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  • Review Article
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Challenges in the diagnosis, classification and prognosis of ANCA-associated vasculitis

Nature Reviews Rheumatology volume 21, pages 719–736 (2025) Cite this article

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Abstract

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) encompasses three rare yet interrelated diseases: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Despite increasing recognition, the diagnosis of AAV remains challenging, even in specialized medical centres, owing to its clinical heterogeneity, overlap with mimicking conditions, and the variable performance of ANCA testing. The assessment of a patient suspected of AAV requires a timely synthesis of symptoms, physical examination, laboratory tests, histopathology and imaging data to substantiate the diagnosis, exclude alternative diagnoses, assess disease activity and extent, and enable rapid initiation of appropriate therapies. Classification is similarly complex, and evolving classification systems are based on clinical phenotype, ANCA specificity or a combination of both, each with implications for disease monitoring, therapeutic decisions and trial design. Assessing disease severity and predicting prognosis are fundamental but complicated by the diverse patterns of organ involvement, relapsing–remitting course and co-morbidities. Although validated tools exist for measuring disease activity, organ damage and prognosis, many limitations remain, particularly in identifying smouldering disease, irreversible damage and risk of relapse. Emerging therapies have improved outcomes, with recovery of kidney function, better overall survival and improved glucocorticoid-related toxicity, but patients with AAV continue to experience high risks of chronic morbidity and early mortality. This Review explores current challenges and opportunities in the diagnosis, classification and prognostic assessment of AAV, and outlines a structured framework to support personalized and outcome-focused care.

Key points

  • Diagnosing ANCA-associated vasculitis (AAV) can be challenging owing to the heterogeneity of the syndromes, the absence of a gold standard and criteria for diagnosis, and the overlapping features with other conditions.

  • The development and revision of classification criteria for AAV have been essential for enhancing the accuracy and consistency of research studies.

  • As research into the genetic and immunological basis of AAV progresses, classification criteria will continue to evolve, assisting patient stratification and personalized treatment.

  • Although the standardized tools — BVAS, VDI and AAV-PRO — have improved our ability to assess disease activity, organ damage and patient quality of life, respectively, comprehensive measures that integrate all these factors remain to be developed.

  • Improved disease stratification, combined with patient-centred approaches, will help to refine prognosis, to personalize treatment and ultimately to improve outcomes for patients with AAV.

  • An integrated, multifaceted approach to assess AAV is essential for improving patient care, including understanding diagnostic tools, classifying disease severity and predicting outcomes based on a combination of factors.

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Fig. 1: Systematic approach to the diagnosis in ANCA-associated vasculitis.
The alternative text for this image may have been generated using AI.
Fig. 2: Classification by clinical presentation versus autoantibody specificity in ANCA-associated vasculitis.
The alternative text for this image may have been generated using AI.
Fig. 3: Combined assessment of disease activity, organ damage and patient-reported outcomes can help to characterize severity in three stereotypical cases of ANCA-associated vasculitis.
The alternative text for this image may have been generated using AI.
Fig. 4: Histopathological assessment of kidney for end-stage kidney disease prediction in AAV-associated glomerulonephritis.
The alternative text for this image may have been generated using AI.

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References

  1. Kronbichler, A., Bajema, I. M., Bruchfeld, A., Mastroianni Kirsztajn, G. & Stone, J. H. Diagnosis and management of ANCA-associated vasculitis. Lancet 403, 683–698 (2024).

    Article  CAS  PubMed  Google Scholar 

  2. Kitching, A. R. et al. ANCA-associated vasculitis. Nat. Rev. Dis. Prim. 6, 71 (2020).

    Article  PubMed  Google Scholar 

  3. Heijl, C., Mohammad, A. J., Westman, K. & Hoglund, P. Long-term patient survival in a Swedish population-based cohort of patients with ANCA-associated vasculitis. RMD Open. 3, e000435 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Chung, S. A. et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Care Res. 73, 1088–1105 (2021).

    Article  Google Scholar 

  5. Casal Moura, M. et al. Management of antineutrophil cytoplasmic antibody-associated vasculitis with glomerulonephritis as proposed by the ACR 2021, EULAR 2022 and KDIGO 2021 guidelines/recommendations. Nephrol. Dial. Transpl. 38, 2637–2651 (2023).

    Article  Google Scholar 

  6. Hellmich, B. et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann. Rheum. Dis. 83, 30–47 (2024).

    Article  PubMed  Google Scholar 

  7. Walsh, M. et al. Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N. Engl. J. Med. 382, 622–631 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jayne, D. R. W., Merkel, P. A., Schall, T. J., Bekker, P. & Group, A. S. Avacopan for the treatment of ANCA-associated vasculitis. N. Engl. J. Med. 384, 599–609 (2021).

    Article  CAS  PubMed  Google Scholar 

  9. Wechsler, M. E. et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N. Engl. J. Med. 376, 1921–1932 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wechsler, M. E. et al. Benralizumab versus mepolizumab for eosinophilic granulomatosis with polyangiitis. N. Engl. J. Med. 390, 911–921 (2024).

    Article  CAS  PubMed  Google Scholar 

  11. Nelveg-Kristensen, K. E. et al. Increasing incidence and improved survival in ANCA-associated vasculitis — a Danish nationwide study. Nephrol. Dial. Transpl. 37, 63–71 (2020).

    Article  Google Scholar 

  12. Rhee, R. L. et al. Trends in long-term outcomes among patients with antineutrophil cytoplasmic antibody-associated vasculitis with renal disease. Arthritis Rheumatol. 68, 1711–1720 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Leavitt, R. Y. et al. The American College of Rheumatology 1990 criteria for the classification of Wegener granulomatosis. Arthritis Rheum. 33, 1101–1107 (1990).

    Article  CAS  PubMed  Google Scholar 

  14. Masi, A. et al. The American College of Rheumatology 1990 criteria for the classification of Churg–Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 33, 1094–1100 (1990).

    Article  CAS  PubMed  Google Scholar 

  15. Jennette, J. C. et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 65, 1–11 (2013).

    Article  CAS  PubMed  Google Scholar 

  16. Robson, J. C. et al. Validation of the ANCA-associated vasculitis patient-reported outcomes (AAV-PRO) questionnaire. Ann. Rheum. Dis. 77, 1157–1164 (2018).

    Article  PubMed  Google Scholar 

  17. Maunz, A. et al. Association of the AAV-PRO questionnaire with established outcome measures in AAV. Rheumatology 63, 174–180 (2024).

    Article  PubMed  Google Scholar 

  18. Walsh, M. et al. Health-related quality of life in patients with newly diagnosed antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Care Res. 63, 1055–1061 (2011).

    Article  Google Scholar 

  19. Merkel, P. A. et al. The OMERACT core set of outcome measures for use in clinical trials of ANCA-associated vasculitis. J. Rheumatol. 38, 1480–1486 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Trivioli, G. et al. Advances in the treatment of ANCA-associated vasculitis. Nat. Rev. Rheumatol. 21, 396–413 (2025).

    Article  CAS  PubMed  Google Scholar 

  21. Sreih, A. G. et al. Diagnostic delays in vasculitis and factors associated with time to diagnosis. Orphanet J. Rare Dis. 16, 184 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Dirikgil, E. et al. Identifying relevant determinants of in-hospital time to diagnosis for ANCA-associated vasculitis patients. Rheumatol. Adv. Pract. 6, rkac045 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Ponte, C., Agueda, A. F. & Luqmani, R. A. Clinical features and structured clinical evaluation of vasculitis. Best. Pract. Res. Clin. Rheumatol. 32, 31–51 (2018).

    Article  CAS  PubMed  Google Scholar 

  24. Aggarwal, R. et al. Distinctions between diagnostic and classification criteria? Arthritis Care Res. 67, 891–897 (2015).

    Article  Google Scholar 

  25. Dejaco, C. & Guillevin, L. New classification criteria for small-vessel vasculitis: is antineutrophil cytoplasmic antibody inclusion their major advance? Arthritis Rheumatol. 74, 383–385 (2022).

    Article  PubMed  Google Scholar 

  26. Hoffman, G. S. et al. Wegener granulomatosis: an analysis of 158 patients. Ann. Intern. Med. 15, 488–498 (1992).

    Article  Google Scholar 

  27. Coordes, A. et al. Saddle nose deformity and septal perforation in granulomatosis with polyangiitis. Clin. Otolaryngol. 43, 291–299 (2018).

    Article  CAS  PubMed  Google Scholar 

  28. Rothschild, P.-R. et al. Ophthalmologic manifestations of systemic necrotizing vasculitides at diagnosis: a retrospective study of 1286 patients and review of the literature. Sem. Arthritis Rheum. 42, 507–514 (2013).

    Article  Google Scholar 

  29. Stone, J. H. Limited versus severe Wegener’s granulomatosis: baseline data on patients in the Wegener’s granulomatosis etanercept trial. Arthritis Rheum. 48, 2299–2309 (2003).

    Article  PubMed  Google Scholar 

  30. Holle, J. U. et al. 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 (2010).

    Article  PubMed  Google Scholar 

  31. Finkielman, J. D. et al. ANCA are detectable in nearly all patients with active severe Wegener’s granulomatosis. Am. J. Med. 120, 643 e649–614 (2007).

    Article  Google Scholar 

  32. Mahr, A., Specks, U. & Jayne, D. Subclassifying ANCA-associated vasculitis: a unifying view of disease spectrum. Rheumatology 58, 1707–1709 (2019).

    Article  PubMed  Google Scholar 

  33. Floyd, L. et al. Clinical presentation and outcomes of antineutrophil cytoplasmic autoantibody-negative pauci-immune glomerulonephritis. Kidney Int. Rep. 10, 1450–1459 (2025).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Casal Moura, M. et al. Granulomatosis with polyangiitis with and without antineutrophil cytoplasmic antibodies: a case–control study. Rheumatology 63, 3279–3288 (2024).

    Article  PubMed  Google Scholar 

  35. Guillevin, L. et al. Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients. Arthritis Rheum. 42, 421–430 (1999).

    Article  CAS  PubMed  Google Scholar 

  36. Gisslander, K. et al. Data-driven subclassification of ANCA-associated vasculitis: model-based clustering of a federated international cohort. Lancet Rheumatol. 6, e762–e770 (2024).

    Article  CAS  PubMed  Google Scholar 

  37. Kronbichler, A. et al. Clinical associations of renal involvement in ANCA-associated vasculitis. Autoimmun. Rev. 19, 102495 (2020).

    Article  CAS  PubMed  Google Scholar 

  38. Borie, R. & Crestani, B. Antineutrophil cytoplasmic antibody-associated lung fibrosis. Semin. Resp. Crit. Care Med. 39, 465–470 (2018).

    Article  Google Scholar 

  39. Suzuki, A. et al. Chest high-resolution CT findings of microscopic polyangiitis: a Japanese first nationwide prospective cohort study. Am. J. Roentgenol. 213, 104–114 (2019).

    Article  Google Scholar 

  40. Emmi, G. et al. Evidence-based guideline for the diagnosis and management of eosinophilic granulomatosis with polyangiitis. Nat. Rev. Rheumatol. 19, 378–393 (2023).

    Article  PubMed  Google Scholar 

  41. Comarmond, C. et al. Eosinophilic granulomatosis with polyangiitis (Churg–Strauss): clinical characteristics and long-term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort. Arthritis Rheum. 65, 270–281 (2013).

    Article  PubMed  Google Scholar 

  42. Neumann, T. et al. Cardiac involvement in Churg–Strauss syndrome: impact of endomyocarditis. Medicine 88, 236–243 (2009).

    Article  PubMed  Google Scholar 

  43. Thompson, G. E. et al. Pleuritis and pericarditis in ANCA-associated vasculitis. Chest 160, 572–581 (2021).

    Article  CAS  PubMed  Google Scholar 

  44. Casal Moura, M. et al. A glance into the future of anti-neutrophil cytoplasmic antibody-associated vasculitis. Ther. Adv. Musculoskelet. Dis. 14, 1759720X221125979 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Cho, H. J. et al. Clinical characteristics and treatment response of peripheral neuropathy in the presence of eosinophilic granulomatosis with polyangiitis (Churg–Strauss Syndrome): experience at a single tertiary center. J. Clin. Neurol. 13, 77–83 (2017).

    Article  PubMed  Google Scholar 

  46. Padoan, R. et al. Overall disability sum score for clinical assessment of neurological involvement in eosinophilic granulomatosis with polyangiitis. J. Clin. Rheumatol. 24, 197–202 (2018).

    Article  PubMed  Google Scholar 

  47. Guillevin, L. et al. Churg–Strauss syndrome. Clinical study and long-term follow-up of 96 patients. Medicine 78, 26–37 (1999).

    Article  CAS  PubMed  Google Scholar 

  48. Sinico, R. A. et al. Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg–Strauss syndrome. Arthritis Rheum. 52, 2926–2935 (2005).

    Article  CAS  PubMed  Google Scholar 

  49. Sablé-Fourtassou, R. et al. Antineutrophil cytoplasmic antibodies and the Churg–Strauss syndrome. Ann. Intern. Med. 143, 632–638 (2005).

    Article  PubMed  Google Scholar 

  50. Lyons, P. A. et al. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status. Nat. Commun. 10, 5120 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Rubenstein, E. et al. Cluster analysis to explore clinical subphenotypes of eosinophilic granulomatosis with polyangiitis. J. Rheumatol. 50, 1446–1453 (2023).

    Article  PubMed  Google Scholar 

  52. Damoiseaux, J. 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. 76, 647–653 (2017).

    Article  CAS  PubMed  Google Scholar 

  53. Bossuyt, X. et al. Position paper: revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis. Nat. Rev. Rheumatol. 13, 683–692 (2017).

    Article  PubMed  Google Scholar 

  54. Guchelaar, N. A. D. et al. The value of anti-neutrophil cytoplasmic antibodies (ANCA) testing for the diagnosis of ANCA-associated vasculitis, a systematic review and meta-analysis. Autoimmun. Rev. 20, 102716 (2021).

    Article  CAS  PubMed  Google Scholar 

  55. Mohammad, A. J. et al. Pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis: the influence of ANCA subtype. J. Rheumatol. 44, 1458–1467 (2017).

    Article  PubMed  Google Scholar 

  56. Alba, M. A. et al. Pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis: the influence of ANCA subtype. J. Rheumatol. 44, 1458–1467 (2017).

    Article  Google Scholar 

  57. Casal Moura, M., Soler, M. J., Sethi, S., Fervenza, F. C. & Specks, U. Kidney histopathology in ANCA-associated vasculitides treated with plasma exchange. J. Am. Soc. Nephrol. 33, 1223–1224 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  58. Quintana, L. F. et al. ANCA serotype and histopathological classification for the prediction of renal outcome in ANCA-associated glomerulonephritis. Nephrol. Dial. Transpl. 29, 1764–1769 (2014).

    Article  CAS  Google Scholar 

  59. Specks, U. et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N. Engl. J. Med. 369, 417–427 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Stone, J. et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N. Engl. J. Med. 363, 221–232 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Unizony, S. et al. Clinical outcomes of treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis based on ANCA type. Ann. Rheum. Dis. 75, 1166–1169 (2016).

    Article  CAS  PubMed  Google Scholar 

  62. Mahr, A. et al. Prevalence of antineutrophil cytoplasmic antibodies in infective endocarditis. Arthritis Rheum. 66, 1672–1677 (2014).

    Article  Google Scholar 

  63. Arad, U. et al. Anti-neutrophil antibody associated vasculitis in systemic sclerosis. Semin. Arthritis Rheum. 41, 223–229 (2011).

    Article  CAS  PubMed  Google Scholar 

  64. Douglas, G., Bird, K., Flume, P., Silver, R. & Bolster, M. Wegener’s granulomatosis in patients with rheumatoid arthritis. J. Rheumatol. 30, 2064–2069 (2003).

    PubMed  Google Scholar 

  65. Nasr, S. H. et al. Membranous glomerulonephritis with ANCA-associated necrotizing and crescentic glomerulonephritis. Clin. J. Am. Soc. Nephrol. 4, 299–308 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Ramos-Casals, M., Brito-Zerón, P. & Font, J. The overlap of Sjögren’s syndrome with other systemic autoimmune diseases. Semin. Arthritis Rheum. 36, 246–255 (2007).

    Article  PubMed  Google Scholar 

  67. McAdoo, S. P. et al. Patients double-seropositive for ANCA and anti-GBM antibodies have varied renal survival, frequency of relapse, and outcomes compared to single-seropositive patients. Kidney Int. 92, 693–702 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Baldallo, C. et al. COVID-19 in a patient with hypocomplementemic urticarial syndrome and MPO-ANCA vasculitis on hemodialysis treated with omalizumab. Nefrologia 41, 354–355 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  69. Jayne, D. Vasculitis — when can biopsy be avoided? Nephrol. Dial. Transpl. 32, 1454–1456 (2017).

    Article  Google Scholar 

  70. van Daalen, E. E. et al. Developments in the histopathological classification of ANCA-associated glomerulonephritis. Clin. J. Am. Soc. Nephrol. 15, 1103–1111 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Bate, S. et al. The improved kidney risk score in ANCA-associated vasculitis for clinical practice and trials. J. Am. Soc. Nephrol. 35, 335–346 (2024).

    Article  PubMed  Google Scholar 

  72. Devaney, K. O. et al. Interpretation of head and neck biopsies in Wegener’s granulomatosis. A pathologic study of 126 biopsies in 70 patients. Am. J. Surg. Pathol. 14, 555–564 (1990).

    Article  CAS  PubMed  Google Scholar 

  73. Daum, T. E. et al. Tracheobronchial involvement in Wegener’s granulomatosis. Am. J. Respir. Crit. Care Med. 151, 522–526 (1995).

    Article  CAS  PubMed  Google Scholar 

  74. Agadi, J. B., Raghav, G., Mahadevan, A. & Shankar, S. K. Usefulness of superficial peroneal nerve/peroneus brevis muscle biopsy in the diagnosis of vasculitic neuropathy. J. Clin. Neurosci. 19, 1392–1396 (2012).

    Article  CAS  PubMed  Google Scholar 

  75. Collins, M. P. et al. Superficial peroneal nerve/peroneus brevis muscle biopsy in vasculitic neuropathy. Neurology 55, 636–643 (2000).

    Article  CAS  PubMed  Google Scholar 

  76. Villeneuve, T., Faguer, S., Collot, S., Pugnet, G. & Prévot, G. HRCT imaging of pulmonary involvement in granulomatosis with polyangiitis and microscopic polyangiitis at disease onset and during follow-up. Semin. Arthritis Rheum. 63, 152307 (2023).

    Article  PubMed  Google Scholar 

  77. Casal Moura, M., Tandon, Y. K., Hartman, T. E., Ryu, J. H. & Baqir, M. Interstitial lung disease in patients with antineutrophil cytoplasmic antibody-associated vasculitis: chest CT patterns and correlation with survival. Semin. Arthritis Rheum. 73, 152726 (2025).

    Article  CAS  PubMed  Google Scholar 

  78. Yamagata, M. et al. Prevalence and responsiveness to treatment of lung abnormalities on chest computed tomography in patients with microscopic polyangiitis: a multicenter, longitudinal, retrospective study of one hundred fifty consecutive hospital-based Japanese patients. Arthritis Rheumatol. 68, 713–723 (2016).

    Article  CAS  PubMed  Google Scholar 

  79. Hazebroek, M. R. et al. Prevalence and prognostic relevance of cardiac involvement in ANCA-associated vasculitis: eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis. Int. J. Cardiol. 199, 170–179 (2015).

    Article  CAS  PubMed  Google Scholar 

  80. Gül, A. et al. The pathogenesis, clinical presentations and treatment of monogenic systemic vasculitis. Nat. Rev. Rheumatol. 21, 414–425 (2025).

    Article  PubMed  Google Scholar 

  81. Triaille, C. et al. The emerging concept of ANCA-associated vasculitis related to inborn errors of immunity. Autoimmun. Rev. 24, 103824 (2025).

    Article  CAS  PubMed  Google Scholar 

  82. Fteiha, B., Bnaya, A., Abu Sneineh, M., Nesher, G. & Breuer, G. S. Clinical implications of ANCA positivity in a hospital setting: a tertiary center experience. Intern. Emerg. Med. 16, 429–436 (2021).

    Article  PubMed  Google Scholar 

  83. Feriozzi, S. et al. Cephotaxime-associated allergic interstitial nephritis and MPO-ANCA positive vasculitis. Ren. Fail. 22, 245–251 (2000).

    Article  CAS  PubMed  Google Scholar 

  84. Sakai, N. et al. Tubulointerstitial nephritis with anti-neutrophil cytoplasmic antibody following indomethacin treatment. Nephrol. Dial. Transpl. 14, 2774 (1999).

    Article  CAS  Google Scholar 

  85. Seeliger, B. et al. Are the 1990 American College of Rheumatology vasculitis classification criteria still valid? Rheumatology 56, 1154–1161 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Watts, R. A., Suppiah, R., Merkel, P. A. & Luqmani, R. Systemic vasculitis — is it time to reclassify? Rheumatology 50, 643–645 (2011).

    Article  PubMed  Google Scholar 

  87. Basu, N. et al. EULAR points to consider in the development of classification and diagnostic criteria in systemic vasculitis. Ann. Rheum. Dis. 69, 1744–1750 (2010).

    Article  PubMed  Google Scholar 

  88. Robson, J. C. et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for granulomatosis with polyangiitis. Arthritis Rheumatol. 74, 393–399 (2022).

    Article  CAS  PubMed  Google Scholar 

  89. Suppiah, R. et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis. Arthritis Rheumatol. 74, 400–406 (2022).

    Article  CAS  PubMed  Google Scholar 

  90. Grayson, P. C. et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for eosinophilic granulomatosis with polyangiitis. Arthritis Rheumatol. 74, 386–392 (2022).

    Article  CAS  PubMed  Google Scholar 

  91. Pagnoux, C. & Springer, J. Editorial: classifying antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides according to ANCA type or phenotypic diagnosis: salt or pepper? Arthritis Rheumatol. 68, 2837–2840 (2016).

    Article  CAS  PubMed  Google Scholar 

  92. Flossmann, O. et al. Long-term patient survival in ANCA-associated vasculitis. Ann. Rheum. Dis. 70, 488–494 (2011).

    Article  PubMed  Google Scholar 

  93. Walsh, M. et al. Risk factors for relapse of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 64, 542–548 (2012).

    Article  CAS  PubMed  Google Scholar 

  94. Booth, A. D. et al. Outcome of ANCA-associated renal vasculitis: a 5-year retrospective study. Am. J. Kidney Dis. 41, 776–784 (2003).

    Article  PubMed  Google Scholar 

  95. Hogan, S. L. et al. Predictors of relapse and treatment resistance in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis. Ann. Intern. Med. 143, 621–631 (2005).

    Article  PubMed  Google Scholar 

  96. Pagnoux, C. et al. Predictors of treatment resistance and relapse in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis: comparison of two independent cohorts. Arthritis Rheum. 58, 2908–2918 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  97. Mahr, A. et al. Revisiting the classification of clinical phenotypes of anti-neutrophil cytoplasmic antibody-associated vasculitis: a cluster analysis. Ann. Rheum. Dis. 72, 1003–1010 (2013).

    Article  PubMed  Google Scholar 

  98. Puéchal, X. 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. 68, 690–701 (2016).

    Article  PubMed  Google Scholar 

  99. Deshayes, S. et al. Clinical impact of subgrouping ANCA-associated vasculitis according to antibody specificity beyond the clinicopathological classification. Rheumatology 58, 1731–1739 (2019).

    Article  CAS  PubMed  Google Scholar 

  100. Lyons, P. A. et al. Genetically distinct subsets within ANCA-associated vasculitis. N. Engl. J. Med. 367, 214–223 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Merkel, P. A. et al. Identification of functional and expression polymorphisms associated with risk for antineutrophil cytoplasmic autoantibody-associated vasculitis. Arthritis Rheumatol. 69, 1054–1066 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Miloslavsky, E. M. et al. Myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)-positive and ANCA-negative patients with granulomatosis with polyangiitis (Wegener’s): distinct patient subsets. Arthritis Rheumatol. 68, 2945–2952 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Ecclestone, T. & Watts, R. A. Classification and epidemiology of vasculitis: emerging concepts. Best. Pract. Res. Clin. Rheumatol. 37, 101845 (2023).

    Article  PubMed  Google Scholar 

  104. Rathmann, J., Segelmark, M. & Mohammad, A. J. Evaluation of the ACR/EULAR 2022 criteria for classification of ANCA-associated vasculitis in a population-based cohort from Sweden. Rheumatology 63, 1965–1972 (2024).

    Article  PubMed  Google Scholar 

  105. Merkel, P. A. et al. Comparison of disease activity measures for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. Ann. Rheum. Dis. 68, 103–106 (2009).

    Article  CAS  PubMed  Google Scholar 

  106. Mukhtyar, C. et al. Modification and validation of the Birmingham Vasculitis Activity Score (version 3). Ann. Rheum. Dis. 68, 1827–1832 (2009).

    Article  CAS  PubMed  Google Scholar 

  107. Stone, J. H. et al. A disease-specific activity index for Wegener’s granulomatosis: modification of the Birmingham Vasculitis Activity Score. Arthritis Rheum. 44, 912–920 (2001).

    Article  CAS  PubMed  Google Scholar 

  108. Luqmani, R. A. et al. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM 87, 671–678 (1994).

    CAS  PubMed  Google Scholar 

  109. Luqmani, R. A. in Rare Diseases of the Immune System: Anti-Neutrophil Cytoplasmic Antibody (ANCA) Associated Vasculitis (eds Albert, R. S. & Guillevin, L.) 57–76 (Springer Nature Switzerland, 2020).

  110. Piccirillo, J. F., Merritt, M. G. Jr. & Richards, M. L. Psychometric and clinimetric validity of the 20-item Sino-Nasal Outcome Test (SNOT-20). Otolaryngol. Head. Neck Surg. 126, 41–47 (2002).

    Article  PubMed  Google Scholar 

  111. Juniper, E. F., O’Byrne, P. M., Guyatt, G. H., Ferrie, P. J. & King, D. R. Development and validation of a questionnaire to measure asthma control. Eur. Resp. J. 14, 902–907 (1999).

    Article  CAS  Google Scholar 

  112. Luqmani, R. A. Disease assessment in systemic vasculitis. Nephrol. Dial. Transpl. 30, i76–i82 (2015).

    Article  CAS  Google Scholar 

  113. Exley, A. R. et al. Development and initial validation of the Vasculitis Damage Index for the standardized clinical assessment of damage in the systemic vasculitides. Arthritis Rheum. 40, 2187–2195 (1997).

    Article  Google Scholar 

  114. Seo, P. et al. The future of damage assessment in vasculitis. J. Rheumatol. 34, 1357–1371 (2007).

    PubMed  Google Scholar 

  115. Robson, J. et al. Glucocorticoid treatment and damage in the anti-neutrophil cytoplasm antibody-associated vasculitides: long-term data from the European Vasculitis Study Group trials. Rheumatology 54, 471–481 (2015).

    Article  CAS  PubMed  Google Scholar 

  116. Bloom, J. L. et al. The association between age at diagnosis and disease characteristics and damage in patients with ANCA-associated vasculitis. Arthritis Rheumatol. 75, 2216–2227 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Scherbacher, P. J., Hellmich, B., Feng, Y. S. & Löffler, C. Prospective study of complications and sequelae of glucocorticoid therapy in ANCA-associated vasculitis. RMD Open 10, e003956 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  118. Stone, J. H. et al. The glucocorticoid toxicity index: measuring change in glucocorticoid toxicity over time. Semin Arthritis Rheum. 55, 152010 (2022).

    Article  CAS  PubMed  Google Scholar 

  119. Miloslavsky, E. M. et al. Development of a glucocorticoid toxicity index (GTI) using multicriteria decision analysis. Ann. Rheum. Dis. 76, 543–546 (2017).

    Article  PubMed  Google Scholar 

  120. Patel, N. J. et al. Glucocorticoid toxicity index scores by domain in patients with antineutrophil cytoplasmic antibody-associated vasculitis treated with avacopan versus standard prednisone taper: post-hoc analysis of data from the ADVOCATE trial. Lancet Rheumatol. 5, e130–e138 (2023).

    Article  CAS  PubMed  Google Scholar 

  121. Desaintjean, C. et al. Mepolizumab and benralizumab in patients with severe asthma and a history of eosinophilic granulomatosis with polyangiitis. Front. Med. 11, 1341310 (2024).

    Article  Google Scholar 

  122. Seo, P., Jayne, D., Luqmani, R. & Merkel, P. A. Assessment of damage in vasculitis: expert ratings of damage. Rheumatology 48, 823–827 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  123. Herlyn, K., Hellmich, B., Seo, P. & Merkel, P. A. Patient-reported outcome assessment in vasculitis may provide important data and a unique perspective. Arthritis Care Res. 62, 1639–1645 (2010).

    Article  Google Scholar 

  124. Tomasson, G. et al. Assessment of health-related quality of life as an outcome measure in granulomatosis with polyangiitis (Wegener’s). Arthritis Care Res. 64, 273–279 (2012).

    Article  Google Scholar 

  125. Strand, V. et al. The impact of treatment with avacopan on health-related quality of life in antineutrophil cytoplasmic antibody-associated vasculitis: a post-hoc analysis of data from the ADVOCATE trial. Lancet Rheumatol. 5, e451–e460 (2023).

    Article  CAS  PubMed  Google Scholar 

  126. Robson, J. C. et al. Health-related quality of life in ANCA-associated vasculitis and item generation for a disease-specific patient-reported outcome measure. Patient Relat. Outcome Meas. 9, 17–34 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  127. Testa, M. A. & Simonson, D. C. Assessment of quality-of-life outcomes. N. Engl. J. Med. 334, 835–840 (1996).

    Article  CAS  PubMed  Google Scholar 

  128. Bevans, M., Ross, A. & Cella, D. Patient-reported outcomes measurement information system (PROMIS): efficient, standardized tools to measure self-reported health and quality of life. Nurs. Outlook 62, 339–345 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  129. Delvino, P. et al. Impact of mepolizumab on the AAV-PRO questionnaire in eosinophilic granulomatosis with polyangiitis: data from a European multicentre study. Rheumatology 64, 4937–4947 (2025).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Quartuccio, L. et al. Unmet needs in ANCA-associated vasculitis: physicians’ and patients’ perspectives. Front. Immunol. 14, 1112899 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Floyd, L. et al. A systematic review of patient-reported outcome measures in patients with anti-neutrophil cytoplasmic antibody associated vasculitis. Rheumatology 63, 2624–2637 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Merkel, P. A. 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. 142, 620–626 (2005).

    Article  PubMed  Google Scholar 

  133. Suppiah, R. et al. A model to predict cardiovascular events in patients with newly diagnosed Wegener’s granulomatosis and microscopic polyangiitis. Arthritis Care Res. 63, 588–596 (2011).

    Article  Google Scholar 

  134. Jayne, D. in Rare Diseases of the Immune System: Anti-Neutrophil Cytoplasmic Antibody (ANCA) Associated Vasculitis (eds Albert, R. S. & Guillevin, L.) 293–311 (Springer Nature Switzerland, 2020).

  135. McClure, M. E. et al. Evaluation of PR3-ANCA status after rituximab for ANCA-associated vasculitis. J. Clin. Rheumatol. 25, 217–223 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  136. Sanchez-Alamo, B. et al. Systematic literature review informing the 2022 update of the EULAR recommendations for the management of ANCA-associated vasculitis (AAV): Part 2 — treatment of eosinophilic granulomatosis with polyangiitis and diagnosis and general management of AAV. RMD Open 9, e003083 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  137. Doubelt, I. et al. Clinical manifestations and long-term outcomes of eosinophilic granulomatosis with polyangiitis in North America. ACR Open Rheumatol. 3, 404–412 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  138. Seror, R. et al. Treatment strategies and outcome of induction-refractory Wegener’s granulomatosis or microscopic polyangiitis: analysis of 32 patients with first-line induction-refractory disease in the WEGENT trial. Ann. Rheum. Dis. 69, 2125–2130 (2010).

    Article  PubMed  Google Scholar 

  139. Guillevin, L. et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N. Engl. J. Med. 371, 1771–1780 (2014).

    Article  PubMed  Google Scholar 

  140. Terrier, B. et al. Long-term efficacy of remission-maintenance regimens for ANCA-associated vasculitides. Ann. Rheum. Dis. 77, 1150–1156 (2018).

    Article  PubMed  Google Scholar 

  141. McClure, M. & Jones, R. B. Treatment of relapses in ANCA-associated vasculitis. Clin. J. Am. Soc. Nephrol. 14, 967–969 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  142. Outh, R. et al. Relapses in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a retrospective study. Clin. Rheumatol. 39, 1601–1608 (2020).

    Article  PubMed  Google Scholar 

  143. Kemna, M. 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. 26, 537–542 (2015).

    Article  CAS  PubMed  Google Scholar 

  144. Fussner, L. A. et al. Factors determining the clinical utility of serial measurements of antineutrophil cytoplasmic antibodies targeting proteinase 3. Arthritis Rheumatol. 68, 1700–1710 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Casal Moura, M. et al. Maintenance of remission and risk of relapse in myeloperoxidase positive antineutrophil cytoplasmic antibody-associated vasculitis with kidney involvement. Clin. J. Am. Soc. Nephrol. 18, 47–59 (2023).

    Article  PubMed  Google Scholar 

  146. van Dam, L. S. et al. Proteinase-3-anti-neutrophil cytoplasmic antibodies (PR3-ANCAs) predict relapses in ANCA-associated vasculitis patients after rituximab. Nephrol. Dial. Transpl. 36, 1408–1417 (2020). 2021.

    Google Scholar 

  147. Gamerith, G. et al. Association of baseline soluble immune checkpoints with the risk of relapse in PR3-ANCA vasculitis following induction of remission. Ann. Rheum. Dis. 82, 253–261 (2023).

    Article  CAS  PubMed  Google Scholar 

  148. Moran, S. M. et al. The clinical application of urine soluble CD163 in ANCA-associated vasculitis. J. Am. Soc. Nephrol. 32, 2920–2932 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Almaani, S. et al. Urine and plasma complement Ba levels during disease flares in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis. Kidney Int. Rep. 8, 2421–2427 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  150. Fauci, A. S., Haynes, B. F., Katz, P. & Wolff, S. M. Wegener’s granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann. Intern. Med. 98, 76–85 (1983).

    Article  CAS  PubMed  Google Scholar 

  151. Berti, A., Cornec, D., Crowson, C. S., Specks, U. & Matteson, E. L. The epidemiology of antineutrophil cytoplasmic autoantibody-associated vasculitis in Olmsted county, Minnesota: a twenty-year US population-based study. Arthritis Rheumatol. 69, 2338–2350 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Jennette, J. C. Rapidly progressive crescentic glomerulonephritis. Kidney Int. 63, 1164–1177 (2003).

    Article  PubMed  Google Scholar 

  153. de Joode, A. A. E. et al. Renal survival in proteinase 3 and myeloperoxidase ANCA-associated systemic vasculitis. Clin. J. Am. Soc. Nephrol. 8, 1709–1717 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  154. Li, Z. Y., Gou, S. J., Chen, M. & Zhao, M. H. Predictors for outcomes in patients with severe ANCA-associated glomerulonephritis who were dialysis-dependent at presentation: a study of 89 cases in a single Chinese center. Semin. Arthritis Rheum. 42, 515–521 (2013).

    Article  CAS  PubMed  Google Scholar 

  155. Lee, T. et al. Predictors of treatment outcomes in ANCA-associated vasculitis with severe kidney failure. Clin. J. Am. Soc. Nephrol. 9, 905–913 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  156. Berden, A. E. et al. Histopathologic classification of ANCA-associated glomerulonephritis. J. Am. Soc. Nephrol. 21, 1628–1636 (2010).

    Article  PubMed  Google Scholar 

  157. Casal Moura, M., Fervenza, F. C., Specks, U. & Sethi, S. Kidney biopsy chronicity grading in antineutrophil cytoplasmic antibody associated vasculitis. Nephrol. Dial. Transpl. 37, 1710–1721 (2021).

    Article  Google Scholar 

  158. Brix, S. R. et al. Development and validation of a renal risk score in ANCA-associated glomerulonephritis. Kidney Int. 94, 1177–1188 (2018).

    Article  CAS  PubMed  Google Scholar 

  159. Takeda, R. et al. Development of a kidney prognostic score in a Japanese cohort of patients with antineutrophil cytoplasmic autoantibody vasculitis. Kidney Int. Rep. 9, 611–623 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  160. Sandino-Bermúdez, M. J., Hernández-Andrade, A., Hinojosa-Azaola, A., Martín-Nares, E. & Mejía-Vilet, J. M. Performance of clinical and histological prognostic scores for kidney survival in ANCA-associated vasculitis. Rheumatology 64, 1981–1988 (2024).

    Article  Google Scholar 

  161. Casal Moura, M., Fervenza, F. C., Specks, U. & Sethi, S. “Normal” glomerular score correlates with outcomes in antineutrophil cytoplasmic autoantibody-associated vasculitis with glomerulonephritis. Kidney Int. Rep. 10, 596–600 (2025).

    Article  PubMed  Google Scholar 

  162. Odler, B. et al. Challenges of defining renal response in ANCA-associated vasculitis: call to action? Clin. Kidney J. 16, 965–975 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Uchida, L. et al. WCN25-1022 long-term kidney function beyond 12 months and kidney relapse after initiation of treatment for ANCA-associated vasculitis. Kidney Int. Rep. 10, S617–S618 (2025).

    Article  Google Scholar 

  164. Moiseev, S. et al. Traditional and disease specific risk factors for cardiovascular events in ANCA-associated vasculitis: a multinational retrospective study. J. Rheumatol. 50, 1094 (2023).

    Article  PubMed  Google Scholar 

  165. Moiseev, S. et al. Association of venous thromboembolic events with skin, pulmonary and kidney involvement in ANCA-associated vasculitis: a multinational study. Rheumatology 60, 4654–4661 (2021).

    Article  CAS  PubMed  Google Scholar 

  166. Steiger, S., Rossaint, J., Zarbock, A. & Anders, H. J. Secondary immunodeficiency related to kidney disease (SIDKD)-definition, unmet need, and mechanisms. J. Am. Soc. Nephrol. 33, 259–278 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Odler, B. et al. Risk factors for serious infections in ANCA-associated vasculitis. Ann. Rheum. Dis. 82, 681–687 (2023).

    Article  CAS  PubMed  Google Scholar 

  168. Windpessl, M. et al. ANCA status or clinical phenotype — what counts more? Curr. Rheumatol. Rep. 23, 37 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Hilhorst, M. et al. Patients with antineutrophil cytoplasmic antibodies associated vasculitis in remission are hypercoagulable. J. Rheumatol. 40, 2042–2046 (2013).

    Article  PubMed  Google Scholar 

  170. Nygaard, L. et al. Increased risk of cardiovascular disease preceding diagnosis of incident ANCA-associated vasculitis: a Danish nationwide study. Rheumatology 63, 1313–1321 (2024).

    Article  PubMed  Google Scholar 

  171. Bramlage, C. P. et al. Management of cardiovascular risk factors in patients with ANCA-associated vasculitis. J. Eval. Clin. Pract. 23, 747–754 (2017).

    Article  PubMed  Google Scholar 

  172. Cetin, B. et al. FRAX scores are increased in patients with ANCA-associated vasculitis. Int. Urol. Nephrol. 53, 2333–2339 (2021).

    Article  CAS  PubMed  Google Scholar 

  173. van Daalen, E. E. et al. Effect of rituximab on malignancy risk in patients with ANCA-associated vasculitis. Ann. Rheum. Dis. 76, 1064–1069 (2017).

    Article  PubMed  Google Scholar 

  174. Pankhurst, T., Savage, C. O., Gordon, C. & Harper, L. Malignancy is increased in ANCA-associated vasculitis. Rheumatology 43, 1532–1535 (2004).

    Article  CAS  PubMed  Google Scholar 

  175. Pecher, A. C., Henes, M. & Henes, J. C. Optimal management of ANCA-associated vasculitis before and during pregnancy: current perspectives. Arch. Gynecol. Obst. 308, 379–385 (2023).

    Article  Google Scholar 

  176. Rüegg, L. et al. EULAR recommendations for use of antirheumatic drugs in reproduction, pregnancy, and lactation: 2024 update. Ann. Rheum. Dis. 84, 910–926 (2025).

    Article  PubMed  Google Scholar 

  177. Westman, K. W., A, B. P., Olsson, H., Ranstam, J. & Wieslander, J. Relapse rate, renal survival, and cancer morbidity in patients with Wegener’s granulomatosis or microscopic polyangiitis with renal involvement. J. Am. Soc. Neph. 9, 842–852 (1997).

    Article  Google Scholar 

  178. Heijl, C. 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. 70, 1415–1421 (2011).

    Article  CAS  PubMed  Google Scholar 

  179. Kronbichler, A., Leierer, J., Gauckler, P. & Shin, J. I. Comorbidities in ANCA-associated vasculitis. Rheumatology 59, iii79–iii83 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Tan, J. A. et al. Mortality in ANCA-associated vasculitis: a meta-analysis of observational studies. Ann. Rheum. Dis. 76, 1566–1574 (2017).

    Article  PubMed  Google Scholar 

  181. Steinberg, A. W., Wechsler, M. E. W. & Fernández Pérez, E. R. Trends in antineutrophil cytoplasmic autoantibody-associated vasculitis-related mortality in the United States, 1999 to 2017. Ann. Intern. Med. 172, 160–163 (2020).

    Article  PubMed  Google Scholar 

  182. Scherlinger, M. et al. Worldwide trends in all-cause mortality of auto-immune systemic diseases between 2001 and 2014. Autoimmun. Rev. 19, 102531 (2020).

    Article  CAS  PubMed  Google Scholar 

  183. Guillevin, L. et al. Prognostic factors in polyarteritis nodosa and Churg–Strauss syndrome. Medicine 75, 17–28 (1996).

    Article  CAS  PubMed  Google Scholar 

  184. Guillevin, L. et al. The five-factor score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French vasculitis study group (FVSG) cohort. Medicine 90, 19–27 (2011).

    Article  PubMed  Google Scholar 

  185. Schirmer, J. H. et al. Clinical presentation and long-term outcome of 144 patients with microscopic polyangiitis in a monocentric German cohort. Rheumatology 55, 71–79 (2016).

    Article  PubMed  Google Scholar 

  186. Moosig, F. et al. A vasculitis centre based management strategy leads to improved outcome in eosinophilic granulomatosis and polyangiitis (Churg–Strauss, EGPA): monocentric experiences in 150 patients. Ann. Rheum. Dis. 72, 1011–1017 (2013).

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  188. Matsushita, K. et al. Incorporating kidney disease measures into cardiovascular risk prediction: development and validation in 9 million adults from 72 datasets. eClinicalMedicine 27, 100552 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  189. Benichou, N. et al. Proteinuria and hematuria after remission induction are associated with outcome in ANCA-associated vasculitis. Kidney Int. 103, 1144–1155 (2023).

    Article  CAS  PubMed  Google Scholar 

  190. Monti, S. et al. Use and reporting of outcome measures in randomized trials for anti-neutrophil cytoplasmic antibody-associated vasculitis: a systematic literature review. Semin. Arthritis Rheum. 50, 1314–1325 (2020).

    Article  CAS  PubMed  Google Scholar 

  191. Quinn, K. A. et al. Developing a composite outcome tool to measure response to treatment in ANCA-associated vasculitis: a mixed methods study from OMERACT 2020. Semin. Arthritis Rheum. 51, 1134–1138 (2021).

    Article  PubMed  Google Scholar 

  192. Chen, D. P. et al. PRTN3 variant correlates with increased autoantigen levels and relapse risk in PR3-ANCA versus MPO-ANCA disease. JCI Insight 8, e166107 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  193. Casal Moura, M. et al. Risk of relapse of ANCA-associated vasculitis among patients homozygous for the proteinase 3 gene Val119Ile polymorphism. RMD Open. 9, e002935 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  194. Zeek, P. M. Periarteritis nodosa and other forms of necrotizing angiitis. N. Engl. J. Med. 248, 764–772 (1953).

    Article  CAS  PubMed  Google Scholar 

  195. Alarcón-Segovia, D. The necrotizing vasculitides. A new pathogenetic classification. Med. Clin. North. Am. 61, 241–260 (1977).

    Article  PubMed  Google Scholar 

  196. Fauci, A. S., Haynes, B. & Katz, P. The spectrum of vasculitis: clinical, pathologic, immunologic and therapeutic considerations. Ann. Intern. Med. 89, 660–676 (1978).

    Article  CAS  PubMed  Google Scholar 

  197. Watts, R. et al. Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies. Ann. Rheum. Dis. 66, 222–227 (2007).

    Article  PubMed  Google Scholar 

  198. Craven, A. et al. ACR/EULAR-endorsed study to develop diagnostic and classification criteria for vasculitis (DCVAS). Clin. Exp. Nephrol. 17, 619–621 (2013).

    Article  CAS  PubMed  Google Scholar 

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Author notes

  1. These authors jointly supervised this work: Marta Casal Moura and Andreas Kronbichler.

Authors and Affiliations

  1. Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA

    Marta Casal Moura & Fernando C. Fervenza

  2. Departamento de Biomedicina, Faculdade de Medicina da Universidade do Porto, Porto, Portugal

    Marta Casal Moura

  3. Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, USA

    Peter A. Merkel

  4. Division of Epidemiology, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA

    Peter A. Merkel

  5. Department of Medicine, University of Cambridge, Cambridge, UK

    David Jayne & Andreas Kronbichler

  6. Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clinic University of Barcelona, Barcelona, Spain

    Maria C. Cid

  7. Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain

    Maria C. Cid

  8. Institute of Infection and Immunity, University of Glasgow, Glasgow, UK

    Neil Basu

  9. Department of Internal Medicine, Rheumatology, Pneumology, Nephrology and Diabetology, Medius Kliniken, University of Tübingen, Kirchheim-Teck, Germany

    Bernhard Hellmich

  10. National Referral Center for Rare Systemic Autoimmune Diseases, Université Paris Cité, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France

    Benjamin Terrier

  11. Vasculitis Expertise Centre Groningen, Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands

    Abraham Rutgers

  12. Vasculitis Foundation, Kansas City, MO, USA

    Jennifer Gordon & Joyce Kullman

  13. Dutch Patient Vasculitis Organization, Maarsen, The Netherlands

    Peter Verhoeven

  14. Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, OH, USA

    Carol A. Langford

  15. Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Ingeborg M. Bajema

  16. Division of Nephrology, Johns Hopkins University, Baltimore, MD, USA

    Duvuru Geetha

  17. Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia

    A. Richard Kitching

  18. Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA

    John H. Stone

  19. Division of Pulmonary and Critical Care, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA

    Ulrich Specks

  20. Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden

    Andreas Kronbichler

  21. Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria

    Andreas Kronbichler

Authors
  1. Marta Casal Moura
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  2. Peter A. Merkel
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  3. David Jayne
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  4. Maria C. Cid
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  5. Neil Basu
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  6. Bernhard Hellmich
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  7. Benjamin Terrier
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  8. Abraham Rutgers
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  9. Jennifer Gordon
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  10. Peter Verhoeven
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  11. Joyce Kullman
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  12. Carol A. Langford
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  13. Ingeborg M. Bajema
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  14. Duvuru Geetha
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  15. Fernando C. Fervenza
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  16. A. Richard Kitching
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  17. John H. Stone
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  18. Ulrich Specks
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  19. Andreas Kronbichler
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Contributions

M.C.M. and A.K. had the idea for this review paper, conceptualized the proposal and the manuscript that generated this work, and coordinated the project. P.A.M. and D.J. provided initial review of, and input into, the proposal and the manuscript. All authors contributed to writing and revising the paper.

Corresponding authors

Correspondence to Marta Casal Moura or Andreas Kronbichler.

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Competing interests

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors. In the past two years, P.A.M. received funds for: consulting from AbbVie, Alpine, Amgen, ArGenx, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Commonwealth Serum Laboratories (CSL) Behring, GlaxoSmithKline, iCell, Interius, Kinevant, Kyverna, Metagenomia, Neutrolis, Novartis, NS Pharma, Q32, Quell, Regeneron, Sanofi, Sparrow, Takeda and Vistera; and for research support from AbbVie, Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eicos, Electra, GlaxoSmithKline, Neutrolis and Takeda; and stock options from Kyverna, Q32, Lifordi and Sparrow; and royalties from UpToDate. D.J. received honoraria or consulting fees from Amgen, AstraZeneca, Aurinia, Bristol-Myers Squibb, Boehringer-Ingelheim, ChemoCentryx, GlaxoSmithKline, the National Institute for Health and Care Excellence, Novartis, Otsuka, Roche/Genentech, Takeda, UCB and CSL Vifor. M.C.C. received consulting fees from GlaxoSmithKline, AbbVie, CSL Vifor, AstraZeneca, Alexion, Boehringer-Ingelheim and Novartis; royalties from UpToDate; and was supported by the Ministerio de Ciencia, Innovación y Universidades AEI/10.13039/501100011033 (PID2023-152265OB-I00), FEDER-EU. N.B. received consulting or advisory board honoraria from CSL Vifor and GlaxoSmithKline, and research grant support from AstraZeneca, CSL Vifor and GlaxoSmithKline. B.H. received consulting fees from Alexion, AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, InflafRx, Novartis and CSL Vifor and honoraria for lectures from AbbVie, Amgen, AstraZeneca, BMS, Boehringer, Chugai, GlaxoSmithKline, Janssen, Merck Sharp & Dohme (MSD), Pfizer, Phadia, Roche and CSL Vifor. B.T. reported consulting fees from AstraZeneca, GlaxoSmithKline, CSL Vifor, Novartis, Laboratoire Français du Fractionnement et des Biotechnologies (LFB) and Boehringer-Ingelheim. C.A.L. received research grants from Bristol-Myers Squibb, AstraZeneca, GlaxoSmithKline, NSD Pharma and non-paid consultancy royalties from Bristol-Myers Squibb, AbbVie and AstraZeneca. I.M.B. received grant support from CSL Vifor and Novartis; educational fees from Astra-Zeneca and CSL Vifor; and consulting fees from GlaxoSmithKline, Aurinia, Novartis, Amgen, Hansa and Alentis Consultancy Boards. I.M.B. also serves on the Glomerular Disease Council (CSL Vifor, Novartis), is owner of BiPath and vice-president of EUVAS. D.G. received consulting fees from Amgen, ChemoCentryx, Otsuka, Calliditas and Vera Therapeutics. F.C.F. received unrestricted research funding from Genentech/Roche. A.R.K. received research support, contract work and consultancy fees (funds to institution) from CSL, Visterra, Alentis, Variant Bio, Patrys and Sitala; speaker fees from CSL Seqirus; royalties from UpToDate; and is the chair of the Australia and New Zealand Vasculitis Society. U.S. received consulting or advisory board honoraria from Amgen, Argenx, AstraZeneca, Boehringer-Ingelheim, ChemoCentryx, CSL Vifor and Novartis; and research grant support from Amgen, AstraZeneca, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, NorthStar Medical Radioisotopes, Novartis and NS-Pharma. A.K. received honoraria or consulting fees from Amgen, AstraZeneca, Boehringer-Ingelheim, CSL Vifor, Delta4, GlaxoSmithKline, Miltenyi Biotec, Novartis, Novo Nordisk, Otsuka, Roche, Sobi and Walden Biosciences. Peer review information; and unrestricted research grants from CSL Vifor and Otsuka received by A.K. He serves on the editorial boards of Glom Dis and Nephrol Dial Transplant. M.C.M., A.R., J.G., P.V., J.K. and J.H.S. have no competing interests to report.

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Nature Reviews Rheumatology thanks Renate Kain, Sang Won Lee and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Related links

AAV-PRO: The score will be provided upon request at: https://innovation.ox.ac.uk/outcome-measures/anca-associated-vasculitis-patient-reported-outcome-aav-pro/

Birmingham vasculitis activity score (BVAS V3.0): https://innovation.ox.ac.uk/wp-content/uploads/2023/11/BVAS-UK-English-SAMPLE-COPY.pdf

Birmingham vasculitis activity score (BVAS): https://vcrc.rarediseasesnetwork.org/sites/default/files/2022-03/VCRC_Resources_Researchers-Clinicians_Birmingham-Vasculitis-Activity-Score-2003-BVAS-2003.pdf

Birmingham vasculitis activity score for granulomatosis with polyangiitis (BVAS-GPA): https://vcrc.rarediseasesnetwork.org/sites/default/files/2022-03/VCRC_Resources_Researchers-Clinicians_Birmingham-Vasculitis-Activity-Score-for-Granulomatosis-with-polyangiitis-Wegeners-GPA-Form-BVAS-WG.pdf

Combined damage assessment (CDA): https://omeract.org/wp-content/uploads/2023/11/26-The-Future-of-Damage-Assessment-in-Vasculitis.pdf

Five-factor score (FFS): https://vcrc.rarediseasesnetwork.org/sites/default/files/2022-03/VCRC_Resources_Researchers-Clinicians_Five-Factor-Score-FFS.pdf

Vasculitis damage index (VDI): https://vcrc.rarediseasesnetwork.org/sites/default/files/2022-03/VCRC_Resources_Researchers-Clinicians_Vasculitis-Damage-Index-VDI.pdf

Supplementary information

Glossary

Alveolar haemorrhage

The presence of blood within the alveoli (air sacs) of the lungs, often caused by injury or disease; it can lead to difficulties in breathing, coughing up blood and impaired gas exchange.

Capillaritis

An inflammatory process that primarily affects capillaries (the smallest blood vessels in the body) and is characterized histologically by neutrophilic infiltration of the capillary walls, leukocytoclastic vasculitis, fibrinoid necrosis of the vessel and erythrocyte extravasation.

Conductive hearing loss

A type of hearing loss that occurs when sound waves cannot efficiently travel through the outer ear, eardrum or middle ear.

Eosinophilia

Eosinophilia is characterized by an increased number of eosinophils in the blood, defined by an absolute eosinophil count greater than 500 cells per microlitre or an eosinophil percentage that exceeds 10% of the total white blood cell count.

Gold standard

The most reliable and accurate method for diagnosing a condition, testing a procedure or assessing treatment effectiveness; it serves as the benchmark against which other methods or treatments are compared.

Granulomatous inflammation

A chronic inflammatory response characterized by the formation of granulomas, which are aggregates of macrophages, often surrounded by lymphocytes and other immune cells; this type of inflammation typically occurs in response to persistent infections, foreign bodies or certain diseases, such as tuberculosis, sarcoidosis and leprosy.

Interstitial lung disease

A group of pulmonary disorders characterized by inflammation and fibrosis of the lung interstitium, leading to impaired gas exchange and respiratory dysfunction; it can result from various causes, including autoimmune diseases, environmental exposures and medications.

Mononeuritis multiplex

Mononeuritis multiplex is characterized by the simultaneous or sequential inflammation and damage of two or more peripheral nerves, typically affecting different anatomical areas; it often results from systemic diseases such as autoimmune disorders, vasculitis or infections; symptoms include pain, weakness and sensory disturbances like numbness or tingling.

Necrotizing and crescentic glomerulonephritis

A severe kidney disorder characterized by rapid glomerular damage and crescent formation, often leading to acute kidney failure; it is often associated with autoimmune diseases and vasculitis.

Orbital pseudotumours

A benign, non-infectious inflammatory condition of the orbit that causes swelling, pain and potential vision changes, often resembling a tumour.

Saddle nose deformity

A condition characterized by a collapse or depression of the nasal bridge, creating a saddle-like appearance. It can result from trauma, congenital conditions, or diseases like syphilis or granulomatosis with polyangiitis (GPA).

Subglottic stenosis

A narrowing of the airway in the subglottic region, located between the vocal cords and the first tracheal ring; symptoms may include inspiratory stridor, dyspnea and voice abnormalities.

Vasculitis

Inflammation of the blood vessels; it can affect the arteries, veins or capillaries, leading to a variety of symptoms, depending on which vessels and organs are involved.

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Casal Moura, M., Merkel, P.A., Jayne, D. et al. Challenges in the diagnosis, classification and prognosis of ANCA-associated vasculitis. Nat Rev Rheumatol 21, 719–736 (2025). https://doi.org/10.1038/s41584-025-01306-w

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