Fibrosis in systemic sclerosis

Fibrosis is the pathological hallmark of systemic sclerosis (SSc). Uncontrolled production of collagens and other extracellular matrix (ECM) proteins by fibroblasts residing in the skin, lungs, and other vital organs leads to excess connective tissue accumulation. Over time, progressive buildup of connective tissue disrupts the normal tissue architecture of affected organs, causing their dysfunction and eventual failure (Fig. 1). Thus, the fibrotic process contributes significantly to the morbidity and mortality of SSc. New research challenges the traditional view that pathological fibrosis is always irreversible. This paradigm shift has profound implications for the design and development of novel treatments aimed directly at fibrosis. This article reviews current understanding of the pathophysiology of fibrosis in SSc, highlighting recent discoveries, insights, and emerging research, and potential opportunities for the development of targeted antifibrotic therapies.