Abstract
Fibrosis, inflammation, and vasculopathy are the main determinants of systemic sclerosis (SSc) pathogenesis. Cyclophosphamide (CYC), an alkylating agent, has been used to treat skin fibrosis and interstitial lung diseases in SSc for many years and still represents a mainstay in hematopoietic stem cell transplantation. Despite significant effect in reducing lung functional impairment and skin tightness, CYC has a significant safety burden, including infection risk and bone marrow and bladder toxicity. Moreover, it can affect fertility and also cause a predisposition for cancer development in the future, particularly in the bladder. This review summarizes the current evidences regarding the use of CYC to treat SSc, its efficacy and safety profile, and currently available or tested alternative drugs for lung and skin involvement in SSc.