a Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine , University of Genova, IRCCS San Martino Polyclinic Hospital Genova , Genova , Italy.
b Department of Internal Medicine , Ghent University , Ghent , Belgium.
Expert Rev Clin Immunol. 2019 Jul;15(7):753-764. doi: 10.1080/1744666X.2019.1614915. Epub 2019 May 13.
: Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease characterized by chronic and progressive tissue and organ fibrosis with broad patient-to-patient variability. Some risk factors are known and include combination of persistent Raynaud's phenomenon, steroid hormone imbalance, selected chemicals, thermal, or other injuries. Endogenous and/or exogenous environmental trigger/risk factors promote epigenetic mechanisms in genetically primed subjects. Disease pathogenesis presents early microvascular changes with endothelial cell dysfunction, followed by the activation of mechanisms promoting their transition into myofibroblasts. A complex autoimmune response, involving innate and adaptive immunity with specific/functional autoantibody production, characterizes the disease. Progressive fibrosis and ischemia involve skin and visceral organs resulting in their irreversible damage/failure. Progenitor circulating cells (monocytes, fibrocytes), together with growth factors and cytokines participate in disease diffusion and evolution. Epigenetic, vascular and immunologic mechanisms implicated in systemic fibrosis, represent major targets for incoming disease modifying therapeutic approaches. : This review discusses current understanding and new insights of SSc pathogenesis, through an overview of the most relevant advancements to present aspects and mechanisms involved in disease pathogenesis. : Considering SSc intricacy/heterogeneity, early combination therapy with vasodilators, immunosuppressive and antifibrotic drugs should successfully downregulate the disease progression, especially if started from the beginning.
系统性硬化症（SSc）是一种复杂的自身免疫性结缔组织疾病，其特征是慢性和进行性的组织和器官纤维化，患者之间存在广泛的变异性。一些已知的风险因素包括持续性雷诺现象、类固醇激素失衡、某些化学物质、热或其他损伤的组合。内源性和/或外源性环境触发/风险因素促进了遗传易感性患者的表观遗传机制。疾病发病机制表现为早期微血管变化伴内皮细胞功能障碍，随后促其向肌成纤维细胞转化的机制被激活。一种涉及固有和适应性免疫以及特异性/功能性自身抗体产生的复杂自身免疫反应是该疾病的特征。进行性纤维化和缺血涉及皮肤和内脏器官，导致其不可逆损伤/衰竭。祖细胞循环细胞（单核细胞、成纤维细胞）、生长因子和细胞因子共同参与疾病的扩散和演变。系统性纤维化中涉及的表观遗传、血管和免疫机制是新的疾病修饰治疗方法的主要靶点。
本文通过概述疾病发病机制中涉及的最新进展和机制，讨论了对 SSc 发病机制的当前认识和新见解。
鉴于 SSc 的复杂性/异质性，如果从一开始就使用血管扩张剂、免疫抑制剂和抗纤维化药物进行早期联合治疗，应该能够成功地下调疾病的进展。
