The association of smoking with immunoglobulin G4-related disease: a case-control study

To evaluate the association between cigarette smoking and the odds of IgG4-related disease (IgG4-RD).

We performed a case-control study of patients with IgG4-RD compared in a 1:5 ratio with age-, race- and sex-matched controls. We included cases evaluated at the Massachusetts General Hospital, a hospital within the Mass General Brigham (MGB) System. Controls were identified from the MGB Biobank. Smoking status at the date of IgG4-RD diagnosis or corresponding index date was determined. Conditional logistic regression was used to estimate the association between cigarette smoking and the odds of having IgG4-RD.

There were 234 IgG4-RD cases and 1170 controls. The mean age (59 years), sex (62% male) and race (75% white) were well balanced. IgG4-RD cases were more likely to be current smokers compared with controls [25 (11%) vs 70 (6%); odds ratio (OR) 1.79 (95% CI 1.08, 2.95)]. This association was strongest among female cases [13 (14%) vs 19 (4%);, OR 3.79 (95% CI 1.71, 8.39)] and those with retroperitoneal fibrosis [RPF; 13 (28%) vs 13 (6%);, OR 6.93 (95% CI 2.78, 17.26)] or normal IgG4 concentrations [21 (21%) vs 21 (4%); OR 6.22 (95% CI 3.09, 12.49)]. When RPF cases were excluded, there was no longer an association between current smoking and the odds of having IgG4-RD [12 (6%) vs 57 (6%); OR 0.95 (95% CI 0.49, 1.86)].

Being a current smoker is associated with greater odds of having IgG4-RD, especially among women and those with RPF or normal IgG4 concentrations. Current smoking is the first recognized modifiable risk factor for IgG4-RD.