Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. fwig@jhmi.edu
Although scleroderma is generally considered a fibrosing disease of the tissues, it is now recognized that the underlying vascular disease is playing a fundamental role in its pathogenesis and associated tissue injury. The exact mechanism for the widespread scleroderma vascular disease is still unknown, but endothelial cell injury induced by infection, immune-mediated cytotoxicity, antiendothelial antibodies, and/or ischemia-reperfusion have all been implicated. The downstream effects of blood vessel perturbation produce "biomarkers" of vascular damage that reflect disease and may predict clinical outcomes. A complex interaction between endothelial cells, smooth muscle cells, extracellular matrix, and intravascular circulating factors is now recognized to contribute to the vascular reactivity, remodeling, and occlusive disease of scleroderma. Understanding the mechanisms underlying these processes provides rationale of novel therapeutic strategies and specific targeted therapy. This review will outline some of the evidence for the causes and consequences of scleroderma vascular disease.