Abstract

Background: Diagnosing IgG4-related periaortitis/retroperitoneal fibrosis (IgG4-PA/RPF) is often challenging, especially in PA/RPF-limited cases, due to the difficulty in obtaining periaortic/retroperitoneal specimens. In 2018, diagnostic criteria were introduced for IgG4-PA/RPF in Japan [1], whereas the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for IgG4-related disease (IgG4-RD) were established in 2019 [2]. Objectives: This study aimed to validate the existing Japanese organ-specific diagnostic criteria as well as the ACR/EULAR classification criteria in a Japanese cohort of patients with IgG4-PA/RPF and formulate an improved version. Methods: In this nationwide multicenter study, we retrospectively analyzed 110 Japanese patients diagnosed with IgG4-RD involving cardiovascular and/or retroperitoneal manifestations, along with 73 mimickers identified by experts. Patients were stratified into derivation (n=88) and validation (n=95) groups. Classification as IgG4-RD or non-IgG4-RD was based on the 2018 diagnostic criteria and various revised versions in addition to the ACR/EULAR classification criteria. Sensitivity and specificity were calculated using experts' diagnosis as the gold standard for the diagnosis of true IgG4-RD and mimickers. Results: The final diagnoses of mimickers mainly consisted of non-IgG4-related idiopathic PA/RPF, lymphoma, Takayasu arteritis, giant cell arteritis, and atherosclerotic or infectious aortic aneurysm. The ACR/EULAR classification criteria had a sensitivity of 52% and a specificity of 95%. In the derivation group, the 2018 Japanese diagnostic criteria showed 59% sensitivity and 100% specificity. The revised version, incorporating "radiologic findings of pericarditis," "eosinophilic infiltration or lymphoid follicles," and "probable diagnosis of extra-PA/RPF lesions," improved sensitivity to 70% while maintaining 100% specificity. In the validation group, the original and revised diagnostic criteria had sensitivities of 68% and 77%, and specificities of 97% and 95%, respectively. When definite, probable, and possible diagnoses were regarded as a diagnosis of IgG4-PA/RPF, the diagnostic criteria showed 100% sensitivity and 92% specificity. Conclusion: The present study suggests that the 2019 ACR/EULAR classification criteria for IgG4-RD and the 2018 Japanese diagnostic criteria for IgG4-PA/RPF have excellent diagnostic specificities but relatively low sensitivities. Proposed 2023 revised IgG4-related cardiovascular/retroperitoneal disease criteria show significantly enhanced sensitivity while preserving high specificity, achieved through the inclusion of new items in radiologic, pathological, and extra-cardiovascular/retroperitoneal organ categories. REFERENCES: [1] Mizushima I, et al. Clinical and pathological characteristics of IgG4-related periaortitis/periarteritis and retroperitoneal fibrosis diagnosed based on experts' diagnosis. Ann Vasc Dis. 2019;12:460-72. [2] Wallace ZS, et al. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Ann Rheum Dis. 2020;79:77-87. Acknowledgements: We sincerely thank all the members of IgG4-related cardiovascular disease working group. Disclosure of Interests: None declared.