Skip to main content
Log in

Update Granulomatose mit Polyangiitis (GPA, Wegener-Granulomatose)

Update on granulomatosis with polyangitis (GPA, Wegener’s granulomatosis)

Zeitschrift für Rheumatologie Aims and scope Submit manuscript

Zusammenfassung

Die Granulomatose mit Polyangiitis (GPA, Wegener-Granulomatose) ist durch eine granulomatöse Entzündung des Respirationstrakts und eine nekrotisierende, ANCA-assoziierte Vaskulitis kleiner bis mittelgroßer Gefäße gekennzeichnet, die eine Prädilektion für Lunge (pulmonale Kapillaritis) und Niere (nekrotisierende Kleingefäßvaskulitis) aufweist. Die Erkrankung verläuft stadienabhängig und beginnt typischerweise mit einer Entzündung des Respirationstrakts und generalisiert im Verlauf. Die Therapie erfolgt heute evidenzbasiert in Abhängigkeit von Aktivität und Krankheitsstadium, was zu einer deutlichen Verbesserung des Langzeitoutcomes geführt hat. Problematisch ist weiterhin die hohe Frühmortalität im ersten Jahr der Behandlung, die vor allem durch Infektionen unter Immunsuppression bedingt ist. Eine Herausforderung ist auch die Therapie refraktärer Organmanifestationen, die vor allem auch durch die granulomatöse Entzündung repräsentiert werden und erhebliche chronische Organschäden nach sich ziehen können.

Abstract

Granulomatosis with polyangitis (GPA, Wegener’s granulomatosis) is characterized by a granulomatous inflammation of the respiratory tract and a necrotizing ANCA-associated small to medium-size vessel vasculitis with a predilection for the lungs (pulmonary capillaritis) and kidneys (necrotizing glomerulonephritis). The disease evolves stage-wise and typically starts as inflammation of the respiratory tract followed by development of systemic vasculitis manifestations. Today, treatment is evidence-based and adapted according to activity and disease stage which has resulted in a significant improvement in long-term outcome. Early mortality during the first year of treatment poses one of the main problems and is a result of infections under immunosuppressive treatment. Furthermore, treatment of refractory disease activity which is often represented by granulomatous manifestations is still a challenge and may result in significant organ damage if not treated successfully.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Casian A (2011) Plasma exchange for severe renal vasculitis: long-term follow-up of the MEPEX trial. Clin Exp Immunol 164(Suppl1):52

    Google Scholar 

  2. Lyons P, Rayner T, Trivedi S et al (2012) Genetically distinct subsets in AAV. N Engl J Med 367:214–223

    Article  PubMed  CAS  Google Scholar 

  3. Arning L, Holle JU, Harper L et al (2011) Are there specific genetic risk factors for the different forms of ANCA-associated vasculitis? Ann Rheum Dis 70:707–708

    Article  PubMed  Google Scholar 

  4. Besada E, Bader L, Nossent H (2011) Sustained hypogammaglobulinemia under rituximab maintenance therapy could increase the risk for serious infections: a report of two cases. Rheumatol Int [Epub ahead of print]

  5. Clowse ME, Copland SC, Hsieh TC et al (2011) Ovarian reserve diminished by oral cyclophosphamide therapy for granulomatosis with polyangiitis (Wegener’s). Arthritis Care Res (Hoboken) 63:1777–1781

    Article  Google Scholar 

  6. Eriksson P, Jacobsson L, Lindell A et al (2009) Improved outcome in Wegener’s granulomatosis and microscopic polyangiitis? A retrospective analysis of 95 cases in two cohorts. J Intern Med 265:496–506

    Article  PubMed  CAS  Google Scholar 

  7. Falk RJ, Gross WL, Guillevin L et al (2011) Granulomatosis with polyangiitis (Wegener’s): an alternative name for Wegener’s granulomatosis. Ann Rheum Dis 70:704

    Article  PubMed  Google Scholar 

  8. Faurschou M, Sorensen IJ, Mellemkjaer L et al (2008) Malignancies in Wegener’s granulomatosis: incidence and relation to cyclophosphamide therapy in a cohort of 293 patients. J Rheumatol 35:100–105

    PubMed  CAS  Google Scholar 

  9. Fujimoto S, Watts RA, Kobayashi S et al (2011) Comparison of the epidemiology of anti-neutrophil cytoplasmic antibody-associated vasculitis between Japan and the U.K. Rheumatology (Oxford) 50:1916–1920

  10. Heckmann M, Holle JU, Arning L et al (2008) The Wegener’s granulomatosis quantitative trait locus on chromosome 6p21.3 as characterised by tagSNP genotyping. Ann Rheum Dis 67:972–979

    Article  PubMed  CAS  Google Scholar 

  11. Heijl C, Harper L, Flossmann O et al (2011) Incidence of malignancy in patients treated for antineutrophil cytoplasm antibody-associated vasculitis: follow-up data from European Vasculitis Study Group clinical trials. Ann Rheum Dis 70:1415–1421

    Article  PubMed  CAS  Google Scholar 

  12. Hellmich B, Flossmann O, Gross WL et al (2007) EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis. Ann Rheum Dis 66:605–617

    Article  PubMed  CAS  Google Scholar 

  13. Hiemstra TF, Walsh M, Mahr A et al (2010) Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA 304:2381–2388

    Article  PubMed  CAS  Google Scholar 

  14. Holle JU, Dubrau C, Herlyn K et al (2012) Rituximab for refractory granulomatosis with polyangiitis (Wegener’s granulomatosis): comparison of efficacy in granulomatous versus vasculitic manifestations. Ann Rheum Dis 71:327–333

    Article  PubMed  CAS  Google Scholar 

  15. Holle JU, Gross WL, Holl-Ulrich K et al (2010) Prospective long-term follow-up of patients with localised Wegener’s granulomatosis: Does it occur as persistent disease stage? Ann Rheum Dis 69:1934–1939

    Article  PubMed  Google Scholar 

  16. Holle JU, Gross WL, Latza U et al (2011) Improved outcome in 445 patients with Wegener’s granulomatosis in a German vasculitis center over four decades. Arthritis Rheum 63:257–266

    Article  PubMed  Google Scholar 

  17. Jayne DR, Chapel H, Adu D et al (2000) Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity. QJM 93:433–439

    Article  PubMed  CAS  Google Scholar 

  18. Jones RB, Ferraro AJ, Chaudhry AN et al (2009) A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 60:2156–2168

    Article  PubMed  CAS  Google Scholar 

  19. Jones RB, Tervaert JW, Hauser T et al (2010) Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 363:211–220

    Article  PubMed  CAS  Google Scholar 

  20. Kain R, Exner M, Brandes R et al (2008) Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. Nat Med 14:1088–1096

    Article  PubMed  CAS  Google Scholar 

  21. Kesel N, Kohler D, Herich L et al (2012) Cartilage destruction in granulomatosis with polyangiitis (Wegener’s granulomatosis) is mediated by human fibroblasts after transplantation into immunodeficient mice. Am J Pathol

  22. Kessenbrock K, Krumbholz M, Schonermarck U et al (2009) Netting neutrophils in autoimmune small-vessel vasculitis. Nat Med 15:623–625

    Article  PubMed  CAS  Google Scholar 

  23. Little MA, Al-Ani B, Ren S et al (2012) Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system. PloS one 7:e28626

    Article  PubMed  CAS  Google Scholar 

  24. Little MA, Nightingale P, Verburgh CA et al (2010) Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis. Ann Rheum Dis 69:1036–1043

    Article  PubMed  Google Scholar 

  25. Mahr AD, Edberg JC, Stone JH et al (2010) Alpha-antitrypsin deficiency-related alleles Z and S and the risk of Wegener’s granulomatosis. Arthritis Rheum 62:3760–3767

    Article  PubMed  CAS  Google Scholar 

  26. McKinney EF, Lyons PA, Carr EJ et al (2010) A CD8+ T cell transcription signature predicts prognosis in autoimmune disease. Nat Med 16:586–591 (581p following 591)

    Article  PubMed  CAS  Google Scholar 

  27. Mukhtyar C, Guillevin L, Cid MC et al (2009) EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis 68:310–317

    Article  PubMed  CAS  Google Scholar 

  28. Reinhold-Keller E, Herlyn K, Wagner-Bastmeyer R et al (2005) Stable incidence of primary systemic vasculitides over five years: results from the German Vasculitis Register. Arthritis Rheum 53:93–99

    Article  PubMed  Google Scholar 

  29. Roth AJ, Brown MC, Smith RN et al (2012) Anti-LAMP-2 antibodies are not prevalent in patients with antineutrophil cytoplasmic autoantibody glomerulonephritis. J Am Soc Nephrol 23:545–555

    Article  PubMed  CAS  Google Scholar 

  30. Seo P, Min YI, Holbrook JT et al (2005) Damage caused by Wegener’s granulomatosis and its treatment: prospective data from the Wegener’s Granulomatosis Etanercept Trial (WGET). Arthritis Rheum 52:2168–2178

    Article  PubMed  CAS  Google Scholar 

  31. Stone JH, Merkel PA, Spiera R et al (2010) Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 363:221–232

    Article  PubMed  CAS  Google Scholar 

  32. Stratta P, Marcuccio C, Campo A et al (2008) Improvement in relative survival of patients with vasculitis: study of 101 cases compared to the general population. Int J Immunopathol Pharmacol 21:631–642

    PubMed  CAS  Google Scholar 

  33. Tesfa D, Ajeganova S, Hagglund H et al (2011) Late-onset neutropenia following rituximab therapy in rheumatic diseases: association with B lymphocyte depletion and infections. Arthritis Rheum 63:2209–2214

    Article  PubMed  CAS  Google Scholar 

  34. Walsh M, Catapano F, Szpirt W et al (2011) Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: a meta-analysis. Am J Kidney Dis 57:566–574

    Article  PubMed  Google Scholar 

  35. Walsh M, Flossmann O, Berden A et al (2012) Risk factors for relapse of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 64:542–548

    Article  PubMed  CAS  Google Scholar 

  36. Westman KW, Bygren PG, Olsson H et al (1998) Relapse rate, renal survival, and cancer morbidity in patients with Wegener’s granulomatosis or microscopic polyangiitis with renal involvement. J Am Soc Nephrol 9:842–852

    PubMed  CAS  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor gibt für sich und seine Koautoren an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J.U. Holle.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Holle, J., Reinhold-Keller, E. & Gross, W. Update Granulomatose mit Polyangiitis (GPA, Wegener-Granulomatose). Z. Rheumatol. 71, 745–753 (2012). https://doi.org/10.1007/s00393-012-0982-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00393-012-0982-z

Schlüsselwörter

Keywords

Navigation