Incidence age is bimodal for myalgic encephalomyelitis/chronic fatigue syndrome, with higher severity burden for...

Myalgic Encephalomyelitis, or Chronic Fatigue Syndrome (ME/CFS), is a disease of uncertain origin. Studies of Norwegian health records have suggested that ME/CFS incidence across age groups is bimodal-a characteristic that could provide insight into the aetiology of the disease. Here, we analysed survey data from over 9000 respondents with ME/CFS from 10 European countries, and observe an early onset peak with a mean of 16.0 years old (standard deviation [SD]: 4.3) and a late onset peak at 36.6 years old (SD: 10.5). Statistical support for multimodal onset age was evident in 7 of the 10 countries examined. Infection as a trigger for ME/CFS was 10 percentage points higher among early compared to late onset disease (p = 2.1 × 10^-13). Early onset ME/CFS was associated with greater odds of being severely or very severely affected (OR = 2.15, 95% CI [1.84-2.51], p < 2 × 10^-16). Those with first degree relatives with ME/CFS had greater odds of early than late onset ME/CFS (OR = 1.43, 95% CI [1.25-1.63], p = 4.4 × 10^-07). We further validated our findings in a UK dataset where we replicated bimodal onset age and observed significantly greater odds of glandular fever/infectious mononucleosis as a trigger in early onset cases (OR = 2.32, 95% CI [1.99-2.71], p = 2.4 × 10^-24). Our findings suggest that incidence of ME/CFS peaks in adolescence and in early middle-age and that early onset ME/CFS is more common in those with affected relatives, more often triggered by infection, and associated with more severe disease.