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International Journal of Rheumatology
Volume 2011, Article ID 824972, 7 pages
Review Article

A System Out of Breath: How Hypoxia Possibly Contributes to the Pathogenesis of Systemic Sclerosis

1Department of Rheumatology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
2Department of Rheumatology, Nijmegen Center for Molecular Life Sciences (NCMLS) and Nijmegen Institute for Infection, Immunity and Inflammation (N4i), Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, 6500 HB Nijmegen, The Netherlands

Received 20 May 2011; Revised 18 August 2011; Accepted 7 September 2011

Academic Editor: Laura K. Hummers

Copyright © 2011 T. W. van Hal et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular alterations and immunological disturbances and fibrosis, the order of which remains to be fully determined. Clinically, patients show clear signs of hypoxia in skin and internal organs. The low oxygen tension is potentially caused by a yet to be indentified circuitry involving the three features that typify SSc. In addition, once present, the hypoxia creates a vicious circle of ongoing pathology. In this paper, we provide an overview of the evidence that points towards the mechanisms causing hypoxia in SSc. In addition, data that suggest how hypoxia itself may orchestrate worsening of symptoms is presented. Altogether, it is clear that hypoxia is an important hallmark in SSc patients. By providing an overview of the mechanisms at play and the possible therapeutic avenues that have emerged, we hope to stimulate researchers to provide novel clues into the conundrum in SSc patients.