Download PDF
Aktuelle Rheumatologie 2023; 48(01): 60-69
DOI: 10.1055/a-1963-7586
Übersichtsarbeit

Granulomatose mit Polyangiitis und mikroskopische Polyangiitis

Granulomatosis with Polyangiitis and Microscopic Polyangiitis
Sebastian Klapa
1   Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany
,
Sabrina Arnold
1   Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany
,
Peter Lamprecht
1   Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Zusammenfassung

Die Granulomatose mit Polyangiitis (GPA) und mikroskopische Polyangiitis (MPA) sind zwei zur ANCA-assoziierten Vaskulitis (AAV) zählende Entitäten. Beiden Erkrankungen liegt eine systemische nekrotisierende Kleingefäßvaskulitis zugrunde, die jedes Organ betreffen kann. Bei der GPA ist zusätzlich eine in der Regel den Respirationstrakt betreffende extravaskuläre nekrotisierende granulomatöse Entzündung vorzufinden. Das klinische Bild wird in der Mehrzahl der Fälle durch ein pulmo-renales Syndrom mit alveolärer Hämorrhagie und rapid-progressiver Glomerulonephritis sowie weitere Organmanifestationen bestimmt. Bei der GPA imponiert zudem die fast regelhafte Mitbeteiligung des oberen Respirationstrakts. Die GPA ist mit Anti-Neutrophilen zytoplasmatischen Autoantikörpern (ANCA) mit einer Spezifität für die Proteinase 3 (PR3-ANCA) und die MPA für Myeloperoxidase (MPO-ANCA) assoziiert. Die immunsuppressive Therapie richtet sich nach der Krankheitsaktivität und Schwere der Organbeteiligung.

Abstract

Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are two entities of ANCA-associated vasculitis (AAV). Both diseases are characterised by systemic necrotising small-vessel vasculitis, which can affect any organ. In GPA, extravascular necrotising granulomatous inflammation, usually affecting the respiratory tract, is found in addition. In the majority of cases, the clinical presentation is dominated by a pulmonary-renal syndrome with alveolar haemorrhage and rapidly progressive glomerulonephritis. Other organ involvement is found as well. In GPA, the upper respiratory tract is commonly affected. GPA is associated with anti-neutrophil cytoplasmic autoantibodies (ANCA) with specificity for proteinase 3 (PR3-ANCA) and MPA with specificity for myeloperoxidase (MPO-ANCA). Immunosuppressive therapy depends on disease activity and the severity of organ involvement.

Schlüsselwörter

ANCA - Vaskulitis - AAV - Granulomatose mit Polyangiitis - Mikroskopische Polyangiitis

Key words

ANCA - AAV - vasculitis - granulomatosis with polyangiitis - microscopic polyangiitis


Publication History

Article published online:
21 November 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • Literatur

  • 1 Jennette JC, Falk RJ, Bacon PA. et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013; 65: 1-11
    CrossrefPubMedSearch in Google Scholar
  • 2 Lamprecht P, Kerstein A, Klapa S. et al. Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides. Front Immunol 2018; 9: 680
    CrossrefPubMedSearch in Google Scholar
  • 3 Kitching AR, Anders HJ, Basu N. et al. ANCA-associated vasculitis. Nat Rev Dis Primers 2020; 6: 71
    CrossrefPubMedSearch in Google Scholar
  • 4 Hellmich B. Update of the EULAR recommendations on the management of ANCA-associated vasculitis. EULAR recommendations session. EULAR 2022 congress; Copenhagen: 01.06.2022
  • 5 Mahr A, Specks U, Jayne D. Subclassifying ANCA-associated vasculitis: a unifying view of disease spectrum. Rheumatology (Oxford) 2019; 58: 1707-1709
    CrossrefPubMedSearch in Google Scholar
  • 6 Lamprecht P, Müller A, Witko-Sarsat V. et al. Comment on: Subclassifying ANCA-associated vasculitis: a unifying view of disease spectrum. Rheumatology (Oxford) 2020; 59: 1185-1187
    CrossrefPubMedSearch in Google Scholar
  • 7 Banerjee S, Grayson PC. Vasculitis Around the World: Epidemiologic Insights into Causality and a Need for Global Partnerships. J Rheumatol 2017; 44: 136-139
    CrossrefPubMedSearch in Google Scholar
  • 8 Hellmich B, Lamprecht P, Spearpoint P. et al. New insights into the epidemiology of ANCA-associated vasculitides in Germany: results from a claims data study. Rheumatology (Oxford) 2021; 60: 4868-4873
    CrossrefPubMedSearch in Google Scholar
  • 9 Walton EW. Giant-cell granuloma of the respiratory tract (Wegener's granulomatosis). Br Med J 1958; 2: 265-270
    CrossrefPubMedSearch in Google Scholar
  • 10 Flossmann O, Berden A, de Groot K. et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis 2011; 70: 488-494
    CrossrefPubMedSearch in Google Scholar
  • 11 Tan JA, Dehghan N, Chen W. et al. Mortality in ANCA-associated vasculitis: a meta-analysis of observational studies. Ann Rheum Dis 2017; 76: 1566-1574
    CrossrefPubMedSearch in Google Scholar
  • 12 Müller A, Krause B, Kerstein-Stähle A. et al. Granulomatous Inflammation in ANCA-Associated Vasculitis. Int J Mol Sci 2021; 22: 6474
    CrossrefPubMedSearch in Google Scholar
  • 13 Arnold S, Holl-Ulrich K, Müller A. et al. Update Ätiopathogenese der Kleingefäßvaskulitis. Z Rheumatol 2022; 81: 270-279
    CrossrefPubMedSearch in Google Scholar
  • 14 Arnold S, Klapa S, Holl-Ulrich K. et al. Granulomatöse Vaskulitiden und Vaskulitiden mit extravaskulärer Granulomatose. Z Rheumatol 2022; 10
    CrossrefPubMedSearch in Google Scholar
  • 15 Rahmattulla C, Mooyaart AL, van Hooven D. et al. Genetic variants in ANCA-associated vasculitis: a meta-analysis. Ann Rheum Dis 2016; 75: 1687-1692
    CrossrefPubMedSearch in Google Scholar
  • 16 Jones BE, Yang J, Muthigi A. et al. Gene-Specific DNA Methylation Changes Predict Remission in Patients with ANCA-Associated Vasculitis. J Am Soc Nephrol 2017; 28: 1175-1187
    CrossrefPubMedSearch in Google Scholar
  • 17 Millet A, Martin KR, Bonnefoy F. et al. Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis. J Clin Invest 2015; 125: 4107-4121
    CrossrefPubMedSearch in Google Scholar
  • 18 Jennette JC, Falk RJ. Pathogenesis of antineutrophil cytoplasmic autoantibody-mediated disease. Nat Rev Rheumatol 2014; 10: 463-473
    CrossrefPubMedSearch in Google Scholar
  • 19 Everts-Graber J, Martin KR, Thieblemont N. et al. Proteomic analysis of neutrophils in ANCA-associated vasculitis reveals a dysregulation in proteinase 3-associated proteins such as annexin-A1 involved in apoptotic cell clearance. Kidney Int 2019; 96: 397-408
    CrossrefPubMedSearch in Google Scholar
  • 20 Rovere-Querini P, Capobianco A, Scaffidi P. et al. HMGB1 is an endogenous immune adjuvant released by necrotic cells. EMBO Rep 2004; 5: 825-830
    CrossrefPubMedSearch in Google Scholar
  • 21 Muñoz LE, Lauber K, Schiller M. et al. The role of defective clearance of apoptotic cells in systemic autoimmunity. Nat Rev Rheumatol 2010; 6: 280-289
    CrossrefPubMedSearch in Google Scholar
  • 22 Schreiber A, Rousselle A, Becker JU. et al. Necroptosis controls NET generation and mediates complement activation, endothelial damage, and autoimmune vasculitis. Proc Natl Acad Sci U S A 2017; 114: E9618-E9625
    CrossrefPubMedSearch in Google Scholar
  • 23 Weppner G, Ohlei O, Hammers CM. et al. In situ detection of PR3-ANCA+B cells and alterations in the variable region of immunoglobulin genes support a role of inflamed tissue in the emergence of auto-reactivity in granulomatosis with polyangiitis. J Autoimmun 2018; 93: 89-103
    CrossrefPubMedSearch in Google Scholar
  • 24 Salama AD, Little MA. Animal models of antineutrophil cytoplasm antibody-associated vasculitis. Curr Opin Rheumatol 2012; 24: 1-7
    CrossrefPubMedSearch in Google Scholar
  • 25 Lamprecht P, Fischer N, Huang J. et al. Changes in the composition of the upper respiratory tract microbial community in granulomatosis with polyangiitis. J Autoimmun 2019; 97: 29-39
    CrossrefPubMedSearch in Google Scholar
  • 26 Laudien M, Gadola SD, Podschun R. et al. Nasal carriage of Staphylococcus aureus and endonasal activity in Wegener s granulomatosis as compared to rheumatoid arthritis and chronic Rhinosinusitis with nasal polyps. Clin Exp Rheumatol. 2010; 28: 51-55
    PubMedSearch in Google Scholar
  • 27 Holle JU, Gross WL, Latza U. et al. Improved outcome in 445 patients with Wegener's granulomatosis in a German vasculitis center over four decades. Arthritis Rheum 2011; 63: 257-266
    CrossrefPubMedSearch in Google Scholar
  • 28 Schirmer JH, Wright MN, Vonthein R. et al. Clinical presentation and long-term outcome of 144 patients with microscopic polyangiitis in a monocentric German cohort. Rheumatology (Oxford) 2016; 55: 71-79
    CrossrefPubMedSearch in Google Scholar
  • 29 Holle JU, Gross WL, Holl-Ulrich K. et al. Prospective long-term follow-up of patients with localised Wegener's granulomatosis: does it occur as persistent disease stage?. Ann Rheum Dis 2010; 69: 1934-1939
    CrossrefPubMedSearch in Google Scholar
  • 30 Holl-Ulrich K. Histopathologie systemischer Vaskulitiden. Pathologe 2010; 31: 67-76
    CrossrefPubMedSearch in Google Scholar
  • 31 Specks U, Merkel PA, Seo P. et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med 2013; 369: 417-427
    CrossrefPubMedSearch in Google Scholar
  • 32 Luqmani RA. Disease assessment in systemic vasculitis. Nephrol Dial Transplant 2015; 30: i76-i82
    CrossrefPubMedSearch in Google Scholar
  • 33 Bossuyt X, Cohen Tervaert JW, Arimura Y. et al. Position paper: Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis. Nat Rev Rheumatol 2017; 13: 683-692
    CrossrefPubMedSearch in Google Scholar
  • 34 Rovin BH, Adler SG, Barratt J. et al. Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. Kidney Int 2021; 100: 753-779
    CrossrefPubMedSearch in Google Scholar
  • 35 Brix SR, Noriega M, Tennstedt P. et al. Development and validation of a renal risk score in ANCA-associated glomerulonephritis. Kidney Int 2018; 94: 1177-1188
    CrossrefPubMedSearch in Google Scholar
  • 36 Kronbichler A, Jayne DRW. ANCA Renal Risk Score: is prediction of end-stage renal disease at baseline possible?. Kidney Int 2018; 94: 1045-1047
    CrossrefPubMedSearch in Google Scholar
  • 37 Robson JC, Grayson PC, Ponte C. et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for granulomatosis with polyangiitis. Ann Rheum Dis 2022; 81: 315-320
    CrossrefPubMedSearch in Google Scholar
  • 38 Suppiah R, Robson JC, Grayson PC. et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis. Ann Rheum Dis 2022; 81: 321-326
    CrossrefPubMedSearch in Google Scholar
  • 39 Mukhtyar C, Lee R, Brown D. et al. Modification and validation of the Birmingham Vasculitis Activity Score (version 3). Ann Rheum Dis 2009; 68: 1827-1832
    CrossrefPubMedSearch in Google Scholar
  • 40 DeRemee RA, McDonald TJ, Harrison EG. et al. Wegener's granulomatosis. Anatomic correlates, a proposed classification. Mayo Clin Proc 1976; 51: 777-781
    PubMedSearch in Google Scholar
  • 41 de Groot K, Gross WL, Herlyn K. et al. Development and validation of a disease extent index for Wegener's granulomatosis. Clin Nephrol 2001; 55: 31-38
    PubMedSearch in Google Scholar
  • 42 Exley AR, Bacon PA, Luqmani RA. et al. Development and initial validation of the Vasculitis Damage Index for the standardized clinical assessment of damage in the systemic vasculitides. Arthritis Rheum 1997; 40: 371-380
    CrossrefPubMedSearch in Google Scholar
  • 43 Jones RB, Tervaert JW, Hauser T. et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 2010; 363: 211-220
    CrossrefPubMedSearch in Google Scholar
  • 44 Stone JH, Merkel PA, Spiera R. et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 2010; 363: 221-232
    CrossrefPubMedSearch in Google Scholar
  • 45 McAdoo SP, Medjeral-Thomas N, Gopaluni S. et al. Long-term follow-up of a combined rituximab and cyclophosphamide regimen in renal anti-neutrophil cytoplasm antibody-associated vasculitis. Nephrol Dial Transplant 2019; 34: 63-73
    CrossrefPubMedSearch in Google Scholar
  • 46 Schinke S, Riemekasten G, Lamprecht P. Therapiedeeskalation bei ANCA-assoziierten Vaskulitiden. Z Rheumatol 2017; 76: 15-20
    CrossrefPubMedSearch in Google Scholar
  • 47 Walsh M, Merkel PA, Peh CA. et al. Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis. N Engl J Med 2020; 382: 622-631
    CrossrefPubMedSearch in Google Scholar
  • 48 Smith RM, Jones RB, Specks U. et al. Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis. Ann Rheum Dis 2020; 79: 1243-1249
    CrossrefPubMedSearch in Google Scholar
  • 49 Chung SA, Langford CA, Maz M. et al. 2021; American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Rheumatol. 2021 Aug 73: 1366-1383
    CrossrefPubMedSearch in Google Scholar
  • 50 Casal Moura M, Irazabal MV, Eirin A. et al. Efficacy of Rituximab and Plasma Exchange in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Severe Kidney Disease. J Am Soc Nephrol 2020; 31: 2688-2704
    CrossrefPubMedSearch in Google Scholar
  • 51 Walsh M, Collister D, Zeng L. et al. The effects of plasma exchange in patients with ANCA-associated vasculitis: an updated systematic review and meta-analysis. BMJ 2022; 376: e064604
    CrossrefPubMedSearch in Google Scholar
  • 52 Jayne DRW, Merkel PA, Schall TJ. et al. Avacopan for the Treatment of ANCA-Associated Vasculitis. N Engl J Med 2021; 384: 599-609
    CrossrefPubMedSearch in Google Scholar
  • 53 De Groot K, Rasmussen N, Bacon PA. et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2005; 52: 2461-2469
    CrossrefPubMedSearch in Google Scholar
  • 54 Guillevin L, Pagnoux C, Karras A. et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med 2014; 371: 1771-1780
    CrossrefPubMedSearch in Google Scholar
  • 55 Charles P, Terrier B, Perrodeau É. et al. Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2). Ann Rheum Dis 2019; 78: e101
    CrossrefPubMedSearch in Google Scholar
  • 56 Cornec D, Berti A, Hummel A. et al. Identification and phenotyping of circulating autoreactive proteinase 3-specific B cells in patients with PR3-ANCA associated vasculitis and healthy controls. J Autoimmun 2017; 84: 122-131
    CrossrefPubMedSearch in Google Scholar
  • 57 Charles P, Perrodeau É, Samson M. et al. Long-Term Rituximab Use to Maintain Remission of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Randomized Trial. Ann Intern Med 2020; 173: 179-187
    CrossrefPubMedSearch in Google Scholar
  • 58 Schirmer JH, Aries PM, de Groot K. et al. S1-Leitlinie Diagnostik und Therapie der ANCA-assoziierten Vaskulitiden. Z Rheumatol 2017; 76: 77-104
    CrossrefPubMedSearch in Google Scholar