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Systemic Capillary Leak Syndrome (SCLS) is an exceedingly rare, life- and limb-threatening disorder characterized by acute and severe recurrent attacks featuring a rapid fall in blood pressure due to the temporary leak of plasma out of the blood circulatory system.
This virtual community is dedicated to the memory of Judith (Judy) Lynne Davis (1958-2009) (judithdavis3), one of its founding members and a victim of a very severe episode of SCLS that took her life in November 2009.
We also mourn the death of seven other SCLS patient members of this community: Mario Gatto (mariogatto) from Naples, Italy, who passed away in December 2009; Denise Weston (mdweston) from Ohio, USA, who died in March 2011; Bruno Galien (bruno) from Nord-Pas-de-Calais, France, who passed on in February 2012; Guy Allen Overland (allenoverland) from the Washington DC area, USA, who died in January 2015; Marilyn Meaux (maire602) from Louisiana, USA, who passed away in March 2017; Julie Eady (jodono) from Perth, Australia, who died in September 2017; and Cara O'Hagan (Cara) from Dublin, Ireland, who passed on in February 2018.
Systemic Capillary Leak Syndrome (SCLS) is an exceedingly rare, life- and limb-threatening disorder characterized by acute and severe recurrent attacks featuring a rapid fall in blood pressure due to the temporary leak of plasma out of the blood circulatory system.
This virtual community is dedicated to the memory of Judith (Judy) Lynne Davis (1958-2009) (judithdavis3), one of its founding members and a victim of a very severe episode of SCLS that took her life in November 2009.
We also mourn the death of seven other SCLS patient members of this community: Mario Gatto (mariogatto) from Naples, Italy, who passed away in December 2009; Denise Weston (mdweston) from Ohio, USA, who died in March 2011; Bruno Galien (bruno) from Nord-Pas-de-Calais, France, who passed on in February 2012; Guy Allen Overland (allenoverland) from the Washington DC area, USA, who died in January 2015; Marilyn Meaux (maire602) from Louisiana, USA, who passed away in March 2017; Julie Eady (jodono) from Perth, Australia, who died in September 2017; and Cara O'Hagan (Cara) from Dublin, Ireland, who passed on in February 2018.
Less than one in 1 million people are affected by this disease.
|Clarkson or Clarkson's Disease
Systemic Capillary Leak Syndrome (SCLS) is idiopathic, and thus at present there are no known causes. Probably a mid-life gene mutation takes place that renders those affected vulnerable -- possibly immune-deficient in some way -- to these curiously self-reversing capillary leaks.
Many patients report having a runny nose, flu-like symptoms, gastro-intestinal disorders, a general weakness or pain in their limbs, swelling in the face or hands and feet, or very cold hands and feet, but others get no particular or consistent warning signs.
|Myalgia is muscle pain
|Rhinorrhea is a runny nose
|Hypotension is abnormally low blood pressure
|Hemoconcentration is the decrease of the fluid content of the blood, with increased concentration of formed elements
|Hypoalbuminemia is low levels of protein in the blood
|Excessive thirst
|Excessive thirst
|Generalized edema
|Generalized edema
|Decline in clinical picture
|Clinical picture declines rapidly within hours
|Cold limbs and sweating
|Cold limbs and sweating
|Rapid swelling and compartment syndrome
|Rapid swelling of all limbs with development of compartment syndrome, especially during IV fluid administration
|Decreased urine output
|Decreased urine output
|Intestinal cramps
The diagnosis of SCLS is made partly by exclusion, namely, by eliminating the possibility of other more common diseases, and is based on measurable, clinical symptoms such as hypotension, hemoconcentration, hypoalbuminemia, and the presence of a protein called Monoclonal Gammopathy of Unknown Significance (MGUS).
Treatment of a fully developed SCLS episode requires recognition that there are two phases. The first phase, which often lasts a couple of days, is called the resuscitation phase because the dual aim of ER/ICU treatment is to stop or control the capillary leak and to raise the patient's blood pressure from near zero. In this initial phase, an albumin and fluid leak from the capillaries into the tissue spaces causes swelling, especially into the extremities rather than the abdomen or organs (such as the lungs). The blood pressure falls and the red cells concentrate. This loss of fluid has similar effects on the circulation as dehydration, slowing both the flow of oxygen carrying blood to tissues and the output of urine.
Glucocorticoids (steroids like methylprednisolone) are recommended to reduce or stop the capillary leak, and albumin and colloids usually help to increase the remaining blood flow to vital organs like the kidneys. Keeping up with the fluid loss is important because sustained low blood pressure can damage vital organs such as the kidneys. Even though blood pressure readings may reach and remain at very low levels, it is important to avoid overly aggressive intravenous fluid administration causing massive swelling of the extremities.
The goal of saline and vasopressors administered should NOT be to restore a "normal" blood pressure (or urine flow), but to maintain it at a minimal level sufficient to avoid permanent damage to vital organs. Measurement of central venous or arterial pressure in an ICU setting is often necessary to achieve this delicate balance. When too much fluid is administered, the result is excessive swelling, and the patient may well require surgical decompression of the limbs. In this procedure, known as a fasciotomy, the skin of the arms and/or legs is incised to release the compressive pressure the retained fluid is having on blood flow to and from the extremities.
The second phase of the treatment is known as the recruitment phase, when fluids and albumin are reabsorbed from the tissues during at least a couple of days. In this phase, the capillary leak has ended and the main threat is fluid overload. If intravenous fluids were given in excess, they usually cause an accumulation of fluid in the lungs and around other vital organs. Most of the patient deaths happen during this recruitment phase so it is important that diuretics be administered to help patients discharge all the fluid previously given -- and to keep them from backing up, especially into the lungs.
As concerns episode prevention, two approaches have been tried: β-agonists like theophylline and terbutaline, and a prophylaxis with IVIG infusions. In recent years, more and more patients have been migrated from the former to the latter in Canada, Europe, the United States and beyond, because IVIG therapy leads to superior results -- no episodes or fewer and lighter episodes than compared to no therapy or the other therapies -- and does not have as many adverse side effects as does treatment with β-agonists like theophylline and terbutaline.
The prognosis is uncertain and depends on (a) how well episodes are managed, in terms of preventing permanent damage to vital organs and extremities; and (b) the ability to prevent episodes altogether.
There are two main treatments to prevent episodes of SCLS. The oldest is the Mayo Clinic's approach of a preventive therapy with theophylline (or aminophylline) and terbutaline tablets taken on a daily basis. However, these medications, meant to reduce endothelial hyperpermeability, have very unpleasant side effects, and often prove ineffective, providing partial and transient improvement.
The newest is the French preventive regimen, which involves monthly infusions of immunoglobulins (IVIG). There is growing evidence that IVIG (usually, 2 gr/kg per month, administered over two consecutive days) has worked for many patients in Europe for over 10 years now, and is proving extremely successful among patients who have tried it in North America and beyond in the past several years, thus having become the standard of care.
|Medical help
|Clinical Study Volunteer
Please see the Disorder Resources section.
Thanks Annmarie. Oh, I wonder if Dave has had a mild form of chronic SCLS if there possibly can be such a thing.
He certainly hasn't suffered as much as some of the folks on this board with full blown attacks chronically.
He also uses triptans, has injections and tablets for pain. Is trying Ajovy injections, one of the migraine preventives that just became available. Not sure if it's helping yet.
Hi David.
I Have also been suffering with migraines and probable Chronic Capillary Leak since approximately the same age of 15. I am now 57. The migraines arrive for 3 days as the fluid is retrieving. I am currently improved on Hyrdacortisone which I have been taking for the last 6 months. If I can control the swelling, I do not get migraine at all. If I swell even a little bit, I will absolutely always get a 3 day migraine in 2-3 days time. I believe that while migraine appears to not be a part of SCLS for most people, I have a predisposition it to as other family members do. The Chronic SCLS seems to be a trigger. I take triptan dugs for the migraines, usually Relpax 80mg
Thanks Arturo. Yes, he did have a bit of a headache on the evening of day one, but not as severe as he's used to. They will premedicate with Benadryl and Tylenol next time
We're so grateful for you Arturo
Glad to hear, and happy to have helped!
I'm happy to report my husband David was approved for IVIG without too much wrangling with insurance company.
They rejected the doctor's first prior authorization request, asking for clinical chart notes confirming the SCLS diagnosis.
When she responded with the notes including Dr. Druey's confirmation, we got a letter saying the appeal would take 30 days, but if a delay would significantly increase risk to his health, we can request an expedited review.
I requested the expedited review via phone, and after being on hold for about 15 minutes got the approval!
He had his first infusion 2 days last week.
Insurance approval is only thru August 2019.
So I guess we have to keep standing on our head to request the infusions indefinately...
Thanks again for all who've gone before us to smooth out the way for this life saving treatment!
My daughter Adele was diagnosed in 2009 and no acute episodes occurred since then. From my profile update:
----- April, 12nd 2019 update -------
Under medical prescription, the therapy for my daughter has been gradually reduced until January 2019, when it has been stopped at all. Since January, as in previous 10 years, no acute episodes occurred, in spite of normal flu that didn't triggered any SCLS symptoms. Great news for us and I think an inspiration for everyone.
Thank you all for you continuous support and information.
Alessandro & Adele
Hello Rita, how do you continue with your Ivigs infusions?
Hi Ritz. My husband (user name is monkeyracing) had a severe episode at the end of 2017 that resulted in persistent inflammation and ulcers in his intestine (five months in hospital). They think it's ischemia from the blood loss but are investigating to be sure it is not Crohn's.
does anyone else have trouble with diarrhea after their IVIG treatments? I just had another colonoscopy to see if there is another cause. I am wondering is this is just a reaction.
You're welcome, Arturo!
I hadn't seen these two articles, so many thanks for the refererrals! I'm going to include the second one under Disorder Resources.
Hey, Annmarie,
My apologize for not getting back to you sooner. I had a busy few weeks and many sick days
Wow! 40 years! That's awful. My heart goes out to you. I find it difficult to imagine living with this condition for another year, let alone another 30. I'm happy to hear that you're getting at least some relief from the hydrocortisone.
I think one of the biggest problems with this condition is that it's under-reported in the literature. The avg physician can't even reference any reports of similar cases for comparison and diagnosis. Once they check off common possible causes of generalized edema such as hereditary angioedema, mastocytosis/mast cell activation disorder, allergies, kidney, heart, liver issues, etc, you're on your own more or less, as a patient.
Even in it's "classic" acute form, the SCLS is still a very poorly defined and under-researched condition, which is why they still refer to it as a syndrome rather than a disease. I've read just about every publicly available published paper and still don't see a clearly defined consensus as to what what SCLS actually is. They describe a constellation of symptoms and abnormal labs but offer no definitive diagnostic markers or underlying cause. I've read a few published reports about cancer patients who develop generalized edema and what sounds like a systemic inflammatory response after receiving chemotherapy agents (Interleukin 2 primarily). They refer to this syndrome as "secondary SCLS". Now, is this the same syndrome that's occurring in the idiopathic acute cases? Nobody knows. Also, there are scattered reports of idiopathic cyclical edema, primarily effecting women during their menstrual cycles. These women develop generalized edema but without the hypovolemia and low blood pressure that characterizes SCLS. Are these women suffering from a similar underlying pathology as SCLS patients? Again, nobody seems to know. It would be helpful if we had a registry of some kind where our physicians could submit reports and possibly share information in order to help others struggling with similar symptoms.
Most (90%) of the published papers on SCLS are simply case studies and reports. There's very little actual research aimed at studying underlying biological mechanisms responsible for the syndrome. The only person I am aware of who has done a fair amount of study in this area is Dr Druey but his research is probably limited by funding.
I'm obviously not a doctor, but I suspect that SCLS is spectrum disease involving varying degrees of abnormal capillary permeability resulting in fluid shifts. The key term here being fluid shifts. It's the loss of vascular fluid along with the edema that distinguishes SCLS from other generalized swelling conditions far as I can tell. That's why SCLS patients are full of edema yet paradoxically dehydrated. There's too much fluid outside the blood vessels and too little fluid inside. Blood vessels even in healthy folks are always permeable to a degree but in the case SCLS the vessels become abnormally permeable which leads to massive fluid loss and edema. On the one end of the spectrum, you've got the classic acute life-threatening cases and on the other end you've got more chronic and difficult to treat cases-- and still other folks who fall somewhere in the middle of the spectrum in terms of their symptoms.
I also think that cytokines and perhaps some other unknown chemical messengers are the main culprits behind the syndrome. If researchers could positively identify these culprits, they could probably get a better handle on managing the condition and possibly develop more definitive diagnostic tests, rather than relying on clinical signs and symptoms. Hemoconcentration, for example, isn't a maker for SCLS but rather a marker of decreased plasma volume (low blood volume). It just means that the blood is concentrated due to fluid loss into tissues. It's not specific for SCLS or any other condition. But that's the best diagnostic test for SCLS that we have at the moment. It would be nice if we had some more definitive and exact blood tests, which would likely lead to more definitive and exact treatments. As it stands now, the best they have to offer in terms of diagnosis are CBC reports, albumin levels and BP monitoring, in addition to clinical signs and symptoms. Patients like myself and perhaps you as well who don't match exactly with the currently proposed diagnostic criteria can easily fly under the radar, IMO. Half the time when I'd show up to ER during an attack, I'd already be urinating off some of the fluid and deflating, so my labs would look normal or near normal.
What they're calling SCLS seems to me like a deranged immune response of some kind, perhaps similar to the biochemical derangement that occur during sepsis and anaphylaxis. For whatever reason, folks who suffer from SCLS seem to develop an inappropriate immune response to normal everyday stimuli that results in abnormal amounts of fluid escaping from the small vessels. If it's severe, it can be lethal; and if it's chronic, it can be very debilitating and possibly lethal as well in the long term. I think this is why it's so difficult to pin down triggers. I'm not sure there are any. I suspect that folks who suffer from SCLS are experiencing an immune reaction to otherwise harmless stimuli, possibly similar to an autoimmune type reaction. The immune system mistakes ordinary stimuli for a life-threatening pathogen and overreacts....Perhaps this is why steroids and the T&T combo work for some patients. Those drugs inhibit the inflammatory response and prevent the vessels from dilating and becoming too permeable...... I have no medical background to back up my theory, though, so my opinion on this matter is basically worthless.
When I first got sick, one of the first symptoms I noticed, in addition to flu-like symptoms and the rapid weight gains and losses, was dehydration and inability to perspire. I'd always sweat quite profusely when active but that stopped after I started swelling. Despite the fluid everywhere else in my body, my mouth was bone dry and the skin on the back of my hands was wrinkled, dry and had the pale complexion of a corpse. Urine output diminished greatly as well and of course blood pressure would drop from my normal 120/80 to 90/50 or thereabouts. My CBC reports showed a total white blood cell count that ranged anywhere from 15k-25k with elevated neutrophils and monocytes as well. This was a consisted abnormality for 8 years but docs at the time never paid attention. They'd always look at the isolated reports and blame it on something transient like an infection, which never made sense to me because I wasn't suffering from any infection that I was aware of. It wasn't until I got fed up with years of misdiagnosis and misdirection that I stapled all the reports together myself and brought them to my GI doc who flipped through the thick stack of abnormal CBC reports lying on her table and immediately referred me to an immunologist. It was only then that I started getting some answers.
I've also had idiopathic pancreatitis and the whole slew of idiopathic inflammatory conditions I mentioned above. My testosterone was very low at one time as well, when I was very sick and swollen, but the levels have returned to low-normal as the swelling has diminished somewhat over the past year. I've had very low early-morning cortisol reading like yourself but they weren't abnormal during ACTH test. These endocrine abnormalities led to misdiagnosis of possible pituitary tumor, which was dismissed after a clean MRI. This was years ago when I was being sent to multiple specialists and getting misdiagnosed repeatedly.
At any rate, thanks for sharing, Annmarie! I believe that the more info we share about this condition the better for both patients and physicians alike.
BTW, here's a published case report of a 64 year old male SCLS patient who presented with multiple endocrine abnormalities like yours which reversed after he was treated with IVIG. His hormone levels returned to normal after his physicians got the SCLS under control. The authors speculate that the hormone abnormalities were a consequence rather than cause of his SCLS. See here : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313677/
Additionally, here's another very recently published paper (2019) on the chronic form of capillary leak syndrome. It's the only published paper and review of the literature I am aware of that focuses exclusively on the handful of reported cases of chronic SCLS . It's just an abstract, unfortunately. I wish I could get my hands on the full paper. See here: https://www.ncbi.nlm.nih.gov/pubmed/30431430?dopt=Abstract
Thanks so much Arturo. Our immunologist resubmitted the request for authorization and I forwarded your documents to her.
Meanwhile I'm collecting hospital and doctors records that we need to apply for the NIH study.
This will take time and I'm very thankful that in case of another leak we're not in the dark about what's happening and how best to help him.
I'll keep you updated on our progress.
Don't lose hope. I'm going to help you file and win your appeal. More details and resources emailed separately.
Our insurance company denied doctor's request for ivigg treatment. And so it begins.
To our group members in New Zealand,
I am so sorry to hear of the terror attack in your country. I am hoping that no one you know has been hurt. It is so hard to go through a terrorist attack on your own soil. I hope your country recovers well.
Has our ever considered finding legal help for the members. I am having trouble with the disability insurance company my former employer contracted with. I have been off work for more than two years since my last major attack. Now the Doctors there think I can go back to work full time. First I am never going to completely recover from coding twice and second I have IVIG treatments every other week. At 61 I fear that finding employment will be impossible.
The law firms I have talked to only cover Socail Security which I have applied for disability, I am still waiting for an answer. My medical cost are high. I can not seem to find help anywhere. I am looking for employment but I am not getting any response.
if anyone knows where I could get help please let me know.
|Hospitals, Doctors, Medical Teams: Navigating Barriers of Rare Diseases (Patient Navigation)
Arturo Porzecanski, a rare disease patient and advocate, gives us some tips on navigating decisions involved in choosing hospitals, doctors, and medical teams.
|Chronic SCLS treatment with IVIG: Case & literature
Chronic systemic capillary leak syndrome treatment with intravenous immune globulin: Case report and review of the literature
Abstract: A rarely described chronic form of SCLS (cSCLS) presents as refractory edema, with pleural and/or pericardial effusions and hypoalbuminemia. These entities are differentiated by massive and periodic episodes of capillary leak, which can result in shock in SCLS, and chronic refractory edema in cSCLS. The etiologies of these disorders are poorly understood, but both acute and chronic forms often present with an associated monoclonal gammopathy. Flares of the SCLS have been reduced by treatment with intravenous immune globulin (IVIG). Only six cases of cSCLS have been reported, and previous treatments have included steroids, terbutaline, and theophylline. Based upon the reported responses of SCLS to IVIG, we present the case of a 54-year-old man with cSCLS where ongoing treatment with IVIG resulted in a marked and sustained improvement in the signs and symptoms of the capillary leak syndrome.
|Whole Exome Sequencing of SCLS Patients
Whole Exome Sequencing of Adult and Pediatric Cohorts of the Rare Vascular Disorder Systemic Capillary Leak Syndrome
Abstract: The extent to which genetic abnormalities contribute to SCLS is unknown. The authors identified pediatric and adult cohorts with characteristic clinical courses and sought to identify a possible genetic contribution to SCLS through the application of Whole Exome Sequencing (WES). On the basis of 9 adult and 8 pediatric SCLS patients and available unaffected first-degree relatives, they did not identify a uniform germline exomic genetic etiology for SCLS. However, WES did identify several candidate genes for future research.
|Idiopathic SCLS (Clarkson syndrome) in childhood
Idiopathic systemic capillary leak syndrome (Clarkson syndrome) in childhood: systematic literature review
Abstract: The authors performed a systematic review of the literature on Clarkson syndrome in subjects less than 18 years of age, and identified 24 reports, published since 1989, providing data on 32 otherwise healthy subjects, who experienced 67 well-documented episodes of SCLS. The condition affected more frequently girls (21, 66%) than boys, presented throughout childhood, and was preceded by a mostly viral illness in 75% of cases. The presence of a monoclonal gammopathy (MGUS) was never reported. Uncompensated circulatory shock, muscle compartment syndrome, acute kidney injury, pulmonary edema, and either pleural or pericardial effusion were, in decreasing order of frequency, the most common complications. Four patients died. In sum, SCLS develops not only in adulthood but also in childhood, but of potential significance is that in this age group the condition is not linked to an MGUS, and thus it could be that it does not play a pivotal pathogenic role.
|Clinical Presentation, Management, and Prognostic Factors of SCLS
Clinical Presentation, Management, and Prognostic Factors of Idiopathic Systemic Capillary Leak Syndrome: A Systematic Review
Abstract: A total of 133 case reports (161 patients) and 5 case series (102 patients) of idiopathic SCLS were included in a survey of articles published through end-2016. The findings include that patients had hypotension (81.4%), edema (64.6%), and previous flu-like illness (34.2%). They were often misdiagnosed as having hypovolemic shock, septic shock, polycythemia vera, or angioedema. Thirty-seven patients died (23%) mainly because of complications from SCLS (78.4%). There were significant differences in the survival rates between patients who were treated with prophylactic b2 agonists, methylxanthines, and intravenous immunoglobulins and those who were not. The estimated 1-, 5-, and 10-year survival rate of patients treated with intravenous immunoglobulins was 100%, 94%, and 94%, respectively. The results of this review suggest that prophylactic use of intravenous immunoglobulins is the most effective treatment in reducing the mortality rate of SCLS patients.
|The Clinical Picture of Severe SCLS Episodes Requiring ICU Admission
The Clinical Picture of Severe SCLS Episodes Requiring ICU Admission
Abstract: SCLS is a very rare cause of recurrent hypovolemic shock. Few data are available on its clinical manifestations, laboratory findings, and outcomes of those patients requiring ICU admission. This study was undertaken to describe the clinical pictures and ICU management of severe SCLS episodes. This multicenter retrospective analysis concerned patients entered in the European Clarkson's disease (EurêClark) Registry and admitted to ICUs between May 1992 and February 2016. Fifty-nine attacks occurring in 37 patients (male-to-female sex ratio, 1.05; mean ± SD age, 51 ± 11.4 yr) were included. Among 34 patients (91.9%) with monoclonal immunoglobulin G gammopathy, 20 (58.8%) had kappa light chains. ICU-admission hemoglobin and proteinemia were respectively median (interquartile range) 20.2 g/dL (17.9-22 g/dL) and 50 g/L (36.5-58.5 g/L). IVIG was infused during 15 episodes (25.4%). A compartment syndrome developed during 12 episodes (20.3%). Eleven (18.6%) in-ICU deaths occurred. Bivariable analyses (the 37 patients' last episodes) retained Sequential Organ-Failure Assessment score greater than 10 (odds ratio, 12.9 [95% CI, 1.2-140]; p = 0.04) and cumulated fluid-therapy volume greater than 10.7 L (odds ratio, 16.8 [1.6-180]; p = 0.02) as independent predictors of hospital mortality. In conclusion, high-volume fluid therapy was independently associated with poorer outcomes. IVIG use was not associated with improved survival; hence, its use in an ICU setting should be considered prudently and needs further evaluation in future studies.
|Intravenous Immunoglobulins Improve Survival in Monoclonal Gammopathy-Associated SCLS
Intravenous Immunoglobulins Improve Survival in Monoclonal Gammopathy-Associated SCLS
Abstract: We conducted a cohort analysis of all patients included in the European Clarkson disease registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (e.g., the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months. Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%).Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Preventive treatment with IVIg and terbutaline were the only factors significantly associated with survival in multivariate analysis. Neither the use of thalidomide nor theophylline was associated with improved survival. Five- and 10-year survival rates in patients treated with IVIg were 91% and 77%, respectively, compared to 47% and 37% in patients not treated with IVIg. Patients treated with IVIg were more likely to be free of recurrence, severe recurrence, and alive at the end of follow-up. Furthermore, all but one patient who did not experience a severe relapse were treated with IVIg. Since preventive treatment with IVIg was the strongest factor associated with survival, the use of IVIg is suggested as the first line in prevention therapy.
|Capillary leak syndrome: etiologies, pathophysiology, and management
Capillary leak syndrome: etiologies, pathophysiology, and management
Abstract: In various human diseases, an increase in capillary permeability to proteins leads to the loss of protein-rich fluid from the intravascular to the interstitial space. Although sepsis is the disease most commonly associated with this phenomenon, many other diseases can lead to a "sepsis-like" syndrome with manifestations of diffuse pitting edema, exudative serous cavity effusions, noncardiogenic pulmonary edema, hypotension, and, in some cases, hypovolemic shock with multiple-organ failure. The term capillary leak syndrome has been used to describe this constellation of disease manifestations associated with an increased capillary permeability to proteins. Diseases other than sepsis that can result in capillary leak syndrome include the idiopathic systemic capillary leak syndrome or Clarkson's disease, engraftment syndrome, differentiation syndrome, the ovarian hyperstimulation syndrome, hemophagocytic lymphohistiocytosis, viral hemorrhagic fevers, autoimmune diseases, snakebite envenomation, and ricin poisoning. Drugs including some interleukins, some monoclonal antibodies, and gemcitabine can also cause capillary leak syndrome. Acute kidney injury is commonly seen in all of these diseases. In addition to hypotension, cytokines are likely to be important in the pathophysiology of acute kidney injury in capillary leak syndrome. Fluid management is a critical part of the treatment of capillary leak syndrome; hypovolemia and hypotension can cause organ injury, whereas capillary leakage of administered fluid can worsen organ edema leading to progressive organ injury. The purpose of this article is to discuss the diseases other than sepsis that produce capillary leak and review their collective pathophysiology and treatment.
|Idiopathic systemic capillary leak syndrome (Clarkson disease)
Idiopathic systemic capillary leak syndrome (Clarkson disease)
Abstract: The enigmatic systemic capillary leak syndrome (SCLS) named for Dr Clarkson is characterized by transient and severe but reversible hemoconcentration and hypoalbuminemia caused by leakage of fluids and macromolecules into tissues. Although less than 500 cases of SCLS have been reported in the literature since 1960, the condition is probably underdiagnosed because of a lack of awareness and a high mortality without treatment. Treatment of acute SCLS remains primarily supportive. Prophylaxis with IVIG appears promising, but this therapy is nonspecific and expensive. Mechanistic understanding of SCLS is in its infancy. As a result, clinicians today cannot predict when or how badly SCLS will flare; targeted therapies do not yet exist, and prolonged remission or cure remains elusive. Our working hypothesis invokes exaggerated microvascular endothelial responses to surges of otherwise routinely encountered inflammatory mediators. This emerging disease model lends itself to innovative patient-centered translational research in the ways highlighted above. It is our hope that detailed and personalized investigation of intraendothelial responses among individual patients with SCLS might illuminate novel genetic and molecular control mechanisms. In turn, such advances could deliver the diagnostic, prognostic, and therapeutic tools sorely needed to combat this devastating disease.
|Sharing the Pain [of living with SCLS]
Sharing the Pain [of living with SCLS]
This article from The Washington Post newspaper tells the story of how this SCLS virtual community was created, the story of its founder and, more generally, of this fantastic RareShare site.
|The Mayo Clinic Experience with SCLS
Idiopathic Systemic Capillary Leak Syndrome (Clarkson's Disease): The Mayo Clinic Experience
Abstract: Of the 34 patients whose records were reviewed, 25 fulfilled all diagnostic criteria for SCLS. The median age at diagnosis of SCLS was 44 years. Median follow-up of surviving patients was 4.9 years, and median time to diagnosis from symptom onset was 1.1 years (interquartile range, 0.5-4.1 years). Flulike illness or myalgia was reported by 14 patients (56%) at onset of an acute attack of SCLS, and rhabdomyolysis developed in 9 patients (36%). Patients with a greater decrease in albumin level had a higher likelihood of developing rhabdomyolysis (P=.03). Monoclonal gammopathy, predominantly of the IgG-kappa type, was found in 19 patients (76%). The progression rate to multiple myeloma was 0.7% per person-year of follow-up. The overall response rate to the different therapies was 76%, and 24% of patients sustained durable (>2 years) complete remission. The estimated 5-year overall survival rate was 76% (95% confidence interval, 59%-97%). In conclusion, SCLS, a rare disease that occurs in those of middle age, is usually diagnosed after a considerable delay from onset of symptoms. The degree of albumin decrement during an attack correlates with development of rhabdomyolysis. A reduction in the frequency and/or the severity of attacks was seen in nearly three-fourths of patients who were offered empiric therapies. The rate of progression to multiple myeloma appears to be comparable to that of monoclonal gammopathy of undetermined significance.
|Genome-Wide SNP Analysis of SCLS
Genome-Wide SNP Analysis of SCLS.
Abstract: Polymorphisms in genes whose functional annotations suggest involvement in cell junctions and signaling, cell adhesion, and cytoskeletal organization, correlate with our previous mechanistic studies of SCLS sera. Such annotations provide a framework for future allelic discrimination strategies to validate top-ranked SNPs discovered here, as well as novel SNPs unique to the SCLS cohort detected by exome capture sequencing. Although the findings must be corroborated in a larger cohort, they provide a springboard for discovery of underlying pathophysiological mechanisms, biomarkers, and avenues for therapy.
|IVIG in SCLS: A Case Report and Review of Literature
IVIG in SCLS: Report and Review of Literature.
Abstract: In recent years, IVIG has become a common first-line prophylactic therapy in most patients with benefits at the dose of 2 gr/kg once a month. Here the authors report the case of a 49-year-old male patient in Italy -- he is a member of this community -- with SCLS treated successfully with a lower dose of IVIG (1 gr/kg monthly) in the maintenance phase. He presented no acute episodes in a follow-up period of 28 months. The authors describe prophylactic treatments for SCLS in the literature and compare their patient to another 18 who received IVIG in follow-up.
|Mechanistic Classification of SCLS
Mechanistic Classification of SCLS.
Abstract: The authors analyzed circulating mediators of vascular permeability and proinflammatory cytokines in acute episodic sera from 14 patients with SCLS, and sera from 37 healthy control subjects. They monitored barrier function of human microvascular endothelial cells (HMVEC) after treatment with SCLS sera using transendothelial electrical resistance assays. Consistent with their previous study, the permeability factor vascular endothelial growth factor (VEGF) was increased in sera from acutely ill subjects with SCLS. An analysis of samples from one SCLS patient who has not responded to any preventive therapies (and who is a member of this Community), suggests that SCLS may have clinically varying forms, and that within the group of patients with SCLS, different cytokines may mediate the capillary leak. Therefore, quantitative molecular and humanized cell-based assays for humoral mediators of permeability should improve diagnostic specificity for SCLS and enable clinicians to screen for effective therapies.
|High-Dose IVIG Therapy for SCLS
High-Dose IVIG Therapy for SCLS.
Abstract: We evaluated IVIG prophylactic therapy in a cohort of 29 patients with Systemic Capillary Leak Syndrome in a longitudinal follow up study. All patients received treatments at the discretion of their primary providers and retrospectively via questionnaire recorded symptoms beginning with their first documented episode of the SCLS until May 31, 2014. Twenty-two out of 29 patients responded to the questionnaire, and 18 out of the 22 respondents received monthly prophylaxis with IVIG during the study period for a median interval of 32 months. The median annual attack frequency was 2.6/patient prior to IVIG therapy and 0/patient following initiation of IVIG prophylaxis (P = 0.001). 15 out of 18 subjects with a history of one or more acute SCLS episodes experienced no further symptoms while on IVIG therapy. In conclusion, IVIG prophylaxis is associated with a dramatic reduction in the occurrence of SCLS attacks in most patients, with minimal side effects.
|SCLS in Children
Idiopathic Systemic Capillary Leak Syndrome in Children
Abstract: Adult subjects with systemic capillary leak syndrome (SCLS) present with acute and recurrent episodes of vascular leak manifesting as severe hypotension, hypoalbuminemia, hemoconcentration, and generalized edema. We studied clinical disease characteristics, serum cytokine profiles, and treatment modalities in a cohort of children with documented SCLS. Six children with SCLS were recruited from the United States, Australia, Canada, and Italy. Serum cytokines from SCLS subjects and a group of 10 healthy children were analyzed. Children with SCLS (aged 5-11 years old) presented with at least 1 acute, severe episode of hypotension, hypoalbuminemia, and hemoconcentration in the absence of underlying causes for these abnormalities. In contrast to what is observed in adult SCLS, identifiable infectious triggers precipitated most episodes in these children, and none of them had a monoclonal gammopathy. We found elevated levels of chemokine (C-C motif) ligand 2 (CCL2), interleukin-8, and tumor necrosis factor α in baseline SCLS sera compared with the control group. All patients are alive and well on prophylactic therapy, with 4 patients receiving intravenous or subcutaneous immunoglobulins at regular intervals. The clinical manifestations of pediatric and adult SCLS are similar, with the notable exceptions of frequent association with infections and the lack of monoclonal gammopathy. Prophylactic medication, including high dose immunoglobulins or theophylline plus verapamil, appears to be safe and efficacious therapy for SCLS in children.
|Systemic capillary leak syndrome: recognition prevents morbidity and mortality
Systemic capillary leak syndrome: recognition prevents morbidity and mortality.
Abstract: The authors report on a case of SCLS in Australia involving a 61-year-old male who was properly diagnosed after his third episode, to increase awareness of the condition and to highlight the benefits of prophylactic intravenous immunoglobulin (IVIG) in this condition. The diagnosis was made by exclusion and clinically by a classic triad of hypotension, hypoalbuminaemia and haemoconcentration. There have been recent advances in understanding the pathophysiological basis for SCLS and in effective prophylaxis, and the authors and patient benefitted from said advances.
|Laboratory Evidence of SCLS and of the Effectiveness of IVIG
Vascular Endothelial Hyperpermeability Induces The Clinical Symptoms of Clarkson Disease (The Systemic Capillary Leak Syndrome)
Abstract: The authors report clinical and molecular findings on 23 subjects, the largest SCLS case series to date. Application of episodic SCLS sera, but neither the purified immunoglobulin fraction nor sera obtained from subjects during remission, to human microvascular endothelial cells caused vascular endothelial cadherin (VE-cadherin) internalization, disruption of inter-endothelial junctions, actin stress fiber formation, and increased permeability in complementary functional assays without inducing endothelial apoptosis. Intravenous immunoglobulin (IVIG), one promising therapy for SCLS, mitigated the permeability effects of episodic sera directly. Consistent with the presence of endogenous, non-immunoglobulin, circulating permeability factor(s) constrained to SCLS episodes, we found that two such proteins, vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2), were elevated in episodic SCLS sera but not in remission sera. Antibody-based inhibition of Ang2 counteracted permeability induced by episodic SCLS sera. Comparable experiments with anti-VEGF antibody (bevacizumab) yielded less interpretable results, likely due to endothelial toxicity of VEGF withdrawal. Our results support a model of SCLS pathogenesis in which non-immunoglobulin humoral factors such as VEGF and Ang2 contribute to transient endothelial contraction, suggesting a molecular mechanism for this highly lethal disorder.
|Successful Treatment of SCLS with IVIG
Successful Treatment of Systemic Capillary Leak Syndrome with Intravenous Immunoglobulins.
Abstract: The authors report on a 48-year-old woman in Spain who had her 1st episode of SCLS in 1997 and was initially put on a regimen of terbutaline and aminophylline, but went on to endure 20 additional episodes in the subsequent 3 years. She was then treated with melphalan-prednisone for a year and the frequency and intensity of her episodes diminished and even disappeared. In 2005, however, the episodes returned and in 2008 she was finally put on a regimen of IVIG (2 g/kg) every 6 weeks. She has had no more episodes since then.
|Comment on SCLS
Comment on The Systemic Capillary Leak Syndrome.
Abstract: The authors report on 2 additional patients from the United States with SCLS in whom prophylaxis with terbutaline and theophylline failed, but who had no further episodes after the initiation of IVIG therapy. There are additional published reports of successful prophylaxis with IVIG cited, and the authors are also aware of yet another case. Given the present state of knowledge and despite the high cost, the authors strongly believe that IVIG is the optimal prophylaxis and should be the initial choice to prevent attacks in patients with SCLS.
|IVIG: A Promising Approach to SCLS
High-dose intravenous immunoglobulins: A promising therapeutic approach for idiopathic systemic capillary leak syndrome.
Abstract: The article reports the case of a 40-year-old woman with chronic SCLS treated in Berne, Switzerland, with high-dose intravenous immunoglobulins (IVIG) after a prophylactic therapy with theophylline and terbutaline (T&T) was poorly tolerated and failed to decrease the frequency and severity of the attacks. During the 5 years she was on T&T the patient suffered from about 20 similar episodes of mild to moderate shock, often requiring hospital re-admission and supportive therapy. So far, 10 months of prophylactic therapy with IVIG (2gr/kg/month) have resulted in an impressive reduction of intensity and frequency of attacks, confirming the finding of other case studies.
|Lessons from 28 European Patients with SCLS
The Systemic Capillary Leak Syndrome: A Case Series of 28 Patients From a European Registry.
Abstract: The article describes the clinical characteristics, laboratory findings, treatments, and outcomes of patients with SCLS who were not previously reported in the literature. These European patients with SCLS were treated and monitored from the start of 1997 until end-July 2010. Survival rates were 89% at 1 year and 73% at 5 years; instances of death were directly related to SCLS attacks in 6 cases (75% of total). Treatments of various kinds increased the chances of survival: Five years after diagnosis, survival rates were 85% in 23 patients who had received a treatment and just 20% in 5 patients who had not. The authors provide additional evidence that a prophylactic treatment with IVIG tends to reduce the frequency and severity of attacks, and may improve the survival of patients with SCLS.
|Mayo Clinic write-up on SCLS
The Mayo Clinic's summary of the diagnosis and treatment of SCLS.
During an episode of systemic capillary leak syndrome, fluids are administered intravenously to maintain the patient's blood pressure and to prevent damage to vital organs such as the kidneys, heart and brain. The amount of fluid must be carefully controlled. An attempt to normalize blood pressure through aggressive fluid administration can cause destructive swelling of the body's extremities and overload the kidneys and lungs when the body needs to eliminate the excess fluids after the episode passes.
Glucocorticoids (steroids) are often injected during an acute capillary leak syndrome attack to reduce or stop the capillary leak. This is sometimes successful. Fluid pressure in muscles may be monitored. Emergency surgery may be needed to relieve pressure and minimize damage to muscles and nerves in the arms and legs.
Once the capillary walls stop leaking and fluids start to be reabsorbed, patients are usually given diuretics to speed up elimination of the fluids before they accumulate in the lungs and other vital organs, which can be a fatal complication.
Patients who avoid organ and limb damage in a capillary leak syndrome episode tend to recover their health after several days, once the capillary walls return to normal and the accumulated fluid is expelled from the body through urination.
Although no cure has been found for systemic capillary leak syndrome, the frequency and/or severity of episodes is often reduced by having patients take certain asthma medications: theophylline and terbutaline. Patients also may benefit from intravenous treatment with immunoglobulin or by taking thalidomide.
Patients may also be prescribed corticosteroid pills such as prednisone to be taken at the first sign of symptoms of another capillary leak.
|IVIG as Treatment for SCLS
Immunoglobulins for Treatment of Systemic Capillary Leak Syndrome
Abstract: A 43-year-old white woman in France diagnosed with SCLS was put on the recommended combination of Theophylline plus Terbutaline, but she nevertheless had 10 episodes of severe capillary leak during 2001-mid-2007, necessitating intensive care unit admission for her last 3 episodes. She was then put on IVIG administered every 6 weeks, and this yielded a dramatic improvement such that she has had no more episodes and has returned to her normal lifestyle.
|IVIG as Treatment for SCLS
High-Dose Intravenous Immunoglobulins Dramatically Reverse Systemic Capillary Leak Syndrome.
Abstract: The objective of this study was to report the dramatic improvement of patients with systemic capillary leak syndrome obtained with high-dose intravenous immunoglobulins. Systemic capillary leak syndrome is a rare and life-threatening disorder characterized by hypotension that can lead to shock, weight gain, hypoalbuminemia, and elevated hematocrit secondary to unexplained episodic capillary fluid extravasation into the interstitial space. Because its cause is unknown, systemic capillary leak syndrome treatment has remained largely supportive. Intravenous immunoglobulins administration to a patient with refractory systemic capillary leak syndrome yielded dramatic improvement. The patient is still alive 11 yrs after systemic capillary leak syndrome diagnosis and receives intravenous immunoglobulins monthly. Later, based on that result, intravenous immunoglobulins were successfully given to two other patients during the acute phase of systemic capillary leak syndrome. Both are still alive 8 and 1.5 yrs after receiving intravenous immunoglobulins at the onset of each flare. In conclusion, intravenous immunoglobulins were effective against systemic capillary leak syndrome symptoms in three patients, but their exact mechanism remains unknown. Their immunomodulatory effect merits further investigation.
|The Systemic Capillary Leak Syndrome
Narrative review: the systemic capillary leak syndrome
Abstract: The systemic capillary leak syndrome (SCLS) is a rare disease of reversible plasma extravasation and vascular collapse accompanied by hemoconcentration and hypoalbuminemia. Its cause is unknown, although it is believed to be a manifestation of transient endothelial dysfunction due to endothelial contraction, apoptosis, injury, or a combination of these. Fewer than 150 cases of SCLS have been reported, but the condition is probably underrecognized because of its nonspecific symptoms and signs and high mortality rate. Patients experience shock and massive edema, often after a nonspecific prodrome of weakness, fatigue, and myalgias, and are at risk for ischemia-induced organ failure, rhabdomyolysis and muscle compartment syndromes, and venous thromboembolism. Shock and edema reverse almost as quickly as they begin, at which time patients are at risk for death from flash pulmonary edema during rapid fluid remobilization. Diagnosis is made clinically and by exclusion of other diseases that cause similar symptoms and signs, most notably sepsis, anaphylaxis, and angioedema. Acute episodes are treated with vasopressor therapy and judicious fluid replacement, possibly with colloid solutions for their osmotic effects, to prevent the sequelae of underperfusion. Prognosis is uncertain, but patients who survive an initial severe SCLS episode are estimated to have a 10-year survival rate greater than 70%. Much remains to be learned about SCLS, and clinicians should consider the diagnosis in patients with unexplained edema, increased hematocrit, and hypotension.
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I had my first episode of what turned out to be SCLS in November 2005, and was very lucky to have survived it (though with permanent disabilities in arms and legs, and thus in hands and feet) and to have been diagnosed correctly within days.
I went on to have 2 other life- and limb-threatening episodes in April 2007 and March 2009, requiring 2+ weeks of Intensive Care hospitalization to keep my organs alive and emergency fasciotomies to preserve the muscles and nerves I still have in my extremities.
I also had 7 episodes of lesser severity (Dec. 2007, June 2008, June 2009, July 2009, September 2009, and two in November 2009), because I realized I was having them early on, which allowed me to get a massive dose of steroids (Prednisone pills and/or injections of Solu-Medrol and Albumin) that effectively stopped the capillary leak phase of SCLS.
Given the increased frequency of my episodes of SCLS, despite having taken the recommended doses of the traditional medications (e.g., Theophylline, Terbutaline and Singulair), I was given my first infusion of IVIG in November 2009 and have had monthly infusions since then with no adverse side effects whatsoever. So far, so very good: I have had no more episodes of SCLS.
While I was among the first SCLS patients in the United States to benefit from an IVIG therapy, most other patients who had previously been getting this medication in Europe, and virtually all patients around the world who have since received IVIG, have stopped having episodes of SCLS.
Our stories are now told in a number of case studies published in various medical journals, and there is also a scientific article showing the efficacy of IVIG in countering SCLS in laboratory conditions based on our blood samples before and after receiving IVIG, as well as several articles with the results of surveys of SCLS patients who have been on IVIG. The evidence that IVIG is the best and almost always successful therapy for the prevention of episodes of SCLS is now overwhelming.
My address is firstname.lastname@example.com
So sorry to hear about your father! It is bad enough to be sick, but it is worse still to be sick and without an appropriate diagnosis -- never mind a suitable therapy.
While I don't have the name of any SCLS expert in South Florida, I have two suggestions good for any place. First, get hold of your father's medical and hospital records and send them to Dr. Kirk Druey at NIH requesting a consultation on his case.
Second, find a new "anchor" physician for your father, preferably a seasoned internist on the faculty of a university hospital, to provide a fresh pair of eyes, consider a possible diagnosis of SCLS, discuss his case with Dr. Druey, coordinate his care, and decide on therapy options including IVIG. It doesn't matter that he or she may not have even heard of SCLS before: by now there is plenty of useful literature, see the Disorder Resources section of this website.
While immunologists are obviously very familiar with IVIG therapies, and one of them could be enlisted to support the initiation of a course of therapy for your father, the clinical judgment and follow-up of an internist will be very important. Involving a hematologist has sometimes helped, but most of them have a narrow interest in oncological cases, so they are often not interested or helpful.
I am wanting to give up smoking but I am having a bit of a hard time, so I was wondering if you had any information on how cigarette smoking can affect someone with SCLS.
A situation of "continuous leakage" is not typical of SCLS, and may originate from other edema-related conditions.
My suggestion is that you have your main physician contact Dr. Druey at NIH asking for a second opinion on your diagnosis, for which purpose he will need to receive an electronic copy of your relevant medical history. See the tab "Disorder Details" and then scroll down to the very bottom, the last entry under "Tips for Living with the Disorder."
We have in our community a few confirmed SCLS patients who are episode-free because they are receiving IVIG therapy, and they are able to lead physically demanding lives (e.g., mountain biking and skiing).
Most of our confirmed SCLS patients, however, have suffered damage to their muscles and nerves, and thus they are limited in their physical activity.
If you are experiencing episodes of edema and fatigue which may be a form of SCLS, and you are not receiving any medication, then it would be prudent for you to listen to what your body is trying to tell you -- namely, that you have a medical problem.
Moreover, if you really have SCLS, then your condition could worsen into the typical, acute case of SCLS involving life- and limb-threatening episodes of hypotension, hemoconcentration, hypoalbuminemia, see the tab "Disorder Details."
Since you mentioned that NIH had experimented with tumeric extract, and I know that they have studied the potential role of MGUS in SCLS, I consulted with NIH researcher Dr. Kirk Druey, and this is what he wrote to me:
"We have conducted clinical trials incorporating this herb in the treatment of MGUS and myeloma.
In terms of SCLS, we don't know for sure if reducing the MGUS levels will affect the frequency of episodes. The medical literature reports several experiments with plasmapheresis or thalidomide or lenalidomide for this purpose, and they have met with limited success.
We ourselves tried reducing MGUS levels to see what would happen, though not with curcumin, and while we were able to reduce them, we were unsuccessful in preventing episodes of SCLS.
We certainly would not recommend anybody to take curcumin instead of IVIG, which is by far the most successful therapy for SCLS to date."
1. How many people receiving IVIG are still having episodes?
2. Has the 5-Minute ICU document been updated since publication of Dr. Druey's report, or is there a more current similar document appropriate to the use of IVIG?
We know from what has been posted by patients in our community that virtually everyone receiving IVIG has stopped having episodes, and this was confirmed by a survey of experience that was recently accepted for publication in a leading medical journal, see Discussion Forum "Publication of Results from Survey of IVIG Therapy."
Sometimes there have been adjustments to the recommended dosage or the timing of the treatments, but oftentimes these have been driven by attempts to minimize side effects of the IVIG, which tend to be temporary, anyway, rather than by the lack of efficacy of IVIG in preventing episodes of SCLS.
As concerns the 5-Minute Consult, no, unfortunately it has not been updated to reflect the knowledge gained in the past couple of years, but it's better to show it to an ambulance driver, an emergency-room receptionist, or a doctor who is trying to understand what is going on with you, than to be empty-handed just when you find yourself ill and incoherent.
You can always supplement it with other materials drawn from the Disorder Details or Disorder Resources section of this website.
In my opinion, there is no reason, especially for patients who were on Theophylline and Terbutaline and yet they had additional episodes, but I'm not a physician and therefore you should discuss this phasing out with your doctor and have him/her consult with Dr. Druey at NIH.
I was on Theophylline and Terbutaline for more than four years and I kept having episodes. Fortunately, I found out that IVIG was being tried with some initial success in Europe and with one patient in Canada and another in the USA, in part thanks to this Community.
When I finally obtained approval for a trial course of IVIG therapy, I was kept on Theophylline and Terbutaline for 5 months just in case the combination might do some good. My doctors then took me off of Theophylline and Terbutaline, and nothing changed for the worse. I stopped having any episodes the moment I started receiving IVIG every 4 weeks -- and I have not had any ever since going off of Theophylline and Terbutaline.
It's been over 5 happy years now, and my experience has been replicated by many patients in this Community.
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Considering the number of cars on road and dependency on motor vehicles to reach the destination garage is a necessity in the modern society. Garages nowadays are not only overnight halt for your luxury cars and other motor vehicles they also serve other important purposes. A person may own a garage in his residence or at his factory. Garage doors play impeccable role in creating the value of a garage. To assist the aesthetic appeal of your property, you can consider garage door replacement to have an impressive ornate.
While residential garage doors are used in houses, commercial doors fit in the factory and warehouse settings. But is it all about the difference between these two? What if you are building a private garage, what kind of door will suit your requirement? Having understanding of the distinctive features of both types of doors will help you make the right choice.
1) Commercial doors are more strong and durable. They withstand the additional wear and tear a residential door may not handle.
2) The residential doors come in variety of styles, they can be opened overhead, sideways and swinging, but commercial doors are mostly designed for overhead use.
3) Residential doors increase the curb appeal of your house but commercial doors come mostly in plain and simple designs.
4) Commercial garage doors seem to be costlier at first glance. But if you look at it closely you will find that their life is much greater than residential counterparts.
5) Size of an average residential garage door is 7 feet of heights. They are good to fit in a garage meant for parking one or two cars. Commercial doors need to allow huge trucks to pass by for which they are considerably taller than residential doors.
6) Commercial doors are too heavy to be lifted in case automatic lifter stops working. Residential garage doors are lighter comparatively.
When you know your garage door is going to be lifted and lowered several times, you should have commercial doors for that garage of yours.

subset: commoncrawl


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Toshiba Portege M800 Netbook
The sales of netbooks have gradually increased in the last year because of their mobile size. In a single month, many netbooks are launched by different leading brands such as Dell, Acer, Sony and Toshiba. Recently, Toshiba launched a new netbook that is called the Toshiba Portege M800. It is fully equipped with standard and specification as well as features.
Toshiba Portege M800 is powered by Intel Core 2 Duo P8400 processor whose maximum clocking frequency is 2.26 GHz. Furthermore, it has 3MB cache memory which is considered as standard for nay processor. There is 3 GB of physical memory (RAM) in this netbook. You can upgrade this RAM to 8 GB as its chipset supports RAM up to 8GB.
This netbook consists of 320 GB hard disk that is certified by S.M.A.R.T. Portege M800 comes with Windows Vista Business 32-bit edition. If you want to have Windows XP Professional edition in this netbook, you can enjoy Windows XP also because Toshiba offers the recovery disc with the pack by which you can downgrade to genuine windows XP professional edition. It has 13.3 inches display which can support 1280 x 800 pixels of resolution. This display is a WXGA TFT type display. Portage also has DVD super multi-drive as optical drive.
As graphic memory has become the necessity thing in computing media devices as the Portege M800 consists of 1340 MB Mobile Intel HMA 4500 MHD graphic card. Maximum refreshing rate of this display is 85 Hz. There is standard Wi-Fi 802/11 a/g/Draft-N, 1 Express card slot, Built in good quality stereo speaker and 86 keys keyboard in the Toshiba Portage M800.
314 x 229 x 27.5 mm is the dimension of the Toshiba Portege M800 netbook. Thickness of 27.5 mm shows it is sleeker in design. It is also a lighter netbook as it weighs around 2 Kg. The battery backup is also standard, it is around 3 hours. Overall performance of this machine is flawless and pretty well. If this performance can satisfy your needs, then go for it. Toshiba also offers 1 year international warranty.


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MWC 15 Special
The Wall Street Journal reports today that Beats Electronics LLC, maker of popular Beats by Dr. Dre headphones and speakers, is looking to buy out HTC's left 25 % stake in the company to bring in a new investor that can provide it with fresh funds for growth. Following the earlier reduction of 25 % (initially HTC took over 50 % of Beats Electronics), this would finally move HTC out of the headphone and loudspeaker business again; even if it is questionable if HTC would also remove its Beats sound enhancements from its upcoming Android devices. However, sources told WSJ.com that Beats is now in talks with an investor that could provide debt financing and possibly take a minority ownership stake in the coming weeks
German and European Football (for the U.S. readers - Soccer) and telecommunication seems to somehow fit. Sony (Ericsson) was once the premium partner of the UEFA and therefore the sponsor of the UEFA Champions League, which HTC became the sponsor of after, including the Europa League. Samsung is one of the few premium sponsors of FC Bayern München who's tricot partner is Deutsche Telekom; and today Huawei announced it will become a "Champion Partner" of Borussia Dortmund, Germany's second best football team (after FC Bayern München). While neither Huawei nor the BVB have unveiled full details, the long-term cooperation is said to include both Huawei areas, the consumer and the enterprise division.
We have recently heard some bad news about possible problems HTC might face at the moment, from missed sales targets to missed revenue outlooks but one thing is for sure - with the HTC One, HTC has 2013's most awarded and recognized smartphone in the portfolio. And if you think HTC has given up, just because it might have failed the one or the other target, you don't know HTC and you are wrong. As announced today, HTC is ready to launch this Wednesday its most ambitious campaign to date which I had the pleasure to have a sneak peek of last Friday. This massive ad-campaign, which alone will be as expensive as last year's whole sales and marketing budget was, is an integrated 2 year long-term strategy that celebrates HTC's 17 years of disruption and innovation in the mobile industry.
As WhatsApp announced on its blog, it just introduced "Voice Messages", a Push to Talk service for its messaging service. According to the WhatsApp blog, Voice Messages is released on all WhatsApp supported platforms simultaneously which means that it's now available for iPhone and Android, which is said to have perfectly working Voice Messages functionality, but the development team also put extra efforts into making sure that BlackBerry, Windows Phone and even S40 users can enjoy the same rich and powerful Voice Messaging experience. Using WhatsApp Voice Messages couldn't be easier: right next to the text entry field you find a microphone icon. Press and hold it, dictate the message and after releasing the icon, the message is sent.
During today's "Press Breakfast", Google introduced a new living room device called Google Chromecast. After Google TV and the Nexus Q failed so badly, Google is trying something new by introducing a small HDMI stick which works similar to HTC's Media Link HD or Miracast but isn't mirroring the PC or device screen at all but receives the content by its own via WiFi. With Chromecast, users can enjoy their favorite online entertainment on their HDTV; incl. movies, TV shows, music and more from Netflix, YouTube, Google Play and Chrome. Chromecast is said to work with devices users already own, including Android tablets and smartphones, iPhones and iPads, Chrome for Mac as well as Chrome for Windows.
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