Different risk factors distinguish myalgic encephalomyelitis/chronic fatigue syndrome from severe fatigue

Fatigue is a common reason that patients seek medical care. Only a fraction of these patients meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To determine if ME/CFS is just a more extreme form of fatigue, or a qualitatively different condition, we assessed whether risk factors for ME/CFS and for Severe Fatigue were similar. An email questionnaire that inquired about symptoms of Severe Fatigue and ME/CFS was completed by 41,802 US female nurses from whom detailed medical and lifestyle information had been collected since 1989: 102 met criteria for ME/CFS, 522 had Severe Fatigue, and 41,178 individuals were without significant chronic fatigue. We used Cox proportional hazards regression to estimate the Hazard Ratio (HR) of Severe Fatigue and of ME/CFS with each of several potential risk factors, according to the level of exposure to each risk factor. The risk of Severe Fatigue was significantly increased among participants who were older, had a higher BMI in adulthood, used hormone therapy, had increased alcohol intake and decreased caffeine intake. In contrast, these risk factor associations were not seen in people with ME/CFS. A self-reported past history of acute infectious mononucleosis was associated with a non-significantly increased Hazard Ratio of later ME/CFS (HR 1.77, 0.87-3.61) and, to a lesser extent, of Severe Fatigue (HR 1.28, 0.98-1.66). The different contribution of various risk factors to Severe Fatigue and ME/CFS suggests that ME/CFS has a qualitatively different underlying biology from the more common state of Severe Fatigue.