Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Overview of the treatment and prognosis of systemic sclerosis (scleroderma) in adults

Christopher P Denton, MD
Section Editor
John S Axford, DSc, MD, FRCP, FRCPCH
Deputy Editor
Monica Ramirez Curtis, MD, MPH


Scleroderma encompasses a spectrum of related disorders, most of which share a characteristic clinical feature of skin thickening due to an excess of collagen fibers. The simplest division of the scleroderma-related disorders is into localized (table 1) and systemic forms (table 2) (see "Overview and classification of scleroderma disorders"). Patients with the systemic forms are more likely to have internal organ involvement, which is usually the target of therapy.

Differentiating between localized and systemic disease and understanding of the systemic sclerosis (SSc) subsets, disease staging, and organ involvement are needed to guide effective use of available therapies.

The etiology and pathogenesis of the scleroderma disorders are poorly understood. As a result, treatment of these conditions is difficult, incomplete, and not curative. (See "Risk factors for and possible causes of systemic sclerosis (scleroderma)" and "Pathogenesis of systemic sclerosis (scleroderma)".)

An overview of the management of adults with SSc will be discussed here. Pretreatment evaluation, systemic immunologic modulation, potentially antifibrotic approaches, and localized and systemic scleroderma disorders in children are discussed separately. (See "Pretreatment evaluation of adults with systemic sclerosis (scleroderma)" and "Immunomodulatory and antifibrotic approaches to the treatment of systemic sclerosis (scleroderma)" and "Localized scleroderma in childhood" and "Juvenile systemic sclerosis (scleroderma)".)


An organ-based pretreatment evaluation is presented separately; however, a few basic principles are discussed below. (See "Pretreatment evaluation of adults with systemic sclerosis (scleroderma)".)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Aug 22, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Denton CP, Hughes M, Gak N, et al. BSR and BHPR guideline for the treatment of systemic sclerosis. Rheumatology (Oxford) 2016; 55:1906.
  2. Kowal-Bielecka O, Fransen J, Avouac J, et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis 2017; 76:1327.
  3. Herrick AL, Lunt M, Whidby N, et al. Observational study of treatment outcome in early diffuse cutaneous systemic sclerosis. J Rheumatol 2010; 37:116.
  4. Frech TM, Shanmugam VK, Shah AA, et al. Treatment of early diffuse systemic sclerosis skin disease. Clin Exp Rheumatol 2013; 31:166.
  5. Herrick AL, Pan X, Peytrignet S, et al. Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS). Ann Rheum Dis 2017; 76:1207.
  6. van den Hoogen FH, Boerbooms AM, Swaak AJ, et al. Comparison of methotrexate with placebo in the treatment of systemic sclerosis: a 24 week randomized double-blind trial, followed by a 24 week observational trial. Br J Rheumatol 1996; 35:364.
  7. Pope JE, Bellamy N, Seibold JR, et al. A randomized, controlled trial of methotrexate versus placebo in early diffuse scleroderma. Arthritis Rheum 2001; 44:1351.
  8. Kowal-Bielecka O, Landewé R, Avouac J, et al. EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis 2009; 68:620.
  9. Derk CT, Grace E, Shenin M, et al. A prospective open-label study of mycophenolate mofetil for the treatment of diffuse systemic sclerosis. Rheumatology (Oxford) 2009; 48:1595.
  10. Mendoza FA, Nagle SJ, Lee JB, Jimenez SA. A prospective observational study of mycophenolate mofetil treatment in progressive diffuse cutaneous systemic sclerosis of recent onset. J Rheumatol 2012; 39:1241.
  11. Le EN, Wigley FM, Shah AA, et al. Long-term experience of mycophenolate mofetil for treatment of diffuse cutaneous systemic sclerosis. Ann Rheum Dis 2011; 70:1104.
  12. Namas R, Tashkin DP, Furst DE, et al. Efficacy of mycophenolate mofetil and oral cyclophosphamide on skin thickness: Post-hoc analyses from the Scleroderma Lung Study I and II. Arthritis Care Res (Hoboken) 2017.
  13. Tashkin DP, Elashoff R, Clements PJ, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 2006; 354:2655.
  14. Apras S, Ertenli I, Ozbalkan Z, et al. Effects of oral cyclophosphamide and prednisolone therapy on the endothelial functions and clinical findings in patients with early diffuse systemic sclerosis. Arthritis Rheum 2003; 48:2256.
  15. Tehlirian CV, Hummers LK, White B, et al. High-dose cyclophosphamide without stem cell rescue in scleroderma. Ann Rheum Dis 2008; 67:775.
  16. Poelman CL, Hummers LK, Wigley FM, et al. Intravenous immunoglobulin may be an effective therapy for refractory, active diffuse cutaneous systemic sclerosis. J Rheumatol 2015; 42:236.
  17. Raja J, Nihtyanova SI, Murray CD, et al. Sustained benefit from intravenous immunoglobulin therapy for gastrointestinal involvement in systemic sclerosis. Rheumatology (Oxford) 2015.
  18. Jordan S, Distler JH, Maurer B, et al. Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis 2015; 74:1188.
  19. Frech TM, Baron M. Understanding itch in systemic sclerosis in order to improve patient quality of life. Clin Exp Rheumatol 2013; 31:81.
  20. Frech T, Novak K, Revelo MP, et al. Low-dose naltrexone for pruritus in systemic sclerosis. Int J Rheumatol 2011; 2011:804296.
  21. Robertson LP, Marshall RW, Hickling P. Treatment of cutaneous calcinosis in limited systemic sclerosis with minocycline. Ann Rheum Dis 2003; 62:267.
  22. Tosounidou S, MacDonald H, Situnayake D. Successful treatment of calcinosis with infliximab in a patient with systemic sclerosis/myositis overlap syndrome. Rheumatology (Oxford) 2014; 53:960.
  23. de Paula DR, Klem FB, Lorencetti PG, et al. Rituximab-induced regression of CREST-related calcinosis. Clin Rheumatol 2013; 32:281.
  24. Daoussis D, Antonopoulos I, Liossis SN, et al. Treatment of systemic sclerosis-associated calcinosis: a case report of rituximab-induced regression of CREST-related calcinosis and review of the literature. Semin Arthritis Rheum 2012; 41:822.
  25. Lapner MA, Goetz TJ. High-speed burr debulking of digital calcinosis cutis in scleroderma patients. J Hand Surg Am 2014; 39:503.
  26. Reiter N, El-Shabrawi L, Leinweber B, et al. Calcinosis cutis: part II. Treatment options. J Am Acad Dermatol 2011; 65:15.
  27. Avouac J, Clements PJ, Khanna D, et al. Articular involvement in systemic sclerosis. Rheumatology (Oxford) 2012; 51:1347.
  28. Elhai M, Meunier M, Matucci-Cerinic M, et al. Outcomes of patients with systemic sclerosis-associated polyarthritis and myopathy treated with tocilizumab or abatacept: a EUSTAR observational study. Ann Rheum Dis 2013; 72:1217.
  29. Omair MA, Phumethum V, Johnson SR. Long-term safety and effectiveness of tumour necrosis factor inhibitors in systemic sclerosis patients with inflammatory arthritis. Clin Exp Rheumatol 2012; 30:S55.
  30. Lam GK, Hummers LK, Woods A, Wigley FM. Efficacy and safety of etanercept in the treatment of scleroderma-associated joint disease. J Rheumatol 2007; 34:1636.
  31. Ostor AJ, Crisp AJ, Somerville MF, Scott DG. Fatal exacerbation of rheumatoid arthritis associated fibrosing alveolitis in patients given infliximab. BMJ 2004; 329:1266.
  32. Allanore Y, Devos-François G, Caramella C, et al. Fatal exacerbation of fibrosing alveolitis associated with systemic sclerosis in a patient treated with adalimumab. Ann Rheum Dis 2006; 65:834.
  33. Jones NF, Imbriglia JE, Steen VD, Medsger TA. Surgery for scleroderma of the hand. J Hand Surg Am 1987; 12:391.
  34. Steen VD, Medsger TA Jr. Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis. Arthritis Rheum 1998; 41:1613.
  35. Pieroni M, De Santis M, Zizzo G, et al. Recognizing and treating myocarditis in recent-onset systemic sclerosis heart disease: potential utility of immunosuppressive therapy in cardiac damage progression. Semin Arthritis Rheum 2014; 43:526.
  36. Vignaux O, Allanore Y, Meune C, et al. Evaluation of the effect of nifedipine upon myocardial perfusion and contractility using cardiac magnetic resonance imaging and tissue Doppler echocardiography in systemic sclerosis. Ann Rheum Dis 2005; 64:1268.
  37. Allanore Y, Meune C, Vonk MC, et al. Prevalence and factors associated with left ventricular dysfunction in the EULAR Scleroderma Trial and Research group (EUSTAR) database of patients with systemic sclerosis. Ann Rheum Dis 2010; 69:218.
  38. Walker UA, Tyndall A, Ruszat R. Erectile dysfunction in systemic sclerosis. Ann Rheum Dis 2009; 68:1083.
  39. Foocharoen C, Tyndall A, Hachulla E, et al. Erectile dysfunction is frequent in systemic sclerosis and associated with severe disease: a study of the EULAR Scleroderma Trial and Research group. Arthritis Res Ther 2012; 14:R37.
  40. Elhai M, Meune C, Avouac J, et al. Trends in mortality in patients with systemic sclerosis over 40 years: a systematic review and meta-analysis of cohort studies. Rheumatology (Oxford) 2012; 51:1017.
  41. Al-Dhaher FF, Pope JE, Ouimet JM. Determinants of morbidity and mortality of systemic sclerosis in Canada. Semin Arthritis Rheum 2010; 39:269.
  42. Steen VD, Medsger TA. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis 2007; 66:940.
  43. Tyndall AJ, Bannert B, Vonk M, et al. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis 2010; 69:1809.
  44. Ioannidis JP, Vlachoyiannopoulos PG, Haidich AB, et al. Mortality in systemic sclerosis: an international meta-analysis of individual patient data. Am J Med 2005; 118:2.
  45. Shand L, Lunt M, Nihtyanova S, et al. Relationship between change in skin score and disease outcome in diffuse cutaneous systemic sclerosis: application of a latent linear trajectory model. Arthritis Rheum 2007; 56:2422.
  46. Nikpour M, Baron M. Mortality in systemic sclerosis: lessons learned from population-based and observational cohort studies. Curr Opin Rheumatol 2014; 26:131.
  47. Mitri GM, Lucas M, Fertig N, et al. A comparison between anti-Th/To- and anticentromere antibody-positive systemic sclerosis patients with limited cutaneous involvement. Arthritis Rheum 2003; 48:203.
  48. Sampaio-Barros PD, Bortoluzzo AB, Marangoni RG, et al. Survival, causes of death, and prognostic factors in systemic sclerosis: analysis of 947 Brazilian patients. J Rheumatol 2012; 39:1971.
  49. Ngian GS, Stevens W, Prior D, et al. Predictors of mortality in connective tissue disease-associated pulmonary arterial hypertension: a cohort study. Arthritis Res Ther 2012; 14:R213.
  50. Alba MA, Velasco C, Simeón CP, et al. Early- versus late-onset systemic sclerosis: differences in clinical presentation and outcome in 1037 patients. Medicine (Baltimore) 2014; 93:73.
  51. Ferri C, Valentini G, Cozzi F, et al. Systemic sclerosis: demographic, clinical, and serologic features and survival in 1,012 Italian patients. Medicine (Baltimore) 2002; 81:139.
  52. Scussel-Lonzetti L, Joyal F, Raynauld JP, et al. Predicting mortality in systemic sclerosis: analysis of a cohort of 309 French Canadian patients with emphasis on features at diagnosis as predictive factors for survival. Medicine (Baltimore) 2002; 81:154.
  53. Nihtyanova SI, Schreiber BE, Ong VH, et al. Prediction of pulmonary complications and long-term survival in systemic sclerosis. Arthritis Rheumatol 2014; 66:1625.