Background/Purpose: IgG4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by tumefactive lesions that can occur at nearly any site, often associated with an elevated serum IgG4 concentration. Despite advances in the recognition and treatment of IgG4-RD, its etiology and pathogenesis remain unknown. Prior studies suggest that cigarette smoking may be a risk factor for IgG4-RD. We performed a case-control study to evaluate the association between cigarette smoking and the risk of IgG4-RD.

Methods: All patients seen in the Center for IgG4-RD at Massachusetts General Hospital who were diagnosed with IgG4-RD between 2010 and 2018 and completed a smoking questionnaire were included in this study. Participants in the Partners HealthCare Biobank who completed a smoking questionnaire (N=30,536) were used a source of controls. For each case and control, a smoking status (never, former, current) was determined. Each case was matched to up to 5 controls based on age (5-year category) and sex. We used conditional logistic regression to compare the proportion of cases and controls with a history of cigarette smoking using odds ratios (OR) and 95% confidence intervals (CIs).

Results: We identified 194 IgG4-RD cases which were matched to 970 controls (Table 1). The mean age for cases and controls was 57 years (±13) and 57 years (±13), respectively, and the majority of patients were male (62% and 62% in both groups). There was a greater proportion of current and former smokers among IgG4-RD cases (Current=23 [12%], Former=58 [30%]) compared with controls (Current=72 [7%], Former=211 [22%]). Compared with controls, IgG4-RD cases had nearly a two-fold higher odds of being current smokers (OR 1.85 [95% CI 1.11-3.07]) or former smokers (OR 1.66 [95% CI 1.16-2.39]). The association between cigarette exposure and the risk of IgG4-RD seemed to be driven by a strong association among the subgroup of patients with retroperitoneal fibrosis (RPF, 16% of cases) (OR 4.91 [95% CI 1.81-13.34]).

Conclusion: In this case-control study of patients with IgG4-RD, current and former smoking statuses were strongly associated with the risk of IgG4-RD, especially among IgG4-RD patients with RPF. Biologically, cigarette smoking is known to stimulate fibrogenesis, a key feature of IgG4-RD. While these findings require additional confirmation, cigarette smoking may be the first recognized modifiable risk factor for IgG4-RD. Further research is necessary to understand the mechanism by which smoking increases the risk of IgG4-RD. Patients with IgG4-RD may need to be counseled against smoking.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cigarette-smoking-is-a-risk-factor-for-igg4-related-disease/