Strategy for treatment of fibrosis in systemic sclerosis: Present and future

Systemic sclerosis (SSc) is a generalized connective tissue disorder characterized by microvascular damage, autoimmunity, and excessive fibrosis of the skin and various internal organs. Regardless of the recent progress in medicine, no radical therapy for SSc has been developed, and the risk of mortality remains high. Therefore, diagnosis in the early disease stage, risk stratification for the development of serious organ involvement and therapeutic intervention with disease-modifying drugs can reduce the maximum degree of fibrosis, leading to improved long-term survival. Recently, new criteria for very early diagnosis of SSc have been proposed, which are expected to be useful for regularly following up patients with very early SSc, regardless of the absence of skin sclerosis, and for detecting the development of internal organ involvement as early as possible. At present, several immunosuppressants, including methotrexate, corticosteroids and cyclophosphamide, are being used for the treatment of fibrosis. Furthermore, mycophenolate mofetil, i.v. immunoglobulins, B-cell depletion, anti-interleukin-6 receptor antibody, autologous hematopoietic stem cell transplantation, rapamycin, pirfenidone and imatinib mesylate are potential candidates for the treatment of SSc, although their efficacy has not been validated. Moreover, targeting transforming growth factor-1 and its signaling pathway or modulating the imbalance between T-helper 1 and 2 immune responses are also attractive therapeutic options. This review describes recent advances in the strategy for treatment of fibrosis in SSc and future perspectives.