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Updated: Jan 6, 2026

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Systemic sclerosis: pathogenic mechanisms and their implications for treatment.

Alain Lescoat1,2,3, Valérie Lecureur4, Johann E Gudjonsson5,6

  • 1Inserm, EHESP, Irset -Institut de Recherche en Santé, Environnement Et Travail-UMRS, University of Rennes CHU Rennes, Rennes, France. alain.lescoat@chu-rennes.fr.

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Systemic sclerosis (SSc) is a rare autoimmune disease involving vascular, immune, and fibrotic pathways. This review covers SSc

Keywords:
AutoimmunityFibroblastsFibrosisMacrophagesSclerodermaSystemic sclerosis

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Area of Science:

  • Rheumatology and Immunology
  • Dermatology
  • Pathology

Background:

  • Systemic sclerosis (SSc) is a rare autoimmune disorder.
  • It involves microvascular dysfunction, immune dysregulation, and fibrosis.
  • Skin and internal organ fibrosis significantly impact patient quality of life and mortality.

Purpose of the Study:

  • To provide a comprehensive overview of Systemic Sclerosis.
  • To explore clinical features, subtypes, epidemiology, etiology, and pathogenesis.
  • To discuss current standards of care and potential therapeutic strategies, with an emphasis on skin manifestations.

Main Methods:

  • Literature review of Systemic Sclerosis.
  • Exploration of clinical features, classification, epidemiology, pathogenesis, and treatment.
  • Focus on SSc-related skin manifestations and other organ involvement.

Main Results:

  • SSc pathogenesis involves endothelial dysfunction, immune activation with autoantibodies, and myofibroblast-driven fibrosis.
  • Skin fibrosis is a hallmark, characterized by dermal collagen accumulation and hypodermal adipocyte atrophy.
  • Visceral manifestations like interstitial lung disease and pulmonary arterial hypertension are critical prognostic factors.

Conclusions:

  • Systemic sclerosis is a complex autoimmune disease with significant morbidity and mortality.
  • Understanding its diverse manifestations and pathogenic mechanisms is crucial for effective management.
  • Further research into therapeutic perspectives is essential for improving patient outcomes.