Overview: Pathogenesis integrated

John Varga*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingForeword/postscript

1 Scopus citations


The pathogenesis of scleroderma is complex, multifactorial and incompletely understood. Evidence of vascular injury, immune dysfunction and tissue remodeling can be detected in every patient with scleroderma. These processes do not occur in isolation but are interrelated and reciprocally modulate each other, as illustrated in Fig. 14.1 and discussed in the following chapters. The triad of vasculopathy, autoimmunity/inflammation and connective tissue remodeling underlies the protean clinical and laboratory manifestations of scleroderma, ranging from Raynaud phenomenon to autoantibody production to pulmonary fibrosis. However, the relative contributions of these distinct pathophysiological processes to the individual disease phenotype, and their roles in driving the natural history of disease vary greatly from one patient to another. This individual variability, which is not well understood but might be genetically determined, accounts for the strikingly heterogeneous clinical picture of scleroderma. Vascular injury and endothelial damage are early and probably primary events in the evolution of the disease, and can be detected at initial evaluation in a majority of patients. While initially vascular injury is associated with reversible functional changes, over time progressive and irreversible structural vascular alterations accrue. Progressive vascular damage with obliteration of small and medium-sized arteries in multiple vascular beds, and associated activation of thrombotic and coagulation cascades follow. Reduced vascular supply leads to tissue hypoxia, ischemia and its myriad complications. In addition, generation of reactive oxygen species contributes to increased oxidative stress and associated damage to protein and lipid macromolecules. Vascular injury also plays a role in activation of the innate and adaptive immune systems, and contributes directly and indirectly to tissue fibrosis.

Original languageEnglish (US)
Title of host publicationScleroderma
Subtitle of host publicationFrom Pathogenesis to Comprehensive Management
PublisherSpringer US
Number of pages2
ISBN (Electronic)9781441957740
ISBN (Print)9781441957733
StatePublished - Jan 1 2012


  • Autoimmunity
  • Fibroblast
  • Fibrosis
  • Integrated view
  • Overview
  • Pathogenesis
  • Reciprocal crossmodulation

ASJC Scopus subject areas

  • Medicine(all)


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