New treatment strategies for pulmonary sarcoidosis: antimetabolites, biological drugs, and other treatment approaches.

About half of patients with sarcoidosis will need systemic therapy for their disease. Oral glucocorticoids are the standard first-line treatment for sarcoidosis. With time, patients might develop substantial morbidity from long-term use of high doses of these drugs. We propose a step-wise approach to the management of pulmonary disease in sarcoidosis and provide details about how and when to use alternatives to glucocorticoids. The antimetabolites, such as methotrexate, azathioprine, leflunomide, and mycophenolate, are often used as alternatives to steroids. For patients who cannot be treated with low-dose glucocorticoids and an antimetabolite, anti-tumour necrosis factor (TNF) monoclonal antibodies have been shown to control disease. Unfortunately, anti-TNF drugs are associated with substantial toxic effects and in some cases are ineffective. The next step in treatment includes new strategies such as rituximab. A new regimen combining four antibiotics (levofloxacin, ethambutol, azithromycin, and rifamycin) has shown some promise in preliminary studies; however, the mechanism of action is unknown. Non-inflammatory effects of sarcoidosis, such as pulmonary hypertension and bronchiectasis, might also contribute to an increase in pulmonary symptoms. In those cases, alternative treatment strategies have to be considered.