CDC Grand Rounds

Chronic Fatigue Syndrome — Advancing Research and Clinical Education

Elizabeth R. Unger, PhD, MD; Jin-Mann Sally Lin, PhD; Dana J. Brimmer, PhD; Charles W. Lapp, MD; Anthony L. Komaroff, MD; Avindra Nath, MD; Susan Laird, MSN; John Iskander, MD


Morbidity and Mortality Weekly Report. 2016;65(5051):1434-1438. 

In This Article

Cause or Causes of ME/CFS

The cause or causes of ME/CFS remain unknown. Patients often report an acute onset after a flu-like illness that does not go away, and some patients have a history of frequent infections before their illness. This suggests that an infection can trigger the illness, though it is less clear that the ongoing chronic illness is perpetuated by an infection. Investigators have looked for, and failed to find, a single etiologic agent. However, chronic fatiguing illnesses have long been described in the medical literature following infection with several different agents. For example, a syndrome with similarities to ME/CFS occurs in approximately 10% of patients with a variety of viral and nonviral pathogens, such as Epstein-Barr Virus, Ross River Virus, Coxiella burnetti (Q fever), or Giardia.[12] The severity of the acute infection was most predictive of subsequent illness, and there is no evidence of unusual persistence of infections in those who remain ill; baseline psychological profile and socioeconomic status did not predict who would become chronically ill.[12] Other studies have found that, compared with healthy controls, persons with ME/CFS have had exposure to significantly more stressors (trauma and other adverse life events) and are more likely to have metabolic syndrome, as well as higher physiologic measures of neuroendocrine response to stress (allostatic load).[13] These associations are not specific to ME/CFS, because stress is a factor in many chronic illnesses. Twin and family studies support the contribution of both genetic and environmental factors in CFS.[14] No single mutation or polymorphism has been found that explains most cases of the illness, and a polygenetic explanation for increased susceptibility is most likely.