Sarcoidosis: immunology, rheumatic involvement, and therapeutics

Sarcoidosis is a systemic granulomatous disorder of unknown cause. It has protean manifestations and can affect any organ, including bones, joints, muscles, and vessels. This article reviews the most recent information on the immunologic and inflammatory pathogenesis of sarcoidosis and its implications for therapy. Sarcoidosis results from an overexuberant T cell-mediated immune response to the unknown antigen. This antigen presentation/T cell antigen recognition event occurs in a microenvironment that is suffused in proinflammatory cytokines and growth factors that promote cell attraction, adhesion, permeability changes, further cytokine production, and release. An amplified cellular immune response ensues, leading to granuloma formation and fibrosis. The article summarizes the new developments in the medical literature related to the rheumatologic manifestations and their detection and management in sarcoidosis patients. Osseous involvement in sarcoidosis is often underdiagnosed because it can be asymptomatic. New imaging techniques improve detection. Management of osteoporosis in sarcoidosis patients requires special attention because these patients often have an underlying disorder in calcium metabolism that results in hypercalcuria and hypercalcemia. Joint manifestations, such as the classic Lofgren syndrome with accompanying erythema nodosum, may be self-limited or may become chronic, presenting an ongoing therapeutic challenge. Sarcoidosis vasculitis can be devastating, affecting virtually any vessel in any organ and causing significant morbidity. Muscle involvement, like the bony involvement, is underdiagnosed. Symptoms of muscle weakness, aches, tenderness, and fatigue should prompt consideration of occult sarcoid myositis, often with accompanying neurogenic atrophy. Sarcoidosis treatment usually starts with a period of observation before pharmacologic intervention. Corticosteroids remain the first-line therapy. Alternatives to corticosteroids are often introduced either because of steroid intolerance or in an attempt to reduce steroid dose and side effects. The advantages and disadvantages of these second line therapies are reviewed. Medical vigilance, with attention to new patient symptoms, is important in the management of sarcoidosis, because of the tendency of this disease to present in so many and diverse patterns.