Systemic Sclerosis

A characteristic feature of systemic sclerosis (SSc) distinguishing it from other autoimmune and connective tissue diseases is the occurrence of widespread parenchymal fibrosis. SSc carries the highest case fatality rate among the connective tissue diseases. Although inflammation, autoimmunity, vascular injury, and damage are prominent early events in SSc with significant roles in the development of progressive tissue damage, fibrosis is the hallmark of the disease. Genetic and epidemiologic studies suggest that SSc occurs in susceptible individuals following exposure to (as yet uncharacterized) environmental triggers. Suppression of pro-fibrotic factor expression and/or function and induction of anti-fibrotic gene expression or activity provide complementary approaches for the prevention and/or treatment of fibrosis. Potential approaches that might be feasible for such anti-fibrotic interventions are illustrated. Several animal models of scleroderma are described, although none reproduce all the cardinal features of human SSc. Robust experimental strategies such as transgenic animal modeling and DNA microarray analysis of gene expression are beginning to yield a coherent picture. Selected novel therapeutic agents with a potential utility in the treatment of SSc-associated fibrosis are listed.