Cyclophosphamide as disease-modifying therapy for scleroderma: pros and cons

Systemic sclerosis (SSc; scleroderma) is an autoimmune connective tissue disorder characterized by microvasculopathy, excessive collagen deposition and autoimmunity. It can affect virtually any organ with the skin, heart, lungs, kidneys and gastrointestinal systems most commonly involved. Early studies have indicated that patients with early active diffuse cutaneous SSc (dcSSc) and significant visceral involvement have a significant mortality of 50% at 5 years [1]. By contrast, recent studies have indicated that 5-year survival amongst patients with early active dcSSc has improved over the last decade. However, approximately half of these patients will either succumb to their illness or develop major internal organ involvement within the first 3 years following onset of their disease [2]. There are many aspects of SSc that support the hypothesis that it is an immune-mediated disease and might therefore respond to immunosuppressive therapy [3]. It is therefore relevant and timely to review the current available literature regarding the use of cyclophosphamide (CYC) in SSc, in particular in the organ-based management of complications related to this disease.