Diagnostic Challenge of IgG4-related Disease: Comparison Between ACR/EULAR, Umehara, and Okazaki Criteria

Rafael Gálvez Sánchez¹, Ivan Ferraz Amaro², Fernando Lopez Gutierrez³, Javier Loricera⁴, Pablo Martínez Calabuig⁵, Jorge Juan Fragío Gil⁶, Roxana González Mazarí⁷, Cristina Hormigos Martín⁸, DALIFER FREITES⁹, Maria Rodríguez Laguna⁸, Patricia Moya Alvarado¹⁰, Marta López I Gómez¹¹, Hector Corominas Macia¹⁰, Maite Silva Díaz¹², Guillermo González Arribas¹², Angel García Aparicio¹³, Judit Font-Urgelles¹⁴, Ivette Casafont Solé¹⁵, Elisabet Castaneda¹⁶, Carolina Merino Argumánez¹⁷, Raquel Zas Vaamonde¹⁸, Juan Molina Collada¹⁹, Sergio Rodríguez Montero²⁰, Rafael Melero Gonzalez²¹, Eva Galíndez Agirregoikoa²², Andrea Hernández²³, Lucia Pantoja Zarza²⁴, Ignacio Braña Abascal²⁵, Vega Jovaní²⁶, Elia Valls Pascual²⁷, Natalia Mena Vázquez²⁸, ADELA MARIA GALLEGO FLORES²⁹, Noelia Cabaleiro Raña³⁰, Raúl Veroz González³¹, Mariano Andrés³², Santos Castañeda Sainz³³ and Ricardo Blanco³⁴, ¹Division of Rheumatology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Immunopathology Group, Santander , Spain, Santander, Spain, ²Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain, ³Hospital Universitario Marqués de Valdecilla, Immunopathology Group -IDIVAL, Reumatología, Santander, Santander, Spain, ⁴Hospital Universitario Marqués de Valdecilla, IDIVAL, Immunopathology Group, Santander , Spain, Santander, Spain, ⁵Hospital General Universitario de Valencia, Spain/ Uversidad Catolica de Valencia San Vicente Martir, Valencia, Spain, Ontinyent, Spain, ⁶Hospital General Universitario, Valencia, Spain, ⁷Hospital General Universitario de Valencia, Reumatología, Valencia, Valencia, Spain, ⁸Hospital Clínico San Carlos, Reumatología, Madrid, Madrid, Spain, ⁹Rheumatology Service, San Carlos Clinical Hospital, Madrid, Madrid, Spain, ¹⁰Hospital de Sant Pau, Reumatología, Barcelona, Barcelona, Spain, ¹¹Hospital Universitario de Araba, Reumatología, Vitoria,, Vitoria, Spain, ¹²Complejo Hospitalario Universitario de A Coruña, Reumatología, A Coruña, Spain, ¹³Hospital Universitario de Toledo, Reumatología, Toledo, Toledo, Spain, ¹⁴Hospital Universitari Germans Trias i Pujol, Badalona, Spain, ¹⁵Hospital German Trias i Pujol, Reumatología, Badalona, Badalona, Spain, ¹⁶Hospital Universitario Infanta Sofía, Reumatología, Madrid, Madrid, Spain, ¹⁷Hospital Universitario Puerta del Hierro, Reumatología, Madrid, Madrid, Spain, ¹⁸Hospital Universitario ¹² de Octubre, Reumatología, Madrid, Madrid, Spain, ¹⁹Hospital General Universitario Gregorio Marañón, Reumatología, Madrid, Madrid, Spain, ²⁰Hospital Universitario de Valme, Reumatología, Sevilla, Sevilla, Spain, ²¹Hospital Alvaro Cunqueiro, Reumatología, Vigo, Vigo, Spain, ²²BASURTO UNIVERSITY HOSPITAL, BILBAO, Spain, ²³Hospital Universitario de Gran Canaria Dr Negrin, Reumatología, Palmas de Gran Canaria, Gran Canaria, Spain, ²⁴Hospital General de Segovia, Reumatología, Segovia, Segovia, Spain, ²⁵Hospital Universitario Central de Asturias, Reumatología, Oviedo, Oviedo, Spain, ²⁶Hospital General Universitario de Alicante, Reumatología, Alicante, Alicante, Comunidad Valenciana, Spain, ²⁷Hospital General de Valencia, Reumatología, Valencia, Valencia, Spain, ²⁸Hospital Regional Universitario de Málaga, Reumatología, Málaga, Malaga, Spain, ²⁹Complejo Hospitalario don Benito Villanueva, Reumatología, Badajoz, Badajoz, Extremadura, Spain, ³⁰Hospital Universitario Montecelo, Reumatología, Pontevedra, Pontevedra, Spain, ³¹Hospital de Mérida, Reumatología, Mérida, Mérida, Spain, ³²Hospital General Universitario de Alicante, Reumatología, Alicante, Alicante, Spain, ³³Hospital Universitario La Princesa, Reumatología, Madrid Grupo de cooperación nacional de enfermedad relacionada con IgG⁴: Blanca García Magallón (Hospital Universitario Puerta del Hierro), Maite Odriozola Gil (Hospital Universitario de Valme), Cristina Arciniega (Hospital de Mérida), Maria Lourdes Mateo Soria (Hospital German Trias i Pujol), Santiago Muñoz (Hospital Universitario Infanta Sofía), Iñigo Jesús Rua Figueroa, (Hospital Universitario de Gran Canaria Dr Negrin), Sabela Fernández Aguado, (Hospital de Montecelo)., Madrid, Spain, ³⁴Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, Immunopathology Group, Santander, Spain, Santander, Cantabria, Spain

Meeting: ACR Convergence 2025

Keywords: autoimmune diseases, classification criteria, Diagnostic criteria, IgG4 Related Disease

Session Information

Date: Sunday, October 26, 2025

Title: (0233–0279) Miscellaneous Rheumatic & Inflammatory Diseases Poster I

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: IgG4-related disease (IgG4-RD) is a rare immune-mediated condition characterized by fibro-sclerosing inflammation, elevated serum and tissue IgG4 levels, and heterogeneous clinical manifestations. Several classification criteria have been proposed, including ACR/EULAR (2019) (1), Umehara (2011) (2), and Okazaki (2012) (3). The objective of this study is to analyze the concordance and differences among the main IgG4-RD classification criteria.

Methods: Observational multicenter study of patients diagnosed with IgG4-RD by expert rheumatologists across 25 Spanish hospitals. The ACR/EULAR, Umehara, and Okazaki classification criteria were applied to determine which patients fulfilled each set. Concordance between the criteria was assessed using PABAK index (prevalence- and bias-adjusted kappa). A Venn diagram was used to represent the overlap among the different criteria, illustrating how many patients fulfilled only one, shared more than one, or met none. Notably, patients who did not fulfill any of the established classification criteria but were diagnosed with IgG4-RD based on expert clinical judgment were categorized as having an exclusive clinical diagnosis. In addition, clinical, demographic, and laboratory data were analyzed for each subgroup.

Results: We include 68 patients (43 men/25 women) diagnosed as IgG4-RD by expert rheumatologists; mean age was 54.4 years. Of them 37 (54.4%) met Okazaki and ACR/EULAR criteria; 16 (23.5) were classified based exclusively on clinical criteria and 13 (19.1%) met Umehara. Concordance between criteria was variable. PABAK showed low-moderate agreement between ACR/EULAR and Umehara (PABAK 0.264), and between Umehara and Okazaki (PABAK 0.441), while the exclusive clinical criterion showed significant discordance, with negative PABAK values (Table 1). Patients classified according to Umehara showed a higher prevalence of pancreatic involvement (47.1%), whereas those classified by ACR/EULAR had more glandular involvement (32.4%). In contrast, the exclusive clinical group exhibited a less typical profile, with lower prevalence of pancreatic involvement (6.2%). Serum IgG4 levels were highest in the Umehara group (303.4 mg/dL). Additional clinical, laboratory, and complementary characteristics are shown in Table 2. When comparing the two most recent criteria, ACR/EULAR and Okazaki, no statistically significant differences were observed. According to the Venn diagram (Figure), only 8 patients met the three criteria simultaneously, 14 met only the Okazaki criteria, 9 met only ACR/EULAR, and none met exclusively Umehara criteria. The greatest overlap was between ACR/EULAR and Okazaki, with 15 patients meeting both sets of criteria.

Conclusion: Concordance among classification criteria was low. These results highlight the inherent challenges in diagnosing IgG4-related disease. Currently available criteria appear to prioritize different aspects of the disease, which may limit their ability to capture the complexity of the clinical picture and hinder their consistent application in clinical practice. A new universally accepted classification criteria for IgG4-related disease are still an unmet need.

Table 1. Concordance of Classification Criteria: PABAK (95% CI) Between ACR/EULAR, Umehara, Okazaki, and Exclusive Clinic

Table 2: Comparison of the Different Classification Criteria for IgG4-Related Disease (Umehara, Exclusive Clinical, Okazaki, and ACR/EULAR), Including Demographic Data, Clinical Manifestations, and Complementary Tests

Figure: Venn diagram showing the overlap of patients classified as IgG4-RD according to each of the ACR/EULAR, Umehara, and Okazaki criteria.

Disclosures: R. Gálvez Sánchez: None; I. Ferraz Amaro: None; F. Lopez Gutierrez: Roche, Galápagos, Novartis, UCB Pharma, MSD, Celgene, Astra Zeneca, Grünenthal, Janssen, Abbvie, Lilly, Pfizer, 12, support for attending meetings and/or travel; J. Loricera: AbbVie/Abbott, 5, AstraZeneca, 2, 5, 6, Celgene, 2, 5, 6, Eli Lilly, 5, Janssen, 5, Merck/MSD, 2, 5, 6, Novartis, 2, 5, 6, Pfizer, 5, Roche, 2, 5, 6, UCB, 2, 5, 6; P. Martínez Calabuig: None; J. Fragío Gil: Quibim, 1; R. González Mazarí: None; C. Hormigos Martín: None; D. FREITES: None; M. Rodríguez Laguna: None; P. Moya Alvarado: None; M. López I Gómez: None; H. Corominas Macia: None; M. Silva Díaz: None; G. González Arribas: None; A. García Aparicio: None; J. Font-Urgelles: None; I. Casafont Solé: None; E. Castaneda: None; C. Merino Argumánez: None; R. Zas Vaamonde: None; J. Molina Collada: None; S. Rodríguez Montero: None; R. Melero Gonzalez: None; E. Galíndez Agirregoikoa: None; A. Hernández: None; L. Pantoja Zarza: None; I. Braña Abascal: None; V. Jovaní: None; E. Valls Pascual: None; N. Mena Vázquez: None; A. GALLEGO FLORES: None; N. Cabaleiro Raña: None; R. Veroz González: None; M. Andrés: None; S. Castañeda Sainz: None; R. Blanco: AbbVie/Abbott, 2, 5, 6, Bristol-Myers Squibb(BMS), 2, 6, Eli Lilly, 2, 6, Janssen, 2, 6, Merck/MSD, 2, 5, 6, Pfizer, 2, 6, Roche, 2, 5, 6.

To cite this abstract in AMA style:

Gálvez Sánchez R, Ferraz Amaro I, Lopez Gutierrez F, Loricera J, Martínez Calabuig P, Fragío Gil J, González Mazarí R, Hormigos Martín C, FREITES D, Rodríguez Laguna M, Moya Alvarado P, López I Gómez M, Corominas Macia H, Silva Díaz M, González Arribas G, García Aparicio A, Font-Urgelles J, Casafont Solé I, Castaneda E, Merino Argumánez C, Zas Vaamonde R, Molina Collada J, Rodríguez Montero S, Melero Gonzalez R, Galíndez Agirregoikoa E, Hernández A, Pantoja Zarza L, Braña Abascal I, Jovaní V, Valls Pascual E, Mena Vázquez N, GALLEGO FLORES A, Cabaleiro Raña N, Veroz González R, Andrés M, Castañeda Sainz S, Blanco R. Diagnostic Challenge of IgG4-related Disease: Comparison Between ACR/EULAR, Umehara, and Okazaki Criteria [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/diagnostic-challenge-of-igg4-related-disease-comparison-between-acr-eular-umehara-and-okazaki-criteria/. Accessed .

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