Background: IgG4-related disease (IgG4-RD) is a rare, immune-mediated fibroinflammatory condition characterized by tissue infiltration with IgG4-positive plasma cells. While solid organ involvement is well documented, data on hematologic manifestations and associated outcomes remain limited. Understanding hematological burden and real-world treatment patterns is essential to guide comprehensive management.

Methods: We conducted a multicenter, retrospective cohort study using the TriNetX Research Network, comprising electronic health records from multiple U.S. healthcare systems. Adults (≥18 years) with a diagnosis of IgG4-RD (ICD-10 codes) were included. Patients with a prior diagnosis of hematologic malignancy were excluded. Demographic characteristics, hematologic manifestations, treatment patterns, and overall mortality were assessed. The median follow-up duration was 519 days.

Results: A total of 2,596 patients with IgG4-RD were identified, of whom 554 (21.3%) exhibited at least one hematologic manifestation. The mean age was 58.1 ± 15.9 years; 53% were male (n=1,379), and 57% were White (n=1,492). Hypertension was the most common comorbidity (44%, n=1,136). Among those with hematologic involvement, key manifestations included lymphadenopathy (n=605, 23.3%), hepatomegaly (n=114, 4.4%), splenomegaly (n=73, 2.8%), eosinophilia (n=71, 2.7%), pancytopenia (n=31, 1.2%), hypergammaglobulinemia (n=71, 2.7%), and monoclonal gammopathy (n=86, 3.3%). Regarding outcomes, 127 of 2,596 patients (4.9%) died during the follow-up period. Among those with hematologic manifestations, 36 of 554 (6.5%) died, indicating a numerically higher mortality rate in this subgroup. Treatment data revealed that all patients received corticosteroids as initial therapy. Additionally, 531 patients (20.4%) received steroid-sparing immunosuppressants. The most used agents included rituximab (6%), azathioprine (6%), mycophenolate mofetil (5%), and methotrexate (3%).

Conclusion: In this large, real-world cohort of patients with IgG4-RD, hematologic manifestations were observed in over one-fifth of patients and were associated with a numerically higher mortality rate. Lymphadenopathy was the most common hematologic feature. Despite the widespread use of corticosteroids, a substantial proportion of patients required steroid-sparing agents. These findings highlight the hematologic complexity of IgG4-RD and underscore the need for multidisciplinary management and prospective studies focused on hematologic outcomes.

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2025
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