Objective:

To assess risk of multiple sclerosis (MS), demyelinating diseases, and other key outcomes in individuals diagnosed with Epstein-Barr Virus-positive infectious mononucleosis (EBV+ IM).

Background:

EBV is implicated in the pathogenesis of multiple conditions, but population-based studies are rare.

Design/Methods:

We studied a population-based cohort of 4,721 individuals diagnosed with EBV+ IM between 01January 1998 and 31December 2022 using data from the Rochester Epidemiology Project (REP). EBV+IM patients were age, sex, and age at index date matched to 14,163 referents without EBV infection. Diagnoses of MS, MS and related demyelinating diseases, splenic rupture, systemic lupus erythematosus (SLE), lymphoid malignancies and death were identified using ICD-9 and ICD-10 codes. Cox proportional hazards models were used to estimate associations between EBV+IM and each outcome. Hazard ratios (HRs) were adjusted for sociodemographic factors, smoking, body mass index, comorbidities, and healthcare utilization the previous year.

Results:

Median follow-up was 6 years for the EBV+ IM cohort and 8 years for the referents. Individuals with EBV+ IM had a significantly higher risk of MS (adjusted HR 3.03,95% Confidence Interval (CI): 1.15, 8.01), any demyelinating disease (HR: 3.77; 95% CI: 1.61, 8.86), splenic rupture (HR 2.41,95% CI: 1.13, 5.17), and lymphoid malignancies (HR 2.14, 95% CI: 1.01, 4.50). No significant increased risks were observed for SLE (HR 0.98, 95% CI: 0.20, 4.73) or death (HR 1.00, 95% CI: 0.66, 1.51).

Conclusions:

EBV+ IM significantly raises risks for MS, demyelinating diseases, splenic rupture and lymphoid malignancies. These findings reinforce the need for EBV-targeted preventive strategies. Further research should focus on outcomes in broader populations and with extended follow-up.