Association of IgG4-Related Disease With History of Malignancy

IgG4-related disease (IgG4-RD) is a fibroinflammatory disease of unclear etiology. Some studies suggest that IgG4-RD predisposes patients to malignancy or is a forme fruste of cancer, but we have frequently observed IgG4-RD patients who have a history of malignancy preceding the clinical onset of IgG4-RD. This study was undertaken to characterize IgG4-RD in the setting of previous malignancy diagnosis.

We identified IgG4-RD patients with a history of invasive malignancy from a well-defined cohort of 125 patients and compared their malignancy history to those of 2 reference groups. First, we calculated a standardized prevalence ratio against general US population estimates from the Surveillance, Epidemiology, and End Results (SEER) database. Second, we identified up to 5 age- and sex-matched controls for each case and calculated the odds of malignancy among those with IgG4-RD compared to controls, using conditional logistic regression.

The mean ± SD age at IgG4-RD onset was 50.3 ± 14.9 years, and 61% of the patients were male. Twenty (16%) had been diagnosed as having malignancies (total 21 malignancies) before the diagnosis of IgG4-RD. The observed prevalence of malignancy in this cohort was 2.5 times higher (95% confidence interval [95% CI] 1.1-3.6) than expected compared to the SEER database. Compared to matched controls, the frequency of history of malignancy was >3-fold higher in IgG4-RD patients (95% CI 1.6-6.2).

Our findings suggest that, in a subset of patients with IgG4-RD, malignancy may be associated with subsequent IgG4-RD development. Potential explanations include shared risk factors for both IgG4-RD and cancer, the triggering by cancer of autoantigen expression leading to IgG4-RD, and an increased risk of IgG4-RD resulting from cancer treatment.