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Rheumatology 2009 48(Supplement 3):iii1-iii2; doi:10.1093/rheumatology/kep111
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

This article appears in the following Rheumatology issue: Ten years of partnership: translating ideas into progress in systemic sclerosis [View the issue table of contents]

Editorial

Progress in systemic sclerosis: a 10-year perspective

C. M. Black1, M. Matucci-Cerinic2 and L. Guillevin3

1Royal Free and University College Medical School, London, UK, 2Department of Biomedicine, Centre DenoThe, Division of Rheumatology, AOUC University of Florence, Florence, Italy and 3Department of Internal Medicine and Immunopathology, Hospital Cochin, Paris, France

Correspondence to: C. M. Black, Centre for Rheumatology, Hampstead Campus, Rowland Hill Street, Hampstead, London NW3 2PF, UK. E-mail: profblack{at}btinternet.com

SSc is a chronic CTD that affects the skin and internal organs, and is characterized by excessive fibrosis, inflammation and vasculopathy [1–3]. The progressive occlusive vasculopathy is central to the clinical manifestations of SSc and is reflected in its characteristic complications, which include renal crisis, digital ulceration and pulmonary arterial hypertension (PAH) [4]. These manifestations have a considerable impact on prognosis and are responsible for SSc having the highest case-specific mortality of the rheumatological disorders [5]. The unpredictable, multisystemic and heterogeneous nature of SSc makes it a tremendously challenging condition to manage.

The articles in this supplement to Rheumatology address current knowledge of the pathogenesis of SSc and its associated complications, along with practical issues of disease management. Although the pathogenesis of SSc has not been fully elucidated, an increasing amount of information has identified the principal targets for therapeutic intervention. Vascular dysfunction is a major feature of SSc, with endothelial activation being followed by inflammatory changes and fibrosis [6]. An increased understanding of the pathophysiology of SSc has enabled a more comprehensive approach to disease management, with strategies to target the underlying disease processes. For example, there is a growing body of evidence that supports a key mediatory role for endothelin, both in the pathogenesis of SSc and some of its complications [7–10]. Resulting effective treatments have led to improvements in prognosis and survival.

In the first article in this supplement to Rheumatology, Abraham et al. [11] discuss the pathogenesis of SSc, examining the roles of epithelium, fibroblasts and immunological mediators in dysregulated vascular remodelling and, ultimately, vasculopathy. In the second article in this supplement, Matucci-Cerinic et al. [12] discuss the complexities faced by physicians in managing SSc, in particular its screening and diagnosis.

Having gained an understanding of the pathogenesis, screening and management, our colleagues turn their attention to the many tissue- and organ-specific manifestations of SSc. Krieg and Takehara [13] examine skin manifestations, the cardinal feature of SSc. The article by Steen et al. [14] reviews digital ulcer disease, a frequent, debilitating and persistent complication of SSc and an overt manifestation of vasculopathy.

Pulmonary manifestations are leading causes of disease-related morbidity and mortality in SSc [15]. The article by McLaughlin et al. [16] examines the classification and treatment of PAH in SSc, a devastating complication with a strikingly similar vasculopathy to digital ulceration. In their review, Wells et al. [17] discuss key clinical issues for the management of pulmonary complications of SSc, including the diagnosis of patients and their management and monitoring.

Denton et al. [18] focus on the renal manifestations of SSc and scleroderma renal crisis (SRC). They review the clinical presentation of SRC, and explore the factors influencing risk and outcome. The clinical management and future developments in the treatment of SRC are also discussed.

The gastrointestinal tract can frequently be affected by manifestations of SSc, with severe and distressing symptoms for patients. Forbes and Marie [19] consider the individual implications of oesophageal, gastric, intestinal and rectal manifestations of SSc, and current diagnostic and treatment strategies.

Whilst cardiac manifestations are common in SSc, they remain subclinical for the majority of patients [20–22]. Our colleagues Kahan et al. [23] explore and evaluate the primary cardiac manifestations of SSc, and use a case illustration to highlight problems associated with diagnosis and management.

Tyndall et al. [24] examine how research into the pathogenesis of CTDs and their complex signalling networks is identifying potential future targets for the treatment of SSc. They also consider the potential of autologous haematopoietic stem cell transplantation and the best use of currently available therapies for the treatment of lung fibrosis [24]. In the final article of this supplement, Guillevin [25] describes vasculitides in SSc, their classification, management and future therapeutic options.

This supplement to Rheumatology reports the proceedings of the first International SSc Forum, which was held in Athens, Greece, on 10–11 February 2007. The forum was dedicated exclusively to physicians managing SSc and other CTDs, and brought together expertise and knowledge in all aspects of SSc. The first International SSc Forum marked 10 years of commitment to research in the field of orphan diseases and endothelin receptor antagonism by Actelion Pharmaceuticals Ltd.

These collected articles are intended to supply rheumatologists, and physicians of other disciplines who are involved in the day-to-day management of SSc, with insights into its pathogenesis, diverse manifestations and approaches to challenging clinical presentations. As the articles in this supplement illustrate, clinical trials have and will continue to play an important role in developing evidence-based treatment strategies for the management this tremendously challenging disease. Our colleagues hope to illustrate that the future for SSc patients is no longer hopeless; advances in therapy have made it a serious but treatable condition. Following 10 years of partnership in SSc, we believe this to be the case.

Acknowledgements

The authors received editorial assistance from Elements Communications, supported by an educational grant from Actelion Pharmaceuticals Limited (Allschwil, Switzerland).

Supplement: This paper forms part of the supplement entitled ‘Ten years of partnership: translating ideas into progress in systemic sclerosis.’ This supplement was supported by an unrestricted grant from Actelion Pharmaceuticals Ltd.

Disclosure statement: L.G. has received lecture fees from Actelion Pharma. All other authors have declared no conflicts of interest.

References

  1. LeRoy EC, Black C, Fleischmajer R, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol (1988) 15:202–5.[Web of Science][Medline]
  2. Coghlan JG, Mukerjee D. The heart and pulmonary vasculature in scleroderma: clinical features and pathobiology. Curr Opin Rheumatol (2001) 13:495–9.[CrossRef][Web of Science][Medline]
  3. Charles C, Clements P, Furst DE. Systemic sclerosis: hypothesis-driven treatment strategies. Lancet (2006) 367:1683–91.[CrossRef][Web of Science][Medline]
  4. Fleming JN, Schwartz SM. The pathology of scleroderma vascular disease. Rheum Dis Clin North Am (2008) 34:41–55.[CrossRef][Web of Science][Medline]
  5. Nihtyanova SI, Brough GM, Black CM, Denton CP. Mycophenolate mofetil in diffuse cutaneous systemic sclerosis—a retrospective analysis. Rheumatology (2007) 46:442–5.[Abstract/Free Full Text]
  6. Abraham D, Distler O. How does endothelial cell injury start? The role of endothelin in systemic sclerosis. Arthritis Res Ther (2007) 9(Suppl. 2):S2.
  7. Denton CP, Black CM. Scleroderma—clinical and pathological advances. Best Pract Res Clin Rheumatol (2004) 18:271–90.[Medline]
  8. Korn JH, Mayes M, Matucci-Cerinic M, et al. Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin receptor antagonist. Arthritis Rheum (2004) 50:3985–93.[CrossRef][Web of Science][Medline]
  9. Hoeper MM, Galiè N, Simonneau G, Rubin LJ. New treatments for pulmonary arterial hypertension. Am J Respir Crit Care Med (2002) 165:1209–16.[Free Full Text]
  10. Humbert M, Morrell NW, Archer SL, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol (2004) 43(12 Suppl. S):13S–24S.[Abstract/Free Full Text]
  11. Abraham D, Krieg T, Distler J, Distler O. Overview of pathogenesis of systemic sclerosis. Rheumatology (2009) 48(Suppl. 1). 2009.
  12. Matucci-Cerinic M, Steen V, Nash P, Hachulla E. The complexity of managing systemic sclerosis: screening and diagnosis. Rheumatology (2009) 48(Suppl. 1). doi:10.1093/rheumatology/ken482.
  13. Krieg T, Takehara K. Skin disease: a cardinal feature of systemic sclerosis. Rheumatology (2009) 48(Suppl. 1). 2009.
  14. Steen V, Pope J, Matucci-Cerinic M. Digital ulcers: overt vascular disease in systemic sclerosis. Rheumatology (2009) 48(Suppl. 1). 2009.
  15. Steen VD, Medsger TA. Changes in causes of death in systemic sclerosis, 1972–2002. Ann Rheum Dis (2007) 66:940–4.[Abstract/Free Full Text]
  16. McLaughlin V, Humbert M, Coghlan G, Nash P, Steen V. Pulmonary arterial hypertension: the most devastating vascular complication of systemic sclerosis. Rheumatology (2009) 48(Suppl. 1). 2009.
  17. Wells A, Steen V, Valentini G. Pulmonary complications: one of the most challenging complications of systemic sclerosis. Rheumatology (2009) 48(Suppl. 1). 2009.
  18. Denton CP, Lapadula G, Mouthon L, Müller-Ladner U. Renal complications and scleroderma renal crisis. Rheumatology (2009) 48(Suppl. 1). 2009.
  19. Forbes A, Marie I. Gastrointestinal complications: the most frequent internal complication of systemic sclerosis. Rheumatology (2009) 48(Suppl. 1). 2009.
  20. Follansbee WP, Curtiss EI, Medsger TA Jr, et al. Physiologic abnormalities of cardiac function in progressive systemic sclerosis with diffuse scleroderma. N Engl J Med (1984) 310:142–8.[Abstract]
  21. Kahan A, Devaux JY, Amor B, et al. Nifedipine and thallium-201 myocardial perfusion in progressive systemic sclerosis. N Engl J Med (1986) 314:1397–402.[Abstract]
  22. Candell-Riera J, Armadans-Gil L, Simeon CP, et al. Comprehensive noninvasive assessment of cardiac involvement in limited systemic sclerosis. Arthritis Rheum (1996) 39:1138–45.[Medline]
  23. Kahan A, Coghlan G, McLaughlin V. Cardiac complications of systemic sclerosis. Rheumatology (2009) 48(Suppl. 1). 2009.
  24. Tyndall A, Matucci-Cerinic M, Müller-Ladner U. Future targets in the management of systemic sclerosis. Rheumatology (2009) 48(Suppl. 1). 2009.
  25. Guillevin L. Vasculopathy and pulmonary arterial hypertension. Rheumatology (2009) 48(Suppl. 1). 2009.
Accepted 2 April 2009


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