Skip to main content
SpringerLink
Log in

Combination therapies for systemic sclerosis

  • Chapter
Combination Treatment in Autoimmune Diseases

  • 103 Accesses

Abstract

Systemic sclerosis (SSc) is a multisystem autoimmune rheumatic disease which forms part of the scleroderma spectrum of disorders. These diverse conditions are listed in Table 1. There are common features to these disorders and some clinical overlap between them but they can be separated into three main categories, those with skin sclerosis but no vascular or internal organ involvement such as morphea, conditions with vascular manifestations only, including primary Raynaud’s phenomenon, and the different subsets of systemic sclerosis, which form the main focus of this article. The frequency of the disorders has proven difficult to ascertain but North American studies suggest a prevalence of Raynaud’s phenomenon of around 10% of the adult female population (6% overall), and an annual prevalence of SSc of 15 cases per 100,000. Data from the UK has previously estimated a much lower prevalence but a comprehensive local study has led to estimates being revised to levels similar to the North American figures [28].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Amlot P, Bacon P, Belch JJF, Black CM, Bois RM du, Briggs D, Denton CP, UK Sceleroderma Study Group (1998) How can treatment of systemic sclerosis be improved ? BMJ 1998; 317: 294

    Article  Google Scholar 

  2. Badesch DB, Tapson VF, McGoon MD, Brundage BH, Rubin LJ, Wigley FM, Rich S, Barst RJ, Barrett PS, Kral KM, Jobsis MM, Loyd JE, Murali S, Frost A, Girgis R, Bourge RC, Ralph DD, Elliott CG, Hill NS, Langleben D, Schilz RI, McLaughlin VV, Robbins IM, Groves BM, Shapiro S, Medsger TA (2000) Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann Intern Med 132: 425

    Google Scholar 

  3. Barst RJ, Rubin LJ, Long WA, McGoon MD, Rich S, Badesch DB, Groves BM, Tapson VF, Bourge RC, Brundage BH (1996) A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. The Primary Pulmonary Hypertension Study Group. N Engl J Med 334: 296

    Google Scholar 

  4. Black CM, Halkier-Sorensen L, Belch II, Ullman S, Madhok R, Smit AJ, Banga JD, Watson HR (1998) Oral iloprost in Raynaud’s phenomenon secondary to systemic sclerosis: a multicentre, placebo-controlled, dose-comparison study. Br J Rheumatol 37: 952

    Article  PubMed  CAS  Google Scholar 

  5. Black CM, Silman AJ, Herrick Al, Denton CP, Wilson H, Newman J,Pompon L, Shi-Wen X (1999) Interferon-alpha does not improve outcome at one year in patients with diffuse cutaneous scleroderma: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 42: 299

    PubMed  CAS  Google Scholar 

  6. Briggs DC, Vaughan RW, Welsh KI, Myers A, Bois RM du, Black CM (1991) Immunogenetic prediction of pulmonary fibrosis in systemic sclerosis. Lancet 338: 661

    Article  PubMed  CAS  Google Scholar 

  7. Bruckdorfer KR, Hillary JB, Bunce T, Vancheeswaran R, Black CM (1995) Increased susceptibility to oxidation of low-density lipoproteins isolated from patients with systemic sclerosis. Arthritis Rheum 38, 1060

    Article  PubMed  CAS  Google Scholar 

  8. Bunn CC, Denton CP, Shi-wen X, Knight C, Black CM (1998) Anti-RNA polymerases and other auto-antibody specificities in systemic sclerosis. Br J Rheumat 37: 15

    Article  CAS  Google Scholar 

  9. Casciola-Rosen L, Wigley F, Rosen A (1997) Scleroderma autoantigens are uniquely fragmented by metal-catalyzed oxidation reactions: implications for pathogenesis. J Exp Med 185: 71

    Article  PubMed  CAS  Google Scholar 

  10. Casoli P, Carretti C, Tumiati B (1994) Scleroderma renal crisis as a possible complication of cyclosporin A withdrawal. Clin Rheumat 13: 126

    Article  CAS  Google Scholar 

  11. Ciatti S, Varga J, Greenbaum S (1996) The 585 nm flashlamp-pumped pulsed dye laser for the treatment of telangiectases in patients with scleroderma. J Am Acad Dermatol 35: 487

    Article  PubMed  CAS  Google Scholar 

  12. Clements PJ, Furst DE, Wong WK, Mayes M, White B, Wigley F, Weisman MH, Barr W, Moreland LW, Medsger TA Jr, Steen V, Martin, RW, Collier D, Weinstein A, Lally E, Varga J, Weiner S, Andrews B, Abeles M, Seibold JR (1999) High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis: analysis of a two-year, double-blind, randomized, controlled clinical trial. Arthritis Rheum 42: 1194

    Article  PubMed  CAS  Google Scholar 

  13. Clements PI, Furst DE (1997) Choosing appropriate patients with systemic sclerosis for treatment by autologous stem cell transplantation. J Rheumatol 48: 85

    CAS  Google Scholar 

  14. Clements PJ, Lachenbruch PA, Sterz M, Danovitch G, Hawkins R, 1ppoliti A, Paulus HE (1993) Cyclosporine in systemic sclerosis. Results of a forty-eight-week open safety study in ten patients. Arthritis Rheum 36: 75

    Google Scholar 

  15. Denton CP, Bickerstaff MC, Shiwen X, Carulli MT, Haskard DO, Dubois RM, Black CM (1995) Serial circulating adhesion molecule levels reflect disease severity in systemic sclerosis. Br J Rheumatol 34: 1048

    Article  PubMed  CAS  Google Scholar 

  16. Denton CP, Bunce TD, Darado MB, Roberts Z, Wilson H, Howell K, Bruckdorfer KR, Black CM (1999) Probucol improves symptoms and reduces lipoprotein oxidation susceptibility in patients with Raynaud’s phenomenon. Rheumatology 38: 309

    Article  PubMed  CAS  Google Scholar 

  17. Denton CP, Cailes JB, Phillips GD, Wells AU, Black CM, Bois RM du (1997) Comparison of Doppler-echocardiography and right heart catheterisation to assess pulmonary hypertension in systemic sclerosis. Br J Rheumatol 36: 239

    Article  PubMed  CAS  Google Scholar 

  18. Denton CP, Sweny P, Abdulla A, Black CM (1994) Acute renal failure occurring in scleroderma treated with cyclosporin A: a report of three cases. Br J Rheumatol 33: 90

    Article  PubMed  CAS  Google Scholar 

  19. Dziadzio M, Denton CP, Smith R, Howell K, Blann A, Bowers E, Black CM (1999) Related Articles Losartan therapy for Raynaud’s phenomenon and scleroderma: clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial. Arthritis Rheum 42: 2646

    Article  PubMed  CAS  Google Scholar 

  20. Ellman MH, MacDonald PA, Hayes FA (2000) Etanercept as treatment for diffuse scleroderma: a pilot study. Arthritis Rheum 43: S392

    Google Scholar 

  21. Furst DE, Clements PJ, Steen VD, Medsger TA Jr, Masi AT, D’Angelo WA, Lachenbruch PA, Grau RG, Seibold JR (1998) The modified Rodnan skin score is an accurate reflection of skin biopsy thickness in systemic sclerosis. J Rheumatol 25: 84

    PubMed  CAS  Google Scholar 

  22. Furst DE, McSweeney P, Nelson JL, Nash R, Wener M, Sullivan KM (1998) Intensive immunosuppression and stem cell transplantation in scleroderma. Arthritis Rheum 41:S 102

    Google Scholar 

  23. Gisslinger H, Burghuber OC, Stacher G, Schwarz W, Punzengruber C, Graninger W, Luger TA, Wolff K, Smolen JS (1991) Efficacy of cyclosporin A in systemic sclerosis. Clin Exp Rheumatol 9: 383

    PubMed  CAS  Google Scholar 

  24. Gough A, Andrews D, Bacon PA, Emery P (1995) Evidence of omeprazole-induced small bowel bacterial overgrowth in patients with scleroderma. Br J Rheumatol 34: 976

    Article  PubMed  CAS  Google Scholar 

  25. Grassegger A, Schuler G, Hessenberger G, Walder-Hantich B, Jabkowski J, MacHeiner W, Salmhofer W, Zahel B, Pinter G, Herold M, Klein G, Fritsch PO (1998) Interferon-gamma in the treatment of systemic sclerosis: a randomized controlled multicentre trial. Br J Dermat 139: 639

    Article  CAS  Google Scholar 

  26. Harrison NK, Glanville AR, Strickland B, Haslam PL, Corrin B, Addis BJ, Lawrence R, Millar AB, Black CM, Turner-Warwick M (1989) Pulmonary involvement in systemic sclerosis: the detection of early changes by thin section CT scan, bronchoalveolar lavage and 99mTc-DTPA clearance. Respir Med 83: 403

    Article  PubMed  CAS  Google Scholar 

  27. Heickendorff L, Zachariae H, Bjerring P, Halkier-Sorensen L, Sondergaard K (1995) The use of serologic markers for collagen synthesis and degradation in systemic sclerosis. J Am Acad Dermatol 32: 584

    Article  PubMed  CAS  Google Scholar 

  28. Hopkinson ND (2000) Prevalence of systemic sclerosis in a semi-rural population. Rheumatology [Suppl]

    Google Scholar 

  29. Hunzelmann N, Risteli J, Risteli L, Sacher C, Vancheeswaran R, Black C, Krieg T (1998) Circulating type I collagen degradation products: a new serum marker for clinical severity in patients with scleroderma? Br J Dermatol 139: 1020

    Article  PubMed  CAS  Google Scholar 

  30. Jimenez SA, Sigal SH (1991) A 15-year prospective study of treatment of rapidly progressive systemic sclerosis with D-penicillamine. J Rheumatol 18: 1496

    PubMed  CAS  Google Scholar 

  31. Jonsson CA, Erlandsson M, Svensson L, Molne J, Carlsten H (1999) Mycophenolate mofetil ameliorates perivascular T lymphocyte inflammation and reduces the double-negative T cell population in SLE-prone MRLIpr/lpr mice. Cell Immunol 197: 136

    Article  PubMed  CAS  Google Scholar 

  32. Krasagakis K, Dippel E, Rameker J, Owsianowski M, Orfanos CE (1998) Management of severe scleroderma with long-term extracorporeal photopheresis. Dermatology 196: 309

    Article  PubMed  CAS  Google Scholar 

  33. Levi-Schaffer F, Nagler A, Slavin S, Knopov V, Pines M (1996) Inhibition of collagen synthesis and changes in skin morphology in murine graft-versus-host disease and tight skin mice: effect of halofuginone. J Invest Dermatol 106: 84

    Article  PubMed  CAS  Google Scholar 

  34. Liberski SM, McGarrity TJ, Hartle R J, Varano V, Reynolds D (1994) The watermelon stomach: longterm outcome in patients treated with Nd:YAG laser therapy. Gastrointest Endosc 40: 584

    Article  PubMed  CAS  Google Scholar 

  35. Loperfido F, Fiorilli R, Santarelli P, Bellocci F, Zecchi P (1982) Severe involvement of the conduction system in a patient with sclerodermal heart disease. An electrophysiological study. Acta Cardiol 37: 31

    Google Scholar 

  36. Lopez-Ovejero JA, Saal SD, D’Angelo WA, Cheigh JS, Stenzel KH, Laragh JH (1979) Reversal of vascular and renal crises of sclerodenna by oral angiotensin-converting enzyme blockade. N Engl J Med 300: 1417

    Article  PubMed  CAS  Google Scholar 

  37. MacGregor AJ, Davrashvili J, Knight C, Denton CP, Lipkin DP, Black CM (1996) Early pulmonary hypertension in systemic sclerosis: risk of progression and consequences for survival. Arthritis Rheum 39: 5151

    Google Scholar 

  38. Matteson EL, Shbeeb MI, McCarthy TG, Calamia KT, Mertz LE, Goronzy JJ (1996) Pilot study of an-tithymocyte globulin in systemic sclerosis. Arthritis Rheum 39: 1132

    Article  PubMed  CAS  Google Scholar 

  39. Mayes MD, Giannini EH, Pachman LM, Buyon JP, Fleckman P (1997) Connective tissue disease registries. Arthritis Rheum 40: 1556

    Article  PubMed  CAS  Google Scholar 

  40. McKown KM, Carbone LD, Bustillo J, Seyer JM, Kang AH, Postlethwaite AE (2000) Induction of immune tolerance to human type I collagen in patients with systemic sclerosis by oral administration of bovine type I collagen. Arthritis Rheum 43: 1054

    Article  PubMed  CAS  Google Scholar 

  41. Medsger TA Jr, Silman AJ, Steen VD, Black CM, Akesson A, Bacon PA, Harris CA, Jablonska S, Jayson MI, Jimenez SA, Krieg T, Leroy EC, Maddison PJ, Russell ML, Schachter RK, Wollheim FA, Zacharaie H. A disease severity scale for systemic sclerosis: development and testing. J Rheumatol 1999 Oct; 26 (10): 2159–2167

    PubMed  Google Scholar 

  42. Morton SJ, Powell RJ (2000) Cyclosporin and tacrolimus: their use in a routine clinical setting for scleroderma. Rheumatology 39: 865

    Article  PubMed  CAS  Google Scholar 

  43. Pines M, Knopov V, Genina O, Lavelin I, Nagler A (1997) Halofuginone, a specific inhibitor of collagen type I synthesis, prevents dimethylnitrosamine-induced liver cirrhosis. J Hepatol 27: 391

    Article  PubMed  CAS  Google Scholar 

  44. Poormoghim H, Lucas M, Fertig N, Medsger TA Jr (2000) Systemic sclerosis sine scleroderma: demographic, clinical, and serologic features and survival in forty-eight patients. Arthritis Rheum 43: 444

    Article  PubMed  CAS  Google Scholar 

  45. Pope J, Bellamy N, Seibold J, Furst D, Baron M, Ellman M, Carette S, Smith CD, Chalmers I, O’Hanlon D, Kaminska E, Markland J, Sibley J, Catoggio L (1998) A randomized controlled trial of methotrexate versus placebo in early diffuse scleroderma — preliminary analysis. Arthritis Rheum 41: S420

    Google Scholar 

  46. Scorza R, Rivolta R, Mascagni B, Berruti V, Bazzi S, Castagnone D, Quarto di Palo F (1997) Effect of iloprost infusion on the resistance index of renal vessels of patients with systemic sclerosis. J Rheumatol 24: 1944

    PubMed  CAS  Google Scholar 

  47. Steen V (1998) An open trial of FK506 in the treatment of early diffuse scleroderma. Arthritis Rheumatism 41:S 103

    Google Scholar 

  48. Seibold JR, Clements PJ, Furst DE, Mayes MD, McCloskey DA, Moreland LW, White B, Wigley FM, Rocco S, Erikson M, Hannigan JF, Sanders ME, Amento EP (1998) Safety and pharmacokinetics of recombinant human relaxin in systemic sclerosis. J Rheumatol 25: 302

    PubMed  CAS  Google Scholar 

  49. Seibold JR, Korn JH, Simms R, Clements PJ, Moreland LW, Mayes MD, Furst DE, Rothfield N, Steen V, Weisman M, Collier D, Wigley FM, Merkel PA, Csuka ME, Hsu V, Rocco S, Erikson M, Hannigan J, Harkonen WS, Sanders ME (2000) Recombinant human relaxin in the treatment of scleroderma. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 132: 871

    Google Scholar 

  50. Sgreccia A, Morelli S, Ferrante L, Perrone C, De Marzio P, De Vincentiis G, Scopinaro F (1998) QT interval and QT dispersion in systemic sclerosis (scleroderma). J Intern Med 243: 127

    PubMed  CAS  Google Scholar 

  51. Silman A, Akesson A, Newman J, Henriksson H, Sandquist G, Nihill M, Palfrey S, Lomas R, Wollheim F, Black C (1998) Assessment of functional ability in patients with scleroderma: a proposed new disability assessment instrument. J Rheumatol 25: 79

    PubMed  CAS  Google Scholar 

  52. Steen VD, Lanz JK Jr, Conte C, Owens GR, Medsger TA (1994) Therapy for severe interstitial lung disease in systemic sclerosis. A retrospective study. Arthritis Rheum 37: 1290

    Google Scholar 

  53. Steen VD, Medsger TA (1997) The palpable tendon friction rub: an important physical examination finding in patients with systemic sclerosis. Arthritis Rheum 40: 1146

    Article  PubMed  CAS  Google Scholar 

  54. Steen VD, Medsger TA (1998) Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis. Arthritis Rheum 41: 1613

    Article  PubMed  CAS  Google Scholar 

  55. Steen VD, Medsger TA (1997) The value of the Health Assessment Questionnaire and special patient-generated scales to demonstrate change in systemic sclerosis patients over time. Arthritis Rheum 40: 1984

    Article  PubMed  CAS  Google Scholar 

  56. Stevens W, Vancheeswaran R, Black CM (1992) Alpha interferon-2a (Roferon-A) in the treatment of diffuse cutaneous systemic sclerosis:a pilot study. UK Systemic Sclerosis Study Group. Br J Rheumat 31: 683

    Google Scholar 

  57. Stratton RJ, Wilson H, Black CM (2001) Pilot study of anti-thymocyte globulin plus mycophenolate mofetil in recent-onset diffuse scleroderma. Rheumatology 40: 84–88

    Article  PubMed  CAS  Google Scholar 

  58. Tarkowski A, Andersson-Gare B, Aurell M (1993) Use of anti-thymocyte globulin in the management of refractory systemic autoimmune diseases. Scand J Rheumatol 22: 261

    Article  PubMed  CAS  Google Scholar 

  59. Unemori EN, Pickford LB, Salles AL, Piercy CE, Grove BH, Erikson ME, Amento EP (1996) Relaxin induces an extracellular matrix-degrading phenotype in human lung fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo. J Clin Invest 98: 2739

    Article  PubMed  CAS  Google Scholar 

  60. Van den Hoogen FH, Boerbooms AM, Swaak AJ, Rasker JJ, Lier HI van, Putte LB van de (1996) 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 35: 364

    Article  PubMed  Google Scholar 

  61. Varai G, Earle L, Jimenez SA, Steiner RM, Varga J (1998) A pilot study of intermittent intravenous cyclophosphamide for the treatment of systemic sclerosis associated lung disease. J Rheumatol 25: 1325

    PubMed  CAS  Google Scholar 

  62. Vayssairat M (1999) Preventive effect of an oral prostacyclin analog, beraprost sodium, on digital necrosis in systemic sclerosis. French Microcirculation Society Multicenter Group for the Study of Vascular Acrosyndromes. J Rheumatol 26: 2173

    PubMed  CAS  Google Scholar 

  63. Wells AU, Cullinan P, Hansell DM, Rubens MB, Black CM, Newman-TaylorAJ, Du Bois RM (1994) Fibrosing alveolitis associated with systemic sclerosis has a better prognosis than lone cryptogenic fibrosing alveolitis. Am J Respir Crit Care Med 149: 1583

    Google Scholar 

  64. White B, Bauer EA, Goldsmith LA, Hochberg MC, Katz LM, Korn JH, Lachenbruch PA, LeRoy EC, Mitrane MP, Paulus HE, Postlethwaite AE, Steen VD (1995) Guidelines for clinical trials in systemic sclerosis (scleroderma). I. Disease-modifying interventions. The American College of Rheumatology Committee on Design and Outcomes in Clinical Trials in Systemic Sclerosis. Arthritis Rheum 38: 351

    Google Scholar 

  65. White B, Moore WC, Wigley FM, Xiao HQ, Wise RA (2000) Cyclophosphamide is associated with pulmonary function and survival benefit in patients with scleroderma and alveolitis. Ann Intern Med 132: 947

    PubMed  CAS  Google Scholar 

  66. Wigley FM, Wise RA, Seibold JR, McCloskey DA, Kujala G, Medsger TA Jr, Steen VD, Varga J, Jimenez S, Mayes M, Clements PJ, Weiner SR, Porter J, Ellman M, Wise C, Kaufmann LD, Williams J, Dole W (1994) Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study. Ann Intern Med 120 (3): 199

    PubMed  CAS  Google Scholar 

  67. Wollersheim H, Thien T, Laar A van’t (1987) Nifedipine in primary Raynaud’s phenomenon and in scleroderma: oral versus sublingual hemodynamic effects. J Clin Pharmacol 27: 907

    PubMed  CAS  Google Scholar 

  68. Zachariae H, Halkier-Sorensen L, Heickendorff L, Zachariae E, Hansen HE (1990) Cyclosporin A treatment of systemic sclerosis. Br J Dermatol 122: 677

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Rheumatology, Royal Free Campus, University College London, Rowland Hill Street, Hampstead, UK

    C. P. Denton & Carol M. Black

Authors
  1. C. P. Denton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carol M. Black
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carol M. Black .

Editor information

Editors and Affiliations

  1. Novartis Pharmaceuticals, Australia Pty. Ltd., Waterloo Road 54, 2113, NSW, North Ryde, Australia

    W. B. Harrison

  2. Academic Hospital, Department of Rheumatology, Vrije Universiteit, P. O. Box 7057, 1007 MB, Amsterdam, The Netherlands

    B. A. C. Dijkmans

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Denton, C.P., Black, C.M. (2002). Combination therapies for systemic sclerosis. In: Harrison, W.B., Dijkmans, B.A.C. (eds) Combination Treatment in Autoimmune Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-04759-0_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-04759-0_9

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-07704-3

  • Online ISBN: 978-3-662-04759-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation