Update on the etiopathogenesis of systemic sclerosis

Abstract

Systemic Sclerosis (SSc) is an autoimmune disease of multifactorial etiology, triggered by a combination of genetic and environmental factors. Its varied clinical expression re- sults from the complex physiopathogenic interaction of three main elements: prolifera- tive vasculopathy, immune dysregulation and abnormal deposition and remodeling of the extracellular matrix (ECM), of which the characteristic disease fibrosis is the result. Early physiopathogenic events appear to be endothelial injury and imbalance in vascular repair with the activation of endothelial cells, the immune system and platelets, with the release of multiple mediators such as TH2 proinflammatory cytokines and growth factors, triggering a sequence of simultaneous or cascading events that involve several intracel- lular signaling pathways.The most important result of these events is the hyperactivation of fibroblasts, the main effector cells of fibrosis, which will then produce large amounts of ECM constituents and secrete multiple growth factors and cytokines that perpetuate the process. In this article we review the main factors potentially involved in the etiology of SSc and reexamine the current knowledge about the most important mechanisms involved in the development of lesions that are characteristic of the disease. A better understanding of these physiopatho- genic mechanisms will help identify potential therapeutic targets, which may result in advances in the management of this complex and debilitating disease.