Skip to main content
SpringerLink
Log in

Progressive Systemic Scleroderm

  • Chapter
Autoimmune Diseases of the Skin

  • 1816 Accesses

Summary

Despite intense research efforts and major advances in the understanding of particular aspects of the disease process, the etiology of SSc is still unknown and the pathogenesis only partly understood. Survival has markedly improved over the past two decades, with the 10-year survival rate approaching 80%, although to date with the exception of cyclophosphamide there is no effective disease-modifying treatment of SSc. The introduction of drugs that treat organ complications has changed markedly, the mortality and life quality of subgroups of SSc. The associated side effects and lack of efficacy in certain subgroups of organ involvement indicate however, that the available treatment options are still unsatisfactory (e.g. in pulmonary fibrosis or kidney failure). Therefore, future treatments should be designed to specifically target distinct pathogenetic pathways in SSc.

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 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

  • Alarcon GS (2000) Unclassified or undifferentiated connective tissue disease. Baillieres Best Pract Res Clin Rheumatol 14:125–137

    Article  PubMed  CAS  Google Scholar 

  • Artlett CM, Smith CB, Jimenez SA (1998) Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis. N Engl J Med 338:1186–1191

    Article  PubMed  CAS  Google Scholar 

  • Badesch D, Tapson VF, McGoon MD (2000) Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. Ann Int Med 132:425–434

    PubMed  CAS  Google Scholar 

  • Baroni SS, Santillo M, Bevilacqua F, Luchetti M, Spadoni T, Mancini M et al. (2006) Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N Engl J Med 22;354(25):2667–2276

    Article  CAS  Google Scholar 

  • Beyer C, Schett G, Gay S, Distler O, Distler JH (2009) Hypoxia. Hypoxia in the pathogenesis of systemic sclerosis. Arthritis Res Ther 11(2):220

    Article  PubMed  Google Scholar 

  • Black CM, Silman SJ, Herrick AI (1998) 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 42:299–305

    Article  Google Scholar 

  • Blockmans D, Beyens G, Verhaege R (1996) Predictive value of nailfold capillaroscopy in the diagnosis of connective tissue diseases. Clin Rheumatol 15:148–153

    Article  PubMed  CAS  Google Scholar 

  • Bottomley WW, Goodfield MJ, Sheehan-Dare RA (1996) Digital calcification in systemic sclerosis: effective treatment with good tissue preservation using the carbon dioxide laser. Br J Dermatol 135:302–304

    Article  PubMed  CAS  Google Scholar 

  • Bunn CC, Denton CP, Shi-Wen X, Knight C, Black CM (1998) Anti-RNA Polymerases and other autoantibody specificities in systemic sclerosis. Br J Rheumatol 37:15–20

    Article  PubMed  CAS  Google Scholar 

  • Burastero SE, Galbiati S, Vassallo A, Sabbadini MG, Bellone M, Marchionni L et al. (2003) Cellular microchimerism as a lifelong physiologic status in parous women: an immunologic basis for its amplification in patients with systemic sclerosis. Arthiritis Rheum 48:1109–1116

    Article  Google Scholar 

  • Chang YJ, Spiera H (1999) Renal transplantation in scleroderma. Medicine 78:382–385

    Article  PubMed  CAS  Google Scholar 

  • Clements PJ, Lachenbruch PA, Ng SC (1990) Skin score. A semiquantitative measure of cutaneous involvement that improves prediction of prognosis in systemic sclerosis. Arthritis Rheum 33:1256–1263

    Article  PubMed  CAS  Google Scholar 

  • Clements PJ, Furst DE, Wong WK (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 42:1194–1203

    Article  PubMed  CAS  Google Scholar 

  • 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 33:90–92

    Article  PubMed  CAS  Google Scholar 

  • Dong C, Zhu S, Wang T, Yoon W, Li Z, Alvarez RJ et al. (2002) Deficient Smad 7 expression: aputative molecular defect in scleroderma. PNAS 99:3908–3913

    Article  PubMed  CAS  Google Scholar 

  • Distler JH, Jüngel A, Huber LC et al. 2007 Imatinib mesylate reduces production of extracellular matrix and prevents development of experimental dermal fibrosis. Arthritis Rheum; 56(1):311–322

    Article  PubMed  CAS  Google Scholar 

  • Duncan MR, Hasan A, Berman B (1995) Pentoxifylline, pentifylline and interferons decrease type I and III procollagen mRNA levels in dermal fibroblasts: evidence for mediation by nuclear factor 1 downregulation. J Invest Dermatol 104:282–286

    Article  PubMed  CAS  Google Scholar 

  • Dziadzio M, Denton CP Smith R (1999) Losartan therapy for raynauds phenomenon and scleroderma: clinical and biochemical findings in a fifteen-week, randomized, parallel group, controlled trial. Arthritis Rheum 42:2646–2455

    Article  PubMed  CAS  Google Scholar 

  • Enomoto, Mekkes JR, Bossuyt PM (1999) Treatment of patients with systemic sclerosis with extra-corporeal photochemotherapy (photopheresis). J Am Acad Dermatol 41:915–922

    Article  PubMed  CAS  Google Scholar 

  • Evans PC, Lambert N, Maloney S (1999) Long term fetal microchimerism in peripheral blood mono-nuclear scell subsets in healthy women and women with scleroderma. Blood 93:2033–2037

    PubMed  CAS  Google Scholar 

  • Fleming JN, Nash RA, McLeod DO, Fiorentino DF, Shulman HM, Connolly MK et al. (2008) Capillary regeneration in scleroderma: stem cell therapy reverses phenotype? PLoS One 16;3(1):e1452

    Article  Google Scholar 

  • Fritzler MJ (1993) Autoantibodies in scleroderma. J Dermatol 20:257–268

    PubMed  CAS  Google Scholar 

  • Furst DE, Clements PJ, Steen VD (1998) The modified rodnan skin score is an accurate reflection of skin biopsy thickness in systemic sclerosis. J Rheumatol 25:84–88

    PubMed  CAS  Google Scholar 

  • Gabrielli A, Avvedimento EV, Krieg T (2009) Scleroderma. N Engl J Med 7;360(19): 1989–2003

    Article  CAS  Google Scholar 

  • Genth E, Mierau R, Genetzky P (1990) Immunogenetic associations of scleroderma-related anti-nuclear antibodies. Arthritis Rheum 33:657–665

    Article  PubMed  CAS  Google Scholar 

  • Jablonska S, Blaszyk M (1999) Scleroderma Overlap Syndromes. Adv Exp Med Biol 455:85–92

    PubMed  CAS  Google Scholar 

  • Janowsky EC, Kupper LL, Hulka BS (2000) Meta-analyses of the relation between silicone breast implants and the risk of connective tissue. N Engl J Med 342:781–790

    Article  PubMed  CAS  Google Scholar 

  • Haustein UF, Anderegg U (1998) Silica induced scleroderma — clinical and experimental aspects. J Rheumatol 25:1917–1926

    PubMed  CAS  Google Scholar 

  • Hebbar M, Peyrat JP, Hornez L, Hatron PY, Hachulla E, Devulder B. (2000) Increased concentrations of the circulating angiogenesis inhibitor endostatin in patients with systemic sclerosis. Arthritis Rheum 43:889–893

    Article  PubMed  CAS  Google Scholar 

  • 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 32:584–588

    Article  PubMed  CAS  Google Scholar 

  • Herrmann K, Heckmann M, Kulozik M, Haustein UF, Krieg T (1991) Steady state mRNA levels of collagens I,III, fibronectin and collagenase in skin biopsies of systemic sclerosis patients. J Invest Dermatol 97:219–225

    Article  PubMed  CAS  Google Scholar 

  • Herrmann G, Wlaschek M, Lange TS, Prenzel K, Goerz G, Scharffetter-Kochanek K (1993) UVA irradiation stimulates the synthesis of various matrix-metalloproteinases (MMPs) in cultured human fibroblasts. Exp Dermatol 2:92–97

    Article  PubMed  CAS  Google Scholar 

  • Hoeper MM et al. (2000) Long term treatment of primary pulmonary hypertension with aerolized iloprost, a prostacyclin analogue. N Engl J Med 342:1866–1870

    Article  PubMed  CAS  Google Scholar 

  • Hunzelmann N, Anders S, Fierlbeck G, Hein R, Herrmann K, Albrecht M et al. (1997) Systemic scleroderma: multicenter trial of one year treatment with recombinant interferon-gamma. Arch Dermatol 133:609–613

    Article  PubMed  CAS  Google Scholar 

  • Hunzelmann N, Risteli J, Risteli L, Sacher C, Black CM, Krieg T (1998a) Increased circulating concentrations of the type I collagen specific degradation product ICTP in systemic sclerosis reflect the extent of skin involvement: A new serum marker for clinical severity in SSc patients. Br J Dermatol 139:1020–1025

    Article  PubMed  CAS  Google Scholar 

  • Hunzelmann N, Scharfetter-Kochanek K, Hager C, Krieg T (1998b) Management of localized scleroderma. Sem Cutan Med Surg 17:34–41

    Article  CAS  Google Scholar 

  • Hunzelmann N, Genth E, Krieg T, Lehmacher W, Melchers I, Meurer M et al.; Registry of the German Network for Systemic Scleroderma (2008) The registry of the German Network for Systemic Scleroderma: frequency of disease subsets and patterns of organ involvement. Rheumatology (Oxford) Aug;47(8):1185–1192

    Article  CAS  Google Scholar 

  • Hunzelmann N, Genth E, Krieg T, Meurer M, Melchers I, Moinzadeh P et al.; German Network for Systemic Sclerosis (2008) Organ-specific diagnosis in patients with systemic sclerosis: Recommendations of the German Network for Systemic Sclerosis (DNSS). Z Rheumatol 67(4):334–336, 337–40

    Article  PubMed  CAS  Google Scholar 

  • Hunzelmann N, Moinzadeh P, Genth E, Krieg T, Lehmacher W, Melchers I et al.; German Network for Systemic Scleroderma Centers (2009) High frequency of corticosteroid and immunosuppressive therapy in patients with systemic sclerosis despite limited evidence for efficacy. Arthritis Res Ther 11(2):R30

    PubMed  Google Scholar 

  • Hunzelmann N, Brinckmann J (2010) What are the new milestones in the pathogenesis of systemic sclerosis? Ann Rheum Dis 69Suppl 1:i52–i56

    Article  PubMed  CAS  Google Scholar 

  • Igarashi A, Nashiro K, Kikuchi K (1995) Significant correlation between connective tissue growth factor gene expression and skin sclerosis in tissue sections from patients with systemic sclerosis. J Invest Dermatol 105:280–284

    Article  PubMed  CAS  Google Scholar 

  • Kahaleh MB, Sultany GL, Smith EA, Huffstetter JE, Loadholt CB, LeRoy EC (1986) A modified scleroderma skin scoring method. Clin Exp Rheumatol 4:367–369

    PubMed  CAS  Google Scholar 

  • Kahaleh M, Fan PS (1997) Mechanism of serum mediated endothelial injury in scleroderma: identification of a granular enzyme in scleroderma skin and sera. Clin Immunol Immunopathol 83:32–40

    Article  PubMed  CAS  Google Scholar 

  • Kerscher M, Meurer M, Sander C, Volkenandt M, Lehmann P, Plewig G, Röcken M (1996) PUVA bath photochemotherapy for localized scleroderma. Arch Dermatol 132:1280–1282

    Article  PubMed  CAS  Google Scholar 

  • Kowal-Bielecka O, Landewé R, Avouac J, Chwiesko S, Miniati I, Czirjak L et al.; EUSTAR Co-Authors (2009) EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis 68(5):620–628

    Article  PubMed  CAS  Google Scholar 

  • Kulozik M, Hogg A, Lankat-Buttgereit B, Krieg T (1990) Co-localization of transforming growth factor ß2 with a1(1) procollagen mRNA in tissue sections of patients with systemic sclerosis. J Clin Invest 86:917–921

    Article  PubMed  CAS  Google Scholar 

  • LeRoy EC (1974) Increased collagen synthesis by scleroderma fibroblasts in vitro. J Clin Invest 54:880–889

    Article  PubMed  CAS  Google Scholar 

  • LeRoy EC, Maricq HR, Kahaleh MB (1980) Undifferentiated connective tissue syndromes. Arthritis Rheum 23:341–343

    Article  PubMed  CAS  Google Scholar 

  • Majewski S, Hunzelmann N, Johnson JP, Jung C, Mauch C, Ziegler-Heitbrock H et al. (1991) Expression of intercellular adhesion molecule-1 (ICAM-1) on fibroblasts in the skin of patients with systemic sclerosis. J Invest Dermatol 97:667–671

    Article  PubMed  CAS  Google Scholar 

  • Marguerie C (1992) The clinical and immunogenetic features of patients with autoantibodies to the nucleolar anitgen PM-Scl. Medicine 71:327–336

    Article  PubMed  CAS  Google Scholar 

  • Maricq H, LeRoy E, Dangelo W (1980) Diagnostic potential of in vivo capillary microscopy in scleroderma and related disorders. Arthritis Rheum 23:183–189

    Article  PubMed  CAS  Google Scholar 

  • Mauch C (1998) Regulation of connective tissue turnover by cell-matrix interactions. Arch Dermatol Res 290: S30–S36

    Article  PubMed  Google Scholar 

  • McCormick LL, Zhang Y, Tootell E, Gilliam AC (1999) Anti-TGF-beta treatment prevents skin and lung fibrosis in murine sclerodermatous graft-versus-host disease: a model for human scleroderma. J Immunol 163:5693–5699

    PubMed  CAS  Google Scholar 

  • McLaughlin V, Humbert M, Coghlan G, Nash P, Steen V (2009) Pulmonary arterial hypertension: the most devastating vascular complication of systemic sclerosis. Rheumatology (Oxford) 48Suppl 3:iii25–iii31

    Article  Google Scholar 

  • Perlish JS, Lemlich G, Fleischmajer R (1988) Identification of collagen fibrils in scleroderma skin. J Invest Dermatol 90:48–54

    Article  PubMed  CAS  Google Scholar 

  • Pigula FA, Griffith BP, Zenati MA (1997) Lung transplantation for respiratory failure resulting from systemic disease. Ann Thorac Surg 64:1630–1634

    Article  PubMed  CAS  Google Scholar 

  • Poormoghim H, Lucas M, Fertig N, Medsger TA (2000) Systemic sclerosis sine scleroderma: demographic, clinical, and serologic features and survival in forty eight patients. Arthritis Rheum 43:444–451

    Article  PubMed  CAS  Google Scholar 

  • Pope J, Bellamy N, Seibold J (1998) A controlled trial of methotrexate versus placebo in early diffuse scleroderma — preliminary analysis. Arthritis Rheum 41: S420

    Google Scholar 

  • Pope J, Fenlon D, Thompson A (2000) Iloprost and cisaprost for Raynaud’s phenomenon in progressive systemic sclerosis. Cochrane Database Syst Rev 2: CD000953

    PubMed  Google Scholar 

  • Prescott RJ, Freemont A, Jones C (1992) Sequential dermal microvascular and perivascular changes in the development of scleroderma. J Pathol 166:255–263

    Article  PubMed  CAS  Google Scholar 

  • Rook AH, Freundlich B, Jegasothy BV (1992) Treatment of systemic sclerosis with extracorporeal photochemotherapy. Results of a multicenter trial. Arch Dermatol 128:337–346

    Article  PubMed  CAS  Google Scholar 

  • Rubin LJ, Badesch DB, Barst RJ, Galie N, Black CM et al. (2002) Bosentan therapy for pulmonary hypertension. NEJM 346:896–903

    Article  PubMed  CAS  Google Scholar 

  • Scharffetter K, Lankat-Buttgereit B, Krieg T (1988) Localization of collagen mRNA in normal and scleroderma skin by in situ hybridization. Eur J Clin Invest 18:9–17

    Article  PubMed  CAS  Google Scholar 

  • Scharffetter K, Wlaschek M, Hogg A, Bolsen K, Schothorst A, Goerz G, Krieg T, Plewig G (1991) UVA irradiation induces collagenase in human dermal fibroblasts in vitro and in vivo. Arch Dermatol Res 283:506–511

    Article  PubMed  CAS  Google Scholar 

  • Seibold J (1994) Systemic sclerosis. In: Klipped J, Dieppe P, Mosby St. Louis (Eds) Rheumatology, 8.1–8.14

    Google Scholar 

  • Seibold J, Korn J, Simms R (2000) Recombinant human relaxin in the treatment of scleroderma. A randomized, double blind, placebo-controlled study. Ann Int Med 132:871–879

    PubMed  CAS  Google Scholar 

  • Sgonc R, Gruschwitz M, Dietrich H (1996) Endothelial cell apoptosis is a primary pathogenetic event underlying skin lesions in avian and human scleroderma. J Clin Invest 98:785–792

    Article  PubMed  CAS  Google Scholar 

  • Shi-Wen X, Pennington D, Holmes A (2000) Autocrine overexpression of CTGF maintains fibrosis: RDA analysis of fibrosis genes in systemic sclerosis. Exp Cell Res 25:213–224

    Article  Google Scholar 

  • Steen VD, Constantino JP, Shapiro AP, Medsger TA (1990) Outcome of renal crisis in systemic sclerosis: relation to availability of angiotensin converting enzyme (ACE) inhibitors. Ann Int Med 113:352–357

    PubMed  CAS  Google Scholar 

  • Steen VD, Follansbee WP, Conte CG, Medsger TA (1996) Thallium perfusion defects predict subsequent cardiac dysfunction in patients with systemic sclerosis. Arthritis Rheum 39:677–681

    Article  PubMed  CAS  Google Scholar 

  • 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 41:1613–1619

    Article  PubMed  CAS  Google Scholar 

  • Stege H, Berneburg M, Humke S (1997) High-dose UVA1 radiation therapy for localized scleroderma. J Am Acad Dermatol 36:938–944

    Article  PubMed  CAS  Google Scholar 

  • Straniero NR, Furst DE (1989) Environmentally induced systemic sclerosis like illness. Baillieres Clin Rheumatol 3:63–79

    Article  PubMed  CAS  Google Scholar 

  • Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnosis and Therapeutic Criteria Committee (1980) Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23:581–590

    Article  Google Scholar 

  • Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE et al.; Scleroderma Lung Study Research Group (2006) Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 22;354(25):2655–2666

    Article  CAS  Google Scholar 

  • Tyndall A, Black C, Finke J, Peter H, Gratwohl A (1997) Treatment of systemic sclerosis with autologous hemopoetic stem cell transplantation. The Lancet 349:254–356

    Article  CAS  Google Scholar 

  • Uitto J, Bauer EA, Eisen AZ (1979) Scleroderma. Increased biosynthesis of triple helical type I and type III procollagen associated with unaltered expression of collagenase by skin fibroblasts in culture. J Clin Invest 64:921–930

    Article  PubMed  CAS  Google Scholar 

  • van den Hoogen FH, Boerbooms AM, Swaak AJ (1996) Comparison of methotrexate with placebo in the treatment of systemic sclerosis: a 24 week randomized double blind trial, followed by a 24 week observation trial. Br J Rheumatol 35:364–372

    Article  PubMed  Google Scholar 

  • Walker UA, Tyndall A, Czirják L, Denton C, Farge-Bancel D, Kowal-Bielecka O et al. (2007) Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database. Ann Rheum Dis 66(6):754–763

    Article  PubMed  CAS  Google Scholar 

  • White B, Moore WC, Wigley FM (2000) Cyclophosphamide is associated with pulmonary function and survival benefit in patients with scleroderma and alveolitis. Ann Int Med 132:947–954

    PubMed  CAS  Google Scholar 

  • Williams HJ, Alarcon GS, Joks R (1999) Early undifferentiated connective tissue disease. VI an inception cohort after 10 years: disease remissions and changes in diagnoses in well established and undiflferentiated CTD. J Rheumatol 26:816–825

    PubMed  CAS  Google Scholar 

  • Zachariae H, Halkier-Sorensen L, Bjerring P, Heickendorflf L (1996) Treatment of ischemic digital ulcers and prevention of gangrene with intravenous iloprost in systemic sclerosis. Acta Derm Venereol 76:236–238

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, University of Cologne, J.-Stelzmann-Str. 9, D-50924, Köln, Germany

    Nicolas Hunzelmann MD

  2. Department of Dermatology and Allergology, University of Köln, Kerpener Str. 62, D-50937, Köln, Germany

    Thomas Krieg MD

Authors
  1. Nicolas Hunzelmann MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Krieg MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Michael Hertl

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag/Wien

About this chapter

Cite this chapter

Hunzelmann, N., Krieg, T. (2011). Progressive Systemic Scleroderm. In: Hertl, M. (eds) Autoimmune Diseases of the Skin. Springer, Vienna. https://doi.org/10.1007/978-3-211-99225-8_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-211-99225-8_8

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-99224-1

  • Online ISBN: 978-3-211-99225-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation