SARCOIDOSIS

Abstract

Sarcoidosis is a multisystem granulomatous disorder primarily affecting young adults. Lung involvement occurs most frequently and is characterized by varying degrees of alveolitis, granulomatous inflammation, and interstitial fibrosis. Enlargement of intrathoracic lymph nodes frequently accompanies pulmonary parenchymal involvement. Whereas the cause remains unknown, major advances have been made in our understanding of the pathogenesis of sarcoidosis. In this regard, it has become clear that this disorder is characterized by the accumulation of activated macrophages and CD4+ helper T lymphocytes within the lung, and that elaboration of mediators by these cells perpetuates the inflammatory process, drives granuloma formation, and regulates fibrosis. Activation of cellular immune processes appears to be restricted to sites of inflammation and does not occur in the peripheral blood. The diagnosis of sarcoidosis rests on the demonstration of noncaseating granulomas in association with characteristic clinico-radiographic features. Other causes of granulomatous inflammation must be excluded in order to firmly establish the diagnosis. The unpredictable natural history of this disease, with frequent spontaneous remissions, makes it difficult to define rigid criteria for therapeutic intervention, but in general, patients with significant radiographic or physiological abnormalities should be considered for treatment. Corticosteroids are currently the agents of choice and can bring about at least temporary clinical, radiographic, and physiologic improvement. Despite their widespread use in the treatment of sarcoidosis, however, the ability of corticosteroids to impact significantly on the long-term course of disease remains uncertain. Experience with other immunosuppressive and cytotoxic agents is limited, but use of these agents should be considered in patients with severe, progressive disease unresponsive to corticosteroids. The design and institution of more effective treatment regimens awaits further insight into the origin and pathogenesis of this disorder.