Pharmacotherapy of systemic sclerosis

Abstract

Importance of the field-Systemic-sclerosis (SSc) is an uncommon autoimmune disease with variable degrees of fibroproliferation in blood vessels and certain organs of the body. Presently, there is no cure for SSc. The purpose of this article is to review the current literature regarding pathogenesis and treatment of complications of SSc.Areas covered in this review-All available articles regarding research related to SSc pathogenesis and treatment listed in the PubMed.gov database were searched, relevant articles were then reviewed and used as sources of information for this review.What the reader will gain-This review attempts for the reader to highlight some current thought regarding mechanisms of SSc pathogenesis and how autoimmunity relates to vascular changes and fibrogenesis of the disease plus provide a review of results of completed clinical trials and current on-going clinical trials that address organ specific or global therapies for this disease which can aid physicians who provide medical care for patients with SSc.

High reactive oxygen species in fibrotic and nonfibrotic skin of patients with diffuse cutaneous systemic sclerosis

“…Even though the pathogenesis of SSc is unclear, fibrosis is proposed to be the outcome of a combination of autoimmune and proliferative/obliterative vasculopathy mechanisms [4,5,6].…”

Vascular involvement in systemic sclerosis (scleroderma)

“…This conclusion is reached because multiple fibrogenic mediators have been detected in SSc fibrotic tissues or in plasma/sera of patients with SSc. These include TGF-β1 and -β2, PDGF, IL-4, CTGF, IL-13, IL-6, oncostatin M, tryptase, IL-17, IL-5, monocyte chemoattractant protein (MCP)-1, S1P, and LPA 10,20,105. Which mediators drive fibrogenesis in SSc may also depend on disease subset type and/or disease duration.…”

“…Myofibroblasts are not increased in nonlesional SSc tissue. Myofibroblasts can be induced from: 1) resident fibroblasts by TGF-β1, TGF-β3, GMCSF, IL-6, IL-4, thrombin, bradykinin, and histamine or tryptase from mast cells; 2) epithelial cells by oncostatin M and TGF-β1; 3) endothelial cells by tumor necrosis factor-α; 4) pericytes by TGF-β1; and 5) circulating fibrocytes by TGF-β1, IL-4, IL-13, PDGF-B, and ET-1 10. Which of these sources is/are responsible for the predominant presence of myofibroblasts in SSc fibrotic tissue is yet to be determined.…”

“…We will briefly summarize the evidence for the central role of immune/inflammatory cells in the pathogenesis of SSc since more detailed descriptions are given in other recent reviews 10,105. The autoimmune state in SSc may partially be the result of a permissive genetic background and reduced suppressive function of T regs 154.…”

Sclerodermatous skin: An immunohistochemical study

“…Despite some characteristics distinguishing the two types from each other, they share the common feature of fibrosis involving excessive extracellular matrix (ECM) production that impairs usual tissue characteristics to cause organ failure late in the disease course [5]. Although a large body of novel scientific knowledge has been acquired about the molecular mechanisms of pathophysiology of SSc [6][7][8], we are far from stopping or even slowing down the ongoing fibrotic process characterizing the disease [9][10][11].…”