You are here

  • Home
  • Archive
  • Volume 81, Issue 3
  • 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis

Article Text

Article menu
Criteria
2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis
  1. Ravi Suppiah1,
  2. Joanna C Robson2,
  3. Peter C Grayson3,
  4. Cristina Ponte4,
  5. Anthea Craven5,
  6. Sara Khalid5,
  7. Andrew Judge6,7,
  8. Andrew Hutchings8,
  9. Peter A Merkel9,
  10. Raashid A Luqmani5,
  11. Richard A Watts5,10
  12. THE DCVAS INVESTIGATORS
  1. 1 Auckland District Health Board, Auckland, New Zealand
  2. 2 Centre for Health and Clinical Research, University of the West of England and University Hospitals and Weston NHS Foundation Trust, Bristol, UK
  3. 3 National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, USA
  4. 4 Hospital de Santa Maria, Centro Hospitalar Universitario Lisboa Norte, Universidade de Lisboa, and Centro Académico deMedicina de Lisboa, Lisbon, Portugal
  5. 5 Oxford NIHR Biomedical Research Centre and University of Oxford, Oxford, UK
  6. 6 Bristol NIHR Biomedical Research Centre and University of Bristol, Bristol, UK
  7. 7 Centre for Statistics in Medicine, University of Oxford, Oxford, UK
  8. 8 London School of Hygiene and Tropical Medicine, London, UK
  9. 9 University of Pennsylvania, Philadelphia, Pennsylvania, USA
  10. 10 University of East Anglia, Norwich, UK
  1. Correspondence to Professor Peter A Merkel, Division of Rheumatology, University of Pennsylvania, White Building, Fifth Floor, 3400 Spruce Street, Philadelphia, Pennsylvania, USA; pmerkel{at}upenn.edu

Abstract

Objective To develop and validate classification criteria for microscopic polyangiitis (MPA).

Methods Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.

Results The development set for MPA consisted of 149 cases of MPA and 408 comparators. The validation set consisted of an additional 142 cases of MPA and 414 comparators. From 91 candidate items, regression analysis identified 10 items for MPA, 6 of which were retained. The final criteria and their weights were as follows: perinuclear antineutrophil cytoplasmic antibody (ANCA) or anti-myeloperoxidase-ANCA positivity (+6), pauci-immune glomerulonephritis (+3), lung fibrosis or interstitial lung disease (+3), sino-nasal symptoms or signs (−3), cytoplasmic ANCA or anti-proteinase 3 ANCA positivity (−1) and eosinophil count ≥1×109/L (−4). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having MPA with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 91% (95% CI 85% to 95%) and the specificity was 94% (95% CI 92% to 96%).

Conclusion The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for MPA are now validated for use in clinical research.

  • rehabilitation
  • arthritis
  • rheumatoid

http://dx.doi.org/10.1136/annrheumdis-2021-221796

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Introduction

    The first description of ‘periarteritis nodosa’ was made by Kussmaul and Maier in 1866.1 In 1948, Davson et al described 14 cases at autopsy that fitted the clinical description of periarteritis nodosa.2 They divided the cases into two groups based on the histological findings in the kidneys. The clinical presentations of both groups were similar, but their pathological features differed: nine patients showed a distinctive pattern of necrotising glomerulonephritis with no arterial aneurysms, whereas the other five patients showed no glomerular lesions in the kidney but had widespread renal arterial aneurysms and renal infarcts. This is the first time that a clear distinction was made between the microscopic form of polyarteritis nodosa (now called microscopic polyangiitis (MPA)) and classic polyarteritis nodosa (PAN). The 1990 American College of Rheumatology (ACR) criteria for the classification of vasculitis did not make this distinction; instead both entities were included under the term ‘polyarteritis nodosa’3 or possibly ‘granulomatosis with polyangiitis’ (then called Wegener’s granulomatosis).

    The publication that resulted from the 1994 Chapel Hill Consensus Conference (CHCC) aimed to standardise the nomenclature and commented that ‘different names are being used for the same disease and the same name is being used for different diseases’.4 The distinction between MPA and PAN is recognised in the CHCC definitions. The main discriminating feature between MPA and PAN is the presence in MPA of pauci-immune vasculitis in arterioles, venules or capillaries. PAN is restricted to a medium-vessel disease, and MPA is a predominantly small-vessel vasculitis that can also involve medium-sized vessels.

    The resulting inconsistency between disease definitions and existing classification criteria highlights an important need to update the classification criteria and to include MPA as its own entity. Additionally, over time there have been improvements in our understanding of the different forms of vasculitis, which have been informed in part by routine testing for antineutrophil cytoplasmic antibody (ANCA) in patients with vasculitis and increased utilisation of cross-sectional imaging, both of which have occurred since the 1990 ACR criteria were published. Indeed, most investigators regard MPA as part of the group of small-vessel vasculitides related to the presence of ANCA. This article outlines the development and validation of the new ACR/European Alliance of Associations for Rheumatology (EULAR)—endorsed classification criteria for MPA.

    Methods

    A detailed and complete description of the methods involved in the development and validation of the classification criteria for MPA is provided in online supplemental appendix 1. Briefly, an international Steering Committee comprising clinician investigators with expertise in vasculitis, statisticians and data managers was established to oversee the overall Diagnostic and Classification Criteria in Vasculitis (DCVAS) project. The Steering Committee established a 5-stage plan using data-driven and consensus methodology to develop the criteria for each of six forms of vasculitis.

    Stage 1: generation of candidate classification items for the systemic vasculitides

    Candidate classification items were generated by expert opinion and reviewed by a group of vasculitis experts across a range of specialties using a nominal group technique.

    Stage 2: DCVAS prospective observational study

    A prospective, international multisite observational study was conducted (see collaborators for study investigators and sites). Consecutive patients representing the full spectrum of disease were recruited from academic and community practices. Patients were included if they were 18 years or older and had a diagnosis of vasculitis or a condition that mimics vasculitis. Patients with ANCA-associated vasculitis (AAV) could only be enrolled within 2 years of diagnosis. Only data present at diagnosis were recorded.

    Stage 3: refinement of candidate items specifically for AAV

    The Steering Committee conducted a data-driven process to reduce the number of candidate items of relevance to cases and comparators for AAV. Items were selected for exclusion if they had a prevalence of <5% within the data set and/or they were not clinically relevant for classification criteria (eg, related to infection, malignancy or demographic characteristics). Low-frequency items of clinical importance could be combined, when appropriate.

    Stage 4: expert review to derive a gold standard—defined set of cases of AAV

    Experts in vasculitis from a wide range of geographic locations and specialties reviewed all submitted cases of vasculitis and a random selection of mimics of vasculitis. Each reviewer was asked to review ~50 submitted cases to confirm the diagnosis and to specify the certainty of their diagnosis as follows: very certain, moderately certain, uncertain or very uncertain. Only cases agreed on with at least moderate certainty were retained for further analysis.

    Stage 5: derivation and validation of the final classification criteria for MPA

    The DCVAS AAV data set was randomly split into development (50%) and validation (50%) sets. Comparisons were performed between cases of MPA and a comparator group randomly selected from the DCVAS cohort in the following proportions: another type of AAV (including granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA)), 60%; another form of small-vessel vasculitis (eg, cryoglobulinaemic vasculitis) or medium-vessel vasculitis (eg, PAN), 40%. Least absolute shrinkage and selection operator (Lasso) logistic regression was used to identify items from the data set and create a parsimonious model including only the most important items. The final items in the model were formulated into a clinical risk-scoring tool with each factor assigned a weight based on its respective regression coefficient. A threshold that best balanced sensitivity and specificity was identified for classification.

    In sensitivity analyses, the final classification criteria were applied to an unselected population of cases and comparators from the DCVAS data set based on the submitting physician diagnosis.

    Results

    Generation of candidate classification items for the systemic vasculitides

    The Steering Committee identified >1000 candidate items for the DCVAS case report form (see online supplemental appendix 2.

    DCVAS prospective observational study

    Between January 2011 and December 2017, the DCVAS study recruited 6991 participants from 136 sites in 32 countries. Information on the DCVAS sites, investigators and participants is listed in online supplemental appendices 3–5.

    Refinement of candidate items specifically for AAV

    Following a data-driven and expert consensus process, 91 items from the DCVAS case report form were retained for regression analysis, including 45 clinical (14 composite), 18 laboratory (2 composite), 12 imaging (all composite) and 16 biopsy (1 composite) items. Some clinical items were removed in favour of similar but more specific pathophysiological descriptors. For example, ‘Hearing loss or reduction’ was removed, and the composite item ‘Conductive hearing loss/sensorineural hearing loss’ was retained. See online supplemental appendix 6 for the final candidate items used in the derivation of the classification criteria for GPA, MPA and EGPA.

    Expert review to derive a gold standard—defined final set of cases of AAV

    Fifty-five independent experts reviewed vignettes derived from the case report forms for 2871 cases submitted with a diagnosis of either small-vessel vasculitis (90% of case report forms) or another type of vasculitis or a mimic of vasculitis (10% of case report forms). The characteristics of the expert reviewers are shown in online supplemental appendix 7. A flow chart showing the results of the expert review process is shown in online supplemental appendix 8. A total of 2072 cases (72%) passed the process and were designated as cases of vasculitis; these cases were used for the stage 5 analyses.

    After expert panel review by 55 investigators, 269 of 404 of the cases retained the submitting physician diagnosis of MPA and 22 additional cases were reclassified as having MPA by consensus of two expert reviewers. Compared with the 291 patients with a reference diagnosis of MPA, the 135 cases that were excluded had lower rates of perinuclear ANCA (pANCA) or anti-myeloperoxidase-ANCA (anti-MPO-ANCA) positivity (76% vs 98%; p<0.01), were less likely to have pauci-immune glomerulonephritis (16% vs 49%; p<0.01), were more likely to have maximum eosinophil counts ≥1×109/L (12% vs 6%; p=0.02), and were more likely to be cytoplasmic ANCA positive or proteinase 3-ANCA-positive (20% vs 4%; p<0.01). There were 822 comparators randomly selected for analysis. Table 1 shows the demographic and disease features of the 1113 cases included in this analysis (291 patients with MPA and 822 comparators), of which 557 (50%; 149 patients with MPA and 408 comparators) were in the development set and 556 (50%; 142 patients with MPA and 414 comparators) were in the validation set.

    View this table:
    Table 1

    Demographic and disease features of cases of MPA and comparators*

    Derivation and validation of the final classification criteria for MPA

    Lasso regression of the previously selected 91 items yielded 10 independent items for MPA (see online supplemental appendix 9C. Each item was then adjudicated by the DCVAS Steering Committee for inclusion based on clinical relevance and specificity to MPA, resulting in six final items. Weighting of an individual criterion was based on logistic regression fitted to the six selected items (see online supplemental appendix 10C.

    Model performance

    Use of a cut-off of ≥5 in total risk score (see online supplemental appendix 11C, for different cut points) yielded a sensitivity of 90.8% (95% CI 84.9% to 95.0%) and a specificity of 94.2% (95% CI 91.5% to 96.3%) in the validation set. The area under the curve for the model was 0.98 (95% CI 0.97 to 0.99) in the development set and 0.97 (95% CI 0.95 to 0.98) in the validation set for the final MPA classification criteria (online supplemental appendix 12C). The final classification criteria for MPA are shown in figure 1 (for the slide presentation version, see online supplemental figure 1).

    Figure 1
    Figure 1

    2022 American College of Rheumatology /European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis.

    Sensitivity analysis

    The classification criteria for MPA were applied to 2871 patients in the DCVAS database using the original physician-submitted diagnosis (n=404 cases of MPA and 2467 randomly selected comparators). Use of the same cut point of ≥5 points for the classification for MPA yielded a similar specificity of 92.5% but a lower sensitivity of 82.4%. This is consistent with the a priori hypothesis that specificity would remain unchanged but sensitivity would be reduced in a population with fewer clearcut diagnoses of MPA (ie, cases that did not pass expert panel review).

    Discussion

    Presented here are the 2022 ACR/EULAR MPA classification criteria. These are the first formal criteria for MPA. A 5-stage approach has been used, underpinned by data from the multinational prospective DCVAS study and informed by expert review and consensus at each stage. The comparator group for developing and validating the criteria were predominantly patients with other forms of AAV and other small- and medium-vessel vasculitides, the clinical entities where discrimination from MPA is difficult, but important. The new criteria for MPA have excellent sensitivity and specificity and incorporate ANCA testing and modern imaging techniques. The criteria were designed to have face and content validity for use in clinical trials and other research studies.

    These criteria are validated and intended for the purpose of classification of vasculitis and are not appropriate for use in establishing a diagnosis of vasculitis. The aim of the classification criteria is to differentiate cases of MPA from similar types of vasculitis in research settings. Therefore, the criteria should only be applied when a diagnosis of small- or medium-vessel vasculitis has been made and all potential ‘vasculitis mimics’ have been excluded. The exclusion of mimics is a key aspect of many classification criteria, including those for Sjögren’s syndrome5 and rheumatoid arthritis.5 The 1990 ACR classification criteria for vasculitis perform poorly when used for diagnosis (ie, when used to differentiate between cases of vasculitis vs mimics without vasculitis),6 and it is expected that the 2022 criteria would also perform poorly if used inappropriately as diagnostic criteria in people in whom alternative diagnoses, such as infection or other non-vasculitis inflammatory diseases, are still being considered. The relatively low weight assigned to glomerulonephritis in these classification criteria highlights the distinction between classification and diagnostic criteria. While detection of kidney disease is important to diagnose MPA, glomerulonephritis is common among patients with either GPA or MPA and thus does not function as a strong classifier between these conditions.

    MPA was not recognised as a separate entity in the 1990 ACR classification criteria for vasculitis, although the disease was recognised as pathologically distinct from PAN over 40 years earlier. This omission of MPA caused difficulties in defining clear homogeneous populations for research; thus, over the last two decades, investigators have often relied on the disease definitions of the CHCC nomenclature for eligibility criteria when enrolling patients with MPA into clinical trials.4 7–10 This approach resulted in heterogeneity between patients enrolled in therapeutic trials and epidemiological studies.11 Due to inconsistent methods employed by researchers when applying the 1990 ACR criteria and the CHCC definitions in parallel, the European Medicines Agency (EMA) convened meetings to develop a consensus on how to use the two systems, leading to the publication of the EMA algorithm in 2007.12 The algorithm works by first excluding EGPA and GPA, and then relying on the CHCC histological descriptions to discriminate between MPA and PAN. The new 2022 ACR/EULAR classification criteria for MPA and other vasculitides provide validated criteria that can replace the EMA interim solution and should harmonise future research studies.

    A potential limitation of these new criteria is that, through the expert panel consensus methodology, only the most definite cases were included in the analyses. However, the purpose of these criteria is to enable homogeneous groupings so that individual diseases can be studied. Overall, the use of more definitive cases is consistent with the purpose of classification criteria. Additionally, positive testing for MPO-ANCA is weighted heavily in the criteria, and it is theoretically possible to classify a patient as having MPA on the basis of a positive test for MPO-ANCA only. However, the criteria are intended to only be applied to patients with an established diagnosis of small- or medium-vessel vasculitis; in this setting, the criteria sets should result in a reduction of the score away from a classification of MPA if the patient has features of another form of AAV. When criteria were tested in a much less clearly defined population using the submitting physician diagnosis as the gold standard, the sensitivity of the criteria fell substantially despite 91% of this group being pANCApositive or MPO-ANCA positive, which supports the contention that ANCA positivity is not overly dominant for the classification. Nonetheless, ANCA testing is obviously a key discriminator between the different forms of AAV and other small- and medium-vessel vasculitides.

    There are some additional study limitations to consider. Although this was the largest international study ever conducted in vasculitis, most patients were recruited from Europe, Asia and North America. The performance characteristics of the criteria should be further tested in African and South American populations, which may have different clinical presentations of vasculitis. These criteria were developed using data collected from adult patients with vasculitis. Although the clinical characteristics of MPA and the other vasculitides which these criteria were tested against are not known to differ substantially between adults and children, these criteria should be applied to children with some caution. The scope of the criteria is intentionally narrow and applies only to patients who have been diagnosed as having vasculitis. Diagnostic criteria are not specified. The criteria are intended to identify homogenous populations of disease and, therefore, may not be appropriate for studies focused on the full spectrum of clinical heterogeneity in these conditions. To maximise relevance and face validity of the new criteria, study sites and expert reviewers were recruited from a broad range of countries and different medical specialties. Nonetheless, the majority of patients were recruited from academic rheumatology or nephrology units, which could have introduced referral bias.

    The 2022 ACR/EULAR classification criteria for MPA are the product of a rigorous methodological process that used an extensive data set generated by the work of a remarkable international group of collaborators. These are the first classification criteria for this disease. The criteria can now be applied to patients who have been diagnosed as having a small- or medium-vessel vasculitis. These criteria have been endorsed by the ACR and EULAR and are now ready for use to differentiate one type of vasculitis from another to define populations in research studies.

    Ethics statements

    Patient consent for publication

    Ethics approval

    Ethical approval was obtained from national and local ethics committees. This study does not involve human participants.

    Acknowledgments

    We acknowledge the patients and clinicians who provided data to the DCVAS project.

    References

    1. ↵
      2. Kussmaul A ,
      3. Maier R
      . Ueber eine bisher nicht beschriebene eigenthumliche Arterienerkrankung (periarteritis nodosa), die MIT morbus Brightti und rapid fortschreitender allgemeiner Muskellahmung einhergeht. Dtsch Arch Klin Med 1866;1:484–518.
      OpenUrl
    2. ↵
      2. Davson J ,
      3. Ball J ,
      4. Platt R
      . The kidney in periarteritis nodosa. Q J Med 1948;17:175–202.pmid:http://www.ncbi.nlm.nih.gov/pubmed/18888962
      OpenUrlPubMed
    3. ↵
      2. Lightfoot RW ,
      3. Michel BA ,
      4. Bloch DA , et al
      . The American College of rheumatology 1990 criteria for the classification of polyarteritis nodosa. Arthritis Rheum 1990;33:1088–93.doi:10.1002/art.1780330805 pmid:http://www.ncbi.nlm.nih.gov/pubmed/1975174
      OpenUrlPubMedWeb of Science
    4. ↵
      2. Jennette JC ,
      3. Falk RJ ,
      4. Andrassy K , et al
      . Nomenclature of systemic vasculitides. proposal of an international consensus conference. Arthritis Rheum 1994;37:10.1002/art.1780370206:187–92.doi:10.1002/art.1780370206 pmid:http://www.ncbi.nlm.nih.gov/pubmed/8129773
      OpenUrlPubMed
    5. ↵
      2. Aletaha D ,
      3. Neogi T ,
      4. Silman AJ , et al
      . 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League against rheumatism collaborative initiative. Arthritis Rheum 2010;62:2569–81.doi:10.1002/art.27584 pmid:http://www.ncbi.nlm.nih.gov/pubmed/20872595
      OpenUrlCrossRefPubMedWeb of Science
    6. ↵
      2. Rao JK ,
      3. Allen NB ,
      4. Pincus T
      . Limitations of the 1990 American College of rheumatology classification criteria in the diagnosis of vasculitis. Ann Intern Med 1998;129:10.7326/0003-4819-129-5-199809010-00001:345–52.doi:10.7326/0003-4819-129-5-199809010-00001 pmid:http://www.ncbi.nlm.nih.gov/pubmed/9735061
      OpenUrlPubMed
    7. ↵
      2. de Groot K ,
      3. Harper L ,
      4. Jayne DRW , 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.doi:10.7326/0003-4819-150-10-200905190-00004 pmid:http://www.ncbi.nlm.nih.gov/pubmed/19451574
      OpenUrlCrossRefPubMedWeb of Science
    8. ↵
      2. De Groot K ,
      3. Rasmussen N ,
      4. 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.doi:10.1002/art.21142 pmid:http://www.ncbi.nlm.nih.gov/pubmed/16052573
      OpenUrlCrossRefPubMedWeb of Science
    9. ↵
      2. Jayne D ,
      3. Rasmussen N ,
      4. 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.doi:10.1056/NEJMoa020286 pmid:http://www.ncbi.nlm.nih.gov/pubmed/12840090
      OpenUrlCrossRefPubMedWeb of Science
    10. ↵
      2. Jayne DRW ,
      3. Gaskin G ,
      4. Rasmussen N , et al
      . Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol 2007;18:2180–8.doi:10.1681/ASN.2007010090 pmid:http://www.ncbi.nlm.nih.gov/pubmed/17582159
      OpenUrlAbstract/FREE Full Text
    11. ↵
      2. Watts RA ,
      3. Lane SE ,
      4. Scott DG , et al
      . Epidemiology of vasculitis in Europe. Ann Rheum Dis 2001;60:1156a–7.doi:10.1136/ard.60.12.1156a pmid:http://www.ncbi.nlm.nih.gov/pubmed/11760724
      OpenUrlPubMed
    12. ↵
      2. Watts R ,
      3. Lane S ,
      4. Hanslik T , 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 2007;66:10.1136/ard.2006.054593:222–7.doi:10.1136/ard.2006.054593 pmid:http://www.ncbi.nlm.nih.gov/pubmed/16901958
      OpenUrlPubMed

    Supplementary materials

    Footnotes

    • Presented at This article is published simultaneously in Arthritis & Rheumatology.

    • Collaborators The DCVAS study investigators are as follows: Paul Gatenby (ANU Medical Centre, Canberra, Australia); Catherine Hill (Central Adelaide Local Health Network: The Queen Elizabeth Hospital, Australia); Dwarakanathan Ranganathan (Royal Brisbane and Women’s Hospital, Australia); Andreas Kronbichler (Medical University Innsbruck, Austria); Daniel Blockmans (University Hospitals Leuven, Belgium); Lillian Barra (Lawson Health Research Institute, London, Ontario, Canada); Simon Carette, Christian Pagnoux (Mount Sinai Hospital, Toronto, Canada); Navjot Dhindsa (University of Manitoba, Winnipeg, Canada); Aurore Fifi-Mah (University of Calgary, Alberta, Canada); Nader Khalidi (St Joseph’s Healthcare, Hamilton, Ontario, Canada); Patrick Liang (Sherbrooke University Hospital Centre, Canada); Nataliya Milman (University of Ottawa, Canada); Christian Pineau (McGill University, Canada); Xinping Tian (Peking Union Medical College Hospital, Beijing, China); Guochun Wang (China-Japan Friendship Hospital, Beijing, China); Tian Wang (Anzhen Hospital, Capital Medical University, China); Ming-hui Zhao (Peking University First Hospital, China); Vladimir Tesar (General University Hospital, Prague, Czech Republic); Bo Baslund (University Hospital, Copenhagen [Rigshospitalet], Denmark); Nevin Hammam (Assiut University, Egypt); Amira Shahin (Cairo University, Egypt); Laura Pirila (Turku University Hospital, Finland); Jukka Putaala (Helsinki University Central Hospital, Finland); Bernhard Hellmich (Kreiskliniken Esslingen, Germany); Jörg Henes (Universitätsklinikum Tübingen, Germany); Peter Lamprecht (Klinikum Bad Bramstedt, Germany); Thomas Neumann (Universitätsklinikum Jena, Germany); Wolfgang Schmidt (Immanuel Krankenhaus Berlin, Germany); Cord Sunderkoetter (Universitätsklinikum Müenster, Germany); Zoltan Szekanecz (University of Debrecen Medical and Health Science Center, Hungary); Debashish Danda (Christian Medical College & Hospital, Vellore, India); Siddharth Das (Chatrapathi Shahuji Maharaj Medical Center, Lucknow [IP], India); Rajiva Gupta (Medanta, Delhi, India); Liza Rajasekhar (NIMS, Hyderabad, India); Aman Sharma (Postgraduate Institute of Medical Education and Research, Chandigarh, India); Shrikant Wagh (Jehangir Clinical Development Centre, Pune [IP], India); Michael Clarkson (Cork University Hospital, Ireland); Eamonn Molloy (St. Vincent’s University Hospital, Dublin, Ireland); Carlo Salvarani (Santa Maria Nuova Hospital, Reggio Emilia, Italy); Franco Schiavon (L’Azienda Ospedaliera of University of Padua, Italy); Enrico Tombetti (Università Vita-Salute San Raffaele Milano, Italy); Augusto Vaglio (University of Parma, Italy); Koichi Amano (Saitama Medical University, Japan); Yoshihiro Arimura (Kyorin University Hospital, Japan); Hiroaki Dobashi (Kagawa University Hospital, Japan); Shouichi Fujimoto (Miyazaki University Hospital (HUB), Japan); Masayoshi Harigai, Fumio Hirano (Tokyo Medical and Dental University Hospital, Japan); Junichi Hirahashi (University Tokyo Hospital, Japan); Sakae Honma (Toho University Hospital, Japan); Tamihiro Kawakami (St. Marianna University Hospital Dermatology, Japan); Shigeto Kobayashi (Juntendo University Koshigaya Hospital, Japan); Hajime Kono (Teikyo University, Japan); Hirofumi Makino (Okayama University Hospital, Japan); Kazuo Matsui (Kameda Medical Centre, Kamogawa, Japan); Eri Muso (Kitano Hospital, Japan); Kazuo Suzuki, Kei Ikeda (Chiba University Hospital, Japan); Tsutomu Takeuchi (Keio University Hospital, Japan); Tatsuo Tsukamoto (Kyoto University Hospital, Japan); Shunya Uchida (Teikyo University Hospital, Japan); Takashi Wada (Kanazawa University Hospital, Japan); Hidehiro Yamada (St. Marianna University Hospital Internal Medicine, Japan); Kunihiro Yamagata (Tsukuba University Hospital, Japan); Wako Yumura (IUHW Hospital [Jichi Medical University Hospital], Japan); Kan Sow Lai (Penang General Hospital, Malaysia); Luis Felipe Flores- Suarez (Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico); Andrea Hinojosa (Instituto Nacional de Ciencias Médicas y Nutricion Salvador Zubiran, Mexico City, Mexico); Bram Rutgers (University Hospital Groningen, Netherlands); Paul-Peter Tak (Academic Medical Centre, University of Amsterdam, Netherlands); Rebecca Grainger (Wellington, Otago, New Zealand); Vicki Quincey (Waikato District Health Board, New Zealand); Lisa Stamp (University of Otago, Christchurch, New Zealand); Ravi Suppiah (Auckland District Health Board, New Zealand); Emilio Besada (Tromsø, Northern Norway, Norway); Andreas Diamantopoulos (Hospital of Southern Norway, Kristiansand, Norway); Jan Sznajd (University of Jagiellonian, Poland); Elsa Azevedo (Centro Hospitalar de S~ao Jo~ao, Porto, Portugal); Ruth Geraldes (Hospital de Santa Maria, Lisbon, Portugal); Miguel Rodrigues (Hospital Garcia de Orta, Almada, Portugal); Ernestina Santos (Hospital Santo Antonio, Porto, Portugal); Yeong-Wook Song (Seoul National University Hospital, Republic of Korea); Sergey Moiseev (First Moscow State Medical University, Russia); Alojzija Hocˇevar (University Medical Centre Ljubljana, Slovenia); Maria Cinta Cid (Hospital Clinic de Barcelona, Spain); Xavier Solanich Moreno (Hospital de Bellvitge-Idibell, Spain); Inoshi Atukorala (University of Colombo, Sri Lanka); Ewa Berglin (Umeå University Hospital, Sweden); Aladdin Mohammed (Lund-Malmo University, Sweden); Mårten Segelmark (Linköping University, Sweden); Thomas Daikeler (University Hospital Basel, Switzerland); Haner Direskeneli (Marmara University Medical School, Turkey); Gulen Hatemi (Istanbul University, Cerrahpasa Medical School, Turkey); Sevil Kamali (Istanbul University, Istanbul Medical School, Turkey); Ömer Karadag (Hacettepe University, Turkey); Seval Pehlevan (Fatih University Medical Faculty, Turkey); Matthew Adler (Frimley Health NHS Foundation Trust, Wexham Park Hospital, UK); Neil Basu (NHS Grampian, Aberdeen Royal Infirmary, UK); Iain Bruce (Manchester University Hospitals NHS Foundation Trust, UK); Kuntal Chakravarty (Barking, Havering and Redbridge University Hospitals NHS Trust, UK); Bhaskar Dasgupta (Southend University Hospital NHS Foundation Trust, UK); Oliver Flossmann (Royal Berkshire NHS Foundation Trust, UK); Nagui Gendi (Basildon and Thurrock University Hospitals NHS Foundation Trust, UK); Alaa Hassan (North Cumbria University Hospitals, UK); Rachel Hoyles (Oxford University Hospitals NHS Foundation Trust, UK); David Jayne (Cambridge University Hospitals NHS Foundation Trust, UK); Colin Jones (York Teaching Hospitals NHS Foundation Trust, UK); Rainer Klocke (The Dudley Group NHS Foundation Trust, UK); Peter Lanyon (Nottingham University Hospitals NHS Trust, UK); Cathy Laversuch (Taunton & Somerset NHS Foundation Trust, Musgrove Park Hospital, UK); Raashid Luqmani, Joanna Robson (Nuffield Orthopaedic Centre, Oxford, UK); Malgorzata Magliano (Buckinghamshire Healthcare NHS Trust, UK); Justin Mason (Imperial College Healthcare NHS Trust, UK); Win Win Maw (Mid Essex Hospital Services NHS Trust, UK); Iain McInnes (NHS Greater Glasgow & Clyde, Gartnavel Hospital & GRI, UK); John Mclaren (NHS Fife, Whyteman’s Brae Hospital, UK); Matthew Morgan (University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, UK); Ann Morgan (Leeds Teaching Hospitals NHS Trust, UK); Chetan Mukhtyar (Norfolk and Norwich University Hospitals NHS Foundation Trust, UK); Edmond O’Riordan (Salford Royal NHS Foundation Trust, UK); Sanjeev Patel (Epsom and St Helier University Hospitals NHS Trust, UK); Adrian Peall (Wye Valley NHS Trust, Hereford County Hospital, UK); Joanna Robson (University Hospitals Bristol NHS Foundation Trust, UK); Srinivasan Venkatachalam (The Royal Wolverhampton NHS Trust, UK); Erin Vermaak, Ajit Menon (Staffordshire & Stoke on Trent Partnership NHS Trust, Haywood Hospital, UK); Richard Watts (East Suffolk and North Essex NHS Foundation Trust, UK); Chee-Seng Yee (Doncaster and Bassetlaw Hospitals NHS Foundation Trust, UK); Daniel Albert (Dartmouth-Hitchcock Medical Center, US); Leonard Calabrese (Cleveland Clinic Foundation, US); Sharon Chung (University of California, San Francisco, US); Lindsy Forbess (Cedars-Sinai Medical Center, US); Angelo Gaffo (University of Alabama at Birmingham, US); Ora Gewurz- Singer (University of Michigan, US); Peter Grayson (Boston University School of Medicine, US); Kimberly Liang (University of Pittsburgh, US); Eric Matteson (Mayo Clinic, US); Peter A. Merkel (University of Pennsylvania, US); Jason Springer (University of Kansas Medical Center Research Institute, US); and Antoine Sreih (Rush University Medical Center, US).

    • Contributors All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. PAM had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design: RS,JR, PCG, CP, AC, AJ, AH, PAM, RAL, RAW. Acquisition of data: RS, JR, PCG, CP, AC, OM, RAL, RAW. Analysis and interpretation of data: RS, JR, PCG, CP, AC, SK, AJ, AH, PAM, RAL, RAW.

    • Funding The Diagnostic and Classification Criteria in Vasculitis (DCVAS) study, of which the development of these classification criteria was a part, was funded by grants from the American College of Rheumatology (ACR), the European Alliance of Associations for Rheumatology (EULAR), the Vasculitis Foundation and the University of Pennsylvania Vasculitis Center.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; internally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.