Sarcoidosis, also called sarcoid (from the Greek ‘sark’ and ‘oid’ meaning “flesh-like”) or Besnier-Boeck disease, is an immune system disorder characterized by non-caseating granulomas (small inflammatory nodules) that most commonly arises in young adults. The cause of the disease is still unknown. Virtually any organ can be affected; however, granulomas most often appear in the lungs or the lymph nodes. Symptoms can occasionally appear suddenly but usually appear gradually. The clinical course generally varies and ranges from asymptomatic disease to a debilitating chronic condition that may lead to death.
Sarcoidosis most commonly affects young adults of both sexes, with a slight preponderance for women having been reported by most studies. Incidence is highest for individuals younger than 40 and peaks in the age-group from 20 to 29 years, a second peak is observed for women over 50  .
Sarcoidosis occurs throughout the world in all races with an average incidence of 16.5/100,000 in men and 19/100,000 in women. The disease is most prevalent in Northern European countries, and the highest annual incidence of 60 per 100,000 is found in Sweden and Iceland. In the United States, sarcoidosis is more common in people of African descent than Caucasians, with annual incidence reported as 35.5 and 10.9 per 100,000, respectively. Sarcoidosis is less commonly reported in South America, Spain and India.
The differing incidence across the world may be at least partially attributable to the lack of screening programs in certain regions of the world and the overshadowing presence of other granulomatous diseases such as tuberculosis, that may interfere with the diagnosis of sarcoidosis where they are prevalent.
There may also be racial differences in the severity of the disease. Several studies suggest that the presentation in people of African origin may be more severe and disseminated than for Caucasians, who are more likely to have asymptomatic disease.
Manifestation appears to be slightly different according to race and gender, erythema nodosum is far more common in men than women and Caucasians than other races. In Japanese opthalmologic and cardiac involvement is more common than in other races.
Sarcoidosis is a systemic disease that can affect any organ. Common symptoms are vague, such as fatigue unchanged by sleep, lack of energy, weight loss, aches and pains, arthralgia, dry eyes, blurry vision, shortness of breath, a dry hacking cough or skin lesions. The cutaneous symptoms vary, and range from rashes and noduli (small bumps) to erythema nodosum or lupus pernio. It is often asymptomatic.
The combination of erythema nodosum, bilateral hilar lymphadenopathy and arthralgia is called Löfgren syndrome. This syndrome has a relatively good prognosis.
Renal, liver (including portal hypertension), heart or brain involvement may cause further symptoms and altered functioning. Manifestations in the eye include uveitis, uveoparotitis, and retinal inflammation, which may result in loss of visual acuity or blindness. Sarcoidosis affecting the brain or nerves is known as neurosarcoidosis.
Hypercalcemia (high calcium levels) and its symptoms may be the result of excessive conversion of vitamin D to its active form by epitheliod macrophages.
Sarcoidosis most often manifests as a restrictive disease of the lungs, causing a decrease in lung volume and decreased compliance (the ability to stretch). The disease typically limits the amount of air drawn into the lungs, but produces higher than normal expiratory flow ratios. The vital capacity (full breath in, to full breath out) is decreased, and most of this air can be blown out in the first second. This means the FEV1/FVC ratio is increased from the normal of about 80%, to 90%. Obstructive lung changes, causing a decrease in the amount of air that can be exhaled, may occur when enlarged lymph nodes in the chest compress airways or when internal inflammation or nodules impede airflow.
Because sarcoidosis can affect multiple organ systems, follow-up on a patient with sarcoidosis should always include an electrocardiogram, ocular examination by an optometrist or ophthalmologist, liver function tests, serum calcium and 24-hour urine calcium.
In female patients sarcoidosis is significantly associated with hypothyroidism, hyperthyroidism and other thyroid diseases, hence close surveillance of thyroid function is recommended  .
On the one hand the disease is characterised by increased macrophage and CD4 helper T-cell activation resulting in accelerated inflammation – on the other hand the immune system of patients shows suppressed response to antigen challenges such as tuberculin. This paradoxic state of hyper- and hypo- activity at the same time is suggestive of a state of anergy. The anergy may also be responsible for the increased risk of infections and cancer. It appears that regulatory T-lymphocytes in the periphery of sarcoid granulomas suppress IL-2 secretion which is hypothesized to cause the state of anergy by preventing antigen-specific memory responses .
While it is widely believed that TNF-alpha plays an important role in the formation of granulomas it was observed that sarcoidosis can be triggered by treatment with the TNF-alpha antagonist etanercept  .
Investigations of genetic susceptibility yielded many candidate genes but only few were confirmed by further investigations and no reliable genetic markers are known. Currently most interesting candidate gene is BTNL2, several HLA-DRB risk alleles are also investigated.  Siblings have only a modestly increased risk (hazard ratio 5-6) to develop the disease, indicating that genetic susceptibility plays only a small role. The alternate hypothesis that family members share similar exposures to environmental pathogens is quite plausible to explain the apparent hereditary factor.
There have also been reports of transmission of sarcoidosis via organ transplants.
Prolactin is frequently increased in sarcoidosis, between 3–32% cases have hyperprolactinemia , this frequently leads to amenorrhea, galactorrhea or nonpuerperal mastitis in women. Prolactin also has a broad spectrum of effects on the immune system and increased prolactin levels are associated with disease activity or may exacerbate symptoms in many autoimmune diseases and treatment with prolactin lowering medication has been shown effective in some cases.  However it is unknown if this relation holds in sarcoidosis and the gender prediletion in sarcoidosis is less pronounced than in some other autoimmune diseases where such relation has been established. In pregnancy the effects of prolactin and estrogen counteract each other to some degree, with a slight trend to improve pulmonary manifestations of sarcoidosis while lupus, uveitis and arthralgia might slightly worsen. Lupus, uveitis and arthralgia are known to be in some cases associated with increased prolactin levels and respond to bromocriptin treatment but so far this has not been investigated specifically for sarcoidosis. The reasons for increased prolactin levels in sarcoidosis are hitherto uncertain. It has been observed that prolactin is produced by T-lymphocytes in some autoimmune disorders in amounts high enough to affect the feedback by the hypothalamic dopaminergic system  . The extrapituitary prolactin is believed to play a role as a cytokine like proinflammatory factor. Prolactin antibodies are believed to play a role in hyperprolactinemia in other autoimmune disorders and high prevalence endocrine autoimmunity has been observed in patients with sarcoidosis  . It may also be a consequence of renal disease or treatment with steroids. Neurosarcoidosis may occasionally cause hypopituiarism but has not been reported to cause hyperprolactinemia.
In women a substantial association of thyroid disease and sarcoidosis has been reported. The association is less marked but still significant for male patients. Female patients have a significantly elevated risk for hypothyroidism, hyperthyroidism and thyroid autoimmunity and it appears that autoimmunity is very important in the pathogenesis of thyroid disease in this population. Thyroid granulomatosis on the other hand is uncommon  .
Association of autoimmune disorders has been frequently observed. The exact mechanism of this relation is not known but some evidence supports the hypothesis that this is a consequence of Th1 lymhokine prevalence .
Sarcoidosis has been associated with celiac disease. Celiac disease is a condition in which there is a chronic reaction to certain protein chains, commonly referred to as glutens, found in some cereal grains. This reaction causes destruction of the villi in the small intestine, with resulting malabsorption of nutrients.
While disputed, some cases have been associated with inhalation of the dust from the collapse of the World Trade Center after the September 11, 2001 attacks. See Health effects arising from the September 11, 2001 attacks for more information.
Sarcoidosis generally does not prevent successful pregnancy and delivery, the endogenous estrogen in pregnancy may even have a slightly beneficial immunomodulatory effect. In most cases the course of sarcoidosis is unaffected by pregnancy, there is improvement in a few cases and worsening of symptoms in very few cases.
Between 30 to 70% of patients do not require therapy.Corticosteroids, most commonly prednisone, have been the standard treatment for many years. In some patients, this treatment can slow or reverse the course of the disease, but other patients do not respond to steroid therapy. The use of corticosteroids in mild disease is controversial because in many cases the disease remits spontaneously.  Additionally, corticosteroids have many recognized dose- and duration-related side effects (which can be reduced through the use of alternate-day dosing for those on chronic prednisone therapy ), and their use is generally limited to severe, progressive, or organ-threatening disease. The influence of corticosteroids or other immunosuppressants on the natural history is unclear.
Severe symptoms are generally treated with steroids, and steroid-sparing agents such as azathioprine and methotrexate are often used. Rarely, cyclophosphamide has also been used. As the granulomas are caused by collections of immune system cells, particularly T cells, there has been some early indications of success using immunosuppressants, interleukin-2 inhibitors or anti-tumor necrosis factor-alpha treatment (such as infliximab). Unfortunately, none of these has provided reliable treatment, and there can be significant side effects such as an increased risk of reactivating latent tuberculosis. Anti-tumor necrosis factor-alpha treatment with etanercept in rheumatoid arthritis has been observed to actually cause sarcoidosis  .
Avoidance of sunlight and Vitamin D foods may be helpful in patients who are susceptible to developing hypercalcemia.
Approximately half of the cases resolve or can be cured within 12-36 months and most within 5 years. Some cases persist several decades.
^ a b Baughman RP, Lower EE, du Bois RM. Sarcoidosis. The Lancet 2003/3/29;361(9363):1111-8.
^ a b c d Nunes H, Bouvry D, Soler P, Valeyre D (2007). “Sarcoidosis“. Orphanet J Rare Dis 2: 46. doi:10.1186/1750-1172-2-46. PMID 18021432.
^ Henke, C. E., G. Henke, L. R. Elveback, C. M. Beard, D. J. Ballard and L. T. Kurland. 1986. The epidemiology of sarcoidosis in Rochester, Minnesota: a population-based study of incidence and survival. Am. J. Epidemiol. 123:840–845.
^ “American Thoracic Society: Statement on Sarcoidosis. Am J Respir Crit Care Med 1999;160:736-755.
^ a b c Antonelli A, Fazzi P, Fallahi P, Ferrari SM, Ferrannini E (August 2006). “Prevalence of hypothyroidism and Graves disease in sarcoidosis”. Chest 130 (2): 526–32. doi:10.1378/chest.130.2.526. PMID 16899854.
^ Rossman MD, Kreider ME (August 2007). “Lesson learned from ACCESS (A Case Controlled Etiologic Study of Sarcoidosis)”. Proc Am Thorac Soc 4 (5): 453–6. doi:10.1513/pats.200607-138MS. PMID 17684288.
^ Kettritz R, Goebel U, Fiebeler A, Schneider W, Luft F (October 2006). “The protean face of sarcoidosis revisited”. Nephrol. Dial. Transplant. 21 (10): 2690–4. doi:10.1093/ndt/gfl369. PMID 16861724.
^ a b Verschueren K, Van Essche E, Verschueren P, Taelman V, Westhovens R (November 2007). “Development of sarcoidosis in etanercept-treated rheumatoid arthritis patients”. Clin. Rheumatol. 26 (11): 1969–71. doi:10.1007/s10067-007-0594-1. PMID 17340045.
^ Stokes MB, Foster K, Markowitz GS, et al (July 2005). “Development of glomerulonephritis during anti-TNF-alpha therapy for rheumatoid arthritis”. Nephrol. Dial. Transplant. 20 (7): 1400–6. doi:10.1093/ndt/gfh832. PMID 15840673.
^ Iannuzzi MC (August 2007). “Advances in the genetics of sarcoidosis”. Proc Am Thorac Soc 4 (5): 457–60. doi:10.1513/pats.200606-136MS. PMID 17684289.
^ Hiramatsu J, Kataoka M, Nakata Y, et al (October 2003). “Propionibacterium acnes DNA detected in bronchoalveolar lavage cells from patients with sarcoidosis”. Sarcoidosis Vasc Diffuse Lung Dis 20 (3): 197–203. PMID 14620162.
^ Inoue Y, Suga M (2008). “[Granulomatous diseases and pathogenic microorganism]” (in Japanese). Kekkaku 83 (2): 115–30. PMID 18326339.
^ Gupta D, Agarwal R, Aggarwal AN, Jindal SK (September 2007). “Molecular evidence for the role of mycobacteria in sarcoidosis: a meta-analysis”. Eur. Respir. J. 30 (3): 508–16. doi:10.1183/09031936.00002607. PMID 17537780.
^ Almenoff PL, Johnson A, Lesser M, Mattman LH. Growth of acid fast L forms from the blood of patients with sarcoidosis. Thorax 1996;51:530-3. PMID 8711683.
^ Padilla ML, Schilero GJ, Teirstein AS. Donor-acquired sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2002;19:18-24. PMID 12002380.
^ Barbour GL, Coburn JW, Slatopolsky E, Norman AW, Horst RL. Hypercalcemia in an anephric patient with sarcoidosis: evidence for extrarenal generation of 1,25-dihydroxyvitamin D. N Engl J Med 1981;305:440-3. PMID 6894783.
^ a b c Subramanian P, Chinthalapalli H, Krishnan M, et al (September 2004). “Pregnancy and sarcoidosis: an insight into the pathogenesis of hypercalciuria”. Chest 126 (3): 995–8. doi:10.1378/chest.126.3.995. PMID 15364785.
^ Porter N, Beynon HL, Randeva HS (2003). “Endocrine and reproductive manifestations of sarcoidosis“. QJM 96 (8): 553–61. PMID 12897340.
^ Yu-Lee LY (2002). “Prolactin modulation of immune and inflammatory responses“. Recent Prog. Horm. Res. 57: 435–55. PMID 12017556.
^ Méndez I, Alcocer-Varela J, Parra A, et al (2004). “Neuroendocrine dopaminergic regulation of prolactin release in systemic lupus erythematosus: a possible role of lymphocyte-derived prolactin“. Lupus 13 (1): 45–53. PMID 14870917.
^ Papadopoulos KI, Hörnblad Y, Liljebladh H, Hallengren B (March 1996). “High frequency of endocrine autoimmunity in patients with sarcoidosis”. Eur. J. Endocrinol. 134 (3): 331–6. PMID 8616531.
^ Romagnani S (June 1997). “The Th1/Th2 paradigm“. Immunol. Today 18 (6): 263–6. PMID 9190109.