sarcoidosis n : a chronic disease of unknown cause marked by the formation of nodules in the lungs and liver and lymph glands and salivary glands
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 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. 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 than for Caucasians, who are more likely to have asymptomatic disease.
Signs and symptomsSarcoidosis 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.
The combination of anterior uveitis, parotitis and fever is called uveoparotitis, and is associated with Heerfordt-Waldenstrom syndrome. ()
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.
Chest X-ray changes are divided into four stages
- Stage 1 bihilar lymphadenopathy
- Stage 2 bihilar lymphadenopathy and reticulonodular infiltrates
- Stage 3 bilateral infiltrates
- Stage 4 fibrocystic sarcoidosis typically with upward hilar retraction, cystic & bullous changes
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.
Causes and pathophysiologyThe exact cause of sarcoidosis is not known, the current working hypothesis is that in genetically susceptible individuals sarcoidosis is caused through alteration in immune response after exposure to an environmental, occupational, or infectious agent.
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 suggests 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 .
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) 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.
Several infectious agents appear to be significantly associated with sarcoidosis but none of the known associations is specific enough to suggest a direct causative role. Propionibacterium acnes can be found in bronchoalveolar lavage of approximately 70% patients and is associated with disease activity, however it can be also found in 23% of controls. . A recent meta-analysis investigating the role of mycobacteria in sarcoidosis found it was present in 26.4% of cases, however the meta-analysis also detected a possible publication bias, so the results need further confirmation
There have also been reports of transmission of sarcoidosis via organ transplants.
Sarcoidosis frequently causes a dysregulation of vitamin D production with an increase in extrarenal (outside the kidney) production. Specifically, macrophages inside the granulomas convert vitamin D to its active form, resulting in elevated levels of the hormone 1,25-dihydroxyvitamin D and symptoms of hypervitaminosis D that may include fatigue, lack of strength or energy, irritability, metallic taste, temporary memory loss or cognitive problems. Physiological compensatory responses (e.g. suppression of the parathyroid hormone levels) may mean the patient does not develop frank hypercalcemia. This condition may be aggravated by high levels of estradiol and prolactin such as in pregnancy, leading to hypercalciuria and/or compensatory hypoparathyroidism While pregnancy can have an effect on sarcoidosis, the reverse has not been found to occur. 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
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.
TreatmentCorticosteroids, 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.
Avoidance of sunlight and Vitamin D foods may be helpful in patients who are susceptible to developing hypercalcemia.
- The Foundation for Sarcoidosis Research
- Pathology Images of Sarcoidosis and Other Granulomatous Diseases Yale Rosen, M.D.
- [http://22.214.171.124/eAtlas/RESP/1654b.htm Microscopy of granulomas in sarcoidosis]
- The Sarcoidosis Community is The Foundation for Sarcoidosis Research's online community
- MedPix Pulmonary Sarcoid- Bilateral Hilar Adenopathy
sarcoidosis in Danish: Sarkoidose
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sarcoidosis in Modern Greek (1453-): Σαρκοείδωση
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