A New Era in the Treatment of Scleroderma-associated Interstitial Lung Disease?

Abstract

Pulmonary involvement in systemic sclerosis or scleroderma (SSc) is mainly represented by SSc-associated interstitial lung disease (SSc-ILD) and pulmonary hypertension1,2. SSc-ILD is a major challenge: It is both a very frequent and a very severe complication of SSc. According to the literature, SSc-ILD is or will be present in around one-half of patients with diffuse SSc, and one-third of patients with limited cutaneous SSc3. SSc-ILD is now one of the leading causes of death in SSc4. This explains why much effort has been expended to understand and better know the characteristics of patients with SSc-ILD as well as to manage them properly. However, despite decades of observational studies and a few randomized ones, the optimal management of patients with SSc-ILD is still a matter of debate. From an historic point of view, the cornerstone of SSc-ILD treatment has mainly been immunosuppressants. This can be explained by the fact that SSc is a connective tissue disease in which inflammation and immune abnormalities play a central role5. The immune system, especially in regards to B and T lymphocytes, is fully involved in fibroblast activation and fibrogenesis by secreting proinflammatory and profibrotic cytokines and growth factors6. The most common immunosuppressant, cyclophosphamide (CYC), has been tested in many open-label studies and a few randomized control trials (RCT), as well as being recommended in the European League Against Rheumatism Scleroderma Trials and Research group guidelines7. However, the results of those RCT are still dividing the medical community. In the FAST study, there was no significant … Address correspondence to Prof. D. Launay, Service de Medecine Interne, Hopital Claude-Huriez, CHRU Lille, rue Michel Polonovski, F-59037 LILLE Cedex, France. E-mail: david.launay{at}univ-lille2.fr