Seminars in respiratory and critical care medicine
-
Sarcoidosis is a chronic granulomatous disorder characterized by an accumulation of activated lymphocytes, predominantly T helper cells, expressing the Th1 phenotype and macrophages at sites of disease activity. Although the cause of sarcoidosis has not been elucidated, several lines of evidence suggest that granuloma formation results from exposure to one or more antigens, eliciting a T lymphocyte response. ⋯ This article discusses in depth the key cellular elements and signals that generate and orchestrate the sarcoid granulomatous response. The precise factors inciting the sarcoid granulomatous response have not yet been identified, but chronic exposure to microbial agents, their products, or inorganic substances may be important in the pathogenesis.
-
Sarcoidosis can affect any organ in the body. Frequently extrapulmonary manifestations of the disease are the major cause of morbidity. Treatment of extrapulmonary sarcoidosis often requires consideration of alternative immunosuppressive agents, topical therapy, or therapy that is not specifically directed against the granulomatous inflammation of the disease. This article reviews the clinical presentation and therapy of extrapulmonary sarcoidosis.
-
Sarcoidosis is a multisystemic granulomatous disease of unknown etiology that may involve virtually any organ. Pulmonary involvement predominates, but sarcoidosis can involve multiple organs, with or without concomitant lung involvement. Aberrations on chest radiographs are present in more than 90% of patients with sarcoidosis. ⋯ Although HRCT is not necessary to manage all cases of sarcoidosis, HRCT may be invaluable in SELECTED patients with stage II or III sarcoidosis to discriminate alveolitis (which may be amenable to therapy) from fibrosis. Additionally, radionuclide techniques may have a role in extrapulmonary sarcoidosis (particularly when central nervous system or cardiac involvement is suspected). We review the salient features and role of magnetic resonance imaging and diverse radionuclide techniques to diagnose or follow selected cases of extrapulmonary sarcoidosis.
-
Sarcoidosis likely results from an interplay of environmental and genetic factors. Despite a recent large multicenter study, A Case-Control Etiologic Study of Sarcoidosis (ACCESS), no single causative environmental agent has been identified. Family clustering and differences in racial incidence of sarcoidosis support an inherited susceptibility to sarcoidosis. ⋯ One in African Americans reporting linkage to chromosome 5 and the other in German families reporting linkage to chromosome 6. Follow-up studies on chromosome 6 identified the BTNL2 gene, a B7 family costimulatory molecule to be associated with sarcoidosis. Advances in genotyping and statistical analysis are helping to elucidate the genetics of sarcoidosis.
-
The role of pathology in the diagnosis of sarcoidosis is identification of granulomas in tissue specimens and performance of studies to exclude known causes of granulomatous inflammation. The granulomas of sarcoidosis are nonspecific lesions that, by themselves and in the absence of an identifiable etiologic agent, are not diagnostic of sarcoidosis or any other specific disease. Among the diseases to be excluded are mycobacterial, fungal, and parasitic infections, chronic beryllium disease and other pneumoconiosis, hypersensitivity pneumonitis, and Wegener's granulomatosis. ⋯ In cases that exhibit necrotizing granulomas with more than minimal, focal necrosis, extrathoracic involvement only, and/or incompatible clinical and radiological findings, the diagnosis of sarcoidosis should be approached with great caution. The diagnosis is most secure when compatible clinical and radiological findings are supported by the demonstration of microorganism-negative, nonnecrotizing granulomas in a biopsy specimen accompanied by biopsy evidence or strong clinical evidence of multisystem involvement, and negative cultures for bacteria, mycobacteria, and fungi. A positive Kveim-Siltzbach test provides strong support for the diagnosis of sarcoidosis.