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| DiseaseID |
HGD65 |
| Genetic
Disorder |
Sarcoidosis
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| Gene
Name |
nucleotide-binding oligomerization domain containing 2 |
| Description |
Sarcoidosis, also called sarcoid (from the Greek 'sark' and 'oid' meaning "flesh-like") or Besnier-Boeck disease, is an immune system disorder characterised 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.
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| Symptoms |
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 Lφfgren 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.
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| Causes |
Doctors don't know the exact cause of sarcoidosis, although they think it may occur when your immune system overreacts to an unknown toxin, drug or pathogen that enters your body through your airways.
Some experts speculate that the causative agent may be a nontuberculous mycobacterium, a noncontagious member of the family of bacteria that cause tuberculosis. In a small portion of people, sarcoidosis may have a genetic component. Studies are ongoing to investigate the genetic and environmental components of this disease.
Normally, your immune system helps protect your body from foreign substances and invading microorganisms, such as bacteria and viruses. But in sarcoidosis, T-helper lymphocytes white blood cells that play a key role in your immune response seem to respond too strongly to a perceived threat. This triggers small areas of inflammation called granulomas.
As the disease progresses, granulomas and scarring (fibrosis) may occur in the tissue between the air sacs, stiffening your lungs and reducing the amount of air your lungs can hold. |
| Diagnosis |
Sarcoidosis produces few signs and symptoms in its early stages, and when they do occur, they often resemble those of other illnesses. For that reason, your doctor will diagnose sarcoidosis only after ruling out diseases with similar features, such as lymph cancer (lymphoma), tuberculosis, rheumatoid arthritis, rheumatic fever and fungal infections.
Even then, doctors can miss sarcoidosis. In the majority of cases, undiagnosed sarcoidosis disappears spontaneously, but a few people go on to develop more severe signs and symptoms usually over a period of years.
No single noninvasive test can positively identify sarcoidosis, but initially, your doctor is likely to order a chest X-ray. Depending on the results, you may then have one or more of the following:
Lung function tests. Noninvasive pulmonary function tests measure how much air your lungs can hold and the flow of air in and out of your lungs. They can also measure the amount of gases exchanged across the membrane between your lung wall and capillary membrane. During the tests, you're usually asked to blow into a simple instrument called a spirometer. You're most likely to have pulmonary function tests if you're short of breath or a chest X-ray shows changes in your lungs.
Blood tests. These are used to check your liver function and the amount of calcium in your blood. For reasons that aren't clear, some people with sarcoidosis have higher than normal blood-calcium levels. Blood tests can also measure a substance called angiotensin-converting enzyme (ACE). Many but not all people with sarcoidosis have high levels of ACE, which is produced by the cells that make up granulomas. High ACE levels can also result from other illnesses.
Bronchoscopy. In this procedure, your doctor uses a thin, flexible tube (bronchoscope) to examine the inside of your air passages and to take a small tissue sample (biopsy) for laboratory analysis. The sample can tell your doctor whether noncaseating granulomas microscopic changes in tissue that occur in sarcoidosis have formed in your lungs.
Tissue sample. If parts of your body other than your lungs appear to be affected your skin, lymph nodes or the outer membrane (conjunctiva) of your eye your doctor is likely to arrange for a specialist to take a tissue sample (biopsy) from these areas. The samples are then examined for noncaseating granulomas. Because these granulomas can result from a number of conditions, their presence alone can't confirm a diagnosis of sarcoidosis. Other subtle infections can produce granulomas.
Mediastinoscopy. In this procedure, your surgeon removes a sample of lymph nodes from the space between your lungs (mediastinum) using one or more small incisions. If you have sarcoidosis, the disease is likely to have spread to the lymph nodes in your chest cavity even if the nodes aren't enlarged on a chest X-ray or computerized tomography scan. Risks of the procedure include bleeding, temporary hoarseness and reaction to the anesthetic.
Slit-lamp examination. In this exam, your doctor uses a high-intensity lamp to examine the inside of your eyes for damage from sarcoidosis.
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| Treatment |
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 have 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. |
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