Hypothesis for the pathogenesis of systemic sclerosis.

An hypothesis for the pathogenesis of systemic sclerosis is introduced. It posits a genetic background with environmental stimuli that activate immune cells. The immune cells, in turn, may damage vascular endothelium, cause proliferation of fibroblasts, or stimulate fibroblasts to produce collagen. Endothelial cell damage can also activate the immune system or induce fibroblast proliferation. Associated with fibroblast proliferation may be immune activation or collagen production. Finally, collagen production and end organ damage can induce immune activation thus perpetuating the cycle. Raynaud's phenomenon, an early finding in systemic sclerosis can cause vascular damage, thus entering the cycle at a different point than other environmental stimuli. This hypothesis will undoubtedly require change as data emerge, but it presents a conceptual model for testing and modification.