Pathogenesis of sarcoidosis
- Andrew Fontenot, MD
Andrew Fontenot, MD
- Henry N. Claman Professor of Medicine, Division Head, Allergy and Clinical Immunology
- University of Colorado, School of Medicine
- Talmadge E King, Jr, MD
Talmadge E King, Jr, MD
- Editor-in-Chief — Pulmonary and Critical Care Medicine
- Section Editor — Interstitial Lung Disease
- Dean, School of Medicine
- Vice Chancellor, Medical Affairs
- University of California San Francisco
- Section Editors
- Kevin R Flaherty, MD, MS
Kevin R Flaherty, MD, MS
- Section Editor — Interstitial Lung Disease
- Associate Professor of Medicine
- University of Michigan Health System
- Andrew Nicholson, MD
Andrew Nicholson, MD
- Section Editor — Pulmonary Pathology
- Professor of Respiratory Pathology
- Imperial College School of Medicine, London
Sarcoidosis is a multisystem disorder of unknown etiology characterized by the accumulation of T lymphocytes, mononuclear phagocytes, and noncaseating granulomas in involved tissues [1,2]. The lungs are affected in approximately 90 percent of patients, and pulmonary disease accounts for the majority of the morbidity and mortality associated with this disease. Other tissues commonly involved include the skin, eyes, and lymph nodes (table 1). (See "Clinical manifestations and diagnosis of pulmonary sarcoidosis".)
The initial lesion within the pulmonary system is a CD4+ T cell alveolitis, followed by the development of noncaseating granulomata [2-6]. The granulomas have a tightly packed central area composed of macrophages, epithelioid cells, and multinucleated giant cells surrounded by lymphocytes, monocytes, mast cells, and fibroblasts . Within the lung, granulomas tend to occur in a bronchocentric fashion that can lead to either obstructive or restrictive pulmonary physiology. (See "Clinical manifestations and diagnosis of pulmonary sarcoidosis", section on 'Pulmonary function testing'.)
The sarcoid granuloma can resolve without sequelae or undergo obliterative fibrosis, with the resultant development of interstitial fibrosis [2,8]. The presence of granulomatous inflammation is thought to result from an exaggerated cell-mediated immune response to one or more unidentified antigen(s) [2-4].
Despite advances in our knowledge of the immunopathogenesis of sarcoidosis, the antigenic stimulus that initiates the disease process remains elusive. The multicenter NIH-funded ACCESS case-control study of over 700 patients and nearly 30,000 relatives has been completed, and no single etiologic agent or genetic locus was clearly implicated in the pathogenesis of sarcoidosis [9-11]. Several possible associations have been investigated, as outlined below.
Occupational and environmental exposures — It has been hypothesized that sarcoidosis is associated with several occupational and environmental exposures. However, only beryllium and its salts have been shown to produce granulomata that are similar to that seen in sarcoidosis. Despite intensive efforts, studies have largely failed to identify an external agent or agents responsible for sarcoidosis .
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- POSSIBLE ETIOLOGIES
- Occupational and environmental exposures
- Kveim-Siltzbach reagent
- Infectious agents
- Major histocompatibility complex
- Other genes
- T cell abnormalities
- - T cell receptor
- OTHER ASSOCIATIONS
- Abnormal calcium homeostasis
- Common variable immunodeficiency
- INFORMATION FOR PATIENTS