PATHOGENESIS, DIAGNOSIS, AND TREATMENT OF SYSTEMIC SCLEROSIS – AN INTEGRATIVE REVIEW OF THE CURRENT APPROACHES

Abstract

Systemic sclerosis is a rare autoimmune connective tissue disorder marked by immunological dysregulation, vasculopathy, and progressive fibrosis of the skin and internal organs, resulting in considerable morbidity and mortality. The disease results from a complex interaction between genetic susceptibility, epigenetic modifications, environmental triggers, endothelial dysfunction, and aberrant immune responses. These mechanisms promote persistent inflammation, stimulation of fibroblasts and abundant extracellular matrix deposition, eventually causing irreversible tissue fibrosis and organ dysfunction. The diagnosis is based on clinical manifestations, supported by specific antibodies detection, capillaroscopy, and appropriate functional and imaging tests. To facilitate diagnosis, the American College of Rheumatology/European League Against Rheumatism issued guidelines in 2013, enabling earlier diagnosis and more accurate prognostic assessment. Although no curative therapy is currently available, treatment has advanced considerably and focuses on suppressing disease activity, slowing fibrosis, and preventing organ complications. Current therapeutic strategies include immunosuppressive agents, biologic therapies, antifibrotic drugs, and targeted vasodilator treatments tailored to individual organ involvement. Emerging approaches, such as JAK-STAT pathway inhibitors, CAR-T cell therapy, and stem cell transplantation, may further improve long-term outcomes in selected patients. Despite substantial progress in understanding disease mechanisms and expanding therapeutic options, systemic sclerosis remains a clinically heterogeneous disorder requiring early diagnosis, multidisciplinary management, and individualized treatment to optimize survival and quality of life.