Journal of Cell Communication and Signaling

, Volume 6, Issue 4, pp 187–190 | Cite as

Immunosuppression for interstitial lung disease in systemic sclerosis – novel insights and opportunities for translational research

  • Marie HudsonEmail author
  • Russell Steele
  • Canadian Scleroderma Research Group
  • Murray Baron

Systemic sclerosis (SSc) is a chronic inflammatory disorder characterized by a disturbance in fibroblast function culminating in the telltale skin thickening and fibrosis of visceral organs. Interstitial lung disease (ILD) is common (Steele et al. 2011) and is the leading cause of death in this disease (Steen and Medsger 2007). The immunohistopathogenesis of SSc-ILD is characterized by immune dysfunction and inflammation. Thus, immunosuppression has been hypothesized as a useful treatment for SSc-ILD. However, randomized clinical trials (RCTs) have thus far only revealed a modest effect of immunosuppression (Hoyles et al. 2006; Tashkin et al. 2006). We believe that these small observed effects are due, at least in part, to the actual design of the RCTs, in particular subject selection, which did not properly identify patients likely to respond to treatment.

SSc is an uncommon disease, with an estimated prevalence ranging from 7–489/million and incidence from 0.6–122/million/year...


Immunosuppression Interstitial lung disease Outcomes research Systemic sclerosis Translational research 



This study was funded in part by the Canadian Institutes of Health Research, the Scleroderma Society of Canada and educational grants from Actelion Pharmaceuticals and Pfizer Inc. Dr. Hudson is supported by a Chercheur-clinicien boursier award from the Fonds de la Recherche en Santé du Québec. The funding sources had no role in the design of the study, analysis of the data, preparation of the manuscript and decision to submit for publication.


  1. Assassi S, Sharif R et al (2010) Predictors of interstitial lung disease in early systemic sclerosis: a prospective longitudinal study of the GENISOS cohort. Arthritis Res Ther 12(5):R166PubMedCrossRefGoogle Scholar
  2. Barnett AJ (1978) Scleroderma (progressive systemic sclerosis): progress and course based on a personal series of 118 cases. Med J Aust 2(4):129–134PubMedGoogle Scholar
  3. Chifflot H, Fautrel B et al (2008) Incidence and prevalence of systemic sclerosis: a systematic literature review. Semin Arthritis Rheum 37:223–235PubMedCrossRefGoogle Scholar
  4. Choi HK, Hernan MA et al (2002) Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 359(9313):1173–1177PubMedCrossRefGoogle Scholar
  5. Clements PJ (1995) Measuring disease activity and severity in scleroderma. Curr Opin Rheumatol 7(6):517–521PubMedCrossRefGoogle Scholar
  6. Cotter D, Zhang Y et al (2008) The effect of epoetin dose on hematocrit. Kidney Int 73(3):347–353PubMedCrossRefGoogle Scholar
  7. Goh NS, Desai SR et al (2008) Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med 177(11):1248–1254PubMedCrossRefGoogle Scholar
  8. Greidinger EL, Flaherty KT et al (1998). “African-American race and antibodies to topoisomerase I are associated with increased severity of scleroderma lung disease.” 114:801–807Google Scholar
  9. Hernán M, Brumback B et al (2001) Marginal structural models to estimate the joint causal effect of nonrandomized treatments. J Am Stat Assoc 96(454):440–448CrossRefGoogle Scholar
  10. Hernan MA, Brumback BA et al (2002) Estimating the causal effect of zidovudine on CD4 count with a marginal structural model for repeated measures. Stat Med 21(12):1689–1709PubMedCrossRefGoogle Scholar
  11. Hoyles RK, Ellis RW et al (2006) A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma. Arthritis Rheum 54(12):3962–3970PubMedCrossRefGoogle Scholar
  12. Hudson M, Baron M et al (2011) Observational data to study medication outcomes in systemic sclerosis. J Rheumatol 38(3):575–577PubMedCrossRefGoogle Scholar
  13. MacKenzie EJ, Rivara FP et al (2006) A national evaluation of the effect of trauma-center care on mortality. N Engl J Med 354(4):366–378PubMedCrossRefGoogle Scholar
  14. Palella FJ Jr, Armon C et al (2009) The association of HIV susceptibility testing with survival among HIV-infected patients receiving antiretroviral therapy: a cohort study. Ann Intern Med 151(2):73–84PubMedGoogle Scholar
  15. Plastiras SC, Karadimitrakis SP et al (2006) Scleroderma lung: initial forced vital capacity as predictor of pulmonary function decline. Arthritis Rheum 55(4):598–602PubMedCrossRefGoogle Scholar
  16. Rawlins M (2008) De testimonio: on the evidence for decisions about the use of therapeutic interventions. Lancet 372(9656):2152–2161PubMedCrossRefGoogle Scholar
  17. Roth MD, Tseng CH et al (2011) Predicting treatment outcomes and responder subsets in scleroderma-related interstitial lung disease. Arthritis Rheum 63(9):2797–2808PubMedCrossRefGoogle Scholar
  18. Rubin DB (1997) Estimating causal effects from large data sets using propensity scores. Ann Intern Med 127(8 Pt 2):757–763PubMedGoogle Scholar
  19. Steele R, Hudson M et al (2011) A clinical decision rule to predict the presence of interstitial lung disease in systemic sclerosis. Arthritis Care Res (Hoboken) 64(4):519–524CrossRefGoogle Scholar
  20. Steen VD, Medsger TA (2007) Changes in causes of death in systemic sclerosis, 1972–2002. Ann Rheum Dis 66(7):940–944PubMedCrossRefGoogle Scholar
  21. Steen VD, Owens GR et al (1985) The effect of D-penicillamine on pulmonary findings in systemic sclerosis. Arthritis Rheum 28(8):882–888PubMedCrossRefGoogle Scholar
  22. Steen VD, Conte C et al (1994) Severe restrictive lung disease in systemic sclerosis. Arthritis Rheum 37(9):1283–1289PubMedCrossRefGoogle Scholar
  23. Sterne JA, Hernan MA et al (2005) Long-term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study. Lancet 366(9483):378–384PubMedCrossRefGoogle Scholar
  24. Tashkin DP, Elashoff R et al (2006) Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 354(25):2655–2666PubMedCrossRefGoogle Scholar
  25. White B (2003) Interstitial lung disease in scleroderma. Rheum Dis Clin N Am 29(2):371–390CrossRefGoogle Scholar

Copyright information

© The International CCN Society 2012

Authors and Affiliations

  • Marie Hudson
    • 1
    • 2
    Email author
  • Russell Steele
    • 1
  • Canadian Scleroderma Research Group
  • Murray Baron
    • 1
  1. 1.Jewish General HospitalLady Davis Institute for Medical Research and McGill UniversityMontrealCanada
  2. 2.Jewish General HospitalMontrealCanada

Personalised recommendations