IgG4-related disease is not associated with an increased incidence of malignancy in a large, single-centre cohort

Immunoglobulin G4-related disease (IgG4-RD) is a systemic, immune-mediated disease-causing inflammation and fibrosis in multiple organs, often associated with elevated serum IgG4 concentrations. Whether IgG4-RD is associated with malignancy remains unclear. We investigated whether there is an association between IgG4-RD and incident malignancy.

We performed a single-centre, retrospective cohort study of patients who fulfilled the American College of Rheumatology/European Alliance of Associations for Rheumatology IgG4-RD Classification Criteria. Malignancy history was collected by survey and medical record review. Age- and sex-stratified malignancy incidence rates in the cohort were compared with rates in the general US population. Cox proportional hazards were used to identify disease characteristics associated with incident malignancy.

Of the 348 patients with IgG4-RD in our cohort, 34 (10%) developed incident malignancies over a median follow-up of 8.04 years (IQR, 1.35-14.72 years). The most common malignancies were lymphoma (n = 6, 16% of malignancies), prostate cancer (n = 6, 16%), and lung cancer (n = 5, 13%). Compared with the general US population, there was no increased incidence of malignancy in patients with IgG4-RD (standardised incidence ratio, 0.88 [0.61-1.23]). Among patients with IgG4-RD, those who ever smoked (adjusted hazard ratio [HR], 2.46 [1.16-5.24]) or were older (HR, 1.35 [1.00-1.83] per decade) had increased risk of malignancy, whereas female patients (HR, 0.37 [0.14-0.96]) and those with submandibular gland involvement (HR, 0.25 [0.10-0.61]) had decreased risk.

IgG4-RD was not associated with an increased incidence of malignancy following IgG4-RD onset. Among patients with IgG4-RD, smoking and older age at IgG4-RD onset were associated with higher malignancy risk. Female sex and submandibular gland involvement were associated with lower malignancy risk.