Influenza and risk of later celiac disease: a cohort study of 2.6 million people

Abstract

Objectives: Influenza has been linked to autoimmune conditions, but its relationship to subsequent celiac disease (CD) is unknown. Our primary aim was to determine the risk of CD after influenza. A secondary analysis examined the risk of CD following pandemic influenza vaccination.

Methods: This nationwide register-based cohort study included 2,637,746 Norwegians (born between 1967–2013) followed during 2006–2014 with information on influenza diagnosed in primary or non-primary care, pandemic vaccination (Pandemrix), and subsequent CD. Cox regression yielded hazard ratios adjusted (HR) for socio-demographic characteristics and earlier healthcare use.

Results: During 13,011,323 person-years of follow-up 7321 individuals were diagnosed with CD (56/100,000 person-years). There were 351,666 individuals diagnosed with influenza, including 82,980 during the 2009–2010 pandemic, and 969,968 individuals were vaccinated. Compared with participants without influenza, who had a CD incidence of 55/100,000 person-years, those diagnosed with seasonal and pandemic influenza had a rate of 68 and 78, per 100,000 person-years, respectively. The HR for CD was 1.29 (95%CI, 1.21–1.38) after seasonal influenza and 1.29 (95%CI, 1.15–1.44) after pandemic influenza; HRs remained significantly increased one year after exposure, when restricted to laboratory-confirmed influenza, and after multivariate adjustments. The reverse association, i.e., risk of influenza after CD, was not significant (HR 1.05; 95%CI, 0.98–1.12). The HR for CD after pandemic vaccination was 1.08 (95%CI, 1.03–1.14).

Conclusion: A positive association with influenza diagnosis is consistent with the hypothesis that infections may play a role in CD development. We could neither confirm a causal association with pandemic vaccination, nor refute entirely a small excess risk.

Keywords:

• Celiac disease
• cohort studies
• influenza a virus (H1N1 subtype)
• mass vaccination

Disclosure statement

All authors have completed and submitted the ICMJE Form for disclosure of potential conflicts of interest. The authors declare no conflicts of interest, including no relationships with GlaxoSmithKline (manufacturer of the vaccine Pandemrix), or other companies that might have an interest in the submitted work.

Additional information

Funding

The study was funded by the Norwegian Institute of Public Health. Dr Størdal was supported by an unrestricted grant from Oak Foundation, Geneva, Switzerland. The funders had no role in the design and conduct of the study or in the management, analysis and interpretation of the data