Mononucleosis in youth may increase risk for MS diagnosis

Infectious mononucleosis in childhood, especially in adolescence, appeared to increase risk for an MS diagnosis, independent of shared familial factors, according to results of a population-based cohort study published in JAMA Network Open.

“Infectious mononucleosis has previously been associated with MS, but it has been suggested that this is because people with genetic susceptibility to MS have an immune system that is more reactive to Epstein-Barr virus infection (the virus that causes infectious mononucleosis),” Scott Montgomery, PhD, director of clinical epidemiology and biostatistics at Örebro University Hospital in Sweden, told Healio Neurology. “This would mean that more severe infectious mononucleosis, possibly resulting in hospital admission, would be observed more often in people who would go on to develop MS anyway, irrespective of whether they had infectious mononucleosis or not.

“It has also been argued that family circumstances in childhood might influence both infectious mononucleosis risk and MS risk, such that the infection is an epiphenomenon rather than a cause of MS,” Montgomery added.

In the current study, Montgomery and colleagues sought to determine whether hospital-diagnosed infectious mononucleosis in childhood, adolescence or young adulthood was linked to subsequent MS diagnosis unrelated to shared familial factors. According to Montgomery, if infectious mononucleosis is indeed a risk factor for MS, comparing siblings would show this connection, and associations that arise entirely from shared familial characteristics would not appear.

The researchers analyzed data of 2,492,980 individuals (52.63% men) included in the Swedish Total Population Register who were born in Sweden between 1958 and 1994. Follow-up occurred among participants beginning at age 20 years in 1978 and continued until 2018, with a median follow-up of 15.38 years. Infectious mononucleosis diagnosis before age 25 years served as the exposure. MS diagnoses from age 20 years served as the main outcome. Montgomery and colleagues used conventional and stratified Cox proportional hazards regression to address familial environmental or genetic confounding and, in turn, estimate the risk for an MS diagnosis linked to infectious mononucleosis from childhood, adolescence and early adulthood.

Results showed an MS diagnosis among 5,867 (0.24%) participants from age 20 years (median age, 31.5 years). Infectious mononucleosis in childhood (HR = 1.98; 95% CI, 1.21-3.23) and adolescence (HR = 3; 95% CI, 2.48-3.63) correlated with an increased risk for an MS diagnosis. This risk remained significant after controlling for shared familial factors in stratified Cox proportional hazards regression. Infectious mononucleosis in early adulthood also correlated with risk for a subsequent MS diagnosis (HR = 1.89; 95% CI, 1.18-3.05); however, controlling for shared familial factors attenuated this risk and made it nonsignificant (HR = 1.51; 95% CI, 0.82-2.76).

“MS should be considered as a potential diagnosis at an earlier time in patients with neurological symptoms and signs and a history of infectious mononucleosis in adolescence,” Montgomery said. “Although only a small proportion of those who have severe infectious mononucleosis in adolescence will go on to develop MS, limiting acute CNS involvement may have long-term benefits for this minority.”