Infectious mononucleosis (IM) is suspected to be associated with inflammatory bowel disease (IBD) development. Using a Danish nationwide cohort of people developing severe IM and their age-, sex-, and socioeconomic (SES) index-matched counterparts, we investigated the subsequent risk of IBD, Crohn’s disease (CD), or ulcerative colitis (UC) development from 1977 to 2021. Among 39,684 severe IM patients we find a sex-, age-, and SES index-adjusted HR for IBD of 1.35 (95% CI: 1.22–1.49). This significantly increased risk was seen for both CD (HR: 1.56; 95% CI: 1.34–1.83) and to a lesser extent UC (HR: 1.23; 95% CI: 1.08–1.40) and remains following negative control matching with a cohort diagnosed with Chlamydia trachomatis infection (HR: 1.39; 95% CI: 1.01–1.91). Those with severe IM at 0–9 years had a particularly increased risk for CD (HR: 1.77; 95% CI: 1.26–2.49). Here we show an increased risk for IBD diagnosis following IM hospitalisation, indicating an association between severe EBV disease and later IBD development. Further exploration of the potential factors contributing to IBD susceptibility following EBV disease is warranted.
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