Sarcoidosis

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**Sarcoidosis**
*Classification & external resources*
ICD-10	D 86.
ICD-9	135
OMIM	181000
DiseasesDB	11797
MedlinePlus	000076
eMedicine	med/2063

Sarcoidosis (also called sarcoid or Besnier-Boeck disease) 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 (D 86.0) or the lymph nodes (D 86.1). Symptoms can occasionally appear suddenly but usually appear gradually. When viewing X-rays of the lungs, sarcoidosis can have the appearance of tuberculosis or lymphoma.

1 Epidemiology
2 Signs and symptoms
3 Investigations
4 Causes and pathophysiology
5 Treatment
6 References
7 External links

[edit] Epidemiology

Sarcoidosis occurs throughout the world in all races. It is more commonly seen in people of African descent than Caucasians, primarily people of northern European descent in the latter case. Pulmonary involvement is the most common presentation of sarcoidosis, but it can manifest in any organ.

[edit] Signs and symptoms

Sarcoidosis in a Lymph Node.

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 are protean, 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 Lofgren 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 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 are called Heerfordt-Waldenstrom syndrome. (D 86.8)

[edit] Investigations

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 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 EKG, ophthalmologic exam, liver function tests, serum calcium and 24hour urine calcium.

[edit] 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^[1]. 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 hypothesis is that family members share similar exposures to environmental pathogens. There have also been reports of transmission of sarcoidosis via organ transplants^[2].

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^[3]. 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.

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.

[edit] 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 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, corticosteroids have many recognized dose- and duration-related side effects, 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 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 prone to develop hypercalcemia.

Antibiotic therapy has been reported to be effective for lung, lymph and cutaneous manifestations of sarcoidosis^[4] but this therapy is not currently the standard of care. On March 28, 2006, the U.S. FDA Office of Orphan Products Development designated Minocycline in the treatment of sarcoidosis,[1]

[edit] References

^ 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.
^ Bachelez H, Senet P, Cadranel J, Kaoukhov A, Dubertret L. The use of tetracyclines for the treatment of sarcoidosis. Arch Dermatol 2001;137:69-73. PMID 11176663.