The pathogenesis of SSc (Adapted from ). SSc is initiated by microvascular injury, inducing inflammation, an autoimmune response, and fibroblast activation and differentiation. Activated myofibroblasts perform a series of functions, culminating in excess deposition of extracellular matrix and the development of fibrosis. Republished with permission of The Journal of Clinical Investigation, from Systemic sclerosis: a prototypic multisystem fibrotic disorder, Varga J and Abraham D, Volume No. 117, Edition No. 3, 2007; permission conveyed through Copyright Clearance Center, Inc.