Sarcoidosis immune system disorder
Sarcoidosis is an immune system disorder characterised by non-necrotising granulomas (small inflammatory nodules).
Virtually any organ can be affected, however, granulomas most often appear in the lungs or the lymph nodes.
Symptoms can occasionally appear suddenly but more often than not appear gradually.
When viewing X-rays of the lungs, sarcoidosis can have the appearance of tuberculosis or lymphoma.
Sarcoidosis occurs throughout the world in any race. It is more commonly seen in blacks than whites, primarily people of northern European descent in the latter case.
Pulmonary involvement is the most common presentation of sarcoidosis. Signs and symptoms Sarcoidosis is a systemic disease that can affect any organ.
Common symptoms are vague, such as fatigue unchanged by sleep, lack of energy, aches and pains, arthralgia, dry eyes, blurry vision, shortness of breath, a dry hacking cough or skin lesions.
The cutaneous symptoms are protean, and range from rashes and noduli (small bumps) to erythema nodosum or lupus pernio. The combination of erythema nodosum, bilateral hilar lymphadenopathy and arthralgia is called Lofgren syndrome.
This syndrome has a relatively good prognosis. Renal, liver, heart or brain involvement may cause further symptoms and altered functioning.
Manifestations in the eye include uveitis 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 Heerfordt-Waldenstrom syndrome.
Hypercalcemia (high calcium levels) and its symptoms may be the result of excessive vitamin D production.
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 externally compress airways or when internal inflammation or nodules impede airflow.
Causes and pathophysiology
No direct cause of sarcoidosis has been identified, although there have been reports of cell wall deficient bacteria that may be possible
pathogens. These bacteria are not identified in standard laboratory analysis.
It has been thought that there may be a hereditary factor because some families have multiple members with sarcoidosis. To date, no reliable genetic markers have been identified, and an alternate hypotheses is that family members share similar exposures to environmental pathogens.
There have also been reports of transmission of sarcoidosis via organ transplants. Sarcoidosis frequently causes a dysregulation of vitamin D production; extrarenal (outside the kidney) production can be marked.
Production of vitamin D goes on outside the kidneys. This results 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.
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 unfortunately do not respond to steroid therapy.
The use of corticosteroids in mild disease is controversial because many times the disease can remit spontaneously.
Additionally, corticoteroids have many recognized dose- and duration-related side effects, and their use has been linked to relapses and worsening of the disease. Severe symptoms have generally been treated with steroids, and later with steroid-sparing agents.
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 treatment (such as infliximab).
Unfortunately, none of these have provided reliable treatment and there can be signficant side effects such as an increased risk of reactivating latent tuberculosis.
Disciplined avoidance of sunlight and vitamin D foods is necessary in patients who are prone to develop hypercalcemia and will help relieve symptoms in all sarcoidosis patients.
Antibiotic therapy has been reported to be effective for lung, lymph and cutaneous manifestations of sarcoidosis but this therapy is not currently the standard of care.
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