Background:Recently, the 2019 ACR/EULAR classification criteria for IgG4-related disease (IgG4-RD) were published mainly to identify more homogeneous subjects for inclusion in clinical trials and observational studies [1]. However, although their high specificity is presumed to be useful to differentiate IgG4-RD from various mimickers, their value in daily clinical practice needs to be evaluated.Objectives:This study aimed to clarify the usefulness of the 2019 ACR/EULAR classification criteria for IgG4-RD and characteristics of false-negative patients in daily clinical practice.Methods:We retrospectively reviewed the medical records of 162 patients with IgG4-RD and 130 consecutive non-IgG4-RD patients (mimickers) diagnosed by experts whose serum IgG4 levels were measured at a single center in Japan. Using the collected data, we calculated sensitivity, specificity, and fulfillment rates for the entry criteria, exclusion criteria, and threshold of inclusion criteria points. In addition, to clarify the characteristics of false-negative cases in IgG4-RD, we performed an intergroup comparison of their clinical features including disease-specific autoantibodies.Results:Both the patients with IgG4-RD and mimickers were relatively old (66 and 65 years) with male predominance (67% and 60%). The final diagnoses of mimickers mainly consisted of cancer, lymphoma, vasculitis, sarcoidosis, multicentric Castleman’s disease, and atherosclerotic or infectious aortic aneurysm. The classification criteria had a sensitivity of 72.8% and a specificity of 100%. Of the 44 false-negative cases, one did not fulfill the entry criteria, 20 fulfilled one exclusion criterion, and 27 did not achieve sufficient inclusion criteria points. Compared with the true-positive cases, the false-negative cases had significantly fewer affected organs, lower serum IgG4 levels, higher serum CH50 levels, and lower prevalence of salivary/lacrimal gland and renal parenchymal lesions. They were also less likely to have had biopsies (61% vs 97%). Of note, positivity of disease-specific autoantibodies including SSA/Ro antibody, ANCA, ds-DNA antibody, and ACPA was the most common exclusion criterion fulfilled in 18 patients, only 2 of whom were diagnosed with a specific autoimmune disease (rheumatoid arthritis) complicated by IgG4-RD. The remaining 16 patients had no specific clinical symptoms related to such autoantibodies. In addition, compared with IgG4-RD patients without disease-specific autoantibodies, the 18 patients with them had almost equal serum IgG4 and complement levels, number of affected organs, and histopathology and immunostaining scores despite higher serum IgG and CRP levels.Conclusion:The present study suggests that the 2019 ACR/EULAR classification criteria for IgG4-RD has excellent diagnostic specificity and moderate sensitivity in daily clinical practice. Positive disease-specific autoantibodies alone, which lowered the sensitivity in this study, may have little clinical significance concerning the diagnosis of IgG4-RD.References:[1]Wallace ZS et al. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Ann Rheum Dis. 2020 Jan;79(1):77-87.Disclosure of Interests:None declared
A Case of Immunoglobulin G4-Related Disease with Extensive Multiorgan Involvements
