The Association of Smoking with IgG4-Related Disease: A Case-Control Study

Objective To evaluate the association between cigarette smoking and the odds of IgG4-related disease (IgG4-RD). Methods 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 Massachusetts General Hospital, a hospital within the Mass General Brigham (MGB) System. Controls were identified from the MGB Biobank. Smoking status at date of IgG4-RD diagnosis or corresponding index date was determined. Conditional logistic regression was used to estimate the association between cigarette smoking and odds of having IgG4-RD. Results There were 234 IgG4-RD cases and 1,170 controls. 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%], 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]). Conclusion 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.