Skip to main content
SpringerLink
Log in

Glucocorticoide: Stellenwert in der Therapie der Vaskulitis

The role of glucocorticoids in the treatment of vasculitis

  • BEITRAG ZUM SCHWERPUNKTTHEMA
  • Published:
Zeitschrift für Rheumatologie Aims and scope Submit manuscript

Zusammenfassung

Erst die chemische Modifikation der natürlichen Steroide in den 50er Jahren konnte die notwendigen strukturellen Voraussetzungen für die biologische Aktivität der Glucocorticoide (GC) nachweisen. Während die delta-4,3-keto-11-beta, 17-alpha,21-trihydroxyl Konfiguration Voraussetzung für die GC-Aktivität ist, konnte durch die künstliche Einführung einer zusätzlichen Doppelbindung in Position 1 und 2 die GC-Aktivität um das 4fache erhöht werden. Von diesen synthetischen GC ist das Prednison das am häufigsten verwendete GC in der medikamentösen Therapie. Aufgrund des raschen Wirkungseintritts sind die GC in der Therapie der Vaskulitis inzwischen unverzichtbar geworden. Die Dosis, Therapiedauer und Applikationsform richten sich nach der Diagnose, Krankheitsstadium bzw. -ausdehnung sowie Krankheitsaktivität. Bei der Abwägung zwischen dem therapeutischen Nutzen und therapiebedingten Nebenwirkungen der GC sind die Erfahrungen aus den Ende der 80er Jahre publizierten Kohortenstudien von entscheidender Bedeutung. Für die Arteriitis temporalis zeigte sich, dass zur Remissionsinduktion auch GC-Dosen von unter <60mg/d ausreichen. Dabei ist bezüglich eines drohenden Visusverlustes der Zeitpunkt der Therapieeinleitung von vorrangiger Bedeutung, weniger die Höhe der initialen GC-Therapie. Bei den ANCA-assoziierten Vaskulitiden führten die GC, später in Kombination mit Cyclophosphamid zu einer entscheidenden Senkung der krankheitsassoziierten Mortalität. Durch den Übergang von einer akut lebensbedrohlichen in eine chronische Erkrankung steht die therapieassoziierte Morbidität zunehmend im Vordergrund. Es besteht nachweislich eine direkte Korrelation zwischen der Höhe bzw. Dauer der GC-Therapie und dem Risiko für GC-assoziierte Nebenwirkungen, insbesondere der Inzidenz schwerwiegender Infektionen. Diese Übersicht enthält einen kurzen Überblick über die vorliegenden Daten zu dem Stellenwert der GC bei der Therapie der Arteriitis temporalis und den ANCA-assoziierten Kleingefäßvaskulitiden. Im Besonderen wird auf die Bedeutung der GC-assoziierten Nebenwirkungen bei den genannten Erkrankungen eingegangen.

Summary

Only the modification of natural steroids in the middle of the last centure gave insights into the structural requirements for the biological activity of the glucocorticoids (GC). While the delta-4,3-keto-11-beta, 17-alpha,21-trihydroxyl configuration is needed for the GC-activity, an artificial additional dubblebinding in position 1 and 2 lead to a four fold increase of the GC-activity. Of the artifical GC, prednisolone is the most frequently used compound and essential in the therapy of vasculitis today. Dosage, duration and way of application depend on the diagnosis, diseasestage, -extend as well as -activity. Considering the use and side-effects of the GC, experiences from cohort-studies of the late 80-ties help at clinical decision making. For giant cell arteritis (GCA) it was shown, that doses of less then 60 mg/day are needed for the induction of remission. Concerning the visual loss in GCA, time of initiating GC-therapy seems more important than the dosage. In the treatment of ANCA-associated vasculitis therapy with GC, later in combination with cyclophosphamide, lead to a significant reduction of mortality. Due to the fact of an increasing survivalrate, therapy-related morbidity becomes a more and more important issue. There is a proven correlation between the dosage respectively duration of the GC-therapy and the risk of GC-associated side-effects, especially the incidence of severe infections. This article gives a short review of the present data of the role of GC in the treatment of vasculitis.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Mowat AG, Hazleman BL (1974) Polymyalgia rheumatica—a clinical study with particular reference to arterial disease. J Rheumatol 1:190–202

    Google Scholar 

  2. Nesher G, Rubinow A (1997) Sonnenblick M. Clin Exp Rheuma 15:303–306

    Google Scholar 

  3. Hunder GG, Sheps SG, Allen GL, Joyce JW (1975) Daily and alternateday corticosteroid regimens in treatment of giant cell arteritis: comparison in a prospective study. Ann Intern Med 82:613–618

    Google Scholar 

  4. Ruegsegger P, Medici TC, Anliker M (1983) Corticosteroid-induced bone loss. A longitudinal study of alternate day therapy in patients with bronchial asthma using quantitative computed tomography. Eur J Clin Pharmacol 25:615–620

    Google Scholar 

  5. Chevalet P, Barrier JH, Pottier P, Magadur-Joly G, Pottier MA, Hamidou M, Planchon B, El Kouri D, Connan L, Dupond JL, De Wazieres B, Dien G, Duhamel E, Grosbois B, Jego P, Le Strat A, Capdeville J, Letellier P, Agron L (2000) A randomized, multicenter, controlled trial using intravenous pulses of methylprednisolone in the initial treatment of simple forms of giant cell arteritis: a one year followup study of 164 patients. J Rheumatol 27:1484–1491

    Google Scholar 

  6. Weyand CM, Tetzlaff N, Bjornsson J, Brack A, Younge B, Goronzy JJ (1997) Disease patterns and tissue cytokine profiles in giant cell arteritis. Arthritis Rheum 40:19–26

    Google Scholar 

  7. Font C, Cid MC, Coll-Vinent B, Lopez-Soto A, Grau JM (1997) Clinical features in patients with permanent visual loss due to biopsy-proven giant cell arteritis. Br J Rheumatol. 36:251–254

    Google Scholar 

  8. Birkhead NC, Wagener HP, Schick RM (1957) Treatment of temporal arteritis with edrenal corticoids: Results in 55 cases in which lesion was proven at biopsy. JAMA 163:821–827

    Google Scholar 

  9. Foroozan R, Deramo VA, Buono LM et al (2003) Recovery of visual function in patients with biopsy proven giant cell arteritis. Ophthalmology 110:539–542

    Google Scholar 

  10. Mc Cluskey P, Powell RJ (2004) The eye in systemicinflammatory diseases. Lancet 364:2125–2133

    Google Scholar 

  11. Gonzales-Gay MA, Blanco R, Rodriguez-Valverde V et al (1998) Permanent visual loss and cerebrovascular accidents in giant cell arteritis: predictors and response to treatment. Arthritis Rheum 41:1497–1504

    Google Scholar 

  12. Kyle V, Hazelman BL (1990) Stopping steroids in polymyalgia rheumatica and giant cell arteritis. BMJ 300:344–345

    Google Scholar 

  13. Delecoeuillerie G, Joly P, Cohen de Lara A, Paolaggi JB (1988) Polymyalgia rheumatica and temporal arteritis: a retrospective analysis of prognostic features and different corticosteroid regimens (11 year survey of 210 patients). Ann Rheum Dis 47:733–739

    Google Scholar 

  14. Nesher G, Sonnenblick M, Friedlander Y (1994) Analysis of steroid related complications and mortality in temporal arteritis: a 15-year survey of 43 patients. J Rheumatol. 21:1283–1286

    Google Scholar 

  15. Kyle V, Hazleman BL (1989) Treatment of polymyalgia rheumatica and giant cell arteritis. II. Relation between steroid dose and steroid associated side effects. Ann Rheum Dis 48:662–666

    Google Scholar 

  16. Gabriel SE, Sunku J, Salvarani C, O’Fallon WM, Hunder GG (1997) Adverse outcomes of antiinflammatory therapy among patients with polymyalgia rheumatica. Arthritis Rheum 40:1873–1878

    Google Scholar 

  17. Proven A, Gabriel SE, Orces C, O’Fallon WM, Hunder GG (2003) Glucocorticoid therapy in giant cell arteritis: duration and adverse outcomes. Arthritis Rheum 49:703–708

    Google Scholar 

  18. Rauzy O, Fort M, Nourhashemi F, Alric L, Juchet H, Ecoiffier M, Abbal M, Adoue D (1998) Relation between HLA DRB1 alleles and corticosteroid resistance in giant cell arteritis. Ann Rheum Dis 57:380–382

    Google Scholar 

  19. Weyand CM, Goronzy JJ (2003) Giant-cell arteritis and polymyalgia rheumatica. Ann Intern Med 139:505–515

    Google Scholar 

  20. Brack A, Rittner HL, Younge BR, Kaltschmidt C, Weyand CM, Goronzy JJ (1997) Glucocorticoid-mediated repression of cytokine gene transcription in human arteritis-SCID chimeras. J Clin Invest 99:2842–2850

    Google Scholar 

  21. Weyand CM, Goronzy JJ (2003) Medium-and large-vessel vasculitis. N Engl J Med 349:160–169

    Google Scholar 

  22. Jover JA, Hernandez-Garcya C, Morado IC, Vargas E, Banares A, Fernandez-Gutierrez B (2001) Combined Treatment of Giant-Cell Arteritis with Methotrexate and Prednisone: A Randomized, Double-Blind, Placebo-Controlled Trial, Ann Intern Med 134:106–114

    Google Scholar 

  23. Spiera RF, Mitnick HJ, Kupersmith M, Richmond M, Spiera H, Peterson MGE, Paget SA (2001) A prospective, double-blind, randomized, placebo controlled trial of methotrexate in the treatment of giant cell arteritis, Clinical and Experimental Rheumatology 19:495–501

    Google Scholar 

  24. Hoffman GS, Cid MC, Hellmann DB, Guillevin L, Stone JH, et al (2002) International Network for the Study of Systemic Vasculitides. A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis. Arthritis Rheum 46:1309–1318

    Google Scholar 

  25. Frohnert PP, Sheps SG (1967) Long-term follow-up study of periarteritis nodosa. Am J Med 43:8–14

    Google Scholar 

  26. Guillevin L, Fain O, Lhote F, Jarrousse B, Le Thi Huong D, Bussel A, Leon A (1992) Lack of superiority of steroids plus plasma exchange to steroids alone in the treatment of polyarteritis nodosa and Churg-Strauss syndrome. A prospective, randomized trial in 78 patients. Arthritis Rheum 35:208–215

    Google Scholar 

  27. Leib ES, Restivo C, Paulus HE (1979) Immunosuppressive and corticosteroid therapy of polyarteritis nodosa. Am J Med 67:941–947

    Google Scholar 

  28. Koldingsnes W, Nossent JC (2003) Baseline features and initial treatment as predictors of remission and relapse in Wegener’s granulomatosis. J Rheumatol 30:80–88

    Google Scholar 

  29. Koldingsnes W, Nossent H (2002) Predictors of survival and organ damage in Wegener’s granulomatosis. Rheumatology 41:572–581

    Google Scholar 

  30. Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, Rottem M, Fauci AS (1992) Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 116:488–498

    Google Scholar 

  31. Guillevin L, Durand-Gasselin B, Cevallos R, Gayraud M, Lhote F, Callard P, Amouroux J, Casassus P, Jarrousse B (1999) Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients. Arthritis Rheum 42:421–430

    Google Scholar 

  32. Reinhold-Keller E, Beuge N, Latza U, de Groot K, Rudert H, Nolle B, Heller M, Gross WL (2000) An interdisciplinary approach to the care of patients with Wegener‘s granulomatosis: long-term outcome in 155 patients. Arthritis Rheum 43:1021–1032

    Google Scholar 

  33. Bradley JD, Brandt KD, Katz BP (1989) Infectious complications of cyclophosphamide treatment for vasculitis. Arthritis Rheum 32:45–53

    Google Scholar 

  34. Ognibene FP, Shelhamer JH, Hoffman GS, Kerr GS, Reda D, Fauci AS, Leavitt RY (1995) Pneumocystis carinii pneumonia: a major complication of immunosuppressive therapy in patients with Wegener’s granulomatosis. Am J Respir Crit Care Med 151:795–799

    Google Scholar 

  35. Godeau B, Mainardi JL, Roudot-Thoraval F, Hachulla E, Guillevin L, Huong Du LT, Jarrousse B, Remy P, Schaeffer A, Piette JC (1995) Factors associated with Pneumocystis carinii pneumonia in Wegener‘s granulomatosis. Ann Rheum Dis. 54:991–994

    Google Scholar 

  36. Chung JB, Armstrong K, Schwartz JS, Albert D (2000) Cost-effectiveness of prophylaxis against Pneumocystis carinii pneumonia in patients with Wegner’s granulomatosis undergoing immunosuppressive therapy. Arthritis Rheum 43:1841–1848

    Google Scholar 

  37. van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C (2000) Oral corticoids and fracture risk: relationship to daily and cumulatice doses. Rheumatol 39:1383–1389

    Google Scholar 

  38. van Staa TP, Leufkens HG, Cooper C (2002) The epidemiology of corticoid-induced osteoporosis: a metaanalysis. Osteoporosis Int 13:777–787

    Google Scholar 

  39. Pearce G, Ryan PF, Delmas PD, Tabensky DA, Seeman E (1998) The deleterious effects of low-dose corticosteroids on bone density in patients with polymyalgia rheumatica. Br J Rheumatol 37:292–299

    Google Scholar 

  40. Robb-Nicholson C, Chang RW, Anderson S, Roberts WN, Longtine J, Corson J, Larson M, George D, Green J, Bryant G et al (1988) Diagnostic value of the history and examination in giant cell arteritis: a clinical pathological study of 81 temporal artery biopsies. J Rheumatol 15:1793–1796

    Google Scholar 

  41. Salvarani C, Cantini F, Boiardi L, Hunder GG (2002) Polymyalgia rheumatica and giant-cell arteritis. N Engl J Med. 347(4):261–271

    Google Scholar 

  42. Adachi JD, Bensen WG, Bianchi F, Cividino A, Pillersdorf S, Sebaldt RJ, Tugwell P, Gordon M, Steele M, Webber C, Goldsmith CH (1996) Vitamin D and calcium in the prevention of corticosteroid induced osteoporosis: a 3 year followup. J Rheumatol 23:995–1000

    Google Scholar 

  43. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. Amercican College of Rheumatology ad hoc committee on glucocorticoid-induced osteoporosis. Arthritis Rheum 44:1496–503

Download references

Author information

Authors and Affiliations

  1. Universitätsklinikum Schleswig Holstein, Campus Lübeck und Rheumaklinik Bad Bramstedt, Oskar-Alexander-Straße 26, 24576, Bad Bramstedt, Germany

    P. M. Aries, B. Hellmich & W. L. Gross

Authors
  1. P. M. Aries
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Hellmich
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. L. Gross
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. M. Aries.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aries, P.M., Hellmich, B. & Gross, W.L. Glucocorticoide: Stellenwert in der Therapie der Vaskulitis. Z. Rheumatol. 64, 155–161 (2005). https://doi.org/10.1007/s00393-005-0717-5

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00393-005-0717-5

Schlüsselwörter

Key words

Search

Navigation