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Risk factors for and possible causes of systemic sclerosis (scleroderma)

John Varga, MD
Section Editor
John S Axford, DSc, MD, FRCP, FRCPCH
Deputy Editor
Monica Ramirez Curtis, MD, MPH


The pathogenesis of systemic sclerosis (SSc; scleroderma) involves vascular, fibrotic, inflammatory, and immunologic processes. Although a great deal is known about the abnormalities in immune, endothelial, and fibroblast cell function in SSc, it is unclear how these pathogenic pathways are initiated.

The etiology of SSc is unknown. The remarkable complexity of its pathogenesis suggests that no single gene or environmental trigger is, by itself, likely to be responsible for the developments of SSc. Genetic factors clearly influence disease susceptibility as well as patterns of disease expression. The occurrence of SSc-like disease in response to certain environmental agents and the possible relationship of SSc to environmental exposures suggest that certain triggers lead to variable disease expression in genetically susceptible hosts.

A review of the risk factors for and possible causes of SSc is presented here. The pathogenesis of SSc, including vascular and endothelial changes, fibroblast activity, and the role of different cytokines, is discussed separately. (See "Pathogenesis of systemic sclerosis (scleroderma)".)


Exposure to viruses or to certain environmental toxins and drugs appears to trigger the development of disease in genetically susceptible hosts.


Evidence for genetic factors contributing to disease susceptibility in systemic sclerosis (SSc) comes from a variety of studies. Studies of the Choctaw Native Americans in Oklahoma showed that the prevalence of SSc was 20 times higher than in the general population [1,2]. Furthermore, disease expression was remarkably homogeneous, with diffuse skin disease, lung involvement, and anti-topoisomerase I (Scl-70) antibodies detected in almost all affected individuals. The risk of SSc in first-degree relatives of individuals with SSc is markedly increased.


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Literature review current through: Sep 2016. | This topic last updated: Jan 4, 2016.
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