Sarcoidosis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: :Roshan Dinparasti Saleh M.D.
Overview
Sarcoidosis is a multisystem disorder of unknown etiology characterized by noncaseating granulomas in involved tissues. The lungs are affected most commonly, 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.
Pathophysiology
Granuloma formation is a hallmark of sarcoidosis disease. The underlying immunologic events include (1) exposure to antigens, (2) activation of antigen-presenting cells (macrophages and/or dendritic cells), (3) a T cell response in an effort to eliminate the antigen, and (4) granuloma formation. macrophages differentiate into epithelioid cells, which gain secretory capability, lose phagocytic capacity, and fuse to form multinucleated giant cells which are cellular basis of granulomas. Th2 cells also contribute to granuloma formation. These cells secrete fibronectin and CCL18, which finally lead to macrophage-mediated collagen formation and fibrosis in 25% of patients with sarcoidosis [1]. It is estimaed that two possible immunologic scenarios play role in sarcoidosis: an intense immune reaction in patients with active disease, finally resulting in antigen clearance, or chronic disease with less inflammation but the inability to eradicate the antigen and chronic stimulation of the immune response, resulting in organ damage such as lung fibrosis[2].
Histopathological Findings
Granulomatous inlammation is necessary/but not sufficient to establish a diagnosis of sarcoidosis in most cases[3]. Histologic features that suggest sarcoidosis:
- Compact (organized) collection of mononuclear phagocytes (macrophages and epithelioid cells)
- No necrosis within the sarcoid granuloma
- Inclusions may be present within the sarcoid granuloma, including asteroid bodies, Schaumann bodies, birefringent crystals, and Hamazaki-Wesenberg bodies(neither specific nor diagnostic)
- Granulomatous inlammation in at least two organs(although not routinely performed)
The first histopathological finding in the lung is a CD4+ T cell alveolitis, followed by the development of noncaseating granuloma[4] Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology
References
- ↑ Iannuzzi MC, Rybicki BA, Teirstein AS: Sarcoidosis. N Engl J Med 357:2153–2165, 2007.
- ↑ Zissel G: Cellular activation in the immune response of sarcoidosis. Semin Respir Crit Care Med 35:307–315, 2014.
- ↑ Statement on sarcoidosis: Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med 160:736–755, 1999.
- ↑ Thomas PD, Hunninghake GW: Current concepts of the pathogenesis of sarcoidosis. The American review of respiratory disease 1987, 135(3):747-760.