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The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease
  1. Zachary S Wallace1,
  2. Ray P Naden2,
  3. Suresh Chari3,
  4. Hyon K Choi4,
  5. Emanuel Della-Torre5,
  6. Jean-Francois Dicaire6,
  7. Phillip A Hart3,
  8. Dai Inoue7,
  9. Mitsuhiro Kawano8,
  10. Arezou Khosroshahi9,
  11. Marco Lanzillotta10,
  12. Kazuichi Okazaki11,
  13. Cory A Perugino12,
  14. Amita Sharma13,
  15. Takako Saeki14,
  16. Nicolas Schleinitz15,
  17. Naoki Takahashi16,
  18. Hisanori Umehara17,
  19. Yoh Zen18,
  20. John H Stone19
  21. Members of the ACR/EULAR IgG4-RD Classification Criteria Working Group
    1. 1 Rheumatology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
    2. 2 Maternal-Fetal Medicine, McMaster University Faculty of Health Sciences, Hamilton, Ontario, Canada
    3. 3 Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota, USA
    4. 4 Rheumatology, Harvard Medical School, Boston, Massachusetts, USA
    5. 5 Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA
    6. 6 Pinnacle Inc, Montreal, Ontario, Canada
    7. 7 Department of Radiology, Kanazawa University, Kanazawa, Japan
    8. 8 Division of Rheumatology, Department of Internal Medicine, Kanazawa University Hospital, Kanazawa, Japan
    9. 9 Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA
    10. 10 Università Vita-Salute San Raffaele, School of Medicine, Unit of Internal Medicine, Ospedale San Raffaele, Milano, Lombardia, Italy
    11. 11 Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan
    12. 12 Rheumatology, MGH, Boston, Massachusetts, USA
    13. 13 Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA
    14. 14 Department of Internal Medicine, Nagaoka Red Cross Hospital, Nagaoka, Japan
    15. 15 Internal Medicine, Groupe hospitalier Timone, Assistance publique-Hôpitaux de Marseille, Aix-Marseille Université, Marseille, France
    16. 16 Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
    17. 17 Rheumatology and Immunology, Shiritsu Nagahama Byoin, Nagahama, Shiga, Japan
    18. 18 Diagnostic Pathology, Kobe University, Kobe, Japan
    19. 19 Massachusetts General Hospital Rheumatology Unit, Harvard Medical School, Boston, Massachusetts, USA
    1. Correspondence to Dr John H Stone, Massachusetts General Hospital Rheumatology Unit, Harvard Medical School, Boston, MA 02114, USA; jhstone{at}


    IgG4-related disease (IgG4-RD) can cause fibroinflammatory lesions in nearly any organ. Correlation among clinical, serological, radiological and pathological data is required for diagnosis. This work was undertaken to develop and validate an international set of classification criteria for IgG4-RD. An international multispecialty group of 86 physicians was assembled by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). Investigators used consensus exercises; existing literature; derivation and validation cohorts of 1879 subjects (1086 cases, 793 mimickers); and multicriterion decision analysis to identify, weight and test potential classification criteria. Two independent validation cohorts were included. A three-step classification process was developed. First, it must be demonstrated that a potential IgG4-RD case has involvement of at least one of 11 possible organs in a manner consistent with IgG4-RD. Second, exclusion criteria consisting of a total of 32 clinical, serological, radiological and pathological items must be applied; the presence of any of these criteria eliminates the patient from IgG4-RD classification. Third, eight weighted inclusion criteria domains, addressing clinical findings, serological results, radiological assessments and pathological interpretations, are applied. In the first validation cohort, a threshold of 20 points had a specificity of 99.2% (95% CI 97.2% to 99.8%) and a sensitivity of 85.5% (95% CI 81.9% to 88.5%). In the second, the specificity was 97.8% (95% CI 93.7% to 99.2%) and the sensitivity was 82.0% (95% CI 77.0% to 86.1%). The criteria were shown to have robust test characteristics over a wide range of thresholds. ACR/EULAR classification criteria for IgG4-RD have been developed and validated in a large cohort of patients. These criteria demonstrate excellent test performance and should contribute substantially to future clinical, epidemiological and basic science investigations.

    • rheumatoid arthritis
    • Sjøgren's syndrome
    • inflammation

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    • Presented at This article is published simultaneously in the January 2020 issue of Arthritis & Rheumatology.

    • Collaborators Members of the ACR/EULAR IgG4-RD Classification Criteria Working Group are as follows: Drs Takashi Akamizu, Mitsuhiro Akiyama, Lillian Barra, Adrian Bateman, Daniel Blockmans, Pilar Brito-Zeron, Corrado Campochiaro, Mollie Carruthers, Tsutomu Chiba, Lynn Cornell, Emma Culver, Saman Darabian, Vikram Deshpande, Lingli Dong, Mikael Ebbo, Andreu Fernández-Codina, Judith A Ferry, George Fragkoulis, Fabian Frost, Luca Frulloni,Gabriela Hernandez-Molina, Haihan Ji, Karuna Keat, Terumi Kamisawa, Shigeyuki Kawa, H. Kobayashi, Yuzo Kodama, Satoshi Kubo, Kensuke Kubota, Haiyang Leng, Markus Lerch, Yanying Liu, Zhifu Liu, Matthias Löhr, Eduardo Martin-Nares, Ferran Martinez-Valle, Chiara Marvisi, Yasufumi Masaki, Shoko Matsui, Ichiro Mizushima, Seiji Nakamura, Jan Nordeide, Kenji Notohara, Sergio Paira, Jovan Popovic, Manel Ramos-Casals, James Rosenbaum, Jay Ryu, Yasuharu Sato, Hiroshi Sekiguchi, Evgeniya V. Sokol, James R Stone, Wenwu Sun, Hiroki Takahashi, Masayuki Takahira, Yoshiya Tanaka, Augusto Vaglio, Alejandra Villamil, Yoko Wada, George Webster, Kazunori Yamada, Motohisa Yamamoto, Joanne Yi, Yinlan Yi, Giuseppe Zamboni, Wen Zhang.

    • 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. JHS had full access to all 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; acquisition of data; analysis and interpretation of data: ZSW, RPN, SC, HKC, ED-T, J-FD, PAH, DI, MK, AK, KK, ML, KO, CAP, AS, TS, HS, NS, JRS, NT, HU, GW, YZ and JHS.

    • Funding Supported by the ACR and the EULAR.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval This criteria set has been approved by the EULAR Executive Committee and the ACR Board of Directors. This signifies that the criteria set has been quantitatively validated using patient data, and it has undergone validation based on an independent data set. All ACR/EULAR-approved criteria sets are expected to undergo intermittent updates. The ACR is an independent, professional, medical and scientific society that does not guarantee, warrant, or endorse any commercial product or service.

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