by Nathan Wei, MD, FACP, FACR
Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.
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Sarcoidosis is a systemic granulomatous disease of unknown cause affecting young and middle-aged adults.
Patients commonly present with bilateral hilar lymphadenopathy, pulmonary infiltrates, and eye and skin lesions. The heart, liver, spleen, salivary glands, muscles, bones, kidneys, and central nervous system also may be involved. Diagnosis is based on clinical, x-ray, plus histologic evidence of noncaseating epithelioid granulomas, and exclusion of other granulomatous diseases.
Prognosis correlates with mode of onset, initial clinical course, and extent of disease. The optimal management of sarcoidosis has not been well defined. Although corticosteroids remain the mainstay of treatment, there is conflicting data regarding the optimal initiation, dosage, or duration of therapy.
It is not known whether steroids improve long-term lung function or favorably alter disease progression. One recent study that examined follow-up after therapy with oral and inhaled steroids concluded that immediate treatment of stages II and III sarcoidosis, but not stage I, improved the five-year prognosis with regard to lung-function.
Data suggest that oral steroids should be used in patients with stages II and III disease, with moderate to severe or progressive symptoms and chest x-ray changes. It is unclear if asymptomatic patients will ever need therapy, even if they have diffuse lung infiltration. Because there is no consensus, the course is individualized for each patient.
The risk of osteoporosis must be addressed in patients taking prolonged systemic corticosteroids.
Cytotoxic agents may benefit patients who do not respond to corticosteroids. They are usually combined with oral steroids. Limited evidence exists to guide physicians in the initiation, dosage, and duration of therapy. Because of safety factors, methotrexate (Rheumatrex) and azathioprine (Imuran) are the preferred agents.
Clinical data on the effects of methotrexate in the treatment of pulmonary sarcoidosis are limited to a few series and some case reports. A recent small study showed that 12 months of therapy with methotrexate was beneficial in patients with acute, symptomatic sarcoidosis. Other trials using methotrexate at 10 to 25 mg per week show its possible benefit as a steroid-sparing agent. Relapses were frequent after discontinuation of treatment, suggesting that methotrexate suppresses but does not cure the disease.
Azathioprine has been shown to be effective in a limited number of cases. Small clinical trials have demonstrated that azathioprine, when used for treatment of chronic pulmonary sarcoidosis, is effective as a corticosteroid-sparing agent.
Immunomodulators have been used successfully in select patients with pulmonary sarcoidosis. Many of them modulate the activity of tumor necrosis factor alpha (TNF-alpha). TNF-alpha secreted by activated T-lymphocytes and macrophages has been implicated in both the chronic inflammatory responses as well as granuloma formation. Theoretically, TNF- alpha blockade should be beneficial.
Through its anti-TNF-alpha activity, infliximab (Remicade) has presumptive usefulness in sarcoidosis treatment. Data limited to case reports show promising results in the treatment of complicated or refractory pulmonary sarcoidosis.
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