Modern Strategies for the Comprehensive Treatment of Systemic Sclerosis: From Pathogenesis to Personalized Therapy

Abstract

Systemic sclerosis (SSc) is a severe autoimmune connective tissue disease characterized by immune dysregulation, vasculopathy, and progressive fibrosis of the skin and internal organs. The clinical heterogeneity of SSc presents significant challenges in early diagnosis and treatment. Over the past decade, the therapeutic paradigm has shifted from symptomatic management to pathogenetically oriented strategies, including immunosuppression, targeted immunomodulation, and antifibrotic therapy, underpinned by a “treat-to-target” approach and risk stratification. This review synthesizes contemporary evidence on comprehensive, domain-based management of SSc. We detail the central roles of immunosuppressants like mycophenolate mofetil and cyclophosphamide in interstitial lung disease (ILD), the antifibrotic agent nintedanib for SSc-ILD, and targeted therapies such as the IL-6 receptor inhibitor tocilizumab and the B-cell depleting agent rituximab. The importance of early diagnosis within a “window of opportunity,” rigorous screening for organ involvement, and a mandatory multidisciplinary approach is emphasized. The article concludes that modern SSc management requires a personalized strategy integrating early phenotypic characterization, continuous monitoring, and rational combination therapy to modify disease progression and improve patient outcomes.