Zusammenfassung
Drei Charakteristika kennzeichnen die klinischen Manifestationen der systemischen Sklerose (Sklerodermie, SSc): Autoimmunität/Entzündung, Gefäßschädigung (Vaskulopathie) sowie (Organ-) Fibrose. Inzwischen sind medikamentöse und andere Therapieansätze für jedes dieser Charakteristika verfügbar. Aufgrund der Seltenheit der Erkrankung und ihrer klinischen Heterogenität fehlen jedoch oftmals gute Therapiestudien. Eine Initiative der „EULAR Scleroderma Trials and Research Group“ (EUSTAR, eine Arbeitsgruppe innerhalb der „European League Against Rheumatism“, EULAR) hat deshalb begonnen, die bisher verfügbaren Therapien zu bewerten und Empfehlungen auszusprechen. In diesem Artikel werden diejenigen Therapieansätze diskutiert, die über diese Empfehlungen hinaus zur Behandlung der systemischen Sklerose eingesetzt werden können. Es ist zu erwarten, dass durch die Etablierung von nationalen und internationalen Netzwerken (z. B. Deutsches Netzwerk für Systemische Sklerodermie, DNSS, oder EUSTAR) über die Auswertung großer Registerdaten und Durchführung gezielter Therapiestudien die Evidenz zur Behandlung für die systemische Sklerose zukünftig verbessert werden kann.
Abstract
The clinical manifestations of systemic sclerosis (scleroderma, SSc) are characterized by three prominent features: autoimmunity/inflammation, vascular lesions (vasculopathy) and (organ) fibrosis. Drugs and other therapies are now available for each of these features. However, due to the low prevalence and high variation in clinical signs and symptoms of the disease, there are only few high quality clinical trials. The EULAR Scleroderma Trials and Research Group (EUSTAR, a subgroup of the European League Against Rheumatism, EULAR) has therefore started to assess the therapies available today and make recommendations. The present article discusses treatment options in systemic sclerosis beyond these recommendations. It is to be expected that the establishment of national and international networks for systemic sclerosis research (e.g. the German Network for Systemic Sclerosis, DNSS, and EUSTAR) will raise the standards of evidence-based therapy for systemic sclerosis in the future by analyzing large data sets and performing clinical trials.
Literatur
Müller-Ladner U (2008) Systemische Sklerose. Internist (Berl) 49:278–285
Avouac J, Kowal-Bielecka O, Landewe R et al (2009) European League Against Rheumatism (EULAR) Scleroderma Trial and Research group (EUSTAR) recommendations for the treatment of systemic sclerosis: methods of elaboration and results of systematic literature research. Ann Rheum Dis 68:629–634
Kowal-Bielecka O, Landewé R, Avouac J et al (2009) EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis 68:620–628
Schmeiser T, Müller-Ladner U (2009) EULAR-Empfehlungen zur Behandlung der systemischen Sklerose. Z Rheumatol 69:87–92
Bérezné A, Ranque B, Valeyre D et al (2008) Therapeutic strategy combining intravenous cyclophosphamide followed by oral azathioprine to treat worsening interstitial lung disease associated with systemic sclerosis: a retrospective multicenter open-label study. J Rheumatol 35:1064–1072
Hoyles RK, Ellis RW, Wellsbury J 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 54:3962–3970
Swigris JJ, Olson AL, Fischer A et al (2006) Mycophenolate mofetil is safe, well tolerated and preserves lung function in patients with connective tissue disease-related interstitial lung disease. Chest 130:30–36
Nihtyanova SI, Brough GM, Black CM, Denton CP (2007) Mycophenolate mofetil in diffuse cutaneous systemic sclerosis – a retrospective analysis. Rheumatology 46:442–445
Gerbino AJ, Goss CH, Molitor JA (2008) Effect of mycophenolate mofetil on pulmonary function in scleroderma-associated interstitial lung disease. Chest 133:455–460
Amjadi S, Maranian P, Furst DE et al (2009) Course of the modified Rodnan skin thickness score in systemic sclerosis clinical trials: analysis of three large multicenter, double-blind, randomized controlled trials. Arthritis Rheum 60:2490–2498
Clements PJ, Furst DE, Wong WK et al (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
Hunzelmann N, Genth E, Krieg T et al (2009) The registry of the German network for systemic scleroderma: frequency of disease subsets and patterns of organ involvement. Rheumatology 47:1185–1192
Steen VD, Medsger TA Jr (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
Teixeira L, Mouthon L, Mahr A et al (2008) Mortality and risk factors of scleroderma renal crisis: a French retrospective study of 50 patients. Ann Rheum Dis 67:110–116
Morton SJ, Powell RJ (2000) Cyclosporin and tacrolimus: their use in a routine clinical setting for scleroderma. Rheumatology 39:865–869
Filaci G, Cutolo M, Scudeletti M et al (1999) Cyclosporin A and iloprost treatment of systemic sclerosis: clinical results and interleukin-6 serum changes after 12 months of therapy. Rheumatology 38:992–996
Su TI, Khanna D, Furst DE et al (2009) Rapamycin versus methotrexate in early diffuse systemic sclerosis: results from a randomized, single-blind pilot study. Arthritis Rheum 60:3821–3830
Denton CP, Engelhart M, Tvede N et al (2009) An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis. Ann Rheum Dis 68:1433–1439
Lam GK, Hummers LK, Woods A, Wigley FM (2007) Efficacy and safety of etanercept in the treatment of scleroderma-associated joint disease. J Rheumatol 34:1636–1637
Allanore Y, Devos-François G, Caramella C et al (2006) Fatal exacerbation of fibrosing alveolitis associated with systemic sclerosis in a patient treated with adalimumab. Ann Rheum Dis 65:834–835
Christopher-Stine L, Wigley F (2003) Tumor necrosis factor-alpha antagonists induce lupus-like syndrome in patients with scleroderma overlap/mixed connective tissue disease. J Rheumatol 30:2725–2727
Liozon E, Ouattara B, Loustaud-Ratti V, Vidal E (2007) Severe polymyositis and flare in autoimmunity following treatment with adalimumab in a patient with overlapping features of polyarthritis and scleroderma. Scand J Rheumatol 36:484–486
Lafyatis R, Kissin E, York M et al (2009) B cell depletion with rituximab in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum 60:578–583
Smith V, Van Praet JT, Vandooren B et al (2010) Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study. Ann Rheum Dis 69:193–197
Daoussis D, Liossis SN, Tsamandas AC et al (2010) Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study. Rheumatology 49:271–280
Matteson EL, Shbeeb MI, McCarthy TG et al (1996) Pilot study of antithymocyte globulin in systemic sclerosis. Arthritis Rheum 39:1132–1137
Lytton SD, Denton CP, Nutzenberger AM (2007) Treatment of autoimmune disease with rabbit anti-T lymphocyte globulin: clinical efficacy and potential mechanisms of action. Ann N Y Acad Sci 1110:285–296
Scherer HU, Burmester GR, Riemekasten G (2006) Targeting activated T cells: successful use of anti-CD25 monoclonal antibody basiliximab in a patient with systemic sclerosis. Ann Rheum Dis 65:1245–1247
Levy Y, Amital H, Langevitz P et al (2004) Intravenous immunoglobulin modulates cutaneous involvement and reduces skin fibrosis in systemic sclerosis: an open-label study. Arthritis Rheum 50:1005–1007
Gabrielli A, Svegliati S, Moroncini G, Avvedimento EV (2007) Pathogenic autoantibodies in systemic sclerosis. Curr Opin Immunol 19:640–645
Akesson A, Wollheim FA, Thysell H et al (1988) Visceral improvement following combined plasmapheresis and immunosuppressive drug therapy in progressive systemic sclerosis. Scand J Rheumatol 17:313–323
Szekanecz Z, Aleksza M, Antal-Szalmás P et al (2009) Combined plasmapheresis and high-dose intravenous immunoglobulin treatment in systemic sclerosis for 12 months: follow-up of immunopathological and clinical effects. Clin Rheumatol 28:347–350
Jacobs MJ, Jörning PJ, Van Rhede van der Kloot EJ et al (1991) Plasmapheresis in Raynaud’s phenomenon in systemic sclerosis: a microcirculatory study. Int J Microcirc Clin Exp 10:1–11
Knobler RM, French LE, Kim Y et al (2006) A randomized, double-blind, placebo-controlled trial of photopheresis in systemic sclerosis. J Am Acad Dermatol 54:793–799
Laar JM van, Farge D, Tyndall A (2008) Stem cell transplantation: a treatment option for severe systemic sclerosis? Ann Rheum Dis 67 (Suppl 3):iii35–iii38
Keysser G, Müller L, Schendel M, Schmoll HJ (2009) Therapeutische Anwendung mesenchymaler Stromazellen bei Autoimmunerkrankungen. Z Rheumatol 68:220, 222–227
Brueckner CS, Becker MO, Kroencke T et al (2009) Effect of sildenafil on digital ulcers in systemic sclerosis – analysis from a single centre pilot study. Ann Rheum Dis [Epub ahead of print]
Fries R, Shariat K, Wilmowsky H von, Böhm M (2005) Sildenafil in the treatment of Raynaud’s phenomenon resistant to vasodilatory therapy. Circulation 112:2980–2985
Chung L (2007) Therapeutic options for digital ulcers in patients with systemic sclerosis. J Dtsch Dermatol Ges 5:460–465
Meyer MF, Daigeler A, Lehnhardt M et al (2007) Therapeutisches Management akraler Manifestationen der systemischen Sklerose. Med Klin (Munich) 102:209–218
Souza RB de, Macedo AR, Kuruma KA et al (2009) Pentoxyphylline in association with vitamin E reduces cutaneous fibrosis in systemic sclerosis. Clin Rheumatol 28:1207–1212
Abou-Raya A, Abou-Raya S, Helmii M (2008) Statins: potentially useful in therapy of systemic sclerosis-related Raynaud’s phenomenon and digital ulcers. J Rheumatol 35:1801–1808
Kuwana M, Okazaki Y, Kaburaki J (2009) Long-term beneficial effects of statins on vascular manifestations in patients with systemic sclerosis. Mod Rheumatol 19:530–535
Rosato E, Borghese F, Pisarri S, Salsano F (2009) The treatment with N-acetylcysteine of Raynaud’s phenomenon and ischemic ulcers therapy in sclerodermic patients: a prospective observational study of 50 patients. Clin Rheumatol 28:1379–1384
Denton CP, Merkel PA, Furst DE et al (2007) Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192. Arthritis Rheum 56:323–333
Chung L, Fiorentino DF, Benbarak MJ et al (2009) Molecular framework for response to imatinib mesylate in systemic sclerosis. Arthritis Rheum 60:584–591
Daele PL van, Dik WA, Thio HB et al (2008) Is imatinib mesylate a promising drug in systemic sclerosis? Arthritis Rheum 58:2549–2552
Postlethwaite AE, Wong WK, Clements P et al (2008) A multicenter, randomized, double-blind, placebo-controlled trial of oral type I collagen treatment in patients with diffuse cutaneous systemic sclerosis: I. oral type I collagen does not improve skin in all patients, but may improve skin in late-phase disease. Arthritis Rheum 58:1810–1822
Khanna D, Clements PJ, Furst DE et al (2009) Recombinant human relaxin in the treatment of systemic sclerosis with diffuse cutaneous involvement: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 60:1102–1111
Sallam H, McNearney TA, Doshi D, Chen JD (2007) Transcutaneous electrical nerve stimulation (TENS) improves upper GI symptoms and balances the sympathovagal activity in scleroderma patients. Dig Dis Sci 52:1329–1337
Maddali Bongi S, Del Rosso A, Galluccio F et al (2009) Efficacy of a tailored rehabilitation program for systemic sclerosis. Clin Exp Rheumatol 27 (3 Suppl 54):44–50
Mancuso T, Poole JL (2009) The effect of paraffin and exercise on hand function in persons with scleroderma: a series of single case studies. J Hand Ther 22:71–77
Bongi SM, Del Rosso A, Galluccio F et al (2009) Efficacy of connective tissue massage and Mc Mennell joint manipulation in the rehabilitative treatment of the hands in systemic sclerosis. Clin Rheumatol 28:1167–1173
Sandqvist G, Akesson A, Eklund M (2004) Evaluation of paraffin bath treatment in patients with systemic sclerosis. Disabil Rehabil 26:981–987
Fiori G, Galluccio F, Braschi F et al (2009) Vitamin E gel reduces time of healing of digital ulcers in systemic sclerosis. Clin Exp Rheumatol 27(3 Suppl 54):51–54
Robertson LP, Marshall RW, Hickling P (2003) Treatment of cutaneous calcinosis in limited systemic sclerosis with minocycline. Ann Rheum Dis 62:267–269
Shetty S, Moore TL, Jackson S et al (2005) A pilot study of acetic acid iontophoresis and ultrasound in the treatment of systemic sclerosis-related calcinosis. Rheumatology 44:536–538
Cukierman T, Elinav E, Korem M, Chajek-Shaul T (2004) Low dose warfarin treatment for calcinosis in patients with systemic sclerosis. Ann Rheum Dis 63:1341–1343
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Becker, M., Müller-Ladner, U. & Riemekasten, G. Implementation von Leitlinien für eine Therapie der systemischen Sklerose (Sklerodermie). Z. Rheumatol. 69, 310–317 (2010). https://doi.org/10.1007/s00393-009-0523-6
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DOI: https://doi.org/10.1007/s00393-009-0523-6