests (basic or comprehensive metabolic panel)
CT scan of the abdomen
MRI of the abdomen
Stool examination for the cause of diarrhea and electrolyte levels
Vasoactive intestinal peptide (VIP) level in the blood
Treatment
The first goal of treatment is to correct dehydration. Fluids are often given through a vein (intravenous fluids) to replace fluids lost in diarrhea.
The next goal is to slow the diarrhea. Some medications can help control diarrhea. Octreotide, which is a human-made form of the natural hormone somatostatin, blocks the action of VIP.The best chance for a cure is surgery to remove the tumor. If the tumor has not spread to other organs, surgery can often cure the condition.For metastatic disease, peptide receptor radionuclide therapy (PRRT) can be highly effective. This treatment involves attaching a radionuclide (Lutetium-177 or Yttrium-90) to a somatostatin analogue (octreotate or octreotide). This is a novel way to deliver high doses of beta radiation to kill tumours. Some people seem to respond to a combination chemo called capecitabine and temozolomide but there is no report that it totally cured people of VIPoma.
Prognosis
Surgery can usually cure VIPomas. However, in one-third to one-half of patients, the tumor has spread by the time of diagnosis and cannot be cured.
References
Jensen RT, Norton JA. Endocrine tumors of the pancreas and gastrointestinal tract. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtrans Gastrointestinal and Liver Disease . 9th ed. Philadelphia, Pa: Saunders Elsevier; 2010:chap 32.
National Cancer Institute. Islet cell tumors (pancreatic) treatment PDQ. Updated October 31, 2008.
== External links == |
Folate deficiency | Folate deficiency, also known as vitamin B9 deficiency, is a low level of folate and derivatives in the body. Signs of folate deficiency are often subtle. A low number of red blood cells (anemia) is a late finding in folate deficiency and folate deficiency anemia is the term given for this medical condition. It is characterized by the appearance of large-sized, abnormal red blood cells (megaloblasts), which form when there are inadequate stores of folic acid within the body.
Signs and symptoms
Loss of appetite and weight loss can occur. Additional signs are weakness, sore tongue, headaches, heart palpitations, irritability, and behavioral disorders. In adults, anemia (macrocytic, megaloblastic anemia) can be a sign of advanced folate deficiency.
Women with folate deficiency who become pregnant are more likely to give birth to low birth weight premature infants, and infants with neural tube defects and even spina bifida. In infants and children, folate deficiency can lead to failure to thrive or slow growth rate, diarrhea, oral ulcers, megaloblastic anemia, neurological deterioration. An abnormally small head, irritability, developmental delay, seizures, blindness and cerebellar ataxia can also be observed.
Causes
A deficiency of folate can occur when the bodys need for folate is increased, when dietary intake or absorption of folate is inadequate, or when the body excretes (or loses) more folate than usual. Medications that interfere with the bodys ability to use folate may also increase the need for this vitamin. Some research indicates that exposure to ultraviolet light, including the use of tanning beds, can lead to a folate deficiency. The deficiency is more common in pregnant women, infants, children, and adolescents. It may also be due to poor diet or a consequence of alcoholism.Additionally, a defect in homocysteine methyltransferase or a deficiency of vitamin B12 may lead to a so-called "methyl-trap" of tetrahydrofolate (THF), in which THF is converted to a reservoir of methyl-THF which thereafter has no way of being metabolized, and serves as a sink of THF that causes a subsequent deficiency in folate. Thus, a deficiency in B12 can generate a large pool of methyl-THF that is unable to undergo reactions and will mimic folate deficiency.
Folate (pteroylmonoglutamate) is absorbed throughout the small intestine, though mainly in the jejunum. Important steps in the absorption are reduction of the polyglutamate chain by pteroylpolyglutamate hydrolase (gamma-glutamyl hydrolase) and then transport across the brush border membrane by the proton-coupled folate transporter (SLC46A1). Diffuse inflammatory or degenerative diseases of the small intestine, such as Crohn disease, celiac disease, chronic enteritis or the presence of an entero-enteric fistula may reduce absorption.
Situational
Some situations that increase the need for folate include:
bleeding
kidney dialysis
liver disease
malabsorption, including celiac disease and fructose malabsorption
pregnancy and lactation (breastfeeding)
tobacco smoking
alcohol consumption
Medication
Medications can interfere with folate metabolism, including:
anticonvulsant medications (such as phenytoin, primidone, carbamazepine or valproate)
metformin (sometimes prescribed to control blood sugar in type 2 diabetes)
methotrexate, an anti-cancer drug also used to control inflammation associated with Crohn disease, ulcerative colitis and rheumatoid arthritis.
5-fluorouracil
hydroxyurea
trimethoprim
sulfasalazine (used to control inflammation associated with Crohn disease, ulcerative colitis and rheumatoid arthritis)
triamterene (a diuretic)
birth control pills (also related to the duration use of birth control pills) may reduce serum folate levels but without inducing clinically significant folate deficiency.When methotrexate is prescribed, folic acid supplements are sometimes given with the methotrexate. The therapeutic effects of methotrexate are due to its inhibition of dihydrofolate reductase and thereby reduce the rate de novo purine and pyrimidine synthesis and cell division. Methotrexate inhibits cell division and is particularly toxic to fast dividing cells, such as rapidly dividing cancer cells and the progenitor cells of the immune system. Folate supplementation is beneficial in patients being treated with long-term, low-dose methotrexate for inflammatory conditions, such as rheumatoid arthritis (RA) or psoriasis, to avoid macrocytic anemia caused by folate deficiency. Folate is often also supplemented before some high dose chemotherapy treatments in an effort to protect healthy tissue. However, it may be counterproductive to take a folic acid supplement with methotrexate in cancer treatment.
Cerebral folate deficiency
Cerebral folate deficiency is when levels of 5-methyltetrahydrofolate are low in the brain as measured in the cerebral spinal fluid despite being normal in the blood. Symptoms typically appear at about five months of age. Without treatment there may be poor muscle tone, trouble with coordination, trouble talking, and seizures. The causes of cerebral folate deficiency include mutations of genes responsible for folate metabolism and transport. Mutations of the SLC46A1 gene that encodes the proton-coupled folate transporter (PCFT) result in CFD syndromes with both systemic folate deficiency and cerebral folate deficiency. Even when the systemic deficiency is corrected by folate, the cerebral deficiency remains and must be treated with folinic acid.
Pregnancy
Folate deficiency can occur during pregnancy as a result of the increasing number of cells of the growing fetus, decreased absorption and intake of folate, maternal hormones that mediate its metabolism, vascular circulation of maternal and fetal blood and an increasing amount of blood resulting in dilution. Sickle cell anemia and living in areas of malaria result in even higher folate needs for women who are pregnant. When supplemented with 450 micrograms of folic acid per day, the risk of developing birth defects, specifically neural tube defects, is decreased. Supplementation to prevent birth defects is most effective one month prior to and during the first twelve weeks of pregnancy. Utilization of folic acid supplementation before conception has shown to result in a decrease in neural tube defects by 70%.
Diagnosis
Folate deficiency is diagnosed with a blood test to measure the serum level of folate, measured as methyltetrahydrofolate (in practice, "folate" refers to all derivatives of folic acid, but methylhydrofolate is the quasi unique form of "folate" in the blood).
Homocysteine is elevated (5-MTHF is used to convert homocysteine to methionine) as in vitamin B12 deficiency, whereas methylmalonic acid is normal (elevated in vitamin B12 deficiency).
More specifically, according to a 2014 UK guideline,
A serum folate level of less than 7 nmol/L (3 μg/L) is indicative of folate deficiency;
Red blood cell folate testing is not routinely performed, since serum folate is sufficient in most cases, however, if there is a strong suspicion of folate deficiency despite a normal serum folate level, a red cell folate test may be performed.
Plasma total homocysteine is only measured in special circumstances. A level above 15 μmol/L could be indicative of a folate deficiency, but local reference ranges should be taken into account.
Prevention and treatment
Diet
Folate is acquired in the diet by the consumption of leafy green vegetables, legumes and organ meats. When cooking, use of steaming, a food steamer, or a microwave oven can help keep more folate content in the cooked foods.
Supplementation
Folic acid is a synthetic derivative of folate and is acquired by dietary supplementation. Multi-vitamin dietary supplements contain folic acid as well as other B vitamins. Non-prescription folic acid is available as a dietary supplement in some countries, and some countries require the fortification of wheat flour, corn meal or rice with folic acid with the intention of promoting public health through increasing blood folate levels in the population.
Fortification
After the discovery of the link between insufficient folic acid and neural tube defects, governments and health organizations worldwide made recommendations concerning folic acid supplementation for women intending to become pregnant. Because the neural tube closes in the first four weeks of gestation, often before many women even know they are pregnant, many countries in time decided to implement mandatory food fortification programs. A meta-analysis of global birth prevalence of spina bifida showed that when mandatory fortification was compared to countries with healthcare professionals advising women but no mandatory fortification program, there was a 30% reduction in live births with spina bifida, with some countries reported a greater than 50% reduction.Over 80 countries require folic acid fortification in some foods. Fortification of rice is common. The USDA has required the fortification of flour since 1998. Since then, Hispanics in the United States have seen the greatest reduction of neural tube defects. Canada has mandated folic acid fortification of flour since 1998 which has resulted in a 42% decrease in neural tube defects. Fortification of wheat and corn flour, milk and rice is required in Costa Rica which has led to a reduction of neural tube defects of as much as 60%.
Epidemiology
Folate deficiency is very rare in countries with folic acid fortification programs. Overall, the worldwide prevalence of anemia due to folic acid deficiency is very low. However, data on the prevalence of deficiency amongst specific high risk groups is lacking.
Research
Folate deficiency during gestation or infancy due to development by the fetus or infant of autoantibodies to the folate receptor might result in various developmental disorders.Studies suggest that insufficient folate and vitamin B12 status may contribute to major depressive disorder and that supplementation might be useful in this condition.
The role of vitamin B12 and folate in depression is due to their role in transmethylation reactions, which are crucial for the formation of neurotransmitters (e.g. serotonin, epinephrine, nicotinamides, purines, phospholipids). The proposed mechanism, is that low levels of folate or vitamin B12 can disrupt transmethylation reaction, leading to an accumulation of homocysteine (hyperhomocysteinemia) and to impaired metabolism of neurotransmitters (especially the hydroxylation of dopamine and serotonin from tyrosine and tryptophan), phospholipids, myelin, and receptors. High homocysteine levels in the blood can lead to vascular injuries by oxidative mechanisms which can contribute to cerebral dysfunction. All of these can lead to the development of various disorders, including depression.
References
== External links == |
Bruxism | Bruxism is excessive teeth grinding or jaw clenching. It is an oral parafunctional activity; i.e., it is unrelated to normal function such as eating or talking. Bruxism is a common behavior; reports of prevalence range from 8% to 31% in the general population. Several symptoms are commonly associated with bruxism, including hypersensitive teeth, aching jaw muscles, headaches, tooth wear, and damage to dental restorations (e.g. crowns and fillings). Symptoms may be minimal, without patient awareness of the condition. If nothing is done, after a while many teeth start wearing down until the whole tooth is gone.
There are two main types of bruxism: one occurs during sleep (nocturnal bruxism) and one during wakefulness (awake bruxism). Dental damage may be similar in both types, but the symptoms of sleep bruxism tend to be worse on waking and improve during the course of the day, and the symptoms of awake bruxism may not be present at all on waking, and then worsen over the day. The causes of bruxism are not completely understood, but probably involve multiple factors. Awake bruxism is more common in women, whereas men and women are affected in equal proportions by sleep bruxism. Awake bruxism is thought to have different causes from sleep bruxism. Several treatments are in use, although there is little evidence of robust efficacy for any particular treatment.
Epidemiology
There is a wide variation in reported epidemiologic data for bruxism, and this is largely due to differences in the definition, diagnosis and research methodologies of these studies. E.g. several studies use self-reported bruxism as a measure of bruxism, and since many people with bruxism are not aware of their habit, self-reported tooth grinding and clenching habits may be a poor measure of the true prevalence.The ICSD-R states that 85–90% of the general population grind their teeth to a degree at some point during their life, although only 5% will develop a clinical condition. Some studies have reported that awake bruxism affects females more commonly than males, while in sleep bruxism, males and females are affected equally.Children are reported to brux as commonly as adults. It is possible for sleep bruxism to occur as early as the first year of life – after the first teeth (deciduous incisors) erupt into the mouth, and the overall prevalence in children is about 14–20%. The ICSD-R states that sleep bruxism may occur in over 50% of normal infants. Often sleep bruxism develops during adolescence, and the prevalence in 18- to 29-year-olds is about 13%. The overall prevalence in adults is reported to be 8%, and people over the age of 60 are less likely to be affected, with the prevalence dropping to about 3% in this group.A 2013 systematic review of the epidemiologic reports of bruxism concluded a prevalence of about 22.1–31% for awake bruxism, 9.7–15.9% for sleep bruxism, and an overall prevalence of about 8–31.4% of bruxism generally. The review also concluded that overall, bruxism affects males and females equally, and affects elderly people less commonly.
Signs and symptoms
Most people who brux are unaware of the problem, either because there are no symptoms, or because the symptoms are not understood to be associated with a clenching and grinding problem. The symptoms of sleep bruxism are usually most intense immediately after waking, and then slowly abate, and the symptoms of a grinding habit which occurs mainly while awake tend to worsen through the day, and may not be present on waking. Bruxism may cause a variety of signs and symptoms, including:
A grinding or tapping noise during sleep, sometimes detected by a partner or a parent. This noise can be surprisingly loud and unpleasant, and can wake a sleeping partner. Noises are rarely associated with awake bruxism.
Other parafunctional activity which may occur together with bruxism: cheek biting (which may manifest as morsicatio buccarum and/or linea alba), and/or lip biting.
A burning sensation on the tongue (see: glossodynia), possibly related to a coexistent "tongue thrusting" parafunctional activity.
Indentations of the teeth in the tongue ("crenated tongue" or "scalloped tongue").
Hypertrophy of the muscles of mastication (increase in the size of the muscles that move the jaw), particularly the masseter muscle.
Tenderness, pain or fatigue of the muscles of mastication, which may get worse during chewing or other jaw movement.
Trismus (restricted mouth opening).
Pain or tenderness of the temporomandibular joints, which may manifest as preauricular pain (in front of the ear), or pain referred to the ear (otalgia).
Clicking of the temporomandibular joints.
Headaches, particularly pain in the temples, caused by muscle pain associated with the temporalis muscle.
Excessive tooth wear, particularly attrition, which flattens the occlusal (biting) surface, but also possibly other types of tooth wear such as abfraction, where notches form around the neck of the teeth at the gumline.
Tooth fractures, and repeated failure of dental restorations (fillings, crowns, etc.).
Hypersensitive teeth, (e.g. dental pain when drinking a cold liquid) caused by wearing away of the thickness of insulating layers of dentin and enamel around the dental pulp.
Inflammation of the periodontal ligament of teeth, which may make them sore to bite on, and possibly also a degree of loosening of the teeth.Bruxism is usually detected because of the effects of the process (most commonly tooth wear and pain), rather than the process itself. The large forces that can be generated during bruxism can have detrimental effects on the components of masticatory system, namely the teeth, the periodontium and the articulation of the mandible with the skull (the temporomandibular joints). The muscles of mastication that act to move the jaw can also be affected since they are being utilized over and above of normal function.
Pain
Most people with bruxism will experience no pain. The presence or degree of pain does not necessarily correlate with the severity of grinding or clenching. The pain in the muscles of mastication caused by bruxism can be likened to muscle pain after exercise. The pain may be felt over the angle of the jaw (masseter) or in the temple (temporalis), and may be described as a headache or an aching jaw. Most (but not all) bruxism includes clenching force provided by masseter and temporalis muscle groups; but some bruxers clench and grind front teeth only, which involves minimal action of the masseter and temporalis muscles. The temporomandibular joints themselves may also become painful, which is usually felt just in front of the ear, or inside the ear itself. Clicking of the jaw joint may also develop. The forces exerted on the teeth are more than the periodontal ligament is biologically designed to handle, and so inflammation may result. A tooth may become sore to bite on, and further, tooth wear may reduce the insulating width of enamel and dentin that protects the pulp of the tooth and result in hypersensitivity, e.g. to cold stimuli.
The relationship of bruxism with temporomandibular joint dysfunction (TMD, or temporomandibular pain dysfunction syndrome) is debated. Many suggest that sleep bruxism can be a causative or contributory factor to pain symptoms in TMD. Indeed, the symptoms of TMD overlap with those of bruxism. Others suggest that there is no strong association between TMD and bruxism. A systematic review investigating the possible relationship concluded that when self-reported bruxism is used to diagnose bruxism, there is a positive association with TMD pain, and when stricter diagnostic criteria for bruxism are used, the association with TMD symptoms is much lower. In severe, chronic cases, bruxism can lead to myofascial pain and arthritis of the temporomandibular joints.
Tooth wear
Many publications list tooth wear as a consequence of bruxism, but some report a lack of a positive relationship between tooth wear and bruxism. Tooth wear caused by tooth-to-tooth contact is termed attrition. This is the most usual type of tooth wear that occurs in bruxism, and affects the occlusal surface (the biting surface) of the teeth. The exact location and pattern of attrition depends on how the bruxism occurs, e.g., when the canines and incisors of the opposing arches are moved against each other laterally, by the action of the medial pterygoid muscles, this can lead to the wearing down of the incisal edges of the teeth. To grind the front teeth, most people need to posture their mandible forwards, unless there is an existing edge to edge, class III incisal relationship. People with bruxism may also grind their posterior teeth (back teeth), which wears down the cusps of the occlusal surface. Once tooth wear progresses through the enamel layer, the exposed dentin layer is softer and more vulnerable to wear and tooth decay. If enough of the tooth is worn away or decayed, the tooth will effectively be weakened, and may fracture under the increased forces that occur in bruxism.
Abfraction is another type of tooth wear that is postulated to occur with bruxism, although some still argue whether this type of tooth wear is a reality. Abfraction cavities are said to occur usually on the facial aspect of teeth, in the cervical region as V-shaped defects caused by flexing of the tooth under occlusal forces. It is argued that similar lesions can be caused by long-term forceful toothbrushing. However, the fact that the cavities are V-shaped does not suggest that the damage is caused by toothbrush abrasion, and that some abfraction cavities occur below the level of the gumline, i.e., in an area shielded from toothbrush abrasion, supports the validity of this mechanism of tooth wear. In addition to attrition, erosion is said to synergistically contribute to tooth wear in some bruxists, according to some sources.
Tooth mobility
The view that occlusal trauma (as may occur during bruxism) is a causative factor in gingivitis and periodontitis is not widely accepted. It is thought that the periodontal ligament may respond to increased occlusal (biting) forces by resorbing some of the bone of the alveolar crest, which may result in increased tooth mobility, however these changes are reversible if the occlusal force is reduced. Tooth movement that occurs during occlusal loading is sometimes termed fremitus. It is generally accepted that increased occlusal forces are able to increase the rate of progression of pre-existing periodontal disease (gum disease), however the main stay treatment is plaque control rather than elaborate occlusal adjustments. It is also generally accepted that periodontal disease is a far more common cause of tooth mobility and pathological tooth migration than any influence of bruxism, although bruxism may much less commonly be involved in both.
Causes
The muscles of mastication (the temporalis, masseter, medial and lateral pterygoid muscles) are paired on either side and work together to move the mandible, which hinges and slides around its dual articulation with the skull at the temporomandibular joints. Some of the muscles work to elevate the mandible (close the mouth), and others also are involved in lateral (side to side), protrusive or retractive movements. Mastication (chewing) is a complex neuromuscular activity that can be controlled either by subconscious processes or by conscious processes. In individuals without bruxism or other parafunctional activities, during wakefulness the jaw is generally at rest and the teeth are not in contact, except while speaking, swallowing or chewing. It is estimated that the teeth are in contact for less than 20 minutes per day, mostly during chewing and swallowing. Normally during sleep, the voluntary muscles are inactive due to physiologic motor paralysis, and the jaw is usually open.Some bruxism activity is rhythmic with bite force pulses of tenths of a second (like chewing), and some have longer bite force pulses of 1 to 30 seconds (clenching). Some individuals clench without significant lateral movements. Bruxism can also be regarded as a disorder of repetitive, unconscious contraction of muscles. This typically involves the masseter muscle and the anterior portion of the temporalis (the large outer muscles that clench), and the lateral pterygoids, relatively small bilateral muscles that act together to perform sideways grinding.
Multiple causes
The cause of bruxism is largely unknown, but it is generally accepted to have multiple possible causes. Bruxism is a parafunctional activity, but it is debated whether this represents a subconscious habit or is entirely involuntary. The relative importance of the various identified possible causative factors is also debated.
Awake bruxism is thought to be usually semivoluntary, and often associated with stress caused by family responsibilities or work pressures. Some suggest that in children, bruxism may occasionally represent a response to earache or teething. Awake bruxism usually involves clenching (sometimes the term "awake clenching" is used instead of awake bruxism), but also possibly grinding, and is often associated with other semivoluntary oral habits such as cheek biting, nail biting, chewing on a pen or pencil absent mindedly, or tongue thrusting (where the tongue is pushed against the front teeth forcefully).There is evidence that sleep bruxism is caused by mechanisms related to the central nervous system, involving sleep arousal and neurotransmitter abnormalities. Underlying these factors may be psychosocial factors including daytime stress which is disrupting peaceful sleep. Sleep bruxism is mainly characterized by "rhythmic masticatory muscle activity" (RMMA) at a frequency of about once per second, and also with occasional tooth grinding. It has been shown that the majority (86%) of sleep bruxism episodes occur during periods of sleep arousal. One study reported that sleep arousals which were experimentally induced with sensory stimulation in sleeping bruxists triggered episodes of sleep bruxism. Sleep arousals are a sudden change in the depth of the sleep stage, and may also be accompanied by increased heart rate, respiratory changes and muscular activity, such as leg movements. Initial reports have suggested that episodes of sleep bruxism may be accompanied by gastroesophageal reflux, decreased esophageal pH (acidity), swallowing, and decreased salivary flow. Another report suggested a link between episodes of sleep bruxism and a supine sleeping position (lying face up).Disturbance of the dopaminergic system in the central nervous system has also been suggested to be involved in the etiology of bruxism. Evidence for this comes from observations of the modifying effect of medications which alter dopamine release on bruxing activity, such as levodopa, amphetamines or nicotine. Nicotine stimulates release of dopamine, which is postulated to explain why bruxism is twice as common in smokers compared to non-smokers.
Historical focus
Historically, many believed that problems with the bite were the sole cause for bruxism. It was often claimed that a person would grind at the interfering area in a subconscious, instinctive attempt to wear this down and "self equiliberate" their occlusion. However, occlusal interferences are extremely common and usually do not cause any problems. It is unclear whether people with bruxism tend to notice problems with the bite because of their clenching and grinding habit, or whether these act as a causative factor in the development of the condition. In sleep bruxism especially, there is no evidence that removal of occlusal interferences has any impact on the condition. People with no teeth at all who wear dentures can still have bruxism, although dentures also often change the original bite. Most modern sources state that there is no relationship, or at most a minimal relationship, between bruxism and occlusal factors. The findings of one study, which used self-reported tooth grinding rather than clinical examination to detect bruxism, suggested that there may be more of a relationship between occlusal factors and bruxism in children. However, the role of occlusal factors in bruxism cannot be completely discounted due to insufficient evidence and problems with the design of studies. A minority of researchers continue to claim that various adjustments to the mechanics of the bite are capable of curing bruxism (see Occlusal adjustment/reorganization).
Psychosocial factors
Many studies have reported significant psychosocial risk factors for bruxism, particularly a stressful lifestyle, and this evidence is growing, but still not conclusive. Some consider emotional stress and anxiety to be the main triggering factors. It has been reported that persons with bruxism respond differently to depression, hostility and stress compared to people without bruxism. Stress has a stronger relationship to awake bruxism, but the role of stress in sleep bruxism is less clear, with some stating that there is no evidence for a relationship with sleep bruxism. However, children with sleep bruxism have been shown to have greater levels of anxiety than other children. People aged 50 with bruxism are more likely to be single and have a high level of education. Work-related stress and irregular work shifts may also be involved. Personality traits are also commonly discussed in publications concerning the causes of bruxism, e.g. aggressive, competitive or hyperactive personality types. Some suggest that suppressed anger or frustration can contribute to bruxism. Stressful periods such as examinations, family bereavement, marriage, divorce, or relocation have been suggested to intensify bruxism. Awake bruxism often occurs during periods of concentration such as while working at a computer, driving or reading. Animal studies have also suggested a link between bruxism and psychosocial factors. Rosales et al. electrically shocked lab rats, and then observed high levels of bruxism-like muscular activity in rats that were allowed to watch this treatment compared to rats that did not see it. They proposed that the rats who witnessed the electrical shocking of other rats were under emotional stress which may have caused the bruxism-like behavior.
Genetic factors
Some research suggests that there may be a degree of inherited susceptibility to develop sleep bruxism. 21–50% of people with sleep bruxism have a direct family member who had sleep bruxism during childhood, suggesting that there are genetic factors involved, although no genetic markers have yet been identified. Offspring of people who have sleep bruxism are more likely to also have sleep bruxism than children of people who do not have bruxism, or people with awake bruxism rather than sleep bruxism.
Medications
Certain stimulant drugs, including both prescribed and recreational drugs, are thought by some to cause the development of bruxism. However, others argue that there is insufficient evidence to draw such a conclusion. Examples may include dopamine agonists, dopamine antagonists, tricyclic antidepressants, selective serotonin reuptake inhibitors, alcohol, cocaine, and amphetamines (including those taken for medical reasons). In some reported cases where bruxism is thought to have been initiated by selective serotonin reuptake inhibitors, decreasing the dose resolved the side effect. Other sources state that reports of selective serotonin reuptake inhibitors causing bruxism are rare, or only occur with long-term use.Specific examples include levodopa (when used in the long term, as in Parkinsons disease), fluoxetine, metoclopramide, lithium, cocaine, venlafaxine, citalopram, fluvoxamine, methylenedioxyamphetamine (MDA), methylphenidate (used in attention deficit hyperactive disorder), and gamma-hydroxybutyric acid (GHB) and similar gamma-aminobutyric acid-inducing analogues such as phenibut. Bruxism can also be exacerbated by excessive consumption of caffeine, as in coffee, tea or chocolate. Bruxism has also been reported to occur commonly comorbid with drug addiction. Methylenedioxymethamphetamine (MDMA, ecstasy) has been reported to be associated with bruxism, which occurs immediately after taking the drug and for several days afterwards. Tooth wear in people who take ecstasy is also frequently much more severe than in people with bruxism not associated with ecstasy.
Occlusal factors
Occlusion is defined most simply as "contacts between teeth", and is the meeting of teeth during biting and chewing. The term does not imply any disease. Malocclusion is a medical term referring to less than ideal positioning of the upper teeth relative to the lower teeth, which can occur both when the upper jaw is ideally proportioned to the lower jaw, or where there is a discrepancy between the size of the upper jaw relative to the lower jaw. Malocclusion of some sort is so common that the concept of an "ideal occlusion" is called into question, and it can be considered "normal to be abnormal". An occlusal interference may refer to a problem which interferes with the normal path of the bite, and is usually used to describe a localized problem with the position or shape of a single tooth or group of teeth. A premature contact is one part of the bite meeting sooner than other parts, meaning that the rest of the teeth meet later or are held open, e.g., a new dental restoration on a tooth (e.g., a crown) which has a slightly different shape or position to the original tooth may contact too soon in the bite. A deflective contact/interference is an interference with the bite that changes the normal path of the bite. A common example of a deflective interference is an over-erupted upper wisdom tooth, often because the lower wisdom tooth has been removed or is impacted. In this example, when the jaws are brought together, the lower back teeth contact the prominent upper wisdom tooth before the other teeth, and the lower jaw has to move forward to allow the rest of the teeth to meet. The difference between a premature contact and a deflective interference is that the latter implies a dynamic abnormality in the bite.
Possible associations
Several associations between bruxism and other conditions, usually neurological or psychiatric disorders, have rarely been reported, with varying degrees of evidence (often in the form of case reports). Examples include:
Diagnosis
Early diagnosis of bruxism is advantageous, but difficult. Early diagnosis can prevent damage that may be incurred and the detrimental effect on quality of life. A diagnosis of bruxism is usually made clinically, and is mainly based on the persons history (e.g. reports of grinding noises) and the presence of typical signs and symptoms, including tooth mobility, tooth wear, masseteric hypertrophy, indentations on the tongue, hypersensitive teeth (which may be misdiagnosed as reversible pulpitis), pain in the muscles of mastication, and clicking or locking of the temporomandibular joints. Questionnaires can be used to screen for bruxism in both the clinical and research settings.For tooth grinders who live in same household with other people, diagnosis of grinding is straightforward: Housemates or family members would advise a bruxer of recurrent grinding. Grinders who live alone can likewise resort to a sound-activated tape recorder. To confirm the condition of clenching, on the other hand, bruxers may rely on such devices as the Bruxchecker, Bruxcore, or a beeswax-bearing biteplate.The Individual (personal) Tooth-Wear Index was developed to objectively quantify the degree of tooth wear in an individual, without being affected by the number of missing teeth. Bruxism is not the only cause of tooth wear. Another possible cause of tooth wear is acid erosion, which may occur in people who drink a lot of acidic liquids such as concentrated fruit juice, or in people who frequently vomit or regurgitate stomach acid, which itself can occur for various reasons. People also demonstrate a normal level of tooth wear, associated with normal function. The presence of tooth wear only indicates that it had occurred at some point in the past, and does not necessarily indicate that the loss of tooth substance is ongoing. People who clench and perform minimal grinding will also not show much tooth wear. Occlusal splints are usually employed as a treatment for bruxism, but they can also be of diagnostic use, e.g. to observe the presence or absence of wear on the splint after a certain period of wearing it at night.The most usual trigger in sleep bruxism that leads a person to seek medical or dental advice is being informed by sleeping partner of unpleasant grinding noises during sleep. The diagnosis of sleep bruxism is usually straightforward, and involves the exclusion of dental diseases, temporomandibular disorders, and the rhythmic jaw movements that occur with seizure disorders (e.g. epilepsy). This usually involves a dental examination, and possibly electroencephalography if a seizure disorder is suspected. Polysomnography shows increased masseter and temporalis muscular activity during sleep. Polysomnography may involve electroencephalography, electromyography, electrocardiography, air flow monitoring and audio–video recording. It may be useful to help exclude other sleep disorders; however, due to the expense of the use of a sleep lab, polysomnography is mostly of relevance to research rather than routine clinical diagnosis of bruxism.Tooth wear may be brought to the persons attention during routine dental examination. With awake bruxism, most people will often initially deny clenching and grinding because they are unaware of the habit. Often, the person may re-attend soon after the first visit and report that they have now become aware of such a habit.
Several devices have been developed that aim to objectively measure bruxism activity, either in terms of muscular activity or bite forces. They have been criticized for introducing a possible change in the bruxing habit, whether increasing or decreasing it, and are therefore poorly representative to the native bruxing activity. These are mostly of relevance to research, and are rarely used in the routine clinical diagnosis of bruxism. Examples include the "Bruxcore Bruxism-Monitoring Device" (BBMD, "Bruxcore Plate"), the "intra-splint force detector" (ISFD), and electromyographic devices to measure masseter or temporalis muscle activity (e.g. the "BiteStrip", and the "Grindcare").
ICSD-R diagnostic criteria
The ICSD-R listed diagnostic criteria for sleep bruxism. The minimal criteria include both of the following:
A. symptom of tooth-grinding or tooth-clenching during sleep, and
B. One or more of the following:
Abnormal tooth wear
Grinding sounds
Discomfort of the jaw musclesWith the following criteria supporting the diagnosis:
C. polysomnography shows both:
Activity of jaw muscles during sleep
No associated epileptic activity
D. No other medical or mental disorders (e.g., sleep-related epilepsy, which may cause abnormal movement during sleep).
E. The presence of other sleep disorders (e.g., obstructive sleep apnea syndrome).
Definition examples
Bruxism is derived from the Greek word βρύκειν (brykein) "to bite, or to gnash, grind the teeth". People with bruxism are called bruxists or bruxers and the verb itself is "to brux". There is no widely accepted definition of bruxism. Examples of definitions include:
"Bruxism is a repetitive jaw-muscle activity characterized by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible. Bruxism has two distinct circadian manifestations: it can occur during sleep (indicated as sleep bruxism) or during wakefulness (indicated as awake bruxism)."All forms of bruxism entail forceful contact between the biting surfaces of the upper and lower teeth. In grinding and tapping this contact involves movement of the mandible and unpleasant sounds which can often awaken sleeping partners and even people asleep in adjacent rooms. Clenching (or clamping), on the other hand, involves inaudible, sustained, forceful tooth contact unaccompanied by mandibular movements."A movement disorder of the masticatory system characterized by teeth-grinding and clenching during sleep as well as wakefulness."
"Non-functional contact |
Bruxism | of the mandibular and maxillary teeth resulting in clenching or tooth grinding due to repetitive, unconscious contraction of the masseter and temporalis muscles."
"Parafunctional grinding of teeth or an oral habit consisting of involuntary rhythmic or spasmodic non-functional gnashing, grinding or clenching of teeth in other than chewing movements of the mandible which may lead to occlusal trauma."
"Periodic repetitive clenching or rhythmic forceful grinding of the teeth."
Classification by temporal pattern
Bruxism can be subdivided into two types based upon when the parafunctional activity occurs – during sleep ("sleep bruxism"), or while awake ("awake bruxism"). This is the most widely used classification since sleep bruxism generally has different causes to awake bruxism, although the effects on the condition on the teeth may be the same. The treatment is also often dependent upon whether the bruxism happens during sleep or while awake, e.g., an occlusal splint worn during sleep in a person who only bruxes when awake will probably have no benefit. Some have even suggested that sleep bruxism is an entirely different disorder and is not associated with awake bruxism. Awake bruxism is sometimes abbreviated to AB, and is also termed "diurnal bruxism", DB, or "daytime bruxing". Sleep bruxism is sometimes abbreviated to SB, and is also termed "sleep-related bruxism", "nocturnal bruxism", or "nocturnal tooth grinding". According to the International Classification of Sleep Disorders revised edition (ICSD-R), the term "sleep bruxism" is the most appropriate since this type occurs during sleep specifically rather than being associated with a particular time of day, i.e., if a person with sleep bruxism were to sleep during the day and stay awake at night then the condition would not occur during the night but during the day. The ICDS-R defined sleep bruxism as "a stereotyped movement disorder characterized by grinding or clenching of the teeth during sleep", classifying it as a parasomnia. The second edition (ICSD-2) however reclassified bruxism to a "sleep related movement disorder" rather than a parasomnia.
Classification by cause
Alternatively, bruxism can be divided into primary bruxism (also termed "idiopathic bruxism"), where the disorder is not related to any other medical condition, or secondary bruxism, where the disorder is associated with other medical conditions. Secondary bruxism includes iatrogenic causes, such as the side effect of prescribed medications. Another source divides the causes of bruxism into three groups, namely central or pathophysiological factors, psychosocial factors and peripheral factors. The World Health Organizations International Classification of Diseases 10th revision does not have an entry called bruxism, instead listing "tooth grinding" under somatoform disorders. To describe bruxism as a purely somatoform disorder does not reflect the mainstream, modern view of this condition (see causes).
Classification by severity
The ICSD-R described three different severities of sleep bruxism, defining mild as occurring less than nightly, with no damage to teeth or psychosocial impairment; moderate as occurring nightly, with mild impairment of psychosocial functioning; and severe as occurring nightly, and with damage to the teeth, tempormandibular disorders and other physical injuries, and severe psychosocial impairment.
Classification by duration
The ICSD-R also described three different types of sleep bruxism according to the duration the condition is present, namely acute, which lasts for less than one week; subacute, which lasts for more than a week and less than one month; and chronic which lasts for over a month.
Management
Treatment for bruxism revolves around repairing the damage to teeth that has already occurred, and also often, via one or more of several available methods, attempting to prevent further damage and manage symptoms, but there is no widely accepted, best treatment. Since bruxism is not life-threatening, and there is little evidence of the efficacy of any treatment, it has been recommended that only conservative treatment which is reversible and that carries low risk of morbidity should be used. The main treatments that have been described in awake and sleep bruxism are described below.
Psychosocial interventions
Given the strong association between awake bruxism and psychosocial factors (the relationship between sleep bruxism and psychosocial factors being unclear), the role of psychosocial interventions could be argued to be central to the management. The most simple form of treatment is therefore reassurance that the condition does not represent a serious disease, which may act to alleviate contributing stress.Sleep hygiene education should be provided by the clinician, as well as a clear and short explanation of bruxism (definition, causes and treatment options). Relaxation and tension-reduction have not been found to reduce bruxism symptoms, but have given patients a sense of well-being. One study has reported less grinding and reduction of EMG activity after hypnotherapy.Other interventions include relaxation techniques, stress management, behavioural modification, habit reversal and hypnosis (self hypnosis or with a hypnotherapist). Cognitive behavioral therapy has been recommended by some for treatment of bruxism. In many cases awake bruxism can be reduced by using reminder techniques. Combined with a protocol sheet this can also help to evaluate in which situations bruxism is most prevalent.
Medication
Many different medications have been used to treat bruxism, including benzodiazepines, anticonvulsants, beta blockers, dopamine agents, antidepressants, muscle relaxants, and others. However, there is little, if any, evidence for their respective and comparative efficacies with each other and when compared to a placebo. A multiyear systematic review to investigate the evidence for drug treatments in sleep bruxism published in 2014 (Pharmacotherapy for Sleep Bruxism. Macedo, et al.) found "insufficient evidence on the effectiveness of pharmacotherapy for the treatment of sleep bruxism."Specific drugs that have been studied in sleep bruxism are clonazepam, levodopa, amitriptyline, bromocriptine, pergolide, clonidine, propranolol, and l-tryptophan, with some showing no effect and others appear to have promising initial results; however, it has been suggested that further safety testing is required before any evidence-based clinical recommendations can be made. When bruxism is related to the use of selective serotonin reuptake inhibitors in depression, adding buspirone has been reported to resolve the side effect. Tricyclic antidepressants have also been suggested to be preferable to selective serotonin reuptake inhibitors in people with bruxism, and may help with the pain.
Prevention of dental damage
Bruxism can cause significant tooth wear if it is severe, and sometimes dental restorations (crowns, fillings etc.) are damaged or lost, sometimes repeatedly. Most dentists therefore prefer to keep dental treatment in people with bruxism very simple and only carry it out when essential, since any dental work is likely to fail in the long term. Dental implants, dental ceramics such as Emax crowns and complex bridgework for example are relatively contraindicated in bruxists. In the case of crowns, the strength of the restoration becomes more important, sometimes at the cost of aesthetic considerations. E.g. a full coverage gold crown, which has a degree of flexibility and also involves less removal (and therefore less weakening) of the underlying natural tooth may be more appropriate than other types of crown which are primarily designed for esthetics rather than durability. Porcelain veneers on the incisors are particularly vulnerable to damage, and sometimes a crown can be perforated by occlusal wear.
Occlusal splints (also termed dental guards) are commonly prescribed, mainly by dentists and dental specialists, as a treatment for bruxism. Proponents of their use claim many benefits, however when the evidence is critically examined in systematic reviews of the topic, it is reported that there is insufficient evidence to show that occlusal splints are effective for sleep bruxism as well as bruxism overrall.
Furthermore, occlusal splints are probably ineffective for awake bruxism, since they tend to be worn only during sleep. However, occlusal splints may be of some benefit in reducing the tooth wear that may accompany bruxism, but by mechanically protecting the teeth rather than reducing the bruxing activity itself. In a minority of cases, sleep bruxism may be made worse by an occlusal splint. Some patients will periodically return with splints with holes worn through them, either because the bruxism is aggravated, or unaffected by the presence of the splint. When tooth-to-tooth contact is possible through the holes in a splint, it is offering no protection against tooth wear and needs to be replaced.
Occlusal splints are divided into partial or full-coverage splints according to whether they fit over some or all of the teeth. They are typically made of plastic (e.g. acrylic) and can be hard or soft. A lower appliance can be worn alone, or in combination with an upper appliance. Usually lower splints are better tolerated in people with a sensitive gag reflex. Another problem with wearing a splint can be stimulation of salivary flow, and for this reason some advise to start wearing the splint about 30 mins before going to bed so this does not lead to difficulty falling asleep. As an added measure for hypersensitive teeth in bruxism, desensitizing toothpastes (e.g. containing strontium chloride) can be applied initially inside the splint so the material is in contact with the teeth all night. This can be continued until there is only a normal level of sensitivity from the teeth, although it should be remembered that sensitivity to thermal stimuli is also a symptom of pulpitis, and may indicate the presence of tooth decay rather than merely hypersensitive teeth.
Splints may also reduce muscle strain by allowing the upper and lower jaw to move easily with respect to each other. Treatment goals include: constraining the bruxing pattern to avoid damage to the temporomandibular joints; stabilizing the occlusion by minimizing gradual changes to the positions of the teeth, preventing tooth damage and revealing the extent and patterns of bruxism through examination of the markings on the splints surface. A dental guard is typically worn during every nights sleep on a long-term basis. However, a meta-analysis of occlusal splints (dental guards) used for this purpose concluded "There is not enough evidence to state that the occlusal splint is effective for treating sleep bruxism."A repositioning splint is designed to change the patients occlusion, or bite. The efficacy of such devices is debated. Some writers propose that irreversible complications can result from the long-term use of mouthguards and repositioning splints. Random controlled trials with these type devices generally show no benefit over other therapies.
Another partial splint is the nociceptive trigeminal inhibition tension suppression system (NTI-TSS) dental guard. This splint snaps onto the front teeth only. It is theorized to prevent tissue damages primarily by reducing the bite force from attempts to close the jaw normally into a forward twisting of the lower front teeth. The intent is for the brain to interpret the nerve sensations as undesirable, automatically and subconsciously reducing clenching force. However, there may be potential for the NTI-TSS device to act as a Dahl appliance, holding the posterior teeth out of occlusion and leading to their over-eruption, deranging the occlusion (i.e. it may cause the teeth to move position). This is far more likely if the appliance is worn for excessive periods of time, which is why NTI type appliances are designed for night time use only, and ongoing follow-ups are recommended.A mandibular advancement device (normally used for treatment of obstructive sleep apnea) may reduce sleep bruxism, although its use may be associated with discomfort.
Botulinum toxin
Botulinum neurotoxin (BoNT) is used as a treatment for bruxism. A 2020 overview of systematic reviews found that botulinum toxin type A (BTX-A) showed a significant pain and sleep bruxism frequency reduction when compared to placebo or conventional treatment (behavioral therapy, occlusal splints, and drugs), after 6 and 12 months.Botulinum toxin causes muscle paralysis/atrophy by inhibition of acetylcholine release at neuromuscular junctions. BoNT injections are used in bruxism on the theory that a dilute solution of the toxin will partially paralyze the muscles and lessen their ability to forcefully clench and grind the jaw, while aiming to retain enough muscular function to enable normal activities such as talking and eating. This treatment typically involves five or six injections into the masseter and temporalis muscles, and less often into the lateral pterygoids (given the possible risk of decreasing the ability to swallow) taking a few minutes per side. The effects may be noticeable by the next day, and they may last for about three months. Occasionally, adverse effects may occur, such as bruising, but this is quite rare. The dose of toxin used depends upon the person, and a higher dose may be needed in people with stronger muscles of mastication. With the temporary and partial muscle paralysis, atrophy of disuse may occur, meaning that the future required dose may be smaller or the length of time the effects last may be increased.
Biofeedback
Biofeedback is a process or device that allows an individual to become aware of, and alter physiological activity with the aim of improving health. Although the evidence of biofeedback has not been tested for awake bruxism, there is recent evidence for the efficacy of biofeedback in the management of nocturnal bruxism in small control groups. Electromyographic monitoring devices of the associated muscle groups tied with automatic alerting during periods of clenching and grinding have been prescribed for awake bruxism. Dental appliances with capsules that break and release a taste stimulus when enough force is applied have also been described in sleep bruxism, which would wake the person from sleep in an attempt to prevent bruxism episodes. "Large scale, double-blind, experiment confirming the effectiveness of this approach have yet to be carried out."
Occlusal adjustment/reorganization
As an alternative to simply reactively repairing the damage to teeth and conforming to the existing occlusal scheme, occasionally some dentists will attempt to reorganize the occlusion in the belief that this may redistribute the forces and reduce the amount of damage inflicted on the dentition. Sometimes termed "occlusal rehabilitation" or "occlusal equilibration", this can be a complex procedure, and there is much disagreement between proponents of these techniques on most of the aspects involved, including the indications and the goals. It may involve orthodontics, restorative dentistry or even orthognathic surgery. Some have criticized these occlusal reorganizations as having no evidence base, and irreversibly damaging the dentition on top of the damage already caused by bruxism.
History
Two thousand years ago, Shuowen Jiezi by Xu Shen documented the definition of Chinese character "齘" (bruxism) as "the clenching of teeth" (齒相切也).
In 610, Zhubing Yuanhou Lun by Chao Yuanfang documented the definition of bruxism (齘齒) as "the clenching of teeth during sleep" and explained that it was caused by Qi deficiency and blood stasis. In 978, Taiping Shenghuifang by Wang Huaiyin gave a similar explanation and three prescriptions for treatment."La bruxomanie" (a French term, translates to bruxomania) was suggested by Marie Pietkiewics in 1907. In 1931, Frohman first coined the term bruxism. Occasionally recent medical publications will use the word bruxomania with bruxism, to denote specifically bruxism that occurs while awake; however, this term can be considered historical and the modern equivalent would be awake bruxism or diurnal bruxism. It has been shown that the type of research into bruxism has changed over time. Overall between 1966 and 2007, most of the research published was focused on occlusal adjustments and oral splints. Behavioral approaches in research declined from over 60% of publications in the period 1966–86 to about 10% in the period 1997–2007. In the 1960s, a periodontist named Sigurd Peder Ramfjord championed the theory that occlusal factors were responsible for bruxism. Generations of dentists were educated by this ideology in the prominent textbook on occlusion of the time, however therapy centered around removal of occlusal interference remained unsatisfactory. The belief among dentists that occlusion and bruxism are strongly related is still widespread, however the majority of researchers now disfavor malocclusion as the main etiologic factor in favor of a more multifactorial, biopsychosocial model of bruxism.
Society and culture
Clenching the teeth is generally displayed by humans and other animals as a display of anger, hostility or frustration. It is thought that in humans, clenching the teeth may be an evolutionary instinct to display teeth as weapons, thereby threatening a rival or a predator. The phrase "to grit ones teeth" is the grinding or clenching of the teeth in anger, or to accept a difficult or unpleasant situation and deal with it in a determined way.In the Bible there are several references to "gnashing of teeth" in both the Old Testament, and the New Testament, where the phrase "wailing and gnashing of teeth" describes what an imaginary king believes is occurring in the darkness outside of his sons wedding venue.(Matthew 22:13)
A Chinese proverb has linked Bruxism with psychosocial factors. "If a boy clenches, he hates his family for not being prosperous; if a girl clenches, she hates her mother for not being dead."(男孩咬牙，恨家不起；女孩咬牙，恨妈不死。)In David Lynchs 1977 film Eraserhead, Henry Spencers partner ("Mary X") is shown tossing and turning in her sleep, and snapping her jaws together violently and noisily, depicting sleep bruxism. In Stephen Kings 1988 novel "The Tommyknockers", the sister of central character Bobbi Anderson also had bruxism. In the 2000 film Requiem for a Dream, the character of Sara Goldfarb (Ellen Burstyn) begins taking an amphetamine-based diet pill and develops bruxism. In the 2005 film Beowulf & Grendel, a modern reworking of the Anglo-Saxon poem Beowulf, Selma the witch tells Beowulf that the trolls name Grendel means "grinder of teeth", stating that "he has bad dreams", a possible allusion to Grendel traumatically witnessing the death of his father as a child, at the hands of King Hrothgar. The Geats (the warriors who hunt the troll) alternatively translate the name as "grinder of mens bones" to demonize their prey. In George R. R. Martins A Song of Ice and Fire series, King Stannis Baratheon grinds his teeth regularly, so loudly it can be heard "half a castle away".
In rave culture, recreational use of ecstasy is often reported to cause bruxism. Among people who have taken ecstasy, while dancing it is common to use pacifiers, lollipops or chewing gum in an attempt to reduce the damage to the teeth and to prevent jaw pain. Bruxism is thought to be one of the contributing factors in "meth mouth", a condition potentially associated with long term methamphetamine use.
References
== External links == |
Dengue fever | Dengue fever is a mosquito-borne tropical disease caused by the dengue virus. Symptoms typically begin three to fourteen days after infection. These may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic skin itching and skin rash. Recovery generally takes two to seven days. In a small proportion of cases, the disease develops into a more severe dengue hemorrhagic fever, resulting in bleeding, low levels of blood platelets and blood plasma leakage, or into dengue shock syndrome, where dangerously low blood pressure occurs.Dengue is spread by several species of female mosquitoes of the Aedes genus, principally Aedes aegypti. The virus has five serotypes; infection with one type usually gives lifelong immunity to that type, but only short-term immunity to the others. Subsequent infection with a different type increases the risk of severe complications. A number of tests are available to confirm the diagnosis including detecting antibodies to the virus or its RNA.A vaccine for dengue fever has been approved and is commercially available in a number of countries. As of 2018, the vaccine is only recommended in individuals who have been previously infected, or in populations with a high rate of prior infection by age nine. Other methods of prevention include reducing mosquito habitat and limiting exposure to bites. This may be done by getting rid of or covering standing water and wearing clothing that covers much of the body. Treatment of acute dengue is supportive and includes giving fluid either by mouth or intravenously for mild or moderate disease. For more severe cases, blood transfusion may be required. Paracetamol (acetaminophen) is recommended instead of nonsteroidal anti-inflammatory drugs (NSAIDs) for fever reduction and pain relief in dengue due to an increased risk of bleeding from NSAID use.The earliest descriptions of an outbreak date from 1779. Its viral cause and spread were understood by the early 20th century. Dengue has become a global problem since the Second World War and is common in more than 120 countries, mainly in Southeast Asia, South Asia and South America. About 390 million people are infected per year, about half a million require hospital admission, and approximately 40,000 die. In 2019, a significant increase in the number of cases was seen. Apart from eliminating the mosquitos, work is ongoing for medication targeted directly at the virus. It is classified as a neglected tropical disease.
Signs and symptoms
Typically, people infected with dengue virus are asymptomatic (80%) or have only mild symptoms such as an uncomplicated fever. Others have more severe illness (5%), and in a small proportion it is life-threatening. The incubation period (time between exposure and onset of symptoms) ranges from 3 to 14 days, but most often it is 4 to 7 days. Therefore, travelers returning from endemic areas are unlikely to have dengue fever if symptoms start more than 14 days after arriving home. Children often experience symptoms similar to those of the common cold and gastroenteritis (vomiting and diarrhea) and have a greater risk of severe complications, though initial symptoms are generally mild but include high fever.
Clinical course
The characteristic symptoms of dengue are sudden-onset fever, headache (typically located behind the eyes), muscle and joint pains, and a rash. An alternative name for dengue, "breakbone fever", comes from the associated muscle and joint pains. The course of infection is divided into three phases: febrile, critical, and recovery.The febrile phase involves high fever, potentially over 40 °C (104 °F), and is associated with generalized pain and a headache; this usually lasts two to seven days. Nausea and vomiting may also occur. A rash occurs in 50–80% of those with symptoms in the first or second day of symptoms as flushed skin, or later in the course of illness (days 4–7), as a measles-like rash. A rash described as "islands of white in a sea of red" has also been observed. Some petechiae (small red spots that do not disappear when the skin is pressed, which are caused by broken capillaries) can appear at this point, as may some mild bleeding from the mucous membranes of the mouth and nose. The fever itself is classically biphasic or saddleback in nature, breaking and then returning for one or two days.In some people, the disease proceeds to a critical phase as fever resolves. During this period, there is leakage of plasma from the blood vessels, typically lasting one to two days. This may result in fluid accumulation in the chest and abdominal cavity as well as depletion of fluid from the circulation and decreased blood supply to vital organs. There may also be organ dysfunction and severe bleeding, typically from the gastrointestinal tract. Shock (dengue shock syndrome) and hemorrhage (dengue hemorrhagic fever) occur in less than 5% of all cases of dengue; however, those who have previously been infected with other serotypes of dengue virus ("secondary infection") are at an increased risk. This critical phase, while rare, occurs relatively more commonly in children and young adults.The recovery phase occurs next, with resorption of the leaked fluid into the bloodstream. This usually lasts two to three days. The improvement is often striking, and can be accompanied with severe itching and a slow heart rate. Another rash may occur with either a maculopapular or a vasculitic appearance, which is followed by peeling of the skin. During this stage, a fluid overload state may occur; if it affects the brain, it may cause a reduced level of consciousness or seizures. A feeling of fatigue may last for weeks in adults.
Associated problems
Dengue can occasionally affect several other body systems, either in isolation or along with the classic dengue symptoms. A decreased level of consciousness occurs in 0.5–6% of severe cases, which is attributable either to inflammation of the brain by the virus or indirectly as a result of impairment of vital organs, for example, the liver.Other neurological disorders have been reported in the context of dengue, such as transverse myelitis and Guillain–Barré syndrome. Infection of the heart and acute liver failure are among the rarer complications.A pregnant woman who develops dengue is at higher risk of miscarriage, low birth weight birth, and premature birth.
Cause
Virology
Dengue fever virus (DENV) is an RNA virus of the family Flaviviridae; genus Flavivirus. Other members of the same genus include yellow fever virus, West Nile virus, Zika virus, St. Louis encephalitis virus, Japanese encephalitis virus, tick-borne encephalitis virus, Kyasanur forest disease virus, and Omsk hemorrhagic fever virus. Most are transmitted by arthropods (mosquitos or ticks), and are therefore also referred to as arboviruses (arthropod-borne viruses).The dengue virus genome (genetic material) contains about 11,000 nucleotide bases, which code for the three different types of protein molecules (C, prM and E) that form the virus particle and seven other non-structural protein molecules (NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5) that are found in infected host cells only and are required for replication of the virus. There are five strains of the virus, called serotypes, of which the first four are referred to as DENV-1, DENV-2, DENV-3 and DENV-4. The fifth type was announced in 2013. The distinctions between the serotypes are based on their antigenicity.
Transmission
Dengue virus is primarily transmitted by Aedes mosquitos, particularly A. aegypti. These mosquitos usually live between the latitudes of 35° North and 35° South below an elevation of 1,000 metres (3,300 ft). They typically bite during the early morning and in the evening, but they may bite and thus spread infection at any time of day. Other Aedes species that transmit the disease include A. albopictus, A. polynesiensis and A. scutellaris. Humans are the primary host of the virus, but it also circulates in nonhuman primates. An infection can be acquired via a single bite. A female mosquito that takes a blood meal from a person infected with dengue fever, during the initial 2- to 10-day febrile period, becomes itself infected with the virus in the cells lining its gut. About 8–10 days later, the virus spreads to other tissues including the mosquitos salivary glands and is subsequently released into its saliva. The virus seems to have no detrimental effect on the mosquito, which remains infected for life. Aedes aegypti is particularly involved, as it prefers to lay its eggs in artificial water containers, to live in close proximity to humans, and to feed on people rather than other vertebrates.Dengue can also be transmitted via infected blood products and through organ donation. In countries such as Singapore, where dengue is endemic, the risk is estimated to be between 1.6 and 6 per 10,000 transfusions. Vertical transmission (from mother to child) during pregnancy or at birth has been reported. Other person-to-person modes of transmission, including sexual transmission, have also been reported, but are very unusual. The genetic variation in dengue viruses is region specific, suggestive that establishment into new territories is relatively infrequent, despite dengue emerging in new regions in recent decades.
Predisposition
Severe disease is more common in babies and young children, and in contrast to many other infections, it is more common in children who are relatively well nourished. Other risk factors for severe disease include female sex, high body mass index, and viral load. While each serotype can cause the full spectrum of disease, virus strain is a risk factor. Infection with one serotype is thought to produce lifelong immunity to that type, but only short-term protection against the other three. The risk of severe disease from secondary infection increases if someone previously exposed to serotype DENV-1 contracts serotype DENV-2 or DENV-3, or if someone previously exposed to DENV-3 acquires DENV-2. Dengue can be life-threatening in people with chronic diseases such as diabetes and asthma.Polymorphisms (normal variations) in particular genes have been linked with an increased risk of severe dengue complications. Examples include the genes coding for the proteins TNFα, mannan-binding lectin, CTLA4, TGFβ, DC-SIGN, PLCE1, and particular forms of human leukocyte antigen from gene variations of HLA-B. A common genetic abnormality, especially in Africans, known as glucose-6-phosphate dehydrogenase deficiency, appears to increase the risk. Polymorphisms in the genes for the vitamin D receptor and FcγR seem to offer protection against severe disease in secondary dengue infection.
Mechanism
When a mosquito carrying dengue virus bites a person, the virus enters the skin together with the mosquitos saliva. It binds to and enters white blood cells, and reproduces inside the cells while they move throughout the body. The white blood cells respond by producing several signaling proteins, such as cytokines and interferons, which are responsible for many of the symptoms, such as the fever, the flu-like symptoms, and the severe pains. In severe infection, the virus production inside the body is greatly increased, and many more organs (such as the liver and the bone marrow) can be affected. Fluid from the bloodstream leaks through the wall of small blood vessels into body cavities due to capillary permeability. As a result, less blood circulates in the blood vessels, and the blood pressure becomes so low that it cannot supply sufficient blood to vital organs. Furthermore, dysfunction of the bone marrow due to infection of the stromal cells leads to reduced numbers of platelets, which are necessary for effective blood clotting; this increases the risk of bleeding, the other major complication of dengue fever.
Viral replication
Once inside the skin, dengue virus binds to Langerhans cells (a population of dendritic cells in the skin that identifies pathogens). The virus enters the cells through binding between viral proteins and membrane proteins on the Langerhans cell, specifically, the C-type lectins called DC-SIGN, mannose receptor and CLEC5A. DC-SIGN, a non-specific receptor for foreign material on dendritic cells, seems to be the main point of entry. The dendritic cell moves to the nearest lymph node. Meanwhile, the virus genome is translated in membrane-bound vesicles on the cells endoplasmic reticulum, where the cells protein synthesis apparatus produces new viral proteins that replicate the viral RNA and begin to form viral particles. Immature virus particles are transported to the Golgi apparatus, the part of the cell where some of the proteins receive necessary sugar chains (glycoproteins). The now mature new viruses are released by exocytosis. They are then able to enter other white blood cells, such as monocytes and macrophages.The initial reaction of infected cells is to produce interferon, a cytokine that raises many defenses against viral infection through the innate immune system by augmenting the production of a large group of proteins mediated by the JAK-STAT pathway. Some serotypes of the dengue virus appear to have mechanisms to slow down this process. Interferon also activates the adaptive immune system, which leads to the generation of antibodies against the virus as well as T cells that directly attack any cell infected with the virus. Various antibodies are generated; some bind closely to the viral proteins and target them for phagocytosis (ingestion by specialized cells and destruction), but some bind the virus less well and appear instead to deliver the virus into a part of the phagocytes where it is not destroyed but can replicate further.
Severe disease
It is not entirely clear why secondary infection with a different strain of dengue virus places people at risk of dengue hemorrhagic fever and dengue shock syndrome. The most widely accepted hypothesis is that of antibody-dependent enhancement (ADE). The exact mechanism behind ADE is unclear. It may be caused by poor binding of non-neutralizing antibodies and delivery into the wrong compartment of white blood cells that have ingested the virus for destruction. There is a suspicion that ADE is not the only mechanism underlying severe dengue-related complications, and various lines of research have implied a role for T cells and soluble factors such as cytokines and the complement system.Severe disease is marked by the problems of capillary permeability (an allowance of fluid and protein normally contained within the blood to pass) and disordered blood clotting. These changes appear associated with a disordered state of the endothelial glycocalyx, which acts as a molecular filter of blood components. Leaky capillaries (and the critical phase) are thought to be caused by an immune system response. Other processes of interest include infected cells that become necrotic—which affect both coagulation and fibrinolysis (the opposing systems of blood clotting and clot degradation)—and low platelets in the blood, also a factor in normal clotting.
Diagnosis
The diagnosis of dengue is typically made clinically, on the basis of reported symptoms and physical examination; this applies especially in endemic areas. However, early disease can be difficult to differentiate from other viral infections. A probable diagnosis is based on the findings of fever plus two of the following: nausea and vomiting, rash, generalized pains, low white blood cell count, positive tourniquet test, or any warning sign (see table) in someone who lives in an endemic area. Warning signs typically occur before the onset of severe dengue. The tourniquet test, which is particularly useful in settings where no laboratory investigations are readily available, involves the application of a blood pressure cuff at between the diastolic and systolic pressure for five minutes, followed by the counting of any petechial hemorrhages; a higher number makes a diagnosis of dengue more likely with the cut off being more than 10 to 20 per 1 inch2 (6.25 cm2).The diagnosis should be considered in anyone who develops a fever within two weeks of being in the tropics or subtropics. It can be difficult to distinguish dengue fever and chikungunya, a similar viral infection that shares many symptoms and occurs in similar parts of the world to dengue. Often, investigations are performed to exclude other conditions that cause similar symptoms, such as malaria, leptospirosis, viral hemorrhagic fever, typhoid fever, meningococcal disease, measles, and influenza. Zika fever also has similar symptoms as dengue.The earliest change detectable on laboratory investigations is a low white blood cell count, which may then be followed by low platelets and metabolic acidosis. A moderately elevated level of aminotransferase (AST and ALT) from the liver is commonly associated with low platelets and white blood cells. In severe disease, plasma leakage results in hemoconcentration (as indicated by a rising hematocrit) and hypoalbuminemia. Pleural effusions or ascites can be detected by physical examination when large, but the demonstration of fluid on ultrasound may assist in the early identification of dengue shock syndrome. The use of ultrasound is limited by lack of availability in many settings. Dengue shock syndrome is present if pulse pressure drops to ≤ 20 mm Hg along with peripheral vascular collapse. Peripheral vascular collapse is determined in children via delayed capillary refill, rapid heart rate, or cold extremities. While warning signs are an important aspect for early detection of potential serious disease, the evidence for any specific clinical or laboratory marker is weak.
Classification
The World Health Organizations 2009 classification divides dengue fever into two groups: uncomplicated and severe. This replaces the 1997 WHO classification, which needed to be simplified as it had been found to be too restrictive, though the older classification is still widely used including by the World Health Organizations Regional Office for Southeast Asia as of 2011. Severe dengue is defined as that associated with severe bleeding, severe organ dysfunction, or severe plasma leakage while all other cases are uncomplicated. The 1997 classification divided dengue into an undifferentiated fever, dengue fever, and dengue hemorrhagic fever. Dengue hemorrhagic fever was subdivided further into grades I–IV. Grade I is the presence only of easy bruising or a positive tourniquet test in someone with fever, grade II is the presence of spontaneous bleeding into the skin and elsewhere, grade III is the clinical evidence of shock, and grade IV is shock so severe that blood pressure and pulse cannot be detected. Grades III and IV are referred to as "dengue shock syndrome".
Laboratory tests
The diagnosis of dengue fever may be confirmed by microbiological laboratory testing. This can be done by virus isolation in cell cultures, nucleic acid detection by PCR, viral antigen detection (such as for NS1) or specific antibodies (serology). Virus isolation and nucleic acid detection are more accurate than antigen detection, but these tests are not widely available due to their greater cost. Detection of NS1 during the febrile phase of a primary infection may be greater than 90% sensitive however is only 60–80% in subsequent infections. All tests may be negative in the early stages of the disease. PCR and viral antigen detection are more accurate in the first seven days. In 2012 a PCR test was introduced that can run on equipment used to diagnose influenza; this is likely to improve access to PCR-based diagnosis.These laboratory tests are only of diagnostic value during the acute phase of the illness with the exception of serology. Tests for dengue virus-specific antibodies, types IgG and IgM, can be useful in confirming a diagnosis in the later stages of the infection. Both IgG and IgM are produced after 5–7 days. The highest levels (titres) of IgM are detected following a primary infection, but IgM is also produced in reinfection. IgM becomes undetectable 30–90 days after a primary infection, but earlier following re-infections. IgG, by contrast, remains detectable for over 60 years and, in the absence of symptoms, is a useful indicator of past infection. After a primary infection, IgG reaches peak levels in the blood after 14–21 days. In subsequent re-infections, levels peak earlier and the titres are usually higher. Both IgG and IgM provide protective immunity to the infecting serotype of the virus. In testing for IgG and IgM antibodies there may be cross-reactivity with other flaviviruses which may result in a false positive after recent infections or vaccinations with yellow fever virus or Japanese encephalitis. The detection of IgG alone is not considered diagnostic unless blood samples are collected 14 days apart and a greater than fourfold increase in levels of specific IgG is detected. In a person with symptoms, the detection of IgM is considered diagnostic.
Prevention
Prevention depends on control of and protection from the bites of the mosquito that transmits it. The World Health Organization recommends an Integrated Vector Control program consisting of five elements:
Advocacy, social mobilization and legislation to ensure that public health bodies and communities are strengthened;
Collaboration between the health and other sectors (public and private);
An integrated approach to disease control to maximize the use of resources;
Evidence-based decision making to ensure any interventions are targeted appropriately; and
Capacity-building to ensure an adequate response to the local situation.The primary method of controlling A. aegypti is by eliminating its habitats. This is done by getting rid of open sources of water, or if this is not possible, by adding insecticides or biological control agents to these areas. Generalized spraying with organophosphate or pyrethroid insecticides, while sometimes done, is not thought to be effective. Reducing open collections of water through environmental modification is the preferred method of control, given the concerns of negative health effects from insecticides and greater logistical difficulties with control agents. People can prevent mosquito bites by wearing clothing that fully covers the skin, using mosquito netting while resting, and/or the application of insect repellent (DEET being the most effective). While these measures can be an effective means of reducing an individuals risk of exposure, they do little in terms of mitigating the frequency of outbreaks, which appear to be on the rise in some areas, probably due to urbanization increasing the habitat of A. aegypti. The range of the disease also appears to be expanding possibly due to climate change.
Vaccine
In 2016 a partially effective vaccine for dengue fever became commercially available in the Philippines and Indonesia. It has been approved for use by Mexico, Brazil, El Salvador, Costa Rica, Singapore, Paraguay, much of Europe, and the United States. The vaccine is only recommended in individuals who have had a prior dengue infection or in populations where most (>80%) of people have been infected by age 9. In those who have not had a prior infection there is evidence it may worsen subsequent infections. For this reason Prescrire does not see it as suitable for wide scale immunization, even in areas where the disease is common.The vaccine is produced by Sanofi and goes by the brand name Dengvaxia. It is based on a weakened combination of the yellow fever virus and each of the four dengue serotypes. Studies of the vaccine found it was 66% effective and prevented more than 80 to 90% of severe cases. This is less than wished for by some. In Indonesia it costs about US$207 for the recommended three doses.Given the limitations of the current vaccine, research on vaccines continues, and the fifth serotype may be factored in. One of the concerns is that a vaccine could increase the risk of severe disease through antibody-dependent enhancement (ADE). The ideal vaccine is safe, effective after one or two injections, covers all serotypes, does not contribute to ADE, is easily transported and stored, and is both affordable and cost-effective.
Anti-dengue day
International Anti-Dengue Day is observed every year on 15 June. The idea was first agreed upon in 2010 with the first event held in Jakarta, Indonesia, in 2011. Further events were held in 2012 in Yangon, Myanmar, and in 2013 in Vietnam. Goals are to increase public awareness about dengue, mobilize resources for its prevention and control and, to demonstrate the Southeast Asian regions commitment in tackling the disease.
Management
There are no specific antiviral drugs for dengue; however, maintaining proper fluid balance is important. Treatment depends on the symptoms. Those who can drink, are passing urine, have no "warning signs" and are otherwise healthy can be managed at home with daily follow-up and oral rehydration therapy. Those who have other health problems, have "warning signs", or cannot manage regular follow-up should be cared for in hospital. In those with severe dengue care should be provided in an area where there is access to an intensive care unit.Intravenous hydration, if required, is typically only needed for one or two days. In children with shock due to dengue a rapid dose of 20 mL/kg is reasonable. The rate of fluid administration is then titrated to a urinary output of 0.5–1 mL/kg/h, stable vital signs and normalization of hematocrit. The smallest amount of fluid required to achieve this is recommended.Invasive medical procedures such as nasogastric intubation, intramuscular injections and arterial punctures are avoided, in view of the bleeding risk. Paracetamol (acetaminophen) is used for fever and discomfort while NSAIDs such as ibuprofen and aspirin are avoided as they might aggravate the risk of bleeding. Blood transfusion is initiated early in people presenting with unstable vital signs in the face of a decreasing hematocrit, rather than waiting for the hemoglobin concentration to decrease to some predetermined "transfusion trigger" level. Packed red blood cells or whole blood are recommended, while platelets and fresh frozen plasma are usually not. There is not enough evidence to determine if corticosteroids have a positive or negative effect in dengue fever.During the recovery phase intravenous fluids are discontinued to prevent a state of fluid overload. If fluid overload occurs and vital signs are stable, stopping further fluid may be all that is needed. If a person is outside of the critical phase, a loop diuretic such as furosemide may be used to eliminate excess fluid from the circulation.
Prognosis
Most people with dengue recover without any ongoing problems. The risk of death among those with severe dengue is 0.8% to 2.5%, and with adequate treatment this is less than 1%. However, those who develop significantly low blood pressure may have a fatality rate of up to 26%. The risk of death among children less than five years old is four times greater than among those over the age of 10. Elderly people are also at higher risk of a poor outcome.
Epidemiology
Dengue is common in more than 120 countries. In 2013 it caused about 60 million symptomatic infections worldwide, with 18% admitted to hospital and about 13,600 deaths. The worldwide cost of dengue case is estimated US$9 billion. For the decade of the 2000s, 12 countries in Southeast Asia were estimated to have about 3 million infections and 6,000 deaths annually. In 2019 the Philippines declared a national dengue epidemic due to the deaths reaching 622 people that year. It is reported in at least 22 countries in Africa; but is likely present in all of them with 20% of the population at risk. This makes it one of the most common vector-borne diseases worldwide.Infections are most commonly acquired in urban environments. In recent decades, the expansion of villages, towns and cities in the areas in which it is common, and the increased mobility of people has increased the number of epidemics and circulating viruses. Dengue fever, which was once confined to Southeast Asia, has now spread to southern China in East Asia, countries in the Pacific Ocean and the Americas, and might pose a threat to Europe.Rates of dengue increased 30 fold between 1960 and 2010. This increase is believed to be due to a combination of urbanization, population growth, increased international travel, and global warming. The geographical distribution is around the equator |
Dengue fever | . Of the 2.5 billion people living in areas where it is common 70% are from the WHO Southeast Asia Region and Western Pacific Region. An infection with dengue is second only to malaria as a diagnosed cause of fever among travelers returning from the developing world. It is the most common viral disease transmitted by arthropods, and has a disease burden estimated at 1,600 disability-adjusted life years per million population. The World Health Organization counts dengue as one of seventeen neglected tropical diseases.Like most arboviruses, dengue virus is maintained in nature in cycles that involve preferred blood-sucking vectors and vertebrate hosts. The viruses are maintained in the forests of Southeast Asia and Africa by transmission from female Aedes mosquitos—of species other than A. aegypti—to their offspring and to lower primates. In towns and cities, the virus is primarily transmitted by the highly domesticated A. aegypti. In rural settings the virus is transmitted to humans by A. aegypti and other species of Aedes such as A. albopictus. Both these species had expanding ranges in the second half of the 20th century. In all settings the infected lower primates or humans greatly increase the number of circulating dengue viruses, in a process called amplification. One projection estimates that climate change, urbanization, and other factors could result in more than 6 billion people at risk of dengue infection by 2080.
History
The first record of a case of probable dengue fever is in a Chinese medical encyclopedia from the Jin Dynasty (266–420) which referred to a "water poison" associated with flying insects. The primary vector, A. aegypti, spread out of Africa in the 15th to 19th centuries due in part to increased globalization secondary to the slave trade. There have been descriptions of epidemics in the 17th century, but the most plausible early reports of dengue epidemics are from 1779 and 1780, when an epidemic swept across Southeast Asia, Africa and North America. From that time until 1940, epidemics were infrequent.In 1906, transmission by the Aedes mosquitos was confirmed, and in 1907 dengue was the second disease (after yellow fever) that was shown to be caused by a virus. Further investigations by John Burton Cleland and Joseph Franklin Siler completed the basic understanding of dengue transmission.The marked spread of dengue during and after the Second World War has been attributed to ecologic disruption. The same trends also led to the spread of different serotypes of the disease to new areas and the emergence of dengue hemorrhagic fever. This severe form of the disease was first reported in the Philippines in 1953; by the 1970s, it had become a major cause of child mortality and had emerged in the Pacific and the Americas. Dengue hemorrhagic fever and dengue shock syndrome were first noted in Central and South America in 1981, as DENV-2 was contracted by people who had previously been infected with DENV-1 several years earlier.
Etymology
The name came into English in the early 19th century from West Indian Spanish, which borrowed it from the Kiswahili term dinga (in full kidingapopo, "disease caused by an evil spirit"). The borrowed term changed to dengue in Spanish due to this word existing in Spanish with the meaning "fastidiousness" and this folk etymology referring to the dislike of movement by affected patients. Slaves in the West Indies having contracted dengue were said to have the posture and gait of a dandy, and the disease was known as "dandy fever".The term break-bone fever was applied by physician and United States Founding Father Benjamin Rush, in a 1789 report of the 1780 epidemic in Philadelphia. In the report title he uses the more formal term "bilious remitting fever". The term dengue fever came into general use only after 1828. Other historical terms include "breakheart fever" and "la dengue". Terms for severe disease include "infectious thrombocytopenic purpura" and "Philippine", "Thai", or "Singapore hemorrhagic fever".
Society and culture
Blood donation
Outbreaks of dengue fever increase the need for blood products while decreasing the number of potential blood donors due to potential infection with the virus. Someone who has a dengue infection is typically not allowed to donate blood for at least the next six months.
Awareness efforts
A National Dengue Day is held in India on 16 May in an effort to raise awareness in affected countries. Efforts are ongoing as of 2019 to make it a global event. The Philippines has an awareness month in June since 1998.
Research
Research efforts to prevent and treat dengue include various means of vector control, vaccine development, and antiviral drugs.A vaccine candidate, TAK-003, has shown 73% efficacy in a clinical trial of more than 20,000 children in endemic regions and 90% efficacy for hospitalized patients.
Vector
With regards to vector control, a number of novel methods have been used to reduce mosquito numbers with some success including the placement of the guppy (Poecilia reticulata) or copepods in standing water to eat the mosquito larvae. There are also trials with genetically modified male A. aegypti that after release into the wild mate with females, and render their offspring unable to fly.
Wolbachia
In 2021 research in Yogyakarta, Indonesia, infected A. aegypti with the wMel strain of Wolbachia pipientis. Infected mosquitos were less susceptible to dengue virus infection. Odds ratio of intervention clusters versus control clusters was.23 (95% confidence interval [CI], 0.15 to 0.35; P=0.004).
Treatment
Apart from the attempts to control the spread of the Aedes mosquito there are ongoing efforts to develop antiviral drugs that would be used to treat attacks of dengue fever and prevent severe complications. Discovery of the structure of the viral proteins may aid the development of effective drugs. There are several plausible targets. The first approach is inhibition of the viral RNA-dependent RNA polymerase (coded by NS5), which copies the viral genetic material, with nucleoside analogs. Secondly, it may be possible to develop specific inhibitors of the viral protease (coded by NS3), which splices viral proteins. Finally, it may be possible to develop entry inhibitors, which stop the virus entering cells, or inhibitors of the 5′ capping process, which is required for viral replication.Carica papaya leaf extract has been studied and has been used for treatment and in hospitals. As of 2020, studies have shown positive benefits on clinical blood parameters, but a beneficial effect on disease outcome has yet to be studied, and papaya leaf extract is not considered a standard of practice therapy.
References
External links
Dengue fever at Curlie
This article was submitted to Open Medicine for external academic peer review in 2012 (reviewer reports). The updated content was reintegrated into the Wikipedia page under a CC-BY-SA-3.0 license (2014). The version of record as reviewed is:
James Heilman; Jacob de Wolff; Graham Beards; Brian Basden; et al. (2 October 2014). "Dengue fever: a Wikipedia clinical review". Open Medicine. 8 (4): e105-15. ISSN 1911-2092. PMC 4242787. PMID 25426178. Wikidata Q28651505. |
Intracranial aneurysm | An intracranial aneurysm, also known as a brain aneurysm, is a cerebrovascular disorder in which weakness in the wall of a cerebral artery or vein causes a localized dilation or ballooning of the blood vessel.
Aneurysms in the posterior circulation (basilar artery, vertebral arteries and posterior communicating artery) have a higher risk of rupture. Basilar artery aneurysms represent only 3–5% of all intracranial aneurysms but are the most common aneurysms in the posterior circulation.
Classification
Cerebral aneurysms are classified both by size and shape. Small aneurysms have a diameter of less than 15 mm. Larger aneurysms include those classified as large (15 to 25 mm), giant (25 to 50 mm), and super-giant (over 50 mm).
Berry (saccular) aneurysms
Saccular aneurysms, also known as berry aneurysms, appear as a round outpouching and are the most common form of cerebral aneurysm. Causes include connective tissue disorders, polycystic kidney disease, arteriovenous malformations, untreated hypertension, tobacco smoking, cocaine, and amphetamines, intravenous drug abuse (can cause infectious mycotic aneurysms), alcoholism, heavy caffeine intake, head trauma, and infection in the arterial wall from bacteremia (mycotic aneurysms).
Fusiform aneurysms
Fusiform dolichoectatic aneurysms represent a widening of a segment of an artery around the entire blood vessel, rather than just arising from a side of an arterys wall. They have an estimated annual risk of rupture between 1.6 and 1.9 percent.
Microaneurysms
Microaneurysms, also known as Charcot–Bouchard aneurysms, typically occur in small blood vessels (less than 300 micrometre diameter), most often the lenticulostriate vessels of the basal ganglia, and are associated with chronic hypertension. Charcot–Bouchard aneurysms are a common cause of intracranial hemorrhage.
Signs and symptoms
A small, unchanging aneurysm will produce few, if any, symptoms. Before a larger aneurysm ruptures, the individual may experience such symptoms as a sudden and unusually severe headache, nausea, vision impairment, vomiting, and loss of consciousness, or no symptoms at all.
Subarachnoid bleed
If an aneurysm ruptures, blood leaks into the space around the brain. This is called a subarachnoid hemorrhage. Onset is usually sudden without prodrome, classically presenting as a "thunderclap headache" worse than previous headaches. Symptoms of a subarachnoid hemorrhage differ depending on the site and size of the aneurysm. Symptoms of a ruptured aneurysm can include:
a sudden severe headache that can last from several hours to days
nausea and vomiting
drowsiness, confusion and/or loss of consciousness
visual abnormalities
meningism
dizzinessAlmost all aneurysms rupture at their apex. This leads to hemorrhage in the subarachnoid space and sometimes in brain parenchyma. Minor leakage from aneurysm may precede rupture, causing warning headaches. About 60% of patients die immediately after rupture. Larger aneurysms have a greater tendency to rupture, though most ruptured aneurysms are less than 10 mm in diameter.
Microaneurysms
A ruptured microaneurysm may cause an intracerebral hemorrhage, presenting as a focal neurological deficit.Rebleeding, hydrocephalus (the excessive accumulation of cerebrospinal fluid), vasospasm (spasm, or narrowing, of the blood vessels), or multiple aneurysms may also occur. The risk of rupture from a cerebral aneurysm varies according to the size of an aneurysm, with the risk rising as the aneurysm size increases.
Vasospasm
Vasospasm, referring to blood vessel constriction, can occur secondary to subarachnoid hemorrhage following a ruptured aneurysm. This is most likely to occur within 21 days and is seen radiologically within 60% of such patients. The vasospasm is thought to be secondary to the apoptosis of inflammatory cells such as macrophages and neutrophils that become trapped in the subarachnoid space. These cells initially invade the subarachnoid space from the circulation in order to phagocytose the hemorrhaged red blood cells. Following apoptosis, it is thought there is a massive degranulation of vasoconstrictors, including endothelins and free radicals, that cause the vasospasm.
Risk factors
Intracranial aneurysms may result from diseases acquired during life, or from genetic conditions. Hypertension, smoking, alcoholism, and obesity are associated with the development of brain aneurysms. Cocaine use has also been associated with the development of intracranial aneurysms.Other acquired associations with intracranial aneurysms include head trauma and infections.
Genetic associations
Coarctation of the aorta is also a known risk factor, as is arteriovenous malformation. Genetic conditions associated with connective tissue disease may also be associated with the development of aneurysms. This includes:
autosomal dominant polycystic kidney disease,
neurofibromatosis type I,
Marfan syndrome,
multiple endocrine neoplasia type I,
pseudoxanthoma elasticum,
hereditary hemorrhagic telangiectasia and
Ehlers-Danlos syndrome types II and IV.Specific genes have also had reported association with the development of intracranial aneurysms, including perlecan, elastin, collagen type 1 A2, endothelial nitric oxide synthase, endothelin receptor A and cyclin dependent kinase inhibitor. Recently, several genetic loci have been identified as relevant to the development of intracranial aneurysms. These include 1p34–36, 2p14–15, 7q11, 11q25, and 19q13.1–13.3.
Pathophysiology
Aneurysm means an outpouching of a blood vessel wall that is filled with blood. Aneurysms occur at a point of weakness in the vessel wall. This can be because of acquired disease or hereditary factors. The repeated trauma of blood flow against the vessel wall presses against the point of weakness and causes the aneurysm to enlarge. As described by the law of Young-Laplace, the increasing area increases tension against the aneurysmal walls, leading to enlargement. In addition, a combination of computational fluid dynamics and morphological indices have been proposed as reliable predictors of cerebral aneurysm rupture.Both high and low wall shear stress of flowing blood can cause aneurysm and rupture. However, the mechanism of action is still unknown. It is speculated that low shear stress causes growth and rupture of large aneurysms through inflammatory response while high shear stress causes growth and rupture of small aneurysm through mural response (response from the blood vessel wall). Other risk factors that contributes to the formation of aneurysm are: cigarette smoking, hypertension, female gender, family history of cerebral aneurysm, infection, and trauma. Damage to structural integrity of the arterial wall by shear stress causes an inflammatory response with the recruitment of T cells, macrophages, and mast cells. The inflammatory mediators are: interleukin 1 beta, interleukin 6, tumor necrosis factor alpha (TNF alpha), MMP1, MMP2, MMP9, prostaglandin E2, complement system, reactive oxygen species (ROS), and angiotensin II. However, smooth muscle cells from the tunica media layer of the artery moved into the tunica intima, where the function of the smooth muscle cells changed from contractile function into pro-inflammatory function. This causes the fibrosis of the arterial wall, with reduction of number of smooth muscle cells, abnormal collagen synthesis, resulting in a thinning of the arterial wall and the formation of aneurysm and rupture. No specific gene loci has been identified to be associated with cerebral aneurysms.Generally, aneurysms larger than 7 mm in diameter should be treated because they are prone for rupture. Meanwhile, aneurysms less than 7 mm arise from the anterior and posterior communicating artery and are more easily ruptured when compared to aneurysms arising from other locations.
Saccular aneurysms
Saccular aneurysms are almost always the result of hereditary weaknesses in blood vessels and typically occur within the arteries of the circle of Willis, in order of frequency affecting the following arteries:
Anterior communicating artery
Posterior communicating artery
Middle cerebral artery
Internal carotid artery
Tip of basilar arterySaccular aneurysms tend to have a lack of tunica media and elastic lamina around their dilated locations (congenital), with a wall of sac made up of thickened hyalinized intima and adventitia. In addition, some parts of the brain vasculature are inherently weak—particularly areas along the circle of Willis, where small communicating vessels link the main cerebral vessels. These areas are particularly susceptible to saccular aneurysms. Approximately 25% of patients have multiple aneurysms, predominantly when there is a familial pattern.
Diagnosis
Once suspected, intracranial aneurysms can be diagnosed radiologically using magnetic resonance or CT angiography. But these methods have limited sensitivity for diagnosis of small aneurysms, and often cannot be used to specifically distinguish them from infundibular dilations without performing a formal angiogram. The determination of whether an aneurysm is ruptured is critical to diagnosis. Lumbar puncture (LP) is the gold standard technique for determining aneurysm rupture (subarachnoid hemorrhage). Once an LP is performed, the CSF is evaluated for RBC count, and presence or absence of xanthochromia.
Treatment
Emergency treatment for individuals with a ruptured cerebral aneurysm generally includes restoring deteriorating respiration and reducing intracranial pressure. Currently there are two treatment options for securing intracranial aneurysms: surgical clipping or endovascular coiling. If possible, either surgical clipping or endovascular coiling is typically performed within the first 24 hours after bleeding to occlude the ruptured aneurysm and reduce the risk of recurrent hemorrhage.While a large meta-analysis found the outcomes and risks of surgical clipping and endovascular coiling to be statistically similar, no consensus has been reached. In particular, the large randomised control trial International Subarachnoid Aneurysm Trial appears to indicate a higher rate of recurrence when intracerebral aneurysms are treated using endovascular coiling. Analysis of data from this trial has indicated a 7% lower eight-year mortality rate with coiling, a high rate of aneurysm recurrence in aneurysms treated with coiling—from 28.6 to 33.6% within a year, a 6.9 times greater rate of late retreatment for coiled aneurysms, and a rate of rebleeding 8 times higher than surgically clipped aneurysms.
Surgical clipping
Aneurysms can be treated by clipping the base of the aneurysm with a specially-designed clip. Whilst this is typically carried out by craniotomy, a new endoscopic endonasal approach is being trialled. Surgical clipping was introduced by Walter Dandy of the Johns Hopkins Hospital in 1937.
After clipping, a catheter angiogram or CTA can be performed to confirm complete clipping.
Endovascular coiling
Endovascular coiling refers to the insertion of platinum coils into the aneurysm. A catheter is inserted into a blood vessel, typically the femoral artery, and passed through blood vessels into the cerebral circulation and the aneurysm. Coils are pushed into the aneurysm, or released into the blood stream ahead of the aneurysm. Upon depositing within the aneurysm, the coils expand and initiate a thrombotic reaction within the aneurysm. If successful, this prevents further bleeding from the aneurysm. In the case of broad-based aneurysms, a stent may be passed first into the parent artery to serve as a scaffold for the coils.
Cerebral bypass surgery
Cerebral bypass surgery was developed in the 1960s in Switzerland by Gazi Yasargil. When a patient has an aneurysm involving a blood vessel or a tumor at the base of the skull wrapping around a blood vessel, surgeons eliminate the problem vessel by replacing it with an artery from another part of the body.
Prognosis
Outcomes depend on the size of the aneurysm. Small aneurysms (less than 7 mm) have a low risk of rupture and increase in size slowly. The risk of rupture is less than one percent for aneurysms of this size.The prognosis for a ruptured cerebral aneurysm depends on the extent and location of the aneurysm, the persons age, general health, and neurological condition. Some individuals with a ruptured cerebral aneurysm die from the initial bleeding. Other individuals with cerebral aneurysm recover with little or no neurological deficit. The most significant factors in determining outcome are the Hunt and Hess grade, and age. Generally patients with Hunt and Hess grade I and II hemorrhage on admission to the emergency room and patients who are younger within the typical age range of vulnerability can anticipate a good outcome, without death or permanent disability. Older patients and those with poorer Hunt and Hess grades on admission have a poor prognosis. Generally, about two-thirds of patients have a poor outcome, death, or permanent disability.Increased availability and greater access to medical imaging has caused a rising number of asymptomatic, unruptured cerebral aneurysms to be discovered incidentally during medical imaging investigations. This may lead to surgery including endovascular, or simple monitoring. Recently, an increasing number of aneurysm features have been evaluated in their ability to predict aneurysm rupture status, including aneurysm height, aspect ratio, height-to-width ratio, inflow angle, deviations from ideal spherical or elliptical forms, and radiomics morphological features.
Epidemiology
The prevalence of intracranial aneurysm is about 1–5% (10 million to 12 million persons in the United States) and the incidence is 1 per 10,000 persons per year in the United States (approximately 27,000), with 30- to 60-year-olds being the age group most affected. Intracranial aneurysms occur more in women, by a ratio of 3 to 2, and are rarely seen in pediatric populations.
See also
Interventional neuroradiology
Intradural pseudoaneurysm
References
External links
National Institute of Neurological Disorders and Stroke |
Roseola | Roseola, also known as sixth disease, is an infectious disease caused by certain types of human herpes viruses. Most infections occur before the age of three. Symptoms vary from absent to the classic presentation of a fever of rapid onset followed by a rash. The fever generally lasts for three to five days, while the rash is generally pink and lasts for less than three days. Complications may include febrile seizures, with serious complications being rare.It is caused by human herpesvirus 6 (HHV-6A, HHV-6B) or human herpesvirus 7 (HHV-7). Spread is usually through the saliva of those who are otherwise healthy. However, it may also spread from the mother to baby during pregnancy. Diagnosis is typically based on symptoms and does not need to be confirmed with blood tests (PCR or antigen). Low numbers of white blood cells may also be present.Treatment includes sufficient fluids and medications to treat the fever. Nearly all people are infected at some point in time. Males and females are affected equally often. The disease may reactivate in those with a weakened immune system and may result in significant health problems.The disease was first described in 1910 while the causal virus was determined in 1988. The name "sixth disease" comes from its place on the standard list of rash-causing childhood diseases, which also includes measles (first), scarlet fever (second), rubella (third), Dukes disease (fourth, but is no longer widely accepted as distinct from scarlet fever), and erythema infectiosum (fifth).
Signs and symptoms
Fever
Symptoms begin with a three to six day febrile illness. During this time, temperatures can peak above 40 °C and children can experience increased irritability with general malaise. However, many children in the febrile phase feel well, engaged, and alert. For these patients, fever is usually diagnosed incidentally.The most common complication (10-15% of children between 6 and 18 months) and most common cause of hospitalization in children with primary infection of HHV-6B is febrile seizures which can precipitate status epilepticus due to the sudden rise in body temperature.
Rash
Once the febrile phase subsides, a rash develops. In some cases, the rash can present after one or two days after the fever resolves. The rash is classically described as an erythematous morbilliform exanthem and presents as a distribution of soft pink, discrete, and slightly raised lesions each with a 2-5mm diameter. It classically begins on the trunk (torso) and spreads outward to the neck, extremities, and face. This pattern is referred to as a centrifugal spread. Usually, peeling and itching are not characteristic of this rash. This phase can last anywhere from several hours to 2 days.
Other symptoms
A small percentage of children acquire HHV-6 with few signs or symptoms of the disease. Children with HHV-6 infection can also present with myringitis (inflammation of the tympanic membranes), upper respiratory symptoms, diarrhea, and a bulging fontanelle. In addition, children can experience pharyngitis with lymphoid hyperplasia seen on the soft palate and swelling of the eyelids. These symptoms usually present during the febrile phase of roseola. Cervical and postocciptal lymphadenopathy can also be seen, but this generally presents 2–4 days after the onset of the febrile phase.In rare cases, HHV-6 can become active in an adult previously infected during childhood and can show signs of mononucleosis.
Cause
There are nine known human herpesviruses. Of these, roseola has been linked to two: human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7), which are sometimes referred to collectively as Roseolovirus. These viruses are of the Herpesviridae family and the Betaherpesvirinae subfamily, underwhich Cytomegalovirus is also classified. HHV-6 has been further classified into HHV-6A and HHV-6B, two distinct viruses which share 88% of the same DNA makeup, with HHV-6B the most common cause of roseola.After infection, these viruses enter a latent phase. Roseola caused by HHV-7 has been linked to the ability of HHV-7 infection to reactivate latent HHV-6.
Spread
After exposure to roseola, the causative virus becomes latent in its host but is still present in saliva, skin, and lungs. HHV-6 is thought to be transmitted from previously exposed or infected adults to young children by the shedding of virus through saliva. Even so, most cases of roseola are transmitted without known exposure.
Diagnosis
The diagnosis of roseola is made clinically based on the presence of the two phases: fever and rash. Laboratory testing is seldom used as the results do not alter management of the disease. An exception is in people who are immunocompromised in who serologic tests with viral identification can be used to confirm the diagnosis.Roseola should be differentiated from other similar-appearing illnesses, such as rubella, measles, fifth disease, scarlet fever, and drug reactions. This differentiation may be determined based on symptoms.
Prevention
Many viruses can cause Roseola and are shed by carriers without symptoms. Because of this and the fact that most children with the disease are not seriously ill, there is no particular method of prevention. Proper hygienic measures, like regular handwashing, can be implemented as a routine method of prevention. Those who have been exposed or infected have been shown to shed the virus for the rest of their lives. Because of this, there are no current guidelines regarding children staying home or away from child-care when infected.
Treatment
Most cases of HHV-6 infection improve on their own. Because of this, supportive care is the mainstay treatment. The febrile phase can be managed using acetaminophen to control fever and prevent spikes in temperature which can lead to febrile seizures. In the case of febrile seizures, medical advice should be sought, and treatment aggressively pursued. Antiepileptic drugs are not recommended for patients who develop seizures from Roseola. Once children have entered the rash phase, reassurance is important as this indicates resolution of the infection.If encephalitis occurs in immunocompromised children, ganciclovir or foscarnet have inconsistently shown usefulness in treatment. Treatment of children who are immunocompromised centers around decreasing their levels of immunosuppression as much as possible.
Prognosis
Children infected with roseola generally have a good prognosis. Most recover without intervention and without long-term effects.
Epidemiology
Between the two types of human herpesvirus 6, HHV-6B has been detected much more frequently in hosts. HHV-6B has been shown to affect about 90% of children before the age of 3. Out of these, 20% develop symptoms of roseola, also known as exanthem subitum.Roseola affects girls and boys equally worldwide year-round. Roseola typically affects children between six months and two years of age, with peak prevalence in children between 7 and 13 months old. This correlates with the decrease in maternal antibodies, thus virus protection, that occurs at the age of 6 months. Out of all emergency department visits for children between the ages of 6 months and 12 months who have fever, twenty percent of these are due to HHV-6.Many children who have been exposed and infected can present without symptoms, which makes determining the incidence within the population difficult.
History
John Zahorsky MD wrote extensively on this disease in the early 20th century, his first formal presentation was to the St Louis Pediatric society in 1909 where he described 15 young children with the illness. In a JAMA article published on Oct 18, 1913 he noted that "the name Roseola infantilis had an important place in the medical terminology of writers on skin diseases" but that descriptions of the disease by previous writers tended to confuse it with many other diseases that produce febrile rashes. In this JAMA article Zahorsky reports on 29 more children with Roseola and notes that the only condition that should seriously be considered in the differential diagnosis is German Measles (rubella) but notes that the fever of rubella only lasts a few hours whereas the prodromal fever of Roseola lasts three to five days and disappears with the formation of a morbilliform rash.
Names
Research
HHV-6 has been tentatively linked with neurodegenerative diseases.
See also
Fifth disease
References
External links
DermNet viral/roseola |
Extrapulmonary tuberculosis | Extrapulmonary tuberculosis is tuberculosis (TB) within a location in the body other than the lungs. It accounts for an increasing fraction of active cases, from 20 to 40% according to published reports, and causes other kinds of TB. These are collectively denoted as "extrapulmonary tuberculosis". Extrapulmonary TB occurs more commonly in immunosuppressed persons and young children. In those with HIV, this occurs in more than 50% of cases. Notable extrapulmonary infection sites include the pleura (in tuberculous pleurisy), the central nervous system (in tuberculous meningitis), the lymphatic system (in scrofula of the neck), the genitourinary system (in urogenital tuberculosis), and the bones and joints (in Pott disease of the spine), among others.
Infection of the lymph nodes, known as tubercular lymphadenitis, is the most common extrapulmonary form of tuberculosis. An ulcer originating from nearby infected lymph nodes may occur and is painless. It typically enlarges slowly and has an appearance of "wash leather".
When it spreads to the bones, it is known as skeletal tuberculosis, a form of osteomyelitis. Tuberculosis has been present in humans since ancient times.Central nervous system infections include tuberculous meningitis, intracranial tuberculomas, and spinal tuberculous arachnoiditis.Abdominal infections include gastrointestinal tuberculosis (which is important to distinguish from Crohns disease, since immunosuppressive therapy used for the latter can lead to dissemination), tuberculous peritonitis, and genitourinary tuberculosis.A potentially more serious, widespread form of TB is called "disseminated tuberculosis", also known as miliary tuberculosis. Miliary TB currently makes up about 10% of extrapulmonary cases.
Pleural effusion
This condition is one of the common forms of extrapulmonary tuberculosis. It occurs during acute phase of the disease, with fever, cough, and pain while breathing (pleurisy). Pleural fluid usually contains mostly lymphocytes and the Mycobacterium bacteria. Gold standard of diagnosis is the detection of Mycobacterium in pleural fluid. Other diagnostic test includes the detection of adenosine deaminase (above 40 U/L) and interferon gamma in pleural fluid.
== References == |
Insect bites and stings | Insect bites and stings occur when an insect is agitated and seeks to defend itself through its natural defense mechanisms, or when an insect seeks to feed off the bitten person. Some insects inject formic acid, which can cause an immediate skin reaction often resulting in redness and swelling in the injured area. Stings from fire ants, bees, wasps and hornets are usually painful, and may stimulate a dangerous allergic reaction called anaphylaxis for at-risk patients, and some wasps can also have a powerful bite along with a sting. Bites from mosquitoes and fleas are more likely to cause itching than pain.
The skin reaction to insect bites and stings usually lasts for up to a few days. However, in some cases, the local reaction can last for up to two years. These bites are sometimes misdiagnosed as other types of benign or cancerous lesions.
Signs and symptoms
The reaction to a sting is of three types. The normal reaction involves the area around the bite with redness, itchiness, and pain. A large local reaction occurs when the area of swelling is greater than 5 centimetres (2 in). Systemic reactions are when symptoms occur in areas besides that of the bites.With insect stings a large local reaction may occur (an area of skin redness greater than 10 centimetres (4 in) in size). It can last one to two days. It occurs in about 10% of those bitten.
Feeding bites
Feeding bites have characteristic patterns and symptoms, a function of the feeding habits of the offending pest and the chemistry of its saliva.
Microscopic appearance
The histomorphologic appearance of insect bites is usually characterized by a wedge-shaped superficial dermal perivascular infiltrate consisting of abundant lymphocytes and scattered eosinophils. This appearance is non-specific, i.e. it may be seen in a number of conditions including:
Drug reactions,
Urticarial reactions,
Prevesicular early stage of bullous pemphigoid, and
HIV related dermatoses.
See also
List of biting or stinging arthropods
Spider bite
Insect bite relief stick
Schmidt sting pain index
Bee sting
Allergy
References
External links
Venomous Arthropods chapter in United States Environmental Protection Agency and University of Florida/Institute of Food and Agricultural Sciences National Public Health Pesticide Applicator Training Manual
Burns, Boyd (Bo) D (2020-12-06). "Insect Bites: Background, Pathophysiology, Epidemiology". Medscape Reference. Retrieved 2021-01-22. |
Down syndrome | Down syndrome or Downs syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual disability, and characteristic facial features. The average IQ of a young adult with Down syndrome is 50, equivalent to the mental ability of an eight- or nine-year-old child, but this can vary widely.The parents of the affected individual are usually genetically normal. The probability increases from less than 0.1% in 20-year-old mothers to 3% in those of age 45. The extra chromosome is believed to occur by chance, with no known behavioral activity or environmental factor that changes the probability. Down syndrome can be identified during pregnancy by prenatal screening followed by diagnostic testing or after birth by direct observation and genetic testing. Since the introduction of screening, Down syndrome pregnancies are often aborted.There is no cure for Down syndrome. Education and proper care have been shown to improve quality of life. Some children with Down syndrome are educated in typical school classes, while others require more specialized education. Some individuals with Down syndrome graduate from high school, and a few attend post-secondary education. In adulthood, about 20% in the United States do paid work in some capacity, with many requiring a sheltered work environment. Support in financial and legal matters is often needed. Life expectancy is around 50 to 60 years in the developed world with proper health care. Regular screening for health problems common in Down syndrome is recommended throughout the persons life.Down syndrome is one of the most common chromosome abnormalities in humans. It occurs in about 1 in 1,000 babies born each year. In 2015, Down syndrome was present in 5.4 million individuals globally and resulted in 27,000 deaths, down from 43,000 deaths in 1990. It is named after British doctor John Langdon Down, who fully described the syndrome in 1866. Some aspects of the condition were described earlier by French psychiatrist Jean-Étienne Dominique Esquirol in 1838 and French physician Édouard Séguin in 1844. The genetic cause of Down syndrome was discovered in 1959.
Signs and symptoms
Those with Down syndrome nearly always have physical and intellectual disabilities. As adults, their mental abilities are typically similar to those of an 8- or 9-year-old. They also typically have poor immune function and generally reach developmental milestones at a later age. They have an increased risk of a number of other health problems, including congenital heart defect, epilepsy, leukemia, thyroid diseases, and mental disorders.
Physical
People with Down syndrome may have some or all of these physical characteristics: a small chin, slanted eyes, poor muscle tone, a flat nasal bridge, a single crease of the palm, and a protruding tongue due to a small mouth and relatively large tongue. These airway changes lead to obstructive sleep apnea in around half of those with Down syndrome. Other common features include: a flat and wide face, a short neck, excessive joint flexibility, extra space between big toe and second toe, abnormal patterns on the fingertips and short fingers. Instability of the atlantoaxial joint occurs in about 20% and may lead to spinal cord injury in 1–2%. Hip dislocations may occur without trauma in up to a third of people with Down syndrome.Growth in height is slower, resulting in adults who tend to have short stature—the average height for men is 154 cm (5 ft 1 in) and for women is 142 cm (4 ft 8 in). Individuals with Down syndrome are at increased risk for obesity as they age. Growth charts have been developed specifically for children with Down syndrome.
Neurological
This syndrome causes about a third of cases of intellectual disability. Many developmental milestones are delayed with the ability to crawl typically occurring around 8 months rather than 5 months and the ability to walk independently typically occurring around 21 months rather than 14 months.Most individuals with Down syndrome have mild (IQ: 50–69) or moderate (IQ: 35–50) intellectual disability with some cases having severe (IQ: 20–35) difficulties. Those with mosaic Down syndrome typically have IQ scores 10–30 points higher than that. As they age, people with Down syndrome typically perform worse than their same-age peers.Commonly, individuals with Down syndrome have better language understanding than ability to speak. Between 10 and 45% have either a stutter or rapid and irregular speech, making it difficult to understand them. After reaching 30 years of age, some may lose their ability to speak.They typically do fairly well with social skills. Behavior problems are not generally as great an issue as in other syndromes associated with intellectual disability. In children with Down syndrome, mental illness occurs in nearly 30% with autism occurring in 5–10%. People with Down syndrome experience a wide range of emotions. While people with Down syndrome are generally happy, symptoms of depression and anxiety may develop in early adulthood.Children and adults with Down syndrome are at increased risk of epileptic seizures, which occur in 5–10% of children and up to 50% of adults. This includes an increased risk of a specific type of seizure called infantile spasms. Many (15%) who live 40 years or longer develop Alzheimers disease. In those who reach 60 years of age, 50–70% have the disease.
Senses
Hearing and vision disorders occur in more than half of people with Down syndrome.
Vision problems occur in 38 to 80%. Between 20 and 50% have strabismus, in which the two eyes do not move together. Cataracts (cloudiness of the lens of the eye) occur in 15%, and may be present at birth. Keratoconus (a thin, cone-shaped cornea) and glaucoma (increased eye pressure) are also more common, as are refractive errors requiring glasses or contacts. Brushfield spots (small white or grayish/brown spots on the outer part of the iris) are present in 38 to 85% of individuals.Hearing problems are found in 50–90% of children with Down syndrome. This is often the result of otitis media with effusion which occurs in 50–70% and chronic ear infections which occur in 40 to 60%. Ear infections often begin in the first year of life and are partly due to poor eustachian tube function. Excessive ear wax can also cause hearing loss due to obstruction of the outer ear canal. Even a mild degree of hearing loss can have negative consequences for speech, language understanding, and academics. It is important to rule out hearing loss as a factor in social and cognitive deterioration. Age-related hearing loss of the sensorineural type occurs at a much earlier age and affects 10–70% of people with Down syndrome.
Heart
The rate of congenital heart disease in newborns with Down syndrome is around 40%. Of those with heart disease, about 80% have an atrioventricular septal defect or ventricular septal defect with the former being more common. Mitral valve problems become common as people age, even in those without heart problems at birth. Other problems that may occur include tetralogy of Fallot and patent ductus arteriosus. People with Down syndrome have a lower risk of hardening of the arteries.
Cancer
Although the overall risk of cancer in Down syndrome is not changed, the risk of testicular cancer and certain blood cancers, including acute lymphoblastic leukemia (ALL) and acute megakaryoblastic leukemia (AMKL) is increased while the risk of other non-blood cancers is decreased. People with Down syndrome are believed to have an increased risk of developing cancers derived from germ cells whether these cancers are blood- or non-blood-related.
Blood cancers
Leukemia is 10 to 15 times more common in children with Down syndrome. In particular, acute lymphoblastic leukemia is 20 times more common and the megakaryoblastic form of acute myeloid leukemia (acute megakaryoblastic leukemia), is 500 times more common. Acute megakaryoblastic leukemia (AMKL) is a leukemia of megakaryoblasts, the precursors cells to megakaryocytes which form blood platelets. Acute lymphoblastic leukemia in Down syndrome accounts for 1–3% of all childhood cases of ALL. It occurs most often in those older than nine years or having a white blood cell count greater than 50,000 per microliter and is rare in those younger than one year old. ALL in Down syndrome tends to have poorer outcomes than other cases of ALL in people without Down syndrome.In Down syndrome, AMKL is typically preceded by transient myeloproliferative disease (TMD), a disorder of blood cell production in which non-cancerous megakaryoblasts with a mutation in the GATA1 gene rapidly divide during the later period of pregnancy. The condition affects 3–10% of babies with Down. While it often spontaneously resolves within three months of birth, it can cause serious blood, liver, or other complications. In about 10% of cases, TMD progresses to AMKL during the three months to five years following its resolution.
Non-blood cancers
People with Down syndrome have a lower risk of all major solid cancers, including those of lung, breast, and cervix, with the lowest relative rates occurring in those aged 50 years or older. This low risk is thought due to an increase in the expression of tumor suppressor genes present on chromosome 21. One exception is testicular germ cell cancer which occurs at a higher rate in Down syndrome.
Endocrine
Problems of the thyroid gland occur in 20–50% of individuals with Down syndrome. Low thyroid is the most common form, occurring in almost half of all individuals. Thyroid problems can be due to a poorly or nonfunctioning thyroid at birth (known as congenital hypothyroidism) which occurs in 1% or can develop later due to an attack on the thyroid by the immune system resulting in Graves disease or autoimmune hypothyroidism. Type 1 diabetes mellitus is also more common.
Gastrointestinal
Constipation occurs in nearly half of people with Down syndrome and may result in changes in behavior. One potential cause is Hirschsprungs disease, occurring in 2–15%, which is due to a lack of nerve cells controlling the colon. Other frequent congenital problems include duodenal atresia, pyloric stenosis, Meckel diverticulum, and imperforate anus. Celiac disease affects about 7–20% and gastroesophageal reflux disease is also more common.
Teeth
People with Down syndrome tend to be more susceptible to gingivitis as well as early, severe periodontal disease, necrotising ulcerative gingivitis, and early tooth loss, especially in the lower front teeth. While plaque and poor oral hygiene are contributing factors, the severity of these periodontal diseases cannot be explained solely by external factors. Research suggests that the severity is likely a result of a weakened immune system. The weakened immune system also contributes to increased incidence of yeast infections in the mouth (from Candida albicans).People with Down syndrome also tend to have a more alkaline saliva resulting in a greater resistance to tooth decay, despite decreased quantities of saliva, less effective oral hygiene habits, and higher plaque indexes.Higher rates of tooth wear and bruxism are also common. Other common oral manifestations of Down syndrome include enlarged hypotonic tongue, crusted and hypotonic lips, mouth breathing, narrow palate with crowded teeth, class III malocclusion with an underdeveloped maxilla and posterior crossbite, delayed exfoliation of baby teeth and delayed eruption of adult teeth, shorter roots on teeth, and often missing and malformed (usually smaller) teeth. Less common manifestations include cleft lip and palate and enamel hypocalcification (20% prevalence).Taurodontism, an elongation of the pulp chamber, has a high prevalence in people with DS.
Fertility
Males with Down syndrome usually do not father children, while females have lower rates of fertility relative to those who are unaffected. Fertility is estimated to be present in 30–50% of females. Menopause usually occurs at an earlier age. The poor fertility in males is thought to be due to problems with sperm development; however, it may also be related to not being sexually active. As of 2006, three instances of males with Down syndrome fathering children and 26 cases of females having children have been reported. Without assisted reproductive technologies, around half of the children of someone with Down syndrome will also have the syndrome.
Cause
The cause of the extra full or partial chromosome is still unknown. Most of the time, Down syndrome is caused by a random mistake in cell division during early development of the fetus, but not inherited, and no scientific research shows that environmental factors or the parents activities contribute to Down syndrome. The only factor that has been linked to the increased chance of having a baby with Down syndrome is maternal age.
Down syndrome is caused by having three copies of the genes on chromosome 21, rather than the usual two. The parents of the affected individual are typically genetically normal. Those who have one child with Down syndrome have about a 1% possibility of having a second child with the syndrome, if both parents are found to have normal karyotypes.The extra chromosome content can arise through several different ways. The most common cause (about 92–95% of cases) is a complete extra copy of chromosome 21, resulting in trisomy 21. In 1.0 to 2.5% of cases, some of the cells in the body are normal and others have trisomy 21, known as mosaic Down syndrome. The other common mechanisms that can give rise to Down syndrome include: a Robertsonian translocation, isochromosome, or ring chromosome. These contain additional material from chromosome 21 and occur in about 2.5% of cases. An isochromosome results when the two long arms of a chromosome separate together rather than the long and short arm separating together during egg or sperm development.
Trisomy 21
Trisomy 21 (also known by the karyotype 47,XX,+21 for females and 47,XY,+21 for males) is caused by a failure of the 21st chromosome to separate during egg or sperm development (nondisjunction). As a result, a sperm or egg cell is produced with an extra copy of chromosome 21; this cell thus has 24 chromosomes. When combined with a normal cell from the other parent, the baby has 47 chromosomes, with three copies of chromosome 21. About 88% of cases of trisomy 21 result from nonseparation of the chromosomes in the mother, 8% from nonseparation in the father, and 3% after the egg and sperm have merged.
Mosaicism
Mosaicism is diagnosed when there is a mixture of two types of cells: some cells have three copies of chromosome 21 but some cells have the typical two copies of chromosome 21. Mosaicism is the least common form of Down syndrome and accounts for only about 1% of all cases of Down syndrome. Children with mosaic Down syndrome may have the same features as other children with Down syndrome. However, they may have fewer characteristics of the condition due to the presence of some (or many) cells with a typical number of chromosomes.
Translocation
The extra chromosome 21 material may also occur due to a Robertsonian translocation in 2–4% of cases. In this situation, the long arm of chromosome 21 is attached to another chromosome, often chromosome 14. In a male affected with Down syndrome, it results in a karyotype of 46XY,t(14q21q). This may be a new mutation or previously present in one of the parents. The parent with such a translocation is usually normal physically and mentally; however, during production of egg or sperm cells, a higher chance of creating reproductive cells with extra chromosome 21 material exists. This results in a 15% chance of having a child with Down syndrome when the mother is affected and a less than 5% probability if the father is affected. The probability of this type of Down syndrome is not related to the mothers age. Some children without Down syndrome may inherit the translocation and have a higher probability of having children of their own with Down syndrome. In this case it is sometimes known as familial Down syndrome.
Mechanism
The extra genetic material present in Down syndrome results in overexpression of a portion of the 310 genes located on chromosome 21. This overexpression has been estimated at 50%, due to the third copy of the chromosome present. Some research has suggested the Down syndrome critical region is located at bands 21q22.1–q22.3, with this area including genes for the amyloid precursor protein, superoxide dismutase, and likely the ETS2 proto oncogene. Other research, however, has not confirmed these findings. MicroRNAs are also proposed to be involved.The dementia that occurs in Down syndrome is due to an excess of amyloid beta peptide produced in the brain and is similar to Alzheimers disease, which also involves amyloid beta build-up. Amyloid beta is processed from amyloid precursor protein, the gene for which is located on chromosome 21. Senile plaques and neurofibrillary tangles are present in nearly all by 35 years of age, though dementia may not be present. Those with Down syndrome also lack a normal number of lymphocytes and produce less antibodies which contributes to their increased risk of infection.
Epigenetics
Down syndrome is associated with an increased risk of many chronic diseases that are typically associated with older age such as Alzheimers disease. The accelerated aging suggest that trisomy 21 increases the biological age of tissues, but molecular evidence for this hypothesis is sparse. According to a biomarker of tissue age known as epigenetic clock, trisomy 21 increases the age of blood and brain tissue (on average by 6.6 years).
Diagnosis
Before birth
When screening tests predict a high possibility of Down syndrome, a more invasive diagnostic test (amniocentesis or chorionic villus sampling) is needed to confirm the diagnosis. The false-positive rate with screening is about 2–5% (see section Screening below). Amniocentesis and chorionic villus sampling are more reliable tests, but they increase the risk of miscarriage by between 0.5 and 1%. The risk of limb problems may be increased in the offspring if chorionic villus sampling is performed before 10 weeks. The risk from the procedure is greater the earlier it is performed, thus amniocentesis is not recommended before 15 weeks gestational age and chorionic villus sampling before 10 weeks gestational age.
Abortion rates
About 92% of pregnancies in Europe with a diagnosis of Down syndrome are terminated. As a result, there is almost no one with Down syndrome in Iceland and Denmark, where screening is commonplace. In the United States, the termination rate after diagnosis is around 75%, but varies from 61% to 93% depending on the population surveyed. Rates are lower among women who are younger and have decreased over time. When asked if they would have a termination if their fetus tested positive, 23–33% said yes, when high-risk pregnant women were asked, 46–86% said yes, and when women who screened positive are asked, 89–97% say yes.
After birth
The diagnosis can often be suspected based on the childs physical appearance at birth. An analysis of the childs chromosomes is needed to confirm the diagnosis, and to determine if a translocation is present, as this may help determine the chances of the childs parents having further children with Down syndrome. Parents generally wish to know the possible diagnosis once it is suspected and do not wish pity.
Screening
Guidelines recommend screening for Down syndrome to be offered to all pregnant women, regardless of age. A number of tests are used, with varying levels of accuracy. They are typically used in combination to increase the detection rate. None can be definitive, thus if screening is positive, either amniocentesis or chorionic villus sampling is required to confirm the diagnosis. Screening in both the first and second trimesters is better than just screening in the first trimester. The different screening techniques in use are able to pick up 90–95% of cases, with a false-positive rate of 2–5%. If Down syndrome occurs in one in 500 pregnancies with a 90% detection rate and the test used has a 5% false-positive rate, this means, of 26 women who test positive on screening, only one will have Down syndrome confirmed. If the screening test has a 2% false-positive rate, this means one of eleven who test positive on screening have a fetus with Down syndrome.
Ultrasound
Ultrasound imaging can be used to screen for Down syndrome. Findings that indicate increased chances when seen at 14 to 24 weeks of gestation include a small or no nasal bone, large ventricles, nuchal fold thickness, and an abnormal right subclavian artery, among others. The presence or absence of many markers is more accurate. Increased fetal nuchal translucency (NT) indicates an increased possibility of Down syndrome picking up 75–80% of cases and being falsely positive in 6%.
Blood tests
Several blood markers can be measured to predict the chances of Down syndrome during the first or second trimester. Testing in both trimesters is sometimes recommended and test results are often combined with ultrasound results. In the second trimester, often two or three tests are used in combination with two or three of: α-fetoprotein, unconjugated estriol, total hCG, and free βhCG detecting about 60–70% of cases.Testing of the mothers blood for fetal DNA is being studied and appears promising in the first trimester. The International Society for Prenatal Diagnosis considers it a reasonable screening option for those women whose pregnancies are at a high likelihood of trisomy 21. Accuracy has been reported at 98.6% in the first trimester of pregnancy. Confirmatory testing by invasive techniques (amniocentesis, CVS) is still required to confirm the screening result.
Management
Efforts such as early childhood intervention, screening for common problems, medical treatment where indicated, a good family environment, and work-related training can improve the development of children with Down syndrome. Education and proper care can improve quality of life. Raising a child with Down syndrome is more work for parents than raising an unaffected child. Typical childhood vaccinations are recommended.
Health screening
A number of health organizations have issued recommendations for screening those with Down syndrome for particular diseases. This is recommended to be done systematically.At birth, all children should get an electrocardiogram and ultrasound of the heart. Surgical repair of heart problems may be required as early as three months of age. Heart valve problems may occur in young adults, and further ultrasound evaluation may be needed in adolescents and in early adulthood. Due to the elevated risk of testicular cancer, some recommend checking the persons testicles yearly.
Cognitive development
Hearing aids or other amplification devices can be useful for language learning in those with hearing loss. Speech therapy may be useful and is recommended to be started around nine months of age. As those with Down syndrome typically have good hand-eye coordination, learning sign language may be possible. Augmentative and alternative communication methods, such as pointing, body language, objects, or pictures, are often used to help with communication. Behavioral issues and mental illness are typically managed with counseling or medications.Education programs before reaching school age may be useful. School-age children with Down syndrome may benefit from inclusive education (whereby students of differing abilities are placed in classes with their peers of the same age), provided some adjustments are made to the curriculum. Evidence to support this, however, is not very strong. In the United States, the Individuals with Disabilities Education Act of 1975 requires public schools generally to allow attendance by students with Down syndrome.Individuals with Down syndrome may learn better visually. Drawing may help with language, speech, and reading skills. Children with Down syndrome still often have difficulty with sentence structure and grammar, as well as developing the ability to speak clearly. Several types of early intervention can help with cognitive development. Efforts to develop motor skills include physical therapy, speech and language therapy, and occupational therapy. Physical therapy focuses specifically on motor development and teaching children to interact with their environment. Speech and language therapy can help prepare for later language. Lastly, occupational therapy can help with skills needed for later independence.
Other
Tympanostomy tubes are often needed and often more than one set during the persons childhood. Tonsillectomy is also often done to help with sleep apnea and throat infections. Surgery, however, does not always address the sleep apnea and a continuous positive airway pressure (CPAP) machine may be useful. Physical therapy and participation in physical education may improve motor skills. Evidence to support this in adults, however, is not very good.Efforts to prevent respiratory syncytial virus (RSV) infection with human monoclonal antibodies should be considered, especially in those with heart problems. In those who develop dementia there is no evidence for memantine, donepezil, rivastigmine, or galantamine.Plastic surgery has been suggested as a method of improving the appearance and thus the acceptance of people with Down syndrome. It has also been proposed as a way to improve speech. Evidence, however, does not support a meaningful difference in either of these outcomes. Plastic surgery on children with Down syndrome is uncommon, and continues to be controversial. The U.S. National Down Syndrome Society views the goal as one of mutual respect and acceptance, not appearance.Many alternative medical techniques are used in Down syndrome; however, they are poorly supported by evidence. These include: dietary changes, massage, animal therapy, chiropractic and naturopathy, among others. Some proposed treatments may also be harmful.
Prognosis
Between 5 and 15% of children with Down syndrome in Sweden attend regular school. Some graduate from high school; however, most do not. Of those with intellectual disability in the United States who attended high school about 40% graduated. Many learn to read and write and some are able to do paid work. In adulthood about 20% in the United States do paid work in some capacity. In Sweden, however, less than 1% have regular jobs. Many are able to live semi-independently, but they often require help with financial, medical, and legal matters. Those with mosaic Down syndrome usually have better outcomes.Individuals with Down syndrome have a higher risk of early death than the general population. This is most often from heart problems or infections. Following improved medical care, particularly for heart and gastrointestinal problems, the life expectancy has increased. This increase has been from 12 years in 1912, to 25 years in the 1980s, to 50 to 60 years in the developed world in the 2000s. Currently between 4 and 12% die in the first year of life. The probability of long-term survival is partly determined by the presence of heart problems. In those with congenital heart problems, 60% survive to 10 years and 50% survive to 30 years of age. In those without heart problems, 85% survive to 10 years and 80% survive to 30 years of age. About 10% live to 70 years of age. The National Down Syndrome Society provide information regarding raising a child with Down syndrome.
Epidemiology
Down syndrome is the most common chromosomal abnormality in humans. Globally, as of 2010, Down syndrome occurs in about 1 per 1,000 births and results in about 17,000 deaths. More children are born with Down syndrome in countries where abortion is not allowed and in countries where pregnancy more commonly occurs at a later age. About 1.4 per 1,000 live births in the United States and 1.1 per 1,000 live births in Norway are affected. In the 1950s, in the United States, it occurred in 2 per 1,000 live births with the decrease since then due to prenatal screening and abortions. The number of pregnancies with Down syndrome is more than two times greater with many spontaneously aborting. It is the cause of 8% of all congenital disorders.Maternal age affects the chances of having a pregnancy with Down syndrome. At age 20, the chance is 1 in 1,441; at age 30, it is 1 in 959; at age 40, it is 1 |
Down syndrome | in 84; and at age 50 it is 1 in 44. Although the probability increases with maternal age, 70% of children with Down syndrome are born to women 35 years of age and younger, because younger people have more children. The fathers older age is also a risk factor in women older than 35, but not in women younger than 35, and may partly explain the increase in risk as women age.
Life expectancy
The average life expectancy of a person with Down syndrome is more than 60 years and climbing.
History
English physician John Langdon Down first described Down syndrome in 1862, recognizing it as a distinct type of mental disability, and again in a more widely published report in 1866. Édouard Séguin described it as separate from cretinism in 1844. By the 20th century, Down syndrome had become the most recognizable form of mental disability.
In antiquity, many infants with disabilities were either killed or abandoned.
In June 2020, the earliest incidence of Down syndrome was found in genomic evidence from an infant that was buried before 3200 BC at Poulnabrone dolmen in Ireland.
Researchers believe that a number of historical pieces of art portray Down syndrome, including pottery from the pre-Columbian Tumaco-La Tolita culture in present-day Colombia and Ecuador, and the 16th-century painting The Adoration of the Christ Child.In the 20th century, many individuals with Down syndrome were institutionalized, few of the associated medical problems were treated, and most people died in infancy or early adulthood. With the rise of the eugenics movement, 33 of the then 48 U.S. states and several countries began programs of forced sterilization of individuals with Down syndrome and comparable degrees of disability. Action T4 in Nazi Germany made public policy of a program of systematic involuntary euthanization.With the discovery of karyotype techniques in the 1950s it became possible to identify abnormalities of chromosomal number or shape. In 1959 Jérôme Lejeune reported the discovery that Down syndrome resulted from an extra chromosome. However, Lejeunes claim to the discovery has been disputed, and in 2014 the Scientific Council of the French Federation of Human Genetics unanimously awarded its Grand Prize to his colleague Marthe Gautier for her role in this discovery. The discovery took place in the laboratory of Raymond Turpin at the Hôpital Trousseau in Paris, France. Jérôme Lejeune and Marthe Gautier were both his students.As a result of this discovery, the condition became known as trisomy 21. Even before the discovery of its cause, the presence of the syndrome in all races, its association with older maternal age, and its rarity of recurrence had been noticed. Medical texts had assumed it was caused by a combination of inheritable factors that had not been identified. Other theories had focused on injuries sustained during birth.
Society and culture
Name
Due to his perception that children with Down syndrome shared facial similarities with those of Blumenbachs Mongolian race, John Langdon Down used the term "mongoloid". He felt that the existence of Down syndrome confirmed that all peoples were genetically related. In the 1950s with discovery of the underlying cause as being related to chromosomes, concerns about the race-based nature of the name increased.In 1961, a group of nineteen scientists suggested that "mongolism" had "misleading connotations" and had become "an embarrassing term". The World Health Organization (WHO) dropped the term in 1965 after a request by the delegation from the Mongolian Peoples Republic. While the term mongoloid (also mongolism, Mongolian imbecility or idiocy) continued to be used until the early 1980s, it is now considered unacceptable and is no longer in common use.In 1975, the United States National Institutes of Health (NIH) convened a conference to standardize the naming and recommended replacing the possessive form, "Downs syndrome" with "Down syndrome". However, both the possessive and nonpossessive forms remain in use by the general population. The term "trisomy 21" is also commonly used.
Ethics
Most obstetricians argue that not offering screening for Down syndrome is unethical. As it is a medically reasonable procedure, per informed consent, people should at least be given information about it. It will then be the womans choice, based on her personal beliefs, how much or how little screening she wishes. When results from testing become available, it is also considered unethical not to give the results to the person in question.Some bioethicists deem it reasonable for parents to select a child who would have the highest well-being. One criticism of this reasoning is that it often values those with disabilities less. Some parents argue that Down syndrome should not be prevented or cured and that eliminating Down syndrome amounts to genocide. The disability rights movement does not have a position on screening, although some members consider testing and abortion discriminatory. Some in the United States who are anti-abortion support abortion if the fetus is disabled, while others do not. Of a group of 40 mothers in the United States who have had one child with Down syndrome, half agreed to screening in the next pregnancy.Within the US, some Protestant denominations see abortion as acceptable when a fetus has Down syndrome while Orthodox Christianity and Roman Catholicism do not. Some of those against screening refer to it as a form of eugenics. Disagreement exists within Islam regarding the acceptability of abortion in those carrying a fetus with Down syndrome. Some Islamic countries allow abortion, while others do not. Parents may be stigmatized whichever decision they make.
Advocacy groups
Advocacy groups for individuals with Down syndrome began to be formed after the Second World War. These were organizations advocating for the inclusion of people with Down syndrome into the general school system and for a greater understanding of the condition among the general population, as well as groups providing support for families with children living with Down syndrome. Before this individuals with Down syndrome were often placed in mental hospitals or asylums. Organizations included the Royal Society for Handicapped Children and Adults founded in the UK in 1946 by Judy Fryd, Kobato Kai founded in Japan in 1964, the National Down Syndrome Congress founded in the United States in 1973 by Kathryn McGee and others, and the National Down Syndrome Society founded in 1979 in the United States. The first Roman Catholic order of nuns for women with Down Syndrome, Little Sisters Disciples of the Lamb, was founded in 1985 in France.The first World Down Syndrome Day was held on 21 March 2006. The day and month were chosen to correspond with 21 and trisomy, respectively. It was recognized by the United Nations General Assembly in 2011.
Research
Efforts are underway to determine how the extra chromosome 21 material causes Down syndrome, as currently this is unknown, and to develop treatments to improve intelligence in those with the syndrome. Two efforts being studied are the use stem cells and gene therapy. Other methods being studied include the use of antioxidants, gamma secretase inhibition, adrenergic agonists, and memantine. Research is often carried out on an animal model, the Ts65Dn mouse.
Other hominids
Down syndrome may also occur in hominids other than humans. In great apes chromosome 22 corresponds to the human chromosome 21 and thus trisomy 22 causes Down syndrome in apes. The condition was observed in a common chimpanzee in 1969 and a Bornean orangutan in 1979, but neither lived very long. The common chimpanzee Kanako (born around 1993, in Japan) has become the longest-lived known example of this condition. Kanako has some of the same symptoms that are common in human Down syndrome. It is unknown how common this condition is in chimps but it is plausible it could be roughly as common as Down syndrome is in humans.
In popular culture
Struck by Lightning, an Australian film by Jerzy Domaradzki and starring Garry McDonald, is a comedy-drama depicting the efforts by a newly appointed physical education teacher to introduce soccer to a specialized school for youths with Down syndrome.
References
External links
Thompson, S.B.N. (2000). "The Central Executive System in people with Downs syndrome and dementia". Clinical Gerontologist. 21 (3): 3–32. Taylor & Francis (Routledge). DOI 10.1300/j018v21n03_02. eISSN 1545-2301. OCLC 1106716083. S2CID 218575706.
Thompson, S.B.N. (2000). "Investigation into Downs syndrome and dementia". Journal of the Association of Practitioners in Learning Disability, 17(3): 10–14.
Thompson, S.B.N. (1999). "Examining dementia in Downs syndrome (DS): decline in social abilities in DS compared with other learning disabilities". Clinical Gerontologist, 20(3): 23–44. Taylor & Francis (Routledge). DOI 10.1300/j018v20n03_04 eISSN 1545-2301 OCLC 1106716083
Fox, Nikki (2021-11-26). "World-leading Downs syndrome bill clears first hurdle in Parliament". BBC News. Archived from the original on 2021-11-27. Retrieved 2021-11-27.
External links
Down syndrome at Curlie
Downs syndrome by the UK National Health Service |
Joint dislocation | A joint dislocation, also called luxation, occurs when there is an abnormal separation in the joint, where two or more bones meet. A partial dislocation is referred to as a subluxation. Dislocations are often caused by sudden trauma on the joint like an impact or fall. A joint dislocation can cause damage to the surrounding ligaments, tendons, muscles, and nerves. Dislocations can occur in any major joint (shoulder, knees, etc.) or minor joint (toes, fingers, etc.). The most common joint dislocation is a shoulder dislocation.Treatment for joint dislocation is usually by closed reduction, that is, skilled manipulation to return the bones to their normal position. Reduction should only be performed by trained medical professionals, because it can cause injury to soft tissue and/or the nerves and vascular structures around the dislocation.
Symptoms and signs
The following symptoms are common with any type of dislocation.
Intense pain
Joint instability
Deformity of the joint area
Reduced muscle strength
Bruising or redness of joint area
Difficulty moving joint
Stiffness
Causes
Joint dislocations are caused by trauma to the joint or when an individual falls on a specific joint. Great and sudden force applied, by either a blow or fall, to the joint can cause the bones in the joint to be displaced or dislocated from normal position. With each dislocation, the ligaments keeping the bones fixed in the correct position can be damaged or loosened, making it easier for the joint to be dislocated in the future.Some individuals are prone to dislocations due to congenital conditions, such as hypermobility syndrome and Ehlers-Danlos Syndrome. Hypermobility syndrome is genetically inherited disorder that is thought to affect the encoding of the connective tissue protein’s collagen in the ligament of joints. The loosened or stretched ligaments in the joint provide little stability and allow for the joint to be easily dislocated.
Diagnosis
Initial evaluation of a suspected joint dislocation should begin with a thorough patient history, including mechanism of injury, and physical examination. Special attention should be focused on the neurovascular exam both before and after reduction, as injury to these structures may occur during the injury or during the reduction process. Subsequent imaging studies are frequently obtained to assist with diagnosis.
Standard plain radiographs, usually a minimum of 2 views
Generally, pre- and post-reduction X-rays are recommended. Initial X-ray can confirm the diagnosis as well as evaluate for any concomitant fractures. Post-reduction radiographs confirm successful reduction alignment and can exclude any other bony injuries that may have been caused during the reduction procedure.
In certain instances if initial X-rays are normal but injury is suspected, there is possible benefit of stress/weight-bearing views to further assess for disruption of ligamentous structures and/or need for surgical intervention. This may be utilized with AC joint separations.
Nomenclature: Joint dislocations are named based on the distal component in relation to the proximal one.
Ultrasound
Ultrasound may be useful in an acute setting, particularly with suspected shoulder dislocations. Although it may not be as accurate in detecting any associated fractures, in one observational study ultrasonography identified 100% of shoulder dislocations, and was 100% sensitive in identifying successful reduction when compared to plain radiographs. Ultrasound may also have utility in diagnosing AC joint dislocations.
In infants <6 months of age with suspected developmental dysplasia of the hip (congenital hip dislocation), ultrasound is the imaging study of choice as the proximal femoral epiphysis has not significantly ossified at this age.
Cross-sectional imaging (CT or MRI)
Plain films are generally sufficient in making a joint dislocation diagnosis. However, cross-sectional imaging can subsequently be used to better define and evaluate abnormalities that may be missed or not clearly seen on plain X-rays. CT is useful in further analyzing any bony aberrations, and CT angiogram may be utilized if vascular injury is suspected. In addition to improved visualization of bony abnormalities, MRI permits for a more detailed inspection of the joint-supporting structures in order to assess for ligamentous and other soft tissue injury.
Treatment
A dislocated joint usually can be successfully reduced into its normal position only by a trained medical professional. Trying to reduce a joint without any training could substantially worsen the injury.X-rays are usually taken to confirm a diagnosis and detect any fractures which may also have occurred at the time of dislocation. A dislocation is easily seen on an X-ray.Once a diagnosis is confirmed, the joint is usually manipulated back into position. This can be a very painful process, therefore this is typically done either in the emergency department under sedation or in an operating room under a general anaesthetic.It is important the joint is reduced as soon as possible, as in the state of dislocation, the blood supply to the joint (or distal anatomy) may be compromised. This is especially true in the case of a dislocated ankle, due to the anatomy of the blood supply to the foot.Shoulder injuries can also be surgically stabilized, depending on the severity, using arthroscopic surgery. The most common treatment method for a dislocation of the Glenohumeral Joint (GH Joint/Shoulder Joint) is exercise based management. Another method of treatment is to place the injured arm in a sling or in another immobilizing device in order to keep the joint stable.Some joints are more at risk of becoming dislocated again after an initial injury. This is due to the weakening of the muscles and ligaments which hold the joint in place. The shoulder is a prime example of this. Any shoulder dislocation should be followed up with thorough physiotherapy.On field reduction is crucial for joint dislocations. As they are extremely common in sports events, managing them correctly at the game at the time of injury, can reduce long term issues. They require prompt evaluation, diagnosis, reduction, and postreduction management before the person can be evaluated at a medical facility.
After care
After a dislocation, injured joints are usually held in place by a splint (for straight joints like fingers and toes) or a bandage (for complex joints like shoulders). Additionally, the joint muscles, tendons and ligaments must also be strengthened. This is usually done through a course of physiotherapy, which will also help reduce the chances of repeated dislocations of the same joint.For glenohumeral instability, the therapeutic program depends on specific characteristics of the instability pattern, severity, recurrence and direction with adaptations made based on the needs of the patient. In general, the therapeutic program should focus on restoration of strength, normalization of range of motion and optimization of flexibility and muscular performance. Throughout all stages of the rehabilitation program, it is important to take all related joints and structures into consideration.
Epidemiology
Each joint in the body can be dislocated, however, there are common sites where most dislocations occur. The following structures are the most common sites of joint dislocations:
Dislocated shoulder
Shoulder dislocations account for 45% of all dislocation visits to the emergency room. Anterior shoulder dislocation, the most common type of shoulder dislocation (96-98% of the time) occurs when the arm is in external rotation and abduction (away from the body) produces a force that displaces the humeral head anteriorly and downwardly. Vessel and nerve injuries during a shoulder dislocation is rare, but can cause many impairments and requires a longer recovery process. There is a 39% average rate of recurrence of anterior shoulder dislocation, with age, sex, hyperlaxity and greater tuberosity fractures being the key risk factors.
Knee: Patellar dislocation
Many different knee injuries can happen. Three percent of knee injuries are acute traumatic patellar dislocations. Because dislocations make the knee unstable, 15% of patellas will re-dislocate.
Patellar dislocations occur when the knee is in full extension and sustains a trauma from the lateral to medial side.
Elbow: Posterior dislocation, 90% of all elbow dislocations
Wrist: Lunate and Perilunate dislocation most common
Finger: Interphalangeal (IP) or metacarpophalangeal (MCP) joint dislocationsIn the United States, men are most likely to sustain a finger dislocation with an incidence rate of 17.8 per 100,000 person-years. Women have an incidence rate of 4.65 per 100,000 person-years. The average age group that sustain a finger dislocation are between 15 and 19 years old.
Hip: Posterior and anterior dislocation of hip
Anterior dislocations are less common than posterior dislocations. 10% of all dislocations are anterior and this is broken down into superior and inferior types. Superior dislocations account for 10% of all anterior dislocations, and inferior dislocations account for 90%. 16-40 year old males are more likely to receive dislocations due to a car accident. When an individual receives a hip dislocation, there is an incidence rate of 95% that they will receive an injury to another part of their body as well. 46–84% of hip dislocations occur secondary to traffic accidents, the remaining percentage is due based on falls, industrial accidents or sporting injury.
Foot and Ankle:
Lisfranc injury is a dislocation or fracture-dislocation injury at the tarsometatarsal joints
Subtalar dislocation, or talocalcaneonavicular dislocation, is a simultaneous dislocation of the talar joints at the talocalcaneal and talonavicular levels. Subtalar dislocations without associated fractures represent about 1% of all traumatic injuries of the foot and 1-2 % of all dislocations, and they are associated with high energy trauma. Early closed reduction is recommended, otherwise open reduction without further delay.
Total talar dislocation is very rare and has very high rates of complications.
Ankle Sprains primarily occur as a result of tearing the ATFL (anterior talofibular ligament) in the Talocrural Joint. The ATFL tears most easily when the foot is in plantarflexion and inversion.
Ankle dislocation without fracture is rare.
Gallery
See also
Buddy wrapping
Major trauma
Physical therapy
Projectional radiography
Listhesis, olisthesis, or olisthy
References
External links |
Gilberts syndrome | Gilbert syndrome (GS) is a syndrome in which the liver of affected individuals processes bilirubin more slowly than the majority. Many people never have symptoms. Occasionally jaundice (a slight yellowish color of the skin or whites of the eyes) may occur.Gilbert syndrome is due to a genetic variant in the UGT1A1 gene which results in decreased activity of the bilirubin uridine diphosphate glucuronosyltransferase enzyme. It is typically inherited in an autosomal recessive pattern and occasionally in an autosomal dominant pattern depending on the type of variant. Episodes of jaundice may be triggered by stress such as exercise, menstruation, or not eating. Diagnosis is based on higher levels of unconjugated bilirubin in the blood without either signs of other liver problems or red blood cell breakdown.Typically no treatment is needed. Gilbert syndrome is associated with decreased cardiovascular health risks. If jaundice is significant phenobarbital may be used, which aids in the conjugation of bilirubin. Gilbert syndrome affects about 5% of people in the United States. Males are more often diagnosed than females. It is often not noticed until late childhood to early adulthood. The condition was first described in 1901 by Augustin Nicolas Gilbert.
Signs and symptoms
Jaundice
Gilbert syndrome produces an elevated level of unconjugated bilirubin in the bloodstream, but normally has no consequences. Mild jaundice may appear under conditions of exertion, stress, fasting, and infections, but the condition is otherwise usually asymptomatic. Severe cases are seen by yellowing of the skin tone and yellowing of the conjunctiva in the eye.Gilbert syndrome has been reported to contribute to an accelerated onset of neonatal jaundice. The syndrome cannot cause severe indirect hyperbilirubinemia in neonates by itself, but it may have a summative effect on rising bilirubin when combined with other factors, for example in the presence of increased red blood cell destruction due to diseases such as G6PD deficiency. This situation can be especially dangerous if not quickly treated, as the high bilirubin causes irreversible neurological disability in the form of kernicterus.
Detoxification of certain drugs
The enzymes that are defective in GS – UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) – are also responsible for some of the livers ability to detoxify certain drugs. For example, Gilbert syndrome is associated with severe diarrhea and neutropenia in patients who are treated with irinotecan, which is metabolized by UGT1A1.While paracetamol (acetaminophen) is not metabolized by UGT1A1, it is metabolized by one of the other enzymes also deficient in some people with GS. A subset of people with GS may have an increased risk of paracetamol toxicity.
Cardiovascular effects
The mild increase in unconjugated bilirubin due to Gilbert syndrome is closely related to the reduction in the prevalence of chronic diseases, especially cardiovascular disease and type 2 diabetes, related risk factors, and all-cause mortality. Observational studies emphasize that the antioxidant effects of unconjugated bilirubin may bring survival benefits to patients.Several analyses have found a significantly decreased risk of coronary artery disease (CAD) in individuals with GS.Specifically, people with mildly elevated levels of bilirubin (1.1 mg/dl to 2.7 mg/dl) were at lower risk for CAD and at lower risk for future heart disease. These researchers went on to perform a meta-analysis of data available up to 2002, and confirmed the incidence of atherosclerotic disease (hardening of the arteries) in subjects with GS had a close and inverse relationship to the serum bilirubin. This beneficial effect was attributed to bilirubin IXα which is recognized as a potent antioxidant, rather than confounding factors such as high-density lipoprotein levels.This association was also seen in long-term data from the Framingham Heart Study. Moderately elevated levels of bilirubin in people with GS and the (TA)7/(TA)7 genotype were associated with one-third the risk for both coronary heart disease and cardiovascular disease as compared to those with the (TA)6/(TA)6 genotype (i.e. a normal, nonmutated gene locus).Platelet counts and MPV (mean platelet volume) are decreased in patients with Gilberts syndrome. The elevated levels of bilirubin and decreasing levels of MPV and CRP in Gilberts syndrome patients may have an effect on the slowing down of the atherosclerotic process.
Other
Symptoms, whether connected or not to GS, have been reported in a subset of those affected: fatigue (feeling tired all the time), difficulty maintaining concentration, unusual patterns of anxiety, loss of appetite, nausea, abdominal pain, loss of weight, itching (with no rash), and others, such as humor change or depression. But scientific studies found no clear pattern of adverse symptoms related to the elevated levels of unconjugated bilirubin in adults. However, other substances glucuronidized by the affected enzymes in those with Gilberts syndrome could theoretically, at their toxic levels, cause these symptoms. Consequently, debate exists about whether GS should be classified as a disease. However, Gilbert syndrome has been linked to an increased risk of gallstones.
Cause
Mutations in the UGT1A1 gene lead to Gilbert Syndrome. The gene provides instructions for making the bilirubin uridine diphosphate glucuronosyltransferase (bilirubin-UGT) enzyme, which can be found in the liver cells and responsible for the removal of bilirubin from the body.The bilirubin-UGT enzyme performs a chemical reaction called glucuronidation. Glucuronic acid is transferred to unconjugated bilirubin, which is a yellowish pigment made when your body breaks down old red blood cells, and then being converted to conjugated bilirubin during the reaction. Conjugated bilirubin passes from the liver into the intestines with bile. Its then excreted in stool.
People with Gilbert syndrome have approximately 30 percent of normal bilirubin-UGT enzyme function, which contributes to a lower rate of glucuronidation of unconjugated bilirubin. This toxic substance then accumulates in the body, causing mild hyperbilirubinemia.
Genetics
Gilbert syndrome is a phenotypic effect, mostly associated with increased blood bilirubin levels, but also sometimes characterized by mild jaundice due to increased unconjugated bilirubin, that arises from several different genotypic variants of the gene for the enzyme responsible for changing bilirubin to the conjugated form.Gilberts syndrome is characterized by a 70–80% reduction in the glucuronidation activity of the enzyme (UGT1A1). The UGT1A1 gene is located on human chromosome 2.More than 100 polymorphisms of the UGT1A1 gene are known, designated as UGT1A1*n (where n is the general chronological order of discovery), either of the gene itself or of its promoter region. UGT1A1 is associated with a TATA box promoter region; this region most commonly contains the genetic sequence A(TA)6TAA; this variant accounts for about 50% of alleles in many populations. However, several allelic polymorphic variants of this region occur, the most common of which results from adding another dinucleotide repeat TA to the promoter region, resulting in A(TA)7TAA, which is called UGT1A1*28; this common variant accounts for about 40% of alleles in some populations, but is seen less often, around 3% of alleles, in Southeast and East Asian people and Pacific Islanders.In most populations, Gilbert syndrome is most commonly associated with homozygous A(TA)7TAA alleles. In 94% of GS cases, two other glucuronosyltransferase enzymes, UGT1A6 (rendered 50% inactive) and UGT1A7 (rendered 83% ineffective), are also affected.However, Gilbert syndrome can arise without TATA box promoter polymorphic variants; in some populations, particularly healthy Southeast and East Asians, Gilberts syndrome is more often a consequence of heterozygote missense mutations (such as Gly71Arg also known as UGT1A1*6, Tyr486Asp also known as UGT1A1*7, Pro364Leu also known as UGT1A1*73) in the actual gene coding region, which may be associated with significantly higher bilirubin levels.Because of its effects on drug and bilirubin breakdown and because of its genetic inheritance, Gilberts syndrome can be classed as a minor inborn error of metabolism.
Diagnosis
People with GS predominantly have elevated unconjugated bilirubin, while conjugated bilirubin is usually within the normal range or is less than 20% of the total. Levels of bilirubin in GS patients are reported to be from 20 μM to 90 μM (1.2 to 5.3 mg/dl) compared to the normal amount of < 20 μM. GS patients have a ratio of unconjugated/conjugated (indirect/direct) bilirubin commensurately higher than those without GS.The level of total bilirubin is often further increased if the blood sample is taken after fasting for two days, and a fast can, therefore, be useful diagnostically. A further conceptual step that is rarely necessary or appropriate is to give a low dose of phenobarbital: the bilirubin will decrease substantially.
Tests can also detect DNA variants of UGT1A1 by polymerase chain reaction or DNA fragment sequencing.
Differential diagnosis
While Gilbert syndrome is considered harmless, it is clinically important because it may give rise to a concern about a blood or liver condition, which could be more dangerous. However, these conditions have additional indicators:
In GS, unless another disease of the liver is also present, the liver enzymes ALT/SGPT and AST/SGOT, as well as albumin, are within normal ranges.
More severe types of glucuronyl transferase disorders such as Crigler–Najjar syndrome (types I and II) are much more severe, with 0–10% UGT1A1 activity, with affected individuals at risk of brain damage in infancy (type I) and teenage years (type II).
Hemolysis of any cause can be excluded by a full blood count, haptoglobin, lactate dehydrogenase levels, and the absence of reticulocytosis (elevated reticulocytes in the blood would usually be observed in haemolytic anaemia).
Dubin–Johnson syndrome and Rotor syndrome are rarer autosomal recessive disorders characterized by an increase of conjugated bilirubin.
Viral hepatitis associated with increase of conjugated bilirubin can be excluded by negative blood samples for antigens specific to the different hepatitis viruses.
Cholestasis can be excluded by normal levels of bile acids in plasma, the absence of lactate dehydrogenase, low levels of conjugated bilirubin, and ultrasound scan of the bile ducts.
Vitamin B12 deficiency - elevated bilirubin levels (and MCV counts above 90–92) can be associated with a vitamin B12 deficiency.
Treatment
Typically no treatment is needed. If jaundice is significant phenobarbital may be used.
History
Gilbert syndrome was first described by French gastroenterologist Augustin Nicolas Gilbert and co-workers in 1901. In German literature, it is commonly associated with Jens Einar Meulengracht.Alternative, less common names for this disorder include:
Familial benign unconjugated hyperbilirubinaemia
Constitutional liver dysfunction
Familial non-hemolytic non-obstructive jaundice
Icterus intermittens juvenilis
Low-grade chronic hyperbilirubinemia
Unconjugated benign bilirubinemia
Society and culture
Notable cases
Napoleon
Arthur Kornberg, Nobel laureate in Physiology or Medicine, 1959
Nicky Wire, Manic Street Preachers bassist
Alexandr Dolgopolov (tennis player)
Jonas Folger, MotoGP riderHuo Yuanjia (master of Chinese martial art)David Barnea (Mossad Chief)
References
External links
Understanding Gilberts Syndrome and living better with Gilberts Syndrome symptoms
Gilberts syndrome at NIHs Office of Rare Diseases
Gilberts Syndrome BMJ Best Practices monograph |
Hip dysplasia | Hip dysplasia is an abnormality of the hip joint where the socket portion does not fully cover the ball portion, resulting in an increased risk for joint dislocation. Hip dysplasia may occur at birth or develop in early life. Regardless, it does not typically produce symptoms in babies less than a year old. Occasionally one leg may be shorter than the other. The left hip is more often affected than the right. Complications without treatment can include arthritis, limping, and low back pain.Risk factors for hip dysplasia include family history, certain swaddling practices, and breech birth. If one identical twin is affected, there is a 40% risk the other will also be affected. Screening all babies for the condition by physical examination is recommended. Ultrasonography may also be useful.Many of those with mild instability resolve without specific treatment. In more significant cases, if detected early, bracing may be all that is required. In cases that are detected later, surgery and casting may be needed. About 7.5% of hip replacements are done to treat problems which have arisen from hip dysplasia.About 1 in 1,000 babies have hip dysplasia. Hip instability of meaningful importance occurs in one to two percent of babies born at term. Females are affected more often than males. Hip dysplasia was described at least as early as the 300s BC by Hippocrates.
Signs and symptoms
Hip dysplasia can range from barely detectable to severely malformed or dislocated.
The congenital form, teratologic or non-reducible dislocation occurs as part of more complex conditions.The condition can be bilateral or unilateral:
If both hip joints are affected, one speaks of "bilateral" dysplasia. In this case, some diagnostic indicators like asymmetric folds and leg-length inequality do not apply.
In unilateral dysplasia only one joint shows deformity, the contralateral side may show resulting effects. In the majority of unilateral cases, the left hip has the dysplasia.If the joint is fully dislocated a false acetabulum often forms (often higher up on the pelvis) opposite the dislocated femoral head position.
In acetabular dysplasia, the acetabulum (socket) is too shallow or deformed. The center-edge angle is measured as described by Wiberg. Two forms of femoral dysplasia are coxa vara, in which the femur head grows at too narrow an angle to the shaft, and coxa valga, in which the angle is too wide.
A rare type, the "Beukes familial hip dysplasia" is found among Afrikaners that are members of the Beukes family. The femur head is flat and irregular. People develop osteoarthritis at an early age.
Causes
Hip dysplasia is considered to be a multifactorial condition. That means that several factors are involved in causing the condition to manifest.The cause of this condition is unknown; however, some factors of congenital hip dislocation are through heredity and racial background. It is also thought that the higher rates in some ethnic groups (such as some Native American groups) is due to the practice of swaddling of infants, which is known to be a potential risk factor for developing dysplasia. It also has a low risk in African Americans and southern Chinese.
Congenital
Some studies suggest a hormonal link. Specifically, the hormone relaxin has been indicated.A genetic factor is indicated since the trait runs in families and there is an increased occurrence in some ethnic populations (e.g., Native Americans, Lapps / Sami people). A locus has been described on chromosome 13. Beukes familial dysplasia, on the other hand, was found to map to an 11-cM region on chromosome 4q35, with nonpenetrant carriers not affected.
Acquired
As an acquired condition it has often been linked to traditions of swaddling infants, use of overly restrictive baby seats, carriers and other methods of transporting babies, or use of a cradle board which locks the hip joint in an "adducted" position (pulling the knees together tends to pull the heads of the femur bone out of the sockets or acetabulae) for extended periods. Modern swaddling techniques, such as the hip healthy swaddle have been developed to relieve stress on hip joints caused by traditional swaddling methods.Further risk factors include breech birth, gender, genetics (family history), and firstborns. In breech position the femoral head tends to get pushed out of the socket. A narrow uterus also facilitates hip joint dislocation during fetal development and birth.
Diagnosis
Most countries have standard newborn exams that include a hip joint exam screening for early detection of hip dysplasia.
Sometimes during an exam a "click" or more precisely "clunk" in the hip may be detected (although not all clicks indicate hip dysplasia). When a hip click (also known as "clicky hips" in the UK) is detected, the childs hips are tracked with additional screenings to determine if developmental dysplasia of the hip is caused.Two maneuvers commonly employed for diagnosis in neonatal exams are the Ortolani maneuver and the Barlow maneuver.In order to do the Ortolani maneuver it is recommended that the examiner put the newborn baby in a position in which the contralateral hip is held still while the thigh of the hip being tested is abducted and gently pulled anteriorly. If a "clunk" is heard (the sound of the femoral head moving over the acetabulum), the joint is normal, but absence of the "clunk" sound indicates that the acetabulum is not fully developed. The next method that can be used is called the Barlow maneuver. It is done by adducting the hip while pushing the thigh posteriorly. If the hip goes out of the socket it means it is dislocated, and the newborn has a congenital hip dislocation. The baby is laid on its back for examination by separation of its legs. If a clicking sound can be heard, it indicates that the baby may have a dislocated hip. It is highly recommended that these maneuvers be done when the baby is not fussing, because the baby may inhibit hip movement.Asymmetrical gluteal folds and an apparent limb-length inequality can further indicate unilateral hip dysplasia. Most vexingly, many newborn hips show a certain ligamentous laxity, on the other hand severely malformed joints can appear stable. That is one reason why follow-up exams and developmental monitoring are important. Frequency and methods of routine screenings in children is still in debate however physical examination of newborns followed by appropriate use of hip ultrasound is widely accepted.The Harris hip score (developed by William H. Harris MD, an orthopedist from Massachusetts) is one way to evaluate hip function following surgery. Other scoring methods are based on patients evaluation like e.g. the Oxford hip score, HOOS and WOMAC score. Childrens Hospital Oakland Hip Evaluation Scale (CHOHES) is a modification of the Harris hip score that is currently being evaluated.Hip dysplasia can develop in older age. Adolescents and adults with hip dysplasia may present with hip pain and in some cases hip labral tears. X-rays are used to confirm a diagnosis of hip dysplasia. CT scans and MRI scans are occasionally used too.
Terminology
Some sources prefer "developmental dysplasia of the hip" (DDH) to "congenital dislocation of the hip" (CDH), finding the latter term insufficiently flexible in describing the diversity of potential complications.The use of the word congenital can also imply that the condition already exists at birth. This terminology introduces challenges, because the joint in a newborn is formed from cartilage and is still malleable, making the onset difficult to ascertain. The newer term DDH also encompasses occult dysplasia (e.g. an underdeveloped joint) without dislocation and a dislocation developing after the "newborn" phase.The term is not used consistently. In pediatric/neonatal orthopedics it is used to describe unstable/dislocatable hips and poorly developed acetabula. For adults it describes hips showing abnormal femur head or acetabular x-rays.Some sources prefer the term "hip dysplasia" over DDH, considering it to be "simpler and more accurate", partly because of the redundancy created by the use of the terms developmental and dysplasia. Types of DDH include subluxation, dysplasia, and dislocation. The main types are the result of either laxity of the supporting capsule or an abnormal acetabulum.
Imaging
Hip dysplasia diagnosed by ultrasound and projectional radiography ("X-ray"). Ultrasound imaging is generally preferred at up to 4 months due to limited ossification of the skeleton.Despite the widespread of ultrasound, pelvis X-ray is still frequently used to diagnose or monitor hip dysplasia or for assessing other congenital conditions or bone tumors. The most useful lines and angles that can be drawn in the pediatric pelvis assessing hip dysplasia are as follows: Different measurements are used in adults.
Treatment
Hip dysplasia presents a nearly perfect equilibrium between the arthritis, movement/mobility problems and pain associated with the developmental malformation, and the arthritis, movement/mobility problems and pain that are, as often as not in moderate to severe cases, inflicted by the treatment itself.However, given the very real possibility of a limp, constant and/or debilitating pain, complicated treatment and impaired mobility later in life, careful developmental monitoring is indicated and early intervention is often the best result. The worst possible consequence of non treatment is developing early arthritis, sometimes even during teenage years. All treatment aims to delay the onset of arthritis, but no treatment is fully successful in avoiding it; and, all available treatments bear the risk of inflicting equivalent damage. Most unfortunately, studies have as yet been unable to find a method of predicting outcomes in either the surgical/orthopedic treatment of the condition in infants and young children, or the surgical treatment of these early treatments negative outcomes later in life (such as arthritis, avascular necrosis, trochanteric bursitis, and bone spurs of up to 3.5 cm just medial of the gluteus maximus insertion point on the greater trochanter due to excessive friction).
Harnesses, casts, and traction
Early hip dysplasia can often be treated using a Pavlik harness (see photograph) or the Frejka pillow/splint in the first year of life with usually normal results. Complications can occur when using the Pavlik harness. Cases of femoral nerve palsy and avascular necrosis of the femoral head have been reported with the use of the Pavlik harness, but whether these cases were due to improper application of the device or a complication encountered in the course of the disorder remains unresolved. Complications arise mainly because the sheet of the iliopsoas muscle pushes the circumflex artery against the neck of the femur and decreases blood flow to the femoral head, so the Frejka pillow is not indicated in all the forms of the developmental dysplasia of the hip.
Other devices employed include the spica cast, particularly following surgical closed reduction, open reduction, or osteotomy in babies and young children. Traction is sometimes used in the weeks leading up to a surgery to help stretch ligaments in the hip joint, although its use is controversial and varies amongst physicians.
Surgery
In older children the adductor and iliopsoas muscles may have to be treated surgically because they adapt to the dislocated joint position (contracture).
Braces and splints are often used following either of these methods to continue treatment.
Although some children "outgrow" untreated mild hip dysplasia and some forms of untreated dysplasia cause little or no impairment of quality of life, studies have as yet been unable to find a method of predicting outcomes. On the other hand, it has often been documented that starting treatment late leads to complications and ends in poor results.
Hip replacement and osteotomy
Hip dysplasia is often cited as causing osteoarthritis of the hip at a comparatively young age. Dislocated load bearing surfaces lead to increased and unusual wear, although there are studies that contradict these findings (see). Peri-acetabular osteotomy (PAO) surgery can be used to realign the hip joint in some adolescents and adults. Subsequent treatment with total hip arthroplasty (hip replacement) is complicated by a need for revision surgery (replacing the artificial joint) owing to skeletal changes as the body matures, loosening/wear or bone resorption. Hip resurfacing is another option for correcting hip dysplasia in adults. It is a type of hip replacement that preserves more bone, and may work for younger hip dysplasia patients.Osteotomies are either used in conjunction with arthroplasty or by themselves to correct misalignment.
Epidemiology
Determining the incidence can be difficult. In addition there is a wide margin in diagnostic results. A German study comparing two methods resulted in twice the usual rate for one method. The condition is eight times more frequent in females than in males.Native Americans are more likely to have congenital hip dislocation than any of the other races. The risk for Native Americans is about 25–50 in 1000. The overall frequency of developmental dysplasia of the hip is approximately 1 case per 1000 individuals; however, Barlow believed that the incidence of hip instability in newborns can be as high as 1 case for every 60 newborns, with the rate dropping to 1:240 at one week.
History
The Frejka pillow splint was named after Dr. Bedrich Frejka (1890-1972), a Czech orthopedic surgeon. The Pavlik harness was named after Dr. Arnold Pavlik (1902-1962), also a Czech orthopedic surgeon.
Society and culture
In the television program ER, Kerry Weaver uses a crutch owing to congenital hip dysplasia. In season 12, she undergoes a hip replacement to cure her dysplasia when her previously untreated joint worsens.
Research
One avenue of research is using stem cells. They are applied in grafting (bone grafting) or by seeding porous arthroplasty prosthesis with autologous fibroblasts or chondrocyte progenitor cells to assist in firmly anchoring the artificial material in the bone bed.
Other animals
In dogs, hip dysplasia is an abnormal formation of the hip socket that, in its more severe form, can eventually cause crippling lameness and painful arthritis of the joints. It is a genetic (polygenic) trait that is affected by environmental factors. It is common in many dog breeds, particularly the larger breeds.Hip dysplasia is one of the most studied veterinary conditions in dogs, and the most common single cause of arthritis of the hips. Cats are also known to have this condition, especially Siamese.
Notes
References
External links
Online orthopedic textbook |
Hypothermia | Hypothermia is defined as a body core temperature below 35.0 °C (95.0 °F) in humans. Symptoms depend on the temperature. In mild hypothermia, there is shivering and mental confusion. In moderate hypothermia, shivering stops and confusion increases. In severe hypothermia, there may be hallucinations and paradoxical undressing, in which a person removes their clothing, as well as an increased risk of the heart stopping.Hypothermia has two main types of causes. It classically occurs from exposure to cold weather and cold water immersion. It may also occur from any condition that decreases heat production or increases heat loss. Commonly, this includes alcohol intoxication but may also include low blood sugar, anorexia and advanced age. Body temperature is usually maintained near a constant level of 36.5–37.5 °C (97.7–99.5 °F) through thermoregulation. Efforts to increase body temperature involve shivering, increased voluntary activity, and putting on warmer clothing. Hypothermia may be diagnosed based on either a persons symptoms in the presence of risk factors or by measuring a persons core temperature.The treatment of mild hypothermia involves warm drinks, warm clothing, and voluntary physical activity. In those with moderate hypothermia, heating blankets and warmed intravenous fluids are recommended. People with moderate or severe hypothermia should be moved gently. In severe hypothermia, extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass may be useful. In those without a pulse, cardiopulmonary resuscitation (CPR) is indicated along with the above measures. Rewarming is typically continued until a persons temperature is greater than 32 °C (90 °F). If there is no improvement at this point or the blood potassium level is greater than 12 mmol/liter at any time, resuscitation may be discontinued.Hypothermia is the cause of at least 1,500 deaths a year in the United States. It is more common in older people and males. One of the lowest documented body temperatures from which someone with accidental hypothermia has survived is 13.0 °C (55.4 °F) in a near-drowning of a 7-year-old girl in Sweden. Survival after more than six hours of CPR has been described. In individuals for whom ECMO or bypass is used, survival is around 50%. Deaths due to hypothermia have played an important role in many wars.The term is from Greek ῠ̔πο (ypo), meaning "under", and θέρμη (thérmē), meaning "heat". The opposite of hypothermia is hyperthermia, an increased body temperature due to failed thermoregulation.
Classification
Hypothermia is often defined as any body temperature below 35.0 °C (95.0 °F). With this method it is divided into degrees of severity based on the core temperature.Another classification system, the Swiss staging system, divides hypothermia based on the presenting symptoms which is preferred when it is not possible to determine an accurate core temperature.Other cold-related injuries that can be present either alone or in combination with hypothermia include:
Chilblains: condition caused by repeated exposure of skin to temperatures just above freezing. The cold causes damage to small blood vessels in the skin. This damage is permanent and the redness and itching will return with additional exposure. The redness and itching typically occurs on cheeks, ears, fingers, and toes.
Frostbite: the freezing and destruction of tissue, which happens below the freezing point of water
Frostnip: a superficial cooling of tissues without cellular destruction
Trench foot or immersion foot: a condition caused by repetitive exposure to water at non-freezing temperaturesThe normal human body temperature is often stated as 36.5–37.5 °C (97.7–99.5 °F). Hyperthermia and fever, are defined as a temperature of greater than 37.5–38.3 °C (99.5–100.9 °F).
Signs and symptoms
Signs and symptoms vary depending on the degree of hypothermia, and may be divided by the three stages of severity. People with hypothermia may appear pale and feel cold to touch.
Infants with hypothermia may feel cold when touched, with bright red skin and an unusual lack of energy.Cold stress refers to a near-normal body temperature with low skin temperature, signs include shivering. Cold stress is caused by cold exposure and it can lead to hypothermia and frostbite if not treated.
Individuals with hypothermia often have impaired judgement, impaired sense of time and place, unusual aggression and numbness. A person with hypothermia can be euphoric and hallucinating.
Mild
Symptoms of mild hypothermia may be vague, with sympathetic nervous system excitation (shivering, high blood pressure, fast heart rate, fast respiratory rate, and contraction of blood vessels). These are all physiological responses to preserve heat. Increased urine production due to cold, mental confusion, and liver dysfunction may also be present. Hyperglycemia may be present, as glucose consumption by cells and insulin secretion both decrease, and tissue sensitivity to insulin may be blunted. Sympathetic activation also releases glucose from the liver. In many cases, however, especially in people with alcoholic intoxication, hypoglycemia appears to be a more common cause. Hypoglycemia is also found in many people with hypothermia, as hypothermia may be a result of hypoglycemia.
Moderate
As hypothermia progresses, symptoms include: mental status changes such as amnesia, confusion, slurred speech, decreased reflexes, and loss of fine motor skills.
Severe
As the temperature decreases, further physiological systems falter and heart rate, respiratory rate, and blood pressure all decrease. This results in an expected heart rate in the 30s at a temperature of 28 °C (82 °F).There is often cold, inflamed skin, hallucinations, lack of reflexes, fixed dilated pupils, low blood pressure, pulmonary edema, and shivering is often absent. Pulse and respiration rates decrease significantly, but fast heart rates (ventricular tachycardia, atrial fibrillation) can also occur. Atrial fibrillation is not typically a concern in and of itself.
Paradoxical undressing
Twenty to fifty percent of hypothermia deaths are associated with paradoxical undressing. This typically occurs during moderate and severe hypothermia, as the person becomes disoriented, confused, and combative. They may begin discarding their clothing, which, in turn, increases the rate of heat loss.Rescuers who are trained in mountain survival techniques are taught to expect this; however, people who die from hypothermia in urban environments who are found in an undressed state are sometimes incorrectly assumed to have been subjected to sexual assault.One explanation for the effect is a cold-induced malfunction of the hypothalamus, the part of the brain that regulates body temperature. Another explanation is that the muscles contracting peripheral blood vessels become exhausted (known as a loss of vasomotor tone) and relax, leading to a sudden surge of blood (and heat) to the extremities, causing the person to feel overheated.
Terminal burrowing
An apparent self-protective behaviour, known as "terminal burrowing", or "hide-and-die syndrome", occurs in the final stages of hypothermia. Those affected will enter small, enclosed spaces, such as underneath beds or behind wardrobes. It is often associated with paradoxical undressing. Researchers in Germany claim this is "obviously an autonomous process of the brain stem, which is triggered in the final state of hypothermia and produces a primitive and burrowing-like behavior of protection, as seen in hibernating mammals". This happens mostly in cases where temperature drops slowly.
Causes
Hypothermia usually occurs from exposure to low temperatures, and is frequently complicated by alcohol consumption. Any condition that decreases heat production, increases heat loss, or impairs thermoregulation, however, may contribute. Thus, hypothermia risk factors include: substance use disorders (including alcohol use disorder), homelessness, any condition that affects judgment (such as hypoglycemia), the extremes of age, poor clothing, chronic medical conditions (such as hypothyroidism and sepsis), and living in a cold environment. Hypothermia occurs frequently in major trauma, and is also observed in severe cases of anorexia nervosa. Hypothermia is also associated with worse outcomes in people with sepsis. While most people with sepsis develop fevers (elevated body temperature), some develop hypothermia.In urban areas, hypothermia frequently occurs with chronic cold exposure, such as in cases of homelessness, as well as with immersion accidents involving drugs, alcohol or mental illness. While studies have shown that people experiencing homelessness are at risk of premature death from hypothermia, the true incidence of hypothermia-related deaths in this population is difficult to determine. In more rural environments, the incidence of hypothermia is higher among people with significant comorbidities and less able to move independently. With rising interest in wilderness exploration, and outdoor and water sports, the incidence of hypothermia secondary to accidental exposure may become more frequent in the general population.
Alcohol
Alcohol consumption increases the risk of hypothermia in two ways: vasodilation and temperature controlling systems in the brain. Vasodilation increases blood flow to the skin, resulting in heat being lost to the environment. This produces the effect of feeling warm, when one is actually losing heat. Alcohol also affects the temperature-regulating system in the brain, decreasing the bodys ability to shiver and use energy that would normally aid the body in generating heat. The overall effects of alcohol lead to a decrease in body temperature and a decreased ability to generate body heat in response to cold environments. Alcohol is a common risk factor for death due to hypothermia. Between 33% and 73% of hypothermia cases are complicated by alcohol.
Water immersion
Hypothermia continues to be a major limitation to swimming or diving in cold water. The reduction in finger dexterity due to pain or numbness decreases general safety and work capacity, which consequently increases the risk of other injuries.Other factors predisposing to immersion hypothermia include dehydration, inadequate rewarming between repetitive dives, starting a dive while wearing cold, wet dry suit undergarments, sweating with work, inadequate thermal insulation (for example, thin dry suit undergarment), and poor physical conditioning.Heat is lost much more quickly in water than in air. Thus, water temperatures that would be quite reasonable as outdoor air temperatures can lead to hypothermia in survivors, although this is not usually the direct clinical cause of death for those who are not rescued. A water temperature of 10 °C (50 °F) can lead to death in as little as one hour, and water temperatures near freezing can cause death in as little as 15 minutes. During the sinking of the Titanic, most people who entered the −2 °C (28 °F) water died in 15–30 minutes.The actual cause of death in cold water is usually the bodily reactions to heat loss and to freezing water, rather than hypothermia (loss of core temperature) itself. For example, plunged into freezing seas, around 20% of victims die within two minutes from cold shock (uncontrolled rapid breathing, and gasping, causing water inhalation, massive increase in blood pressure and cardiac strain leading to cardiac arrest, and panic); another 50% die within 15–30 minutes from cold incapacitation: inability to use or control limbs and hands for swimming or gripping, as the body "protectively" shuts down the peripheral muscles of the limbs to protect its core. Exhaustion and unconsciousness cause drowning, claiming the rest within a similar time.
Pathophysiology
Heat is primarily generated in muscle tissue, including the heart, and in the liver, while it is lost through the skin (90%) and lungs (10%). Heat production may be increased two- to four-fold through muscle contractions (i.e. exercise and shivering). The rate of heat loss is determined, as with any object, by convection, conduction, and radiation. The rates of these can be affected by body mass index, body surface area to volume ratios, clothing and other environmental conditions.Many changes to physiology occur as body temperatures decrease. These occur in the cardiovascular system leading to the Osborn J wave and other dysrhythmias, decreased central nervous system electrical activity, cold diuresis, and non-cardiogenic pulmonary edema.Research has shown that glomerular filtration rates (GFR) decrease as a result of hypothermia. In essence, hypothermia increases preglomerular vasoconstriction, thus decreasing both renal blood flow (RBF) and GFR.
Diagnosis
Accurate determination of core temperature often requires a special low temperature thermometer, as most clinical thermometers do not measure accurately below 34.4 °C (93.9 °F). A low temperature thermometer can be placed in the rectum, esophagus or bladder. Esophageal measurements are the most accurate and are recommended once a person is intubated. Other methods of measurement such as in the mouth, under the arm, or using an infrared ear thermometer are often not accurate.As a hypothermic persons heart rate may be very slow, prolonged feeling for a pulse could be required before detecting. In 2005, the American Heart Association recommended at least 30–45 seconds to verify the absence of a pulse before initiating CPR. Others recommend a 60-second check.The classical ECG finding of hypothermia is the Osborn J wave. Also, ventricular fibrillation frequently occurs below 28 °C (82 °F) and asystole below 20 °C (68 °F). The Osborn J may look very similar to those of an acute ST elevation myocardial infarction. Thrombolysis as a reaction to the presence of Osborn J waves is not indicated, as it would only worsen the underlying coagulopathy caused by hypothermia.
Prevention
Proper clothing helps to prevent hypothermia. Synthetic and wool fabrics are superior to cotton as they provide better insulation when wet and dry. Some synthetic fabrics, such as polypropylene and polyester, are used in clothing designed to wick perspiration away from the body, such as liner socks and moisture-wicking undergarments. Clothing should be loose fitting, as tight clothing reduces the circulation of warm blood. In planning outdoor activity, prepare appropriately for possible cold weather. Those who drink alcohol before or during outdoor activity should ensure at least one sober person is present responsible for safety.Covering the head is effective, but no more effective than covering any other part of the body. While common folklore says that people lose most of their heat through their heads, heat loss from the head is no more significant than that from other uncovered parts of the body. However, heat loss from the head is significant in infants, whose head is larger relative to the rest of the body than in adults. Several studies have shown that for uncovered infants, lined hats significantly reduce heat loss and thermal stress. Children have a larger surface area per unit mass, and other things being equal should have one more layer of clothing than adults in similar conditions, and the time they spend in cold environments should be limited. However children are often more active than adults, and may generate more heat. In both adults and children, overexertion causes sweating and thus increases heat loss.Building a shelter can aid survival where there is danger of death from exposure. Shelters can be of many different types, metal can conduct heat away from the occupants and is sometimes best avoided. The shelter should not be too big so body warmth stays near the occupants. Good ventilation is essential especially if a fire will be lit in the shelter. Fires should be put out before the occupants sleep to prevent carbon monoxide poisoning. People caught in very cold, snowy conditions can build an igloo or snow cave to shelter.The United States Coast Guard promotes using life vests to protect against hypothermia through the 50/50/50 rule: If someone is in 50 °F (10 °C) water for 50 minutes, he/she has a 50 percent better chance of survival if wearing a life jacket. A heat escape lessening position can be used to increase survival in cold water.
Babies should sleep at 16–20 °C (61–68 °F) and housebound people should be checked regularly to make sure the temperature of the home is at least 18 °C (64 °F).
Management
Aggressiveness of treatment is matched to the degree of hypothermia. Treatment ranges from noninvasive, passive external warming to active external rewarming, to active core rewarming. In severe cases resuscitation begins with simultaneous removal from the cold environment and management of the airway, breathing, and circulation. Rapid rewarming is then commenced. Moving the person as little and as gently as possible is recommended as aggressive handling may increase risks of a dysrhythmia.Hypoglycemia is a frequent complication and needs to be tested for and treated. Intravenous thiamine and glucose is often recommended, as many causes of hypothermia are complicated by Wernickes encephalopathy.The UK National Health Service advises against putting a person in a hot bath, massaging their arms and legs, using a heating pad, or giving them alcohol. These measures can cause a rapid fall in blood pressure and potential cardiac arrest.
Rewarming
Rewarming can be done with a number of methods including passive external rewarming, active external rewarming, and active internal rewarming. Passive external rewarming involves the use of a persons own ability to generate heat by providing properly insulated dry clothing and moving to a warm environment. Passive external rewarming is recommended for those with mild hypothermia.Active external rewarming involves applying warming devices externally, such as a heating blanket. These may function by warmed forced air (Bair Hugger is a commonly used device), chemical reactions, or electricity. In wilderness environments, hypothermia may be helped by placing hot water bottles in both armpits and in the groin. Active external rewarming is recommended for moderate hypothermia. Active core rewarming involves the use of intravenous warmed fluids, irrigation of body cavities with warmed fluids (the chest or abdomen), use of warm humidified inhaled air, or use of extracorporeal rewarming such as via a heart lung machine or extracorporeal membrane oxygenation (ECMO). Extracorporeal rewarming is the fastest method for those with severe hypothermia. When severe hypothermia has led to cardiac arrest, effective extracorporeal warming results in survival with normal mental function about 50% of the time. Chest irrigation is recommended if bypass or ECMO is not possible.Rewarming shock (or rewarming collapse) is a sudden drop in blood pressure in combination with a low cardiac output which may occur during active treatment of a severely hypothermic person. There was a theoretical concern that external rewarming rather than internal rewarming may increase the risk. These concerns were partly believed to be due to afterdrop, a situation detected during laboratory experiments where there is a continued decrease in core temperature after rewarming has been started. Recent studies have not supported these concerns, and problems are not found with active external rewarming.
Fluids
For people who are alert and able to swallow, drinking warm sweetened liquids can help raise the temperature. Many recommend alcohol and caffeinated drinks be avoided. As most people are moderately dehydrated due to cold-induced diuresis, warmed intravenous fluids to a temperature of 38–45 °C (100–113 °F) are often recommended.
Cardiac arrest
In those without signs of life, cardiopulmonary resuscitation (CPR) should be continued during active rewarming. For ventricular fibrillation or ventricular tachycardia, a single defibrillation should be attempted. However, people with severe hypothermia may not respond to pacing or defibrillation. It is not known if further defibrillation should be withheld until the core temperature reaches 30 °C (86 °F). In Europe, epinephrine is not recommended until the persons core temperature reaches 30 °C (86 °F), while the American Heart Association recommends up to three doses of epinephrine before a core temperature of 30 °C (86 °F) is reached. Once a temperature of 30 °C (86 °F) has been reached, normal ACLS protocols should be followed.
Prognosis
It is usually recommended not to declare a person dead until their body is warmed to a near normal body temperature of greater than 32 °C (90 °F), since extreme hypothermia can suppress heart and brain function. Exceptions include if there are obvious fatal injuries or the chest is frozen so that it cannot be compressed. If a person was buried in an avalanche for more than 35 minutes and is found with a mouth packed full of snow without a pulse, stopping early may also be reasonable. This is also the case if a persons blood potassium is greater than 12 mmol/L.Those who are stiff with pupils that do not move may survive if treated aggressively. Survival with good function also occasionally occurs even after the need for hours of CPR. Children who have near-drowning accidents in water near 0 °C (32 °F) can occasionally be revived, even over an hour after losing consciousness. The cold water lowers the metabolism, allowing the brain to withstand a much longer period of hypoxia. While survival is possible, mortality from severe or profound hypothermia remains high despite optimal treatment. Studies estimate mortality at between 38% and 75%.In those who have hypothermia due to another underlying health problem, when death occurs it is frequently from that underlying health problem.
Epidemiology
Between 1995 and 2004 in the United States, an average of 1560 cold-related emergency department visits occurred per year and in the years 1999 to 2004, an average of 647 people died per year due to hypothermia. Of deaths reported between 1999 and 2002 in the US, 49% of those affected were 65 years or older and two-thirds were male. Most deaths were not work related (63%) and 23% of affected people were at home. Hypothermia was most common during the autumn and winter months of October through March. In the United Kingdom, an estimated 300 deaths per year are due to hypothermia, whereas the annual incidence of hypothermia-related deaths in Canada is 8000.
History
Hypothermia has played a major role in the success or failure of many military campaigns, from Hannibals loss of nearly half his men in the Second Punic War (218 B.C.) to the near destruction of Napoleons armies in Russia in 1812. Men wandered around confused by hypothermia, some lost consciousness and died, others shivered, later developed torpor, and tended to sleep. Others too weak to walk fell on their knees; some stayed that way for some time resisting death. The pulse of some was weak and hard to detect; others groaned; yet others had eyes open and wild with quiet delirium. Deaths from hypothermia in Russian regions continued through the first and second world wars, especially in the Battle of Stalingrad.Civilian examples of deaths caused by hypothermia occurred during the sinkings of the RMS Titanic and RMS Lusitania, and more recently of the MS Estonia.Antarctic explorers developed hypothermia; Ernest Shackleton and his team measured body temperatures "below 94.2°, which spells death at home", though this probably referred to oral temperatures rather than core temperature and corresponded to mild hypothermia. One of Scotts team, Atkinson, became confused through hypothermia.Nazi human experimentation during World War II amounting to medical torture included hypothermia experiments, which killed many victims. There were 360 to 400 experiments and 280 to 300 subjects, indicating some had more than one experiment performed on them. Various methods of rewarming were attempted: "One assistant later testified that some victims were thrown into boiling water for rewarming".
Medical use
Various degrees of hypothermia may be deliberately induced in medicine for purposes of treatment of brain injury, or lowering metabolism so that total brain ischemia can be tolerated for a short time. Deep hypothermic circulatory arrest is a medical technique in which the brain is cooled as low as 10 °C, which allows the heart to be stopped and blood pressure to be lowered to zero, for the treatment of aneurysms and other circulatory problems that do not tolerate arterial pressure or blood flow. The time limit for this technique, as also for accidental arrest in ice water (which internal temperatures may drop to as low as 15 °C), is about one hour.
Other animals
Hypothermia can happen in most mammals in cold weather and can be fatal. Baby mammals, kittens for example, are unable to regulate their body temperatures and have great risk of hypothermia if they are not kept warm by their mothers.
Many animals other than humans often induce hypothermia during hibernation or torpor.Water bears (Tardigrade), microscopic multicellular organisms, can survive freezing at low temperatures by replacing most of their internal water with the sugar trehalose, preventing the crystallization that otherwise damages cell membranes.
See also
Diving reflex – The physiological responses to immersion of air-breathing vertebrates
"To Build a Fire" – Short story by Jack London, two versions of a short story by Jack London portraying the effects of cold and hypothermia
"The Little Match Girl" – Fairy tale by Hans Christian Andersen, a short story by Hans Christian Andersen about a child dying of hypothermia
Dyatlov Pass incident
References
Bibliography
External links
CDC - NIOSH Workplace Safety & Health Topic: Cold Stress |
Baby colic | Baby colic, also known as infantile colic, is defined as episodes of crying for more than three hours a day, for more than three days a week, for three weeks in an otherwise healthy child. Often crying occurs in the evening. It typically does not result in long-term problems. The crying can result in frustration of the parents, depression following delivery, excess visits to the doctor, and child abuse.The cause of colic is unknown. Some believe it is due to gastrointestinal discomfort like intestinal cramping. Diagnosis requires ruling out other possible causes. Concerning findings include a fever, poor activity, or a swollen abdomen. Fewer than 5% of infants with excess crying have an underlying organic disease.Treatment is generally conservative, with little to no role for either medications or alternative therapies. Extra support for the parents may be useful. Tentative evidence supports certain probiotics for the baby and a low-allergen diet by the mother in those who are breastfed. Hydrolyzed formula may be useful in those who are bottlefed.Colic affects 10–40% of babies. Equally common in bottle and breast-fed infants, it begins during the second week of life, peaks at 6 weeks, and resolves between 12 and 16 weeks. It rarely lasts up to one year of age. It occurs at the same rate in boys and in girls. The first detailed medical description of the problem was published in 1954.
Signs and symptoms
Colic is defined as episodes of crying for more than three hours a day, for more than three days a week for at least a three-week duration in an otherwise healthy child. It is most common around six weeks of age and gets better by six months of age. By contrast, infants normally cry an average of just over two hours a day, with the duration peaking at six weeks. With colic, periods of crying most commonly happen in the evening and for no obvious reason. Associated symptoms may include legs pulled up to the stomach, a flushed face, clenched hands, and a wrinkled brow. The cry is often high pitched (piercing).
Effect on the family
An infant with colic may affect family stability and be a cause of short-term anxiety or depression in the father and mother. It may also contribute to exhaustion and stress in the parents.Persistent infant crying has been associated with severe marital discord, postpartum depression, early termination of breastfeeding, frequent visits to doctors, and a quadrupling of excessive laboratory tests and prescription of medication for acid reflux. Babies with colic may be exposed to abuse, especially shaken baby syndrome.In 2019 Cochrane conducted a systematic review on parent training programs for managing infantile colic. Seven studies with over 1100 participants met inclusion criteria. Limited evidence was found for the effectiveness of such programs, one meta-analysis showed some reduction in crying time.
Causes
The cause of colic is generally unknown. Fewer than 5% of infants who cry excessively turn out to have an underlying organic disease, such as constipation, gastroesophageal reflux disease, lactose intolerance, anal fissures, subdural hematomas, or infantile migraine. Babies fed cows milk have been shown to develop antibody responses to the bovine protein, causing colic. Studies performed showed conflicting evidence about the role of cows milk allergy. While previously believed to be related to gas pains, this does not appear to be the case. Another theory holds that colic is related to hyperperistalsis of the digestive tube (increased level of activity of contraction and relaxation). The evidence that the use of anticholinergic agents improve colic symptoms supports this hypothesis.Psychological and social factors have been proposed as a cause, but there is no evidence. Studies performed do not support the theory that maternal (or paternal) personality or anxiety causes colic, nor that it is a consequence of a difficult temperament of the baby, but families with colicky children may eventually develop anxiety, fatigue and problems with family functioning as a result. There is some evidence that cigarette smoke may increase the risk. It seems unrelated to breast or bottle feeding with rates similar in both groups. Reflux does not appear to be related to colic.
Diagnosis
Colic is diagnosed after other potential causes of crying are excluded. This can typically be done via a history and physical exam, and in most cases tests such as X-rays or blood tests are not needed. Babies who cry may simply be hungry, uncomfortable, or ill. Less than 10% of babies who would meet the definition of colic based on the amount they cry have an identifiable underlying disease.Cause for concern include: an elevated temperature, a history of breathing problems or a child who is not appropriately gaining weight.Indications that further investigations may be needed include:
Vomiting (vomit that is green or yellow, bloody or occurring more than five times a day)
Change in stool (constipation or diarrhea, especially with blood or mucous)
Abnormal temperature (a rectal temperature less than 97.0 °F (36.1 °C) or over 100.4 °F (38.0 °C)
Irritability (crying all day with few calm periods in between)
Lethargy (excess sleepiness, lack of smiles or interested gaze, weak sucking lasting over six hours)
Poor weight gain (gaining less than 15 grams a day)Problems to consider when the above are present include:
Infections (e.g. ear infection, urine infection, meningitis, appendicitis)
Intestinal pain (e.g. food allergy, acid reflux, constipation, intestinal blockage)
Trouble breathing (e.g. from a cold, excessive dust, congenital nasal blockage, oversized tongue)
Increased brain pressure (e.g. hematoma, hydrocephalus)
Skin pain (e.g. a loose diaper pin, irritated rash, a hair wrapped around a toe)
Mouth pain (e.g. yeast infection)
Kidney pain (e.g. blockage of the urinary system)
Eye pain (e.g. scratched cornea, glaucoma)
Overdose (e.g. excessive Vitamin D, excessive sodium)
Others (e.g. migraine headache, heart failure, hyperthyroidism)Persistently fussy babies with poor weight gain, vomiting more than five times a day, or other significant feeding problems should be evaluated for other illnesses (e.g. urinary infection, intestinal obstruction, acid reflux).
Treatment
Management of colic is generally conservative and involves the reassurance of parents. Calming measures may be used and include soothing motions, limiting stimulation, pacifier use, and carrying the baby around in a carrier, although it is not entirely clear if these actions have any effect beyond placebo. Swaddling does not appear to help.
Medication
No medications have been found to be both safe and effective. Simethicone is safe but does not work, while dicyclomine works but is not safe. Evidence does not support the use of cimetropium bromide, and there is little evidence for alternative medications or techniques. While medications to treat reflux are common, there is no evidence that they are useful.
Diet
Dietary changes by infants are generally not needed. In mothers who are breastfeeding, a hypoallergenic diet by the mother—not eating milk and dairy products, eggs, wheat, and nuts—may improve matters, while elimination of only cows milk does not seem to produce any improvement. In formula-fed infants, switching to a soy-based or hydrolyzed protein formula may help. Evidence of benefit is greater for hydrolyzed protein formula with the benefit from soy based formula being disputed. Both these formulas have greater cost and are not as palatable. Supplementation with fiber has not been shown to have any benefit. A 2018 Cochrane review of 15 randomized controlled trials involving 1,121 infants was unable to recommend any dietary interventions. A 2019 review determined that probiotics were no more effective than placebo although a reduction in crying time was measured.
Complimentary and alternative medicine
No clear beneficial effect from spinal manipulation or massage has been shown. Further, as there is no evidence of safety for cervical manipulation for baby colic, it is not advised. There is a case of a three-month-old dying following manipulation of the neck area.Little clinical evidence supports the efficacy of "gripe water" and caution in use is needed, especially in formulations that include alcohol or sugar. Evidence does not support lactase supplementation. The use of probiotics, specifically Lactobacillus reuteri, decreases crying time at three weeks by 46 minutes in breastfeed babies but has unclear effects in those who are formula fed. Fennel also appears effective.
Prognosis
Infants who are colicky do just as well as their non colicky peers with respect to temperament at one year of age.
Epidemiology
Colic affects 10–40% of children, occurring at the same rate in boys and in girls.
History
The word "colic" is derived from the ancient Greek word for intestine (sharing the same root as the word "colon").It has been an age-old practice to drug crying infants. During the second century AD, the Greek physician Galen prescribed opium to calm fussy babies, and during the Middle Ages in Europe, mothers and wet nurses smeared their nipples with opium lotions before each feeding. Alcohol was also commonly given to infants.In past decades, doctors recommended treating colicky babies with sedative medications (e.g. phenobarbital, Valium, alcohol), analgesics (e.g. opium) or anti-spasm drugs (e.g. scopolamine, Donnatal, dicyclomine), but all of these are no longer recommended because of potential serious side-effects, including death.
References
External links
Baby colic at Curlie |
Cleft lip and cleft palate | A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The term orofacial cleft refers to either condition or to both occurring together. These disorders can result in feeding problems, speech problems, hearing problems, and frequent ear infections. Less than half the time the condition is associated with other disorders.Cleft lip and palate are the result of tissues of the face not joining properly during development. As such, they are a type of birth defect. The cause is unknown in most cases. Risk factors include smoking during pregnancy, diabetes, obesity, an older mother, and certain medications (such as some used to treat seizures). Cleft lip and cleft palate can often be diagnosed during pregnancy with an ultrasound exam.A cleft lip or palate can be successfully treated with surgery. This is often done in the first few months of life for cleft lip and before eighteen months for cleft palate. Speech therapy and dental care may also be needed. With appropriate treatment, outcomes are good.Cleft lip and palate occurs in about 1 to 2 per 1000 births in the developed world. Cleft lip is about twice as common in males as females, while cleft palate without cleft lip is more common in females. In 2017, it resulted in about 3,800 deaths globally, down from 14,600 deaths in 1990. The condition was formerly known as a "hare-lip" because of its resemblance to a hare or rabbit, but that term is now generally considered to be offensive.
Signs and symptoms
Cleft lip
If the cleft does not affect the palate structure of the mouth, it is referred to as cleft lip. Cleft lip is formed in the top of the lip as either a small gap or an indentation in the lip (partial or incomplete cleft), or it continues into the nose (complete cleft). Lip cleft can occur as a one-sided (unilateral) or two-sided (bilateral) condition. It is due to the failure of fusion of the maxillary prominence and medial nasal processes (formation of the primary palate).
A mild form of a cleft lip is a microform cleft. A microform cleft can appear as small as a little dent in the red part of the lip or look like a scar from the lip up to the nostril. In some cases muscle tissue in the lip underneath the scar is affected and might require reconstructive surgery. It is advised to have newborn infants with a microform cleft checked with a craniofacial team as soon as possible to determine the severity of the cleft.
Cleft palate
Cleft palate is a condition in which the two plates of the skull that form the hard palate (roof of the mouth) are not completely joined. The soft palate is in these cases cleft as well. In most cases, cleft lip is also present.
Palate cleft can occur as complete (soft and hard palate, possibly including a gap in the jaw) or incomplete (a hole in the roof of the mouth, usually as a cleft soft palate). When cleft palate occurs, the uvula is usually split. It occurs due to the failure of fusion of the lateral palatine processes, the nasal septum, or the median palatine processes (formation of the secondary palate).
The hole in the roof of the mouth caused by a cleft connects the mouth directly to the inside of the nose.
Note: the next images show the roof of the mouth. The top shows the nose, the lips are colored pink. For clarity the images depict a toothless infant.
A result of an open connection between the mouth and inside the nose is called velopharyngeal insufficiency (VPI). Because of the gap, air leaks into the nasal cavity resulting in a hypernasal voice resonance and nasal emissions while talking. Secondary effects of VPI include speech articulation errors (e.g., distortions, substitutions, and omissions) and compensatory misarticulations and mispronunciations (e.g., glottal stops and posterior nasal fricatives). Possible treatment options include speech therapy, prosthetics, augmentation of the posterior pharyngeal wall, lengthening of the palate, and surgical procedures.Submucous cleft palate can also occur, which is a cleft of the soft palate with a split uvula, a furrow along the midline of the soft palate, and a notch in the back margin of the hard palate. The diagnosis of submucous cleft palate often occurs late in children as a result of the nature of the cleft. While the muscles of the soft palate are not joined, the mucosal membranes covering the roof of the mouth appear relatively normal and intact.
Teeth
Tooth development can be delayed with increasing severity of CLP. Some of the dental problems affect the primary teeth, but most of the problems arise after the permanent teeth erupts. Problems may include fused teeth, missing teeth, and extra teeth erupting behind normal teeth. Missing teeth or extra teeth are both normal occurrences. Typically, the lateral incisors are missing. The enamel (outermost layer of the tooth) is commonly found to be hypomineralized and hypoplastic, making the teeth more likely to decay. As CLP can make oral hygiene more difficult, there is an increased rate of cavities. In addition, abnormal positioning of individual teeth may affect occlusion, which can create an open bite or cross bite. This in turn can then affect the patients speech.
Complications
Cleft may cause problems with feeding, ear disease, speech, socialization, and cognition.
Due to lack of suction, an infant with a cleft may have trouble feeding. An infant with a cleft palate will have greater success feeding in a more upright position. Gravity will help prevent milk from coming through the babys nose if he/she has cleft palate. Gravity feeding can be accomplished by using specialized equipment, such as the Haberman Feeder. Another equipment commonly used for gravity feeding is a customized bottle with a combination of nipples and bottle inserts. A large hole, crosscut, or slit in the nipple, a protruding nipple and rhythmically squeezing the bottle insert can result in controllable flow to the infant without the stigma caused by specialized equipment.
Individuals with cleft also face many middle ear infections which may eventually lead to hearing loss. The Eustachian tubes and external ear canals may be angled or tortuous, leading to food or other contamination of a part of the body that is normally self-cleaning. Hearing is related to learning to speak. Babies with palatal clefts may have compromised hearing and therefore, if the baby cannot hear, it cannot try to mimic the sounds of speech. Thus, even before expressive language acquisition, the baby with the cleft palate is at risk for receptive language acquisition. Because the lips and palate are both used in pronunciation, individuals with cleft usually need the aid of a speech therapist.
Tentative evidence has found that those with clefts perform less well at language.
Psychosocial issues
There is research dedicated to the psychosocial development of individuals with cleft palate. A cleft palate/lip may impact an individuals self-esteem, social skills and behavior. Self-concept may be adversely affected by the presence of a cleft lip or cleft palate, particularly among girls. Negative outcomes can also be associated with the long durations of hospitalization. Psychological issues could extend not just to the individual with CLP but also to their families, particularly their mothers, that experience varying levels of depression and anxiety.Research has shown that during the early preschool years (ages 3–5), children with cleft lip or cleft palate tend to have a self-concept that is similar to their peers without a cleft. However, as they grow older and their social interactions increase, children with clefts tend to report more dissatisfaction with peer relationships and higher levels of social anxiety. Experts conclude that this is probably due to the associated stigma of visible deformities and possible speech impediments. Children who are judged as attractive tend to be perceived as more intelligent, exhibit more positive social behaviors, and are treated more positively than children with cleft lip or cleft palate. Children with clefts tend to report feelings of anger, sadness, fear, and alienation from their peers, but these children were similar to their peers in regard to "how well they liked themselves."
The relationship between parental attitudes and a childs self-concept is crucial during the preschool years. It has been reported that elevated stress levels in mothers correlated with reduced social skills in their children. Strong parent support networks may help to prevent the development of negative self-concept in children with cleft palate. In the later preschool and early elementary years, the development of social skills is no longer only impacted by parental attitudes but is beginning to be shaped by their peers. A cleft lip or cleft palate may affect the behavior of preschoolers. Experts suggest that parents discuss with their children ways to handle negative social situations related to their cleft lip or cleft palate. A child who is entering school should learn the proper (and age-appropriate) terms related to the cleft. The ability to confidently explain the condition to others may limit feelings of awkwardness and embarrassment and reduce negative social experiences.As children reach adolescence, the period of time between age 13 and 19, the dynamics of the parent-child relationship change as peer groups are now the focus of attention. An adolescent with cleft lip or cleft palate will deal with the typical challenges faced by most of their peers including issues related to self-esteem, dating and social acceptance. Adolescents, however, view appearance as the most important characteristic, above intelligence and humor. This being the case, adolescents are susceptible to additional problems because they cannot hide their facial differences from their peers. Adolescent boys typically deal with issues relating to withdrawal, attention, thought, and internalizing problems, and may possibly develop anxiousness-depression and aggressive behaviors. Adolescent girls are more likely to develop problems relating to self-concept and appearance. Individuals with cleft lip or cleft palate often deal with threats to their quality of life for multiple reasons including unsuccessful social relationships, deviance in social appearance, and multiple surgeries.
Cause
Most clefts are polygenic and multifactorial in origin with many genetic and environmental factors contributing. Genetic factors cause clefts in 20% to 50% of the cases and the remaining clefts are attributable to either environmental factors (such as teratogens) or gene-environment interactions. The polygenic/multifactorial inheritance model predicts that most individuals will be born without clefts; however with a number of genetic or environmental factors, it can result in cleft formation.The development of the face is coordinated by complex morphogenetic events and rapid proliferative expansion, and is thus highly susceptible to environmental and genetic factors, rationalising the high incidence of facial malformations. During the first six to eight weeks of pregnancy, the shape of the embryos head is formed. Five primitive tissue lobes grow:
If these tissues fail to meet, a gap appears where the tissues should have joined (fused). This may happen in any single joining site, or simultaneously in several or all of them. The resulting birth defect reflects the locations and severity of individual fusion failures (e.g., from a small lip or palate fissure up to a completely malformed face).
The upper lip is formed earlier than the palate, from the first three lobes named a to c above. Formation of the palate is the last step in joining the five embryonic facial lobes, and involves the back portions of the lobes b and c. These back portions are called palatal shelves, which grow towards each other until they fuse in the middle. This process is very vulnerable to multiple toxic substances, environmental pollutants, and nutritional imbalance. The biologic mechanisms of mutual recognition of the two cabinets, and the way they are glued together, are quite complex and obscure despite intensive scientific research.Orofacial clefts may be associated with a syndrome (syndromic) or may not be associated with a syndrome (nonsyndromic). Syndromic clefts are part of syndromes that are caused by a variety of factors such as environment and genetics or an unknown cause. Nonsyndromic clefts, which are not as common as syndromic clefts, also have a genetic cause.
Genetics
Genetic factors contributing to cleft lip and cleft palate formation have been identified for some syndromic cases. Many clefts run in families, even though in some cases there does not seem to be an identifiable syndrome present. A number of genes are involved including cleft lip and palate transmembrane protein 1 and GAD1, One study found an association between mutations in the HYAL2 gene and cleft lip and cleft palate formation.
Syndromes
The Van der Woude syndrome is caused by a specific variation in the gene IRF6 that increases the occurrence of these deformities threefold. Mutations in interferon regulatory factor 6 (IRF6) that cause cleft lip palate are also implicated in neural tube defects such as spina bifida.
Another syndrome, Siderius X-linked intellectual disability, is caused by mutations in the PHF8 gene (OMIM: 300263); in addition to cleft lip or palate, symptoms include facial dysmorphism and mild intellectual disability.In some cases, cleft palate is caused by syndromes that also cause other problems:
Stickler syndrome can cause cleft lip and palate, joint pain, and myopia.
Loeys–Dietz syndrome can cause cleft palate or bifid uvula, hypertelorism, and aortic aneurysm.
Hardikar syndrome can cause cleft lip and palate, Hydronephrosis, Intestinal obstruction and other symptoms.
Cleft lip/palate may be present in many different chromosome disorders including Patau syndrome (trisomy 13).
Malpuech facial clefting syndrome
Hearing loss with craniofacial syndromes
Popliteal pterygium syndrome
Cornelia de Lange syndrome
Treacher Collins syndrome
Pierre Robin syndrome
Specific genes
Many genes associated with syndromic cases of cleft lip/palate (see above) have been identified to contribute to the incidence of isolated cases of cleft lip/palate. This includes in particular sequence variants in the genes IRF6, PVRL1 and MSX1. The understanding of the genetic complexities involved in the morphogenesis of the midface, including molecular and cellular processes, has been greatly aided by research on animal models, including of the genes BMP4, SHH, SHOX2, FGF10 and MSX1.
Environmental factors
Environmental influences may also cause, or interact with genetics to produce, orofacial clefts. An example of the link between environmental factors and genetics comes from a research on mutations in the gene PHF8. The research found that PHF8 encodes for a histone lysine demethylase, and is involved in epigenetic regulation. The catalytic activity of PHF8 depends on molecular oxygen, a factor considered important from reports on increased incidence of cleft lip/palate in mice that have been exposed to hypoxia early during pregnancy.Cleft lip and other congenital abnormalities have also been linked to maternal hypoxia caused by maternal smoking, with the estimated attributable fraction of orofacial clefts due to smoking in early pregnancy being 6.1%. Orofacial clefts occur very early in pregnancy and so smoking cessation right after recognition of pregnancy is unlikely to reduce the exposure during the critical time period.Maternal alcohol use has also been linked to cleft lip and palate due to the effects on the cranial neural crest cells. The degree of the effect, however, is unknown and requires further research. Some forms of maternal hypertension treatment have been linked to cleft lip and palate. Other environmental factors that have been studied include seasonal causes (such as pesticide exposure); maternal diet and vitamin intake; retinoids (members of the vitamin A family); anticonvulsant drugs; nitrate compounds; organic solvents; parental exposure to lead; alcohol; cigarette use; and a number of other psychoactive drugs (e.g. cocaine, crack cocaine, heroin).
Current research continues to investigate the extent to which folic acid can reduce the incidence of clefting. Folic acid alone or in combination with vitamins and minerals prevents neural tube defects but does not have a clear effect on cleft lip palate incidence. The mechanism behind beneficial folate supplementation is due to folate playing a pivotal role in DNA synthesis and methylation and contributes to both development and gene expression.
Diagnosis
Traditionally, the diagnosis is made at the time of birth by physical examination. Recent advances in prenatal diagnosis have allowed obstetricians to diagnose facial clefts in utero with ultrasonography.Clefts can also affect other parts of the face, such as the eyes, ears, nose, cheeks, and forehead. In 1976, Paul Tessier described fifteen lines of cleft. Most of these craniofacial clefts are even rarer and are frequently described as Tessier clefts using the numerical locator devised by Tessier.
Classification
Cleft lip and cleft palate is an "umbrella term" for a collection of orofacial clefts. It includes clefting of the upper lip, the maxillary alveolus (dental arch), and the hard or soft palate, in various combinations. Proposed anatomic combinations include:
cleft lip
cleft lip and alveolus
cleft lip, alveolus, and palate
cleft lip and palate (with an intact alveolus)
cleft palate
Prenatal diagnosis
Cleft lip with or without palate is classified as the most common congenital birth defect. It has been noted that the prevalence of orofacial clefts varies by race. The highest number of cases have been recorded among Asians and Native Americans, followed by Europeans, Hispanics and African-Americans. The critical period for cleft development ranges from the 4th to the 12th week of intrauterine life. Clefts of the primary palate develop between the 4th and 7th weeks of intrauterine life, while clefts of the secondary palate develop between the 8th and 12th embryonic weeks.
Accurate evaluation of craniofacial malformations is usually possible with the ultrasound scan performed during pregnancy. This is however not a routine procedure according to the American Institute of Ultrasound in Medicine. The accuracy of ultrasonography for prenatal diagnosis of cleft lip +/- palate is dependent on the experience of the sonologist, maternal body type, foetal position, the amount of amniotic fluid and the type of cleft.
Prenatal diagnosis enables appropriate and timely education and discussion with parents by the cleft team. This helps improve the quality of treatment received by the child and improves quality of life.
An accurate prenatal diagnosis of the CLP anomaly is critical for establishing long-term treatment planning, prediction of treatment outcome, and discussion and education of the parent. Although there is no intrauterine treatment for CLP, both mother and child benefit from early diagnosis and education. A multidisciplinary team approach is now accepted as the standard of care in dealing with CLP patients.
The time period immediately after the diagnosis and the first year after the birth is most challenging for parents. A systematically planned treatment plan and support system will help assist parents. The ultimate aim is to help educate parents and create awareness so as to improve care provided for the child.
Treatment
Cleft lip and palate is very treatable; however, the kind of treatment depends on the type and severity of the cleft.
Most children with a form of clefting are monitored by a cleft palate team or craniofacial team through young adulthood. Care can be lifelong and are looked after by craniofacial cleft teams often consist of: cleft surgeons, orthodontists, speech and language therapists, restorative dentists, psychologists, ENT surgeons and audio-logical physicians. Treatment procedures can vary between craniofacial teams. For example, some teams wait on jaw correction until the child is aged 10 to 12 (argument: growth is less influential as deciduous teeth are replaced by permanent teeth, thus saving the child from repeated corrective surgeries), while other teams correct the jaw earlier (argument: less speech therapy is needed than at a later age when speech therapy becomes harder). Within teams, treatment can differ between individual cases depending on the type and severity of the cleft.
Cleft lip
Within the first 2–3 months after birth, surgery is performed to close the cleft lip. While surgery to repair a cleft lip can be performed soon after birth, often the preferred age is at approximately 10 weeks of age, following the "rule of 10s" coined by surgeons Wilhelmmesen and Musgrave in 1969 (the child is at least 10 weeks of age; weighs at least 10 pounds, and has at least 10g hemoglobin). If the cleft is bilateral and extensive, two surgeries may be required to close the cleft, one side first, and the second side a few weeks later. The most common procedure to repair a cleft lip is the Millard procedure pioneered by Ralph Millard. Millard performed the first procedure at a Mobile Army Surgical Hospital (MASH) unit in Korea.Often an incomplete cleft lip requires the same surgery as complete cleft. This is done for two reasons. Firstly the group of muscles required to purse the lips run through the upper lip. To restore the complete group a full incision must be made. Secondly, to create a less obvious scar the surgeon tries to line up the scar with the natural lines in the upper lip (such as the edges of the philtrum) and tuck away stitches as far up the nose as possible. Incomplete cleft gives the surgeon more tissue to work with, creating a more supple and natural-looking upper lip.
Pre-surgical devices
In some cases of a severe bilateral complete cleft, the premaxillary segment will be protruded far outside the mouth.
Nasoalveolar molding prior to surgery can improve long-term nasal symmetry where there is complete unilateral cleft lip–cleft palate, compared to correction by surgery alone, according to a retrospective cohort study. In this study, significant improvements in nasal symmetry were observed in multiple areas including measurements of the projected length of the nasal ala (lateral surface of the external nose), position of the superoinferior alar groove, position of the mediolateral nasal dome, and nasal bridge deviation. "The nasal ala projection length demonstrated an average ratio of 93.0 percent in the surgery-alone group and 96.5 percent in the nasoalveolar molding group," this study concluded. A systematic review found in conclusion that nasoalveolar molding had a positive effect on the primary surgery of cleft lip/or palate treatment and aesthetics.
Cleft palate
Often a cleft palate is temporarily covered by a palatal obturator (a prosthetic device made to fit the roof of the mouth covering the gap). This device re-positions displaced alveolar segments and helps reduce the cleft lip separation. The obturator will improve speech as theres now proper airflow and improve feeding and breathing as the gap in the hard and soft palate is closed over so cannot affect it.Cleft palate can also be corrected by surgery, usually performed between 6 and 12 months. Approximately 20–25% only require one palatal surgery to achieve a competent velopharyngeal valve capable of producing normal, non-hypernasal speech. However, combinations of surgical methods and repeated surgeries are often necessary as the child grows. One of the new innovations of cleft lip and cleft palate repair is the Latham appliance. The Latham is surgically inserted by use of pins during the childs fourth or fifth month. After it is in place, the doctor, or parents, turn a screw daily to bring the cleft together to assist with future lip or palate repair.
If the cleft extends into the maxillary alveolar ridge, the gap is usually corrected by filling the gap with bone tissue. The bone tissue can be acquired from the individuals own chin, rib or hip.
At age 1–7 years the child is regularly reviewed by the cleft team.Age 7–12 years, for the children born with alveolar clefts, they may need to have a secondary alveolar bone graft. This is where autogenous cancellous bone from a donor site (often the pelvic bone) is transplanted into the alveolar cleft region. This transplant of bone will close the osseous cleft of the alveolus, close any oro-nasal fistulae and will become integrated with the maxillary bone. It provides bone for teeth to erupt into and to allow implants to be placed as a possible future treatment option. The procedure should be carried out before the upper canine has erupted. Ideally the root of the canine should be one to two-thirds formed and that there is a space available to place the bone graft. Radio-graphs are taken to determine the quantity of missing bone in the cleft area.
Other surgeries
Orthognathic surgery – surgical cutting of bone to realign the upper jaw (osteotomy). The bone is cut then re-positioned and held together by wires or rigid fixation plates to ensure theres no anterior-posterior discrepancy, also to reduce scarring as it reduces growth. Single piece or multi-piece osteotomy exist. Single piece osteotomy is carried out where there is sufficient alveolar continuity achieved from a successful bone graft. Multi piece osteotomy is performed when there is a notable residual alveolar defect with a dental gap and oronasal fistula (communication between the oral and nasal cavities). The goal of both single and multi piece osteotomy is to displace the maxilla forward to obtain adequate occlusion as well to provide better support for upper lip and the nose and to close any fistulae.Distraction osteogenesis – bone lengthening by gradual distraction. This involves cutting bone and moving ends apart incrementally to allow new bone to form in the gap. This consists of several phases. After attachment of the distracting device and the bone cuts, there is a latency phase of 3–7 days when a callus forms. In the activation phase distraction of the callus induces bony ingrowth which can last up to 15 days depending on the required distraction. Once the required bone length is reached, the distraction device is left to remain in situ as it acts as a rigid skeletal fixation device until the new bone has matured (known as the consolidation period).
Speech
Velopharyngeal insufficiency (VPI) can occur as a result of an unrepaired or repaired cleft lip and palate. VPI is the inability of the soft palate to close tightly against the back of the throat during speech, resulting in incomplete velopharyngeal closure. In turn, this results in speech abnormalities. Velopharyngeal closure is necessary during speech because it forms a seal between the nose and mouth, allowing the production of normal speech sounds. VPI can cause hypernasality (excessive nasal resonance), hyponasality (reduced nasal resonance), or a mixed nasal resonance, which is when hypernasality and hyponasality occur simultaneously. In addition, CLP may cause abnormal positioning of individual teeth, which can in turn affect the patients ability to make certain sounds when speaking such as the "f" or "v" sound and can also result in a lisp. The changes in speech may also be a manifestation on CLPs effects on the patients occlusion.
Hearing
Children with cleft palate have a very high risk of developing a middle ear infection, specifically otitis media. This is due to the immature development of the different bones and muscles in the ear. Otitis media is caused by the obstruction of the Eustachian tube, negative middle ear pressure and fluid build-up in the normally air-filled space of the middle ear. This is associated with hearing impairment or loss. The insertion of a ventilation tube into the eardrum is a surgical treatment option commonly used to improve hearing in children with otitis media. In addition, breast milk has been proven to decrease the incidence of otitis media in infants with clefts.
Feeding
There are different options on how to feed a baby with cleft lip or cleft palate which include: breast-feeding, bottle feeding, spoon feeding and syringe feeding. Although breast-feeding is challenging, it improves weight-gain compared to spoon-feeding. Nasal regurg |
Cleft lip and cleft palate | itation is common due to the open space between the oral cavity and the nasal cavity. Bottle feeding can help (with squeezable bottles being easier to use than rigid bottles). In addition, maxillary plates can be added to aid in feeding. Whatever feeding method is established, it is important to keep the babys weight gain and hydration monitored. Infants with cleft lip or palate may require supplemental feeds for adequate growth and nutrition. Breast feeding position as suggested by specialists can also improve success rate.
Breast-feeding
Babies with cleft lip are more likely to breastfeed successfully than those with cleft palate and cleft lip and palate. Larger clefts of the soft or hard palate may not be able to generate suction as the oral cavity cannot be separated from the nasal cavity when feeding which leads to fatigue, prolonged feeding time, impaired growth and nutrition. Changes in swallowing mechanics may result in coughing, choking, gagging and nasal regurgitation. Even after cleft repair, the problem may still persist as significant motor learning of swallowing and sucking was absent for many months before repair. These difficulties in feeding may result in secondary problems such as poor weight gain, excessive energy expenditure during feeding, lengthy feeding times, discomfort during feeding, and stressful feeding interactions between the infant and the mother. A potential source of discomfort for the baby during or after feeding is bloating or frequent "spit up" which is due to the excessive air intake through the nose and mouth in the open cleft. Babies with cleft lip and or palate should be evaluated individually taking into account the size and location of the cleft and the mothers previous experience with breastfeeding.Another option is feeding breast milk via bottle or syringe. Since babies with clip lip and cleft palate generate less section when breastfeeding, their nutrition, hydration and weight gain may be affected. This may result in the need for supplemental feeds. Modifying the position of holding the baby may increase the effectiveness and efficiency of breastfeeding.
Alternative Feeding Methods
Preoperative feeding – using a squeezable bottle instead of a rigid bottle can allow a higher volume of food intake and less effort to extract food. Using a syringe is practical, easy to perform and allows greater administered volume of food. It also means there will be weight gain and less time spent feeding.Post-operative feeding (isolated lip repair, or lip repair associated or not with palatoplasty) – post palatoplasty, some studies believe that inappropriate negative pressure on the suture line may affect results. Babies can be fed by a nasogastric tube instead. Studies suggest babies required less analgesics and shorter hospital stay with nasogastric feeding post-surgery. With bottle-feeding, there was higher feeding rejection and pain and required more frequent and prolonged feeding times.
Treatment schedule
Each persons treatment schedule is individualized. The table below shows a common sample treatment schedule. The colored squares indicate the average timeframe in which the indicated procedure occurs. In some cases, this is usually one procedure, for example lip repair. In other cases, it is an ongoing therapy, for example speech therapy. In most cases of cleft lip and palate that involve the alveolar bone, patients will need a treatment plan including the prevention of cavities, orthodontics, alveolar bone grafting, and possibly jaw surgery.
Cleft team
People with CLP present with a multiplicity of problems. Therefore, effective management of CLP involves a wide range of specialists. The current model for delivery of this care is the multidisciplinary cleft team. This is a group of individuals from different specialist backgrounds who work closely together to provide patients with comprehensive care from birth through adolescence. This system of delivery of care enables the individuals within the team to function in an interdisciplinary way, so that all aspects of care for CLP patients can be provided in the best way possible.
Outcomes assessment
Measuring the outcomes of CLP treatment has been laden with difficulty due to the complexity and longitudinal nature of cleft care, which spans birth through young adulthood. Prior attempts to study the effectiveness of specific interventions or overall treatment protocols have been hindered by a lack of data standards for outcomes assessment in cleft care.The International Consortium for Health Outcome Measurement (ICHOM) has proposed the Standard Set of Outcome Measures for Cleft Lip and Palate. The ICHOM Standard Set includes measures for many of the important outcome domains in cleft care (hearing, breathing, eating/drinking, speech, oral health, appearance and psychosocial well-being). It includes clinician-reported, patient-reported, and family-reported outcome measures.
Epidemiology
Cleft lip and palate occurs in about 1 to 2 per 1000 births in the developed world.Rates for cleft lip with or without cleft palate and cleft palate alone varies within different ethnic groups.
According to CDC, the prevalence of cleft palate in the United States is 6.35/10000 births and the prevalence of cleft lip with or without cleft palate is 10.63/10000 births. The highest prevalence rates for cleft lip, either with or without cleft palate are reported for Native Americans and Asians. Africans have the lowest prevalence rates.
Native Americans: 3.74/1000
Japanese: 0.82/1000 to 3.36/1000
Chinese: 1.45/1000 to 4.04/1000
Caucasians: 1.43/1000 to 1.86/1000
Latin Americans: 1.04/1000
Africans: 0.18/1000 to 1.67/1000Cleft lip and cleft palate caused about 3,800 deaths globally in 2017, down from 14,600 deaths in 1990.Prevalence of "cleft uvula" has varied from 0.02% to 18.8% with the highest numbers found among Chippewa and Navajo and the lowest generally in Africans.
Society and culture
Abortion controversy
In some countries, cleft lip or palate deformities are considered reasons (either generally tolerated or officially sanctioned) to perform an abortion beyond the legal fetal age limit, even though the fetus is not in jeopardy of life or limb. Some human rights activists contend that this practice of what they refer to as "cosmetic murder" amounts to eugenics.
Works of fiction
The eponymous hero of J.M. Coetzees 1983 novel Life & Times of Michael K has a cleft lip that is never corrected. In the 1920 novel Growth of the Soil, by Norwegian writer Knut Hamsun, Inger (wife of the main character) has an uncorrected cleft lip which puts heavy limitations on her life, even causing her to kill her own child, who is also born with a cleft lip. The protagonist of the 1924 novel Precious Bane, by English writer Mary Webb, is a young woman living in 19th-century rural Shropshire who eventually comes to feel that her deformity is the source of her spiritual strength. The book was later adapted for television by both the BBC and ORTF in France. Similarly, the main character in Graham Greenes 1936 crime noir novel A Gun for Sale, Raven, has a cleft lip which he is sensitive about, and is described as "an ugly man dedicated to ugly deeds". In the 1976 Patricia A. McKillip novel The Night Gift, one of the high-school aged protagonists is shy because she has a cleft lip, but learns to have more confidence in herself.
In the first edition of Harry Potter and the Chamber of Secrets, one of the people Gilderoy Lockhart stole credit from was a witch with a harelip who banished the Bandon Banshee. In later editions, this was changed to a witch with a hairy chin.In chapter 26 of Mark Twains The Adventures of Huckleberry Finn, Huck Finn meets the three Wilks sisters, Mary Jane, Susan, and Joanna. Joanna is described as, "the one who gives herself to good works and has a hare-lip." As a form of offensive synecdoche, Huck Finn refers to Joanna as "the hare-lip" rather than by her name.
In Inheritance, the final title of Christopher Paolinis Inheritance Cycle, the main character Eragon heals a newborn girl with this condition in a display of complicated healing magic. It is stated that those within Eragons society born with this condition are often not allowed to live as they face a very hard life.Cleft lip and cleft palate are often portrayed negatively in popular culture. Examples include Oddjob, the secondary villain of the James Bond novel Goldfinger by Ian Fleming (the film adaptation does not mention this but leaves it implied) and serial killer Francis Dolarhyde in the novel Red Dragon and its screen adaptations, Manhunter, Red Dragon, and Hannibal. The portrayal of enemy characters with cleft lips and cleft palates, dubbed mutants, in the 2019 video game Rage 2 left Chris Plante of Polygon wondering if the condition would ever be portrayed positively.
Notable cases
Other animals
Cleft lips and palates are occasionally seen in cattle and dogs, and rarely in goats, sheep, cats, horses, pandas and ferrets. Most commonly, the defect involves the lip, rhinarium, and premaxilla. Clefts of the hard and soft palate are sometimes seen with a cleft lip. The cause is usually hereditary. Brachycephalic dogs such as Boxers and Boston Terriers are most commonly affected. An inherited disorder with incomplete penetrance has also been suggested in Shih tzus, Swiss Sheepdogs, Bulldogs, and Pointers. In horses, it is a rare condition usually involving the caudal soft palate. In Charolais cattle, clefts are seen in combination with arthrogryposis, which is inherited as an autosomal recessive trait. It is also inherited as an autosomal recessive trait in Texel sheep. Other contributing factors may include maternal nutritional deficiencies, exposure in utero to viral infections, trauma, drugs, or chemicals, or ingestion of toxins by the mother, such as certain lupines by cattle during the second or third month of gestation. The use of corticosteroids during pregnancy in dogs and the ingestion of Veratrum californicum by pregnant sheep have also been associated with cleft formation.Difficulty with nursing is the most common problem associated with clefts, but aspiration pneumonia, regurgitation, and malnutrition are often seen with cleft palate and is a common cause of death. Providing nutrition through a feeding tube is often necessary, but corrective surgery in dogs can be done by the age of twelve weeks. For cleft palate, there is a high rate of surgical failure resulting in repeated surgeries. Surgical techniques for cleft palate in dogs include prosthesis, mucosal flaps, and microvascular free flaps. Affected animals should not be bred due to the hereditary nature of this condition.
See also
Smile Pinki
Palatal obturator
Vomer flap surgery
Cleft lip and palate organisations
Face and neck development of the embryo
References
Notes
Further reading
FIGURE 1 | Development of the lip and palate and FIGURE 2 | Types of cleft in Dixon MJ, Marazita ML, Beaty TH, Murray JC (March 2011). "Cleft lip and palate: understanding genetic and environmental influences". Nature Reviews. Genetics. 12 (3): 167–78. doi:10.1038/nrg2933. PMC 3086810. PMID 21331089.
Berkowitz S (February 26, 2013). Cleft Lip and Palate: Diagnosis and Management. Springer. ISBN 978-3-642-30770-6.
External links
Cleft lip and cleft palate at Curlie |
Cocaine dependence | Cocaine dependence is a neurological disorder that is characterized by withdrawal symptoms upon cessation from cocaine use. It also often coincides with cocaine addiction which is a biopsychosocial disorder characterized by persistent use of cocaine and/or crack despite substantial harm and adverse consequences. The Diagnostic and Statistical Manual of Mental Disorders (5th ed., abbreviated DSM-5), classifies problematic cocaine use as a "Stimulant use disorder". The International Classification of Diseases (11th rev., abbreviated ICD-11), includes "Cocaine dependence" as a classification (diagnosis) under "Disorders due to use of cocaine”.The use of cocaine creates euphoria and high amounts of energy. If taken in large doses, it is possible to cause mood swings, paranoia, insomnia, psychosis, high blood pressure, a fast heart rate, panic attacks, cognitive impairments and drastic changes in personality. Cocaine overdose may result in cardiovascular and brain damage, such as: constricting blood vessels in the brain, causing strokes and constricting arteries in the heart; causing heart attacks.The symptoms of cocaine withdrawal range from moderate to severe: dysphoria, depression, anxiety, decreased libido, psychological and physical weakness, pain, and compulsive cravings.
Signs and symptoms
Cocaine is a powerful stimulant known to make users feel energetic, cheerful, talkative, etc. In time, negative side effects include increased body temperature, irregular or rapid heart rate, high blood pressure, increased risk of heart attacks, strokes and even sudden death from cardiac arrest. Many people who habitually use cocaine develop a transient, manic-like condition similar to amphetamine psychosis and schizophrenia, whose symptoms include aggression, severe paranoia, restlessness, confusion and tactile hallucinations; which can include the feeling of something crawling under the skin (formication), also known as "coke bugs", during binges. Different ingestion techniques have their own symptoms that accompany them. Snorting it can cause a loss of sense of smell, nose bleeds, problems swallowing and an inflamed, runny nose. Smoking it causes lung damage and injecting it puts users at risk of contracting infectious diseases like HIV and hepatitis C. Heavy users of cocaine have also reported having thoughts of suicide, unusual weight loss, trouble maintaining relationships, and an unhealthy, pale appearance.
Withdrawal symptoms
When used habitually, cocaine, because of its highly addictive nature, can change brain structure and function. Circuits within the brain structure, that play a part in stress signals become more sensitive. When cocaine is not being used this increases an individuals displeasure and negative moods. In 1986, Gawin and Kleber led an important study on the withdrawal symptoms of cocaine users. In this study, three distinct phases were reported. These phases are the crash, withdrawal and extinction. The crash phase or phase 1 occurs directly after cocaine is not being used anymore. Withdrawal symptoms for this phase are exhaustion, hypersomnia, no cravings to use, dysthymia, increased appetite, restlessness, and irritability. The second phase, or withdrawal phase occurs 1–10 weeks after cocaine users quit, symptoms include: lethargy, anxiety, erratic sleep, strong craving, emotional lability, irritability, depression, poor concentration, and bowel issues. Finally the last phase or the extinction phase occurs up to 28 weeks after discontinued use, symptoms include: episodic cravings and some dysphoria.
Epidemiology and prevalence rates
In the United States, past year cocaine users in 2019 was 5.5 million for people aged 12 or older. When broken into age groups, ages 12–17 had 97,000 users; ages 18–25 had 1.8 million users and ages 26 or older had 3.6 million users.Past year cocaine users with a cocaine use disorder in 2019 was 1 million for people aged 12 or older. When broken into age groups, ages 12–17 had 5,000 people with a cocaine use disorder; ages 18–25 had 250,000 people with a cocaine use disorder and ages 26 or older had 756,000 people with a cocaine use disorderIn the United States, cocaine use overdose deaths have been on the rise and in 2019, the CDC reported over 16,000 deaths from cocaine overdose.
Risk
A study consisting of 1,081 U.S. residents who had first used cocaine within the previous 24 months was conducted. It was found that the risk of becoming dependent on cocaine within two years of first use was 5–6%. The risk of becoming dependent within 10 years of first use increased to 15–16%. These were the aggregate rates for all types of use considered, such as smoking, snorting, and injecting. Among recent-onset users individual rates of dependency were higher for smoking (3.4 times) and much higher for injecting. Women were 3.3 times more likely to become dependent, compared with men. Users who started at ages 12 or 13 were four times as likely to become dependent compared to those who started between ages 18 and 20.However, a study of non-deviant users in Amsterdam found a "relative absence of destructive and compulsive use patterns over a ten year period" and concluded that cocaine users can and do exercise control. "Our respondents applied two basic types of controls to themselves: 1) restricting use to certain situations and to emotional states in which cocaines effects would be most positive, and 2) limiting mode of ingestion to snorting of modest amounts of cocaine, staying below 2.5 grams a week for some, and below 0.5 grams a week for most. Nevertheless, those whose use level exceeded 2.5 grams a week all returned to lower levels".
Treatment
Therapy
Twelve-step programs such as Cocaine Anonymous (modeled on Alcoholics Anonymous) have been widely used to help those with cocaine addiction. Cognitive behavioral therapy (CBT), dialectical behavior therapy (DBT), rational emotive behavior therapy (REBT), and motivational interviewing (MI) can be especially powerful approaches to treating cocaine addiction. Cognitive behavioral therapy (CBT) combined with motivational therapy (MT) have proven to be more helpful than 12 step programs in treating cocaine dependency. However, both these approaches have a fairly low success rate as research suggests that the withdrawal symptoms can last for several weeks. For instance, one of the main predictors of a successful recovery is dependent on the number of continuous days a user is able to stay off of the substance. Alternative holistic treatments such as physical exercise and Meditation has been proven effective in reducing cocaine cravings. Other non-pharmacological treatments such as acupuncture and hypnosis have been explored, but without conclusive results.
Medications
Numerous medications have been investigated for use in cocaine dependence, but as of 2015, none of them were considered to be effective. Anticonvulsants, such as carbamazepine, gabapentin, lamotrigine, and topiramate, do not appear to be effective as treatment. Limited evidence suggests that antipsychotics are also ineffective for treatment of cocaine dependence. Few studies have examined bupropion (a novel antidepressant) for cocaine dependence; however, trials performed thus far have not shown it to be an effective form of treatment for this purpose.The National Institute on Drug Abuse (NIDA) of the U.S. National Institutes of Health is researching modafinil, a narcolepsy drug and mild stimulant, as a potential cocaine treatment. Ibogaine has been under investigation as a treatment for cocaine dependency and is used in clinics in Mexico, the Netherlands and Canada. It was legal for a time in Costa Rica, but has been illegal since 2018. It is illegal to use in many countries, such as Sweden, Norway, the United Kingdom, and in the United States. Other medications that have been investigated for this purpose include acetylcysteine, baclofen, and vanoxerine. Medications such as phenelzine, have been used to cause an "aversion reaction" when administered with cocaine.
Vaccine
TA-CD is an active vaccine developed by the Xenova Group which is used to negate the effects of cocaine, making it suitable for use in treatment of addiction. It is created by combining norcocaine with inactivated cholera toxin.
Research
Transcranial magnetic stimulation (TMS) is being studied as a treatment for cocaine addiction, although definitive evidence for efficacy does not yet exist.Other research on rodents has suggested that cocaine use leads to complexes of dopamine transporters, which build up tolerance to the drug. Its possible that future treatment for cocaine addiction might target those complexes.
See also
SB-277011-A – a dopamine D3 receptor antagonist, used in the study of cocaine addiction. Where cocaine reduces the threshold for brain electrical self-stimulation in rats, an indication of cocaines rewarding effects, SB-277011-A completely reverses this effect.
Notes
References
Reference notes
== External links == |
Elder abuse | Elder abuse (also called "elder mistreatment", "senior abuse", "abuse in later life", "abuse of older adults", "abuse of older women", and "abuse of older men") is "a single, or repeated act, or lack of appropriate action, occurring within any relationship where there is an expectation of trust, which causes harm or distress to an older person." This definition has been adopted by of the World Health Organization (WHO) from a definition put forward by Hourglass (formerly Action on Elder Abuse) in the UK. Laws protecting the elderly from abuse are similar to and related to laws protecting dependent adults from abuse.
It includes harms by people, the older person knows, or has a relationship with, such as a spouse, partner, or family member; a friend or neighbor; or people that the older person relies on for services. Many forms of elder abuse are recognized as types of domestic violence or family violence since they are committed by family members. Paid caregivers have also been known to prey on their elderly patients.
While a variety of circumstances are considered elder abuse, it does not include general criminal activities against older persons, such as home break-ins, "muggings" in the street, or "distraction burglary," where a stranger distracts an older person at the doorstep while another person enters the property to steal.
The abuse of elders by caregivers is a worldwide issue. In 2002, WHO brought international attention to the issue of elder abuse. Over the years, government agencies and community professional groups, worldwide, have specified elder abuse as a social problem. In 2006, the International Network for Prevention of Elder Abuse (INPEA) designated June 15 as World Elder Abuse Awareness Day (WEAAD), and an increasing number of events are held across the globe on this day to raise awareness of elder abuse and highlight ways to challenge such abuse.
Types
Although there are common themes of elder abuse across nations, there are also unique manifestations based upon history, culture, economic strength, and societal perceptions of older people within nations themselves. The fundamental common denominator is the use of power and control by one individual to affect the well-being and status of another older individual.
There are several types of abuse of older people that are generally recognized as being elder abuse, including:
Physical: e.g. hitting, punching, slapping, burning, pushing, kicking, restraining, false imprisonment/confinement, or giving excessive or improper medication as well as withholding treatment and medication.
Psychological/Emotional: e.g. humiliating a person. A common theme is a perpetrator who identifies something that matters to an older person and then uses it to coerce an older person into a particular action. It may take verbal forms such as yelling, name-calling, ridiculing, constantly criticizing, accusations, blaming, or nonverbal forms such as ignoring, silence, shunning or withdrawing affection.
Elder financial abuse: also known as financial exploitation, involving misappropriation of financial resources by family members, caregivers, or strangers, or the use of financial means to control the person or facilitate other types of abuse. Also, failure to pay financial support to impoverished elders in jurisdictions which have filial responsibility laws, such as France, Germany, and most of the United States.
Sexual: e.g. forcing a person to take part in any sexual activity without his or her consent, including forcing them to participate in conversations of a sexual nature against their will; which may also include situations where the person is no longer able to give consent (dementia).
Neglect: e.g. depriving a person of proper medical treatment, food, heat, clothing, comfort, essential medication, or depriving a person of needed services to force certain kinds of actions, financial and otherwise. Neglect can include leaving an at-risk (i.e. fall risk) elder person unattended. The deprivation may be intentional (active neglect) or happen out of lack of knowledge or resources (passive neglect).In addition, some U.S. state laws also recognize the following as elder abuse:
Abandonment: deserting a dependent person with the intent to abandon them or leave them unattended at a place for such a time period that may be likely to endanger their health or welfare.
Rights abuse: denying the civil and constitutional rights of a person who is old, but not declared by court to be mentally incapacitated. This is an aspect of elder abuse that is increasingly being recognized and adopted by nations.
Self-neglect: any persons neglecting themselves by not caring about their own health, well-being or safety. Self-neglect (harm by self) is treated as conceptually different than abuse (harm by others). Elder self-neglect can lead to illness, injury, or even death. Common needs that older adults may deny themselves or ignore include the following: sustenance (food or water); cleanliness (bathing and personal hygiene); adequate clothing for climate protection; proper shelter; adequate safety; clean and healthy surroundings; medical attention for serious illness; and essential medications. Self-neglect is often created by an individuals declining mental awareness or capability. Some older adults may choose to deny themselves some health or safety benefits, which may not be self-neglect. This may simply be their personal choice. Caregivers and other responsible individuals must honor these choices if the older adult is sound of mind. In other instances, the older adult may lack the needed resources, as a result of poverty, or other social condition. This is also not considered "self-neglect."
Institutional abuse refers to physical or psychological harm, as well as rights violations in settings where care and assistance is provided to dependent older adults or others, such as nursing homes. Recent studies of approximately 2,000 nursing home facility residents in the United States reported a growing abuse rate of 44% and neglect up to 95%, making elder abuse in nursing homes a growing danger. Exact statistics are rare due to elder abuse in general and specifically in nursing homes being a silent condition.
Warning signs
The key to prevention and intervention of elder abuse is the ability to recognize the warning signs of its occurrence. Signs of elder abuse differ depending on the type of abuse the victim is suffering. Each type of abuse has distinct signs associated with it.
Physical abuse can be detected by visible signs on the body including bruises, scratches, scars, sprains, or broken bones. More subtle indications of physical abuse include signs of restraint such as rope marks on the wrist or broken eyeglasses.
Emotional abuse often accompanies the other types of abuse and can usually be detected by changes in the persons personality or behavior. The elder may also exhibit behavior mimicking dementia, such as rocking or mumbling. Emotional abuse is the most under reported abuse of elder abuse. Elder abuse occurs when a person fails to treat an elder with respect and includes verbal abuse. The elder experiences social isolation or lack of acknowledgement in this type of abuse. Some indicators of the emotional effects of elder abuse is the elder adult being unresponsive or uncommunicative. Also they can be unreasonably suspicious or fearful, more isolated, and not wanting to be as social as they may have been before. Emotional abuse is under reported but can have the most damaging effects because it leads to more physical and mental health problems.
Financial exploitation is a more subtle form of abuse, in comparison to other types, and may be more challenging to notice. Signs of financial exploitation include significant withdrawals from accounts, belongings or money missing from the home, unpaid bills, and unnecessary goods or services.
Sexual abuse, like physical abuse, can be detected by visible signs on the body, especially around the breasts or genital area. Other signs include inexplicable infections, bleeding, and torn underclothing.
Neglect is a type of abuse in that it can be inflicted either by the caregiver or oneself. Signs of neglect include malnutrition and dehydration, poor hygiene, noncompliance to a prescription medication, and unsafe living conditions.In addition to observing signs in the elderly individual, abuse can also be detected by monitoring changes in the caregivers behavior. For example, the caregiver may not allow them to speak to or receive visitors, exhibit indifference or a lack of affection towards the elder, or refer to the elder as "a burden." Caregivers who have a history of substance abuse or mental illness are more likely to commit elder abuse than other individuals.Abuse can sometimes be subtle and therefore difficult to detect. Regardless, awareness organizations and research advise to take any suspicion seriously and to address concerns adequately and immediately.
Signs of elder abuse
Lacks medical aids such as glasses, walker, hearing aids
Displays signs of emotional trauma
Broken eyeglasses/frames, or physical signs of punishment or being restrained
Displays signs of insufficient care or unpaid bills despite adequate financial resources
Broken bones or fractures
Poor physical appearance
Changes in mental status
Frequent infections
Bruising, scratches, welts, or cuts
Unexplained weight loss
Refusal to speak
Signs of dehydration
Lack of cleanliness
Health consequences
The health consequences of elder abuse are serious. Elder abuse can destroy an elderly persons quality of life in the forms of:
Declining functional abilities
Increased dependency, sense of helplessness, and stress
Worsening psychological decline
Premature mortality and morbidity
Depression and dementia
Malnutrition
Bedsores
DeathThe risk of death for elder abuse victims are three times higher than for non-victims.
Common abusers
An abuser can be a caregiver, spouse, partner, relative, friend, neighbor, volunteer worker, paid worker, practitioner, solicitor, or any other individual with the intent to deprive a vulnerable person of their resources. Relatives include adult children and their spouses or partners, their offspring, and other extended family members. Children and living relatives who have a history of substance abuse or have had other life troubles are of particular concern. For example, Hybrid Financial Exploitation (HFE) abusive individuals are more likely to be a relative, chronically unemployed, and dependent on the elderly person. Additionally, past studies have estimated that between 16% and 38% of all elder abusers have a history of mental illness. Elder abuse perpetrated by individuals with mental illnesses can be decreased by lessening the level of dependency that persons with serious mental illness have on family members. This can be done by funneling more resources into housing assistance programs, intensive care management services, and better welfare benefits for individuals with serious mental illness. People with substance abuse and mental health disorders typically have very small social networks, and this confinement contributes to the overall occurrence of elder abuse.Perpetrators of elder abuse can include anyone in a position of trust, control or authority over the individual. Family relationships, neighbors and friends, are all socially considered relationships of trust, whether or not the older adult actually thinks of the people as "trustworthy." Some perpetrators may "groom" an older person (befriend or build a relationship with them) in order to establish a relationship of trust. Older people living alone who have no adult children living nearby are particularly vulnerable to "grooming" by neighbors and friends who would hope to gain control of their estates.
The majority of abusers are relatives, typically the older adults spouse/partner or sons and daughters, although the type of abuse differs according to the relationship. In some situations the abuse is "domestic violence grown old," a situation in which the abusive behavior of a spouse or partner continues into old age. In some situations, an older couple may be attempting to care and support each other and failing, in the absence of external support. In the case of sons and daughters, it tends to be that of financial abuse, justified by a belief that it is nothing more than the "advance inheritance" of property, valuables, and money.
Though corporate abusers, such as brokerage firms and bank trust companies have been considered too regulated to be able to abuse the elderly, cases of such abuse have been reported. Such corporate abuse might escape notice both because they have more aptitude at methods of abuse that can go undetected and because they are protected by attorneys and the government in ways that individuals are not.
Within paid care environments, abuse can occur for a variety of reasons. Some abuse is the willful act of cruelty inflicted by a single individual upon an older person. In fact, a case study in Canada suggests that the high elder abuse statistics are from repeat offenders who, like in other forms of abuse, practice elder abuse for the schadenfreude associated with the act. More commonly, institutional abuses or neglect may reflect lack of knowledge, lack of training, lack of support, or insufficient resourcing. Institutional abuse may be the consequence of common practices or processes that are part of running of a care institution or service. Sometimes this type of abuse is referred to as "poor practice," although this term reflects the motive of the perpetrator (the causation) rather than the impact upon the older person.
With the aging of todays population, there is the potential that elder abuse will increase unless it is more comprehensively recognized and addressed.
Elder abuse is not a direct parallel to child maltreatment, as perpetrators of elder abuse do not have the same legal protection of rights as parents of children do. For example, a court order is needed to remove a child from their home but not to remove a victim of elder abuse from theirs.
Risk factors for elder abuse
Various risk factors increase the likelihood that an elderly person will become a victim of elder abuse, including an elderly person who:
Has memory problems (such as dementia)
Has a mental illness, either long-standing or recent
Has physical disabilities
Has depression, loneliness, or lack of social support
Abuses alcohol or other substances
Takes prescribed medications that impair judgment
Is verbally or physically combative with the caregiver
Has a shared living situation
Has a criminal historySeveral other risk factors increase the likelihood that a caregiver will participate in elder abuse, including a caregiver who:
Feels overwhelmed or resentful
Has a history of substance abuse or a history of abusing others
Is dependent on the older person for housing, finances, or other needs
Has mental health problems
Is unemployed
Has a criminal history
Has a shared living situationIn addition:
Lower income or poverty has been found to be associated with elder abuse. Low economic resources have been conceptualized as a contextual or situational stressor contributing to elder abuse.
Living with a large number of household members other than a spouse is associated with an increased risk of abuse, especially financial abuse.Risk factors can also be categorized into individual, relationship, community, and sociocultural levels. At the individual level, elders who have poor physical and mental health are at higher risk. At the relationship level, a shared living situation is a huge risk factor for the elderly, and living in the same area as the abuser is more likely to result in abuse. At the community level, caregivers may knowingly or inadvertently cause social isolation of the elderly. At the sociocultural level, a representation of an older person as weak and dependent, lack of funds to pay for care, elderly people who need assistance but live alone, and destruction of bonds between the generation of a family are possible factors in elder abuse.
Research and statistics
There has been a general lack of reliable data in this area and it is often argued that the absence of data is a reflection of the low priority given to work associated with older people. However, over the past decade there has been a growing amount of research into the nature and extent of elder abuse. The research still varies considerably in the definitions being used, who is being asked, and what is being asked. As a result, the statistics used in this area vary considerably.
One study suggests that around 25% of vulnerable older adults will report abuse in the previous month, totaling up to 6% of the general elderly population. However, some consistent themes are beginning to emerge from interactions with abused elders, and through limited and small scale research projects. Work undertaken in Canada suggests that approximately 70% of elder abuse is perpetrated against women and this is supported by evidence from the Hourglass helpline in the UK, which identifies women as victims in 67% of calls. Also domestic violence in later life may be a continuation of long term partner abuse and in some cases, abuse may begin with retirement or the onset of a health condition. Certainly, abuse increases with age, with 78% of victims being over 70 years of age.The higher proportion of spousal homicides supports the suggestion that abuse of older women is often a continuation of long term spousal abuse against women. In contrast, the risk of homicide for older men was far greater outside the family than within. This is an important point because the domestic violence of older people is often not recognized and consequently strategies, which have proved effective within the domestic violence arena, have not been routinely transferred into circumstances involving the family abuse of older people.
According to the Hourglass helpline in the UK, abuse occurs primarily in the family home (64%), followed by residential care (23%), and then hospitals (5%), although a helpline does not necessarily provide a true reflection of such situations as it is based upon the physical and mental ability of people to utilize such a resource.Research conducted in New Zealand broadly supports the above findings, with some variations. Of 1288 cases in 2002–2004, 1201 individuals, 42 couples, and 45 groups were found to have been abused. Of these, 70 percent were female. Psychological abuse (59%), followed by material/financial (42%), and physical abuse (12%) were the most frequently identified types of abuse. Sexual abuse occurred in 2% of reported cases.Age Concern New Zealand found that most abusers are family members (70%), most commonly sons or daughters (40%). Older abusers (those over 65 years) are more likely to be husbands.In 2007, 4766 cases of suspected abuse, neglect, or financial exploitation involving older adults were reported, an increase of 9 percent over 2006. 19 incidents were related to a death, and a total of 303 incidents were considered life-threatening. About one in 11 incidents involved a life-threatening or fatal situation.In 2012, the study called Pure Financial Exploitation vs. Hybrid Exploitation Co-Occurring With Physical Abuse and/or Neglect of Elderly Persons by Shelly L. Jackson and Thomas L. Hafemeister brought attention to the hybrid abuse that elderly persons can experience. This study revealed that victims of hybrid financial exploitation or HFE lost an average of $185,574, a range of $20–$750,000.
Barriers to obtaining statistics
Several conditions make it hard for researchers to obtain accurate statistics on elder abuse. Researchers may have difficulty obtaining accurate elder abuse statistics for the following reasons:
Elder abuse is largely a hidden problem and tends to be committed in the privacy of the elderly persons home, mostly by his or her family members.
Elder abuse victims are often unwilling to report their abuse for fear of others disbelief, fear of loss of independence, fear of being institutionalized, fear of losing their only social support (especially if the perpetrator is a relative), and fear of being subject to future retaliation by the perpetrator(s).
Elder abuse victims cognitive decline and ill health may prevent them from reporting their abuse.
Lack of proper training of service providers, such as social workers, law enforcement, nurses, etc., about elder abuse, therefore the number of cases reported tend to be low.
The subjective nature of elder abuse, which largely depends on ones interpretation.
Another reason why there is a lack of accurate statistics is the debate of whether to include self-neglect or not. Many are unsure if it should be included since it does not involve another person as an abuser. Those opposed to the inclusion of self-neglect make the claim that it is a different form of abuse and thus, should not be included in the statistics. Due to this discrepancy and the others mentioned above, it is difficult to get accurate data concerning the abuse of the elderly.
Prevention
Doctors, nurses, and other medical personnel can play a vital role in assisting elder abuse victims. Studies have shown that elderly individuals, on average, make 13.9 visits per year to a physician. Although there has been an increase in awareness of elder abuse over the years, physicians tend to only report 2% of elder abuse cases. Reasons for lack of reporting by physicians include a lack of current knowledge concerning state laws on elder abuse, concern about angering the abuser and ruining the relationship with the elderly patient, possible court appearances, lack of cooperation from elderly patients or families, and lack of time and reimbursement. Through education and training on elder abuse, health care professionals can better assist elder abuse victims.
Educating and training those in the criminal justice system, such as police, prosecutors, and the judiciary on elder abuse, as well as increased legislation to protect elders, will also help to minimize elder abuse. Increased legislation to protect elders and will also provide improved assistance to victims of elder abuse.
In addition, community involvement in responding to elder abuse can contribute to elderly persons safety. In general, preventing the occurrence or recurrence of elder abuse helps not only the elder but it may also improve the anxiety and depression of their caregivers too. Communities can develop programs that are structured around meeting the needs of elderly persons. For example, several communities throughout the United States have created Financial Abuse Specialist Teams, which are multidisciplinary groups that consist of public and private professionals who volunteer their time to advise Adult Protective Services (APS), law enforcement, and private attorneys on matters of vulnerable adult financial abuse.
False accusations of elder abuse
It is important to recognize that false accusations of elder abuse are very common. An elderly person who has dementia or a mental illness may falsely claim to be a victim of abuse. By one estimate, 70% of elderly people with mental impairments such as dementia, delusions, or paranoia falsely accuse caregivers of stealing. Mentally impaired elders may claim that a caregiver is feeding them poisoned food or holding them prisoner. Websites such as Alzlive.com and DailyCaring.com offer advice for caregivers who are falsely accused of elder abuse or other crimes.
Examples
Stephen Akinmurele
Juana Barraza
Kenneth Erskine
Dana Sue Gray
Delroy Grant
Reta Mays
Thierry Paulin
Kaspars Petrovs
Dorothea Puente
Irina Gaidamachuk
John Wayne Glover
Charles Rogers (murder suspect)
Murder of Esther Brown
Murder of Valerie Graves
Murder of Patricia OConnor
Murder of Janie Perrin
Murders of William and Patricia Wycherley
Sereni Orizzonti
See also
References
Further reading
Nerenberg, Lisa Elder Abuse Prevention: Emerging Trends and Promising Strategies (2007)
External links
World Health Organization website
https://ncea.acl.gov/whatwedo/research/statistics.html
National Center on Elder Abuse (NCEA)
Senior Abuse Awareness & Prevention Infographic
End of Life Care – Dying with Dignity at Home
Elder abuse Centers for Disease Control and Prevention |
Factitious disorder | A factitious disorder is a condition in which a person, without a malingering motive, acts as if they have an illness by deliberately producing, feigning, or exaggerating symptoms, purely to attain (for themselves or for another) a patients role. People with a factitious disorder may produce symptoms by contaminating urine samples, taking hallucinogens, injecting fecal material to produce abscesses, and similar behaviour.
Factitious disorder imposed on self (also called Munchausen syndrome) was for some time the umbrella term for all such disorders. Factitious disorder imposed on another (also called Munchausen syndrome by proxy, Munchausen by proxy, or factitious disorder by proxy) is a condition in which a person deliberately produces, feigns, or exaggerates the symptoms of someone in their care. In either case, the perpetrators motive is to perpetrate factitious disorders, either as a patient or by proxy as a caregiver, in order to attain (for themselves or for another) a patients role. Malingering differs fundamentally from factitious disorders in that the malingerer simulates illness intending to obtain a material benefit or avoid an obligation or responsibility. Somatic symptom disorders, though also diagnoses of exclusion, are characterized by physical complaints that are not produced intentionally.
Causes
The causes are mostly unknown. One possible cause is trauma but the rest is still going through a testing process. It is also been suspected that it might be hereditary, like depression. There are still many possible causes for this disorder which havent been defined yet.These individuals may be trying to reenact unresolved issues with their parents. A history of frequent illnesses may also contribute to the development of this disorder. In some cases, individuals with factitious disorder are accustomed to actually being sick, and thus return to their previous state to recapture what they once considered the "norm". Another cause is a history of close contact with someone (a friend or family member) who had a severe or chronic condition. The patients found themselves subconsciously envious of the attention said relation received, and felt that they themselves faded into the background. Thus medical attention makes them feel glamorous and special.
Diagnosis
Criteria for diagnosis include intentionally fabricating to produce physical or psychological signs or symptoms and the absence of any other mental disorder. Motivation for their behavior must be to assume the "sick" role, and they do not act sick for personal gain as in the case of malingering sentiments. When the individual applies this pretended sickness to a dependent, for example, a child, it is often referred to as "factitious disorder by proxy".The DSM-5 differentiates among two types:
Factitious disorder imposed on self (Munchausen syndrome)
Factitious disorder imposed on another (Munchausen syndrome by proxy), defined as: When an individual falsifies illness in another, whether that be a child, pet, or older adult.
Factitious disorder imposed on self
Factitious disorder imposed on self, previously called Munchausen syndrome, or factitious disorder with predominantly physical signs and symptoms, has specified symptoms. Factitious disorder symptoms may seem exaggerated; individuals undergo major surgery repeatedly, and they "hospital jump" or migrate to avoid detection.
Factitious disorder imposed on another
Factitious disorder imposed on another, previously Munchausen syndrome by proxy, is the involuntary use of another individual to play the patient role. For example, false symptoms are produced in children by the caregivers or parents, to produce the appearance of illness, or they may give misleading medical histories about their children. The parent may falsify the childs medical history or tamper with laboratory tests to make the child appear sick. Occasionally, in Munchausen by proxy, the caregiver actually injures the child or makes them sick to ensure that the child is treated. For instance, a father whose son has celiac disease might knowingly introduce gluten into the diet. Such parents may be validated by the attention that they receive from having a sick child.
Ganser syndrome
Ganser syndrome was once considered a separate factitious disorder, but is now considered a dissociative disorder. It is a disorder of extreme stress or an organic condition. The patient experiences approximation or giving absurd answers to simple questions. The syndrome is sometimes diagnosed as merely malingering—however, it is more often defined as a factitious disorder. This has been seen in prisoners following solitary confinement, and the symptoms are consistent in different prisons, though the patients do not know one another.Symptoms include a clouding of consciousness, somatic conversion symptoms, confusion, stress, loss of personal identity, echolalia, and echopraxia. Individuals also give approximate answers to simple questions such as, "How many legs on a cat?" "Three"; "Whats the day after Wednesday?" "Friday"; and so on. The disorder is extraordinarily rare with fewer than 100 recorded cases. While individuals of all backgrounds have been reported with the disorder, there is a higher inclination towards males (75% or more). The average age of those with Ganser syndrome is 32, though it stretches from ages 15–62 years old.
Differential diagnosis
Factitious disorder should be distinguished from somatic symptom disorder (formerly called somatization disorder), in which the patient is truly experiencing the symptoms and has no intention to deceive.
In conversion disorder (previously called hysteria), a neurological deficit appears with no organic cause. The patient, again, is truly experiencing the symptoms and signs and has no intention to deceive.
The differential also includes body dysmorphic disorder and pain disorder.
Treatment
No true psychiatric medications are prescribed for factitious disorder. However, selective serotonin reuptake inhibitors (SSRIs) can help manage underlying problems. Medicines such as SSRIs that are used to treat mood disorders can be used to treat factitious disorder, as a mood disorder may be the underlying cause of factitious disorder. Some authors (such as Prior and Gordon 1997) also report good responses to antipsychotic drugs such as Pimozide. Family therapy can also help. In such therapy, families are helped to better understand patients (the individual in the family with factitious disorder) and that persons need for attention.
In this therapeutic setting, the family is urged not to condone or reward the factitious disorder individuals behavior. This form of treatment can be unsuccessful if the family is uncooperative or displays signs of denial and/or antisocial disorder. Psychotherapy is another method used to treat the disorder. These sessions should focus on the psychiatrists establishing and maintaining a relationship with the patient. Such a relationship may help to contain symptoms of factitious disorder. Monitoring is also a form that may be indicated for the factitious disorder patients own good; factitious disorder (especially proxy) can be detrimental to an individuals health—if they are, in fact, causing true physiological illnesses. Even faked illnesses and injuries can be dangerous and might be monitored for fear that unnecessary surgery may subsequently be performed.
Prognosis
Some individuals experience only a few outbreaks of the disorder. However, in most cases, factitious disorder is a chronic long-term condition that is difficult to treat. There are relatively few positive outcomes for this disorder; in fact, treatment provided a lower percentage of positive outcomes than did the treatment of individuals with obvious psychotic symptoms such as people with schizophrenia. In addition, many individuals with factitious disorder do not present for treatment, often insisting their symptoms are genuine. Some degree of recovery, however, is possible. The passage of time seems to help the disorder greatly. There are many possible explanations for this occurrence, although none are currently considered definitive. It may be that a factitious disorder individual has mastered the art of feigning sickness over so many years of practice that the disorder can no longer be discerned. Another hypothesis is that many times a factitious disorder individual is placed in a home, or experiences health issues that are not self-induced or feigned. In this way, the problem with obtaining the "patient" status is resolved because symptoms arise without any effort on the part of the individual.
History
Previously, the DSM-IV differentiated among three types:
Factitious disorders with predominantly psychological signs and symptoms: if psychological signs and symptoms predominate in the clinical presentation
Factitious disorders with predominantly physical signs and symptoms: if physical signs and symptoms predominate in the clinical presentation
Factitious disorders with combined psychological and physical signs and symptoms: if both psychological and physical signs and symptoms are present and neither predominates in the clinical presentation
See also
Attention seeking
Somatic symptom disorder
Victim playing
References
== External links == |
Acute lymphoblastic leukemia | Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, or bone pain. As an acute leukemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated.In most cases, the cause is unknown. Genetic risk factors may include Down syndrome, Li-Fraumeni syndrome, or neurofibromatosis type 1. Environmental risk factors may include significant radiation exposure or prior chemotherapy. Evidence regarding electromagnetic fields or pesticides is unclear. Some hypothesize that an abnormal immune response to a common infection may be a trigger. The underlying mechanism involves multiple genetic mutations that results in rapid cell division. The excessive immature lymphocytes in the bone marrow interfere with the production of new red blood cells, white blood cells, and platelets. Diagnosis is typically based on blood tests and bone marrow examination.ALL is typically treated initially with chemotherapy aimed at bringing about remission. This is then followed by further chemotherapy typically over a number of years. Treatment usually also includes intrathecal chemotherapy since systemic chemotherapy can have limited penetration into the central nervous system and the central nervous system is a common site for relapse of acute lymphoblastic leukemia.Treatment can also include radiation therapy if spread to the brain has occurred. Stem cell transplantation may be used if the disease recurs following standard treatment. Additional treatments such as Chimeric antigen receptor T cell immunotherapy are being used and further studied.ALL affected about 876,000 people globally in 2015 and resulted in about 111,000 deaths. It occurs most commonly in children, particularly those between the ages of two and five. In the United States it is the most common cause of cancer and death from cancer among children. ALL is notable for being the first disseminated cancer to be cured. Survival for children increased from under 10% in the 1960s to 90% in 2015. Survival rates remain lower for babies (50%) and adults (35%). According to the National Cancer Intelligence Network (NCIN), generally for people with ALL: around 70 out of 100 people (70%) will survive their leukemia for 5 years or more after they are diagnosed.
Signs and symptoms
Initial symptoms can be nonspecific, particularly in children. Over 50% of children with leukemia had one or more of five features: a liver one can feel (64%), a spleen one can feel (61%), pale complexion (54%), fever (53%), and bruising (52%). Additionally, recurrent infections, feeling tired, arm or leg pain, and enlarged lymph nodes can be prominent features. The B symptoms, such as fever, night sweats, and weight loss, are often present as well.Central nervous system (CNS) symptoms such as cranial neuropathies due to meningeal infiltration are identified in less than 10% of adults and less than 5% of children, particularly mature B-cell ALL (Burkitt leukemia) at presentation.The signs and symptoms of ALL are variable and include:
Generalized weakness and feeling tired
Anemia
Dizziness
Headache, vomiting, lethargy, neck stiffness, or cranial nerve palsies (CNS involvement)
Frequent or unexplained fever and infection
Weight loss and/or loss of appetite
Excessive and unexplained bruising
Bone pain, joint pain (caused by the spread of "blast" cells to the surface of the bone or into the joint from the marrow cavity)
Breathlessness
Enlarged lymph nodes, liver, and/or spleen
Pitting edema (swelling) in the lower limbs and/or abdomen
Petechiae, which are tiny red spots or lines in the skin due to low platelet levels
Testicular enlargement
Mediastinal mass
Cause
The cancerous cell in ALL is the lymphoblast. Normal lymphoblasts develop into mature, infection-fighting B-cells or T-cells, also called lymphocytes. Signals in the body control the number of lymphocytes so neither too few nor too many are made. In ALL, both the normal development of some lymphocytes and the control over the number of lymphoid cells become defective.ALL emerges when a single lymphoblast gains many mutations to genes that affect blood cell development and proliferation. In childhood ALL, this process begins at conception with the inheritance of some of these genes. These genes, in turn, increase the risk that more mutations will occur in developing lymphoid cells. Certain genetic syndromes, like Down Syndrome, have the same effect. Environmental risk factors are also needed to help create enough genetic mutations to cause disease. Evidence for the role of the environment is seen in childhood ALL among twins, where only 10–15% of both genetically identical twins get ALL. Since they have the same genes, different environmental exposures explain why one twin gets ALL and the other does not.Infant ALL is a rare variant that occurs in babies less than one-year-old. KMT2A (formerly MLL) gene rearrangements are most common and occur in the embryo or fetus before birth. These rearrangements result in increased expression of blood cell development genes by promoting gene transcription and through epigenetic changes. In contrast to childhood ALL, environmental factors are not thought to play a significant role. Aside from the KMT2A rearrangement, only one extra mutation is typically found. Environmental exposures are not needed to help create more mutations.
Risk factors
Genetics
Common inherited risk factors include mutations in ARID5B, CDKN2A/2B, CEBPE, IKZF1, GATA3, PIP4K2A and, more rarely, TP53. These genes play important roles in cellular development, proliferation, and differentiation. Individually, most of these mutations are low risk for ALL. Significant risk of disease occurs when a person inherits several of these mutations together.The uneven distribution of genetic risk factors may help explain differences in disease rates among ethnic groups. For instance, the ARID5B mutation is less common in ethnic African populations.Several genetic syndrome also carry increased risk of ALL. These include: Down syndrome, Fanconi anemia, Bloom syndrome, X-linked agammaglobulinemia, severe combined immunodeficiency, Shwachman-Diamond syndrome, Kostmann syndrome, neurofibromatosis type 1, ataxia-telangiectasia, paroxysmal nocturnal hemoglobinuria, and Li-Fraumeni syndrome. Fewer than 5% of cases are associated with a known genetic syndrome.Rare mutations in ETV6 and PAX5 are associated with a familial form of ALL with autosomal dominant patterns of inheritance.
Environmental
The environmental exposures that contribute to emergence of ALL is contentious and a subject of ongoing debate.High levels of radiation exposure from nuclear fallout is a known risk factor for developing leukemia. Evidence whether lesser radiation, as from x-ray imaging during pregnancy, increases risk of disease remains inconclusive. Studies that have identified an association between x-ray imaging during pregnancy and ALL found only a slightly increased risk. Exposure to strong electromagnetic radiation from power lines has also been associated with a slightly increased risk of ALL. This result is questioned as no causal mechanism linking electromagnetic radiation with cancer is known.High birth weight (greater than 4000g or 8.8lbs) is also associated with a small increased risk. The mechanism connecting high birth weight to ALL is also not known.Evidence suggests that secondary leukemia can develop in individuals treated with certain types of chemotherapy, such as epipodophyllotoxins and cyclophosphamide.
Infections
There is some evidence that a common infection, such as influenza, may indirectly promote the emergence of ALL. The delayed-infection hypothesis states that ALL results from an abnormal immune response to infection in a person with genetic risk factors. Delayed development of the immune system due to limited disease exposure may result in excessive production of lymphocytes and increased mutation rate during an illness. Several studies have identified lower rates of ALL among children with greater exposure to illness early in life. Very young children who attend daycare have lower rates of ALL. Evidence from many other studies looking at disease exposure and ALL is inconclusive. Some researchers have linked the hygiene hypothesis.
Mechanism
Several characteristic genetic changes lead to the creation of a leukemic lymphoblast. These changes include chromosomal translocations, intrachromosomal rearrangements, changes in the number of chromosomes in leukemic cells, and additional mutations in individual genes. Chromosomal translocations involve moving a large region of DNA from one chromosome to another. This move can result in placing a gene from one chromosome that promotes cell division to a more actively transcribed area on another chromosome. The result is a cell that divides more often. An example of this includes the translocation of C-MYC, a gene that encodes a transcription factor that leads to increased cell division, next to the immunoglobulin heavy- or light-chain gene enhancers, leading to increased C-MYC expression and increased cell division. Other large changes in chromosomal structure can result in the placement of two genes directly next to each other. The result is the combination of two usually separate proteins into a new fusion protein. This protein can have a new function that promotes the development of cancer. Examples of this include the ETV6–RUNX1 fusion gene that combines two factors that promote blood cell development and the BCR-ABL1 fusion gene of the Philadelphia chromosome. BCR–ABL1 encodes an always-activated tyrosine kinase that causes frequent cell division. These mutations produce a cell that divides more often, even in the absence of growth factors.Other genetic changes in B-cell ALL include changes to the number of chromosomes within the leukemic cells. Gaining at least five additional chromosomes, called high hyperdiploidy, occurs more commonly. Less often, chromosomes are lost, called hypodiploidy, which is associated with a poorer prognosis. Additional common genetic changes in B-cell ALL involve non-inherited mutations to PAX5 and IKZF1. In T-cell ALL, LYL1, TAL1, TLX1, and TLX3 rearrangements can occur.ALL results when enough of these genetic changes are present in a single lymphoblast. In childhood ALL, for example, one fusion gene translocation is often found along with six to eight other ALL-related genetic changes. The initial leukemic lymphoblast copies itself into an excessive number of new lymphoblasts, none of which can develop into functioning lymphocytes. These lymphoblasts build up in the bone marrow and may spread to other sites in the body, such as lymph nodes, the mediastinum, the spleen, the testicles, and the brain, leading to the common symptoms of the disease.
Diagnosis
Diagnosing ALL begins with a thorough medical history, physical examination, complete blood count, and blood smears. While many symptoms of ALL can be found in common illnesses, persistent or unexplained symptoms raise suspicion of cancer. Because many features on the medical history and exam are not specific to ALL, further testing is often needed. A large number of white blood cells and lymphoblasts in the circulating blood can be suspicious for ALL because they indicate a rapid production of lymphoid cells in the marrow. The higher these numbers typically point to a worse prognosis. While white blood cell counts at initial presentation can vary significantly, circulating lymphoblast cells are seen on peripheral blood smears in the majority of cases.A bone marrow biopsy provides conclusive proof of ALL, typically with >20% of all cells being leukemic lymphoblasts. A lumbar puncture (also known as a spinal tap) can determine whether the spinal column and brain have been invaded. Brain and spinal column involvement can be diagnosed either through confirmation of leukemic cells in the lumbar puncture or through clinical signs of CNS leukemia as described above. Laboratory tests that might show abnormalities include blood count, kidney function, electrolyte, and liver enzyme tests.Pathological examination, cytogenetics (in particular the presence of Philadelphia chromosome), and immunophenotyping establish whether the leukemic cells are myeloblastic (neutrophils, eosinophils, or basophils) or lymphoblastic (B lymphocytes or T lymphocytes). Cytogenetic testing on the marrow samples can help classify disease and predict how aggressive the disease course will be. Different mutations have been associated with shorter or longer survival. Immunohistochemical testing may reveal TdT or CALLA antigens on the surface of leukemic cells. TdT is a protein expressed early in the development of pre-T and pre-B cells, whereas CALLA is an antigen found in 80% of ALL cases and also in the "blast crisis" of CML.
Medical imaging (such as ultrasound or CT scanning) can find invasion of other organs commonly the lung, liver, spleen, lymph nodes, brain, kidneys, and reproductive organs.
Immunophenotyping
In addition to cell morphology and cytogenetics, immunophenotyping, a laboratory technique used to identify proteins that are expressed on their cell surface, is a key component in the diagnosis of ALL. The preferred method of immunophenotyping is through flow cytometry. In the malignant lymphoblasts of ALL, expression of terminal deoxynucleotidyl transferase (TdT) on the cell surface can help differentiate malignant lymphocyte cells from reactive lymphocytes, white blood cells that are reacting normally to an infection in the body. On the other hand, myeloperoxidase (MPO), a marker for the myeloid lineage, is typically not expressed. Because precursor B cell and precursor T cells look the same, immunophenotyping can help differentiate the subtype of ALL and the level of maturity of the malignant white blood cells. The subtypes of ALL as determined by immunophenotype and according to the stages of maturation.
An extensive panel of monoclonal antibodies to cell surface markers, particularly CD or cluster of differentiation markers, are used to classify cells by lineage. Below are immunological markers associated with B cell and T cell ALL.
Cytogenetics
Cytogenetic analysis has shown different proportions and frequencies of genetic abnormalities in cases of ALL from different age groups. This information is particularly valuable for classification and can in part explain the different prognoses of these groups. In regards to genetic analysis, cases can be stratified according to ploidy, a number of sets of chromosomes in the cell, and specific genetic abnormalities, such as translocations. Hyperdiploid cells are defined as cells with more than 50 chromosomes, while hypodiploid are defined as cells with less than 44 chromosomes. Hyperdiploid cases tend to carry a good prognosis while hypodiploid cases do not. For example, the most common specific abnormality in childhood B-ALL is the t(12;21) ETV6–RUNX1 translocation, in which the RUNX1 gene, encoding a protein involved in transcriptional control of hemopoiesis, has been translocated and repressed by the ETV6–RUNX1 fusion protein.Below is a table with the frequencies of some cytogenetic translocations and molecular genetic abnormalities in ALL.
Classification
French-American-British
Historically, prior to 2008, ALL was classified morphologically using the French-American-British (FAB) system that heavily relied on morphological assessment. The FAB system takes into account information on size, cytoplasm, nucleoli, basophilia (color of cytoplasm), and vacuolation (bubble-like properties).
While some clinicians still use the FAB scheme to describe tumor cell appearance, much of this classification has been abandoned because of its limited impact on treatment choice and prognostic value.: 491 World Health Organization
In 2008, the World Health Organization classification of acute lymphoblastic leukemia was developed in an attempt to create a classification system that was more clinically relevant and could produce meaningful prognostic and treatment decisions. This system recognized differences in genetic, immunophenotype, molecular, and morphological features found through cytogenetic and molecular diagnostics tests.: 1531–1535 This subtyping helps determine the prognosis and the most appropriate treatment for each specific case of ALL.
The WHO subtypes related to ALL are:
B-lymphoblastic leukemia/lymphoma
Not otherwise specified (NOS)
with recurrent genetic abnormalities
with t(9;22)(q34.1;q11.2);BCR-ABL1
with t(v;11q23.3);KMT2A rearranged
with t(12;21)(p13.2;q22.1); ETV6-RUNX1
with t(5;14)(q31.1;q32.3) IL3-IGH
with t(1;19)(q23;p13.3);TCF3-PBX1
with hyperdiploidy
with hypodiploidy
T-lymphoblastic leukemia/lymphoma
Acute leukemias of ambiguous lineage
Acute undifferentiated leukemia
Mixed phenotype acute leukemia (MPAL) with t(9;22)(q34.1;q11.2); BCR–ABL1
MPAL with t(v;11q23.3); KMT2A rearranged
MPAL, B/myeloid, NOS
MPAL, T/myeloid, NOS
MicroRNA signature
A systematic review of miRNA levels in pediatric B-ALL compared with controls revealed that miR-155 is the most frequently reported upregulated miRNA (followed by miR-146a, miR-181b, miR-222 and miR-708; two citations for miR-16, miR-21, miR-34a, miR-100, miR-128-1, miR-181a, miR-181c, miR-195, miR-210, miR-320a and miR-660), whereas the most frequently reported downregulated miRNA is miR-374a (two citations for miR-27a, miR-30c, miR-196b, miR-223 and miR-494). To date, there is no consensus miRNA signature and this is mainly attributed to different miRNA signatures across ALL subtypes and methodology of conducted studies.
Treatment
The aim of treatment is to induce a lasting remission, defined as the absence of detectable cancer cells in the body (usually less than 5% blast cells in the bone marrow).
Over the past several decades, there have been strides to increase the efficacy of treatment regimens, resulting in increased survival rates. Possible treatments for acute leukemia include chemotherapy, steroids, radiation therapy, intensive combined treatments (including bone marrow or stem cell transplants), targeted therapy, and/or growth factors.
Chemotherapy
Chemotherapy is the initial treatment of choice, and most people with ALL receive a combination of medications. There are no surgical options because of the body-wide distribution of the malignant cells. In general, cytotoxic chemotherapy for ALL combines multiple antileukemic drugs tailored to each person. Chemotherapy for ALL consists of three phases: remission induction, intensification, and maintenance therapy.
Due to the presence of CNS involvement in 10–40% of adults with ALL at diagnosis, most providers start Central nervous system (CNS) prophylaxis and treatment during the induction phase, and continue it during the consolidation/intensification period.
Adult chemotherapy regimens mimic those of childhood ALL; however, are linked with a higher risk of disease relapse with chemotherapy alone. It should be known that 2 subtypes of ALL (B-cell ALL and T-cell ALL) require special considerations when it comes to selecting an appropriate treatment regimen in adults with ALL. B-cell ALL is often associated with cytogenetic abnormalities (specifically, t(8;14), t (2;8), and t(8;22)), which require aggressive therapy consisting of brief, high-intensity regimens. T-cell ALL responds to cyclophosphamide-containing agents the most.As the chemotherapy regimens can be intensive and protracted, many people have an intravenous catheter inserted into a large vein (termed a central venous catheter or a Hickman line), or a Portacath, usually placed near the collar bone, for lower infection risks and the long-term viability of the device. Males usually endure a longer course of treatment than females as the testicles can act as a reservoir for cancer.
Radiation therapy
Radiation therapy (or radiotherapy) is used on painful bony areas, in high disease burdens, or as part of the preparations for a bone marrow transplant (total body irradiation). In the past, physicians commonly utilized radiation in the form of whole-brain radiation for central nervous system prophylaxis, to prevent the occurrence and/or recurrence of leukemia in the brain. Recent studies showed that CNS chemotherapy provided results as favorable but with fewer developmental side effects. As a result, the use of whole-brain radiation has been more limited. Most specialists in adult leukemia have abandoned the use of radiation therapy for CNS prophylaxis, instead using intrathecal chemotherapy.
Biological therapy
Selection of biological targets on the basis of their combinatorial effects on the leukemic lymphoblasts can lead to clinical trials for improvement in the effects of ALL treatment. Tyrosine-kinase inhibitors (TKIs), such as imatinib, are often incorporated into the treatment plan for people with Bcr-Abl1+ (Ph+) ALL. However, this subtype of ALL is frequently resistant to the combination of chemotherapy and TKIs and allogeneic stem cell transplantation is often recommended upon relapse.
Immunotherapy
Chimeric antigen receptors (CARs) have been developed as a promising immunotherapy for ALL. This technology uses a single chain variable fragment (scFv) designed to recognize the cell surface marker CD19 as a method of treating ALL.
CD19 is a molecule found on all B-cells and can be used as a means of distinguishing the potentially malignant B-cell population. In this therapy, mice are immunized with the CD19 antigen and produce anti-CD19 antibodies. Hybridomas developed from mouse spleen cells fused to a myeloma cell line can be developed as a source for the cDNA encoding the CD19 specific antibody. The cDNA is sequenced and the sequence encoding the variable heavy and variable light chains of these antibodies are cloned together using a small peptide linker. This resulting sequence encodes the scFv. This can be cloned into a transgene, encoding what will become the endodomain of the CAR. Varying arrangements of subunits serve as the endodomain, but they generally consist of the hinge region that attaches to the scFv, a transmembrane region, the intracellular region of a costimulatory molecule such as CD28, and the intracellular domain of CD3-zeta containing ITAM repeats. Other sequences frequently included are: 4-1bb and OX40. The final transgene sequence, containing the scFv and endodomain sequences is then inserted into immune effector cells that are obtained from the person and expanded in vitro. In trials these have been a type of T-cell capable of cytotoxicity.Inserting the DNA into the effector cell can be accomplished by several methods. Most commonly, this is done using a lentivirus that encodes the transgene. Pseudotyped, self-inactivating lentiviruses are an effective method for the stable insertion of a desired transgene into the target cell. Other methods include electroporation and transfection, but these are limited in their efficacy as transgene expression diminishes over time.
The gene-modified effector cells are then transplanted back into the person. Typically this process is done in conjunction with a conditioning regimen such as cyclophosphamide, which has been shown to potentiate the effects of infused T-cells. This effect has been attributed to making an immunologic space within which the cells populate. The process as a whole result in an effector cell, typically a T-cell, that can recognize a tumor cell antigen in a manner that is independent of the major histocompatibility complex and which can initiate a cytotoxic response.
In 2017, tisagenlecleucel was approved by the FDA as a CAR-T therapy for people with acute B-cell lymphoblastic leukaemia who did not respond adequately to other treatments or have relapsed. In a 22-day process, the "drug" is customized for each person. T cells purified from each person are modified by a virus that inserts genes that encode a chimaeric antigen receptor into their DNA, one that recognizes leukemia cells.
Relapsed ALL
Typically, people who experience a relapse in their ALL after initial treatment have a poorer prognosis than those who remain in complete remission after induction therapy. It is unlikely that recurrent leukemia will respond favorably to the standard chemotherapy regimen that was initially implemented, and instead, these people should be trialed on reinduction chemotherapy followed by allogeneic bone marrow transplantation. These people in relapse may also receive blinatumomab, as it has shown to increase remission rates and overall survival rates, without increased toxic effects.Low dose palliative radiation may also help reduce the burden of tumor inside or outside the central nervous system and alleviate some symptoms.
Recently, there has also been evidence and approval of use for dasatinib, a tyrosine kinase inhibitor. It has shown efficacy in cases of people with Ph1-positive and imatinib-resistant ALL, but more research needs to be done on long-term survival and time to relapse.
Side effects
Chemotherapies or stem cell transplantations may require a platelet transfusion to prevent bleeding. Moreover, patients undergoing a stem cell transplantation can develop a graft-versus-host disease (GvHD). It was evaluated whether mesenchymal stromal cells can be used to prevent a GvHD. The evidence is very uncertain about the therapeutic effect of mesenchymal stromal cells to treat graft-versus-host diseases after a stem cell transplantation on the all-cause mortality and complete disappear of chronic acute graft-versus-host diseases. Mesenchymal stromal cells may results in little to no difference in the all-cause mortality, relapse of malignant disease and incidence of acute and chronic graft-versus-host diseases if they are used for prophylactic reason.
Supportive therapy
Adding physical exercises to the standard treatment for adult patients with haematological malignancies like ALL may result in little to no difference in mortality, the quality of life, and physical functioning. These exercises may result in a slight reduction in depression. Furthermore, aerobic physical exercises probably reduce fatigue. The evidence is very uncertain about the effect on anxiety and serious adverse events.
Gene therapy
Brexucabtagene autoleucel (Tecartus) was approved for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia in October 2021.Each dose of brexucabtagene autoleucel is a customized treatment created using the recipients own immune system to help fight the lymphoma. The recipients T cells, a type of white blood cell, are collected and genetically modified to include a new gene that facilitates the targeting and killing of the lymphoma cells. These modified T cells are then infused back into the recipient.
Prognosis
Prior to the development of chemotherapy regimens and hematopoietic stem cell transplant, children were surviving a median length of 3 months, largely due to either infection or bleeding. Since the advent of chemotherapy, the prognosis for childhood leukemia has improved greatly and children with ALL are estimated to have a 95% probability of achieving a successful remission after 4 weeks of initiating treatment. People in pediatric care with ALL in developed countries have a greater than 80% five-year survival rate. It is estimated that 60–80% of adults undergoing induction chemotherapy achieve complete remission after 4 weeks, and those over the age of 70 have a cure rate of 5%.
However, there are differing prognoses for ALL among individuals depending on a variety of factors:
Gender: Females tend to fare better than males.
Ethnicity: Caucasians are more likely to develop acute leukemia than African-Americans, Asians, or Hispanics. However, they also tend to have a better prognosis than non-Caucasians.
Age at diagnosis: children 1–10 years of age are most likely to develop ALL and to be cured of it. Cases in older people are more likely to result from chromosomal abnormalities (e.g., the Philadelphia chromosome) that make treatment more difficult and prognoses poorer. Older people are also likely to have co-morbid medical conditions that make it even more difficult to tolerate ALL treatment.
White blood cell count at diagnosis of greater than 30,000 (B-ALL) or |
Acute lymphoblastic leukemia | 100,000 (T-ALL) is associated with worse outcomes
Cancer spreading into the Central nervous system (brain or spinal cord) has worse outcomes.
Morphological, immunological, and genetic subtypes
Persons response to initial treatment and longer length of time required (greater than 4 weeks) to reach complete remission
Early relapse of ALL
Minimal residual disease
Genetic disorders, such as Down syndrome, and other chromosomal abnormalities (aneuploidy and translocations)Cytogenetics, the study of characteristic large changes in the chromosomes of cancer cells, is an important predictor of outcome. Some cytogenetic subtypes have a worse prognosis than others. These include:
Person with t(9,22) positive-ALL (30% of adult ALL cases) and other Bcr-abl-rearranged leukemias are more likely to have a poor prognosis, but survival rates may rise with treatment consisting of chemotherapy and Bcr-abl tyrosine kinase inhibitors.
A translocation between chromosomes 4 and 11 occurs in about 4% of cases and is most common in infants under 12 months.Hyperdiploidy (>50 chromosomes) and t(12;21) are good prognostic factors and also makeup 50% of pediatric ALL cases.Unclassified ALL is considered to have an intermediate prognosis risk, somewhere in-between the good and poor risk categories.
Epidemiology
ALL affected about 876,000 people and resulted in 111,000 deaths globally in 2015. It occurs in both children and adults with highest rates seen between the ages three and seven years. Around 75% of cases occur before the age of 6 with a secondary rise after the age of 40. It is estimated to affect 1 in 1500 children.Accounting for the broad age profiles of those affected, ALL newly occurs in about 1.7 per 100,000 people per year. ALL represents approximately 20% of adults and 80% of childhood leukemias, making it the most common childhood cancer. Although 80 to 90% of children will have a long term complete response with treatment,: 1527 it remains the leading cause of cancer-related deaths among children. 85% of cases are of B-cell lineage and have an equal number of cases in both males and females. The remaining 15% of T-cell lineage have a male predominance.
Globally, ALL typically occurs more often in Caucasians, Hispanics, and Latin Americans than in Africans.: 1617 In the US, ALL is more common in children from Caucasian (36 cases/million) and Hispanic (41 cases/million) descent when compared to those from African (15 cases/million) descent.
Pregnancy
Leukemia is rarely associated with pregnancy, affecting only about 1 in 10,000 pregnant women. The management of leukemia in a pregnant woman depends primarily on the type of leukemia. Acute leukemias normally require prompt, aggressive treatment, despite significant risks of pregnancy loss and birth defects, especially if chemotherapy is given during the developmentally sensitive first trimester.
References
External links
Acute Lymphocytic Leukemia Archived 16 November 2009 at the Wayback Machine at the American Cancer Society
Childhood ALL Treatment at the National Cancer Institute |
Bed bug | Bed bugs are insects from the genus Cimex that feed on blood, usually at night. Their bites can result in a number of health impacts including skin rashes, psychological effects, and allergic symptoms. Bed bug bites may lead to skin changes ranging from small areas of redness to prominent blisters. Symptoms may take between minutes to days to appear and itchiness is generally present. Some individuals may feel tired or have a fever. Typically, uncovered areas of the body are affected. Their bites are not known to transmit any infectious disease. Complications may rarely include areas of dead skin or vasculitis.Bed bug bites are caused primarily by two species of insects: Cimex lectularius (the common bed bug) and Cimex hemipterus, found primarily in the tropics. Their size ranges between 1 and 7 mm. They spread by crawling between nearby locations or by being carried within personal items. Infestation is rarely due to a lack of hygiene but is more common in high-density areas. Diagnosis involves both finding the bugs and the occurrence of compatible symptoms. Bed bugs spend much of their time in dark, hidden locations like mattress seams, or cracks in a wall.Treatment is directed towards the symptoms. Eliminating bed bugs from the home is often difficult, partly because bed bugs can survive up to 70 days without feeding. Repeated treatments of a home may be required. These treatments may include heating the room to 50 °C (122 °F) for more than 90 minutes, frequent vacuuming, washing clothing at high temperatures, and the use of various pesticides.Bed bugs occur in all regions of the globe. Infestations are relatively common, following an increase since the 1990s. The exact causes of this increase are unclear; theories including increased human travel, more frequent exchange of second-hand furnishings, a greater focus on control of other pests, and increasing resistance to pesticides. Bed bugs have been known human parasites for thousands of years.
Signs and symptoms
Skin
The most common skin findings associated with bed bugs are pruritic, maculopapular, erythematous lesions. Each lesion is about 2–5 mm but may be as large as 2 cm in diameter and there may or may not be the presence of a central punctum. Bites are usually present on areas of exposed skin, especially exposed areas not covered by sheets or blankets, such as arms, legs, feet, face or neck. Individual responses to bites vary, ranging from no visible effect (in about 20–70%), to small flat (macular) spots, to the formation of prominent blisters (wheals and bullae) along with intense itching that may last several days. Vesicles and nodules may also form. The lesions due to bites may become secondarily infected due to scratching but systemic effects from bed bug bites are very rare. A central spot of bleeding may also occur due to the release of blood thinning substances in the bugs saliva.Symptoms may not appear until some days after the bites have occurred. Reactions often become brisker after multiple bites due to possible sensitization to the salivary proteins of the bed bug. Numerous bites may lead to a red rash or hives.
Psychological
Serious infestations and chronic attacks can cause anxiety, stress, and sleep difficulties. Development of refractory delusional parasitosis is possible, as a person develops an overwhelming obsession with bed bugs.
Other
A number of other symptoms may occur from either the bite of the bed bugs or from their exposure. Serious allergic reactions including anaphylaxis from the injection of serum and other nonspecific proteins have been rarely documented. Due to each bite taking a tiny amount of blood, the chronic or severe infestation may lead to anemia. Bacterial skin infection may occur due to skin breakdown from scratching.
Systemic poisoning may occur if the bites are numerous. Exposure to bed bugs may trigger an asthma attack via the effects of airborne allergens although evidence of this association is limited. There is no evidence that bed bugs transmit infectious diseases even though they appear physically capable of carrying pathogens and this possibility has been investigated. The bite itself may be painful thus resulting in poor sleep and worse work performance.Bed bugs can feed on warm-blooded animals other than humans, such as pets. The signs left by the bites are the same as in the case of people and cause identical symptoms (skin irritation, scratching etc.). Bed bugs can infest poultry sheds and cause anemia and a decrease in egg production in hens.
Insect
Bed bug infestations are primarily the result of two species of insects from genus Cimex: Cimex lectularius (the common bed bug) and Cimex hemipterus (the tropical bed bug). These insects feed exclusively on blood and, at any stage of development, may survive up to 70 days without feeding. Adult Cimex are light brown to reddish-brown, flat, oval, and have no hind wings. The front wings are vestigial and reduced to pad-like structures. Adults grow to 4–5 mm (0.16–0.20 in) long and 1.5–3 mm (0.059–0.118 in) wide. Female common bed bugs can lay 1–10 eggs per day and 200–500 eggs in their lifetime, whereas female tropical bed bugs can lay about 50 eggs in their lifetime .Bed bugs have five immature nymph life stages and a final sexually mature adult stage. Bed bugs need at least one blood meal in order to advance to the next stage of development. They shed their skins through ecdysis at each stage, discarding their outer exoskeleton. Newly hatched nymphs are translucent, lighter in color, and become browner as they moult and reach maturity. Bed bugs may be mistaken for other insects, such as booklice, small cockroaches, or carpet beetles; however, when warm and active, their movements are more ant-like, and like most other true bugs, they emit a characteristic disagreeable odor when crushed.
Bed bugs are obligatory bloodsuckers. They have mouth parts that saw through the skin and inject saliva with anticoagulants and painkillers. Sensitivity of humans varies from extreme allergic reaction to no reaction at all (about 20%). The bite usually produces a swelling with no red spot, but when many bugs feed on a small area, reddish spots may appear after the swelling subsides. Bedbugs prefer exposed skin, preferably the face, neck, and arms of a sleeping person.
Bed bugs are attracted to their hosts primarily by carbon dioxide, secondarily by warmth, and also by certain chemicals. There is strong evidence that bed bugs can respond and orient towards human odors, independently of all other host cues. Cimex lectularius feeds only every five to seven days, which suggests that it does not spend the majority of its life searching for a host. When a bed bug is starved, it leaves its shelter and searches for a host. It returns to its shelter after successful feeding or if it encounters exposure to light. Cimex lectularius aggregate under all life stages and mating conditions. Bed bugs may choose to aggregate because of predation, resistance to desiccation, and more opportunities to find a mate. Airborne pheromones are responsible for aggregations.
Spread
Infestation is rarely caused by a lack of hygiene. Transfer to new places is usually in the personal items of the human they feed upon. Dwellings can become infested with bed bugs in a variety of ways, such as:
Bugs and eggs inadvertently brought in from other infested dwellings on a visiting persons clothing or luggage;
Infested items (such as furniture especially beds or couches, clothing, or backpacks) brought into a home or business;
Proximity of infested dwellings or items, if easy routes are available for travel, e.g. through ducts or false ceilings;
Wild animals (such as bats or birds) that may also harbour bed bugs or related species such as the bat bug;
People visiting an infested area (e.g. dwelling, means of transport, entertainment venue, or lodging) and carrying the bugs to another area on their clothing, luggage, or bodies. Bedbugs are increasingly found in air travel.Though bed bugs will opportunistically feed on pets, they do not live or travel on the skin of their hosts, and pets are not believed to be a factor in their spread.
Diagnosis
A definitive diagnosis of health effects due to bed bugs requires a search for and finding of the insect in the sleeping environment as symptoms are not sufficiently specific. It is difficult to distinguish bed bug bites from other arthropod bites and the linear pattern of bites (known colloquially as "breakfast, lunch and dinner" bites) is not specific for bed bugs. If the number in a house is large a pungent sweet odour may be described. There are specially trained dogs that can detect this smell.
Detection
Bed bugs can exist singly but tend to congregate once established. Although strictly parasitic, they spend only a tiny fraction of their lives physically attached to hosts. Once a bed bug finishes feeding, it follows a chemical trail to return to a nearby harborage, commonly in or near beds or couches, where they live in clusters of adults, juveniles, and eggs. These places may include luggage, vehicles interiors, furniture, bedside clutter—even inside electrical sockets or laptop computers. Bed bugs may also lodge near animals that have nested within a dwelling, such as bats, birds, or rodents. They are also capable of surviving on domestic cats and dogs, though humans are the preferred host of C. lectularius.
Bed bugs can also be detected by their characteristic smell of rotting raspberries. Bed bug detection dogs are trained to pinpoint infestations, with a possible accuracy rate between 11% and 83%.Homemade detectors have been developed. Bedbug detectors, often referred to as "monitors" or "traps", use attractant based methods such as lactic acid or carbon dioxide (associated with the presence of a human body) or pheromones to trap bugs in a container. Bedbug detectors can confirm a bedbug infestation but they are not effective for eradication.
Differential diagnosis
Other possible conditions with which these conditions can be confused include scabies, gamasoidosis, allergic reactions, mosquito bites, spider bites, chicken pox and bacterial skin infections.
Prevention
To prevent bringing home bed bugs, travelers are advised to take precautions after visiting an infested site: generally, these include checking shoes on leaving the site, changing clothes outside the house before entering, and putting the used clothes in a clothes dryer outside the house. When visiting a new lodging, it is advised to check the bed before taking suitcases into the sleeping area, and putting the suitcase on a raised stand to make bedbugs less likely to crawl in. An extreme measure would be putting the suitcase in the tub. Clothes should be hung up or left in the suitcase, and never left on the floor. Additional preventative measures include sealing cracks and crevices (which are often the sites of bed bug harborages), inspecting furniture, and for exposed travelers to decontaminate clothes and luggage upon returning home. The founder of a company dedicated to bedbug extermination said that 5% of hotel rooms he books into were infested. He advised people never to sit down on public transport; check office chairs, plane seats, and hotel mattresses; and monitor and vacuum home beds once a month. Close all wall openings or gaps; bed bugs tend to hide in dark places and cracked walls are a perfect spot for them to infest.
Management
Treatment of bed bug bites requires keeping the person from being repeatedly bitten, and possible symptomatic use of antihistamines and corticosteroids (either topically or systemically). There however is no evidence that medications improve outcomes, and symptoms usually resolve without treatment in 1–2 weeks.Avoiding repeated bites can be difficult since it usually requires eradicating bed bugs from a home or workplace; eradication is most effective using non-chemical control methods. Non-chemical control methods include vacuuming carpet and furniture (often with scraping) into a disposable bag which is then sealed into a plastic bag to prevent re-infestation. Other methods include removing textile materials from an area and washing them in hot water (at least 60 degrees Celsius) or freezing them at −20 °C (−4 °F). Most consumer grade freezers are inadequate to kill bedbugs due to not having low enough temperatures. Unremovable textiles such as mattresses can be steamed at least 60 °C (140 °F) and this method can penetrate deep into the textile to effectively kill bed bugs quickly (under 1 minute). Heating tents or chambers can be used for infested materials or entire rooms can be heated to at least 55 °C (131 °F) to effectively eradicate infestation.There is no evidence to indicate that a combination of non-chemical methods plus insecticides is more effective than non-chemical methods alone with regards to eradication of bed bug infestations.Insecticides are mostly ineffective for the eradication of bedbug infestations as most bedbugs are resistant to insecticides, including pyrethroids which are found in approximately 90% of commercial grade insecticides. Furthermore, insect foggers (known as "bug bombs") are ineffective in the eradication of bed bug infestation as they are unable to penetrate bed bug harborages. Resistance to pesticides has increased significantly over time, and there are concerns about harm to health from their use.Once established, bed bugs are extremely difficult to get rid of. Bed bugs are particularly difficult to eradicate in apartment complexes as harbors can exist in other areas of the building when single units are treated.Mechanical approaches, such as vacuuming up the insects and heat-treating or wrapping mattresses, are effective. An hour at a temperature of 45 °C (113 °F) or over, or two hours at less than −17 °C (1 °F) kills them. This may include a domestic clothes drier for fabric or a commercial steamer. Bed bugs and their eggs will die on contact when exposed to surface temperatures above 180 °F (82 °C) and a steamer can reach well above 230 °F (110 °C). A study found 100% mortality rates for bed bugs exposed to temperatures greater than 50 °C (122 °F) for more than 2 minutes. The study recommended maintaining temperatures of above 48 °C (118 °F) for more than 20 min to effectively kill all life stages of bed bugs, and because in practice treatment times of 6 to 8 hours are used to account for cracks and indoor clutter. This method is expensive and has caused fires. Starving bedbugs is not effective, as they can survive without eating for 100 to 300 days, depending on temperature.It was stated in 2012 that no truly effective insecticides were available. Insecticides that have historically been found effective include pyrethroids, dichlorvos, and malathion. Resistance to pesticides has increased significantly in recent decades. The carbamate insecticide propoxur is highly toxic to bed bugs, but it has potential toxicity to children exposed to it, and the US Environmental Protection Agency has been reluctant to approve it for indoor use. Boric acid, occasionally applied as a safe indoor insecticide, is not effective against bed bugs because they do not groom.
Epidemiology
Bed bugs occur around the world. Before the 1950s about 30% of houses in the United States had bedbugs. This percentage has since fallen, which is believed to be partly due to the use of DDT to kill cockroaches. The invention of the vacuum cleaner and simplification of furniture design may have also played a role in the decrease. Others believe it might simply be the cyclical nature of the organism.However, rates of infestation in developed countries have increased dramatically since the 1980s. This is thought to be due to greater foreign travel, increased immigration from the developing world to the developed world, more frequent exchange of second-hand furnishings among homes, a greater focus on control of other pests, resulting in neglect of bed bug countermeasures, and increasing bedbug resistance to pesticides. Lower cockroach populations due to insecticide use may have aided bed bugs resurgence, since cockroaches are known to sometimes predate them. Steadily-rising resistance to DDT and other potent pesticides may have also contributed; bans on DDT may have contributed as well, though studies have shown resistance continued to rise in countries where they continued to be used.The U.S. National Pest Management Association reported a 71% increase in bed bug calls between 2000 and 2005. The number of reported incidents in New York City alone rose from 500 in 2004 to 10,000 in 2009. In 2013, Chicago was listed as the number one city in the United States for bedbug infestations. As a result, the Chicago City Council passed a bed bug control ordinance to limit their spread. Additionally, bed bugs are reaching places in which they never established before, such as southern South America.The rise in infestations has been hard to track because bed bugs are not an easily identifiable problem and is one that people prefer not to discuss. Most of the reports are collected from pest-control companies, local authorities, and hotel chains. Therefore, the problem may be more severe than is currently believed.
Species
The common bed bug (Cimex lectularius) is the species best adapted to human environments but is also known from birds, Chiroptera, Gallus (chickens and relatives), Myotis myotis, and sheep (Ovis aries). It is found in temperate climates throughout the world. Other species include C. hemipterus, found in tropical regions, which also infests poultry (including Gallus) and bats, and Leptocimex boueti, a relative of C. lectularius adapted for the tropics of West Africa and South America, which infests bats and humans. C. pilosellus and C. pipistrella primarily infest bats, while Haematosiphon inodora, a species of North America, primarily infests poultry.
Evolution
Cimicidae, the ancestor of modern bed bugs, first emerged approximately 115 million years ago, more than 30 million years before bats—their previously presumed initial host—first appeared. From unknown ancestral hosts, a variety of different lineages evolved which specialized in either bats or birds. The common (C. lectularius) and tropical bed bug (C. hemipterus), split 40 million years before Homo evolution. Humans became hosts to bed bugs through host specialist extension (rather than switching) on three separate occasions.
History
Bed bugs were first mentioned in ancient Greece as early as 400 BC, and later by Aristotle. Plinys Natural History, first published circa AD 77 in Rome, claimed bed bugs had medicinal value in treating ailments such as snake bites and ear infections. Belief in the medicinal use of bed bugs persisted until at least the 18th century, when Guettard recommended their use in the treatment of hysteria.Bed bugs were also mentioned in Germany in the 11th century, in France in the 13th century, and in England in 1583, though they remained rare in England until 1670. Some in the 18th century believed bed bugs had been brought to London with supplies of wood to rebuild the city after the Great Fire of London (1666). Giovanni Antonio Scopoli noted their presence in Carniola (roughly equivalent to present-day Slovenia) in the 18th century.Traditional methods of repelling and/or killing bed bugs include the use of plants, fungi, and insects (or their extracts), such as black pepper; black cohosh (Actaea racemosa); Pseudarthria hookeri; Laggera alata (Chinese yángmáo cǎo | 羊毛草); Eucalyptus saligna oil; henna (Lawsonia inermis or camphire); "infused oil of Melolontha vulgaris" (presumably cockchafer); fly agaric (Amanita muscaria); tobacco; "heated oil of Terebinthina" (i.e. true turpentine); wild mint (Mentha arvensis); narrow-leaved pepperwort (Lepidium ruderale); Myrica spp. (e.g. bayberry); Robert geranium (Geranium robertianum); bugbane (Cimicifuga spp.); "herb and seeds of Cannabis"; "opulus" berries (possibly maple or European cranberrybush); masked hunter bugs (Reduvius personatus), "and many others".In the mid-19th century, smoke from peat fires was recommended as an indoor domestic fumigant against bed bugs.Dusts have been used to ward off insects from grain storage for centuries, including plant ash, lime, dolomite, certain types of soil, and diatomaceous earth or Kieselguhr. Of these, diatomaceous earth in particular has seen a revival as a nontoxic (when in amorphous form) residual pesticide for bed bug abatement. While diatomaceous earth often performs poorly, silica gel may be effective.Basket-work panels were put around beds and shaken out in the morning in the UK and in France in the 19th century. Scattering leaves of plants with microscopic hooked hairs around a bed at night, then sweeping them up in the morning and burning them, was a technique reportedly used in Southern Rhodesia and in the Balkans.Bean leaves have been used historically to trap bedbugs in houses in Eastern Europe. The trichomes on the bean leaves capture the insects by impaling the feet (tarsi) of the insects. The leaves are then destroyed.
20th century
Before the mid-20th century, bed bugs were very common. According to a report by the UK Ministry of Health, in 1933, all the houses in many areas had some degree of bed bug infestation. The increase in bed bug populations in the early 20th century has been attributed to the advent of electric heating, which allowed bed bugs to thrive year-round instead of only in warm weather.Bed bugs were a serious problem at US military bases during World War II. Initially, the problem was solved by fumigation, using Zyklon Discoids that released hydrogen cyanide gas, a rather dangerous procedure. Later, DDT was used to good effect, though bedbugs have since become largely resistant to it.The decline of bed bug populations in the 20th century is often credited to potent pesticides that had not previously been widely available. Other contributing factors that are less frequently mentioned in news reports are increased public awareness and slum clearance programs that combined pesticide use with steam disinfection, relocation of slum dwellers to new housing, and in some cases also follow-up inspections for several months after relocated tenants moved into their new housing.
Society and culture
Legal action
Bed bugs are an increasing cause for litigation. Courts have, in some cases, exacted large punitive damage judgments on some hotels. Many of New York Citys Upper East Side homeowners have been afflicted, but they tend to remain publicly silent in order not to ruin their property values and be seen as suffering a blight typically associated with "lower classes." Local Law 69 in New York City requires owners of buildings with three or more units to provide their tenants and potential tenants with reports of bedbug history in each unit. They must also prominently post these listings and reports in their building.
Idiom
"Good night, sleep tight, dont let the bed bugs bite," is a traditional saying.
Literature
The Bedbug (Russian: Клоп, Klop) is a play by Vladimir Mayakovsky written in 1928–1929
How the Bed Bug Infiltrated Our Bedrooms and Took Over the World was written by Brooke Borel.
Research
Bed bug secretions can inhibit the growth of some bacteria and fungi; antibacterial components from the bed bug could be used against human pathogens, and be a source of pharmacologically active molecules as a resource for the discovery of new drugs.
References
External links
Bed bug on the University of Florida/IFAS Featured Creatures Web site
National Geographic segment on Bed bugs on YouTube
Bed bugs – University of Sydney and Westmead Hospital Department of Medical Entomology
Understanding and Controlling Bed Bugs – National Pesticide Information Center
CISR: Center for Invasive Species Research More information on Bed Bugs, with many photos and video
EPA bedbugs information page
A Code of Practice for the Control of Bed Bugs in Australia, ICPMR & AEPMA, Sydney Australia, September 2011. ISBN 1-74080-135-0."Bed Bug Home Page". Bedbug.org.au. 14 October 2005. Retrieved 11 November 2013. |
DiGeorge syndrome | DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by a microdeletion on the long arm of chromosome 22. While the symptoms can vary, they often include congenital heart problems, specific facial features, frequent infections, developmental delay, learning problems and cleft palate. Associated conditions include kidney problems, schizophrenia, hearing loss and autoimmune disorders such as rheumatoid arthritis or Graves disease.DiGeorge syndrome is typically due to the deletion of 30 to 40 genes in the middle of chromosome 22 at a location known as 22q11.2. About 90% of cases occur due to a new mutation during early development, while 10% are inherited from a persons parents. It is autosomal dominant, meaning that only one affected chromosome is needed for the condition to occur. Diagnosis is suspected based on the symptoms and confirmed by genetic testing.Although there is no cure, treatment can improve symptoms. This often includes a multidisciplinary approach with efforts to improve the function of the potentially many organ systems involved. Long-term outcomes depend on the symptoms present and the severity of the heart and immune system problems. With treatment, life expectancy may be normal.DiGeorge syndrome occurs in about 1 in 4,000 people. The syndrome was first described in 1968 by American physician Angelo DiGeorge. In late 1981, the underlying genetics were determined.
Signs and symptoms
The features of this syndrome vary widely, even among members of the same family, and affect many parts of the body. Characteristic signs and symptoms may include birth defects such as congenital heart disease, defects in the palate, most commonly related to neuromuscular problems with closure (velopharyngeal insufficiency), learning disabilities, mild differences in facial features, and recurrent infections. Infections are common in children due to problems with the immune systems T cell-mediated response that in some patients is due to an absent or hypoplastic thymus. DiGeorge syndrome may be first spotted when an affected newborn has heart defects or convulsions from hypocalcemia due to malfunctioning parathyroid glands and low levels of parathyroid hormone (parathormone).Affected individuals may also have other kinds of birth defects including kidney abnormalities and significant feeding difficulties as babies. Gastrointestinal issues are also very common in this patient population. Digestive motility issues may result in constipation. Disorders such as hypothyroidism and hypoparathyroidism or thrombocytopenia (low platelet levels), and psychiatric illnesses are common late-occurring features.Microdeletions in chromosomal region 22q11.2 are associated with a 20 to 30-fold increased risk of schizophrenia. Studies provide various rates of 22q11.2DS in schizophrenia, ranging from 0.5 to 2.0% and averaging about 1.0%, compared with the overall estimated 0.025% risk of the 22q11.2DS in the general population.Salient features can be summarized using the mnemonic CATCH-22 to describe 22q11.2DS, with the 22 signifying the chromosomal abnormality is found on the 22nd chromosome, as below:
Cardiac abnormality (commonly interrupted aortic arch, truncus arteriosus and tetralogy of Fallot)
Abnormal facies
Thymic aplasia or hypoplasia
Cleft palate
Hypocalcemia/hypoparathyroidism early in lifeIndividuals can have many possible features, ranging in number of associated features and from the mild to the very serious. Symptoms shown to be common include:
This syndrome is characterized by incomplete penetrance. Therefore, there is a marked variability in clinical expression between the different patients. This often makes early diagnosis difficult.
Cognitive impairments
Children with DiGeorge syndrome have a specific profile in neuropsychological tests. They usually have a below-borderline normal IQ, with most individuals having higher scores in the verbal than the nonverbal domains. Some are able to attend main-stream schools, while others are home-schooled or in special classes. The severity of hypocalcemia early in childhood is associated with autism-like behavioral difficulties.Adults with DiGeorge syndrome are a specifically high-risk group for developing schizophrenia. About 30% have at least one episode of psychosis and about a quarter develop schizophrenia by adulthood.Individuals with DiGeorge syndrome also have a higher risk of developing early onset Parkinsons disease (PD). Diagnosis of Parkinsons can be delayed by up to 10 years due to the use of antipsychotics, which can cause parkinsonian symptoms.
Speech and language
Current research demonstrates a unique profile of speech and language impairments is associated with 22q11.2DS. Children often perform lower on speech and language evaluations in comparison to their nonverbal IQ scores. Common problems include hypernasality, language delays, and speech sound errors.Hypernasality occurs when air escapes through the nose during the production of oral speech sounds, resulting in reduced intelligibility. This is a common characteristic in the speech and language profile because 69% of children have palatal abnormalities. If the structure of the soft palate velum is such that it does not stop the flow of air from going up to the nasal cavity, it will cause hypernasal speech. This phenomenon is referred as velopharyngeal inadequacy (VPI). Hearing loss can also contribute to increased hypernasality because children with hearing impairments can have difficulty self monitoring their oral speech output. The treatment options available for VPI include prosthesis and surgery.Difficulties acquiring vocabulary and formulating spoken language (expressive language deficits) at the onset of language development are also part of the speech and language profile associated with the 22q11.2 deletion. Vocabulary acquisition is often severely delayed for preschool-age children. In some recent studies, children had a severely limited vocabulary or were still not verbal at 2–3 years of age. School-age children do make progress with expressive language as they mature, but many continue to have delays and demonstrate difficulty when presented with language tasks such as verbally recalling narratives and producing longer and more complex sentences. Receptive language, which is the ability to comprehend, retain, or process spoken language, can also be impaired, although not usually with the same severity as expressive language impairments.Articulation errors are commonly present in children with DiGeorge syndrome. These errors include a limited phonemic (speech sound) inventory and the use of compensatory articulation strategies resulting in reduced intelligibility. The phonemic inventory typically produced consists of sounds made in the front or back of the oral cavity such as: /p/, /w/, /m/, /n/, and glottal stops. Sound made in the middle of the mouth are completely absent. Compensatory articulation errors made by this population of children include: glottal stops, nasal substitutions, pharyngeal fricatives, linguapalatal sibilants, reduced pressure on consonant sounds, or a combination of these symptoms. Of these errors, glottal stops have the highest frequency of occurrence. It is reasoned that a limited phonemic inventory and the use of compensatory articulation strategies is present due to the structural abnormalities of the palate. The speech impairments exhibited by this population are more severe during the younger ages and show a trend of gradual improvement as the child matures.
Genetics
DiGeorge syndrome is caused by a heterozygous deletion of part of the long arm (q) of chromosome 22, region 1, band 1, sub-band 2 (22q11.2). Approximately 80-90% of patients have a deletion of 3 Mb and 8% have a deletion of 1.5Mb. The number of genes affected by the deletion has been cited as approximately 30 to 50. Very rarely, patients with somewhat similar clinical features may have deletions on the short arm of chromosome 10. The disorder has an autosomal dominant inheritance pattern.
A French study of 749 people diagnosed between 1995 and 2013 found that the mutation was inherited in 15% of patients, of which 85.5% was from the mother. Other studies have found inheritance rates of 6-10%. The majority cases are a result of a de novo (new to the family) deletion. This is because the 22q11 region has a structure that makes it highly prone to rearrangements during sperm or egg formation.The exact mechanism that causes all of the associated features of the syndrome is unknown. Of the 30–50 genes in the deleted region, a number have been identified as possibly playing a role in the development of some of the signs and symptoms.
TBX1
Haploinsufficiency of the TBX1 gene (T-box transcription factor TBX1) is thought to be the cause of some of the symptoms observed. Point mutations in this gene have also been observed in individuals with DiGeorge syndrome. TBX1 is part of the T-box family of genes which have an important role in tissue and organ formation during embryonic development and it may have a role in the regulation of differentiation of post migration neural crest cells. The neural crest forms many of the structures affected in DiGeorge syndrome, including the skull bones, mesenchyme of the face and palate, the outflow tract of the heart, and the thymus and parathyroid stroma. When there is a loss of expression of FGF18 during the development of the pharyngeal arches, neural crest cell death is seen. Although neither FGF18 or TBX1 are expressed in the neural crest cells, TBX1 might have a role in the regulation of FGF18 expression, ensuring that the differentiation of these cells in the pharyngeal region is correct. Therefore, dysfunction of TBX1 may be responsible for some of the symptoms in DiGeorge syndrome.Research in mouse models has shown that deletion of Tbx1 leads to several defects similar to those seen in humans, mainly affecting development of the great arteries and the thymus.The abnormalities seen in the great arteries of mice deficient of Tbx1 are a consequence of abnormal formation and remodelling of the aortic arches during early development. The role of Tbx1 for correct formation and remodelling of the aortic arches has been extensively studied in various mouse models suggesting the key role of Tbx1 for cardiovascular development and the phenotypes seen in DiGeorge syndrome.
DGCR8
In mice, haploinsufficiency of the DGCR8 gene has been linked to improper regulation of the microRNA miR-338 and 22q11.2 deletion phenotypes.
TANGO2
Transport and golgi organization 2 homolog (TANGO2) also known as chromosome 22 open reading frame 25 (C22orf25) is a protein that in humans is encoded by the TANGO2 gene.The gene coding for C22orf25 is located on chromosome 22 and the location q11.21, so it is often associated with 22q11.2 deletion syndrome. But with TANGO2 disorder being autosomal recessive, will not occur in all cases.
Mutations in the TANGO2 gene may cause defects in mitochondrial β-oxidation and increased endoplasmic reticulum stress and a reduction in Golgi volume density. These mutations results in early onset hypoglycemia, hyperammonemia, rhabdomyolysis, cardiac arrhythmias, and encephalopathy that later develops into cognitive impairment.
Parkinsons disease genes
22q11.2DS has been associated with a higher risk of early onset Parkinsons disease (PD). The neuropathology seen is similar to LRRK2-associated PD. None of the genes affected in individuals with 22q11.2DS have previously been linked to PD but there are a number that are likely candidates. These include DGCR8 which is important for biogenesis of brain microDNA, SRPT5 which encodes a protein that interacts with the PARK2 protein, COMT which is involved in regulating dopamine levels, and microRNA miR-185 which is thought to target known PD loci LRRK2.
Diagnosis
Diagnosis of DiGeorge syndrome can be difficult due to the number of potential symptoms and the variation in phenotypes between individuals. It is suspected in patients with one or more signs of the deletion. In these cases a diagnosis of 22q11.2DS is confirmed by observation of a deletion of part of the long arm (q) of chromosome 22, region 1, band 1, sub-band 2. Genetic analysis is normally performed using fluorescence in situ hybridization (FISH), which is able to detect microdeletions that standard karyotyping (e.g. G-banding) miss. Newer methods of analysis include multiplex ligation-dependent probe amplification assay (MLPA) and quantitative polymerase chain reaction (qPCR), both of which can detect atypical deletions in 22q11.2 that are not detected by FISH. qPCR analysis is also quicker than FISH, which can have a turn around of 3 to 14 days.A 2008 study of a new high-definition MLPA probe developed to detect copy number variation at 37 points on chromosome 22q found it to be as reliable as FISH in detecting normal 22q11.2 deletions. It was also able to detect smaller atypical deletions that are easily missed using FISH. These factors, along with the lower expense and easier testing mean that this MLPA probe could replace FISH in clinical testing.Genetic testing using BACs-on-Beads has been successful in detecting deletions consistent with 22q11.2DS during prenatal testing. Array-comparative genomic hybridization (array-CGH) uses a large number of probes embossed in a chip to screen the entire genome for deletions or duplications. It can be used in post and pre-natal diagnosis of 22q11.2.Fewer than 5% of individuals with symptoms of DiGeorge syndrome have normal routine cytogenetic studies and negative FISH testing. In these cases, atypical deletions are the cause. Some cases of 22q11.2 deletion syndrome have defects in other chromosomes, notably a deletion in chromosome region 10p14.
Treatment
No cure is known for DiGeorge syndrome. Certain individual features are treatable using standard treatments. The key is to identify each of the associated features and manage each using the best available treatments.For example, in children, it is important that the immune problems are identified early, as special precautions are required regarding blood transfusion and immunization with live vaccines. Thymus transplantation can be used to address absence of the thymus in the rare, so-called "complete" DiGeorge syndrome. Bacterial infections are treated with antibiotics. Cardiac surgery is often required for congenital heart abnormalities. Hypoparathyroidism causing hypocalcaemia often requires lifelong vitamin D and calcium supplements. Specialty clinics that provide multi-system care allow for individuals with DiGeorge syndrome to be evaluated for all of their health needs and allow for careful monitoring of the patients. An example of this type of system is the 22q Deletion Clinic at SickKids Hospital in Toronto, Canada, which provides children with 22q11 deletion syndrome ongoing support, medical care and information from a team of health care workers.Metirosine (methyltyrosine) is used as an off-label treatment for DiGeorge syndrome.
Epidemiology
DiGeorge syndrome is estimated to affect between one in 2000 and one in 4000 live births. This estimate is based on major birth defects and may be an underestimate, because some individuals with the deletion have few symptoms and may not have been formally diagnosed. It is one of the most common causes of intellectual disability due to a genetic deletion syndrome.The number of people affected has been expected to rise because of multiple reasons: (1) surgical and medical advances, an increasing number of people are surviving heart defects associated with the syndrome. These individuals are in turn having children. The chances of a person with DiGeorge syndrome having an affected child is 50% for each pregnancy; (2) Parents who have affected children, but who were unaware of their own genetic conditions, are now being diagnosed as genetic testing become available; (3) Molecular genetics techniques such as FISH (fluorescence in situ hybridization) have limitations and have not been able to detect all 22q11.2 deletions. Newer technologies have been able to detect these atypical deletions.
Etymology
The signs and symptoms of DiGeorge syndrome are so varied that different groupings of its features were once regarded as separate conditions. These original classifications included velocardiofacial syndrome, Shprintzen syndrome, DiGeorge sequence/syndrome, Sedlackova syndrome, and conotruncal anomaly face syndrome. All are now understood to be presentations of a single syndrome.
ICD-10 2015 version mentions DiGeorge syndrome using two codes: D82.1 (Di George syndrome) and Q93.81 (Velo-cardio-facial syndrome). The ICD-11 Beta Draft discusses the syndrome under “LD50.P1 CATCH 22 phenotype". However, since this syndrome is caused by the deletion of a small piece of chromosome 22, some recommend that the name "22q11.2 deletion syndrome (22q11.2DS)" be used. Some experts support changing the name of both DiGeorge and velocardiofacial syndromes to CATCH-22. The International 22q11.2 Foundation, through its "Same Name Campaign", advocates for the name 22q11.2 deletion syndrome.
See also
References
This article incorporates public domain text from The U.S. National Library of Medicine
External links
DiGeorge syndrome at Curlie
McDonald-McGinn DM, Emanuel BS, Zackai EH (December 16, 2005). "22q11.2 Deletion Syndrome". In Pagon RA, Bird TD, Dolan CR, Stephens K (eds.). GeneReviews. University of Washington, Seattle. PMID 20301696. NBK1523.
Firth HV (February 17, 2009). "22q11.2 Duplication". In Pagon RA, Bird TD, Dolan CR, Stephens K (eds.). GeneReviews. University of Washington, Seattle. PMID 20301749. NBK3823. |
Patellofemoral pain syndrome | Patellofemoral pain syndrome (PFPS; not to be confused with jumpers knee) is knee pain as a result of problems between the kneecap and the femur. The pain is generally in the front of the knee and comes on gradually. Pain may worsen with sitting, excessive use, or climbing and descending stairs.While the exact cause is unclear, it is believed to be due to overuse. Risk factors include trauma, increased training, and a weak quadriceps muscle. It is particularly common among runners. The diagnosis is generally based on the symptoms and examination. If pushing the kneecap into the femur increases the pain, the diagnosis is more likely.Treatment typically involves rest and rehabilitation with a Physical Therapist. Runners may need to switch to activities such as cycling or swimming. Insoles may help some people. Symptoms may last for years despite treatment. Patellofemoral pain syndrome is the most common cause of knee pain, affecting more than 20% of young adults. It occurs about 2.5 times more often in females than males.
Signs and symptoms
The onset of the condition is usually gradual, although some cases may appear suddenly following trauma. The most common symptom is diffuse vague pain around the kneecap (peripatellar) and localized pain focused behind the kneecap (retropatellar). Affected individuals typically have difficulty describing the location of the pain. They may place their hands over the anterior patella or describe a circle around the patella. This is often called the "circle sign". Pain is usually initiated when weight is put on the knee extensor mechanism, such as when ascending or descending stairs or slopes, squatting, kneeling, cycling, or running. Pain during prolonged sitting is sometimes termed the "movie sign" or "theatre sign" because individuals might experience pain while sitting to watch a film or similar activity. The pain is typically aching and occasionally sharp. Pain may be exacerbated by activities. The knee joint may exhibit noises such as clicking. However, this has no relation to pain and function. Giving-way of the knee may be reported. Reduced knee flexion may be experienced during activities.
Causes
In most patients with PFPS an examination of their history will highlight a precipitating event that caused the injury. Changes in activity patterns such as excessive increases in running mileage, repetitions such as running up steps and the addition of strength exercises that affect the patellofemoral joint are commonly associated with symptom onset. Excessively worn or poorly fitted footwear may be a contributing factor. To prevent recurrence the causal behaviour should be identified and managed correctly.The medical cause of PFPS is thought to be increased pressure on the patellofemoral joint. There are several theorized mechanisms relating to how this increased pressure occurs:
Increased levels of physical activity
Malalignment of the patella as it moves through the femoral groove
Quadriceps muscle imbalance
Tight anatomical structures, e.g. retinaculum or iliotibial band.Causes can also be a result of excessive genu valgum and the above-mentioned repetitive motions leading to abnormal lateral patellar tracking. Individuals with genu valgum have larger than normal Q-angles causing the weight-bearing line to fall lateral to the centre of the knee causing overstretching of the MCL and stressing the lateral meniscus and cartilages.The cause of pain and dysfunction often results from either abnormal forces (e.g. increased pull of the lateral quadriceps retinaculum with acute or chronic lateral PF subluxation/dislocation) or prolonged repetitive compressive or shearing forces (running or jumping) on the PF joint. The result is synovial irritation and inflammation and subchondral bony changes in the distal femur or patella known as "bone bruises". Secondary causes of PF Syndrome are fractures, internal knee derangement, osteoarthritis of the knee and bony tumors in or around the knee.
Diagnosis
Examination
People can be observed standing and walking to determine patellar alignment. The Q-angle, lateral hypermobility, and J-sign are commonly used determined to determine patellar maltracking. The patellofemoral glide, tilt, and grind tests (Clarkes sign), when performed, can provide strong evidence for PFPS. Lastly, lateral instability can be assessed via the patellar apprehension test, which is deemed positive when there is pain or discomfort associated with lateral translation of the patella. Various clinical tests have been investigated for diagnostic accuracy. The Active Instability Test, knee pain during stair climbing, Clarkes test, pain with prolonged sitting, patellar inferior pole tilt, and pain during squatting have demonstrated the best accuracy. However, careful consideration is still needed when using these tests to make a differential diagnosis of PFPS.
Individuals with PFP may be exhibit higher pain level and lower function.Magnetic resonance imaging rarely can give useful information for managing patellofemoral pain syndrome and treatment should focus on an appropriate rehabilitation program including correcting strength and flexibility concerns. In the uncommon cases where a patient has mechanical symptoms like a locked knee, knee effusion, or failure to improve following physical therapy, then an MRI may give more insight into diagnosis and treatment.
Classification
PFPS is one of a handful of conditions sometimes referred to as runners knee; the other conditions being chondromalacia patellae, iliotibial band syndrome, and plica syndrome.
Chondromalacia patellae is a term sometimes used synonymously with PFPS. However, there is general consensus that PFPS applies only to individuals without cartilage damage, thereby distinguishing it from chondromalacia patellae, a condition with softening of the patellar articular cartilage. Despite this distinction, the diagnosis of PFPS is typically made based only on the history and physical examination rather than on the results of any medical imaging. Therefore, it is unknown whether most persons with a diagnosis of PFPS have cartilage damage or not, making the difference between PFPS and chondromalacia theoretical rather than practical. It is thought that only some individuals with anterior knee pain will have true chondromalacia patellae.
Differential diagnosis
The diagnosis of patellofemoral pain syndrome is made by ruling out patellar tendinitis, prepatellar bursitis, plica syndrome, Sinding-Larsen and Johansson syndrome, and Osgood–Schlatter disease. Currently, there is not a gold standard assessment to diagnose PFPS.
Treatment
A variety of treatments for patellofemoral pain syndrome are available. Most people respond well to conservative therapy.
Exercises
Patellofemoral pain syndrome may also result from overuse or overload of the PF joint. For this reason, knee activity should be reduced until the pain is resolved.There is consistent but low quality evidence that exercise therapy for PFPS reduces pain, improves function and aids long-term recovery. However, there is insufficient evidence to compare the effectiveness of different types of exercises with each other, and exercises with other forms of treatment.Exercise therapy is the recommended first line treatment of PFPS. Various exercises have been studied and recommended. Exercises are described according to 3 parameters:
Type of muscle activity (concentric, eccentric or isometric)
Type of joint movement (dynamic, isometric or static)
Reaction forces (closed or open kinetic chain)The majority of exercise programs intended to treat PFPS are designed to strengthen the quadriceps muscles. Quadriceps strengthening is considered to be the "gold" standard treatment for PFPS. Quadriceps strengthening is commonly suggested because the quadriceps muscles help to stabilize the patella. Quadriceps weakness and muscle imbalance may contribute to abnormal patellar tracking.If the strength of the vastus medialis muscle is inadequate, the usually larger and stronger vastus lateralis muscle will pull sideways (laterally) on the kneecap. Strengthening the vastus medialis to prevent or counter the lateral force of the vastus lateralis is one way of relieving PFPS. However, there is growing evidence that shows proximal factors play a much larger role than vastus medialis (VMO) strength deficits or quadriceps imbalance. Hip abductor, extensor, and external rotator strengthening may help.Emphasis during exercise may be placed on coordinated contraction of the medial and lateral parts of the quadriceps as well as of the hip adductor, hip abductor and gluteal muscles. Many exercise programs include stretches designed to improve lower limb flexibility. Electromyographic biofeedback allows visualization of specific muscle contractions and may help individuals performing the exercises to target the intended muscles during the exercise. Neuromuscular electrical stimulation to strengthen quadracep muscles is sometimes suggested, however the effectiveness of this treatment is not certain.Inflexibility has often been cited as a source of patellofemoral pain syndrome. Stretching of the lateral knee has been suggested to help.Knee and lumbar joint mobilization are not recommended as primary interventions for PFPS. It can be used as combination intervention, but as we continue to promote use of active and physical interventions for PFPS, passive interventions such as joint mobilizations are not recommended.
Manual Therapy
Manual therapy in addition to exercises helps in reducing pain, improving function, and knee range of motion in patients with PFPS. Manual therapy such as patellar joint mobilization, manipulation and soft tissue mobilization along with Physical therapy exercises is found to be effective in treating PFPS. However, there is no enough evidence that supports lumbopelvic spine manipulation has any effect on the quadriceps muscle activation to improve function & reduce pain.
Medication
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat PFPS; however, there is only very limited evidence that they are effective. NSAIDs may reduce pain in the short term; overall, however, after three months pain is not improved. There is no evidence that one type of NSAID is superior to another in PFPS, and therefore some authors have recommended that the NSAID with fewest side effects and which is cheapest should be used.Glycosaminoglycan polysulfate (GAGPS) inhibits proteolytic enzymes and increases synthesis and degree of polymerization of hyaluronic acid in synovial fluid. There is contradictory evidence that it is effective in PFPS.
Braces and taping
There is no difference in pain symptoms between taping and non-taping in individuals with PFPS. Although taping alone is not shown to reduce pain, studies show that taping in conjunction with therapeutic exercise can have a significant effect on pain reduction.Knee braces are ineffective in treating PFPS. The technique of McConnell taping involves pulling the patella medially with tape (medial glide). Findings from some studies suggest that there is limited benefit with patella taping or bracing when compared to quadriceps exercises alone. There is a lack of evidence to show that knee braces, sleeves, or straps are effective.
Insoles
Low arches can cause overpronation or the feet to roll inward too much increasing load on the patellofemoral joint. Poor lower extremity biomechanics may cause stress on the knees and can be related to the development of patellofemoral pain syndrome, although the exact mechanism linking joint loading to the development of the condition is not clear. Foot orthoses can help to improve lower extremity biomechanics and may be used as a component of overall treatment. Foot orthoses may be useful for reducing knee pain in the short term, and may be combined with exercise programs or physical therapy. However, there is no evidence supporting use of combined exercise with foot orthoses as intervention beyond 12 months for adults. Evidence for long term use of foot orthoses for adolescents is uncertain. No evidence supports use of custom made foot orthoses.
Surgery
The scientific consensus is that surgery should be avoided except in very severe cases in which conservative treatments fail. The majority of individuals with PFPS receive nonsurgical treatment.
Alternative medicine
The use of electrophysical agents and therapeutic modalities are not recommended as passive treatments should not be the focus of the plan of care. There is no evidence to support the use of acupuncture or low-level laser therapy. Most studies claiming benefits of alternative therapies for PFPS were conducted with flawed experimental design, and therefore did not produce reliable results.
Prognosis
Patellarfemoral pain syndrome can become a chronic injury, with an estimated 50% of people reporting persistent patellar-femoral pain after a year. Risk factors for a prolonged recovery (or persistent condition) include age (older athletes), females, increased body weight, a reduction in muscle strength, time to seek care, and in those who experience symptoms for more than two months.
Epidemiology
Patellofemoral pain syndrome is the most common cause of anterior knee pain in the outpatient. Specific populations at high risk of primary PFPS include runners, bicyclists, basketball players, young athletes and females.BMI did not significantly increase risk of developing PFPS in adolescents. However, adults with PFPS have higher BMI than those without. It is suggested that higher BMI is associated with limited physical activity in people with PFPS as physical activity levels decrease as a result of pain associated with the condition. However, no longitudinal studies are able to show that BMI can be a predictor of development or progression of the condition.
References
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Crohns disease | Crohns disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension, and weight loss. Complications outside of the gastrointestinal tract may include anemia, skin rashes, arthritis, inflammation of the eye, and fatigue. The skin rashes may be due to infections as well as pyoderma gangrenosum or erythema nodosum. Bowel obstruction may occur as a complication of chronic inflammation, and those with the disease are at greater risk of colon cancer and small bowel cancer.While the precise causes of Crohns disease (CD) are unknown, it is believed to be caused by a combination of environmental, immune, and bacterial factors in genetically susceptible individuals. It results in a chronic inflammatory disorder, in which the bodys immune system defends the gastrointestinal tract, possibly targeting microbial antigens. While Crohns is an immune-related disease, it does not appear to be an autoimmune disease (in that the immune system is not being triggered by the body itself). The exact underlying immune problem is not clear; however, it may be an immunodeficiency state.About half of the overall risk is related to genetics, with more than 70 genes having been found to be involved. Tobacco smokers are twice as likely to develop Crohns disease as nonsmokers. It also often begins after gastroenteritis. Diagnosis is based on a number of findings, including biopsy and appearance of the bowel wall, medical imaging, and description of the disease. Other conditions that can present similarly include irritable bowel syndrome and Behçets disease.There is no known cure for Crohns disease. Treatment options are intended to help with symptoms, maintain remission, and prevent relapse. In those newly diagnosed, a corticosteroid may be used for a brief period of time to rapidly improve symptoms, alongside another medication such as either methotrexate or a thiopurine used to prevent recurrence. Stopping smoking is recommended in people with Crohns disease. One in five people with the disease is admitted to the hospital each year, and half of those with the disease will require surgery for the disease at some point over a ten-year period. While surgery should be used as little as possible, it is necessary to address some abscesses, certain bowel obstructions, and cancers. Checking for bowel cancer via colonoscopy is recommended every few years, starting eight years after the disease has begun.Crohns disease affects about 3.2 per 1,000 people in Europe, North America, and the UK. It is less common in Asia and Africa. It has historically been more common in the developed world. Rates have, however, been increasing, particularly in the developing world, since the 1970s. Inflammatory bowel disease resulted in 47,400 deaths in 2015, and those with Crohns disease have a slightly reduced life expectancy. It tends to start in young adulthood, though it can occur at any age. Males and females are equally affected.
Name
The disease was named after gastroenterologist Burrill Bernard Crohn, who in 1932, together with two colleagues at Mount Sinai Hospital in New York, described a series of patients with inflammation of the terminal ileum of the small intestine, the area most commonly affected by the illness.
Signs and symptoms
Gastrointestinal
Many people with Crohns disease have symptoms for years before the diagnosis. The usual onset is in the teens and twenties, but can occur at any age. Because of the patchy nature of the gastrointestinal disease and the depth of tissue involvement, initial symptoms can be more subtle than those of ulcerative colitis. People with Crohns disease experience chronic recurring periods of flare-ups and remission. The symptoms experienced can change over time as inflammation increases and spreads. Symptoms can also be different depending on which organs are involved. It is generally thought that the presentation of Crohns disease is different for each patient due to the high variability of symptoms, organ involvement, and initial presentation.
Perianal
Perianal discomfort may also be prominent in Crohns disease. Itchiness or pain around the anus may be suggestive of inflammation of the anus, or perianal complications such as anal fissures, fistulae, or abscesses around the anal area. Perianal skin tags are also common in Crohns disease, and may appear with or without the presence of colorectal polyps. Fecal incontinence may accompany perianal Crohns disease.
Intestines
The intestines, especially the colon and terminal ileum, are the most commonly affected areas of the body. Abdominal pain is a common initial symptom of Crohns disease, especially in the lower right abdomen. Flatulence, bloating, and abdominal distension are additional symptoms and may also add to the intestinal discomfort. Pain is often accompanied by diarrhea, which may or may not be bloody. Inflammation in different areas of the intestinal tract can affect the quality of the feces. Ileitis typically results in large-volume, watery feces, while colitis may result in a smaller volume of feces of higher frequency. Fecal consistency may range from solid to watery. In severe cases, an individual may have more than 20 bowel movements per day, and may need to awaken at night to defecate. Visible bleeding in the feces is less common in Crohns disease than in ulcerative colitis, but is not unusual. Bloody bowel movements are usually intermittent, and may be bright red, dark maroon, or even black in color. The color of bloody stool depends on the location of the bleed. In severe Crohns colitis, bleeding may be copious.
Stomach and Esophagus
The stomach is rarely the sole or predominant site of CD. To date there are only a few documented case reports of adults with isolated gastric CD and no reports in the pediatric population. Isolated stomach involvement is very unusual presentation accounting for less than 0.07% of all gastrointestinal CD. Rarely, the esophagus and stomach may be involved in Crohns disease. These can cause symptoms including difficulty swallowing (dysphagia), upper abdominal pain, and vomiting.
Oropharynx (Mouth)
The mouth may be affected by recurrent sores (aphthous ulcers). Recurrent aphthous ulcers are common; however, it is not clear whether this is due to Crohns disease or simply that they are common in the general population. Other findings may include diffuse or nodular swelling of the mouth, a cobblestone appearance inside the mouth, granulomatous ulcers, or pyostomatitis vegetans. Medications that are commonly prescribed to treat CD, such as anti-inflammatory and sulfa-containing drugs, may cause lichenoid drug reactions in the mouth. Fungal infection such as candidiasis is also common due to the immunosuppression required in the treatment of the disease. Signs of anemia such as pallor and angular cheilitis or glossitis are also common due to nutritional malabsorption.People with Crohns disease are also susceptible to Angular Stomatitis, an inflammation of the corners of the mouth, and Pyostomatitis Vegetans.
Systemic
Like many other chronic, inflammatory diseases, Crohns disease can cause a variety of systemic symptoms. Among children, growth failure is common. Many children are first diagnosed with Crohns disease based on inability to maintain growth. As it may manifest at the time of the growth spurt in puberty, up to 30% of children with Crohns disease may have retardation of growth. Fever may also be present, though fevers greater than 38.5 °C (101.3 °F) are uncommon unless there is a complication such as an abscess. Among older individuals, Crohns disease may manifest as weight loss, usually related to decreased food intake, since individuals with intestinal symptoms from Crohns disease often feel better when they do not eat and might lose their appetite. People with extensive small intestine disease may also have malabsorption of carbohydrates or lipids, which can further exacerbate weight loss.
Extraintestinal
Crohns disease can affect many organ systems beyond the gastrointestinal tract.
Visual
Inflammation of the interior portion of the eye, known as uveitis, can cause blurred vision and eye pain, especially when exposed to light (photophobia). Uveitis can lead to loss of vision if untreated.Inflammation may also involve the white part of the eye (sclera) or the overlying connective tissue (episclera), which causes conditions called scleritis and episcleritis, respectively.Other very rare ophthalmological manifestations include: conjunctivitis, glaucoma, and retinal vascular disease.Gallbladder and Liver
Crohns disease that affects the ileum may result in an increased risk of gallstones. This is due to a decrease in bile acid resorption in the ileum, and the bile gets excreted in the stool. As a result, the cholesterol/bile ratio increases in the gallbladder, resulting in an increased risk for gallstones. Although the association is greater in the context of ulcerative colitis, Crohns disease may also be associated with primary sclerosing cholangitis, a type of inflammation of the bile ducts.Liver involvement of Crohns disease can include cirrhosis and steatosis. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are relatively common and can slowly progress to end-stage liver disease. NAFLD sensitizes the liver to injury and increases the risk of developing acute or chronic liver failure following another liver injury.Other rare hepatobiliary manifestations of Crohns disease include: cholangiocarcinoma, granulomatous hepatitis, cholelithiasis, autoimmune hepatitis, hepatic abscess, and pericholangitis.Renal and Urological
Nephrolithiasis, obstructive uropathy, and fistulization of the urinary tract directly result from the underlying disease process. Nephrolithiasis is due to calcium oxalate or uric acid stones. Calcium oxalate is due to hyperoxaluria typically associated with either distal ileal CD or ileal resection. Oxalate absorption increases in the presence of unabsorbed fatty acids in the colon. The fatty acids compete with oxalate to bind calcium, displacing the oxalate, which can then be absorbed as unbound sodium oxalate across colonocytes and excreted into the urine. Because sodium oxalate only is absorbed in the colon, calcium-oxalate stones form only in patients with an intact colon. Patients with an ileostomy are prone to formation of uric-acid stones because of frequent dehydration. The sudden onset of severe abdominal, back, or flank pain in patients with IBD, particularly if different from the usual discomfort, should lead to inclusion of a renal stone in the differential diagnosis.Urological manifestations in patients with IBD may include ureteral calculi, enterovesical fistula, perivesical infection, perinephric abscess, and obstructive uropathy with hydronephrosis. Ureteral compression is associated with retroperitoneal extension of the phlegmonous inflammatory process involving the terminal ileum and cecum, and may result in hydronephrosis severe enough to cause hypertension.Immune complex glomerulonephritis presenting with proteinuria and hematuria has been described in children and adults with CD or UC. Diagnosis is by renal biopsy, and treatment parallels the underlying IBD.Amyloidosis (see endocrinological involvement) secondary to Crohns disease has been described and is known to affect the kidneys.Pancreatic
Pancreatitis may be associated with both UC and CD. The most common cause is iatrogenic and involves sensitivity to medications used to treat IBD (3% of patients), including sulfasalazine, mesalamine, 6-mercaptopurine, and azathioprine. Pancreatitis may present as symptomatic (in 2%) or more commonly asymptomatic (8–21%) disease in adults with IBD.Cardiovascular and Circulatory
Children and adults with IBD have been rarely (<1%) reported developing pleuropericarditis either at initial presentation or during active or quiescent disease. The pathogenesis of pleuropericarditis is unknown, although certain medications (e.g., sulfasalazine and mesalamine derivatives) have been implicated in some cases. The clinical presentation may include chest pain, dyspnea, or in severe cases pericardial tamponade requiring rapid drainage. Nonsteroidal anti-inflammatory drugs have been used as therapy, although this should be weighed against the hypothetical risk of exacerbating the underlying IBD.In rare cases, cardiomyopathy, endocarditis, and myocarditis have been described.Crohns disease also increases the risk of blood clots; painful swelling of the lower legs can be a sign of deep venous thrombosis, while difficulty breathing may be a result of pulmonary embolism.
Respiratory
Laryngeal involvement in inflammatory bowel disease is extremely rare. Only 12 cases of laryngeal involvement in Crohn disease have been reported until now. Moreover, only one case of laryngeal manifestations in ulcerative colitis has been reported so far. 9 patients complained of difficulty in breathing due to edema and ulceration from the larynx to the hypopharynx Hoarseness, sore throat, and odynophagia are other symptoms of laryngeal involvement of Crohns disease.Considering extraintestinal manifestations of CD, those involving the lung are relatively rare. However, there is a wide array of lung manifestations, ranging from subclinical alterations, airway diseases and lung parenchymal diseases to pleural diseases and drug-related diseases. The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis. There are a number of mechanisms by which the lungs may become involved in CD. These include the same embryological origin of the lung and gastrointestinal tract by ancestral intestine, similar immune systems in the pulmonary and intestinal mucosa, the presence of circulating immune complexes and auto-antibodies, and the adverse pulmonary effects of some drugs. A complete list of known pulmonary manifestations include: Fibrosing alveolitis, Pulmonary vasculitis, Apical fibrosis, Bronchiectasis, Bronchitis, Bronchiolitis, Tracheal stenosis, Granulomatous lung disease, and Abnormal pulmonary function.Musculoskeletal
Crohns disease is associated with a type of rheumatologic disease known as seronegative spondyloarthropathy. This group of diseases is characterized by inflammation of one or more joints (arthritis) or muscle insertions (enthesitis). The arthritis in Crohns disease can be divided into two types. The first type affects larger weight-bearing joints such as the knee (most common), hips, shoulders, wrists, or elbows. The second type symmetrically involves five or more of the small joints of the hands and feet. The arthritis may also involve the spine, leading to ankylosing spondylitis if the entire spine is involved, or simply sacroiliitis if only the sacroiliac joint is involved. The symptoms of arthritis include painful, warm, swollen, stiff joints, and loss of joint mobility or function.Crohns disease increases the risk of osteoporosis or thinning of the bones. Individuals with osteoporosis are at increased risk of bone fractures.
Dermatological
Crohns disease may also involve the skin, blood, and endocrine system. Erythema nodosum is the most common type of skin problem, occurring in around 8% of people with Crohns disease, producing raised, tender red nodules usually appearing on the shins. Erythema nodosum is due to inflammation of the underlying subcutaneous tissue, and is characterized by septal panniculitis.Pyoderma gangrenosum is a less common skin problem, occurring in under 2%, and is typically a painful ulcerating nodule.Clubbing, a deformity of the ends of the fingers, may also be a result of Crohns disease.
Other very rare dermatological manifestations include: Pyostomatitis vegetans, Psoriasis, Erythema multiforme, Epidermolysis bullosa acquista (described in a case report), and Metastatic CD (the spread of Crohns inflammation to the skin). It is unknown if Sweets Syndrome is connected to Crohns disease.Neurological
Crohns disease can also cause neurological complications (reportedly in up to 15%). The most common of these are seizures, stroke, myopathy, peripheral neuropathy, headache, and depression.Central and peripheral neurological disorders are described in patients with IBD and include peripheral neuropathies, myopathies, focal central nervous system defects, convulsions, confusional episodes, meningitis, syncope, optic neuritis, and sensorineural loss. Autoimmune mechanisms are proposed for involvement with IBD. Nutritional deficiencies associated with neurological manifestations, such as vitamin B12 deficiency, should be investigated. Spinal abscess has been reported in both a child and an adult with initial complaints of severe back pain due to extension of a psoas abscess from the epidural space to the subarachnoid space.Psychiatric and psychological
Crohns disease is linked to many psychological disorders, including depression and anxiety, denial of your disease, the need for dependence or dependent behaviors, feeling overwhelmed, and having a poor self-image.Endocrinological or Hematological
Autoimmune hemolytic anemia, a condition in which the immune system attacks the red blood cells, is also more common in Crohns disease and may cause fatigue, a pale appearance, and other symptoms common in anemia.
Secondary amyloidosis (AA) is another rare but serious complication of inflammatory bowel disease (IBD), generally seen in Crohns disease. At least 1% of patients with Crohns disease develop amyloidosis. In the literature, the time lapse between the onset of Crohns disease and the diagnosis of amyloidosis has been reported to range from one to 21 years.
Leukocytosis and thrombocytopenia are usually due to immunosuppressant treatments or sulfasalazine. Plasma erythropoietin levels often are lower in patients with IBD than expected, in conjunction with severe anemia.Thrombocytosis and thromboembolic events resulting from a hypercoagulable state in patients with IBD can lead to pulmonary embolism or thrombosis elsewhere in the body. Thrombosis has been reported in 1.8% of patients with UC and 3.1% of patients with CD. Thromboembolism and thrombosis are less frequently reported among pediatric patients, with 3 patients with UC and 1 with CD described in case reports.In rare cases, hypercoagulation disorders and portal vein thrombosis have been described.Malnutrition Symptoms
People with Crohns disease may develop anemia due to vitamin B12, folate, iron deficiency, or due to anemia of chronic disease. The most common is iron deficiency anemia from chronic blood loss, reduced dietary intake, and persistent inflammation leading to increased hepcidin levels, restricting iron absorption in the duodenum. As Crohns disease most commonly affects the terminal ileum where the vitamin B12/intrinsic factor complex is absorbed, B12 deficiency may be seen. This is particularly common after surgery to remove the ileum. Involvement of the duodenum and jejunum can impair the absorption of many other nutrients including folate. People with Crohns often also have issues with small bowel bacterial overgrowth syndrome, which can produce micronutrient deficiencies.
Complications
Intestinal Damage
Crohns disease can lead to several mechanical complications within the intestines, including obstruction, fistulae, and abscesses. Obstruction typically occurs from strictures or adhesions that narrow the lumen, blocking the passage of the intestinal contents. A fistula can develop between two loops of bowel, between the bowel and bladder, between the bowel and vagina, and between the bowel and skin. Abscesses are walled-off concentrations of infection, which can occur in the abdomen or in the perianal area. Crohns is responsible for 10% of vesicoenteric fistulae, and is the most common cause of ileovesical fistulae.Symptoms caused by intestinal stenosis, or the tightening and narrowing of the bowel, are also common in Crohns disease. Abdominal pain is often most severe in areas of the bowel with stenosis. Persistent vomiting and nausea may indicate stenosis from small bowel obstruction or disease involving the stomach, pylorus, or duodenum.Intestinal granulomas are a walled-off portions of the intestine by macrophages in order to isolate infections. Granuloma formation is more often seen in younger patients, and mainly in the severe, active penetrating disease. Granuloma is considered the hallmark of microscopic diagnosis in Crohns disease (CD), but granulomas can be detected in only 21-60% of CD patients.
Cancer
Crohns disease also increases the risk of cancer in the area of inflammation. For example, individuals with Crohns disease involving the small bowel are at higher risk for small intestinal cancer. Similarly, people with Crohns colitis have a relative risk of 5.6 for developing colon cancer. Screening for colon cancer with colonoscopy is recommended for anyone who has had Crohns colitis for at least eight years.Some studies suggest there is a role for chemoprotection in the prevention of colorectal cancer in Crohns involving the colon; two agents have been suggested, folate and mesalamine preparations. Also, immunomodulators and biologic agents used to treat this disease may promote developing extra-intestinal cancers.Some cancers, such as Acute Myelocytic Leukaemia have been described in cases of Crohns disease. Hepatosplenic T-cell lymphoma (HSTCL) is a rare, lethal disease generally seen in young male patients with inflammatory bowel disease. TNF-α Inhibitor treatments (infliximab, adalimumab, certolizumab, natalizumab, and etanercept) are thought to be the cause of this rare disease.
Major complications
Major complications of Crohns disease include bowel obstruction, abscesses, free perforation, and hemorrhage, which in rare cases may be fatal.
Other Complications
Individuals with Crohns disease are at risk of malnutrition for many reasons, including decreased food intake and malabsorption. The risk increases following resection of the small bowel. Such individuals may require oral supplements to increase their caloric intake, or in severe cases, total parenteral nutrition (TPN). Most people with moderate or severe Crohns disease are referred to a dietitian for assistance in nutrition.Small intestinal bacterial overgrowth (SIBO) is characterized by excessive proliferation of colonic bacterial species in the small bowel. Potential causes of SIBO include fistulae, strictures, or motility disturbances. Hence, patients with Crohns disease are especially predisposed to develop SIBO. As result, CD patients may experience malabsorption and report symptoms such as weight loss, watery diarrhea, meteorism, flatulence, and abdominal pain, mimicking acute flare in these patients.
Pregnancy
Crohns disease can be problematic during pregnancy, and some medications can cause adverse outcomes for the fetus or mother. Consultation with an obstetrician and gastroenterologist about Crohns disease and all medications facilitates preventive measures. In some cases, remission occurs during pregnancy. Certain medications can also lower sperm count or otherwise adversely affect a mans fertility.
Ostomy-related complications
Common complications of an ostomy (a common surgery in Crohns disease) are: Mucosal edema, Peristomal dermatitis, Retraction, Ostomy prolapse, Mucosal/skin detachment, Hematoma, Necrosis, Parastomal hernia, and Stenosis.
Etiology
The etiology of Crohns disease is unknown. Many theories have been disputed, with four main theories hypothesized to be the primary mechanism of Crohns disease. In autoimmune diseases, antibodies and T lymphocytes are the primary mode of inflammation. These cells and bodies are part of the adaptive immune system, or the part of the immune system that learns to fight foreign bodies when first identified. Autoinflammatory diseases are diseases where the innate immune system, or the immune system we are genetically coded with, is designed to attack our own cells. Crohns disease likely has involvement of both the adaptive and innate immune systems.
Autoinflammatory theory
Crohns disease can be described as a multifactorial autoinflammatory disease. The etiopathogenesis of Crohns disease is still unknown. In any event, a loss of the regulatory capacity of the immune apparatus would be implicated in the onset of the disease. In this respect interestingly enough, as for Blaus disease (a monogenic autoinflammatory disease), the NOD2 gene mutations have been linked to Crohns disease. However, in Crohns disease, NOD2 mutations act as a risk factor, being more common among Crohns disease patients than the background population, while in Blaus disease NOD2 mutations are linked directly to this syndrome, as it is an autosomal-dominant disease. All this new knowledge in the pathogenesis of Crohns disease allows us to put this multifactorial disease in the group of autoinflammatory syndromes.Some examples of how the innate immune system affects bowel inflammation have been described. A meta-analysis of CD genome-wide association studies revealed 71 distinct CD-susceptibility loci. Interestingly, three very important CD-susceptibility genes (the intracellular pathogen-recognition receptor, NOD2; the autophagy-related 16-like 1, ATG16L1 and the immunity-related GTPase M, IRGM) are involved in innate immune responses against gut microbiota, while one (the X-box binding protein 1) is involved in regulation of the [adaptive] immune pathway via MHC class II, resulting in autoinflammatory inflammation. Studies have also found that increased ILC3 can overexpress major histocompatibility complex (MHC) II. MHC class II can induce CD4+ T cell apoptosis, thus avoiding the T cell response to normal bowel micro bacteria. Further studies of IBD patients compared with non-IBD patients found that the expression of MHC II by ILC3 was significantly reduced in IBD patients, thus causing an immune reaction against intestinal cells or normal bowel bacteria and damaging the intestines. This can also make the intestines more susceptible to environmental factors, such as food or bacteria.The thinking is, that because Crohns disease has strong innate immune system involvement and has NOD2 mutations as a predisposition, Crohns disease is more likely an autoinflammatory disease than an autoimmune disease.
Immunodeficiency theory
A substantial body of data has emerged in recent years to suggest that the primary defect in Crohns disease is actually one of relative immunodeficiency. This view has been bolstered recently by novel immunological and clinical studies that have confirmed gross aberrations in this early response, consistent with subsequent genetic studies that highlighted molecules important for innate immune function. The suggestion therefore is that Crohns pathogenesis actually results from partial immunodeficiency, a theory that coincides with the frequent recognition of a virtually identical, non-infectious inflammatory bowel disease arising in patients with congenital monogenic disorders impairing phagocyte function.
Causes
While the exact cause or causes are unknown, Crohns disease seems to be due to a combination of environmental factors and genetic predisposition. Crohns is the first genetically complex disease in which the relationship between genetic risk factors and the immune system is understood in considerable detail. Each individual risk mutation makes a small contribution to the overall risk of Crohns (approximately 1:200). The genetic data, and direct assessment of immunity, indicates a malfunction in the innate immune system. In this view, the chronic inflammation of Crohns is caused when the adaptive immune system tries to compensate for a deficient innate immune system.
Genetics
Crohns has a genetic component. |
Crohns disease | Because of this, siblings of known people with Crohns are 30 times more likely to develop Crohns than the general population.The first mutation found to be associated with Crohns was a frameshift in the NOD2 gene (also known as the CARD15 gene), followed by the discovery of point mutations. Over 30 genes have been associated with Crohns; a biological function is known for most of them. For example, one association is with mutations in the XBP1 gene, which is involved in the unfolded protein response pathway of the endoplasmic reticulum. The gene variants of NOD2/CARD15 seem to be related with small-bowel involvement. Other well documented genes which increase the risk of developing Crohns disease are ATG16L1, IL23R, IRGM, and SLC11A1.
There is considerable overlap between susceptibility loci for IBD and mycobacterial infections. Genome-wide association studies have shown that Crohns disease is genetically linked to coeliac disease.Crohns has been linked to the gene LRRK2 with one variant potentially increasing the risk of developing the disease by 70%, while another lowers it by 25%. The gene is responsible for making a protein, which collects and eliminates waste product in cells, and is also associated with Parkinsons disease.
Immune system
There was a prevailing view that Crohns disease is a primary T cell autoimmune disorder; however, a newer theory hypothesizes that Crohns results from an impaired innate immunity. The later hypothesis describes impaired cytokine secretion by macrophages, which contributes to impaired innate immunity and leads to a sustained microbial-induced inflammatory response in the colon, where the bacterial load is high. Another theory is that the inflammation of Crohns was caused by an overactive Th1 and Th17 cytokine response.In 2007, the ATG16L1 gene was implicated in Crohns disease, which may induce autophagy and hinder the bodys ability to attack invasive bacteria. Another study theorized that the human immune system traditionally evolved with the presence of parasites inside the body and that the lack thereof due to modern hygiene standards has weakened the immune system. Test subjects were reintroduced to harmless parasites, with positive responses.
Microbes
It is hypothesized that maintenance of commensal microorganism growth in the GI tract is dysregulated, either as a result or cause of immune dysregulation.There is an apparent connection between Crohns disease, Mycobacterium, other pathogenic bacteria, and genetic markers. A number of studies have suggested a causal role for Mycobacterium avium subspecies paratuberculosis (MAP), which causes a similar disease, Johnes disease, in cattle. In many individuals, genetic factors predispose individuals to Mycobacterium avium subsp. paratuberculosis infection. This bacterium may produce certain compounds containing mannose, which may protect both itself and various other bacteria from phagocytosis, thereby possibly causing a variety of secondary infections.NOD2 is a gene involved in Crohns genetic susceptibility. It is associated with macrophages diminished ability to phagocytize MAP. This same gene may reduce innate and adaptive immunity in gastrointestinal tissue and impair the ability to resist infection by the MAP bacterium. Macrophages that ingest the MAP bacterium are associated with high production of TNF-α.Other studies have linked specific strains of enteroadherent E. coli to the disease. Adherent-invasive Escherichia coli (AIEC), more common in people with CD, have the ability to make strong biofilms compared to non-AIEC strains correlating with high adhesion and invasion indices of neutrophils and the ability to block autophagy at the autolysosomal step, which allows for intracellular survival of the bacteria and induction of inflammation. Inflammation drives the proliferation of AIEC and dysbiosis in the ileum, irrespective of genotype. AIEC strains replicate extensively inside macrophages inducing the secretion of very large amounts of TNF-α.Mouse studies have suggested some symptoms of Crohns disease, ulcerative colitis, and irritable bowel syndrome have the same underlying cause. Biopsy samples taken from the colons of all three patient groups were found to produce elevated levels of a serine protease. Experimental introduction of the serine protease into mice has been found to produce widespread pain associated with irritable bowel syndrome, as well as colitis, which is associated with all three diseases. Regional and temporal variations in those illnesses follow those associated with infection with the protozoan Blastocystis.The "cold-chain" hypothesis is that psychrotrophic bacteria such as Yersinia and Listeria species contribute to the disease. A statistical correlation was found between the advent of the use of refrigeration in the United States and various parts of Europe and the rise of the disease.There is also a tentative association between Candida colonization and Crohns disease.Still, these relationships between specific pathogens and Crohns disease remain unclear.
Environmental factors
The increased incidence of Crohns in the industrialized world indicates an environmental component. Crohns is associated with an increased intake of animal protein, milk protein, and an increased ratio of omega-6 to omega-3 polyunsaturated fatty acids.
Those who consume vegetable proteins appear to have a lower incidence of Crohns disease. Consumption of fish protein has no association.Smoking increases the risk of the return of active disease (flares). The introduction of hormonal contraception in the United States in the 1960s is associated with a dramatic increase in incidence, and one hypothesis is that these drugs work on the digestive system in ways similar to smoking. Isotretinoin is associated with Crohns.Although stress is sometimes claimed to exacerbate Crohns disease, there is no concrete evidence to support such claim. Dietary microparticles, such as those found in toothpaste, have been studied as they produce effects on immunity, but they were not consumed in greater amounts in patients with Crohns. The use of doxycycline has also been associated with increased risk of developing inflammatory bowel diseases. In one large retrospective study, patients who were prescribed doxycycline for their acne had a 2.25-fold greater risk of developing Crohns disease.
Pathophysiology
During a colonoscopy, biopsies of the colon are often taken to confirm the diagnosis. Certain characteristic features of the pathology seen point toward Crohns disease; it shows a transmural pattern of inflammation, meaning the inflammation may span the entire depth of the intestinal wall. Ulceration is an outcome seen in highly active disease. There is usually an abrupt transition between unaffected tissue and the ulcer—a characteristic sign known as skip lesions. Under a microscope, biopsies of the affected colon may show mucosal inflammation, characterized by focal infiltration of neutrophils, a type of inflammatory cell, into the epithelium. This typically occurs in the area overlying lymphoid aggregates. These neutrophils, along with mononuclear cells, may infiltrate the crypts, leading to inflammation (crypititis) or abscess (crypt abscess).Granulomas, aggregates of macrophage derivatives known as giant cells, are found in 50% of cases and are most specific for Crohns disease. The granulomas of Crohns disease do not show "caseation", a cheese-like appearance on microscopic examination characteristic of granulomas associated with infections, such as tuberculosis. Biopsies may also show chronic mucosal damage, as evidenced by blunting of the intestinal villi, atypical branching of the crypts, and a change in the tissue type (metaplasia). One example of such metaplasia, Paneth cell metaplasia, involves the development of Paneth cells (typically found in the small intestine and a key regulator of intestinal microbiota) in other parts of the gastrointestinal system.
Diagnosis
The diagnosis of Crohns disease can sometimes be challenging, and many tests are often required to assist the physician in making the diagnosis. Even with a full battery of tests, it may not be possible to diagnose Crohns with complete certainty; a colonoscopy is approximately 70% effective in diagnosing the disease, with further tests being less effective. Disease in the small bowel is particularly difficult to diagnose, as a traditional colonoscopy allows access to only the colon and lower portions of the small intestines; introduction of the capsule endoscopy aids in endoscopic diagnosis. Giant (multinucleate) cells, a common finding in the lesions of Crohns disease, are less common in the lesions of lichen nitidus.
Classification
Crohns disease is one type of inflammatory bowel disease (IBD). It typically manifests in the gastrointestinal tract and can be categorized by the specific tract region affected. A disease of both the ileum (the last part of the small intestine that connects to the large intestine), and the large intestine, Ileocolic Crohns accounts for fifty percent of cases. Crohns ileitis, manifest in the ileum only, accounts for thirty percent of cases, while Crohns colitis, of the large intestine, accounts for the remaining twenty percent of cases and may be particularly difficult to distinguish from ulcerative colitis.Gastroduodenal Crohns disease causes inflammation in the stomach and the first part of the small intestine called the duodenum. Jejunoileitis causes spotty patches of inflammation in the top half of the small intestine, called the jejunum. The disease can attack any part of the digestive tract, from mouth to anus. However, individuals affected by the disease rarely fall outside these three classifications, with presentations in other areas.Crohns disease may also be categorized by the behavior of disease as it progresses. These categorizations formalized in the Vienna classification of the disease. There are three categories of disease presentation in Crohns disease: stricturing, penetrating, and inflammatory. Stricturing disease causes narrowing of the bowel that may lead to bowel obstruction or changes in the caliber of the feces. Penetrating disease creates abnormal passageways (fistulae) between the bowel and other structures, such as the skin. Inflammatory disease (or nonstricturing, nonpenetrating disease) causes inflammation without causing strictures or fistulae.
Endoscopy
A colonoscopy is the best test for making the diagnosis of Crohns disease, as it allows direct visualization of the colon and the terminal ileum, identifying the pattern of disease involvement. On occasion, the colonoscope can travel past the terminal ileum, but it varies from person to person. During the procedure, the gastroenterologist can also perform a biopsy, taking small samples of tissue for laboratory analysis, which may help confirm a diagnosis. As 30% of Crohns disease involves only the ileum, cannulation of the terminal ileum is required in making the diagnosis. Finding a patchy distribution of disease, with involvement of the colon or ileum, but not the rectum, is suggestive of Crohns disease, as are other endoscopic stigmata.
The utility of capsule endoscopy for this, however, is still uncertain. A "cobblestone"-like appearance is seen in approximately 40% of cases of Crohns disease upon colonoscopy, representing areas of ulceration separated by narrow areas of healthy tissue.
Radiologic tests
A small bowel follow-through may suggest the diagnosis of Crohns disease and is useful when the disease involves only the small intestine. Because colonoscopy and gastroscopy allow direct visualization of only the terminal ileum and beginning of the duodenum, they cannot be used to evaluate the remainder of the small intestine. As a result, a barium follow-through X-ray, wherein barium sulfate suspension is ingested and fluoroscopic images of the bowel are taken over time, is useful for looking for inflammation and narrowing of the small bowel. Barium enemas, in which barium is inserted into the rectum and fluoroscopy is used to image the bowel, are rarely used in the work-up of Crohns disease due to the advent of colonoscopy. They remain useful for identifying anatomical abnormalities when strictures of the colon are too small for a colonoscope to pass through, or in the detection of colonic fistulae (in this case contrast should be performed with iodate substances).CT and MRI scans are useful for evaluating the small bowel with enteroclysis protocols. They are also useful for looking for intra-abdominal complications of Crohns disease, such as abscesses, small bowel obstructions, or fistulae. Magnetic resonance imaging (MRI) is another option for imaging the small bowel as well as looking for complications, though it is more expensive and less readily available. MRI techniques such as diffusion-weighted imaging and high-resolution imaging are more sensitive in detecting ulceration and inflammation compared to CT.
Blood tests
A complete blood count may reveal anemia, which commonly is caused by blood loss leading to iron deficiency or by vitamin B12 deficiency, usually caused by ileal disease impairing vitamin B12 absorption. Rarely autoimmune hemolysis may occur. Ferritin levels help assess if iron deficiency is contributing to the anemia. Erythrocyte sedimentation rate (ESR) and C-reactive protein help assess the degree of inflammation, which is important as ferritin can also be raised in inflammation. Serum iron, total iron binding capacity and transferrin saturation may be more easily interpreted in inflammation. Anemia of chronic disease results in a normocytic anemia.Other causes of anemia include medication used in treatment of inflammatory bowel disease, like azathioprine, which can lead to cytopenia, and sulfasalazine, which can also result in folate deficiency. Testing for Saccharomyces cerevisiae antibodies (ASCA) and antineutrophil cytoplasmic antibodies (ANCA) has been evaluated to identify inflammatory diseases of the intestine and to differentiate Crohns disease from ulcerative colitis. Furthermore, increasing amounts and levels of serological antibodies such as ASCA, antilaminaribioside [Glc(β1,3)Glb(β); ALCA], antichitobioside [GlcNAc(β1,4)GlcNAc(β); ACCA], antimannobioside [Man(α1,3)Man(α)AMCA], antiLaminarin [(Glc(β1,3))3n(Glc(β1,6))n; anti-L] and antichitin [GlcNAc(β1,4)n; anti-C] associate with disease behavior and surgery, and may aid in the prognosis of Crohns disease.Low serum levels of vitamin D are associated with Crohns disease. Further studies are required to determine the significance of this association.
Comparison with ulcerative colitis
The most common disease that mimics the symptoms of Crohns disease is ulcerative colitis, as both are inflammatory bowel diseases that can affect the colon with similar symptoms. It is important to differentiate these diseases, since the course of the diseases and treatments may be different. In some cases, however, it may not be possible to tell the difference, in which case the disease is classified as indeterminate colitis.
Differential diagnosis
Other conditions with similar symptoms as Crohns disease includes intestinal tuberculosis, Behçets disease, ulcerative colitis, nonsteroidal anti-inflammatory drug enteropathy, irritable bowel syndrome and celiac disease. Irritable bowel syndrome is excluded when there are inflammatory changes. Celiac disease cannot be excluded if specific antibodies (anti-transglutaminase antibodies) are negative, nor in absence of intestinal villi atrophy.
Management
There is no cure for Crohns disease and remission may not be possible or prolonged if achieved. In cases where remission is possible, relapse can be prevented and symptoms controlled with medication, lifestyle and dietary changes, changes to eating habits (eating smaller amounts more often), reduction of stress, moderate activity, and exercise. Surgery is generally contraindicated and has not been shown to prevent relapse. Adequately controlled, Crohns disease may not significantly restrict daily living. Treatment for Crohns disease involves first treating the acute problem and its symptoms, then maintaining remission of the disease.
Lifestyle changes
Certain lifestyle changes can reduce symptoms, including dietary adjustments, elemental diet, proper hydration, and smoking cessation.
Patients with Crohns disease are very interested in diet. Recent reviews underlined the importance to adopt diets that are best supported by evidence, even if little is known about the impact of diets on these patients.
Diets that include higher levels of fiber and fruit are associated with reduced risk, while diets rich in total fats, polyunsaturated fatty acids, meat, and omega-6 fatty acids may increase the risk of Crohns. Maintaining a balanced diet with proper portion control can help manage symptoms of the disease. Eating small meals frequently instead of big meals may also help with a low appetite. A food diary may help with identifying foods that trigger symptoms. Despite the recognized importance of dietary fiber for intestinal health, some people should follow a low residue diet to control acute symptoms especially if foods high in insoluble fiber cause symptoms, e.g., due to obstruction or irritation of the bowel. Some find relief in eliminating casein (a protein found in cows milk) and gluten (a protein found in wheat, rye and barley) from their diets. They may have specific dietary intolerances (not allergies), for example, lactose. Fatigue can be helped with regular exercise, a healthy diet, and enough sleep, and for those with malabsorption of vitamin B12 due to disease or surgical resection of the terminal ileum, cobalamin injections. Smoking may worsen symptoms and the course of the disease, and stopping is recommended. Alcohol consumption can also worsen symptoms, and moderation or cessation is advised.
Medication
Acute treatment uses medications to treat any infection (normally antibiotics) and to reduce inflammation (normally aminosalicylate anti-inflammatory drugs and corticosteroids). When symptoms are in remission, treatment enters maintenance, with a goal of avoiding the recurrence of symptoms. Prolonged use of corticosteroids has significant side-effects; as a result, they are, in general, not used for long-term treatment. Alternatives include aminosalicylates alone, though only a minority are able to maintain the treatment, and many require immunosuppressive drugs. It has been also suggested that antibiotics change the enteric flora, and their continuous use may pose the risk of overgrowth with pathogens such as Clostridium difficile.Medications used to treat the symptoms of Crohns disease include 5-aminosalicylic acid (5-ASA) formulations, prednisone, immunomodulators such as azathioprine (given as the prodrug for 6-mercaptopurine), methotrexate, and anti-TNF therapies and monoclonal antibodies, such as infliximab, adalimumab, certolizumab, vedolizumab, ustekinumab, and natalizumab. Hydrocortisone should be used in severe attacks of Crohns disease. Biological therapies are medications used to avoid long-term steroid use, decrease inflammation, and treat people who have fistulas with abscesses. The monoclonal antibody ustekinumab appears to be a safe treatment option, and may help people with moderate to severe active Crohns disease. The long term safety and effectiveness of monoclonal antibody treatment is not known. The monoclonal antibody briakinumab is not effective for people with active Crohns disease and it is no longer being manufactured.The gradual loss of blood from the gastrointestinal tract, as well as chronic inflammation, often leads to anemia, and professional guidelines suggest routinely monitoring for this. Adequate disease control usually improves anemia of chronic disease, but iron deficiency may require treatment with iron supplements. Guidelines vary as to how iron should be administered. Besides, other problems include a limitation in possible daily resorption and an increased growth of intestinal bacteria. Some advise parenteral iron as first line as it works faster, has fewer gastrointestinal side effects, and is unaffected by inflammation reducing enteral absorption.
Other guidelines advise oral iron as first-line with parenteral iron reserved for those that fail to adequately respond as oral iron is considerably cheaper. All agree that severe anemia (hemoglobin under 10g/dL) should be treated with parenteral iron. Blood transfusion should be reserved for those who are cardiovascularly unstable, due to its relatively poor safety profile, lack of long-term efficacy, and cost.
Surgery
Crohns cannot be cured by surgery, as the disease eventually recurs, though it is used in the case of partial or full blockage of the intestine. Surgery may also be required for complications such as obstructions, fistulas, or abscesses, or if the disease does not respond to drugs. After the first surgery, Crohns usually comes back at the site where the diseased intestine was removed and the healthy ends were rejoined; it can also come back in other locations. After a resection, scar tissue builds up, which can cause strictures, which form when the intestines become too small to allow excrement to pass through easily, which can lead to a blockage. After the first resection, another resection may be necessary within five years. For patients with an obstruction due to a stricture, two options for treatment are strictureplasty and resection of that portion of bowel. There is no statistical significance between strictureplasty alone versus strictureplasty and resection in cases of duodenal involvement. In these cases, re-operation rates were 31% and 27%, respectively, indicating that strictureplasty is a safe and effective treatment for selected people with duodenal involvement.Postsurgical recurrence of Crohns disease is relatively common. Crohns lesions are nearly always found at the site of the resected bowel. The join (or anastomosis) after surgery may be inspected, usually during a colonoscopy, and disease activity graded. The "Rutgeerts score" is an endoscopic scoring system for postoperative disease recurrence in Crohns disease. Mild postsurgical recurrences of Crohns disease are graded i1 and i2, moderate to severe recurrences are graded i3 and i4. Fewer lesions result in a lower grade. Based on the score, treatment plans can be designed to give the patient the best chance of managing the recurrence of the disease.Short bowel syndrome (SBS, also short gut syndrome or simply short gut) is caused by the surgical removal of part of the small intestine. It usually develops in those patients who have had half or more of their small intestines removed. Diarrhea is the main symptom, but others may include weight loss, cramping, bloating, and heartburn. Short bowel syndrome is treated with changes in diet, intravenous feeding, vitamin and mineral supplements, and treatment with medications. In some cases of SBS, intestinal transplant surgery may be considered; though the number of transplant centres offering this procedure is quite small and it comes with a high risk due to the chance of infection and rejection of the transplanted intestine.Bile acid diarrhea is another complication following surgery for Crohns disease in which the terminal ileum has been removed. This leads to the development of excessive watery diarrhea. It is usually thought to be due to an inability of the ileum to reabsorb bile acids after resection of the terminal ileum and was the first type of bile acid malabsorption recognized.
Mental health
Crohns may result in anxiety or mood disorders, especially in young people who may have stunted growth or embarrassment from fecal incontinence. Counselling as well as antidepressant or anxiolytic medication may help some people manage.As of 2017 there is a small amount of research looking at mindfulness-based therapies, hypnotherapy, and cognitive behavioural therapy.
Alternative medicine
It is common for people with Crohns disease to try complementary or alternative therapy. These include diets, probiotics, fish oil, and other herbal and nutritional supplements.
Acupuncture is used to treat inflammatory bowel disease in China, and is being used more frequently in Western society. At this time, evidence is insufficient to recommend the use of acupuncture.
A 2006 survey in Germany found that about half of people with IBD used some form of alternative medicine, with the most common being homeopathy, and a study in France found that about 30% used alternative medicine. Homeopathic preparations are not proven with this or any other condition, with large-scale studies finding them to be no more effective than a placebo.
There are contradicting studies regarding the effect of medical cannabis on inflammatory bowel disease, and its effects on management are uncertain.
Prognosis
Crohns disease is a chronic condition for which there is no known cure. It is characterised by periods of improvement followed by episodes when symptoms flare up. With treatment, most people achieve a healthy weight, and the mortality rate for the disease is relatively low. It can vary from being benign to very severe, and people with CD could experience just one episode or have continuous symptoms. It usually reoccurs, although some people can remain disease-free for years or decades. Up to 80% of people with Crohns disease are hospitalized at some point during the course of their disease, with the highest rate occurring in the first year after diagnosis. Most people with Crohns live a normal lifespan. However, Crohns disease is associated with a small increase in risk of small bowel and colorectal carcinoma (bowel cancer).
Epidemiology
The percentage of people with Crohns disease has been determined in Norway and the United States and is similar at 6 to 7.1:100,000. The Crohns and Colitis Foundation of America cites this number as approx 149:100,000; NIH cites 28 to 199 per 100,000. Crohns disease is more common in northern countries, and with higher rates still in the northern areas of these countries. The incidence of Crohns disease is thought to be similar in Europe but lower in Asia and Africa. It also has a higher incidence in Ashkenazi Jews and smokers.Crohns disease begins most commonly in people in their teens and 20s, and people in their 50s through to their 70s. It is rarely diagnosed in early childhood. It usually affects female children more severely than males. However, only slightly more women than men have Crohns disease. Parents, siblings or children of people with Crohns disease are 3 to 20 times more likely to develop the disease. Twin studies find that if one has the disease there is a 55% chance the other will too.The incidence of Crohns disease is increasing in Europe and in newly industrialised countries. For example, in Brazil, there has been an annual increase of 11% in the incidence of Crohns disease since 1990.
History
Inflammatory bowel diseases were described by Giovanni Battista Morgagni (1682–1771) and by Scottish physician T Kennedy Dalziel in 1913.Ileitis terminalis was first described by Polish surgeon Antoni Leśniowski in 1904, although it was not conclusively distinguished from intestinal tuberculosis. In Poland, it is still called Leśniowski-Crohns disease (Polish: choroba Leśniowskiego-Crohna). Burrill Bernard Crohn, an American gastroenterologist at New York Citys Mount Sinai Hospital, described fourteen cases in 1932, and submitted them to the American Medical Association under the rubric of "Terminal ileitis: A new clinical entity". Later that year, he, along with colleagues Leon Ginzburg and Gordon Oppenheimer, published the case series "Regional ileitis: a pathologic and clinical entity". However, due to the precedence of Crohns name in the alphabet, it later became known in the worldwide literature as Crohns disease.
Research
Some evidence supports the hypothesis that the bacterium Mycobacterium avium subspecies paratuberculosis (MAP) is a cause of Crohns disease (see also Johnes disease). As a result, researchers are looking at the eradication of MAP as a therapeutic option. The Crohns MAP Vaccine is an experimental vaccine based on this hypothesis. Treating MAP using specific antibiotics that MAP may be susceptible to has been examined and the results are unclear but tentatively beneficial.Crohns is common in parts of the world where helminthic colonisation is rare and uncommon in those areas where most people carry worms. Infections with helminths may alter the autoimmune response that causes the disease. Trials of extracts from the worm Trichuris suis |
Crohns disease | showed promising results when used in people with IBD. However, these trials (TRUST -I & TRUST -II) failed in Phase 2 clinical trials and were then discontinued after consistent failure in both North America and Europe.There is no good evidence that thalidomide or lenalidomide is useful to bring about or maintain remission.
References
Further reading
Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE (April 2018). "ACG Clinical Guideline: Management of Crohns Disease in Adults". Am. J. Gastroenterol. 113 (4): 481–517. doi:10.1038/ajg.2018.27. PMID 29610508.
External links
"Crohns disease". MedlinePlus. U.S. National Library of Medicine. |
Idiopathic intracranial hypertension | Idiopathic intracranial hypertension (IIH), previously known as pseudotumor cerebri and benign intracranial hypertension, is a condition characterized by increased intracranial pressure (pressure around the brain) without a detectable cause. The main symptoms are headache, vision problems, ringing in the ears, and shoulder pain. Complications may include vision loss.This condition is idiopathic, meaning there is no known cause. Risk factors include being overweight or a recent increase in weight. Tetracycline may also trigger the condition. The diagnosis is based on symptoms and a high opening pressure found during a lumbar puncture with no specific cause found on a brain scan.Treatment includes a healthy diet, salt restriction, and exercise. The medication acetazolamide may also be used along with the above measures. A small percentage of people may require surgery to relieve the pressure.About 2 per 100,000 people are newly affected per year. The condition most commonly affects women aged 20–50. Women are affected about 20 times more often than men. The condition was first described in 1897.
Signs and symptoms
The most common symptom of IIH is headache, which occurs in almost all (92–94%) cases. It is characteristically worse in the morning, generalized in character and throbbing in nature. It may be associated with nausea and vomiting. The headache can be made worse by any activity that further increases the intracranial pressure, such as coughing and sneezing. The pain may also be experienced in the neck and shoulders. Many have pulsatile tinnitus, a whooshing sensation in one or both ears (64–87%); this sound is synchronous with the pulse. Various other symptoms, such as numbness of the extremities, generalized weakness, loss of smell, and loss of coordination, are reported more rarely; none are specific for IIH. In children, numerous nonspecific signs and symptoms may be present.The increased pressure leads to compression and traction of the cranial nerves, a group of nerves that arise from the brain stem and supply the face and neck. Most commonly, the abducens nerve (sixth nerve) is involved. This nerve supplies the muscle that pulls the eye outward. Those with sixth nerve palsy therefore experience horizontal double vision which is worse when looking towards the affected side. More rarely, the oculomotor nerve and trochlear nerve (third and fourth nerve palsy, respectively) are affected; both play a role in eye movements. The facial nerve (seventh cranial nerve) is affected occasionally – the result is total or partial weakness of the muscles of facial expression on one or both sides of the face.The increased pressure leads to papilledema, which is swelling of the optic disc, the spot where the optic nerve enters the eyeball. This occurs in practically all cases of IIH, but not everyone experiences symptoms from this. Those who do experience symptoms typically report "transient visual obscurations", episodes of difficulty seeing that occur in both eyes but not necessarily at the same time. Long-term untreated papilledema leads to visual loss, initially in the periphery but progressively towards the center of vision.Physical examination of the nervous system is typically normal apart from the presence of papilledema, which is seen on examination of the eye with a small device called an ophthalmoscope or in more detail with a fundus camera. If there are cranial nerve abnormalities, these may be noticed on eye examination in the form of a squint (third, fourth, or sixth nerve palsy) or as facial nerve palsy. If the papilledema has been longstanding, visual fields may be constricted and visual acuity may be decreased. Visual field testing by automated (Humphrey) perimetry is recommended as other methods of testing may be less accurate. Longstanding papilledema leads to optic atrophy, in which the disc looks pale and visual loss tends to be advanced.
Causes
"Idiopathic" means of unknown cause. Therefore, IIH can only be diagnosed if there is no alternative explanation for the symptoms. Intracranial pressure may be increased due to medications such as high-dose vitamin A derivatives (e.g., isotretinoin for acne), long-term tetracycline antibiotics (for a variety of skin conditions) and hormonal contraceptives.
There are numerous other diseases, mostly rare conditions, that may lead to intracranial hypertension. If there is an underlying cause, the condition is termed "secondary intracranial hypertension". Common causes of secondary intracranial hypertension include obstructive sleep apnea (a sleep-related breathing disorder), systemic lupus erythematosus (SLE), chronic kidney disease, and Behçets disease.
Mechanism
The cause of IIH is not known. The Monro–Kellie rule states that the intracranial pressure is determined by the amount of brain tissue, cerebrospinal fluid (CSF) and blood inside the bony cranial vault. Three theories therefore exist as to why the pressure might be raised in IIH: an excess of CSF production, increased volume of blood or brain tissue, or obstruction of the veins that drain blood from the brain.The first theory, that of increased production of cerebrospinal fluid, was proposed in early descriptions of the disease. However, there is no experimental data that supports a role for this process in IIH.The second theory posits that either increased blood flow to the brain or increase in the brain tissue itself may result in the raised pressure. Little evidence has accumulated to support the suggestion that increased blood flow plays a role, but recently Bateman et al. in phase contrast MRA studies have quantified cerebral blood flow (CBF) in vivo and suggests that CBF is abnormally elevated in many people with IIH. Both biopsy samples and various types of brain scans have shown an increased water content of the brain tissue. It remains unclear why this might be the case.The third theory suggests that restricted venous drainage from the brain may be impaired resulting in congestion. Many people with IIH have narrowing of the transverse sinuses. It is not clear whether this narrowing is the pathogenesis of the disease or a secondary phenomenon. It has been proposed that a positive biofeedback loop may exist, where raised ICP (intracranial pressure) causes venous narrowing in the transverse sinuses, resulting in venous hypertension (raised venous pressure), decreased CSF resorption via arachnoid granulation and further rise in ICP.
Diagnosis
The diagnosis may be suspected on the basis of the history and examination. To confirm the diagnosis, as well as excluding alternative causes, several investigations are required; more investigations may be performed if the history is not typical or the person is more likely to have an alternative problem: children, men, the elderly, or women who are not overweight.
Investigations
Neuroimaging, usually with computed tomography (CT/CAT) or magnetic resonance imaging (MRI), is used to exclude any mass lesions. In IIH these scans typically appear to be normal, although small or slit-like ventricles, dilatation and buckling of the optic nerve sheaths and "empty sella sign" (flattening of the pituitary gland due to increased pressure) and enlargement of Meckels caves may be seen.
An MR venogram is also performed in most cases to exclude the possibility of venous sinus stenosis/obstruction or cerebral venous sinus thrombosis. A contrast-enhanced MRV (ATECO) scan has a high detection rate for abnormal transverse sinus stenoses. These stenoses can be more adequately identified and assessed with catheter cerebral venography and manometry. Buckling of the bilateral optic nerves with increased perineural fluid is also often noted on MRI imaging.
Lumbar puncture is performed to measure the opening pressure, as well as to obtain cerebrospinal fluid (CSF) to exclude alternative diagnoses. If the opening pressure is increased, CSF may be removed for transient relief (see below). The CSF is examined for abnormal cells, infections, antibody levels, the glucose level, and protein levels. By definition, all of these are within their normal limits in IIH. Occasionally, the CSF pressure measurement may be normal despite very suggestive symptoms. This may be attributable to the fact that CSF pressure may fluctuate over the course of the normal day. If the suspicion of problems remains high, it may be necessary to perform more long-term monitoring of the ICP by a pressure catheter.
Classification
The original criteria for IIH were described by Dandy in 1937.
They were modified by Smith in 1985 to become the "modified Dandy criteria". Smith included the use of more advanced imaging: Dandy had required ventriculography, but Smith replaced this with computed tomography. In a 2001 paper, Digre and Corbett amended Dandys criteria further. They added the requirement that the person is awake and alert, as coma precludes adequate neurological assessment, and require exclusion of venous sinus thrombosis as an underlying cause. Furthermore, they added the requirement that no other cause for the raised ICP is found.
In a 2002 review, Friedman and Jacobson propose an alternative set of criteria, derived from Smiths. These require the absence of symptoms that could not be explained by a diagnosis of IIH, but do not require the actual presence of any symptoms (such as headache) attributable to IIH. These criteria also require that the lumbar puncture is performed with the person lying sideways, as a lumbar puncture performed in the upright sitting position can lead to artificially high pressure measurements. Friedman and Jacobson also do not insist on MR venography for every person; rather, this is only required in atypical cases (see "diagnosis" above).
Treatment
The primary goal in treatment of IIH is the prevention of visual loss and blindness, as well as symptom control. IIH is treated mainly through the reduction of CSF pressure and. IIH may resolve after initial treatment, may go into spontaneous remission (although it can still relapse at a later stage), or may continue chronically.
Lumbar puncture
The first step in symptom control is drainage of cerebrospinal fluid by lumbar puncture. If necessary, this may be performed at the same time as a diagnostic LP (such as done in search of a CSF infection). In some cases, this is sufficient to control the symptoms, and no further treatment is needed.The procedure can be repeated if necessary, but this is generally taken as a clue that additional treatments may be required to control the symptoms and preserve vision. Repeated lumbar punctures are regarded as unpleasant by people, and they present a danger of introducing spinal infections if done too often. Repeated lumbar punctures are sometimes needed to control the ICP urgently if the persons vision deteriorates rapidly.
Medication
The best-studied medical treatment for intracranial hypertension is acetazolamide (Diamox), which acts by inhibiting the enzyme carbonic anhydrase, and it reduces CSF production by six to 57 percent. It can cause the symptoms of hypokalemia (low blood potassium levels), which include muscle weakness and tingling in the fingers. Acetazolamide cannot be used in pregnancy, since it has been shown to cause embryonic abnormalities in animal studies. Also, in human beings it has been shown to cause metabolic acidosis as well as disruptions in the blood electrolyte levels of newborn babies. The diuretic furosemide is sometimes used for a treatment if acetazolamide is not tolerated, but this drug sometimes has little effect on the ICP.Various analgesics (painkillers) may be used in controlling the headaches of intracranial hypertension. In addition to conventional agents such as paracetamol, a low dose of the antidepressant amitriptyline or the anticonvulsant topiramate have shown some additional benefit for pain relief.The use of steroids in the attempt to reduce the ICP is controversial. These may be used in severe papilledema, but otherwise their use is discouraged.
Venous sinus stenting
Venous sinus stenoses leading to venous hypertension appear to play a significant part in relation to raised ICP, and stenting of a transverse sinus may resolve venous hypertension, leading to improved CSF resorption, decreased ICP, cure of papilledema and other symptoms of IIH.A self-expanding metal stent is permanently deployed within the dominant transverse sinus across the stenosis under general anaesthesia. In general, people are discharged the next day. People require double antiplatelet therapy for a period of up to 3 months after the procedure and aspirin therapy for up to 1 year.
In a systematic analysis of 19 studies with 207 cases, there was an 87% improvement in overall symptom rate and 90% cure rate for treatment of papilledema. Major complications only occurred in 3/207 people (1.4%). In the largest single series of transverse sinus stenting there was an 11% rate of recurrence after one stent, requiring further stenting.Due to the permanence of the stent and small but definite risk of complications, most experts will recommend that person with IIH must have papilledema and have failed medical therapy or are intolerant to medication before stenting is undertaken.
Surgery
Two main surgical procedures exist in the treatment of IIH: optic nerve sheath decompression and fenestration and shunting. Surgery would normally only be offered if medical therapy is either unsuccessful or not tolerated. The choice between these two procedures depends on the predominant problem in IIH. Neither procedure is perfect: both may cause significant complications, and both may eventually fail in controlling the symptoms. There are no randomized controlled trials to guide the decision as to which procedure is best.Optic nerve sheath fenestration is an operation that involves the making of an incision in the connective tissue lining of the optic nerve in its portion behind the eye. It is not entirely clear how it protects the eye from the raised pressure, but it may be the result of either diversion of the CSF into the orbit or the creation of an area of scar tissue that lowers the pressure. The effects on the intracranial pressure itself are more modest. Moreover, the procedure may lead to significant complications, including blindness in 1–2%. The procedure is therefore recommended mainly in those who have limited headache symptoms but significant papilledema or threatened vision, or in those who have undergone unsuccessful treatment with a shunt or have a contraindication for shunt surgery.Shunt surgery, usually performed by neurosurgeons, involves the creation of a conduit by which CSF can be drained into another body cavity. The initial procedure is usually a lumboperitoneal (LP) shunt, which connects the subarachnoid space in the lumbar spine with the peritoneal cavity. Generally, a pressure valve is included in the circuit to avoid excessive drainage when the person is erect. LP shunting provides long-term relief in about half the cases; others require revision of the shunt, often on more than one occasion—usually due to shunt obstruction. If the lumboperitoneal shunt needs repeated revisions, a ventriculoatrial or ventriculoperitoneal shunt may be considered. These shunts are inserted in one of the lateral ventricles of the brain, usually by stereotactic surgery, and then connected either to the right atrium of the heart or the peritoneal cavity, respectively. Given the reduced need for revisions in ventricular shunts, it is possible that this procedure will become the first-line type of shunt treatment.It has been shown that in obese people, bariatric surgery (and especially gastric bypass surgery) can lead to resolution of the condition in over 95%.
Prognosis
It is not known what percentage of people with IIH will remit spontaneously, and what percentage will develop chronic disease.IIH does not normally affect life expectancy. The major complications from IIH arise from untreated or treatment-resistant papilledema. In various case series, the long-term risk of ones vision being significantly affected by IIH is reported to lie anywhere between 10 and 25%.
Epidemiology
On average, IIH occurs in about one per 100,000 people, and can occur in children and adults. The median age at diagnosis is 30. IIH occurs predominantly in women, especially in the ages 20 to 45, who are four to eight times more likely than men to be affected. Overweight and obesity strongly predispose a person to IIH: women who are more than ten percent over their ideal body weight are thirteen times more likely to develop IIH, and this figure goes up to nineteen times in women who are more than twenty percent over their ideal body weight. In men this relationship also exists, but the increase is only five-fold in those over 20 percent above their ideal body weight.Despite several reports of IIH in families, there is no known genetic cause for IIH. People from all ethnicities may develop IIH. In children, there is no difference in incidence between males and females.From national hospital admission databases it appears that the need for neurosurgical intervention for IIH has increased markedly over the period between 1988 and 2002. This has been attributed at least in part to the rising prevalence of obesity, although some of this increase may be explained by the increased popularity of shunting over optic nerve sheath fenestration.
History
The first report of IIH was by the German physician Heinrich Quincke, who described it in 1893 under the name serous meningitis The term "pseudotumor cerebri" was introduced in 1904 by his compatriot Max Nonne. Numerous other cases appeared in the literature subsequently; in many cases, the raised intracranial pressure may actually have resulted from underlying conditions. For instance, the otitic hydrocephalus reported by London neurologist Sir Charles Symonds may have resulted from venous sinus thrombosis caused by middle ear infection. Diagnostic criteria for IIH were developed in 1937 by the Baltimore neurosurgeon Walter Dandy; Dandy also introduced subtemporal decompressive surgery in the treatment of the condition.The terms "benign" and "pseudotumor" derive from the fact that increased intracranial pressure may be associated with brain tumors. Those people in whom no tumour was found were therefore diagnosed with "pseudotumor cerebri" (a disease mimicking a brain tumor). The disease was renamed benign intracranial hypertension in 1955 to distinguish it from intracranial hypertension due to life-threatening diseases (such as cancer); however, this was also felt to be misleading because any disease that can blind someone should not be thought of as benign, and the name was therefore revised in 1989 to "idiopathic (of no identifiable cause) intracranial hypertension".Shunt surgery was introduced in 1949; initially, ventriculoperitoneal shunts were used. In 1971, good results were reported with lumboperitoneal shunting. Negative reports on shunting in the 1980s led to a brief period (1988–1993) during which optic nerve fenestration (which had initially been described in an unrelated condition in 1871) was more popular. Since then, shunting is recommended predominantly, with occasional exceptions.
References
External links
Idiopathic intracranial hypertension at Curlie |
Eustachian tube dysfunction | Eustachian tube dysfunction (ETD) is a disorder where pressure abnormalities in the middle ear result in symptoms.
Signs and symptoms
Symptoms include aural fullness, ears popping, a feeling of pressure in the affected ear(s), a feeling that the affected ear(s) is clogged, crackling, ear pain, tinnitus, autophony, and muffled hearing.
Diagnosis
While Eustachian tube dysfunction can be hard to diagnose, due to the Eustachian tubes and the nasopharynx not being easily visible, usually a tympanometry is indicated, along with findings on an otoscopy. For cases of baro-challenge induced Eustachian tube dysfunction, diagnosis usually relies on the history of the patient and their reported symptoms, as otoscopy and tympanometry is sometimes normal at normal ambient pressure. Opening pressure has been proposed as a method for preoperative and intraoperative evaluation of any obstructive process within the Eustachian tube. As well, Valasalva CT scanning using advanced 64 slice or higher machines has been proposed as a way of diagnosing and localizing anatomic obstruction within the Eustachian tube.
Types
Four subtypes have been described:
Anatomic obstruction within the proximal cartilaginous eustachian tube.
Dilatory Eustachian tube dysfunction: Functional, dynamic (muscle failure), or anatomical obstruction of the Eustachian tube
Baro-challenge induced Eustachian tube dysfunction: Eustachian tube dysfunction which generally features a normal otoscopy and normal tympanometry
Patulous Eustachian tube dysfunction
Causes
Eustachian tube dysfunction can be caused by a number of factors. Some common causes include the flu, allergies, a cold, and sinus infections. In patients with chronic ear disease such as cholesteatoma and chronic discharge, studies showed that they have obstructive pathology at the ear side of the Eustachian tube. Given that proximity of that part of the Eustachian tube to the tympanic cavity, the site of frequent infections during childhood, it is logical to conclude that this segment of the tube experiences fibrosis and stenosis from recurrent infections. This is a possible explanation for the increased frequency of chronic ear disease in disadvantaged populations who lack access to medical care including antibiotics and tympanostomy tubes.
Treatment
First-line treatment options are generally aimed at treating the underlying cause and include attempting to "pop" the ears, usually via the Valsalva maneuver, the use of oral or topical decongestants, oral steroids, oral antihistamines, and topical nasal steroid sprays, such as Flonase.If medical management fails, myringotomy, which is a surgical procedure in which an incision is made in the eardrum to drain pus from the middle ear or to relieve pressure caused by a large buildup of fluid, is indicated, and usually accompanied by the insertion of a tympanostomy tube.Tentative evidence supports the use of balloon dilation of the Eustachian tube. In 2018, researchers published a prospective, multicenter, randomized, controlled trial demonstrating efficacy of this technique. Dilatation of the eustachian tube using balloon catheter has gained attention as a method of treating eustachian tube obstruction. There are two methods of performing this procedure depending on the route of the catheter introduction and the area of the Eustachian tube to be dilated.
== References == |
Ménières disease | Ménières disease (MD) is a disease of the inner ear that is characterized by potentially severe and incapacitating episodes of vertigo, tinnitus, hearing loss, and a fullness in the ear. Typically, only one ear is affected initially, but over time, both ears may become involved. Episodes generally last from 20 minutes to a few hours. The time between episodes varies. The hearing loss and ringing in the ears can become constant over time.The cause of Ménières disease is unclear, but likely involves both genetic and environmental factors. A number of theories exist for why it occurs, including constrictions in blood vessels, viral infections, and autoimmune reactions. About 10% of cases run in families. Symptoms are believed to occur as the result of increased fluid buildup in the labyrinth of the inner ear. Diagnosis is based on the symptoms and a hearing test. Other conditions that may produce similar symptoms include vestibular migraine and transient ischemic attack.No cure is known. Attacks are often treated with medications to help with the nausea and anxiety. Measures to prevent attacks are overall poorly supported by the evidence. A low-salt diet, diuretics, and corticosteroids may be tried. Physical therapy may help with balance and counselling may help with anxiety. Injections into the ear or surgery may also be tried if other measures are not effective, but are associated with risks. The use of tympanostomy tubes, while popular, is not supported.Ménières disease was first identified in the early 1800s by Prosper Ménière. It affects between 0.3 and 1.9 per 1,000 people. It most often starts in people 40 to 60 years old. Females are more commonly affected than males. After 5 to 15 years of symptoms, the episodes of the world spinning sometimes stop and the person is left with loss of balance, poor hearing in the affected ear, and ringing or other sounds in the affected ear or ears.
Signs and symptoms
Ménières is characterized by recurrent episodes of vertigo, fluctuating hearing loss, and tinnitus; episodes may be preceded by a headache and a feeling of fullness in the ears. People may also experience additional symptoms related to irregular reactions of the autonomic nervous system. These symptoms are not symptoms of Menieres disease per se, but rather are side effects resulting from failure of the organ of hearing and balance, and include nausea, vomiting, and sweating, which are typically symptoms of vertigo, and not of Ménières. This includes a sensation of being pushed sharply to the floor from behind. Sudden falls without loss of consciousness (drop attacks) may be experienced by some people.
Causes
The cause of Ménières disease is unclear, but likely involves both genetic and environmental factors. A number of theories exist including constrictions in blood vessels, viral infections, and autoimmune reactions.
Mechanism
The initial triggers of Ménières disease are not fully understood, with a variety of potential inflammatory causes that lead to endolymphatic hydrops (EH), a distension of the endolymphatic spaces in the inner ear. EH, in turn, is strongly associated with developing MD, but not everyone with EH develops MD: "The relationship between endolymphatic hydrops and Menieres disease is not a simple, ideal correlation."Additionally, in fully developed MD, the balance system (vestibular system) and the hearing system (cochlea) of the inner ear are affected, but some cases occur where EH affects only one of the two systems enough to cause symptoms. The corresponding subtypes of MD are called vestibular MD, showing symptoms of vertigo, and cochlear MD, showing symptoms of hearing loss and tinnitus.The mechanism of MD is not fully explained by EH, but fully developed EH may mechanically and chemically interfere with the sensory cells for balance and hearing, which can lead to temporary dysfunction and even to death of the sensory cells, which in turn can cause the typical symptoms of MD – vertigo, hearing loss, and tinnitus.
Diagnosis
The diagnostic criteria as of 2015 define definite MD and probable MD as:
Definite
Two or more spontaneous episodes of vertigo, each lasting 20 minutes to 12 hours
Audiometrically documented low- to medium-frequency sensorineural hearing loss in the affected ear on at least one occasion before, during, or after one of the episodes of vertigo
Fluctuating aural symptoms (hearing, tinnitus, or fullness) in the affected ear
Not better accounted for by another vestibular diagnosisProbable
Two or more episodes of vertigo or dizziness, each lasting 20 minutes to 24 hours
Fluctuating aural symptoms (hearing, tinnitus, or fullness) in the reported ear
Not better accounted for by another vestibular diagnosis
A common and important symptom of MD is hypersensitivity to sounds. This hypersensitivity is easily diagnosed by measuring the loudness discomfort levels (LDLs).Symptoms of MD overlap with migraine-associated vertigo (MAV) in many ways, but when hearing loss develops in MAV, it is usually in both ears, and this is rare in MD, and hearing loss generally does not progress in MAV as it does in MD.People who have had a transient ischemic attack (TIA) or stroke can present with symptoms similar to MD, and in people at risk magnetic resonance imaging should be conducted to exclude TIA or stroke.Other vestibular conditions that should be excluded include vestibular paroxysmia, recurrent unilateral vestibulopathy, vestibular schwannoma, or a tumor of the endolymphatic sac.
Management
No cure for Ménières disease is known, but medications, diet, physical therapy, and counseling, and some surgical approaches can be used to manage it.
Medications
During MD episodes, medications to reduce nausea are used, as are drugs to reduce the anxiety caused by vertigo. For longer-term treatment to stop progression, the evidence base is weak for all treatments. Although a causal relation between allergy and Ménières disease is uncertain, medication to control allergies may be helpful. To assist with vertigo and balance problems, glycopyrrolate has been found to be a useful vestibular suppressant in patients with Menieres disease.Diuretics, such as the thiazide-like diuretic chlortalidone, are widely used to manage MD on the theory that it reduces fluid buildup (pressure) in the ear. Based on evidence from multiple but small clinical trials, diuretics appear to be useful for reducing the frequency of episodes of dizziness but do not seem to prevent hearing loss.In cases where hearing loss and continuing severe episodes of vertigo occur, a chemical labyrinthectomy, in which a medication such as gentamicin is injected into the middle ear and kills parts of the vestibular apparatus, may be prescribed. This treatment has the risk of worsening hearing loss.
Diet
People with MD are often advised to reduce their sodium intake. Reducing salt intake, however, has not been well studied.Based on the assumption that MD is similar in nature to a migraine, some advise eliminating "migraine triggers" such as caffeine, but the evidence for this is weak. There is no high-quality evidence that changing diet by restricting salt, caffeine or alcohol improves symptoms.
Physical therapy
While use of physical therapy early after the onset of MD is probably not useful due to the fluctuating disease course, physical therapy to help retraining of the balance system appears to be useful to reduce both subjective and objective deficits in balance over the longer term.
Counseling
The psychological distress caused by the vertigo and hearing loss may worsen the condition in some people. Counseling may be useful to manage the distress, as may education and relaxation techniques.
Surgery
If symptoms do not improve with typical treatment, surgery may be considered. Surgery to decompress the endolymphatic sac is one option. A systematic review in 2015 found that three methods of decompression have been used – simple decompression, insertion of a shunt, and removal of the sac. It found some evidence that all three methods were useful for reducing dizziness, but that the level of evidence was low, as trials were not blinded nor were placebo controls used.Another 2015 review found that, on autopsy, shunts used in these surgeries often turn out to be displaced or misplaced, and recommended their use only in cases where the condition is uncontrolled and affecting both ears. A systematic review from 2014 found that in at least 75% of people, EL sac decompression was effective at controlling vertigo in the short term (>1 year of follow-up) and long term (>24 months).An estimated 30% of people with MD have Eustachian tube dysfunction. While a 2005 review found tentative evidence of benefit from tympanostomy tubes for improvement in the unsteadiness associated with the disease, a 2014 review concluded that their use is not supported.Destructive surgeries are irreversible and involve removing entire functionality of most, if not all, of the affected ear; as of 2013, almost no evidence existed with which to judge whether these surgeries are effective. The inner ear itself can be surgically removed via labyrinthectomy, although hearing is always completely lost in the affected ear with this operation. The surgeon can also cut the nerve to the balance portion of the inner ear in a vestibular neurectomy. The hearing is often mostly preserved; however, the surgery involves cutting open into the lining of the brain, and a hospital stay of a few days for monitoring is required.
Poorly supported
As of 2014, betahistine is often used as it is inexpensive and safe; but evidence does not justify its use in MD.
Transtympanic micropressure pulses were investigated in two systematic reviews. Neither found evidence to justify this technique.
Intratympanic steroids were investigated in three systematic reviews. The data were found to be insufficient to decide if this therapy has positive effects.
Evidence does not support the use of alternative medicine such as acupuncture or herbal supplements.
Prognosis
Ménières disease usually starts confined to one ear; it extends to both ears in about 30% of cases. People may start out with only one symptom, but in MD all three appear with time. Hearing loss usually fluctuates in the beginning stages and becomes more permanent in later stages. MD has a course of 5–15 years, and people generally end up with mild disequilibrium, tinnitus, and moderate hearing loss in one ear.
Epidemiology
From 3 to 11% of diagnosed dizziness in neuro-otological clinics are due to MD. The annual incidence rate is estimated to be about 15 cases per 100,000 people and the prevalence rate is about 218 per 100,000, and around 15% of people with Menieres disease are older than 65. In around 9% of cases, a relative also had MD, indicating a genetic predisposition in some cases.The odds of MD are greater for people of white ethnicity, with severe obesity, and women. Several conditions are often comorbid with MD, including arthritis, psoriasis, gastroesophageal reflux disease, irritable bowel syndrome, and migraine.
History
The condition is named after the French physician Prosper Menière, who in an 1861 article described the main symptoms and was the first to suggest a single disorder for all of the symptoms, in the combined organ of balance and hearing in the inner ear.The American Academy of Otolaryngology–Head and Neck Surgery Committee on Hearing and Equilibrium set criteria for diagnosing MD, as well as defining two subcategories – cochlear (without vertigo) and vestibular (without deafness).In 1972, the academy defined criteria for diagnosing MD as:
Fluctuating, progressive, sensorineural deafness
Episodic, characteristic definitive spells of vertigo lasting 20 minutes to 24 hours with no unconsciousness, vestibular nystagmus always present.
Tinnitus (ringing in the ears, from mild to severe) is accompanied often by ear pain and a feeling of fullness in the affected ear; usually, the tinnitus is more severe before a spell of vertigo and lessens after the vertigo attack.
Attacks are characterized by periods of remission and exacerbation.In 1985, this list changed to alter wording, such as changing "deafness" to "hearing loss associated with tinnitus, characteristically of low frequencies" and requiring more than one attack of vertigo to diagnose. Finally in 1995, the list was again altered to allow for degrees of the disease:
Certain – Definite disease with histopathological confirmation
Definite – Requires two or more definitive episodes of vertigo with hearing loss plus tinnitus and/or aural fullness
Probable – Only one definitive episode of vertigo and the other symptoms and signs
Possible – Definitive vertigo with no associated hearing lossIn 2015, the International Classification for Vestibular Disorders Committee of the Barany Society published consensus diagnostic criteria in collaboration with the American Academy of Otolaryngology – Head and Neck Surgery, the European Academy of Otology and Neurootology, the Japan Society for Equilibrium Research, and the Korean Balance Society.
References
External links
Basura, Gregory J.; Adams, Meredith E.; Monfared, Ashkan; et al. (8 April 2020). "Clinical Practice Guideline: Ménières Disease". Otolaryngology–Head and Neck Surgery. 162 (2 suppl): S1–S55. doi:10.1177/0194599820909438. PMID 32267799. |
Hirschsprungs disease | Hirschsprungs disease (HD or HSCR) is a birth defect in which nerves are missing from parts of the intestine. The most prominent symptom is constipation. Other symptoms may include vomiting, abdominal pain, diarrhea and slow growth. Symptoms usually become apparent in the first two months of life. Complications may include enterocolitis, megacolon, bowel obstruction and intestinal perforation.The disorder may occur by itself or in association with other genetic disorders such as Down syndrome or Waardenburg syndrome. About half of isolated cases are linked to a specific genetic mutation, and about 20% occur within families. Some of these occur in an autosomal dominant manner. The cause of the remaining cases is unclear. If otherwise normal parents have one child with the condition, the next child has a 4% risk of being affected. The condition is divided into two main types, short-segment and long-segment, depending on how much of the bowel is affected. Rarely, the small bowel may be affected, as well. Diagnosis is based on symptoms and confirmed by biopsy.Treatment is generally by surgery to remove the affected section of bowel. The surgical procedure most often carried out is known as a "pull through". Occasionally, an intestinal transplantation may be recommended. Hirschsprungs disease occurs in about one in 5,000 of newborns. Males are more often affected than females. The condition is believed to have first been described in 1691 by Dutch anatomist Frederik Ruysch and is named after Danish physician Harald Hirschsprung following his description in 1888.
Signs and symptoms
Typically, Hirschsprung disease is diagnosed shortly after birth, although it may develop well into adulthood, because of the presence of megacolon, or because the baby fails to pass the first stool (meconium) within 48 hours of delivery. Normally, 90% of babies pass their first meconium within 24 hours, and 99% within 48 hours.Other symptoms include symptoms of bowel perforation such as vomiting, constipation, poor feeding, lethargy, and diarrhea. Symptoms of bowel obstruction would include vomiting of bile and abdominal distension. Those who pass stools after 36 to 48 hours after birth should raise suspicion of Hirschsprung disease. Such suspicion can also be risen if there is only passage of stools after suppository, rectal exam, or enema. Children who do not respond to constipation treatment for six months should also raise suspicion of such disease. Enterocolitis, an acute complication of Hirschsprung disease, is characterised by sudden onset of fever, abdominal distension, vomiting, passage of bloody stools or release of explosive gas or stools after rectal examination.Some cases are diagnosed later, into childhood, but usually before age 10. The child may experience fecal retention, constipation, or abdominal distention.
Associated syndromes
Hirschsprungs disease can also present as part of multi system disorders, such as:
Bardet–Biedl syndrome
Cartilage–hair hypoplasia
Congenital central hypoventilation syndrome
MEN2
Mowat–Wilson syndrome
Smith–Lemli–Opitz syndrome
Trisomy 21 (Down syndrome)
Some forms of Waardenburg syndrome
Cause
The disorder may occur by itself or in association with other genetic disorders such as Down syndrome. About half of isolated cases are linked to a specific genetic mutation and about 20% occur within families. Some of these occur in an autosomal dominant manner. The cause of the remaining cases is unclear. If otherwise normal parents have one child with the condition, the next child has a 4% risk of being affected.
Genetics
Several genes and specific regions on chromosomes (loci) have been shown or suggested to be associated with Hirschsprungs disease:
The RET proto-oncogene accounts for the highest proportion of both familial and sporadic cases, with a wide range of mutations scattered along its entire coding region. A proto-oncogene can cause cancer if it is mutated or overexpressed.
RET proto-oncogene
RET is a gene that codes for proteins that assist cells of the neural crest in their movement through the digestive tract during the development of the embryo. Those neural crest cells eventually form bundles of nerve cells called ganglions. EDNRB codes for proteins that connect these nerve cells to the digestive tract. Thus, mutations in these two genes could directly lead to the absence of certain nerve fibers in the colon. Research suggests that several genes are associated with Hirschsprungs disease. Also, new research suggests that mutations in genomic sequences involved in regulating EDNRB have a bigger impact on Hirschsprungs disease than previously thought.RET can mutate in many ways and is associated with Down syndrome. Since Down syndrome is comorbid in 2% of Hirschsprungs cases, a likelihood exists that RET is involved heavily in both Hirschsprungs disease and Down syndrome. RET is also associated with medullary thyroid cancer and neuroblastoma, which is a type of cancer common in children. Both of these disorders are more common in Hirschsprungs patients than in the general population. One function that RET controls is the travel of the neural crest cells through the intestines in the developing fetus. The earlier the RET mutation occurs in Hirschsprungs disease, the more severe the disorder becomes.
Other genes
Common and rare DNA variations in the neuregulin 1 (NRG1) and NRG3 (NRG3) were first shown to be associated with the disease in Chinese patients through a Genome Wide Association Study by the Hong Kong team in 2009 and 2012, respectively Subsequent studies in both Asian and Caucasian patients confirmed the initial findings by the University of Hong Kong. Both rare and common variants in these two genes have been identified in additional Chinese, Thai, Korean, Indonesian, and Spanish patients. These two genes are known to play a role in the formation of the enteric nervous system; thus, they are likely to be involved in the pathology of Hirschsprungs disease, at least in some cases.Another gene associated with this condition is NADPH oxidase, EF-hand calcium binding domain 5 (NOX5). This gene is located on the long arm of chromosome 15 (15q23).
Pathophysiology
During normal prenatal development, cells from the neural crest migrate into the large intestine (colon) to form the networks of nerves called the myenteric plexus (Auerbach plexus) (between the smooth muscle layers of the gastrointestinal tract wall) and the submucosal plexus (Meissner plexus) (within the submucosa of the gastrointestinal tract wall). In Hirschsprung disease, the migration is not complete and part of the colon lacks these nerve bodies that regulate the activity of the colon. The affected segment of the colon cannot relax and pass stool through the colon, creating an obstruction.The most accepted theory of the cause of Hirschsprung is a defect in the craniocaudal migration of neuroblasts originating from the neural crest that occurs during the first 12 weeks of gestation. Defects in the differentiation of neuroblasts into ganglion cells and accelerated ganglion cell destruction within the intestine may also contribute to the disorder.This lack of ganglion cells in the myenteric and submucosal plexus is well documented in Hirschsprungs disease. With Hirschsprungs disease, the segment lacking neurons (aganglionic) becomes constricted, causing the normal, proximal section of bowel to become distended with feces. This narrowing of the distal colon and the failure of relaxation in the aganglionic segment are thought to be caused by the lack of neurons containing nitric oxide synthase.The most cited feature is absence of ganglion cells: notably in males, 75% have none in the end of the colon (rectosigmoid) and 8% lack ganglion cells in the entire colon. The enlarged section of the bowel is found proximally, while the narrowed, aganglionic section is found distally, closer to the end of the bowel. The absence of ganglion cells results in a persistent overstimulation of nerves in the affected region, resulting in contraction.The equivalent disease in horses is lethal white syndrome.
Diagnosis
Definitive diagnosis is made by suction biopsy of the distally narrowed segment. A histologic examination of the tissue would show a lack of ganglionic nerve cells. Diagnostic techniques involve anorectal manometry, barium enema, and rectal biopsy.
The suction rectal biopsy is considered the current international gold standard in the diagnosis of Hirschsprungs disease.Radiologic findings may also assist with diagnosis. Cineanography (fluoroscopy of contrast medium passing anorectal region) assists in determining the level of the affected intestines.
Treatment
Treatment of Hirschsprungs disease consists of surgical removal (resection) of the abnormal section of the colon, followed by reanastomosis.
Colostomy
The first stage of treatment used to be a reversible colostomy. In this approach, the healthy end of the large intestine is cut and attached to an opening created on the front of the abdomen. The contents of the bowel are discharged through the hole in the abdomen and into a bag. Later, when the patients weight, age, and condition are right, the "new" functional end of the bowel is connected with the anus. The first surgical treatment involving surgical resection followed by reanastomosis without a colostomy occurred as early as 1933 by Doctor Baird in Birmingham on a one-year-old boy.
Other procedures
The Swedish-American surgeon Orvar Swenson (1909–2012), who discovered the cause of Hirschsprungs, first performed its surgical treatment, the pull-through surgery, in 1948. The pull-through procedure repairs the colon by connecting the functioning portion of the bowel to the anus. The pull-through procedure is the typical method for treating Hirschsprungs in younger patients. Swenson devised the original procedure, and the pull-through surgery has been modified many times.
Currently, several different surgical approaches are used, which include the Swenson, Soave, Duhamel, and Boley procedures. The Swenson procedure leaves a small portion of the diseased bowel. The Soave procedure, named after the Italian pediatric surgeon, Franco Soave (1917–1984), leaves the outer wall of the colon unaltered. The Boley procedure, pioneered by the American surgeon, Scott Boley (b. 1941), is a small modification of the Soave procedure, so the term "Soave-Boley" procedure is sometimes used. The Duhamel procedure, named for the French pediatric surgeon Bernard Duhamel (1917–1996), uses a surgical stapler to connect the good and bad bowel.For the 15% of children who do not obtain full bowel control, other treatments are available. Constipation may be remedied by laxatives or a high-fiber diet. In those patients, serious dehydration can play a major factor in their lifestyles. A lack of bowel control may be addressed by an ileostomy – similar to a colostomy, but uses the end of the small intestine rather than the colon. The Malone antegrade colonic enema (ACE) is also an option. In a Malone ACE, a tube goes through the abdominal wall to the appendix, or if available, to the colon. The bowel is then flushed daily. Children as young as 6 years of age may administer this daily flush on their own.If the affected portion of the lower intestine is restricted to the lower portion of the rectum, other surgical procedures may be performed, such as a posterior rectal myectomy. The prognosis is good in 70% of cases. Chronic postoperative constipation is present in 7 to 8% of the operated cases. Postoperative enterocolitis, a severe manifestation, is present in the 10–20% of operated patients.
Epidemiology
According to a 1984 study conducted in Maryland, Hirschsprungs disease appears in 18.6 per 100,000 live births. In Japan, it occurs at a similar rate of about one in 5,000 births (20 per 100,000). It is more common in male than female (4.32:1) and in white rather than nonwhite. Nine percent of the Hirschsprung cases were also diagnosed as having Down syndrome. Most cases are diagnosed before the patient is 10 years of age.
History
The first report of Hirschsprungs disease dates to 1691, when it was described by Dutch anatomist Frederik Ruysch. However, the disease is named after Harald Hirschsprung, the Danish physician who first described two infants who died of this disorder in 1888.Hirschsprungs disease is a congenital disorder of the colon in which certain nerve cells, known as ganglion cells, are absent, causing chronic constipation. In patients with Hirschsprung disease, both myenteric and submucosal plexuses are absent. A barium enema is the mainstay of diagnosis of Hirschsprungs, though a rectal biopsy showing the lack of ganglion cells is the only certain method of diagnosis.The first publication on an important genetic discovery of the disease was from Martucciello Giuseppe et al. in 1992. The authors described a case of a patient with total colonic aganglionosis associated with a 46, XX, del 10 (q11.21 q21.2) karyotype. The major gene of Hirschsprung disease was identified in this chromosomal 10 region, it was the RET proto-oncogene.The usual treatment is "pull-through" surgery where the portion of the colon that does have nerve cells is pulled through and sewn over the part that lacks nerve cells. For a long time, Hirschsprungs was considered a multifactorial disorder, where a combination of nature and nurture was considered to be the cause. However, in August 1993, two articles by independent groups in Nature Genetics said that Hirschsprungs disease could be mapped to a stretch of chromosome 10.This research also suggested that a single gene was responsible for the disorder. However, the researchers were unable to isolate it.
See also
Achalasia
Ileus, failure of peristaltic muscle activity in the gut
Intestinal neuronal dysplasia
Hirschsprungs disease-type D brachydactyly syndrome
References
External links
Hirschsprungs disease at Curlie |
Rib fracture | A rib fracture is a break in a rib bone. This typically results in chest pain that is worse with inspiration. Bruising may occur at the site of the break. When several ribs are broken in several places a flail chest results. Potential complications include a pneumothorax, pulmonary contusion, and pneumonia.Rib fractures usually occur from a direct blow to the chest such as during a motor vehicle collision or from a crush injury. Coughing or metastatic cancer may also result in a broken rib. The middle ribs are most commonly fractured. Fractures of the first or second ribs are more likely to be associated with complications. Diagnosis can be made based on symptoms and supported by medical imaging.Pain control is an important part of treatment. This may include the use of paracetamol (acetaminophen), NSAIDs, or opioids. A nerve block may be another option. While fractured ribs can be wrapped, this may increase complications. In those with a flail chest, surgery may improve outcomes. They are a common injury following trauma.
Signs and symptoms
This typically results in chest pain that is worse with inspiration. Bruising may occur at the site of the break.
Complications
When several ribs are broken in several places a flail chest results. Potential complications include a pneumothorax, pulmonary contusion, and pneumonia.
Causes
Rib fractures can occur with or without direct trauma during recreational activity. Cardiopulmonary resuscitation (CPR) has also been known to cause thoracic injury, including but not limited to rib and sternum fractures. They can also occur as a consequence of diseases such as cancer or rheumatoid arthritis. While for elderly individuals a fall can cause a rib fracture, in adults automobile accidents are a common event for such an injury.
Diagnosis
Signs of a broken rib may include:
Pain on inhalation
Swelling in chest area
Bruise in chest area
Increasing shortness of breath
Coughing up blood (rib may have damaged lung)Plain X-rays often pick up displaced fractures but often miss undisplaced fractures. CT scanning is generally able to pick up both types of fractures.Because children have more flexible chest walls than adults do, their ribs are more likely to bend than to break; therefore the presence of rib fractures in children is evidence of a significant amount of force and may indicate severe thoracic injuries such as pulmonary contusion. Rib fractures are also a sign of more serious injury in elderly people.
Treatment
There is no specific treatment for rib fractures, but various supportive measures can be taken. In simple rib fractures, pain can lead to reduced movement and cough suppression; this can contribute to formation of secondary chest infection. Flail chest is a potentially life-threatening injury and will often require a period of assisted ventilation. Flail chest and first rib fractures are high-energy injuries and should prompt investigation of damage to underlying viscera (e.g., lung contusion) or remotely (e.g., cervical spine injury). Spontaneous fractures in athletes generally require a cessation of the cause, e.g., time off rowing, while maintaining cardiovascular fitness.
Nerve blocks
Nerve blocks that may be used to help with pain and reduce respiratory complications related to rib fractures. These include rhomboid intercostal block, epidural anesthesia, paravertebral block, erector spinae plane block and serratus anterior plane block. There is very little evidence to support the use of one nerve block over another on the basis of analgesia or safety.
Surgery
Treatment options for internal fixation/repair of rib fractures include:
Judet and/or sanchez plates/struts are a metal plate with strips that bend around the rib and then is further secured with sutures.
There are different specialist rib fixation systems on the market. They have two options: a precontoured metal plate that uses screws to secure the plate to the rib; and/or an intramedullary splint which is tunneled into the rib and secured with a set screw.
Anterior locking plates are metal plates that have holes for screws throughout the plate. The plate is positioned over the rib and screwed into the bone at the desired position. The plates may be bent to match the contour of the section.
U-plates can also be used as they clamp on to the superior aspect of the ribs using locking screws.
See also
Pulmonary hygiene
References
== External links == |
Thromboangiitis obliterans | Thromboangiitis obliterans, also known as Buerger disease (English ; German: [ˈbʏʁɡɐ]), is a recurring progressive inflammation and thrombosis (clotting) of small and medium arteries and veins of the hands and feet. It is strongly associated with use of tobacco products, primarily from smoking, but is also associated with smokeless tobacco.
Signs and symptoms
There is a recurrent acute and chronic inflammation and thrombosis of arteries and veins of the hands and feet. The main symptom is pain in the affected areas, at rest and while walking (claudication). The impaired circulation increases sensitivity to cold. Peripheral pulses are diminished or absent. There are color changes in the extremities. The colour may range from cyanotic blue to reddish blue. Skin becomes thin and shiny. Hair growth is reduced. Ulcerations and gangrene in the extremities are common complications, often resulting in the need for amputation of the involved extremity.
Pathophysiology
There are characteristic pathologic findings of acute inflammation and thrombosis (clotting) of arteries and veins of the hands and feet (the lower limbs being more common). The mechanisms underlying Buergers disease are still largely unknown, but smoking and tobacco consumption are major factors associated with it. It has been suggested that the tobacco may trigger an immune response in susceptible persons or it may unmask a clotting defect, either of which could incite an inflammatory reaction of the vessel wall. This eventually leads to vasculitis and ischemic changes in distal parts of limbs.A possible role for Rickettsia in this disease has been proposed.
Diagnosis
A concrete diagnosis of thromboangiitis obliterans is often difficult as it relies heavily on exclusion of other conditions. The commonly followed diagnostic criteria are outlined below although the criteria tend to differ slightly from author to author. Olin (2000) proposes the following criteria:
Typically between 20 and 40 years old and male, although recently females have been diagnosed.
Current (or recent) history of tobacco use.
Presence of distal extremity ischemia (indicated by claudication, pain at rest, ischemic ulcers or gangrene) documented by noninvasive vascular testing such as ultrasound.
Exclusion of other autoimmune diseases, hypercoagulable states, and diabetes mellitus by laboratory tests.
Exclusion of a proximal source of emboli by echocardiography and arteriography.
Consistent arteriographic findings in the clinically involved and noninvolved limbs.Buergers disease can be mimicked by a wide variety of other diseases that cause diminished blood flow to the extremities. These other disorders must be ruled out with an aggressive evaluation, because their treatments differ substantially from that of Buergers disease, for which there is no treatment known to be effective.Some diseases with which Buergers disease may be confused include atherosclerosis (build-up of cholesterol plaques in the arteries), endocarditis (an infection of the lining of the heart), other types of vasculitis, severe Raynauds phenomenon associated with connective tissue disorders (e.g., lupus or scleroderma), clotting disorders or the production of clots in the blood.Angiograms of the upper and lower extremities can be helpful in making the diagnosis of Buergers disease. In the proper clinical setting, certain angiographic findings are diagnostic of Buergers. These findings include a "corkscrew" appearance of arteries that result from vascular damage, particularly the arteries in the region of the wrists and ankles. Collateral circulation gives "tree root" or "spider leg" appearance. Angiograms may also show occlusions (blockages) or stenosis (narrowings) in multiple areas of both the arms and legs. Distal plethysmography also yields useful information about circulatory status in digits.
To rule out other forms of vasculitis (by excluding involvement of vascular regions atypical for Buergers), it is sometimes necessary to perform angiograms of other body regions (e.g., a mesenteric angiogram).Skin biopsies of affected extremities are rarely performed because of the frequent concern that a biopsy site near an area poorly perfused with blood will not heal well.
Prevention
The cause of the disease is thought to be autoimmune in nature and heavily linked to tobacco use in patients with Buergers as primary disease.
Treatment
Smoking cessation has been shown to slow the progression of the disease and decrease the severity of amputation in most patients, but does not halt the progression.
In acute cases, drugs and procedures which cause vasodilation are effective in reducing pain experienced by patient. For example, prostaglandins like Limaprost are vasodilators and give relief of pain, but do not help in changing the course of disease. Epidural anesthesia and hyperbaric oxygen therapy also have vasodilator effect. There is moderate certainty evidence that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for relieving rest pain and healing ischemic ulcers. No difference have been detected between iloprost or clinprost (prostacyclin) and alprostadil (prostaglandin analogue) for relieving pain and healing ulcers.In chronic cases, lumbar sympathectomy may be occasionally helpful. It reduces vasoconstriction and increases blood flow to limb. It aids in healing and giving relief from pain of ischemic ulcers. Bypass can sometimes be helpful in treating limbs with poor perfusion secondary to this disease. Use of vascular growth factor and stem cell injections have been showing promise in clinical studies. There may be a benefit of using bone marrow-derived stem cells in healing ulcers and improving pain-free walking distance, but larger, high-quality trials are needed. Debridement is done in necrotic ulcers. In gangrenous digits, amputation is frequently required. Below-knee and above-knee amputation is rarely required.Streptokinase has been proposed as adjuvant therapy in some cases.Despite the clear presence of inflammation in this disorder, anti-inflammatory agents such as corticosteroids have not been shown to be beneficial in healing, but do have significant anti-inflammatory and pain relief qualities in low dosage intermittent form. Similarly, strategies of anticoagulation have not proven effective.
physical therapy: interferential current therapy to decrease inflammation.
Prognosis
Buergers is not immediately fatal. Amputation is common and major amputations (of limbs rather than fingers/toes) are almost twice as common in patients who continue to smoke. Prognosis markedly improves if a person quits smoking. Female patients tend to show much higher longevity rates than men. The only known way to slow the progression of the disease is to abstain from all tobacco products.
Epidemiology
Buergers is more common among men than women. Although present worldwide, it is more prevalent in the Middle East and Far East. Incidence of thromboangiitis obliterans is 8 to 12 per 100,000 adults in the United States (0.75% of all patients with peripheral vascular disease).
History
Buergers disease was first reported by Felix von Winiwarter in 1879 in Austria. It was not until 1908, however, that the disease was given its first accurate pathological description, by Leo Buerger at Mount Sinai Hospital in New York City. Buerger called it "presenile spontaneous gangrene" after studying amputations in 11 patients.
Notable people affected
As reported by Alan Michie in God Save the Queen, published in 1952 (see pages 194 and following), King George VI was diagnosed with the disease on 12 November 1948. Both legs were affected, the right more seriously than the left. The kings doctors prescribed complete rest and electric treatment to stimulate circulation, but as they were either unaware of the connection between the disease and smoking (the king was a heavy smoker) or unable to persuade the king to stop smoking, the disease failed to respond to their treatment. On 12 March 1949, the king underwent a lumbar sympathectomy, performed at Buckingham Palace by James R. Learmonth. The operation, as such, was successful, but the king was warned that it was a palliative, not a cure, and that there could be no assurance that the disease would not grow worse. From all accounts, the king continued to smoke.The author and journalist John McBeth describes his experiences of the disease, and treatment for it, in the chapter "Year of the Leg" in his book Reporter: Forty Years Covering Asia.Philippine president Rodrigo Duterte disclosed in 2015 that he has Buergers disease.
References
Further reading
External links
00394 at CHORUSArkkila, PE, (2006), Thromboangiitis obliterans (Buergers disease), Orphanet Journal of Rare Diseases |
Dyshidrosis | Dyshidrosis is a type of dermatitis that is characterized by itchy blisters on the palms of the hands and bottoms of the feet. Blisters are generally one to two millimeters in size and heal over three weeks. However, they often recur. Redness is not usually present. Repeated attacks may result in fissures and skin thickening.The cause is unknown. Triggers may include allergens, physical or mental stress, frequent hand washing, or metals. Diagnosis is typically based on what it looks like and the symptoms. Allergy testing and culture may be done to rule out other problems. Other conditions that produce similar symptoms include pustular psoriasis and scabies.Avoiding triggers may be useful, as may a barrier cream. Treatment is generally with steroid cream. High strength steroid creams may be required for the first week or two. Antihistamines may be used to help with the itch. If this is not effective steroid pills, tacrolimus, or psoralen plus ultraviolet A (PUVA) may be tried.About 1 in 2,000 people are affected in Sweden. Males and females appear to be affected equally. It explains about one in five cases of hand dermatitis. The first description was in 1873. The name comes from the word "dyshidrotic", meaning "difficult sweating", as problems with sweating was once believed to be the cause.
Signs and symptoms
Dyshidrosis has been described as having the following characteristics:
Itchiness of the palms or soles, followed by the sudden development of intensely itchy small blisters on the sides of the fingers, the palms or the feet.
These blisters are often described as having a "tapioca pudding" appearance.
After a few weeks, the small blisters eventually disappear as the top layer of skin falls off.
These eruptions do not occur elsewhere on the body.
The eruptions may be symmetrical.
Causes
The exact causes of dyshidrosis are unknown. Food allergens may be involved in certain cases. Cases studies have implicated a wide range of foods including tuna, tomato, pineapple, chocolate, coffee, and spices among others. A number of studies have implicated balsam of Peru. A 2013 study found that dyshydrosis on the hands increased among those allergic to house dust mites, following inhalation of house dust mite allergen.Id reaction and irritant contact dermatitis are possible causes.
Diagnosis
Dyshidrosis is diagnosed clinically, by gathering a patients history and making careful observations (see signs and symptoms section). Severity of symptoms can also be assessed using the dyshidrotic eczema area and severity index (DASI). The DASI has been designed for clinical trials and is not typically used in practice.
Treatment
There are many treatments available for dyshidrosis. However, few of them have been developed or tested specifically on the condition.
Barriers to moisture and irritants, including barrier creams and gloves.
Topical steroids – while useful, can be dangerous long-term due to the skin-thinning side-effects, which are particularly troublesome in the context of hand dyshidrosis, due to the amount of toxins and bacteria the hands typically come in contact with.
Potassium permanganate dilute solution soaks – also popular, and used to dry out the vesicles, and kill off superficial Staphylococcus aureus, but it can also be very painful. Undiluted it may cause significant burning.
Dapsone (diamino-diphenyl sulfone), an antibacterial, has been recommended for the treatment of dyshidrosis in some chronic cases.
Antihistamines: Fexofenadine up to 180 mg per day.
Alitretinoin (9-cis-retinoic acid) has been approved for prescription in the UK. It is specifically used for chronic hand and foot eczema. It is made by Basilea of Switzerland (BAL 4079).
Systemic steroids can be taken orally to treat especially acute and severe cases of dyshidrosis.
Epidemiology
About 1 in 2,000 people are affected in Sweden. Males and females appear to be affected equally.
Synonyms
Dyshidrosis is also known as pompholyx, a term originating from the Greek word for "bubble".
See also
Dermatitis herpetiformis – a similar condition caused by celiac and often mistaken for dyshidrosis.
Epidermolysis bullosa – a genetic disorder that causes similar, albeit more severe, symptoms to those of dyshidrosis.
References
External links
Images of dyshidrotic eczema at Skinsight
Pompholyx at DermNet NZ (New Zealand Dermatological Society Incorporated) |
Testicular torsion | Testicular torsion occurs when the spermatic cord (from which the testicle is suspended) twists, cutting off the blood supply to the testicle. The most common symptom in children is sudden, severe testicular pain. The testicle may be higher than usual in the scrotum and vomiting may occur. In newborns, pain is often absent and instead the scrotum may become discolored or the testicle may disappear from its usual place.Most of those affected have no obvious prior underlying health problems. Testicular tumor or prior trauma may increase risk. Other risk factors include a congenital malformation known as a "bell-clapper deformity" wherein the testis is inadequately attached to the scrotum allowing it to move more freely and thus potentially twist. Cold temperatures may also be a risk factor. The diagnosis should usually be made based on the presenting symptoms, but requires timely diagnosis and treatment to avoid testicular loss. An ultrasound can be useful when the diagnosis is unclear.Treatment is by physically untwisting the testicle, if possible, followed by surgery. Pain can be treated with opioids. Outcome depends on time to correction. If successfully treated within six hours onset, it is often good. However, if delayed for 12 or more hours the testicle is typically not salvageable. About 40% of people require removal of the testicle.It is most common just after birth and during puberty. It occurs in about 1 in 4,000 to 1 in 25,000 males under 25 years of age each year. Of children with testicular pain of rapid onset, testicular torsion is the cause of about 10% of cases. Complications may include an inability to have children. The condition was first described in 1840 by Louis Delasiauve.
Signs and symptoms
Testicular torsion usually presents with severe testicular pain or pain in the groin and lower abdomen. Pain generally begins suddenly and typically involves only one side. There is often associated nausea and vomiting. The testicle may lie higher in the scrotum due to twisting and subsequent shortening of the spermatic cord or may be positioned in a horizontal orientation. Mild warmth and redness of the overlying area may be present. Elevation of the testicle may worsen the pain. Urinary symptoms, such as pain or increased frequency of urination are also typically absent. Symptom onset often follows physical activity or trauma to the testes or scrotum. Children with testicular torsion may awaken with testicular or abdominal pain in the middle of the night or in the morning. There may be a history of previous, similar episodes of scrotal pain due to prior transient testicular torsion with spontaneous resolution.
Complications
Testicular infarction: Testicular damage occurs as a consequence of decreased blood flow, and therefore decreased oxygen and nutrient supply, to the testicle. If the testicle is not viable during surgical exploration, it must be removed to prevent further necrosis, or tissue death.
Infertility: The impact of testicular torsion on long-term fertility is not yet fully understood. However, testicular torsion may cause abnormal sperm function on semen analysis, although these abnormalities are more likely to be found in adolescents and in adults. Torsion does not seem to affect long-term sperm function in neonates. The cause of abnormal sperm function is thought to be due to the following mechanisms:
Immunological theory, also known as "sympathetic orchidopathia": It is thought that following injury to the testicle, the bodys immune system is activated to clean up damaged cells. In the process, it creates anti-testicular cell antibodies, or proteins that cross the injured blood-testis barrier and damage both the affected and contralateral testicles.
Abnormalities in microcirculation within the testicle
Reperfusion injury: This type of injury is seen in tissues that have been deprived of blood supply for a prolonged period.
Gangrene, or a type of tissue damage caused by lack of blood supply, of the testis.
Sepsis, in extremely rare cases (0,03%), if not treated for a long period of time, it could lead to sepsis and cause severe life-threatening infections and injuries through the blood and organs, which could lead to death.
Recurrence of torsion may occur even after surgical fixation, although this is very unlikely.
Psychological impact of losing a testicle.
Risk factors
Most of those affected with testicular torsion have no prior underlying health problems or predisposing conditions. However, there are certain factors that may increase risk of testicular torsion. A larger testicle either due to normal variation or testicular tumor increases the risk of torsion. Similarly, the presence of a mass or malignancy involving the spermatic cord can also predispose to torsion.Age is also an important risk factor for torsion. Torsion most commonly occurs either in the newborn or just before or during puberty. Testicular torsion often occurs before or during puberty, prior to complete testicular descent. Epididymitis is more commonly a postpubertal condition.Several congenital anatomic malformations or variations in the testicle or the surrounding structures may allow for increased scrotal rotation and increase the risk of testicular torsion. A congenital malformation of the processus vaginalis known as "bell-clapper deformity" accounts for 90% of all cases. In this condition, rather than the testes attaching posteriorly to the inner lining of the scrotum by the mesorchium, the mesorchium terminates early and the testis is free floating in the tunica vaginalis. Other anatomic risk factors include horizontal lie of the testicle or a spermatic cord with a long intrascrotal portion. Cryptorchidisim is also a risk factor for torsion with some studies proposing a 10-fold higher risk.
Testicular torsion may also be caused by trauma to the scrotum or exercise (in particular, bicycle riding), however only about 4-8% of cases are the result of trauma. There is thought to be a possible genetic basis for predisposition to torsion, based on multiple published reports of familial testicular torsion. There is controversy whether cold weather months are associated with an increased risk.
Pathophysiology
Testicular torsion occurs when there is mechanical twisting of the spermatic cord, which suspends the testicle within the scrotum and contains the testicular artery and vein. Twisting of the cord reduces or eliminates blood flow to the testicle. The degree of arterial and venous obstruction depends on the duration and severity of the torsion event. Typically, venous blood flow is compromised first. The increase in venous pressure subsequently causes decreased arterial blood flow, leading to decreased oxygen supply to the testicle, and if untreated, testicular infarction.It is also believed that torsion occurring during fetal development can lead to so-called neonatal torsion or vanishing testis, and is one of the causes of an infant being born with monorchism (one testicle).
Intermittent testicular torsion
Intermittent testicular torsion (ITT) is a less serious but chronic variant of torsion. It is characterized by intermittent scrotal or testicular pain, followed by eventual spontaneous detorsion and resolution of pain. Nausea and vomiting may also occur.: 150 Though less pressing, such individuals are at significant risk of complete torsion and possible subsequent orchiectomy and the recommended treatment is elective bilateral orchiopexy. Ninety-seven percent of patients who undergo such surgery experience complete relief from their symptoms.: 316
Extravaginal testicular torsion
Torsion occurring outside of the tunica vaginalis, when the testis and gubernaculum can rotate freely, is termed an extravaginal testicular torsion. This type occurs exclusively in newborns, however, newborns can be affected by other testicular torsion variants as well. Neonates experiencing such a torsion typically present with painless scrotal swelling, discoloration, and a firm, painless mass in the scrotum. Such testes are usually necrotic from birth and must be removed surgically.: 315 The exact cause of or specific risk factors for extravaginal torsion in this population remain unclear.
Intravaginal testicular torsion
Intravaginal testicular torsion occurs when the testicle rotates on the spermatic cord within the tunica vaginalis. This variant more commonly occurs in older children and adults. The "bell-clapper deformity," in which there is inappropriately high attachment of the tunica vaginalis over the spermatic cord and failure of the normal posterior attachment of the testicle to the inner scrotum, which allows the testicle to move freely within the tunica vaginalis and predisposes to intravaginal testicular torsion.
Torsion of the testicular appendix
The testicular appendix is located in the upper pole of the testicle. It is an embryonic remnant that has no known function, but is at risk for torsion events. This type of torsion is the most common cause of acute scrotal pain in boys ages 7–14. Its appearance is similar to that of testicular torsion but the onset of pain is typically more gradual. Palpation reveals a small firm nodule on the upper portion of the testis which displays a characteristic "blue dot sign". This is the appendix of the testis which has become discolored and is noticeably blue through the skin. Unlike other torsions, however, the cremasteric reflex is still active. Typical treatment involves the use of over-the-counter analgesics and the condition resolves within 2–3 days.: 316
Torsion of the undescended testicle
The undescended testis is at increased risk of testicular torsion. The mechanism for torsion in the undescended testicle is not fully understood, though it may be due to abnormal contractions of the cremaster muscle, which covers the testicle and spermatic cord and is responsible for raising and lowering the testicle to regulate scrotal temperature. The undescended testicle is also at higher risk for testicular tumor, which due to the increased weight and size compared to a healthy testicle can predispose to torsion.
Diagnosis
The diagnosis should generally be made based on the presenting symptoms. An ultrasound can be useful when the diagnosis is unclear. However, imaging should not delay surgical intervention as complications develop with prolonged ischemia. Immediate surgery is recommended regardless of imaging findings if there is a high degree of suspicion based on history and physical examination.Given the treatment implications of testicular torsion, it is important to distinguish testicular torsion from other causes of testicular pain, such as epididymitis, which can present similarly. While both conditions can cause testicular pain, the pain of epididymitis is typically localized to the epididymis at the rear pole of the testicle. Epididymitis may also be characterized by discoloration and swelling of the testis, and fever. The cremasteric reflex in epididymitis is usually present. Testicular torsion, or more probably impending testicular infarction, can also produce a low-grade fever. There is often an absent or decreased cremasteric reflex.
Clinical exam
The absence of the cremasteric reflex in an acutely painful testicle is most indicative of testicular torsion (the twisting of the spermatic cord of the testicle makes reflexive responses all but impossible). The cremasteric reflex normally causes elevation of the testicle by stroking the inner thigh. Absence is especially common in children, but its presence does not exclude a diagnosis of testicular torsion.On physical examination, the testis can be swollen, tender, high-riding, and with an abnormal transverse lie.Prehns sign, a classic physical exam finding, has not been reliable in distinguishing torsion from other causes of testicular pain such as epididymitis. The individual will not usually have a fever, though nausea is common.
Imaging
A doppler ultrasound scan of the scrotum can identify the absence of blood flow in the twisted testicle and is nearly 90% accurate in diagnosis. It can also help distinguish torsion from epididymitis.Radionuclide scanning (scintigraphy) of the scrotum is the most accurate imaging technique, but it is not routinely available, particularly with the urgency that might be required. The agent of choice for this purpose is technetium-99m pertechnetate. Initially it provides a radionuclide angiogram, followed by a static image after the radionuclide has perfused the tissue. In the healthy patient, initial images show symmetric flow to the testes, and delayed images show uniformly symmetric activity. In testicular torsion, the images may show heterogenous activity within the affected testicle.
Treatment
Testicular torsion is a surgical emergency that requires immediate intervention to restore the flow of blood to the testicle. If treated either manually or surgically within six hours, there is a high chance (approximately 90%) of saving the testicle. At 12 hours the rate decreases to 50%; at 24 hours it drops to 10%, and after 24 hours the ability to save the testicle approaches 0, although salvage of the testicle has been reported beyond 24 hours. About 40% of cases result in loss of the testicle.With prompt diagnosis and treatment the testicle can often be saved. Typically, when a torsion takes place, the surface of the testicle has rotated towards the midline of the body. Non-surgical correction can sometimes be accomplished by manually rotating the testicle in the opposite direction (i.e., outward, towards the thigh); if this is initially unsuccessful, a forced manual rotation in the other direction may correct the problem.: 149 The success rate of manual detorsion is not known with confidence.
When salvage of the testicle is accomplished, long-term testicular damage is common. Testicular size is often diminished, and injury to the unaffected testicle is common. The effect of a torsion event on long-term fertility is not fully understood.A repeat doppler ultrasound scan may confirm restoration of blood flow to the testicle following manual detorsion. However, surgical exploration is often performed in order to assess the health and viability of the testicle. An orchiopexy is performed to both the affected and unaffected testicles in order to prevent recurrence. If the testis is not viable, it is removed (orchiectomy).
Epidemiology
Torsion is most frequent among adolescents with about 65% of cases presenting between 12 and 18 years of age. It is the most common cause of rapid onset testicular pain and swelling in people under 18 years old. It occurs in about 1 in 4,000 to 1 per 25,000 males per year before 25 years of age; but it can occur at any age, including infancy.: 149
See also
Ovarian torsion – equivalent condition in females.
Epididymitis – can cause testicular pain and present similarly to testicular torsion.
References
== External links == |
Pelvic inflammatory disease | Pelvic inflammatory disease, also known as pelvic inflammatory disorder (PID), is an infection of the upper part of the female reproductive system, namely the uterus, fallopian tubes, and ovaries, and inside of the pelvis. Often, there may be no symptoms. Signs and symptoms, when present, may include lower abdominal pain, vaginal discharge, fever, burning with urination, pain with sex, bleeding after sex, or irregular menstruation. Untreated PID can result in long-term complications including infertility, ectopic pregnancy, chronic pelvic pain, and cancer.The disease is caused by bacteria that spread from the vagina and cervix. Infections by Neisseria gonorrhoeae or Chlamydia trachomatis are present in 75 to 90 percent of cases. Often, multiple different bacteria are involved. Without treatment, about 10 percent of those with a chlamydial infection and 40 percent of those with a gonorrhea infection will develop PID. Risk factors are generally similar to those of sexually transmitted infections and include a high number of sexual partners and drug use. Vaginal douching may also increase the risk. The diagnosis is typically based on the presenting signs and symptoms. It is recommended that the disease be considered in all women of childbearing age who have lower abdominal pain. A definitive diagnosis of PID is made by finding pus involving the fallopian tubes during surgery. Ultrasound may also be useful in diagnosis.Efforts to prevent the disease include not having sex or having few sexual partners and using condoms. Screening women at risk for chlamydial infection followed by treatment decreases the risk of PID. If the diagnosis is suspected, treatment is typically advised. Treating a womans sexual partners should also occur. In those with mild or moderate symptoms, a single injection of the antibiotic ceftriaxone along with two weeks of doxycycline and possibly metronidazole by mouth is recommended. For those who do not improve after three days or who have severe disease, intravenous antibiotics should be used.Globally, about 106 million cases of chlamydia and 106 million cases of gonorrhea occurred in 2008. The number of cases of PID, however, is not clear. It is estimated to affect about 1.5 percent of young women yearly. In the United States, PID is estimated to affect about one million people each year. A type of intrauterine device (IUD) known as the Dalkon shield led to increased rates of PID in the 1970s. Current IUDs are not associated with this problem after the first month.
Signs and symptoms
Symptoms in PID range from none to severe. If there are symptoms, fever, cervical motion tenderness, lower abdominal pain, new or different discharge, painful intercourse, uterine tenderness, adnexal tenderness, or irregular menstruation may be noted.Other complications include endometritis, salpingitis, tubo-ovarian abscess, pelvic peritonitis, periappendicitis, and perihepatitis.
Complications
PID can cause scarring inside the reproductive system, which can later cause serious complications, including chronic pelvic pain, infertility, ectopic pregnancy (the leading cause of pregnancy-related deaths in adult females), and other complications of pregnancy. Occasionally, the infection can spread to the peritoneum causing inflammation and the formation of scar tissue on the external surface of the liver (Fitz-Hugh–Curtis syndrome).
Cause
Chlamydia trachomatis and Neisseria gonorrhoeae are usually the main cause of PID. Data suggest that PID is often polymicrobial. Isolated anaerobes and facultative microorganisms have been obtained from the upper genital tract. N. gonorrhoeae has been isolated from fallopian tubes, facultative and anaerobic organisms were recovered from endometrial tissues.The anatomical structure of the internal organs and tissues of the female reproductive tract provides a pathway for pathogens to ascend from the vagina to the pelvic cavity thorough the infundibulum. The disturbance of the naturally occurring vaginal microbiota associated with bacterial vaginosis increases the risk of PID.N. gonorrhoea and C. trachomatis are the most common organisms. The least common were infections caused exclusively by anaerobes and facultative organisms. Anaerobes and facultative bacteria were also isolated from 50 percent of the patients from whom Chlamydia and Neisseria were recovered; thus, anaerobes and facultative bacteria were present in the upper genital tract of nearly two-thirds of the PID patients. PCR and serological tests have associated extremely fastidious organism with endometritis, PID, and tubal factor infertility. Microorganisms associated with PID are listed below.Rarely cases of PID have developed in people who have stated they have never had sex.
Bacteria
Diagnosis
Upon a pelvic examination, cervical motion, uterine, or adnexal tenderness will be experienced. Mucopurulent cervicitis and or urethritis may be observed. In severe cases more testing may be required such as laparoscopy, intra-abdominal bacteria sampling and culturing, or tissue biopsy.Laparoscopy can visualize "violin-string" adhesions, characteristic of Fitz-Hugh–Curtis perihepatitis and other abscesses that may be present.Other imaging methods, such as ultrasonography, computed tomography (CT), and magnetic imaging (MRI), can aid in diagnosis. Blood tests can also help identify the presence of infection: the erythrocyte sedimentation rate (ESR), the C-reactive protein (CRP) level, and chlamydial and gonococcal DNA probes.Nucleic acid amplification tests (NAATs), direct fluorescein tests (DFA), and enzyme-linked immunosorbent assays (ELISA) are highly sensitive tests that can identify specific pathogens present. Serology testing for antibodies is not as useful since the presence of the microorganisms in healthy people can confound interpreting the antibody titer levels, although antibody levels can indicate whether an infection is recent or long-term.Definitive criteria include histopathologic evidence of endometritis, thickened filled Fallopian tubes, or laparoscopic findings. Gram stain/smear becomes definitive in the identification of rare, atypical and possibly more serious organisms. Two thirds of patients with laparoscopic evidence of previous PID were not aware they had PID, but even asymptomatic PID can cause serious harm.
Laparoscopic identification is helpful in diagnosing tubal disease; a 65 percent to 90 percent positive predictive value exists in patients with presumed PID.Upon gynecologic ultrasound, a potential finding is tubo-ovarian complex, which is edematous and dilated pelvic structures as evidenced by vague margins, but without abscess formation.
Differential diagnosis
A number of other causes may produce similar symptoms including appendicitis, ectopic pregnancy, hemorrhagic or ruptured ovarian cysts, ovarian torsion, and endometriosis and gastroenteritis, peritonitis, and bacterial vaginosis among others.Pelvic inflammatory disease is more likely to reoccur when there is a prior history of the infection, recent sexual contact, recent onset of menses, or an IUD (intrauterine device) in place or if the partner has a sexually transmitted infection.Acute pelvic inflammatory disease is highly unlikely when recent intercourse has not taken place or an IUD is not being used. A sensitive serum pregnancy test is typically obtained to rule out ectopic pregnancy. Culdocentesis will differentiate hemoperitoneum (ruptured ectopic pregnancy or hemorrhagic cyst) from pelvic sepsis (salpingitis, ruptured pelvic abscess, or ruptured appendix).Pelvic and vaginal ultrasounds are helpful in the diagnosis of PID. In the early stages of infection, the ultrasound may appear normal. As the disease progresses, nonspecific findings can include free pelvic fluid, endometrial thickening, uterine cavity distension by fluid or gas. In some instances the borders of the uterus and ovaries appear indistinct. Enlarged ovaries accompanied by increased numbers of small cysts correlates with PID.Laparoscopy is infrequently used to diagnose pelvic inflammatory disease since it is not readily available. Moreover, it might not detect subtle inflammation of the fallopian tubes, and it fails to detect endometritis. Nevertheless, laparoscopy is conducted if the diagnosis is not certain or if the person has not responded to antibiotic therapy after 48 hours.No single test has adequate sensitivity and specificity to diagnose pelvic inflammatory disease. A large multisite U.S. study found that cervical motion tenderness as a minimum clinical criterion increases the sensitivity of the CDC diagnostic criteria from 83 percent to 95 percent. However, even the modified 2002 CDC criteria do not identify women with subclinical disease.
Prevention
Regular testing for sexually transmitted infections is encouraged for prevention. The risk of contracting pelvic inflammatory disease can be reduced by the following:
Using barrier methods such as condoms; see human sexual behaviour for other listings.
Seeking medical attention if you are experiencing symptoms of PID.
Using hormonal combined contraceptive pills also helps in reducing the chances of PID by thickening the cervical mucosal plug & hence preventing the ascent of causative organisms from the lower genital tract.
Seeking medical attention after learning that a current or former sex partner has, or might have had a sexually transmitted infection.
Getting a STI history from your current partner and strongly encouraging they be tested and treated before intercourse.
Diligence in avoiding vaginal activity, particularly intercourse, after the end of a pregnancy (delivery, miscarriage, or abortion) or certain gynecological procedures, to ensure that the cervix closes.
Reducing the number of sexual partners.
Sexual monogamy.
Abstinence
Treatment
Treatment is often started without confirmation of infection because of the serious complications that may result from delayed treatment. Treatment depends on the infectious agent and generally involves the use of antibiotic therapy although there is no clear evidence of which antibiotic regimen is more effective and safe in the management of PID. If there is no improvement within two to three days, the patient is typically advised to seek further medical attention. Hospitalization sometimes becomes necessary if there are other complications. Treating sexual partners for possible STIs can help in treatment and prevention.For women with PID of mild to moderate severity, parenteral and oral therapies appear to be effective. It does not matter to their short- or long-term outcome whether antibiotics are administered to them as inpatients or outpatients. Typical regimens include cefoxitin or cefotetan plus doxycycline, and clindamycin plus gentamicin. An alternative parenteral regimen is ampicillin/sulbactam plus doxycycline. Erythromycin-based medications can also be used. A single study suggests superiority of azithromycin over doxycycline. Another alternative is to use a parenteral regimen with ceftriaxone or cefoxitin plus doxycycline. Clinical experience guides decisions regarding transition from parenteral to oral therapy, which usually can be initiated within 24–48 hours of clinical improvement.
Prognosis
Even when the PID infection is cured, effects of the infection may be permanent. This makes early identification essential. Treatment resulting in cure is very important in the prevention of damage to the reproductive system. Formation of scar tissue due to one or more episodes of PID can lead to tubal blockage, increasing the risk of the inability to get pregnant and long-term pelvic/abdominal pain. Certain occurrences such as a post pelvic operation, the period of time immediately after childbirth (postpartum), miscarriage or abortion increase the risk of acquiring another infection leading to PID.
Epidemiology
Globally about 106 million cases of chlamydia and 106 million cases of gonorrhea occurred in 2008. The number of cases of PID; however, is not clear. It is estimated to affect about 1.5 percent of young women yearly. In the United States PID is estimated to affect about one million people yearly. Rates are highest with teenagers and first time mothers. PID causes over 100,000 women to become infertile in the US each year.
References
External links
CDC
Unpacking PID: Mysterious Microbes, Diagnostic Dilemmas and Triple Treatments Webinar - 2013 |
Yersinia | Yersinia is a genus of bacteria in the family Yersiniaceae. Yersinia species are Gram-negative, coccobacilli bacteria, a few micrometers long and fractions of a micrometer in diameter, and are facultative anaerobes. Some members of Yersinia are pathogenic in humans; in particular, Y. pestis is the causative agent of the plague. Rodents are the natural reservoirs of Yersinia; less frequently, other mammals serve as the host. Infection may occur either through blood (in the case of Y. pestis) or in an alimentary fashion, occasionally via consumption of food products (especially vegetables, milk-derived products, and meat) contaminated with infected urine or feces.
Speculations exist as to whether or not certain Yersinia can also be spread by protozoonotic mechanisms, since Yersinia species are known to be facultative intracellular parasites; studies and discussions of the possibility of amoeba-vectored (through the cyst form of the protozoan) Yersinia propagation and proliferation are now in progress.
Microbial physiology
An interesting feature peculiar to some of the Yersinia bacteria is the ability to not only survive, but also to actively proliferate at temperatures as low as 1–4 °C (e.g., on cut salads and other food products in a refrigerator). Yersinia bacteria are relatively quickly inactivated by oxidizing agents such as hydrogen peroxide and potassium permanganate solutions.
Genetics
Database
The creation of YersiniaBase, a data and tools collection for the reporting and comparison of Yersinia species genome sequence data, was reported in January 2015. The provisional representation of species addressed by the resource has been indicated in the TaxBox on this page by a superscript yb beside the species name. Development of YersiniaBase was funded by the University of Malaya and the Ministry of Education, Malaysia.
Pathogenesis
Y. pestis is the causative agent of plague. The disease caused by Y. enterocolitica is called yersiniosis.
Yersinia may be associated with Crohns disease, an inflammatory autoimmune condition of the gut. Iranian sufferers of Crohns disease were more likely to have had earlier exposure to refrigerators at home, consistent with its unusual ability to thrive at low temperatures.
Yersinia is implicated as one of the causes of reactive arthritis worldwide.Also, the genus is associated with pseudoappendicitis, which is an incorrect diagnosis of appendicitis due to a similar presentation.
History
Y. pestis, the first known species, was identified in 1894 by A.E.J. Yersin, a Swiss bacteriologist, and Kitasato Shibasaburō, a Japanese bacteriologist. It was formerly described as Pasteurella pestis (known trivially as the plague-bacillus) by Lehmann and Neumann in 1896. In 1944, van Loghem reclassified the species P. pestis and P. rondentium into a new genus, Yersinia. Following the introduction of the bacteriological code, it was accepted as valid in 1980.
References
External links
Yersinia Enterocolitis Mimicking Crohns Disease in a Toddler
Sweden: Pork warnings over new stomach illness
Yersinia genomes and related information at PATRIC, a Bioinformatics Resource Center funded by NIAID
YersiniaBase |
Post-nasal drip | Post-nasal drip (PND), also known as upper airway cough syndrome (UACS), occurs when excessive mucus is produced by the nasal mucosa. The excess mucus accumulates in the back of the nose, and eventually in the throat once it drips down the back of the throat. It can be caused by rhinitis, sinusitis, gastroesophageal reflux disease (GERD), or by a disorder of swallowing (such as an esophageal motility disorder). Other causes can be allergy, cold, flu, and side effects from medications.
However, some researchers argue that the flow of mucus down the back of the throat from the nasal cavity is a normal physiologic process that occurs in all healthy individuals. Some researchers challenge post-nasal drip as a syndrome and instead view it as a symptom, also taking into account variation across different societies. Furthermore, this rebuttal is reinforced because of the lack of an accepted definition, pathologic tissue changes, and available biochemical tests.
Signs and symptoms
PND may present itself through the constant presence of discomfort in the upper airways. It is classically described as the sensation of a substance "dripping down the throat" and may also present with rhinorrhea, constant throat clearing, and cough, although its symptoms can be very nonspecific. PND is one of the most common etiologies for chronic cough, defined as a cough persisting beyond 8 weeks.GERD is often associated with a high prevalence of upper-respiratory symptoms similar to those of PND, such as coughing, throat clearing, hoarseness and change in voice. Reflux causes throat irritation, leading to a sensation of increased mucus in the throat, which is believed to aggravate and, in some cases, cause post-nasal drip.Post-nasal drip can be a cause of laryngeal inflammation and hyperresponsiveness, leading to symptoms of vocal cord dysfunction.
Causes
There are multiple causes of PND, which can be acute or chronic.
Allergic rhinitis
Allergic rhinitis (AR) is a common condition where exposure to allergens results in the release of inflammatory mediators, such as histamine, that causes sneezing, rhinorrhea, itchy eyes, and nasal congestion. The increased rhinorrhea and mucus production can result in PND.
Non-allergic rhinitis
Non-allergic rhinitis (NAR) is a condition in which there are symptoms of rhinitis, including rhinorrhea and nasal obstruction, but with negative skin and serum allergy testing results. It can be further categorized into:
Non-allergic rhinitis with eosinophilia (NARES)
Hormonal rhinitis (such as during pregnancy)
Medication-induced rhinitis
Atrophic rhinitis
Irritant and occupational rhinitis (including tobacco smoke, cleaning supplies, etc.)
Idiopathic nonallergic rhinitis
Rhinosinusitis
Rhinosinusitis is inflammation or infection of the sinus cavities. Acute rhinosinusitis has symptoms lasting less than four weeks, while chronic rhinosinusitis lasts greater than 12 weeks. This persistent irritation can lead to increased mucus production as a result of pro-inflammatory pathways, producing symptoms of PND.
Mechanism
The exact mechanism of PND depends on its etiology, but usually involves increased production of mucus from the nasal mucosa. In addition to providing sense of smell, the nasal cavity serves to filter and regulate the temperature and humidity of inspired air. The nasal mucosa can produce secretions, or mucus, that provides lubrication and protection for the nasal cavity. This mucus production is activated by the autonomic nervous system; specifically, cholinergic neuropeptides are responsible for increasing mucus production. Excess mucus can drain posteriorly into the upper and lower airways, which, along with other physical and chemical irritants, can activate receptors in the respiratory tract that results in a protective physiological cough.
Diagnosis
Diagnosis of PND depends on both a detailed history and clinical examination to help determine its etiology. The history may begin with feelings of obstructed nasal breathing or "stuffy nose" with or without nasal discharge. If allergic rhinitis is suspected, a family history of allergic conditions as well as a personal history of other associated conditions such as food allergy, asthma, and atopic dermatitis can be evaluated. Allergic rhinitis classically has more symptoms of sneezing attacks, itchy eyes, and respiratory problems, although it is difficult to distinguish the different types of rhinitis by symptomology alone. Visual inspection can reveal mouth breathing, which is suggestive of nasal obstruction, or a horizontal crease across the nose (caused by the "allergic salute").In the absence of any specific diagnostic tests, it may be difficult to diagnose PND from history of symptoms alone, as the etiology is broad and the symptoms may be very general. As such, suggestive procedures that highlight rhinitis and mucopurulent secretions, such as nasoendoscopy, may instead be utilized because of the vague nature of information available to directly attribute specific symptoms to the syndrome.
Treatment
Treatment options depend on the nature of an individual’s post-nasal drip and its cause. Antibiotics may be prescribed if the PND is the result of bacterial sinusitis. In cases where PND is caused by allergic rhinitis or irritant rhinitis, avoidance of allergens or irritating factors such as dander, cigarette smoke, and cleaning supplies may be beneficial. Antihistamines are particularly useful for allergic rhinitis, and it may be beneficial in some cases of non-allergic rhinitis. First-generation antihistamines such as chlorpheniramine and clemastine are more potent but have greater sedatory effects; later-generation antihistamines may be used to reduce these effects. Azelastine, a topical antihistamine, is approved for both allergic and non-allergic rhinitis due to its unique anti-inflammatory effects separate from its histamine receptor antagonism.Intranasal steroids may also be beneficial in patients who do not respond to antihistamines. In one meta-analysis, intranasal steroids were shown to improve symptoms of non-allergic rhinitis at four weeks better than a placebo. Decongestants such as pseudoephedrine can tighten blood vessels of the nasal mucosa and result in a decrease in mucus production. Anticholinergics such as ipratropium bromide can help reduce secretions by blocking parasympathetic effects on the nasal mucosa.Other methods, such as drinking warm fluids and using saline nasal irrigation, may be useful for managing symptoms of PND but its exact efficacy is unclear in medical literature.
Epidemiology
Because PND is often characterized as a "symptom" rather than a separate condition, the exact incidence is unknown and varies by its etiology. Chronic rhinitis, which includes allergic and non-allergic rhinitis, can affect 30-40% of the population. Non-allergic rhinitis is more common in females than in males.
References
External links
Medline Plus article on Nasal Discharge |
Rotator cuff tear | A rotator cuff tear is an injury where one or more of the tendons or muscles of the rotator cuff of the shoulder get torn. Symptoms may include shoulder pain, which is often worse with movement, limited range of motion, or weakness. This may limit peoples ability to brush their hair or put on clothing. Clicking may also occur with movement of the arm.Tears may occur as the result of a sudden force or gradually over time. Risk factors include certain repetitive activities, smoking, and a family history of the condition. Diagnosis is based on symptoms, examination, and medical imaging. The rotator cuff is made up of the supraspinatus, infraspinatus, teres minor, and subscapularis. The supraspinatus is the most commonly affected.Treatment may include pain medication such as NSAIDs and specific exercises. It is recommended that people who are unable to raise their arm above 90 degrees after 2 weeks should be further assessed. In severe cases surgery may be tried, however benefits of surgery are unclear as of 2019. Rotator cuff tears are common. Those over the age of 40 are most often affected. The condition has been described since at least the early 1800s.
Signs and symptoms
Many rotator cuff tears have no symptoms. Both partial and full thickness tears have been found on post mortem and MRI studies in those without any history of shoulder pain or symptoms. However, the most common presentation is shoulder pain or discomfort. This may occur with activity, particularly shoulder activity above the horizontal position, but may also be present at rest in bed. Pain-restricted movement above the horizontal position may be present, as well as weakness with shoulder flexion and abduction.Abnormal mobility or function of the scapula (scapular dyskinesia) may be present and is related to lower functional scores; it unclear whether scapular dyskinesia is a cause, effect or compensation for rotator cuff pathology.
Risk factors
Epidemiological studies strongly support a relationship between age and cuff tear prevalence, with the most common cause being age-related degeneration and, less frequently, sports injuries or trauma.Those most prone to failed rotator cuff syndrome are people 65 years of age or older; and those with large, sustained tears. Smokers, people with diabetes, individuals with muscle atrophy or fatty infiltration, and those who do not follow postoperative-care recommendations also are at greater risk. In a 2008 study the frequency of such tears increased from 13% in the youngest group (aged 50–59 y) to 20% (aged 60–69 y), 31% (aged 70–79 y), and 51% in the oldest group (aged 80–89 y).Some risk factors such as increased age and height cannot be changed. Increased body mass index is also associated with tearing. Recurrent lifting and overhead motions are at risk for rotator cuff injury as well. This includes jobs that involve repetitive overhead work, such as carpenters, painters, custodians, and servers. People who play sports that involve overhead motions, such as swimming, water polo, volleyball, baseball, tennis, and American football quarterbacks, are at a greater risk of experiencing a rotator cuff tear. Striking-based combat sports, such as boxing, also account for severe rotator cuff injuries of competitors, typically when their punches miss the target, or overusing the shoulder by throwing excessively large amounts of punches. Certain track-and-field activities, such as shot put, javelin throw are also of considerable risk, especially when performing outdoors under cold weather conditions or neglecting warming-up procedures, for proper warm-up of the throwing and/or swinging arm can help reduce the stress on the musculature of the shoulder girdle. Corticosteroid injections around the tendons increases the risk of tendon tear and delay tendon healing.
Mechanisms of injury
The shoulder is a complex mechanism involving bones, ligaments, joints, muscles, and tendons.
The two main causes are acute injury or chronic and cumulative degeneration of the shoulder joint. Mechanisms can be extrinsic, intrinsic or a combination of both.The cuff is responsible for stabilizing the glenohumeral joint to allow abduction and rotation of the humerus. When trauma occurs, these functions can be compromised. Because individuals are dependent on the shoulder for many activities, overuse can lead to tears, with the vast majority being in the supraspinatus tendon.The role of the supraspinatus is to resist downward motion, both while the shoulder is relaxed and carrying weight. Supraspinatus tears usually occurs at its insertion on the humeral head at the greater tubercle. Though the supraspinatus is the most commonly injured tendon in the rotator cuff, the other three can also be injured at the same time.
Acute tears
The amount of stress needed to acutely tear a rotator cuff tendon will depend on the underlying condition of the tendon. If healthy, the stress needed will be high, such as with a fall on the outstretched arm. This stress may occur coincidentally with other injuries such as a dislocation of the shoulder or separation of the acromioclavicular joint. In the case of a tendon with pre-existing degeneration, the force may be more modest, such as with a sudden lift, particularly with the arm above the horizontal position. The type of loading involved with injury is usually eccentric, such as when two people are carrying a load and one lets go, forcing the other to maintain force while the muscle elongates.
Chronic tears
Chronic tears are indicative of extended use in conjunction with other factors such as poor biomechanics or muscular imbalance. Ultimately, most are the result of wear that occurs slowly over time as a natural part of aging. They are more common in the dominant arm, but a tear in one shoulder signals an increased risk of a tear in the opposing shoulder.Several factors contribute to degenerative, or chronic, rotator cuff tears of which repetitive stress is the most significant. This stress consists of repeating the same shoulder motions frequently, such as overhead throwing, rowing, and weightlifting. Many jobs that require frequent shoulder movement such as lifting and overhead movements also contribute. In older populations impairment of blood supply can also be an issue. With age, circulation to the rotator cuff tendons decreases, impairing natural ability to repair, increasing risk for tear. Another potential contributing cause is impingement syndrome, the most common non-sports related injury and which occurs when the tendons of the rotator cuff muscles become irritated and inflamed while passing through the subacromial space beneath the acromion. This relatively small space becomes even smaller when the arm is raised in a forward or upward position. Repetitive impingement can inflame the tendons and bursa, resulting in the syndrome.
Extrinsic factors
Well-documented anatomic factors include the morphologic characteristics of the acromion, a bony projection from the scapula that curves over the shoulder joint. Hooked, curved, and laterally sloping acromia are strongly associated with cuff tears and may cause damage through direct traction on the tendon. Conversely, flat acromia may have an insignificant involvement in cuff disease and consequently may be best treated conservatively. The development of these different acromial shapes is likely both genetic and acquired. In the latter case, there can be a progression from flat to curved or hooked with increasing age. Repetitive mechanical activities such as sports and exercise may contribute to flattening and hooking of the acromion. Cricket bowling, swimming, tennis, baseball, and kayaking are often implicated. Progression to a hooked acromion could be an adaptation to an already damaged, poorly balanced rotator cuff with resultant stress on the coracoacromial arch. Other anatomical factors include an os acromiale and acromial spurs. Environmental factors include age, shoulder overuse, smoking, and medical conditions that affect circulation or impair the inflammatory and healing response, such as diabetes mellitus.
Intrinsic factors
Intrinsic factors refer to injury mechanisms that occur within the rotator cuff itself. The principal is a degenerative-microtrauma model, which supposes that age-related tendon damage compounded by chronic microtrauma results in partial tendon tears that then develop into full rotator cuff tears. As a result of repetitive microtrauma in the setting of a degenerative rotator cuff tendon, inflammatory mediators alter the local environment, and oxidative stress induces tenocyte apoptosis causing further rotator cuff tendon degeneration. A neural theory also exists that suggests neural overstimulation leads to the recruitment of inflammatory cells and may also contribute to tendon degeneration.
Surgical considerations
Depending upon the diagnosis, several treatment alternatives are available. They include revision repair, non-anatomic repair, tendon transfer and arthroplasty. When possible, surgeons make tension-free repairs in which they use grafted tissues rather than stitching to reconnect tendon segments. This can result in a complete repair. Other options are a partial repair, and reconstruction involving a bridge of biologic or synthetic substances. Partial repairs typically are performed on retracted cuff tears.Tendon transfers are prescribed for young, active cuff-tear individual who experience weakness and decreased range of motion, but little pain. The technique is not considered appropriate for older people, or those with pre-operative stiffness or nerve injuries. People diagnosed with glenohumeral arthritis and rotator cuff anthropathy have the alternative of total shoulder arthroplasty, if the cuff is largely intact or repairable. If the cuff is incompetent then a reverse shoulder arthroplasty is available and, although not as robust a prosthesis, does not require an intact cuff to maintain a stable joint.
Diagnosis
Diagnosis is based upon physical assessment and history, including description of previous activities and acute or chronic symptoms. A systematic, physical examination of the shoulder comprises inspection, palpation, range of motion, provocative tests to reproduce the symptoms, neurological examination, and strength testing. The shoulder should also be examined for tenderness and deformity. Since pain arising from the neck is frequently referred to the shoulder, the examination should include an assessment of the cervical spine looking for evidence suggestive of a pinched nerve, osteoarthritis, or rheumatoid arthritis.
Neer promoted the concept of three stages of rotator cuff disease. Stage I, according to Neer, occurred in those younger than 25 years and involved edema and hemorrhage of the tendon and bursa. Stage II involved tendinitis and fibrosis of the rotator cuff in 25- to 40-year-olds. Stage III involved tearing of the rotator cuff (partial or full thickness) and occurred in those older than 40 years. For surgical purposes, tears are also described by location, size or area, and depth. Further subclasses include the acromiohumeral distance, acromial shape, fatty infiltration or degeneration of muscles, muscle atrophy, tendon retraction, vascular proliferation, chondroid metaplasia, and calcification. Again, in surgical planning, age-related degeneration of thinning and disorientation of the collagen fibers, myxoid degeneration, and hyaline degeneration are considered.Diagnostic modalities, dependent on circumstances, include X-ray, MRI, MR arthrography, double-contrast arthrography, and ultrasound. Although MR arthrography is currently considered the gold standard, ultrasound may be most cost-effective. Usually, a tear will be undetected by X-ray, although bone spurs, which can impinge upon the rotator cuff tendons, may be visible. Such spurs suggest chronic severe rotator cuff disease. Double-contrast arthrography involves injecting contrast dye into the shoulder joint to detect leakage out of the injured rotator cuff and its value is influenced by the experience of the operator. The most common diagnostic tool is magnetic resonance imaging (MRI), which can sometimes indicate the size of the tear, as well as its location within the tendon. Furthermore, MRI enables the detection or exclusion of complete rotator cuff tears with reasonable accuracy and is also suitable to diagnose other pathologies of the shoulder joint.The logical use of diagnostic tests is an important component of effective clinical practice.Clinical judgement, rather than over reliance on MRI or any other modality, is strongly advised in determining the cause of shoulder pain, or planning its treatment, since rotator cuff tears are also found in some without pain or symptoms. The role of X-ray, MRI, and ultrasound, is adjunctive to clinical assessment and serves to confirm a diagnosis provisionally made by a thorough history and physical examination. Over-reliance on imaging may lead to overtreatment or distract from the true dysfunction causing symptoms.
Symptoms
Symptoms may occur immediately after trauma (acute) or develop over time (chronic).
Acute injury is less frequent than chronic disease, but may follow bouts of forcefully raising the arm against resistance, as occurs in weightlifting, for example. In addition, falling forcefully on the shoulder can cause acute symptoms. These traumatic tears predominantly affect the supraspinatus tendon or the rotator interval and symptoms include severe pain that radiates through the arm, and limited range of motion, specifically during abduction of the shoulder.
Chronic tears occur among individuals who constantly participate in overhead activities, such as pitching or swimming, but can also develop from shoulder tendinitis or rotator cuff disease. Symptoms arising from chronic tears include sporadic worsening of pain, debilitation, and atrophy of the muscles, noticeable pain during rest, crackling sensations (crepitus) when moving the shoulder, and inability to move or lift the arm sufficiently, especially during abduction and flexion motions.Pain in the anterolateral aspect of the shoulder is not specific to the shoulder, and may arise from, and be referred from, the neck, heart or gut.
Symptoms will often include pain or ache over the front and outer aspect of the shoulder, pain aggravated by leaning on the elbow and pushing upwards on the shoulder (such as leaning on the armrest of a reclining chair), intolerance of overhead activity, pain at night when lying directly on the affected shoulder, pain when reaching forward (e.g. unable to lift a gallon of milk from the refrigerator). Weakness may be reported, but is often masked by pain and is usually found only through examination. With longer-standing pain, the shoulder is favored and gradually loss of motion and weakness may develop, which, due to pain and guarding, are often unrecognized and only brought to attention during the physical exam.Primary shoulder problems may cause pain over the deltoid muscle intensified by abduction against resistance – the impingement sign. This signifies pain arising from the rotator cuff, but cannot distinguish between inflammation, strain, or tear. Individuals may report that they are unable to reach upwards to brush their hair or to lift a food can from an overhead shelf.
Signs
No single physical examination test distinguishes reliably between bursitis, partial-thickness, and full-thickness tears. The most useful single test for infraspinatous tendon tears is the drop sign (the examiner lifts the arm straight out from the body with the palm up, the person then needs to hold it there for 10 seconds) and the external rotation lag sign (with the arm by the side and the elbow bent to 90 degrees the person tries to rotate outwards against resistance).A combination of tests seems to provide the most accurate diagnosis. For impingement, these tests include the Hawkins-Kennedy impingement sign in which an examiner medially rotates the injured individuals flexed arm, forcing the supraspinatus tendon against the coracoacromial ligament and so producing pain if the test is positive a positive painful arc sign, and weakness in external rotation with the arm at the side.
For the diagnosis of full-thickness rotator cuff tear, the best combination appears to include once more the painful arc and weakness in external rotation, and in addition, the drop arm sign. This test is also known as Codmans test. The arm is raised to the side to 90° by the examiner. The injured individual then attempts to look to lower the arm back to neutral, palm down. If the arm drops suddenly or pain is experienced, the test is considered positive.
MRI
Magnetic resonance imaging (MRI) and ultrasound are comparable in efficacy and helpful in diagnosis although both have a false positive rate of 15–20%. MRI can reliably detect most full-thickness tears although very small pinpoint tears may be missed. In such situations, an MRI combined with an injection of contrast material, an MR-arthrogram, may help to confirm the diagnosis. It should be realized that a normal MRI cannot fully rule out a small tear (a false negative) while partial-thickness tears are not as reliably detected. While MRI is sensitive in identifying tendon degeneration (tendinopathy), it may not reliably distinguish between a degenerative tendon and a partially torn tendon. Again, magnetic resonance arthrography can improve the differentiation. An overall sensitivity of 91% (9% false negative rate) has been reported indicating that magnetic resonance arthrography is reliable in the detection of partial-thickness rotator cuff tears. However, its routine use is not advised, since it involves entering the joint with a needle with potential risk of infection. Consequently, the test is reserved for cases in which the diagnosis remains unclear.
Ultrasound
Musculoskeletal ultrasound has been advocated by experienced practitioners, avoiding the radiation of X-ray and the expense of MRI while demonstrating comparable accuracy to MRI for identifying and measuring the size of full-thickness and partial-thickness rotator cuff tears. This modality can also reveal the presence of other conditions that may mimic rotator cuff tear at clinical examination, including tendinosis, calcific tendinitis, subacromial subdeltoid bursitis, greater tuberosity fracture, and adhesive capsulitis. However, MRI provides more information about adjacent structures in the shoulder such as the capsule, glenoid labrum muscles and bone and these factors should be considered in each case when selecting the appropriate study.
Xray
X-ray projectional radiography cannot directly reveal tears of the rotator cuff, a soft tissue, and consequently, normal X-rays cannot exclude a damaged cuff. However, indirect evidence of pathology may be seen in instances where one or more of the tendons have undergone degenerative calcification (calcific tendinitis). The humeral head may migrate upwards (high-riding humeral head) secondary to tears of the infraspinatus, or combined tears of the supraspinatus and infraspinatus. The migration can be measured by the distance between:
A line crossing the center of a line between the superior and inferior rims of the glenoid articular surface (blue in image).
The center of a "best-fit" circle positioned over the humeral articular surface (green in image)Normally, the former is positioned inferiorly to the latter, and a reversal is therefore indicating a rotator cuff tear. Prolonged contact between a high-riding humeral head and the acromion above it, may lead to X-rays findings of wear on the humeral head and acromion and secondary degenerative arthritis of the glenohumeral joint (the ball and socket joint of the shoulder), called cuff arthropathy, may follow. Incidental X-ray findings of bone spurs at the adjacent acromioclavicular joint may show a bone spur growing from the outer edge of the clavicle downwards towards the rotator cuff. Spurs may also be seen on the underside of the acromion, once thought to cause direct fraying of the rotator cuff from contact friction, a concept currently regarded as controversial.
In-office testing
As part of clinical decision-making, a simple, minimally invasive, in-office procedure may be performed, the rotator cuff impingement test. A small amount of a local anesthetic and an injectable corticosteroid are injected into the subacromial space to block pain and to provide anti-inflammatory relief. If pain disappears and shoulder function remains good, no further testing is pursued. The test helps to confirm that the pain arises from the shoulder primarily rather than referred from the neck, heart, or gut.
If pain is relieved, the test is considered positive for rotator-cuff impingement, of which tendinitis and bursitis are major causes. However, partial rotator-cuff tears may also demonstrate good pain relief, so a positive response cannot rule out a partial rotator-cuff tear. However, with demonstration of good, pain-free function, treatment will not change, so the test is useful in helping to avoid overtesting or unnecessary surgery.
Classification
Tears of the rotator cuff tendon are described as partial or full thickness, and full thickness with complete detachment of the tendons from bone.
Partial-thickness tears often appear as fraying of an intact tendon.
Full-thickness tears are "through-and-through". These tears can be small pinpoint, larger buttonhole, or involve the majority of the tendon where it still remains substantially attached to the humeral head and thus maintains function.
Full-thickness tears may also involve complete detachment of the tendon(s) from the humeral head and may result in significantly impaired shoulder motion and function.Shoulder pain is variable and may not be proportional to the size of the tear.
Tears are also sometimes classified based on the trauma that caused the injury:
Acute, as a result of a sudden, powerful movement which might include falling onto an outstretched hand at speed, making a sudden thrust with a paddle in kayaking, or following a powerful pitch/throw
Subacute, arising in similar situations but occurring in one of the five layers of the shoulder anatomy
Chronic, developing over time, and usually occurring at or near the tendon (as a result of the tendon rubbing against the overlying bone), and usually associated with an impingement syndrome
Prevention
Long-term overuse/abuse of the shoulder joint is generally thought to limit range of motion and productivity due to daily wear and tear of the muscles, and many public web sites offer preventive advice. (See external links)
The recommendations usually include:
regular shoulder exercises to maintain strength and flexibility
using proper form when lifting or moving heavy weights
resting the shoulder when experiencing pain
application of cold packs and heat pads to a painful, inflamed shoulder
strengthening program to include the back and shoulder girdle muscles as well as the chest, shoulder and upper arm
adequate rest periods in occupations that require repetitive lifting and reaching
Size
According to a study which measured tendon length against the size of the injured rotator cuff, researchers learned that as rotator cuff tendons decrease in length, the average rotator cuff tear severity is proportionally decreased, as well. This shows that larger individuals are more likely to develop a severe rotator cuff tear if they do not "tighten the shoulder muscles around the joint".
Position
Another study observed 12 different positions of movements and their relative correlation with injuries occurred during those movements. The evidence shows that putting the arm in a neutral position relieves tension on all ligaments and tendons.
Stretching
One article observed the influence of stretching techniques on preventive methods of shoulder injuries. Increased velocity of exercise increases injury, but beginning a fast-movement exercise with a slow stretch may cause muscle/tendon attachment to become more resistant to tearing.
Muscle groups
When exercising, exercising the shoulder as a whole and not one or two muscle groups is also found to be imperative. When the shoulder muscle is exercised in all directions, such as external rotation, flexion, and extension, or vertical abduction, it is less likely to develop a tear of the tendon.
Treatment
A rotator cuff tear can be treated operatively or non-operatively. No benefit is seen from early rather than delayed surgery, and many with partial tears and some with complete tears will respond to nonoperative management. Consequently, an individual may begin with nonsurgical management. However, early surgical treatment may be considered in significant (>1 cm – 1.5 cm) acute tears, or in young individuals with full-thickness tears who have a significant risk for the development of irreparable rotator cuff damage.Rotator-cuff surgery appears to result in similar benefits as nonoperative management. As a conservative approach has less complications and is less expensive it is recommended as initial treatment.
Non-operative treatment
Those with pain but reasonably maintained function are suitable for nonoperative management. This includes medications that provide pain relief such as anti-inflammatory agents, topical pain relievers such as cold packs, and if warranted, subacromial corticosteroid or local anesthetic injection. Topical glyceryl trinitrate appears effective at relieving acute symptoms however, headaches were reported as a side effect. A sling may be offered for short-term comfort, with the understanding that undesirable shoulder stiffness can develop with prolonged immobilization. Early physical therapy may afford pain relief with modalities (e.g. iontophoresis) and help to maintain motion. Ultrasound treatment is not efficacious. As pain decreases, strength deficiencies and biomechanical errors can be corrected.Shock wave therapy has seen widespread use since the 1990s to treat various musculoskeletal disorders including rotator cuff disease, but evidence of its efficacy remains dubious. In a review of 2020, the benefits and harms of shock wave therapy for rotator cuff disease, with or without calcificationcurrently, were investigated. They found low to moderate certainty evidence, that there were very few clinically important benefits of shock wave therapy, and uncertainty regarding its safety.A conservative physical therapy program begins with preliminary rest and restriction from engaging in activities which gave rise to symptoms. Normally, inflammation can usually be controlled within one to two weeks, using a nonsteroidal anti-inflammatory drug and subacromial steroid injections to decrease inflammation, to the point that pain has been significantly decreased to make stretching tolerable. After this short period, rapid stiffening and an increase in pain can result if sufficient stretching has not been implemented.
A gentle, passive range-of-motion program should be started to help prevent stiffness and maintain range of motion during this resting period. Stiffness negatively affects the tendon-bone healing process, a critical part of recovery. Stiffness during rehabilitation is related to worse clinical outcomes, so it is important for the patient to understand the importance of a proactive regimen. Strain induced tendon remodeling, which is part of an accelerated rehabilitation protocol, has been shown to speed up the time to return to daily activities. Exercises, for the anterior, inferior, and posterior shoulder, should be part of this program. Codman exercises (giant, pudding-stirring), to "permit the patient to abduct the arm by gravity, the supraspinatus remains relaxed, and no fulcrum is required" are widely used. The use of NSAIDs, hot and cold packs, and physical therapy modalities, such as ultrasound, phonophoresis, or iontophoresis, can be instituted during this stretching period, if effective. Corticosteroid injections are recommended two to three months apart with a maximum of three injections. Multiple injections (four or more) have been shown to compromise the results of rotator cuff surgery which result in weakening of the tendon. Kinesio taping was compared to sham taping and other conservative treatment for the approach of the rotator cuff disease and has uncertain effects in terms of self‐reported pain, function, pain on motion and active range of motion.Rockwood coined the term orthotherapy to describe the program which is aimed at creating an exercise regimen that initially gently improves motion, then gradually improves strength in the shoulder girdle. This program involves a home therapy kit which includes elastic bands of six different colors and strengths, a pulley set, and a three-piece, one-meter-long stick. The program is individually customized. Participants are asked to use their exercise program whether at home, work, or traveling.
Surgery
Benefits of surgery are unclear as of 2019. Several instances when surgery may be recommended include:
20 to 30-year-old active person with an acute tear and severe functional deficit from a specific event
30 to 50-year-old person with an acute rotator cuff tear secondary to a specific event
a highly competitive athlete who is primarily involved in overhead or throwing sportsThese individuals more often benefit from operative treatment because they are willing to tolerate the risks of surgery to return to their preoperative level of function, and have higher likelihood of a successful outcome. Those who do not respond to, or are unsatisfied with, conservative treatment can seek a surgical opinion.The three general surgical approaches are arthroscopic, mini open, and open-surgical repair.
In the past, small tears were treated arthroscopically, while larger tears would usually require an open procedure. Advances in arthroscopy now allow arthroscopic repair of even the largest tears, and arthroscopic techniques are now required to mobilize many retracted tears. The results match |
Rotator cuff tear | open surgical techniques, while permitting a more thorough evaluation of the shoulder at time of surgery, increasing the diagnostic value of the procedure, as other conditions may simultaneously cause shoulder pain. Arthroscopic surgery also allows for shorter recovery time although differences in postoperative pain or pain medication use are not seen between arthroscopic- and open-surgery. A 2019 review found that the evidence does not support decompression surgery in those with more than 3 months of shoulder pain without a history of trauma.Even for full-thickness rotator cuff tears, conservative care (i.e., nonsurgical treatment) outcomes are usually reasonably good.If a significant bone spur is present, any of the approaches may include an acromioplasty, a subacromial decompression, as part of the procedure. Subacromial decompression, removal of a small portion of the acromion that overlies the rotator cuff, aims to relieve pressure on the rotator cuff in certain conditions and promote healing and recovery. Although subacromial decompression may be beneficial in the management of partial and full-thickness tear repair, it does not repair the tear itself and arthroscopic decompression has more recently been combined with "mini-open" repair of the rotator cuff, allowing for the repair of the cuff without disruption of the deltoid origin. The results of decompression alone tend to degrade with time, but the combination of repair and decompression appears to be more enduring. Subacromial decompression may not improve pain, function, or quality of life.Repair of a complete, full-thickness tear involves tissue suture. The method currently in favor is to place an anchor in the bone at the natural attachment site, with resuture of torn tendon to the anchor. If tissue quality is poor, mesh (collagen, Artelon, or other degradable material) may be used to reinforce the repair. Repair can be performed through an open incision, again requiring detachment of a portion of the deltoid, while a mini-open technique approaches the tear through a deltoid-splitting approach. The latter may cause less injury to muscle and produce better results. Contemporary techniques now use an all arthroscopic approach.
Recovery can take as long as three–six months, with a sling being worn for the first one–six weeks. In the case of partial thickness tears, if surgery is undertaken, tear completion (converting the partial tear to a full tear) and then repair, is associated with better early outcomes than transtendinous repairs (where the intact fibres are preserved) and no difference in failure rates.Biceps tenotomy and tenodesis are often performed concomitantly with rotator cuff repair or as separate procedures, and can also cause shoulder pain. Tenodesis, which may be performed as an arthroscopic or open procedure, generally restores pain free motion it the biceps tendon, or attached portion of the labrum, but can cause pain. Tenotomy is a shorter surgery requiring less rehabilitation, that is more often performed in older patients, though after surgery there can be a cosmetic popeye sign visible in thin arms.In a small minority of cases where extensive arthritis has developed, an option is shoulder joint replacement (arthroplasty). Specifically, this is a reverse shoulder replacement, a more constrained form of shoulder arthroplasty that allows the shoulder to function well even in the presence of large full thickness rotator cuff tears.
Shoulder Replacement
The latest systematic reviews suggests (with low quality evidence) that total shoulder arthroplasty does not provide important benefits over hemiarthroplasty for glenohumeral osteoarthritis and rotator cuff tears. It highlighted the current lack of high-quality evidence and need for randomized controlled trials.
Biologics
The main goal in biological augmentation is to enhance healing. There are a number of potential options. These include injecting an individuals own stem cells, growth factors or platelet rich plasma (PRP) into the repair site, and installing scaffolds as biological or synthetic supports to maintain tissue contour. A 2014 Cochrane review evaluated PRP and found insufficient evidence to make recommendations. Mesenchymal stem cells have no convincing evidence for their use overall, with quality human trials lacking. The greater tuberosity can also be microfractured to create a small blood clot just lateral to the repair site.
Rehabilitation
Rehabilitation after surgery consists of three stages. First, the arm is immobilized so that the muscle can heal. Second, when appropriate, a therapist assists with passive exercises to regain range of motion. Third, the arm is gradually exercised actively, with a goal of regaining and enhancing strength. The empty can and full can exercises are amongst the most effective at isolating and strengthening the supraspinatus.Following arthroscopic rotator-cuff repair surgery, individuals need rehabilitation and physical therapy. Exercise decreases shoulder pain, strengthens the joint, and improves range of motion. Therapists, in conjunction with the surgeon, design exercise regimens specific to the individual and their injury.Traditionally, after injury the shoulder is immobilized for six weeks before rehabilitation. However, the appropriate timing and intensity of therapy are subject to debate. Most surgeons advocate using the sling for at least six weeks, though others advocate early, aggressive rehabilitation. The latter group favors the use of passive motion, which allows an individual to move the shoulder without physical effort. Alternatively, some authorities argue that therapy should be started later and carried out more cautiously. Theoretically, that gives tissues time to heal; though there is conflicting data regarding the benefits of early immobilization. A study of rats suggested that it improved the strength of surgical repairs, while research on rabbits produced contrary evidence. Individuals with a history of rotator cuff injury, particularly those recovering from tears, are prone to reinjury. Rehabbing too soon or too strenuously might increase the risk of retear or failure to heal. However, no research has proven a link between early therapy and the incidence of re-tears. In some studies, those who received earlier and more aggressive therapy reported reduced shoulder pain, less stiffness and better range of motion. Other research has shown that accelerated rehab results in better shoulder function.
There is consensus amongst orthopaedic surgeons and physical therapists regarding rotator cuff repair rehabilitation protocols. The timing and duration of treatments and exercises are based on biologic and biomedical factors involving the rotator cuff. For approximately two to three weeks following surgery, an individual experiences shoulder pain and swelling; no major therapeutic measures are instituted in this window other than oral pain medicine and ice. Those at risk of failure should usually be more conservative with rehabilitations.That is followed by the "proliferative" and "maturation and remodeling" phases of healing, which ensues for the following six to ten weeks. The effect of active or passive motion during any of the phases is unclear, due to conflicting information and a shortage of clinical evidence. Gentle physical therapy guided motion is instituted at this phase, only to prevent stiffness of the shoulder; the rotator cuff remains fragile. At three months after surgery, physical therapy intervention changes substantially to focus on scapular mobilization and stretching of the glenohumeral joint. Once full passive motion is regained (at usually about four to four and a half months after surgery) strengthening exercises are the focus. The strengthening focuses on the rotator cuff and the upper back/scapular stabilizers. Typically at about six months after surgery, most have made a majority of their expected gains.The objective in repairing a rotator cuff is to enable an individual to regain full function. Surgeons and therapists analyze outcomes in several ways. Based on examinations, they compile scores on tests; some examples are those created by the University of California at Los Angeles and the American Shoulder and Elbow Surgeons. Other outcome measures include the Constant score; the Simple Shoulder Test; and the Disabilities of the Arm, Shoulder and Hand score. The tests assess range of motion and the degree of shoulder function.Due to the conflicting information about the relative benefits of rehab conducted early or later, an individualized approach is necessary. The timing and nature of therapeutic activities are adjusted according to age and tissue integrity of the repair. Management is more complex in those who have had multiple tears.
Prognosis
While people with rotator cuff tears may not have any noticeable symptoms, studies have shown that, those with age related tears, over time 40% will have enlargement of the tear over a five-year period. Of those whose tears enlarge, 20% have no symptoms while 80% eventually develop symptoms.Most usually regain function and experience less pain following surgery. For some, however, the joint continues to hurt. Weakness and a limited range of motion also may persist. Those who report such symptoms frequently are diagnosed with failed rotator cuff syndrome. There is no irrefutable evidence that rotator cuff surgery benefits more than non-surgical management and a percentage of individuals never regain full range of motion after surgery.Arthroscopic procedures produce "satisfactory results" more than 90 percent of the time. However, 6-8 percent of patients have "incompetent" rotator cuffs because their repaired tendons either fail to heal or develop additional tears. In some cases, persistent rotator cuff type pain after surgery can be due to disease elsewhere. For example, cervical spine disease and can involve neck pain radiating into the shoulder. Suprascapular neuropathy, shoulder impingement, superior labral anterior-posterior (SLAP) tears and arthritis can all mimic rotator cuff disease and cause persistent pain that does not respond to rotator cuff surgery.
Epidemiology
Rotator cuff tears are among the most common conditions affecting the shoulder.A rotator cuff tear can be caused by the weakening of the rotator cuff tendons. This weakening can be caused by age or how often the rotator cuff is used. Adults over the age of 60 are more susceptible to a rotator cuff tear, with the overall frequency of tears increasing with age. By the age of 50 10% of people with normal shoulders have a rotator cuff tear.In an autopsy study of rotator cuff tears, the incidence of partial tears was 28%, and of complete rupture 30%. Frequently, tears occurred on both sides and occurred more often with females and with increasing age. Other cadaver studies have noted intratendinous tears to be more frequent (7.2%) than bursal-sided (2.4%) or articular-sided tears (3.6%). However, clinically, articular-sided tears are found to be 2 to 3 times more common than bursal-sided tears and among a population of young athletes, articular-sided tears constituted 91% of all partial-thickness tears. Rotator cuff tears may be more common in men between the ages of 50–60, though between 70 and 80 there is minimal difference across genders.In terms of the size of tears, a study compared the ages of patient to the size of tears. It was emphasized the older you are, the more massive of a tear you will have. It was found that mean age increased with larger tear sizes (small tears 59 years, medium tears 62 years, large tears 64 years, and massive tears 66 years).
References
This article contains text from the public domain document "Questions and Answers about Shoulder Problems" (PDF). National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health Public Health Service. U.S. Department of Health and Human Services. March 2006. NIH Publication No. 01-4865. Archived from the original (PDF) on 10 May 2007.
External links
Rotator Cuff Tears. Wheeless Textbook of Orthopedics. A description of rotator cuff tears from Wheeless
Physiotherpy program for rortator cuff tears |
Aortic regurgitation | Aortic regurgitation (AR), also known as aortic insufficiency (AI), is the leaking of the aortic valve of the heart that causes blood to flow in the reverse direction during ventricular diastole, from the aorta into the left ventricle. As a consequence, the cardiac muscle is forced to work harder than normal.
Signs and symptoms
Symptoms of aortic regurgitation are similar to those of heart failure and include the following:
Dyspnea on exertion
Orthopnea
Paroxysmal nocturnal dyspnea
Palpitations
Angina pectoris
Cyanosis (in acute cases)
Causes
In terms of the cause of aortic regurgitation, is often due to the aortic root dilation (annuloaortic ectasia), which is idiopathic in over 80% of cases, but otherwise may result from aging, syphilitic aortitis, osteogenesis imperfecta, aortic dissection, Behçets disease, reactive arthritis and systemic hypertension. Aortic root dilation is the most common cause of aortic regurgitation in developed countries. Additionally, aortic regurgitation has been linked to the use of some medications, specifically medications containing fenfluramine or dexfenfluramine isomers and dopamine agonists. Other potential causes that affect the valve directly include Marfan syndrome, Ehlers–Danlos syndrome, ankylosing spondylitis, and systemic lupus erythematosus. In acute cases of aortic regurgitation, the main causes are infective endocarditis, aortic dissection or trauma.
Pathophysiology
The mechanism of aortic regurgitation, comprises the pressure in the left ventricle falling below the pressure in the aorta, the aortic valve is not able to completely close. This causes a leaking of blood from the aorta into the left ventricle. This means that some of the blood that was already ejected from the heart is regurgitating back into the heart. The percentage of blood that regurgitates back through the aortic valve due to AR is known as the regurgitant fraction. This regurgitant flow causes a decrease in the diastolic blood pressure in the aorta, and therefore an increase in the pulse pressure. Since some of the blood that is ejected during systole regurgitates back into the left ventricle during diastole, there is decreased effective forward flow in AR.While diastolic blood pressure is diminished and the pulse pressure widens, systolic blood pressure generally remains normal or can even be slightly elevated, this is because sympathetic nervous system and the renin-angiotensin-aldosterone axis of the kidneys compensate for the decreased cardiac output. Catecholamines will increase the heart rate and increase the strength of ventricular contraction, directly increasing cardiac output. Catecholamines will also cause peripheral vasoconstriction, which causes increased systemic vascular resistance and ensures that organs are adequately perfused. Renin, a proteolytic enzyme, cleaves angiotensinogen to angiotensin I, which is converted to angiotensin II. In the case of chronic aortic with resultant cardiac remodeling, heart failure will develop, and it is possible to see systolic pressures diminish. Aortic regurgitation causes both volume overload (elevated preload) and pressure overload (elevated afterload) of the heart.The volume overload, due to elevated pulse pressure and the systemic effects of neuroendocrine hormones causes left ventricular hypertrophy (LVH). There is both concentric hypertrophy and eccentric hypertrophy in AI. The concentric hypertrophy is due to the increased left ventricular pressure overload associated with AI, while the eccentric hypertrophy is due to volume overload caused by the regurgitant fraction.Physiologically, in individuals with a normally functioning aortic valve, the valve is only open when the pressure in the left ventricle is higher than the pressure in the aorta. This allows the blood to be ejected from the left ventricle into the aorta during ventricular systole. The amount of blood that is ejected by the heart is known as the stroke volume. Under normal conditions, >50% of the blood in a filled left ventricle is ejected into the aorta to be used by the body. After ventricular systole, the pressure in the left ventricle decreases as it relaxes and begins to fill up with blood from the left atrium. This relaxation of the left ventricle (early ventricular diastole) causes a fall in its pressure. When the pressure in the left ventricle falls below the pressure in the aorta, the aortic valve will close, preventing blood in the aorta from going back into the left ventricle.
Diagnosis
In terms of the diagnosis of aortic regurgitation a common test for the evaluation of the severity is transthoracic echocardiography, which can provide two-dimensional views of the regurgitant jet, allow measurement of velocity, and estimate jet volume. The findings in severe aortic regurgitation, based on the 2012 American College of Cardiology/American Heart Association guidelines include:
Chest X-ray can assist in making the diagnosis, showing left ventricular hypertrophy and dilated aorta. ECG typically indicates left ventricular hypertrophy. Cardiac chamber catheterization assists in assessing the severity of regurgitation and any left ventricular dysfunction.
Physical examination
The physical examination of an individual with aortic regurgitation involves auscultation of the heart to listen for the murmur of aortic regurgitation and the S3 heart sound (S3 gallop correlates with development of LV dysfunction). The murmur of chronic aortic regurgitation is typically described as early diastolic and decrescendo, which is best heard in the third left intercostal space and may radiate along the left sternal border.
If there is increased stroke volume of the left ventricle due to volume overload, an ejection systolic flow murmur may also be present when auscultating the same aortic area. Unless there is concomitant aortic valve stenosis, the murmur should not start with an ejection click. There may also be an Austin Flint murmur, a soft mid-diastolic rumble heard at the apical area; it appears when a regurgitant jet of blood from severe aortic regurgitation partially closes the anterior mitral leaflet. Peripheral physical signs of aortic regurgitation are related to the high pulse pressure and the rapid decrease in blood pressure during diastole due to blood returning to the heart from the aorta through the incompetent aortic valve, although the usefulness of some of the eponymous signs has been questioned: Phonocardiograms detect AI by having electric voltage mimic the sounds the heart makes.Characteristics- indicative of aortic regurgitation are as follow:
Classification
The hemodynamic sequelae of AI are dependent on the rate of onset of AI. Therefore, can be acute or chronic as follows:
Acute aortic regurgitation In acute AR, as may be seen with acute perforation of the aortic valve due to endocarditis, there will be a sudden increase in the volume of blood in the left ventricle. The ventricle is unable to deal with the sudden change in volume. The filling pressure of the left ventricle will increase. This causes pressure in the left atrium to rise, and the individual will develop pulmonary edema. Severe acute aortic regurgitation is considered a medical emergency. There is a high mortality rate if the individual does not undergo immediate surgery for aortic valve replacement.Acute AR usually presents as florid congestive heart failure, and will not have any of the signs associated with chronic AR since the left ventricle had not yet developed the eccentric hypertrophy and dilatation that allow an increased stroke volume, which in turn cause bounding peripheral pulses. On auscultation, there may be a short diastolic murmur and a soft S1. S1 is soft because the elevated filling pressures close the mitral valve in diastole.Chronic aortic regurgitation If the individual survives the initial hemodynamic derailment that acute AR presents, the left ventricle adapts by its eccentric hypertrophy and dilatation with a subsequent compensated volume overload. The left ventricular filling pressures will revert to normal and the individual will no longer have overt heart failure. In this compensated phase, the individual may be totally asymptomatic and may have normal exercise tolerance. Eventually (typically after a latency period) the left ventricle will become decompensated, and filling pressures will increase. Some individuals enter this decompensated phase asymptomatically, treatment for AR involves aortic valve replacement prior to this decompensation phase.
Treatment
Aortic regurgitation can be treated either medically or surgically, depending on the acuteness of presentation, the symptoms and signs associated with the disease process, and the degree of left ventricular dysfunction. Surgical treatment in asymptomatic patients has been recommended if the ejection fraction falls to 50% or below, in the face of progressive and severe left ventricular dilatation, or with symptoms or abnormal response to exercise testing. For both groups of patients, surgery before the development of worsening ejection fraction/LV dilatation is expected to reduce the risk of sudden death, and is associated with lower peri-operative mortality. Also, surgery is optimally performed immediately in acute cases.
Medical treatment
Medical therapy of chronic aortic regurgitation that is stable and asymptomatic involves the use of vasodilators. Trials have shown a short-term benefit in the use of ACE inhibitors or angiotensin II receptor antagonists, nifedipine, and hydralazine in improving left ventricular wall stress, ejection fraction, and mass. The goal in using these pharmacologic agents is to decrease the afterload so that the left ventricle is somewhat spared. The regurgitant fraction may not change significantly, since the gradient between the aortic and left ventricular pressures is usually fairly low at the initiation of treatment. Other rather conservative medical treatments for stable and asymptomatic cases include low sodium diet, diuretics, digoxin, calcium blockers and avoiding very strenuous activity.As of 2007, the American Heart Association no longer recommends antibiotics for endocarditis prophylaxis before certain procedures in patients with aortic regurgitation. Antibiotic prophylaxis to prevent endocarditis before gastrointestinal or genitourinary procedures is no longer recommended for any patient with valvular disease. Cardiac stress test is useful in identifying individuals that may be best suited for surgical intervention. Radionuclide angiography is recommended and useful when the systolic wall stress is calculated and combined to the results.
Surgery
A surgical treatment for AR is aortic valve replacement; this is currently an open-heart procedure. In the case of severe acute aortic regurgitation, all individuals should undergo surgery, if there are no absolute contraindications (for surgery). Individuals with bacteremia with aortic valve endocarditis should not wait for treatment with antibiotics to take effect, given the high mortality associated with the acute AI. Replacement with an aortic valve homograft should be performed if feasible.
Prognosis
The risk of death in individuals with aortic regurgitation, dilated ventricle, normal ejection fraction who are asymptomatic is about 0.2 percent per year. Risk increases if the ejection fraction decreases or if the individual develops symptoms.Individuals with chronic (severe) aortic regurgitation follow a course that once symptoms appear, surgical intervention is needed. AI is fatal in 10 to 20% of individuals who do not undergo surgery for this condition. Left ventricle dysfunction determines to an extent the outlook for severity of aortic regurgitation cases.
References
Further reading
Hamirani, Yasmin S.; Dietl, Charles A.; Voyles, Wyatt; Peralta, Mel; Begay, Darlene; Raizada, Veena (2012-08-28). "Acute Aortic Regurgitation". Circulation. 126 (9): 1121–1126. doi:10.1161/CIRCULATIONAHA.112.113993. ISSN 0009-7322. PMID 22927474.
Dujardin, Karl S.; Enriquez-Sarano, Maurice; Schaff, Hartzell V.; Bailey, Kent R.; Seward, James B.; Tajik, A. Jamil (1999-04-13). "Mortality and Morbidity of Aortic Regurgitation in Clinical Practice A Long-Term Follow-Up Study". Circulation. 99 (14): 1851–1857. doi:10.1161/01.CIR.99.14.1851. ISSN 0009-7322. PMID 10199882.
== External links == |
Carbon monoxide poisoning | Carbon monoxide poisoning typically occurs from breathing in carbon monoxide (CO) at excessive levels. Symptoms are often described as "flu-like" and commonly include headache, dizziness, weakness, vomiting, chest pain, and confusion. Large exposures can result in loss of consciousness, arrhythmias, seizures, or death. The classically described "cherry red skin" rarely occurs. Long-term complications may include chronic fatigue, trouble with memory, and movement problems.CO is a colorless and odorless gas which is initially non-irritating. It is produced during incomplete burning of organic matter. This can occur from motor vehicles, heaters, or cooking equipment that run on carbon-based fuels. Carbon monoxide primarily causes adverse effects by combining with hemoglobin to form carboxyhemoglobin (HbCO) preventing the blood from carrying oxygen and expelling carbon dioxide as carbaminohemoglobin. Additionally, many other hemoproteins such as myoglobin, Cytochrome P450, and mitochondrial cytochrome oxidase are affected, along with other metallic and non-metallic cellular targets.Diagnosis is typically based on a HbCO level of more than 3% among nonsmokers and more than 10% among smokers. The biological threshold for carboxyhemoglobin tolerance is typically accepted to be 15% COHb, meaning toxicity is consistently observed at levels in excess of this concentration. The FDA has previously set a threshold of 14% COHb in certain clinical trials evaluating the therapeutic potential of carbon monoxide. In general, 30% COHb is considered severe carbon monoxide poisoning. The highest reported non-fatal carboxyhemoglobin level was 73% COHb.Efforts to prevent poisoning include carbon monoxide detectors, proper venting of gas appliances, keeping chimneys clean, and keeping exhaust systems of vehicles in good repair. Treatment of poisoning generally consists of giving 100% oxygen along with supportive care. This should generally be carried out until symptoms are no longer present and the HbCO level is less than 3%/10%.Carbon monoxide poisoning is relatively common, resulting in more than 20,000 emergency room visits a year in the United States. It is the most common type of fatal poisoning in many countries. In the United States, non-fire related cases result in more than 400 deaths a year. Poisonings occur more often in the winter, particularly from the use of portable generators during power outages. The toxic effects of CO have been known since ancient history. The discovery that hemoglobin is affected by CO emerged with an investigation by James Watt and Thomas Beddoes into the therapeutic potential of hydrocarbonate in 1793, and later confirmed by Claude Bernard between 1846 and 1857.
Background
Carbon monoxide is not toxic to all forms of life, and the toxicity is a classical dose-dependent example of hormesis. Small amounts of carbon monoxide are naturally produced through many enzymatic and non-enzymatic reactions across phylogenetic kingdoms where it can serve as an important neurotransmitter (subcategorized as a gasotransmitter) and a potential therapeutic agent. In the case of prokaryotes, some bacteria produce, consume and respond to carbon monoxide whereas certain other microbes are susceptible to its toxicity. Currently, there are no known adverse effects on photosynthesizing plants.The harmful effects of carbon monoxide are generally considered to be due to tightly binding with the prosthetic heme moiety of hemoproteins that results in interference with cellular operations, for example: carbon monoxide binds with hemoglobin to form carboxyhemoglobin which affects gas exchange and cellular respiration. Inhaling excessive concentrations of the gas can lead to hypoxic injury, nervous system damage, and even death.
As pioneered by Esther Killick, different species and different people across diverse demographics may have different carbon monoxide tolerance levels. The carbon monoxide tolerance level for any person is altered by several factors, including genetics (hemoglobin mutations), behavior such as activity level, rate of ventilation, a pre-existing cerebral or cardiovascular disease, cardiac output, anemia, sickle cell disease and other hematological disorders, geography and barometric pressure, and metabolic rate.
History
Humans have maintained a complex relationship with carbon monoxide since first learning to control fire circa 800,000 BC. Primitive caveman probably discovered the toxicity of carbon monoxide upon introducing fire into their dwellings. The early development of metallurgy and smelting technologies emerging circa 6,000 BC through the Bronze Age likewise plagued humankind with carbon monoxide exposure. Apart from the toxicity of carbon monoxide, indigenous Native Americans may have experienced the neuroactive properties of carbon monoxide through shamanistic fireside rituals.Early civilizations developed mythological tales to explain the origin of fire, such as Vulcan, Pkharmat, and Prometheus from Greek mythology who shared fire with humans. Aristotle (384–322 BC) first recorded that burning coals produced toxic fumes. Greek physician Galen (129–199 AD) speculated that there was a change in the composition of the air that caused harm when inhaled, and symptoms of CO poisoning appeared in Cassius Iatrosophistas Quaestiones Medicae et Problemata Naturalia circa 130 AD. Julian the Apostate, Caelius Aurelianus, and several others similarly documented early knowledge of the toxicity symptoms of carbon monoxide poisoning as caused by coal fumes in the ancient era.Documented cases by Livy and Cicero allude to carbon monoxide being used as a method of suicide in ancient Rome. Emperor Lucius Verus used smoke to execute prisoners. Many deaths have been linked to carbon monoxide poisoning including Emperor Jovian, Empress Fausta, and Seneca. The most high-profile death by carbon monoxide poisoning may possibly have been Cleopatra or Edgar Allan Poe.In the fifteenth century, coal miners believed sudden death was caused by evil spirits; carbon monoxide poisoning has been linked to supernatural and paranormal experiences, witchcraft, etc. throughout the following centuries including in the modern present day exemplified by Carrie Poppys investigations.Georg Ernst Stahl mentioned carbonarii halitus in 1697 in reference to toxic vapors thought to be carbon monoxide. Friedrich Hoffmann conducted the first modern scientific investigation into carbon monoxide poisoning from coal in 1716, notably rejecting villagers attributing death to demonic superstition. Herman Boerhaave conducted the first scientific experiments on the effect of carbon monoxide (coal fumes) on animals in the 1730s. Joseph Priestley is credited with first synthesizing carbon monoxide in 1772 which he had called heavy inflammable air, and Carl Wilhelm Scheele isolated carbon monoxide from coal in 1773 suggesting it to be the toxic entity.The dose-dependent risk of carbon monoxide poisoning as hydrocarbonate was investigated in the late 1790s by Thomas Beddoes, James Watt, Tiberius Cavallo, James Lind, Humphry Davy, and many others in the context of inhalation of factitious airs, much of which occurred at the Pneumatic Institution.William Cruickshank discovered carbon monoxide as a molecule containing one carbon and one oxygen atom in 1800, thereby initiating the modern era of research exclusively focused on carbon monoxide. The mechanism for toxicity was first suggested by James Watt in 1793, followed by Adrien Chenot in 1854 and finally demonstrated by Claude Bernard after 1846 as published in 1857 and also independently published by Felix Hoppe-Seyler in the same year.The first controlled clinical trial studying the toxicity of carbon monoxide occurred in 1973.
Historical detection
Carbon monoxide poisoning has plagued coal miners for many centuries. In the context of mining, carbon monoxide is widely known as whitedamp. John Scott Haldane identified carbon monoxide as the lethal constituent of afterdamp, the gas created by combustion, after examining many bodies of miners killed in pit explosions. By 1911, Haldane introduced the use of small animals for miners to detect dangerous levels of carbon monoxide underground, either white mice or canaries which have little tolerance for carbon monoxide thereby offering an early warning, i.e. Canary in a coal mine. The canary in British pits was replaced in 1986 by the electronic gas detector.
The first qualitative analytical method to detect carboxyhemoglobin emerged in 1858 with a colorimetric method developed by Felix Hoppe-Seyler, and the first quantitative analysis method emerged in 1880 with Josef von Fodor.
Historical treatment
The use of oxygen emerged with anecdotal reports such as Humphry Davy having been treated with oxygen in 1799 upon inhaling three quarts of hydrocarbonate (water gas). Samuel Witter developed an oxygen inhalation protocol in response to carbon monoxide poisoning in 1814. Similarly, an oxygen inhalation protocol was recommend for malaria (literally translated to "bad air") in 1830 based on malaria symptoms aligning with carbon monoxide poisoning. Other oxygen protocols emerged in the late 1800s. The use of hyperbaric oxygen in rats following poisoning was studied by Haldane in 1895 while its use in humans began in the 1960s.
Incidents
The worst accidental mass poisoning from carbon monoxide was the Balvano train disaster which occurred on 3 March 1944 in Italy, when a freight train with many illegal passengers stalled in a tunnel, leading to the death of over 500 people.Over 50 people are suspected to have died from smoke inhalation as a result of the Branch Davidian Massacre during the Siege of Waco in 1993.
Weaponization
In ancient history, Hannibal executed Roman prisoners with coal fumes during the Second Punic War.The extermination of stray dogs by a carbon monoxide gas chamber was described in 1874. In 1884, an article appeared in Scientific American describing the use of a carbon monoxide gas chamber for slaughterhouse operations as well as euthanizing a variety of animals.As part of the Holocaust during World War II, the Nazis used gas vans at Chelmno extermination camp and elsewhere to murder an estimated over 700,000 people by carbon monoxide poisoning. This method was also used in the gas chambers of several death camps such as Treblinka, Sobibor, and Belzec. Gassing with carbon monoxide started in Action T4. The gas was supplied by IG Farben in pressurized cylinders and fed by tubes into the gas chambers built at various mental hospitals, such as Hartheim Euthanasia Centre. Exhaust fumes from tank engines, for example, were used to supply the gas to the chambers.Recently, carbon monoxide gas chambers have been used to facilitate capital punishment exemplified by execution practices at the San Quentin State Prison.
Physiology
Carbon monoxide is produced naturally by many physiologically relevant enzymatic and non-enzymatic reactions best exemplified by heme oxygenase catalyzing the biotransformation of heme (an iron protoporphyrin) into biliverdin and eventually bilirubin. Aside from physiological signaling, most carbon monoxide is stored as carboxyhemoglobin at non-toxic levels below 3% HbCO.
Therapeutics
Small amounts of CO are beneficial and enzymes exist that produce it at times of oxidative stress. A variety of drugs are being developed to introduce small amounts of CO, these drugs are commonly called carbon monoxide-releasing molecules. Historically, the therapeutic potential of factitious airs, notably carbon monoxide as hydrocarbonate, was investigated by Thomas Beddoes, James Watt, Tiberius Cavallo, James Lind, Humphry Davy, and others in many labs such as the Pneumatic Institution.
Signs and symptoms
On average, exposures at 100 ppm or greater is dangerous to human health. In the United States, the OSHA limits long-term workplace exposure levels to less than 50 ppm averaged over an 8-hour period; in addition, employees are to be removed from any confined space if an upper limit ("ceiling") of 100 ppm is reached.
Acute poisoning
The main manifestations of carbon monoxide poisoning develop in the organ systems most dependent on oxygen use, the central nervous system and the heart. The initial symptoms of acute carbon monoxide poisoning include headache, nausea, malaise, and fatigue. These symptoms are often mistaken for a virus such as influenza or other illnesses such as food poisoning or gastroenteritis. Headache is the most common symptom of acute carbon monoxide poisoning; it is often described as dull, frontal, and continuous. Increasing exposure produces cardiac abnormalities including fast heart rate, low blood pressure, and cardiac arrhythmia; central nervous system symptoms include delirium, hallucinations, dizziness, unsteady gait, confusion, seizures, central nervous system depression, unconsciousness, respiratory arrest, and death. Less common symptoms of acute carbon monoxide poisoning include myocardial ischemia, atrial fibrillation, pneumonia, pulmonary edema, high blood sugar, lactic acidosis, muscle necrosis, acute kidney failure, skin lesions, and visual and auditory problems. Carbon monoxide exposure may lead to a significantly shorter life span due to heart damage.One of the major concerns following acute carbon monoxide poisoning is the severe delayed neurological manifestations that may occur. Problems may include difficulty with higher intellectual functions, short-term memory loss, dementia, amnesia, psychosis, irritability, a strange gait, speech disturbances, Parkinsons disease-like syndromes, cortical blindness, and a depressed mood. Depression may occur in those who did not have pre-existing depression. These delayed neurological sequelae may occur in up to 50% of poisoned people after 2 to 40 days. It is difficult to predict who will develop delayed sequelae; however, advanced age, loss of consciousness while poisoned, and initial neurological abnormalities may increase the chance of developing delayed symptoms.
Chronic poisoning
Chronic exposure to relatively low levels of carbon monoxide may cause persistent headaches, lightheadedness, depression, confusion, memory loss, nausea, hearing disorders and vomiting. It is unknown whether low-level chronic exposure may cause permanent neurological damage. Typically, upon removal from exposure to carbon monoxide, symptoms usually resolve themselves, unless there has been an episode of severe acute poisoning. However, one case noted permanent memory loss and learning problems after a three-year exposure to relatively low levels of carbon monoxide from a faulty furnace.Chronic exposure may worsen cardiovascular symptoms in some people. Chronic carbon monoxide exposure might increase the risk of developing atherosclerosis. Long-term exposures to carbon monoxide present the greatest risk to persons with coronary heart disease and in females who are pregnant.In experimental animals, carbon monoxide appears to worsen noise-induced hearing loss at noise exposure conditions that would have limited effects on hearing otherwise. In humans, hearing loss has been reported following carbon monoxide poisoning. Unlike the findings in animal studies, noise exposure was not a necessary factor for the auditory problems to occur.
Fatal poisoning
One classic sign of carbon monoxide poisoning is more often seen in the dead rather than the living – people have been described as looking red-cheeked and healthy (see below). However, since this "cherry-red" appearance is more common in the dead, it is not considered a useful diagnostic sign in clinical medicine. In autopsy examinations, the appearance of carbon monoxide poisoning is notable because unembalmed dead persons are normally bluish and pale, whereas dead carbon-monoxide poisoned people may appear unusually lifelike in coloration. The colorant effect of carbon monoxide in such postmortem circumstances is thus analogous to its use as a red colorant in the commercial meat-packing industry.
Epidemiology
The true number of cases of carbon monoxide poisoning is unknown, since many non-lethal exposures go undetected. From the available data, carbon monoxide poisoning is the most common cause of injury and death due to poisoning worldwide. Poisoning is typically more common during the winter months. This is due to increased domestic use of gas furnaces, gas or kerosene space heaters, and kitchen stoves during the winter months, which if faulty and/or used without adequate ventilation, may produce excessive carbon monoxide. Carbon monoxide detection and poisoning also increases during power outages, when electric heating and cooking appliances become inoperative and residents may temporarily resort to fuel-burning space heaters, stoves, and grills (some of which are safe only for outdoor use but nonetheless are errantly burned indoors).It has been estimated that more than 40,000 people per year seek medical attention for carbon monoxide poisoning in the United States. 95% of carbon monoxide poisoning deaths in the United States are due to gas space heaters. In many industrialized countries, carbon monoxide is the cause of more than 50% of fatal poisonings. In the United States, approximately 200 people die each year from carbon monoxide poisoning associated with home fuel-burning heating equipment. Carbon monoxide poisoning contributes to the approximately 5613 smoke inhalation deaths each year in the United States. The CDC reports, "Each year, more than 500 Americans die from unintentional carbon monoxide poisoning, and more than 2,000 commit suicide by intentionally poisoning themselves." For the 10-year period from 1979 to 1988, 56,133 deaths from carbon monoxide poisoning occurred in the United States, with 25,889 of those being suicides, leaving 30,244 unintentional deaths. A report from New Zealand showed that 206 people died from carbon monoxide poisoning in the years of 2001 and 2002. In total carbon monoxide poisoning was responsible for 43.9% of deaths by poisoning in that country. In South Korea, 1,950 people had been poisoned by carbon monoxide with 254 deaths from 2001 through 2003. A report from Jerusalem showed 3.53 per 100,000 people were poisoned annually from 2001 through 2006. In Hubei, China, 218 deaths from poisoning were reported over a 10-year period with 16.5% being from carbon monoxide exposure.
Causes
Carbon monoxide is a product of combustion of organic matter under conditions of restricted oxygen supply, which prevents complete oxidation to carbon dioxide (CO2). Sources of carbon monoxide include cigarette smoke, house fires, faulty furnaces, heaters, wood-burning stoves, internal combustion vehicle exhaust, electrical generators, propane-fueled equipment such as portable stoves, and gasoline-powered tools such as leaf blowers, lawn mowers, high-pressure washers, concrete cutting saws, power trowels, and welders. Exposure typically occurs when equipment is used in buildings or semi-enclosed spaces.Riding in the back of pickup trucks has led to poisoning in children. Idling automobiles with the exhaust pipe blocked by snow has led to the poisoning of car occupants. Any perforation between the exhaust manifold and shroud can result in exhaust gases reaching the cabin. Generators and propulsion engines on boats, especially houseboats, has resulted in fatal carbon monoxide exposures.Poisoning may also occur following the use of a self-contained underwater breathing apparatus (SCUBA) due to faulty diving air compressors.In caves carbon monoxide can build up in enclosed chambers due to the presence of decomposing organic matter. In coal mines incomplete combustion may occur during explosions resulting in the production of afterdamp. The gas is up to 3% CO and may be fatal after just a single breath. Following an explosion in a colliery, adjacent interconnected mines may become dangerous due to the afterdamp leaking from mine to mine. Such an incident followed the Trimdon Grange explosion which killed men in the Kelloe mine.Another source of poisoning is exposure to the organic solvent dichloromethane, also known as methylene chloride, found in some paint strippers, as the metabolism of dichloromethane produces carbon monoxide. In November 2019, an EPA ban on dichloromethane in paint strippers for consumer use took effect in the United States.
Prevention
Detectors
Prevention remains a vital public health issue, requiring public education on the safe operation of appliances, heaters, fireplaces, and internal-combustion engines, as well as increased emphasis on the installation of carbon monoxide detectors. Carbon monoxide is tasteless, odourless, and colourless, and therefore can not be detected by visual cues or smell.The United States Consumer Product Safety Commission has stated, "carbon monoxide detectors are as important to home safety as smoke detectors are," and recommends each home have at least one carbon monoxide detector, and preferably one on each level of the building. These devices, which are relatively inexpensive and widely available, are either battery- or AC-powered, with or without battery backup. In buildings, carbon monoxide detectors are usually installed around heaters and other equipment. If a relatively high level of carbon monoxide is detected, the device sounds an alarm, giving people the chance to evacuate and ventilate the building. Unlike smoke detectors, carbon monoxide detectors do not need to be placed near ceiling level.
The use of carbon monoxide detectors has been standardized in many areas. In the US, NFPA 720–2009, the carbon monoxide detector guidelines published by the National Fire Protection Association, mandates the placement of carbon monoxide detectors/alarms on every level of the residence, including the basement, in addition to outside sleeping areas. In new homes, AC-powered detectors must have battery backup and be interconnected to ensure early warning of occupants at all levels. NFPA 720-2009 is the first national carbon monoxide standard to address devices in non-residential buildings. These guidelines, which now pertain to schools, healthcare centers, nursing homes, and other non-residential buildings, include three main points:
1. A secondary power supply (battery backup) must operate all carbon monoxide notification appliances for at least 12 hours,
2. Detectors must be on the ceiling in the same room as permanently installed fuel-burning appliances, and
3. Detectors must be located on every habitable level and in every HVAC zone of the building.Gas organizations will often recommend getting gas appliances serviced at least once a year.
Legal requirements
The NFPA standard is not necessarily enforced by law. As of April 2006, the US state of Massachusetts requires detectors to be present in all residences with potential CO sources, regardless of building age and whether they are owner-occupied or rented. This is enforced by municipal inspectors and was inspired by the death of 7-year-old Nicole Garofalo in 2005 due to snow blocking a home heating vent. Other jurisdictions may have no requirement or only mandate detectors for new construction or at time of sale.
Despite similar deaths in vehicles with clogged exhaust pipes (for example in the Northeastern United States blizzard of 1978 and February 2013 noreaster) and the commercial availability of the equipment, there is no legal requirement for automotive CO detectors.
World Health Organization recommendations
The following guideline values (ppm values rounded) and periods of time-weighted average exposures have been determined in such a way that the carboxyhaemoglobin (COHb) level of 2.5% is not exceeded, even when a normal subject engages in light or moderate exercise:
100 mg/m3 (87 ppm) for 15 min
60 mg/m3 (52 ppm) for 30 min
30 mg/m3 (26 ppm) for 1 h
10 mg/m3 (9 ppm) for 8 h
7 mg/m3 (6 ppm) for 24 h (for indoor air quality, so as not to exceed 2% COHb for chronic exposure)
Diagnosis
As many symptoms of carbon monoxide poisoning also occur with many other types of poisonings and infections (such as the flu), the diagnosis is often difficult. A history of potential carbon monoxide exposure, such as being exposed to a residential fire, may suggest poisoning, but the diagnosis is confirmed by measuring the levels of carbon monoxide in the blood. This can be determined by measuring the amount of carboxyhemoglobin compared to the amount of hemoglobin in the blood.The ratio of carboxyhemoglobin to hemoglobin molecules in an average person may be up to 5%, although cigarette smokers who smoke two packs per day may have levels up to 9%. In symptomatic poisoned people they are often in the 10–30% range, while persons who die may have postmortem blood levels of 30–90%.As people may continue to experience significant symptoms of CO poisoning long after their blood carboxyhemoglobin concentration has returned to normal, presenting to examination with a normal carboxyhemoglobin level (which may happen in late states of poisoning) does not rule out poisoning.
Measuring
Carbon monoxide may be quantitated in blood using spectrophotometric methods or chromatographic techniques in order to confirm a diagnosis of poisoning in a person or to assist in the forensic investigation of a case of fatal exposure.
A CO-oximeter can be used to determine carboxyhemoglobin levels. Pulse CO-oximeters estimate carboxyhemoglobin with a non-invasive finger clip similar to a pulse oximeter. These devices function by passing various wavelengths of light through the fingertip and measuring the light absorption of the different types of hemoglobin in the capillaries. The use of a regular pulse oximeter is not effective in the diagnosis of carbon monoxide poisoning as these devices may be unable to distinguish carboxyhemoglobin from oxyhemoglobin.Breath CO monitoring offers an alternative to pulse CO-oximetry. Carboxyhemoglobin levels have been shown to have a strong correlation with breath CO concentration. However, many of these devices require the user to inhale deeply and hold their breath to allow the CO in the blood to escape into the lung before the measurement can be made. As this is not possible in people who are unresponsive, these devices may not appropriate for use in on-scene emergency care detection of CO poisoning.
Differential diagnosis
There are many conditions to be considered in the differential diagnosis of carbon monoxide poisoning. The earliest symptoms, especially from low level exposures, are often non-specific and readily confused with other illnesses, typically flu-like viral syndromes, depression, chronic fatigue syndrome, chest pain, and migraine or other headaches. Carbon monoxide has been called a "great mimicker" due to the presentation of poisoning being diverse and nonspecific. Other conditions included in the differential diagnosis include acute respiratory distress syndrome, altitude sickness, lactic acidosis, diabetic ketoacidosis, meningitis, methemoglobinemia, or opioid or toxic alcohol poisoning.
Treatment
Initial treatment for carbon monoxide poisoning is to immediately remove the person from the exposure without endangering further people. Those who are unconscious may require CPR on site. Administering oxygen via non-rebreather mask shortens the half-life of carbon monoxide from 320 minutes, when breathing normal air, to only 80 minutes. Oxygen hastens the dissociation of carbon monoxide from carboxyhemoglobin, thus turning it back into hemoglobin. Due to the possible severe effects in the baby, pregnant women are treated with oxygen for longer periods of time than non-pregnant people.
Hyperbaric oxygen
Hyperbaric oxygen is also used in the treatment of carbon monoxide poisoning, as it may hasten dissociation of CO from carboxyhemoglobin and cytochrome oxidase to a greater extent than normal oxygen. Hyperbaric oxygen at three times atmospheric pressure reduces the half life of carbon monoxide to 23 (~80/3 minutes) minutes, compared to 80 minutes for oxygen at regular atmospheric pressure. It may also enhance oxygen transport to the tissues by plasma, partially bypassing the normal transfer through hemoglobin. However, it is controversial whether hyperbaric oxygen actually offers any extra benefits over normal high flow oxygen, in terms of increased survival or improved long-term outcomes. There have been randomized controlled trials in which the two treatment options have been compared; of the six performed, four found hyperbaric oxygen improved outcome and two found no benefit for hyperbaric oxygen. Some of these trials have been criticized for apparent flaws in their implementation. A review of all the literature concluded that the role of hyperbaric oxygen is unclear and the available evidence neither confirms nor denies a medically meaningful benefit. The authors suggested a large, well designed, externally audited, multicentre trial to compare normal oxygen with hyperbaric oxygen. While hyperbaric oxygen therapy is used for severe poisonings, the benefit over standard oxygen delivery is unclear.
Other
Further treatment for other complications such as seizure, hypotension, cardiac abnormalities, pulmonary edema, and acidosis may be required. Increased muscle activity and seizures should be treated with dantrolene or diazepam; diazepam should only be given with appropriate respiratory support. Hypotension requires treatment with intravenous fluids; vasopressors may be |
Carbon monoxide poisoning | required to treat myocardial depression. Cardiac dysrhythmias are treated with standard advanced cardiac life support protocols. If severe, metabolic acidosis is treated with sodium bicarbonate. Treatment with sodium bicarbonate is controversial as acidosis may increase tissue oxygen availability. Treatment of acidosis may only need to consist of oxygen therapy. The delayed development of neuropsychiatric impairment is one of the most serious complications of carbon monoxide poisoning. Brain damage is confirmed following MRI or CAT scans. Extensive follow up and supportive treatment is often required for delayed neurological damage. Outcomes are often difficult to predict following poisoning, especially people who have symptoms of cardiac arrest, coma, metabolic acidosis, or have high carboxyhemoglobin levels. One study reported that approximately 30% of people with severe carbon monoxide poisoning will have a fatal outcome. It has been reported that electroconvulsive therapy (ECT) may increase the likelihood of delayed neuropsychiatric sequelae (DNS) after carbon monoxide (CO) poisoning. A device that also provides some carbon dioxide to stimulate faster breathing (sold under the brand name ClearMate) may also be used.
Pathophysiology
The precise mechanisms by which the effects of carbon monoxide are induced upon bodily systems are complex and not yet fully understood. Known mechanisms include carbon monoxide binding to hemoglobin, myoglobin and mitochondrial cytochrome c oxidase and restricting oxygen supply, and carbon monoxide causing brain lipid peroxidation.
Hemoglobin
Carbon monoxide has a higher diffusion coefficient compared to oxygen, and the main enzyme in the human body that produces carbon monoxide is heme oxygenase, which is located in nearly all cells and platelets. Most endogenously produced CO is stored bound to hemoglobin as carboxyhemoglobin. The simplistic understanding for the mechanism of carbon monoxide toxicity is based on excess carboxyhemoglobin decreasing the oxygen-delivery capacity of the blood to tissues throughout the body. In humans, the affinity between hemoglobin and carbon monoxide is approximately 240 times stronger than the affinity between hemoglobin and oxygen. However, certain mutations such as the Hb-Kirklareli mutation has a relative 80,000 times greater affinity for carbon monoxide than oxygen resulting in systemic carboxyhemoglobin reaching a sustained level of 16% COHb.Hemoglobin is a tetramer with four prosthetic heme groups to serve as oxygen binding sites. The average red blood cell contains 250 million hemoglobin molecules, therefore 1 billion heme sites capable of binding gas. The binding of carbon monoxide at any one of these sites increases the oxygen affinity of the remaining three sites, which causes the hemoglobin molecule to retain oxygen that would otherwise be delivered to the tissue; therefore carbon monoxide binding at any site may be as dangerous as carbon monoxide binding to all sites. Delivery of oxygen is largely driven by the Bohr effect and Haldane effect. To provide a simplified synopsis of the molecular mechanism of systemic gas exchange in laymans terms, upon inhalation of air it was widely thought oxygen binding to any of the heme sites triggers a conformational change in the globin/protein unit of hemoglobin which then enables the binding of additional oxygen to each of the other vacant heme sites. Upon arrival to the cell/tissues, oxygen release into the tissue is driven by "acidification" of the local pH (meaning a relatively higher concentration of acidic protons/hydrogen ions) caused by an increase in the biotransformation of carbon dioxide waste into carbonic acid via carbonic anhydrase. In other words, oxygenated arterial blood arrives at cells in the "hemoglobin R-state" which has deprotonated/unionized amino acid residues (regarding nitrogen/amines) due to the less-acidic arterial pH environment (arterial blood averages pH 7.407 whereas venous blood is slightly more acidic at pH 7.371). The "T-state" of hemoglobin is deoxygenated in venous blood partially due to protonation/ionization caused by the acidic environment hence causing a conformation unsuited for oxygen-binding (in other words, oxygen is ejected upon arrival to the cell because acid "attacks" the amines of hemoglobin causing ionization/protonation of the amine residues resulting in a conformation change unsuited for retaining oxygen). Furthermore, the mechanism for formation of carbaminohemoglobin generates additional acidic hydrogen ions that may further stabilize the protonated/ionized deoxygenated hemoglobin. Upon return of venous blood into the lung and subsequent exhalation of carbon dioxide, the blood is "de-acidified" (see also: hyperventilation) allowing for the deprotonation/unionization of hemoglobin to then re-enable oxygen-binding as part of the transition to arterial blood (note this process is complex due to involvement of chemoreceptors and other physiological functionalities). Carbon monoxide is not ejected due to acid, therefore carbon monoxide poisoning disturbs this physiological process hence the venous blood of poisoning patients is bright red akin to arterial blood since the carbonyl/carbon monoxide is retained. Hemoglobin is dark in deoxygenated venous blood, but it has a bright red color when carrying blood in oxygenated arterial blood and when converted into carboxyhemoglobin in both arterial and venous blood, so poisoned cadavers and even commercial meats treated with carbon monoxide acquire an unnatural lively reddish hue.At toxic concentrations, carbon monoxide as carboxyhemoglobin significantly interferes with respiration and gas exchange by simultaneously inhibiting acquisition and delivery of oxygen to cells and preventing formation of carbaminohemoglobin which accounts for approximately 30% of carbon dioxide exportation. Therefore, a patient with carbon monoxide poisoning may experience severe hypoxia and acidosis (potentially both respiratory acidosis and metabolic acidosis) in addition to the toxicities of excess carbon monoxide inhibiting numerous hemoproteins, metallic and non-metallic targets which affect cellular machinery.
Myoglobin
Carbon monoxide also binds to the hemeprotein myoglobin. It has a high affinity for myoglobin, about 60 times greater than that of oxygen. Carbon monoxide bound to myoglobin may impair its ability to utilize oxygen. This causes reduced cardiac output and hypotension, which may result in brain ischemia. A delayed return of symptoms have been reported. This results following a recurrence of increased carboxyhemoglobin levels; this effect may be due to a late release of carbon monoxide from myoglobin, which subsequently binds to hemoglobin.
Cytochrome oxidase
Another mechanism involves effects on the mitochondrial respiratory enzyme chain that is responsible for effective tissue utilization of oxygen. Carbon monoxide binds to cytochrome oxidase with less affinity than oxygen, so it is possible that it requires significant intracellular hypoxia before binding. This binding interferes with aerobic metabolism and efficient adenosine triphosphate synthesis. Cells respond by switching to anaerobic metabolism, causing anoxia, lactic acidosis, and eventual cell death. The rate of dissociation between carbon monoxide and cytochrome oxidase is slow, causing a relatively prolonged impairment of oxidative metabolism.
Central nervous system effects
The mechanism that is thought to have a significant influence on delayed effects involves formed blood cells and chemical mediators, which cause brain lipid peroxidation (degradation of unsaturated fatty acids). Carbon monoxide causes endothelial cell and platelet release of nitric oxide, and the formation of oxygen free radicals including peroxynitrite. In the brain this causes further mitochondrial dysfunction, capillary leakage, leukocyte sequestration, and apoptosis. The result of these effects is lipid peroxidation, which causes delayed reversible demyelination of white matter in the central nervous system known as Grinker myelinopathy, which can lead to edema and necrosis within the brain. This brain damage occurs mainly during the recovery period. This may result in cognitive defects, especially affecting memory and learning, and movement disorders. These disorders are typically related to damage to the cerebral white matter and basal ganglia. Hallmark pathological changes following poisoning are bilateral necrosis of the white matter, globus pallidus, cerebellum, hippocampus and the cerebral cortex.
Pregnancy
Carbon monoxide poisoning in pregnant women may cause severe adverse fetal effects. Poisoning causes fetal tissue hypoxia by decreasing the release of maternal oxygen to the fetus. Carbon monoxide also crosses the placenta and combines with fetal hemoglobin, causing more direct fetal tissue hypoxia. Additionally, fetal hemoglobin has a 10 to 15% higher affinity for carbon monoxide than adult hemoglobin, causing more severe poisoning in the fetus than in the adult. Elimination of carbon monoxide is slower in the fetus, leading to an accumulation of the toxic chemical. The level of fetal morbidity and mortality in acute carbon monoxide poisoning is significant, so despite mild maternal poisoning or following maternal recovery, severe fetal poisoning or death may still occur.
References
External links
Centers for Disease Control and Prevention (CDC) – Carbon Monoxide – NIOSH Workplace Safety and Health Topic
International Programme on Chemical Safety (1999). Carbon Monoxide, Environmental Health Criteria 213, Geneva: WHO |
Cryptogenic organizing pneumonia | Cryptogenic organizing pneumonia (COP), formerly known as bronchiolitis obliterans organizing pneumonia (BOOP), is an inflammation of the bronchioles (bronchiolitis) and surrounding tissue in the lungs. It is a form of idiopathic interstitial pneumonia.It is often a complication of an existing chronic inflammatory disease such as rheumatoid arthritis, dermatomyositis, or it can be a side effect of certain medications such as amiodarone. COP was first described by Gary Epler in 1985.The clinical features and radiological imaging resemble infectious pneumonia. However, diagnosis is suspected after there is no response to multiple antibiotics, and blood and sputum cultures are negative for organisms.
Terminology
"Organizing" refers to unresolved pneumonia (in which the alveolar exudate persists and eventually undergoes fibrosis) in which fibrous tissue forms in the alveoli. The phase of resolution and/or remodeling following bacterial infections is commonly referred to as organizing pneumonia, both clinically and pathologically.
The American Thoracic Society and the European Respiratory Society hold that "cryptogenic organizing pneumonia" is the preferred clinical term for this disease for multiple reasons:
Avoid confusion with bronchiolitis obliterans, which may not be visualized in every case of this disease.
Avoid confusion with constrictive bronchiolitis
Emphasize the cryptogenic nature of the disease
Signs and symptoms
The classic presentation of COP is the development of nonspecific systemic (e.g., fevers, chills, night sweats, fatigue, weight loss) and respiratory (e.g. difficulty breathing, cough) symptoms in association with filling of the lung alveoli that is visible on chest x-ray. This presentation is usually so suggestive of an infection that the majority of patients with COP have been treated with at least one failed course of antibiotics by the time the true diagnosis is made. Symptoms are usually subacute, occurring over weeks to months with dry cough (seen in 71% of people), dyspnea (shortness of breath)(62%) and fever (44%) being the most common symptoms.
Causes
Pulmonary infection by bacteria, viruses and parasites
Drugs: antineoplastic drugs, erlotinib, amiodarone
Chemical exposure, most notably to diacetylVaping: On October 17, 2019, the American Journal of Clinical Pathology reported that lung biopsies from patients with vaping-associated pulmonary illness show acute lung injury patterns, including organizing pneumonia.
Ionizing radiations
Inflammatory diseases
Systemic lupus
Rheumatoid arthritis (RA-associated COP)
Scleroderma
Bronchial obstruction
Proximal bronchial squamous cell carcinoma
SARS-CoV-2
Analysis of COVID-19 CT imaging along with postmortem lung biopsies and autopsies suggest that the majority of patients with COVID-19 pulmonary involvement also have secondary organizing pneumonia (OP) or its histological variant, acute fibrinous and organizing pneumonia, which are both well-known complications of viral infections. It was identified in 1985, although its symptoms had been noted before but not recognised as a separate lung disease. The risk of COP is higher for people with inflammatory diseases like lupus, dermatomyositis, rheumatoid arthritis, and scleroderma. It most commonly presents in the 5th or 6th decade of life and it is exceedingly rare in children.
Pathophysiology
Organizing pneumonia is usually preceded by some type of lung injury that causes a localized denudation or disruption in continuity of the epithelial basal laminae of the type 1 alveolar pneumocytes that line the alveoli. This injury to the epithelial basal lamina results in inflammatory cells and plasma proteins leaking into the alveolar space and forming fibrin, resulting in an initial fibroblast driven intra-alveolar fibroproliferation. The fibroblasts differentiate into myofibroblasts and continue to form fibrosis resulting in intra-alveolar fibroinflammatory buds (Massons Bodies) that are characteristic of organizing pneumonia. These Massons bodies consist of inflammatory cells contained in an extracellular matrix consisting of type I collagen, fibronectin, procollagen type III, tenascin C and proteoglycans. Angiogenesis , or the formation of blood vessels, occurs in the Massons bodies and this is driven by vascular endothelial growth factor. Remodeling occurs, resulting in the intra-alveolar fibroinflammatory buds (Massons Bodies) moving into the interstitial space and forming collagen globules that are then covered by type 1 alveolar epithelial cells with well developed basement membranes. These type 1 alveolar epithelial cells (pneumocytes) then proliferate, restoring the continuity and function of the alveolar unit. This process is in contrast to the histopathologic changes seen in usual interstitial pneumonia where extensive fibrosis and inflammation occur leading to fibroblastic foci to form in the alveolar spaces resulting in obliteration of the alveolar space, scarring and significant damage to lung architecture (the alveoli).Tissue inhibitors of metalloproteinases (which inhibit breakdown of the extracellular matrix connective tissue) are more active in usual interstitial pneumonia as compared to organizing pneumonia, this is thought to lead to a greater deposition of connective tissue in the alveolar space in interstitial pneumonia as compared to organizing pneumonia and may explain the progressive, irreversible fibrosis seen in usual interstitial pneumonia. Gelatinolytic activity (resulting in the breakdown of extracellular matrix connective tissue) is greater in organizing pneumonia as compared to usual interstitial pneumonia, and this is thought to contribute to the reversible fibroproliferation characteristic of organizing pneumonia.
Diagnosis
On clinical examination, crackles are common, and more rarely, patients may have clubbing (<5% of cases). Laboratory findings are nonspecific but inflammatory markers such as the erythrocyte sedimentation rate or C-reactive protein and the lymphocyte count are frequently elevated. If the organizing pneumonia is secondary to a connective tissue disorder, then the associated laboratory values such as the anti-nuclear antibody, rheumatoid factor, anti-citrullinated protein antibodies, anti-dsDNA antibodies and other similar connective tissue associated antibodies are elevated.Pulmonary function testing in people with organizing pneumonia, either cryptogenic or due to secondary causes, shows a restrictive defect with a decrease in the gas absorptive capacity of the lungs (seen as a decrease in the diffusion capacity of carbon monoxide). Airflow obstruction is usually not seen on pulmonary function testing.Bronchoscopy with bronchoalveolar lavage is recommended in possible cases of organizing pneumonia to rule out infection and other causes of alveolar infiltrates. The bronchoalveolar lavage in organizing pneumonia shows a lymphocytic predominant inflammation of the alveoli with increases in neutrophils and eosinophils. Resolution of inflammatory cells in the bronchoalveolar lavage is usually delayed in organizing pneumonia, lagging behind clinical and radiographic improvement.Biopsy findings in patients with organizing pneumonia consist of loose connective tissue plugs involving the alveoli, alveolar ducts and bronchioles. The loose connective tissue plugs occupying the alveolar spaces often connect to other connective tissue plugs in nearby alveoli via the pores of Kohn creating a characteristic butterfly pattern on histology. There is usually minimal to no interstitial inflammatory changes in biopsies of organizing pneumonia.
Imaging
The chest x-ray is distinctive with features that appear similar to an extensive pneumonia, with both lungs showing widespread white patches. The white patches may seem to migrate from one area of the lung to another as the disease persists or progresses. Computed tomography (CT) may be used to confirm the diagnosis. Often the findings are typical enough to allow the doctor to make a diagnosis without ordering additional tests. To confirm the diagnosis, a doctor may perform a lung biopsy using a bronchoscope. Many times, a larger specimen is needed and must be removed surgically.
Plain chest radiography shows normal lung volumes, with characteristic patchy unilateral or bilateral consolidation. Small nodular opacities occur in up to 50% of patients and large nodules in 15%. On high resolution computed tomography, airspace consolidation with air bronchograms is present in more than 90% of patients, often with a lower zone predominance. A subpleural or peribronchiolar distribution is noted in up to 50% of patients. Ground glass appearance or hazy opacities associated with the consolidation are detected in most patients.
Histologically, cryptogenic organizing pneumonia is characterized by the presence of polypoid plugs of loose organizing connective tissue (Masson bodies) within alveolar ducts, alveoli, and bronchioles.
Unusual presentations of organizing pneumonia
While patchy bilateral disease is typical, there are unusual variants of organizing pneumonia where it may appear as multiple nodules or masses. One rare presentation, focal organizing pneumonia, may be indistinguishable from lung cancer based on imaging alone, requiring biopsy or surgical resection to make the diagnosis.
Complications
Rare cases of COP have induced with lobar cicatricial atelectasis.
Treatment
Systemic steroids are considered the first line treatment for organizing pneumonia, with patients often having clinical improvement within 72 hours of steroid initiation and most patients achieving recovery. A prolonged treatment course is indicated, with patients usually requiring at least 4-6 months of treatment. Patients who are treated with larger doses of steroids require prophylaxis against pneumocystis jirovecii. Relapses may occur and are more likely to occur in severe disease or when steroids are tapered too soon or too quickly. Alternative or adjunct treatment options include macrolide antibiotics (due to anti-inflammatory properties), azathioprine and cyclophosphamide.
References
External links
"Idiopathic Interstitial Pneumonias". Merck Manual Professional. May 2008. |
Alpha-thalassemia | Alpha-thalassemia (α-thalassemia, α-thalassaemia) is a form of thalassemia involving the genes HBA1 and HBA2. Thalassemias are a group of inherited blood conditions which result in the impaired production of hemoglobin, the molecule that carries oxygen in the blood. Normal hemoglobin consists of two alpha chains and two beta chains; in alpha-thalassemia, there is a quantitative decrease in the amount of alpha chains, resulting in fewer normal hemoglobin molecules. Furthermore, alpha-thalassemia leads to the production of unstable beta globin molecules which cause increased red blood cell destruction. The degree of impairment is based on which clinical phenotype is present (how many genes are affected).
Signs and symptoms
The presentation of individuals with alpha-thalassemia consists of:
Cause
Alpha-thalassemias are most commonly inherited in a Mendelian recessive manner. They are also associated with deletions of chromosome 16p. Alpha thalassemia can also be acquired under rare circumstances.
Pathophysiology
The mechanism sees that α thalassemias results in decreased alpha-globin production, therefore fewer alpha-globin chains are produced, resulting in an excess of β chains in adults and excess γ chains in newborns. The excess β chains form unstable tetramers called hemoglobin H or HbH of four beta chains. The excess γ chains form tetramers which are poor carriers of O2 since their affinity for O2 is too high, so it is not dissociated in the periphery. Homozygote α0 thalassaemias, where numerous γ4 but no α-globins occur at all (referred to as Hb Barts), often result in death soon after birth.
Diagnosis
Diagnosis of alpha-thalassemia is primarily by laboratory evaluation and molecular diagnosis. Alpha-thalassemia can be mistaken for iron-deficiency anaemia on a full blood count or blood film, as both conditions have a microcytic anaemia. Serum iron and serum ferritin can be used to exclude iron-deficiency anaemia.
Types
Two genetic loci exist for α globin, thus four alleles are in diploid cells. Two alleles are maternal and two alleles are paternal in origin. The severity of the α-thalassemias is correlated with the number of affected α-globin alleles: the greater, the more severe will be the manifestations of the disease. When noting the genotype, an "α" indicates a functional alpha chain, and - a pathological one.
Laboratory diagnosis
The ability to measure hemoglobin Barts makes it useful in newborn screening tests. If hemoglobin Barts is detected on a newborn screen, the patient is usually referred for further evaluation since detection of hemoglobin Barts can indicate either one alpha globin gene deletion, making the baby a silent alpha thalassemia carrier, two alpha globin gene deletions (alpha thalassemia), or hemoglobin H disease (three alpha globin gene deletions).Deletion of four alpha globin genes was previously felt to be incompatible with life, but there are currently 69 patients who have survived past infancy. All such children too show high level of hemoglobin Barts on newborn screen along with other variants.Post-newborn ages, initial laboratory diagnosis should include a complete blood count and red blood cell indices. As well, a peripheral blood smear should be carefully reviewed. In hemoglobin H disease, red blood cells containing hemoglobin H inclusions can be visualized on the blood smear using new methylene blue or brilliant cresyl blue stain.Hemoglobin analysis is important for the diagnosis of alpha-thalassemia as it determines the types and percentages of types of hemoglobin present. Several different methods of hemoglobin analysis exist, including hemoglobin electrophoresis, capillary electrophoresis and high-performance liquid chromatography.Molecular analysis of DNA sequences (DNA analysis) can be used for the confirmation of a diagnosis of alpha-thalassemia, particularly for the detection of alpha-thalassemia carriers (deletions or mutations in only one or two alpha-globin genes).
Treatment
Treatment for alpha-thalassemia may include blood transfusions to maintain hemoglobin at a level that reduces symptoms of anemia. The decision to initiate transfusions depends on the clinical severity of the disease. Splenectomy is a possible treatment option to increase total hemoglobin levels in cases of worsening anemia due to an overactive or enlarged spleen, or when transfusion therapy is not possible. However, splenectomy is avoided when other options are available due to an increased risk of serious infections and thrombosis.Additionally, gallstones may be a problem that would require surgery. Secondary complications from febrile episode should be monitored, and most individuals live without any need for treatment. Additionally, stem cell transplantation should be considered as a treatment (and cure), which is best done in early age. Other options, such as gene therapy, are still being developed.A study by Kreger et al combining a retrospective review of three cases of alpha thalassemia major and a literature review of 17 cases found that in utero transfusion can lead to favorable outcomes. Successful hematopoietic cell transplantation was eventually carried out in four patients.
Epidemiology
Worldwide distribution of inherited alpha-thalassemia corresponds to areas of malaria exposure, suggesting a protective role. Thus, alpha-thalassemia is common in sub-Saharan Africa, the Mediterranean Basin, and generally tropical (and subtropical) regions. The epidemiology of alpha-thalassemia in the US reflects this global distribution pattern. More specifically, HbH disease is seen in Southeast Asia and the Middle East, while Hb Bart hydrops fetalis is acknowledged in Southeast Asia only.
The data indicate that 15% of the Greek and Turkish Cypriots are carriers of beta-thalassaemia genes, while 10% of the population carry alpha-thalassaemia genes.
See also
Beta-thalassemia
Delta-thalassemia
Hemoglobinopathy
References
Further reading
Anie KA, Massaglia P (March 2014). "Psychological therapies for thalassaemia". The Cochrane Database of Systematic Reviews (3): CD002890. doi:10.1002/14651858.cd002890.pub2. PMC 7138048. PMID 24604627.
Galanello R, Cao A (February 2011). "Gene test review. Alpha-thalassemia". Genetics in Medicine. 13 (2): 83–8. doi:10.1097/GIM.0b013e3181fcb468. PMID 21381239.
External links
"What Are Thalassemias? - NHLBI, NIH". www.nhlbi.nih.gov. Retrieved 15 September 2016. |
Actinomycosis | Actinomycosis is a rare infectious bacterial disease caused by Actinomyces species. The name refers to ray-like appearance of the organisms in the granules. About 70% of infections are due to either Actinomyces israelii or A. gerencseriae. Infection can also be caused by Streptomyces somaliensis and Propionibacterium propionicus. The condition is likely to be a polymicrobial anaerobic infection.
Signs and symptoms
The disease is characterised by the formation of painful abscesses in the mouth, lungs, breast, or gastrointestinal tract. Actinomycosis abscesses grow larger as the disease progresses, often over months. In severe cases, they may penetrate the surrounding bone and muscle to the skin, where they break open and leak large amounts of pus, which often contains characteristic granules filled with progeny bacteria. These granules are often called "sulfur granules" due to their yellow appearance, although they may also be white, gray or brown.
Causes
Actinomycosis is primarily caused by any of several members of the bacterial genus Actinomyces. These bacteria are generally anaerobes. In animals, they normally live in the small spaces between the teeth and gums, causing infection only when they can multiply freely in anoxic environments. An affected human often has recently had dental work, poor oral hygiene, periodontal disease, radiation therapy, or trauma (broken jaw) causing local tissue damage to the oral mucosa, all of which predispose the person to developing actinomycosis. A. israelii is a normal commensal species part of the microbiota species of the lower reproductive tract of women. They are also normal commensals among the gut flora of the caecum; thus, abdominal actinomycosis can occur following removal of the appendix. The three most common sites of infection are decayed teeth, the lungs, and the intestines. Actinomycosis infections are typically polymicrobial, containing additional bacterial species; as Actinomyces itself has little invasive ability, these other species often aid in the infection process.
Diagnosis
The diagnosis of actinomycosis can be a difficult one to make. In addition to microbiological examinations, magnetic resonance imaging and immunoassays may be helpful.
Treatment
Actinomyces bacteria are generally sensitive to penicillin, which is frequently used to treat actinomycosis. In cases of penicillin allergy, doxycycline is used.
Sulfonamides such as sulfamethoxazole may be used as an alternative regimen at a total daily dosage of 2–4 grams. Response to therapy is slow and may take months.
Hyperbaric oxygen therapy may also be used as an adjunct to conventional therapy when the disease process is refractory to antibiotics and surgical treatment.
Epidemiology
Disease incidence is greater in males between the ages of 20 and 60 years than in females. Before antibiotic treatments became available, the incidence in the Netherlands and Germany was one per 100,000 people/year. Incidence in the U.S. in the 1970s was one per 300,000 people/year, while in Germany in 1984, it was estimated to be one per 40,000 people/year. The use of intrauterine devices (IUDs) has increased incidence of genitourinary actinomycosis in females. Incidence of oral actinomycosis, which is harder to diagnose, has increased.
History
In 1877, pathologist Otto Bollinger described the presence of A. bovis in cattle, and shortly afterwards, James Israel discovered A. israelii in humans. In 1890, Eugen Bostroem isolated the causative organism from a culture of grain, grasses, and soil. After Bostroems discovery, a general misconception existed that actinomycosis was a mycosis that affected individuals who chewed grass or straw. The pathogen is still known as the “great masquerader". Bergeys Manual of Systematic Bacteriology classified the organism as bacterial in 1939, but the disease remained classified as a fungus in the 1955 edition of the Control of Communicable Diseases in Man.Violinist Joseph Joachim died of actinomycosis on 15 August 1907.
The Norwegian painter Halfdan Egedius died from actinomycosis on 2 February 1899.
Other animals
Actinomycosis occurs rarely in humans, but rather frequently in cattle as a disease called "lumpy jaw". This name refers to the large abscesses that grow on the head and neck of the infected animal. It can also affect swine, horses, and dogs, and less often wild animals and sheep.
References
Further reading
Anderson, Clifton W.; Jenkins, Ralph H. (December 15, 1938). "Actinomycosis of the Scrotum". New England Journal of Medicine. 219 (24): 953–954. doi:10.1056/NEJM193812152192403.
Codman, E. A. (August 11, 1898). "A Case of Actinomycosis". The Boston Medical and Surgical Journal. 139 (6): 134–135. doi:10.1056/NEJM189808111390606.
Randolph HL Wong; Alan DL Sihoe; KH Thung; Innes YP Wan; Margaret BY Ip; Anthony PC Yim (June 2004). "Actinomycosis: an often forgotten diagnosis". Asian Cardiovasc Thorac Ann. 12 (2): 165–7. doi:10.1177/021849230401200218. PMID 15213087. S2CID 9930882. Review
Munro, John C. (September 13, 1900). "Four Cases of Actinomycosis". The Boston Medical and Surgical Journal. 143 (11): 255–256. doi:10.1056/NEJM190009131431103.
Whitney, W. F. (June 5, 1884). "A Case of Actinomycosis in a Heifer". The Boston Medical and Surgical Journal. 110 (23): 532. doi:10.1056/NEJM188406051102302.
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