The burning question: To use or not to use cyclophosphamide in systemic sclerosis

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 interstitiallung diseases in SSc for many years and still represents a mainstay in hematopoietic stem celltransplantation. 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 totreat SSc, its efficacy and safety profile, and currently available or tested alternative drugs for lung andskin involvement in SSc.