Association Between Immunoglobulin G4–related Disease and Malignancy within 12 Years after Diagnosis: An Analysis after Longterm Followup

Objective. Because it is uncertain whether immunoglobulin G4–related disease (IgG4-RD) is associated with malignancy, we evaluated the incidence of cancer development in a large cohort of patients with IgG4-RD. Methods. The study enrolled 158 patients diagnosed as having IgG4-RD between 1992 and 2012. We calculated the standardized incidence ratio (SIR) and cumulative rate of malignancies in this group and searched for risk factors associated with the occurrence of tumors. Results. A total of 34 malignancies were observed in the patients with IgG4-RD over a mean followup period of 5.95 ± 4.48 years. The overall SIR of malignancies was 2.01 (95% CI 1.34–2.69). The SIR of patients who exhibited a tumor within 1 year after IgG4-RD diagnosis was 3.53 (95% CI 1.23–5.83), while that of subjects forming a malignancy in subsequent years was 1.48 (95% CI 0.99–1.98). The cumulative rate of malignancy development was significantly higher in patients with IgG4-RD within 12 years after diagnosis than in the Japanese general population. Comparable results were obtained for an autoimmune pancreatitis subgroup. The serum concentrations of several disease activity markers at diagnosis were significantly higher in patients with malignancies than in those without. Conclusion. We identified a close association between IgG4-RD and malignancy formation within 12 years after diagnosis, particularly during the first year. An active IgG4-RD state is presumed to be a strong risk factor for malignancy development.