Dtsch Med Wochenschr 2017; 142(01): 24-31
DOI: 10.1055/s-0042-111610
Dossier
© Georg Thieme Verlag KG Stuttgart · New York

Granulomatose mit Polyangiitis

Granulomatosis with polyangiitis
Anja Kerstein
,
Konstanze Holl-Ulrich
,
Antje Müller
,
Gabriela Riemekasten
,
Peter Lamprecht
Further Information

Publication History

Publication Date:
05 January 2017 (online)

Abstract

Granulomatosis with polyangiitis (GPA) is a potentially life-threatening, rare disease. The etiology is unknown. GPA is histomorphologically characterized by extravascular necrotizing granulomatous inflammation and a systemic necrotizing vasculitis of small to medium-sized vessels. Clinically, a pulmonary-renal syndrome with pulmonary infiltrates, alveolar hemorrhage and a rapidly progressive glomerulonephritis is seen in about 80% of the cases with generalized disease. GPA is associated with proteinase 3-specific anti-neutrophil cytoplasmic autoantibodies (PR3-ANCA). Treatment is guided by severity of organ involvement and disease activity. Cytostatic immunosuppressants or the monoclonal anti-CD20 antibody rituximab are applied.

Teaser

Die Granulomatose mit Polyangiitis (GPA) ist eine seltene Erkrankung ungeklärter Ätiologie, die lebensbedrohlich verlaufen kann. Bei der immunsuppressiven Therapie sind jedoch in den letzten Jahren deutliche Fortschritte zu verzeichnen. Der Beitrag schildert die wichtigsten Erkenntnisse zu Pathogenese und Histomorphologie und fasst die aktuellen Empfehlungen zu Diagnostik und Therapie zusammen.

 
  • 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
  • 2 Csernok E. Lamprecht P. Gross WL. Diagnostic significance of ANCA in vasculitis. Nat Clin Pract Rheumatol 2006; 2: 174-175
  • 3 Holl-Ulrich K. Histopathologie systemischer Vaskulitiden. Pathologe 2010; 31: 67-76
  • 4 Jennette JC. Falk RJ. Hu P. et al. Pathogenesis of antineutrophil cytoplasmic autoantibody-associate small-vessel vasculitis. Annu Rev Pathol 2013; 8: 139-160
  • 5 Kallenberg CG. Key advances in the clinical approach to ANCA-associated vasculitis. Nat Rev Rheumatol 2014; 10: 484-493
  • 6 Luqmani R. Suppiah R. Edwards CJ. et al. Mortality in Wegener’s granulomatosis: a bimodal pattern. Rheumatology (Oxford) 2011; 50: 697-702
  • 7 Herlyn K. Buckert F. Gross WL. et al. Doubled prevalence rates of ANCA-associated vasculitides and giant cell arteritis between 1994 and 2006 in northern Germany. Rheumatology (Oxford) 2014; 53: 882-889
  • 8 Ntatsaki E. Watts RA. Scott DG. Epidemiology of ANCA-associated vasculitis. Rheum Dis Clin North Am 2010; 36: 447-461
  • 9 Fujimoto S. Watts RA. Kobayashi S. et al. Comparison of the epidemiology of anti-neutrophil cytoplasmic antibody-associated vasculitis between Japan and the U. K Rheumatology (Oxford) 2011; 50: 1916-1920
  • 10 Jagiello P. Aries P. Arning L. et al. The PTPN22 620W allele is a risk factor for Wegener’s granulomatosis. Arthritis Rheum 2005; 52: 4039-4043
  • 11 Cao Y. Yang J. Colby K. et al. High basal activity of the PTPN22 gain-of-function variant blunts leukocyte responsiveness negatively affecting IL-10 production in ANCA vasculitis. PLoS One 2012; 7: e42783
  • 12 Heckmann M. Holle JU. Arning L. et al. The Wegener’s granulomatosis quantitative trait locus on chromosome 6p21.3 as characterised by tagSNP genotyping. Ann Rheum Dis 2008; 67: 972-979
  • 13 Lyons PA. Rayner TF. Trivedi S. et al. Genetically distinct subsets within ANCA-associated vasculitis. N Engl J Med 2012; 367: 214-223
  • 14 Clayton GM. Wang Y. Crawford F. et al. Structural basis of chronic beryllium disease: linking allergic hypersensitivity and autoimmunity. Cell 2014; 158: 132-142
  • 15 Gómez-Puerta JA. Gedmintas L. Costenbader KH. The association between silica exposure and development of ANCA-associated vasculitis: systematic review and meta-analysis. Autoimmun Rev 2013; 12: 1129-1135
  • 16 Stegeman CA. Tervaert JW. Sluiter WJ. et al. Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis. Ann Intern Med 1994; 120: 12-17
  • 17 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 (01) 51-55
  • 18 Lidar M. Lipschitz N. Langevitz P. et al. Infectious serologies and autoantibodies in Wegener’s granulomatosis and other vasculitides: novel associations disclosed using the Rad BioPlex 2200. Ann N Y Acad Sci 2009; 1173: 649-657
  • 19 Morgan MD. Pachnio A. Begum J. et al. CD4+CD28- T cell expansion in granulomatosis with polyangiitis (Wegener’s) is driven by latent cytomegalovirus infection and is associated with an increased risk of infection and mortality. Arthritis Rheum 2011; 63: 2127-2137
  • 20 Fagin U. Pitann S. Gross WL. et al. Flow cytometric characterization of “early” and “late differentiated” T-cells including PR3-specific cells in granulomatosis with polyangiitis (Wegener’s). Cytometry B Clin Cytom 2012; 82: 173-175
  • 21 Kerstein A. Schüler S. Cabral-Marques O. et al. Multiple factors drive alterations of the total T-cell compartment in granulomatosis with polyangiitis. 44. Kongress der Deutschen Gesellschaft für Rheumatologie. 2016 Abstract 16176
  • 22 Hoffman GS. Kerr GS. Leavitt RY. et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 1992; 116: 488-498
  • 23 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
  • 24 Hellmich B. Flossmann O. Gross WL. et al. EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis. Ann Rheum Dis 2007; 66: 605-617
  • 25 Ullrich S. Gustke H. Lamprecht P. et al. Severe impaired respiratory ciliary function in Wegener granulomatosis. Ann Rheum Dis 2009; 68: 1067-1071
  • 26 Hui Y. Wohlers J. Podschun R. et al. Antimicrobial peptides in nasal secretion and mucosa with respect to S. aureus colonisation in Wegener’s granulomatosis. Clin Exp Rheumatol 2011; 29 (01) S49-S56
  • 27 Laudien M. Häsler R. Wohlers J. et al. Molecular signatures of a disturbed nasal barrier function in the primary tissue of Wegener’s granulomatosis. Mucosal Immunol 2011; 4: 564-573
  • 28 Kerstein A. Müller A. Holl-Ulrich K. et al. High-mobility group box 1 (HMGB1) as a link between the granulomatous inflammation and the induction of autoreactivity in granulomatosis with polyangiitis. Nephron 2015; 129 (Suppl. 02) 205
  • 29 Millet A. Martin KR. Bonnefoy F. et al. Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis. J Clin Invest 2015; 125: 4107-4421
  • 30 Mueller A. Brieske C. Schinke S. et al. Plasma cells within granulomatous inflammation display signs pointing towards autoreactivity and destruction in granulomatosis with polyangiitis. Arthritis Res Ther 2014; 16: R55
  • 31 Little MA. Al-Ani B. Ren S. et al. Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system. PLoS One 2012; 7: e28626
  • 32 Hilhorst M. van Paassen P. van Rie H. et al. Complement in ANCA-associated glomerulonephritis. Nephrol Dial Transplant 2015; pii: gfv288 [Epub ahead of print]
  • 33 Kessenbrock K. Krumbholz M. Schönermarck U. et al. Netting neutrophils in autoimmune small-vessel vasculitis. Nat Med 2009; 15: 623-625
  • 34 Söderberg D. Segelmark M. Neutrophil Extracellular Traps in ANCA-Associated Vasculitis. Front Immunol 2016; 7: 256
  • 35 Kradin RL. Mark EJ. Case records of the Massachusetts General Hospital: Weekly clnicopathological exercises. Case 18-2002, A 48-year-old man with a cough and bloody sputum. New Engl J Med 2002; 346: 1892-1899
  • 36 Holl-Ulrich K. Rose C. Nichtinfektiöse granulomatöse Entzündungen. Schwerpunkt Lunge und Haut. Pathologe 2016; 37: 172-182
  • 37 Kesel N. Köhler D. Herich L. et al. Cartilage destruction in granulomatosis with polyangiitis (Wegener's granulomatosis) is mediated by human fibroblasts after transplantation into immunodeficient mice. Am J Pathol 2012; 180: 2144-2155
  • 38 Harper L. Savage CO. Pathogenesis of ANCA-associated systemic vasculitis. J Pathol 2000; 190: 349-359
  • 39 Berden AE. Ferrario F. Hagen EC. et al. Histopathologic classification of ANCA-associated glomerulonephritis. J Am Soc Nephrol 2010; 21: 1628-1636
  • 40 Berden AE. Jones RB. Erasmus DD. et al. Tubular lesions predict renal outcome in antineutrophil cytoplasmic antibody-associated glomerulonephritis after rituximab therapy. J Am Soc Nephrol 2012; 23: 313-321
  • 41 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
  • 42 Schirmer JH. Wright MN. Herrmann K. et al. Myeloperoxidase-ANCA associated Granulomatosis with polyangiitis is a clinically distinct subset within ANCA-associated vasculitis. Arthritis Rheumatol 2016; DOI: 10.1002/art.39786. [Epub ahead of print]
  • 43 Miloslavsky EM. Lu N. Unizony S. et al. Myeloperoxidase-ANCA-Positive and ANCA-Negative Patients With Granulomatosis With Polyangiitis: Distinct Patient Subsets. Arthritis Rheumatol 2016; DOI: 10.1002/art.39812. [Epub ahead of print]
  • 44 Cornec D. Gall EC. Fervenza FC. et al. ANCA-associated vasculitis – clinical utility of using ANCA specificity to classify patients. Nat Rev Rheumatol 2016; DOI: 10.1038/nrrheum.2016.123. [Epub ahead of print]
  • 45 Suppiah R. Mukhtyar C. Flossmann O. et al. A cross-sectional study of the Birmingham Vasculitis Activity Score version 3 in systemic vasculitis. Rheumatology (Oxford) 2011; 50: 899-905
  • 46 Damoiseaux J. Csernok E. Rasmussen N. et al. Detection of antineutrophil cytoplasmic antibodies (ANCAs): a multicentre European Vasculitis Study Group (EUVAS) evaluation of the value of indirect immunofluorescence (IIF) versus antigen-specific immunoassays. Ann Rheum Dis 2016; pii: annrheumdis-2016-209507 DOI: 10.1136/annrheumdis-2016-209507.
  • 47 Yates M. Watts RA. Bajema IM. et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis 2016; 75: 1583-1594
  • 48 Walsh M. Casian A. Flossmann O. et al. Long-term follow-up of patients with severe ANCA-associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear. Kidney Int 2013; 84: 397-402
  • 49 Cartin-Ceba R. Diaz-Caballero L. Al-Qadi MO. et al. Diffuse Alveolar Hemorrhage Secondary to Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Predictors of Respiratory Failure and Clinical Outcomes. Arthritis Rheumatol 2016; 68: 1467-1476