Sarcoidosis



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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From the National Institutes of Health



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.

Arthritis involvement typically presents with inflammatory changes affecting the small joints of the hands, wrists, and ankles.

In fact, sarcoidosis often presents itself to our clinic as a young person who comes in with very inflamed swollen ankles in the spring time.

Diagnosis is based on clinical and x-ray findings plus histologic evidence of noncaseating epithelioid granulomas, and exclusion of other granulomatous diseases.

Prognosis correlates with mode of onset, host characteristics, 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 little evidence for 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 variables and the need for further treatment.

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 on the optimal dosage or duration of therapy, the course is tailored to the patient.

The risks of prolonged systemic corticosteroids need to be discussed with patients. There is little evidence for the efficacy of inhaled steroids in the treatment of pulmonary sarcoidosis. Inhaled corticosteroids may be considered for the symptomatic relief of cough, although limited evidence supports their use.

Cytotoxic agents may benefit patients who do not respond to corticosteroids. They are usually combined with oral steroids but sometimes used as single agents. Limited evidence exists as to when to initiation, dosage, and duration of therapy. Because of their relative safety, methotrexate 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.

Biologics have been used successfully in select patients with pulmonary sarcoidosis. Many of them block 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.

Pentoxifylline (Trental) inhibits TNF-alpha production from alveolar macrophages in patients with sarcoidosis. In one small clinical trial, pentoxifylline was used as a steroid-sparing agent in progressive pulmonary sarcoidosis. 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. Current randomized controlled studies are being performed.



Other anti- TNF drugs such as Enbrel, Humira, Cimzia, and Simponi also may be effective.



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