Meta-analysis finds high prevalence of allergy, eosinophilia, and hyper-IgE in IgG4-RD

BACKGROUND: IgG4-related disease (IgG4-RD) is an immune-mediated condition characterized by multi-organ involvement. Substantial evidence suggests a close link between allergy and IgG4-RD, supported by the high prevalence of allergic comorbidities in patients and shared immunological features such as eosinophilia and elevated serum IgE. However, the precise mechanistic connections and potential causal relationship between allergy and IgG4-RD remain unclear. This study aimed to systematically quantify the proportion of IgG4-RD patients presenting with allergy, eosinophilia, and hyper-IgE. METHODS: A comprehensive literature search of the PubMed, Web of Science, EMBASE, and the Cochrane Library was conducted up to August 7, 2025. Studies meeting the inclusion criteria were reviewed. Meta-analysis was performed using both random- and fixed-effects models. RESULTS: The search identified 1884 studies, of which 32 were included in the analysis. Among these, 30 studies contributed to the allergy analysis, 15 to eosinophilia, and 9 to hyper-IgE. The meta-analysis showed that the pooled proportion of IgG4-RD patients with allergy was 0.44 (95% CI, 0.39, 0.49; p < 0.01; n = 8233). The pooled proportion with eosinophilia was 0.22 (95% CI, 0.18, 0.26; p < 0.01; n = 4376), and with hyper-IgE was 0.73 (95% CI, 0.63, 0.83; p < 0.01; n = 2353). CONCLUSIONS: A notable proportion of IgG4-RD patients exhibit allergy, eosinophilia, and hyper-IgE. The frequent co-occurrence of these features highlights the need to investigate the underlying mechanisms, clarify the causal relationship between allergy and IgG4-RD, and provide further insights for both mechanistic research and clinical management of IgG4-RD, especially through well-controlled comparative studies to establish whether these features are truly more prevalent in IgG4-RD than in the general population or other conditions.