[Updates in systemic sclerosis pathogenesis: Toward new therapeutic opportunities]

Rev Med Interne. 2019 Oct;40(10):654-663. doi: 10.1016/j.revmed.2019.05.016. Epub 2019 Jul 11.
[Article in French]

Abstract

Systemic sclerosis is a rare connective tissue disease characterized by skin and several internal organ fibrosis, systemic vasculopathy and immune abnormalities. Even if fibroblasts and endothelial cells dysfunction, as well as lymphocytes and other immune cells implication are now well described, the exact origin and chronology of the disease pathogenesis remain unclear. Oxidative stress, influenced by genetic and environmental factors, seems to play a key role. Indeed, it seems to be implicated in the early phases of fibrosis development, vasculopathy and in immune tolerance abnormalities shared by all patients, although disease expression is heterogeneous. To date, no curative treatment is available. Even if immunosuppressive treatment or drugs acting on vascular system are proposed for some patients, overall, treatment efficiency remains modest. Only autologous hematopoietic stem cells transplantation, reserved for patients with severe or rapidly progressive fibrosis, has recently demonstrated efficiency, with lasting regression of fibrosis. Nevertheless, this treatment can expose to important, life-threatening toxicity. In the last decade, new mechanisms implicated in the pathogenesis of systemic sclerosis have been unraveled, bringing new therapeutic opportunities. In this review, we offer to focus on recent insights in the knowledge of systemic sclerosis pathogenesis and its implication in current and future medical care.

Keywords: Pathogenesis; Physiopathologie; Scleroderma; Sclérodermie systémique; Systemic sclerosis; Traitement; Treatment.

Publication types

  • Review

MeSH terms

  • B-Lymphocytes / immunology
  • Dysbiosis / complications
  • Endothelial Cells / physiology
  • Endothelium / physiopathology
  • Fibroblasts / physiology
  • Gene-Environment Interaction
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • Immune Tolerance
  • Immunity, Cellular
  • Immunosuppressive Agents / therapeutic use
  • Oxidative Stress
  • Risk Factors
  • Scleroderma, Systemic / etiology*
  • Scleroderma, Systemic / therapy*
  • Vascular Diseases / complications
  • Vascular Diseases / drug therapy

Substances

  • Immunosuppressive Agents