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Granulomatosis with Polyangiitis

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Anti-Neutrophil Cytoplasmic Antibody (ANCA) Associated Vasculitis

Part of the book series: Rare Diseases of the Immune System ((RDIS))

Abstract

Granulomatosis with polyangiitis (GPA) is a small-vessel necrotizing vasculitis that most characteristically affects the ear, nose, and throat (ENT), lungs, and/or kidneys. The median age at diagnosis is in the fifth decade, but children and older people can be affected. GPA origin remains unknown, although knowledge of the main pathogenic mechanisms has greatly improved, particularly since the discovery of antineutrophil cytoplasmic antibodies (ANCA) in 1985. GPA is typically associated with the presence in serum of these autoantibodies, mainly cANCA by indirect immunofluorescence, directed against proteinase 3 (PR3) on ELISA. However, some patients are ANCA-negative, especially those with “limited” disease forms, and some are positive for pANCA, directed against myeloperoxidase (MPO) on ELISA. In the mid-1950s, the median survival of GPA patients was only 5 months, with 82% of deaths occurring within 1 year of the first symptoms. With current treatments, which include first an induction phase, based on the combination of corticosteroids and an immunosuppressant, then a maintenance treatment phase, remission can be achieved in more than 80% of cases. However, the relapse-free survival rate does not exceed 42–57% at 5 years with conventional maintenance treatments, whose optimal duration is still unclear. Biological marker(s) to reliably monitor disease activity and predict outcomes may finally be identified, and new potential therapeutic targets are being developed at an increasing pace.

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References

  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.

    Article  CAS  PubMed  Google Scholar 

  2. Jennette JC, Falk RJ, Andrassy K, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum. 1994;37:187–92.

    Article  CAS  PubMed  Google Scholar 

  3. Mohammad AJ, Jacobsson LT, Westman KW, Sturfelt G, Segelmark M. Incidence and survival rates in Wegener’s granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and polyarteritis nodosa. Rheumatology (Oxford). 2009;48:1560–5.

    Article  Google Scholar 

  4. Watts RA, Mahr A, Mohammad AJ, Gatenby P, Basu N, Flores-Suarez LF. Classification, epidemiology and clinical subgrouping of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Nephrol Dial Transplant. 2015;30(Suppl 1):i14–22.

    Article  CAS  PubMed  Google Scholar 

  5. Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992;116:488–98.

    Article  CAS  PubMed  Google Scholar 

  6. 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;63:257–66.

    Article  PubMed  Google Scholar 

  7. Jennette JC, Falk RJ, Gasim AH. Pathogenesis of antineutrophil cytoplasmic autoantibody vasculitis. Curr Opin Nephrol Hypertens. 2011;20:263–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Walton EW. Giant-cell granuloma of the respiratory tract (Wegener’s granulomatosis). Br Med J. 1958;2:265–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wallace ZS, Lu N, Unizony S, Stone JH, Choi HK. Improved survival in granulomatosis with polyangiitis: a general population-based study. Semin Arthritis Rheum. 2016;45:483–9.

    Article  PubMed  Google Scholar 

  10. Flossmann O, Berden A, de Groot K, et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis. 2011;70:488–94.

    Article  PubMed  Google Scholar 

  11. Yates M, Watts RA, Bajema IM, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016;75:1583–94.

    Article  CAS  PubMed  Google Scholar 

  12. McGeoch L, Twilt M, Famorca L, et al. CanVasc Recommendations for the Management of Antineutrophil Cytoplasm Antibody-associated Vasculitides. J Rheumatol. 2016;43:97–120.

    Article  CAS  PubMed  Google Scholar 

  13. Mahr AD. Epidemiological features of Wegener’s granulomatosis and microscopic polyangiitis: two diseases or one ‘anti-neutrophil cytoplasm antibodies-associated vasculitis’ entity? APMIS Suppl. 2009;(127):41–7.

    Article  Google Scholar 

  14. Mohammad AJ, Jacobsson LT, Mahr AD, Sturfelt G, Segelmark M. Prevalence of Wegener’s granulomatosis, microscopic polyangiitis, polyarteritis nodosa and Churg-Strauss syndrome within a defined population in southern Sweden. Rheumatology (Oxford). 2007;46:1329–37.

    Article  CAS  Google Scholar 

  15. Abdou NI, Kullman GJ, Hoffman GS, et al. Wegener’s granulomatosis: survey of 701 patients in North America. Changes in outcome in the 1990s. J Rheumatol. 2002;29:309–16.

    PubMed  Google Scholar 

  16. Koldingsnes W, Nossent H. Epidemiology of Wegener’s granulomatosis in northern Norway. Arthritis Rheum. 2000;43:2481–7.

    Article  CAS  PubMed  Google Scholar 

  17. Takala JH, Kautiainen H, Malmberg H, Leirisalo-Repo M. Incidence of Wegener’s granulomatosis in Finland 1981-2000. Clin Exp Rheumatol. 2008;26:S81–5.

    CAS  PubMed  Google Scholar 

  18. Watts RA, Al-Taiar A, Scott DG, Macgregor AJ. Prevalence and incidence of Wegener’s granulomatosis in the UK general practice research database. Arthritis Rheum. 2009;61:1412–6.

    Article  PubMed  Google Scholar 

  19. Watts RA, Mooney J, Skinner J, Scott DG, Macgregor AJ. The contrasting epidemiology of granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis. Rheumatology (Oxford). 2012;51:926–31.

    Article  Google Scholar 

  20. Lane SE, Watts R, Scott DG. Epidemiology of systemic vasculitis. Curr Rheumatol Rep. 2005;7:270–5.

    Article  PubMed  Google Scholar 

  21. van Timmeren MM, Heeringa P. Pathogenesis of ANCA-associated vasculitis: recent insights from animal models. Curr Opin Rheumatol. 2012;24:8–14.

    Article  PubMed  CAS  Google Scholar 

  22. Jennette JC, Falk RJ. Pathogenesis of antineutrophil cytoplasmic autoantibody-mediated disease. Nat Rev Rheumatol. 2014;10:463–73.

    Article  CAS  PubMed  Google Scholar 

  23. Pendergraft WF III, Pressler BM, Jennette JC, Falk RJ, Preston GA. Autoantigen complementarity: a new theory implicating complementary proteins as initiators of autoimmune disease. J Mol Med (Berl). 2005;83:12–25.

    Article  CAS  Google Scholar 

  24. Stegeman CA, Tervaert JW, Sluiter WJ, Manson WL, de Jong PE, Kallenberg CG. Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis. Ann Intern Med. 1994;120:12–7.

    Article  CAS  PubMed  Google Scholar 

  25. Knight A, Sandin S, Askling J. Increased risk of autoimmune disease in families with Wegener’s granulomatosis. J Rheumatol. 2010;37:2553–8.

    Article  PubMed  Google Scholar 

  26. Jagiello P, Gross WL, Epplen JT. Complex genetics of Wegener granulomatosis. Autoimmun Rev. 2005;4:42–7.

    Article  CAS  PubMed  Google Scholar 

  27. Wieczorek S, Holle JU, Epplen JT. Recent progress in the genetics of Wegener’s granulomatosis and Churg-Strauss syndrome. Curr Opin Rheumatol. 2010;22:8–14.

    Article  CAS  PubMed  Google Scholar 

  28. Lyons PA, Rayner TF, Trivedi S, et al. Genetically distinct subsets within ANCA-associated vasculitis. N Engl J Med. 2012;367:214–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Rahmattulla C, Mooyaart AL, van Hooven D, et al. Genetic variants in ANCA-associated vasculitis: a meta-analysis. Ann Rheum Dis. 2016;75:1687–92.

    Article  PubMed  Google Scholar 

  30. Hong Y, Eleftheriou D, Hussain AA, et al. Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles. J Am Soc Nephrol. 2012;23:49–62.

    Article  CAS  PubMed  Google Scholar 

  31. Kessenbrock K, Krumbholz M, Schonermarck U, et al. Netting neutrophils in autoimmune small-vessel vasculitis. Nat Med. 2009;15:623–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kraaij T, Kamerling SWA, van Dam LS, et al. Excessive neutrophil extracellular trap formation in ANCA-associated vasculitis is independent of ANCA. Kidney Int. 2018;94:139.

    Article  CAS  PubMed  Google Scholar 

  33. Xiao H, Heeringa P, Hu P, et al. Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J Clin Invest. 2002;110:955–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Abdulahad WH, Stegeman CA, Limburg PC, Kallenberg CG. CD4-positive effector memory T cells participate in disease expression in ANCA-associated vasculitis. Ann N Y Acad Sci. 2007;1107:22–31.

    Article  CAS  PubMed  Google Scholar 

  35. Abdulahad WH, Stegeman CA, van der Geld YM, Doornbos-van der Meer B, Limburg PC, Kallenberg CG. Functional defect of circulating regulatory CD4+ T cells in patients with Wegener’s granulomatosis in remission. Arthritis Rheum. 2007;56:2080–91.

    Article  CAS  PubMed  Google Scholar 

  36. Regent A, Lofek S, Dib H, et al. Identification of target antigens of anti-endothelial cell antibodies in patients with anti-neutrophil cytoplasmic antibody-associated vasculitides: a proteomic approach. Clin Immunol. 2014;153:123–35.

    Article  CAS  PubMed  Google Scholar 

  37. Holmen C, Elsheikh E, Christensson M, et al. Anti endothelial cell autoantibodies selectively activate SAPK/JNK signalling in Wegener’s granulomatosis. J Am Soc Nephrol. 2007;18:2497–508.

    Article  CAS  PubMed  Google Scholar 

  38. Popa ER, Franssen CF, Limburg PC, Huitema MG, Kallenberg CG, Tervaert JW. In vitro cytokine production and proliferation of T cells from patients with anti-proteinase 3- and antimyeloperoxidase-associated vasculitis, in response to proteinase 3 and myeloperoxidase. Arthritis Rheum. 2002;46:1894–904.

    Article  CAS  PubMed  Google Scholar 

  39. Abdulahad WH, Stegeman CA, Limburg PC, Kallenberg CG. Skewed distribution of Th17 lymphocytes in patients with Wegener’s granulomatosis in remission. Arthritis Rheum. 2008;58:2196–205.

    Article  PubMed  Google Scholar 

  40. Stone JH. Limited versus severe Wegener’s granulomatosis: baseline data on patients in the Wegener’s granulomatosis etanercept trial. Arthritis Rheum. 2003;48:2299–309.

    Article  PubMed  Google Scholar 

  41. Solans-Laque R, Fraile G, Rodriguez-Carballeira M, et al. Clinical characteristics and outcome of Spanish patients with ANCA-associated vasculitides: impact of the vasculitis type, ANCA specificity, and treatment on mortality and morbidity. Medicine (Baltimore). 2017;96:e6083.

    Article  Google Scholar 

  42. Reinhold-Keller E, Beuge N, Latza U, et al. An interdisciplinary approach to the care of patients with Wegener’s granulomatosis: long-term outcome in 155 patients. Arthritis Rheum. 2000;43:1021–32.

    Article  CAS  PubMed  Google Scholar 

  43. Pagnoux C, Wolter NE. Vasculitis of the upper airways. Swiss Med Wkly. 2012;142:w13541.

    PubMed  Google Scholar 

  44. Fasunla JA, Hundt W, Lutz J, Forger F, Thurmel K, Steinbach S. Evaluation of smell and taste in patients with Wegener’s granulomatosis. Eur Arch Otorhinolaryngol. 2012;269:179–86.

    Article  PubMed  Google Scholar 

  45. Martinez Del Pero M, Walsh M, Luqmani R, et al. Long-term damage to the ENT system in Wegener’s granulomatosis. Eur Arch Otorhinolaryngol. 2011;268:733–9.

    Article  PubMed  Google Scholar 

  46. Langford CA, Sneller MC, Hallahan CW, et al. Clinical features and therapeutic management of subglottic stenosis in patients with Wegener’s granulomatosis. Arthritis Rheum. 1996;39:1754–60.

    Article  CAS  PubMed  Google Scholar 

  47. Terrier B, Dechartres A, Girard C, et al. Granulomatosis with polyangiitis: endoscopic management of tracheobronchial stenosis: results from a multicentre experience. Rheumatology (Oxford). 2015;54:1852–7.

    Article  CAS  Google Scholar 

  48. Russell BA, Mohan S, Chahal R, Carette S, Pagnoux C, Canadian Vasculitis N. Prognostic significance of cavitary lung nodules in granulomatosis with polyangiitis - a clinical and imaging study of 225 patients. Arthritis Care Res. 2018;70:1082.

    Article  Google Scholar 

  49. Girard C, Charles P, Terrier B, et al. Tracheobronchial stenoses in granulomatosis with polyangiitis (Wegener’s): a report on 26 cases. Medicine (Baltimore). 2015;94:e1088.

    Article  CAS  Google Scholar 

  50. Berden AE, Ferrario F, Hagen EC, et al. Histopathologic classification of ANCA-associated glomerulonephritis. J Am Soc Nephrol. 2010;21:1628–36.

    Article  PubMed  Google Scholar 

  51. Pagnoux C, Guillevin L. Peripheral neuropathy in systemic vasculitides. Curr Opin Rheumatol. 2005;17:41–8.

    Article  PubMed  Google Scholar 

  52. Nishino H, Rubino FA, DeRemee RA, Swanson JW, Parisi JE. Neurological involvement in Wegener’s granulomatosis: an analysis of 324 consecutive patients at the Mayo Clinic. Ann Neurol. 1993;33:4–9.

    Article  CAS  PubMed  Google Scholar 

  53. de Groot K, Schmidt DK, Arlt AC, Gross WL, Reinhold-Keller E. Standardized neurologic evaluations of 128 patients with Wegener granulomatosis. Arch Neurol. 2001;58:1215–21.

    Article  PubMed  Google Scholar 

  54. De Luna G, Terrier B, Kaminsky P, et al. Central nervous system involvement of granulomatosis with polyangiitis: clinical-radiological presentation distinguishes different outcomes. Rheumatology (Oxford). 2015;54:424–32.

    Article  Google Scholar 

  55. Younger DS. Vasculitis of the nervous system. Curr Opin Neurol. 2004;17:317–36.

    Article  PubMed  Google Scholar 

  56. Goyal M, Kucharczyk W, Keystone E. Granulomatous hypophysitis due to Wegener’s granulomatosis. AJNR Am J Neuroradiol. 2000;21:1466–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Frances C, Du LT, Piette JC, et al. Wegener’s granulomatosis. Dermatological manifestations in 75 cases with clinicopathologic correlation. Arch Dermatol. 1994;130:861–7.

    Article  CAS  PubMed  Google Scholar 

  58. Le Hello C, Bonte I, Mora JJ, Verneuil L, Noel LH, Guillevin L. Pyoderma gangrenosum associated with Wegener’s granulomatosis: partial response to mycophenolate mofetil. Rheumatology (Oxford). 2002;41:236–7.

    Article  Google Scholar 

  59. Rothschild PR, Pagnoux C, Seror R, Brezin AP, Delair E, Guillevin L. Ophthalmologic manifestations of systemic necrotizing vasculitides at diagnosis: a retrospective study of 1286 patients and review of the literature. Semin Arthritis Rheum. 2013;42:507–14.

    Article  PubMed  Google Scholar 

  60. McGeoch L, Carette S, Cuthbertson D, et al. Cardiac Involvement in Granulomatosis with Polyangiitis. J Rheumatol. 2015;42:1209–12.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Morelli S, Gurgo Di Castelmenardo AM, Conti F, et al. Cardiac involvement in patients with Wegener’s granulomatosis. Rheumatol Int. 2000;19:209–12.

    Article  CAS  PubMed  Google Scholar 

  62. Mavrogeni S, Schwitter J, van Rossum A, et al. Cardiac magnetic resonance imaging in myocardial inflammation in autoimmune rheumatic diseases: an appraisal of the diagnostic strengths and limitations of the Lake Louise criteria. Int J Cardiol. 2018;252:216–9.

    Article  PubMed  Google Scholar 

  63. Pugnet G, Gouya H, Puechal X, et al. Cardiac involvement in granulomatosis with polyangiitis: a magnetic resonance imaging study of 31 consecutive patients. Rheumatology (Oxford). 2017;56:947–56.

    Article  CAS  Google Scholar 

  64. Pagnoux C, Mahr A, Cohen P, Guillevin L. Presentation and outcome of gastrointestinal involvement in systemic necrotizing vasculitides: analysis of 62 patients with polyarteritis nodosa, microscopic polyangiitis, Wegener granulomatosis, Churg-Strauss syndrome, or rheumatoid arthritis-associated vasculitis. Medicine (Baltimore). 2005;84:115–28.

    Article  Google Scholar 

  65. Soowamber M, Weizman AV, Pagnoux C. Gastrointestinal aspects of vasculitides. Nat Rev Gastroenterol Hepatol. 2017;14:185–94.

    Article  CAS  PubMed  Google Scholar 

  66. Sy A, Khalidi N, Dehghan N, et al. Vasculitis in patients with inflammatory bowel diseases: a study of 32 patients and systematic review of the literature. Semin Arthritis Rheum. 2016;45:475–82.

    Article  PubMed  Google Scholar 

  67. Gal AA, Masor JJ. Splenic involvement in Wegener’s granulomatosis. Arch Pathol Lab Med. 1996;120:974–7.

    CAS  PubMed  Google Scholar 

  68. McCain M, Quinet R, Davis W, et al. Splenic rupture as the presenting manifestation of vasculitis. Semin Arthritis Rheum. 2002;31:311–6.

    Article  PubMed  Google Scholar 

  69. Arlet JB, Le Thi Huong D, Marinho A, Cluzel P, Wechsler B, Piette JC. Arterial aneurysms in Wegener’s granulomatosis: case report and literature review. Semin Arthritis Rheum. 2008;37:265–8.

    Article  PubMed  Google Scholar 

  70. Lie JT. Wegener’s granulomatosis: histological documentation of common and uncommon manifestations in 216 patients. Vasa. 1997;26:261–70.

    CAS  PubMed  Google Scholar 

  71. Barreto P, Pagnoux C, Luca L, et al. Dorsal prevertebral lesions in Wegener granulomatosis: report on four cases. Joint Bone Spine. 2011;78:88–91.

    Article  PubMed  Google Scholar 

  72. Merkel PA, Lo GH, Holbrook JT, et al. Brief communication: high incidence of venous thrombotic events among patients with Wegener granulomatosis: the Wegener’s Clinical Occurrence of Thrombosis (WeCLOT) Study. Ann Intern Med. 2005;142:620–6.

    Article  PubMed  Google Scholar 

  73. Allenbach Y, Seror R, Pagnoux C, Teixeira L, Guilpain P, Guillevin L. High frequency of venous thromboembolic events in Churg-Strauss syndrome, Wegener’s granulomatosis and microscopic polyangiitis but not polyarteritis nodosa: a systematic retrospective study on 1130 patients. Ann Rheum Dis. 2009;68:564–7.

    Article  CAS  PubMed  Google Scholar 

  74. Kronbichler A, Leierer J, Leierer G, et al. Clinical associations with venous thromboembolism in anti-neutrophil cytoplasm antibody-associated vasculitides. Rheumatology (Oxford). 2017;56:704–8.

    Google Scholar 

  75. Berti A, Matteson EL, Crowson CS, Specks U, Cornec D. Risk of Cardiovascular disease and venous thromboembolism among patients with incident ANCA-associated vasculitis: a 20-year population-based cohort study. Mayo Clin Proc. 2018;93:597.

    Article  PubMed  Google Scholar 

  76. 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;66:605–17.

    Article  CAS  PubMed  Google Scholar 

  77. Hoffman GS. Immunosuppressive therapy is always required for the treatment of limited Wegener’s granulomatosis. Sarcoidosis Vasc Diffuse Lung Dis. 1996;13:249–52.

    CAS  PubMed  Google Scholar 

  78. 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;69:1934–9.

    Article  PubMed  Google Scholar 

  79. Pagnoux C, Stubbe M, Lifermann F, et al. Wegener’s granulomatosis strictly and persistently localized to one organ is rare: assessment of 16 patients from the French Vasculitis Study Group database. J Rheumatol. 2011;38:475–8.

    Article  PubMed  Google Scholar 

  80. Cabral DA, Uribe AG, Benseler S, et al. Classification, presentation, and initial treatment of Wegener’s granulomatosis in childhood. Arthritis Rheum. 2009;60:3413–24.

    Article  PubMed  Google Scholar 

  81. Akikusa JD, Schneider R, Harvey EA, et al. Clinical features and outcome of pediatric Wegener’s granulomatosis. Arthritis Rheum. 2007;57:837–44.

    Article  CAS  PubMed  Google Scholar 

  82. Cabral DA, Canter DL, Muscal E, et al. Comparing presenting clinical features in 48 children with microscopic polyangiitis to 183 children who have granulomatosis with polyangiitis (Wegener’s): an ARChiVe cohort study. Arthritis Rheumatol. 2016;68:2514–26.

    Article  CAS  PubMed  Google Scholar 

  83. Morishita KA, Moorthy LN, Lubieniecka JM, et al. Early outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 2017;69:1470–9.

    Article  CAS  PubMed  Google Scholar 

  84. Iudici M, Pagnoux C, Quartier P, et al. Childhood- versus adult-onset ANCA-associated vasculitides: a nested, matched case-control study from the French Vasculitis Study Group Registry. Autoimmun Rev. 2018;17:108–14.

    Article  PubMed  Google Scholar 

  85. Koldingsnes W, Nossent JC. Baseline features and initial treatment as predictors of remission and relapse in Wegener’s granulomatosis. J Rheumatol. 2003;30:80–8.

    PubMed  Google Scholar 

  86. Karim AF, Verdijk RM, Nagtegaal AP, et al. To distinguish IgG4-related disease from seronegative granulomatosis with polyangiitis. Rheumatology (Oxford). 2017;56:2245–7.

    Article  Google Scholar 

  87. 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;13:683–92.

    Article  PubMed  Google Scholar 

  88. Mahr A, Batteux F, Tubiana S, et al. Brief report: prevalence of antineutrophil cytoplasmic antibodies in infective endocarditis. Arthritis Rheumatol. 2014;66:1672–7.

    Article  PubMed  Google Scholar 

  89. Duna GF, Galperin C, Hoffman GS. Wegener’s granulomatosis. Rheum Dis Clin North Am. 1995;21:949–86.

    CAS  PubMed  Google Scholar 

  90. Gluth MB, Shinners PA, Kasperbauer JL. Subglottic stenosis associated with Wegener’s granulomatosis. Laryngoscope. 2003;113:1304–7.

    Article  PubMed  Google Scholar 

  91. Gwathmey KG, Burns TM, Collins MP, Dyck PJ. Vasculitic neuropathies. Lancet Neurol. 2014;13:67–82.

    Article  PubMed  Google Scholar 

  92. McGeoch L, Silecky WB, Maher J, Carette S, Pagnoux C. Temporal arteritis in the young. Joint Bone Spine. 2013;80:324–7.

    Article  PubMed  Google Scholar 

  93. Bourgarit A, Le Toumelin P, Pagnoux C, et al. Deaths occurring during the first year after treatment onset for polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: a retrospective analysis of causes and factors predictive of mortality based on 595 patients. Medicine (Baltimore). 2005;84:323–30.

    Article  Google Scholar 

  94. Faurschou M, Sorensen IJ, Mellemkjaer L, et al. Malignancies in Wegener’s granulomatosis: incidence and relation to cyclophosphamide therapy in a cohort of 293 patients. J Rheumatol. 2008;35:100–5.

    CAS  PubMed  Google Scholar 

  95. Flossmann O, Jayne DR. Long-term treatment of relapsing Wegener’s granulomatosis with 15-deoxyspergualin. Rheumatology (Oxford). 2010;49:556–62.

    Article  CAS  Google Scholar 

  96. Puechal X, Pagnoux C, Perrodeau E, et al. Long-Term Outcomes Among Participants in the WEGENT Trial of Remission-Maintenance Therapy for Granulomatosis With Polyangiitis (Wegener’s) or Microscopic Polyangiitis. Arthritis Rheumatol. 2016;68:690–701.

    Article  CAS  PubMed  Google Scholar 

  97. Jayne D, Rasmussen N, Andrassy K, et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. 2003;349:36–44.

    Article  CAS  PubMed  Google Scholar 

  98. Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener’s granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med. 1983;98:76–85.

    Article  CAS  PubMed  Google Scholar 

  99. Pagnoux C, Guillevin L. Treatment of granulomatosis with polyangiitis (Wegener’s). Expert Rev Clin Immunol. 2015;11:339–48.

    Article  CAS  PubMed  Google Scholar 

  100. Walsh M, Merkel PA, Mahr A, Jayne D. Effects of duration of glucocorticoid therapy on relapse rate in antineutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis. Arthritis Care Res. 2010;62:1166–73.

    Article  Google Scholar 

  101. Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363:221–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. WGET. Etanercept plus standard therapy for Wegener’s granulomatosis. N Engl J Med. 2005;352:351–61.

    Article  Google Scholar 

  103. Guillevin L, Cordier JF, Lhote F, et al. A prospective, multicenter, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of generalized Wegener’s granulomatosis. Arthritis Rheum. 1997;40:2187–98.

    Article  CAS  PubMed  Google Scholar 

  104. de Groot K, Harper L, Jayne DR, et al. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med. 2009;150:670–80.

    Article  PubMed  Google Scholar 

  105. Lapraik C, Watts R, Bacon P, et al. BSR and BHPR guidelines for the management of adults with ANCA associated vasculitis. Rheumatology (Oxford). 2007;46:1615–6.

    Article  CAS  Google Scholar 

  106. Pagnoux C, Quemeneur T, Ninet J, et al. Treatment of systemic necrotizing vasculitides in patients aged sixty-five years or older: results of a multicenter, open-label, randomized controlled trial of corticosteroid and cyclophosphamide-based induction therapy. Arthritis Rheumatol. 2015;67:1117–27.

    Article  CAS  PubMed  Google Scholar 

  107. Monach PA, Arnold LM, Merkel PA. Incidence and prevention of bladder toxicity from cyclophosphamide in the treatment of rheumatic diseases: a data-driven review. Arthritis Rheum. 2010;62:9–21.

    Article  CAS  PubMed  Google Scholar 

  108. Pagnoux C, FVSG. Vascularites nécrosantes systémiques - protocole national de diagnostic et de soins. 2009. https://www.has-sante.fr.

  109. Haubitz M, Schellong S, Gobel U, et al. Intravenous pulse administration of cyclophosphamide versus daily oral treatment in patients with antineutrophil cytoplasmic antibody-associated vasculitis and renal involvement: a prospective, randomized study. Arthritis Rheum. 1998;41:1835–44.

    Article  CAS  PubMed  Google Scholar 

  110. Harper L, Morgan MD, Walsh M, et al. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up. Ann Rheum Dis. 2012;71:955–60.

    Article  CAS  PubMed  Google Scholar 

  111. Jones RB, Furuta S, Tervaert JW, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis: 2-year results of a randomised trial. Ann Rheum Dis. 2015;74:1178–82.

    Article  CAS  PubMed  Google Scholar 

  112. Specks U, Merkel PA, Seo P, et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med. 2013;369:417–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Westwell-Roper C, Lubieniecka JM, Brown KL, et al. Clinical practice variation and need for pediatric-specific treatment guidelines among rheumatologists caring for children with ANCA-associated vasculitis: an international clinician survey. Pediatr Rheumatol Online J. 2017;15:61.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Holle JU, Dubrau C, Herlyn K, et al. Rituximab for refractory granulomatosis with polyangiitis (Wegener’s granulomatosis): comparison of efficacy in granulomatous versus vasculitic manifestations. Ann Rheum Dis. 2012;71:327–33.

    Article  CAS  PubMed  Google Scholar 

  115. Charles P, Bienvenu B, Bonnotte B, et al. Rituximab: recommendations of the French Vasculitis Study Group (FVSG) for induction and maintenance treatments of adult, antineutrophil cytoplasm antibody-associated necrotizing vasculitides. Presse Med. 2013;42:1317–30.

    Article  PubMed  Google Scholar 

  116. 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;68:1467–76.

    Article  CAS  PubMed  Google Scholar 

  117. Uechi E, Okada M, Fushimi K. Effect of plasma exchange on in-hospital mortality in patients with pulmonary hemorrhage secondary to antineutrophil cytoplasmic antibody-associated vasculitis: a propensity-matched analysis using a nationwide administrative database. PLoS One. 2018;13:e0196009.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. 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.

    Article  CAS  PubMed  Google Scholar 

  119. Walsh M, Catapano F, Szpirt W, et al. Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: a meta-analysis. Am J Kidney Dis. 2011;57:566–74.

    Article  PubMed  Google Scholar 

  120. Walsh M, Merkel PA, Peh CA, et al. Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial. Trials. 2013;14:73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Pagnoux C, Mahr A, Hamidou MA, et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med. 2008;359:2790–803.

    Article  CAS  PubMed  Google Scholar 

  122. Langford CA, Talar-Williams C, Barron KS, Sneller MC. A staged approach to the treatment of Wegener’s granulomatosis: induction of remission with glucocorticoids and daily cyclophosphamide switching to methotrexate for remission maintenance. Arthritis Rheum. 1999;42:2666–73.

    Article  CAS  PubMed  Google Scholar 

  123. Metzler C, Miehle N, Manger K, et al. Elevated relapse rate under oral methotrexate versus leflunomide for maintenance of remission in Wegener’s granulomatosis. Rheumatology (Oxford). 2007;46:1087–91.

    Article  CAS  Google Scholar 

  124. Hiemstra TF, Walsh M, Mahr A, et al. Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA. 2010;304:2381–8.

    Article  CAS  PubMed  Google Scholar 

  125. Reinhold-Keller E, Fink CO, Herlyn K, Gross WL, De Groot K. High rate of renal relapse in 71 patients with Wegener’s granulomatosis under maintenance of remission with low-dose methotrexate. Arthritis Rheum. 2002;47:326–32.

    Article  CAS  PubMed  Google Scholar 

  126. Mahr A, Katsahian S, Varet H, et al. Revisiting the classification of clinical phenotypes of anti-neutrophil cytoplasmic antibody-associated vasculitis: a cluster analysis. Ann Rheum Dis. 2013;72:1003–10.

    Article  PubMed  Google Scholar 

  127. Karras A, Pagnoux C, Haubitz M, et al. Randomised controlled trial of prolonged treatment in the remission phase of ANCA-associated vasculitis. Ann Rheum Dis. 2017;76:1662–8.

    Article  CAS  PubMed  Google Scholar 

  128. Miloslavsky EM, Lu N, Unizony S, et al. Myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)-positive and ANCA-negative patients with granulomatosis with polyangiitis (Wegener’s): distinct patient subsets. Arthritis Rheumatol. 2016;68:2945–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Pagnoux C, Springer J. Editorial: classifying antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides according to ANCA type or phenotypic diagnosis: salt or pepper? Arthritis Rheumatol. 2016;68:2837–40.

    Article  CAS  PubMed  Google Scholar 

  130. Schirmer JH, Wright MN, Herrmann K, et al. Myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)-positive granulomatosis with polyangiitis (Wegener’s) is a clinically distinct subset of ANCA-associated vasculitis: a retrospective analysis of 315 patients from a German vasculitis referral center. Arthritis Rheumatol. 2016;68:2953–63.

    Article  CAS  PubMed  Google Scholar 

  131. McGregor JG, Hogan SL, Hu Y, Jennette CE, Falk RJ, Nachman PH. Glucocorticoids and relapse and infection rates in anti-neutrophil cytoplasmic antibody disease. Clin J Am Soc Nephrol. 2012;7:240–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Cartin-Ceba R, Golbin JM, Keogh KA, et al. Rituximab for remission induction and maintenance in refractory granulomatosis with polyangiitis (Wegener’s): ten-year experience at a single center. Arthritis Rheum. 2012;64:3770–8.

    Article  CAS  PubMed  Google Scholar 

  133. Jones RB, Ferraro AJ, Chaudhry AN, et al. A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2009;60:2156–68.

    Article  CAS  PubMed  Google Scholar 

  134. Smith RM, Jones RB, Guerry MJ, et al. Rituximab for remission maintenance in relapsing antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2012;64:3760–9.

    Article  CAS  PubMed  Google Scholar 

  135. Roubaud-Baudron C, Pagnoux C, Meaux-Ruault N, et al. Rituximab maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis. J Rheumatol. 2012;39:125–30.

    Article  CAS  PubMed  Google Scholar 

  136. Alberici F, Smith RM, Jones RB, et al. Long-term follow-up of patients who received repeat-dose rituximab as maintenance therapy for ANCA-associated vasculitis. Rheumatology (Oxford). 2015;54:1153–60.

    Article  CAS  Google Scholar 

  137. Guillevin L, Pagnoux C, Karras A, et al. Rituximab versus Azathioprine for Maintenance in ANCA-Associated Vasculitis. N Engl J Med. 2014;371:1771–80.

    Article  CAS  PubMed  Google Scholar 

  138. Gopaluni S, Smith RM, Lewin M, et al. Rituximab versus azathioprine as therapy for maintenance of remission for anti-neutrophil cytoplasm antibody-associated vasculitis (RITAZAREM): study protocol for a randomized controlled trial. Trials. 2017;18:112.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  139. Charles P, Terrier B, Perrodeau E, et al. Comparison of individually tailored vs systematic rituximab regimens to maintain ANCA-associated vasculitis remissions: results of a prospective, randomized–controlled, phase 3 trial. Arthritis Rheumatol. 2017;69:Abst 2754.

    Google Scholar 

  140. Unizony S, Villarreal M, Miloslavsky EM, et al. Clinical outcomes of treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis based on ANCA type. Ann Rheum Dis. 2016;75:1166–9.

    Article  CAS  PubMed  Google Scholar 

  141. Azar L, Springer J, Langford CA, Hoffman GS. Rituximab with or without a conventional maintenance agent in the treatment of relapsing granulomatosis with polyangiitis (Wegener’s): a retrospective single-center study. Arthritis Rheumatol. 2014;66:2862–70.

    Article  CAS  PubMed  Google Scholar 

  142. de Groot K, Reinhold-Keller E, Tatsis E, et al. Therapy for the maintenance of remission in sixty-five patients with generalized Wegener’s granulomatosis. Methotrexate versus trimethoprim/sulfamethoxazole. Arthritis Rheum. 1996;39:2052–61.

    Article  PubMed  Google Scholar 

  143. Stegeman CA, Tervaert JW, de Jong PE, Kallenberg CG. Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener’s granulomatosis. Dutch Co-Trimoxazole Wegener Study Group. N Engl J Med. 1996;335:16–20.

    Article  CAS  PubMed  Google Scholar 

  144. Cohen Tervaert JW. Trimethoprim-sulfamethoxazole and antineutrophil cytoplasmic antibodies-associated vasculitis. Curr Opin Rheumatol. 2018;30:388.

    Article  CAS  PubMed  Google Scholar 

  145. Zycinska K, Wardyn KA, Zielonka TM, Krupa R, Lukas W. Co-trimoxazole and prevention of relapses of PR3-ANCA positive vasculitis with pulmonary involvement. Eur J Med Res. 2009;14(Suppl 4):265–7.

    Article  PubMed  PubMed Central  Google Scholar 

  146. Pagnoux C, Hogan SL, Chin H, et al. Predictors of treatment resistance and relapse in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis: comparison of two independent cohorts. Arthritis Rheum. 2008;58:2908–18.

    Article  PubMed  PubMed Central  Google Scholar 

  147. Finkielman JD, Merkel PA, Schroeder D, et al. Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis. Ann Intern Med. 2007;147:611–9.

    Article  PubMed  Google Scholar 

  148. Kemna MJ, Damoiseaux J, Austen J, et al. ANCA as a predictor of relapse: useful in patients with renal involvement but not in patients with nonrenal disease. J Am Soc Nephrol. 2015;26:537–42.

    Article  CAS  PubMed  Google Scholar 

  149. Fussner LA, Hummel AM, Schroeder DR, et al. Factors determining the clinical utility of serial measurements of antineutrophil cytoplasmic antibodies targeting proteinase 3. Arthritis Rheumatol. 2016;68:1700–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Walsh M, Flossmann O, Berden A, et al. Risk factors for relapse of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2012;64:542–8.

    Article  CAS  PubMed  Google Scholar 

  151. Stegeman CA. Anti-neutrophil cytoplasmic antibody (ANCA) levels directed against proteinase-3 and myeloperoxidase are helpful in predicting disease relapse in ANCA-associated small-vessel vasculitis. Nephrol Dial Transplant. 2002;17:2077–80.

    Article  CAS  PubMed  Google Scholar 

  152. 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;52:2461–9.

    Article  PubMed  CAS  Google Scholar 

  153. Hu W, Liu C, Xie H, Chen H, Liu Z, Li L. Mycophenolate mofetil versus cyclophosphamide for inducing remission of ANCA vasculitis with moderate renal involvement. Nephrol Dial Transplant. 2008;23:1307–12.

    Article  CAS  PubMed  Google Scholar 

  154. Jayne DR, Chapel H, Adu D, et al. Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity. QJM. 2000;93:433–9.

    Article  CAS  PubMed  Google Scholar 

  155. Crickx E, Machelart I, Lazaro E, et al. Intravenous immunoglobulin as an immunomodulating agent in antineutrophil cytoplasmic antibody-associated vasculitides: a French nationwide study of ninety-two patients. Arthritis Rheumatol. 2016;68:702–12.

    Article  CAS  PubMed  Google Scholar 

  156. McAdoo SP, Bedi R, Tarzi R, Griffith M, Pusey CD, Cairns TD. Ofatumumab for B cell depletion therapy in ANCA-associated vasculitis: a single-centre case series. Rheumatology (Oxford). 2016;55:1437–42.

    Article  CAS  Google Scholar 

  157. Jayne DRW, Bruchfeld AN, Harper L, et al. Randomized trial of C5a receptor inhibitor avacopan in ANCA-associated vasculitis. J Am Soc Nephrol. 2017;28:2756–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Langford CA, Monach PA, Specks U, et al. An open-label trial of abatacept (CTLA4-Ig) in non-severe relapsing granulomatosis with polyangiitis (Wegener’s). Ann Rheum Dis. 2014;73:1376–9.

    Article  CAS  PubMed  Google Scholar 

  159. Jayne D, Blockmans D, Luqmani R, et al. Efficacy and Safety of Belimumab and Azathioprine for Maintenance of Remission in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Randomized Controlled Study. Arthritis Rheumatol. 2019;71:952–63.

    Google Scholar 

  160. Berti A, Cavalli G, Campochiaro C, et al. Interleukin-6 in ANCA-associated vasculitis: rationale for successful treatment with tocilizumab. Semin Arthritis Rheum. 2015;45:48–54.

    Article  CAS  PubMed  Google Scholar 

  161. Sakai R, Kondo T, Kikuchi J, et al. Corticosteroid-free treatment of tocilizumab monotherapy for microscopic polyangiitis: a single-arm, single-center, clinical trial. Mod Rheumatol. 2016;26:900–7.

    Article  CAS  PubMed  Google Scholar 

  162. Trial U-CC. Clinical trial of tocilizumab versus cyclophosphamide for microscopic polyangiitis and granulomatosis with polyangiitis. 01 May 2017 edn. UMIN-CTR Clinical Trial portal. 2018.

    Google Scholar 

  163. Kusunoki Y, Nakazawa D, Shida H, et al. Peptidylarginine deiminase inhibitor suppresses neutrophil extracellular trap formation and MPO-ANCA production. Front Immunol. 2016;7:227.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  164. Nishide M, Nojima S, Ito D, et al. Semaphorin 4D inhibits neutrophil activation and is involved in the pathogenesis of neutrophil-mediated autoimmune vasculitis. Ann Rheum Dis. 2017;76:1440–8.

    Article  CAS  PubMed  Google Scholar 

  165. Booth A, Harper L, Hammad T, et al. Prospective study of TNF alpha blockade with infliximab in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. J Am Soc Nephrol. 2004;15:717–21.

    Article  CAS  PubMed  Google Scholar 

  166. de Menthon M, Cohen P, Pagnoux C, et al. Infliximab or rituximab for refractory Wegener’s granulomatosis: long-term follow up. A prospective randomised multicentre study on 17 patients. Clin Exp Rheumatol. 2011;29:S63–71.

    PubMed  Google Scholar 

  167. Silva F, Seo P, Schroeder DR, et al. Solid malignancies among etanercept-treated patients with granulomatosis with polyangiitis (Wegener’s): long-term follow up of a multicenter longitudinal cohort. Arthritis Rheum. 2011;63:2495–503.

    Article  PubMed  PubMed Central  Google Scholar 

  168. Walsh M, Chaudhry A, Jayne D. Long-term follow-up of relapsing/refractory anti-neutrophil cytoplasm antibody associated vasculitis treated with the lymphocyte depleting antibody alemtuzumab (CAMPATH-1H). Ann Rheum Dis. 2008;67:1322–7.

    Article  CAS  PubMed  Google Scholar 

  169. Shen J, Gill J, Shangguan M, Sampaio MS, Bunnapradist S. Outcomes of renal transplantation in recipients with Wegener’s granulomatosis. Clin Transplant. 2011;25:380–7.

    Article  PubMed  Google Scholar 

  170. Avina-Zubieta JA, Mai A, Amiri N, et al. Risk of myocardial infarction and stroke in patients with granulomatosis with polyangiitis (Wegener’s): a population-based study. Arthritis Rheumatol. 2016;68:2752–9.

    Article  PubMed  Google Scholar 

  171. Tan JA, Dehghan N, Chen W, Xie H, Esdaile JM, Avina-Zubieta JA. Mortality in ANCA-associated vasculitis: a meta-analysis of observational studies. Ann Rheum Dis. 2017;76:1566–74.

    Article  PubMed  Google Scholar 

  172. Charlier C, Henegar C, Launay O, et al. Risk factors for major infections in Wegener granulomatosis: analysis of 113 patients. Ann Rheum Dis. 2009;68:658–63.

    Article  CAS  PubMed  Google Scholar 

  173. Kostianovsky A, Charles P, Alves JF, et al. Immunogenicity and safety of seasonal and 2009 pandemic A/H1N1 influenza vaccines for patients with autoimmune diseases: a prospective, monocentre trial on 199 patients. Clin Exp Rheumatol. 2012;30:S83–9.

    PubMed  Google Scholar 

  174. Pagnoux C, Mahendira D, Laskin CA. Fertility and pregnancy in vasculitis. Best Pract Res Clin Rheumatol. 2013;27:79–94.

    Article  PubMed  Google Scholar 

  175. Heijl C, Harper L, Flossmann O, et al. 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. 2011;70:1415–21.

    Article  CAS  PubMed  Google Scholar 

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  1. Division of Rheumatology, Vasculitis Clinic, Mount Sinai Hospital, Toronto, ON, Canada

    Christian Pagnoux

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  1. Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Monza e Brianza, Italy

    Renato Alberto Sinico

  2. Department of Medicine, Paris Descartes University Hospital Cochin, Paris, France

    Loïc Guillevin

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Pagnoux, C. (2020). Granulomatosis with Polyangiitis. In: Sinico, R., Guillevin, L. (eds) Anti-Neutrophil Cytoplasmic Antibody (ANCA) Associated Vasculitis. Rare Diseases of the Immune System. Springer, Cham. https://doi.org/10.1007/978-3-030-02239-6_7

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