Chronic Fatigue Syndrome (CFS)

Updated: Aug 29, 2018
  • Author: Jefferson R Roberts, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Chronic fatigue syndrome (CFS) is a disorder characterized by unexplained profound fatigue that is worsened by exertion. The fatigue is accompanied by cognitive dysfunction and impairment of daily functioning that persists for more than 6 months.

CFS was originally termed myalgic encephalomyelitis (ME) because British clinicians noted a skeletal muscle component manifesting as chronic fatigue and an encephalitic component manifesting as cognitive difficulties. However, this term is inappropriate because of a lack of encephalomyelitis in laboratory and imaging studies, and myalgia is not a core symptom of the disease. [1]

In 2015, the Institute of Medicine (IOM) proposed that the condition be renamed systemic exertion intolerance disease (SEID) to better reflect the condition's hallmark defining symptom, postexertional malaise. [2]

​The cause of CFS is unknown, and there are no direct tests to diagnose CFS. If the source of the fatigue can be explained, the patient probably does not have CFS. The diagnosis is one of exclusion that meets the clinical criteria below.

Diagnostic criteria

A diagnosis of CFS requires the following three symptoms: [1]

  • A substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities, that persists for more than 6 months and is accompanied by fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest
  • Postexertional malaise
  • Unrefreshing sleep

At least one of the following must also be present:

  • Cognitive impairment
  • Orthostatic intolerance


CFS is a biological illness, not a psychologic disorder. The exact pathogenesis is unknown. Numerous mechanisms and molecules have been implicated that lead to abnormalities in immune dysfunction, hormonal regulation, metabolism and response to oxidative stress to include impaired natural killer cell function and/or T-cell function, elevated cytokines, and autoantibodies (rheumatic factor, antithyroid antibodies, antigliadin, anti–smooth muscle antibodies, and cold agglutinins). [3, 4] Infections have been suspected; however, no causal role has been established.



Many viruses have been studied as potential causes of CFS; however, no definitive causal relation has been determined. Historically, human herpesvirus type 6, enterovirus, rubella virus, Candida albicans, bornavirus, Mycoplasma, Chlamydia pneumoniae, retroviruses, coxsackie B virus, cytomegalovirus, and xenotropic murine leukemia virus-related virus have been studied and have not been found to cause CFS. [5, 6, 7, 8, 9, 10, 11, 12] Some people infected with Epstein-Barr virus, Ross River virus, Coxiella burnetii, or Giardia have developed criteria for CFS, but not all individuals with CFS have had these infections. [3]

Environmental factors have also been suspected as a trigger for CFS; however, no specific factors have been identified.



CFS affects 836,000 to 2.5 million Americans. [1] An estimated 84%-91% of individuals with the condition have not been diagnosed; therefore, the true prevalence is unknown. Overall, CFS is more common in females than in males and occurs most commonly in young to middle-aged adults. [13] The average age of onset is 33 years, although cases have been reported in patients younger than 10 years and older than 70 years. Patients with CFS experience loss of productivity and high medical costs that contribute to a total economic burden of $17-24 billion annually. [1]



CFS has no cure, its symptoms can persist for years, and its clinical course is punctuated by remissions and relapses. One prospective study suggests that approximately 50% of patients with CFS can return to part-time or full-time work. [14] Longer duration of illness, severe fatigue, comorbid depression, and anxiety are factors associated with a poorer prognosis. [15] Good outcomes are associated with less fatigue severity at baseline, a sense of control over symptoms, and no attribution of the illness to a physical cause. [16] Despite the considerable burden of morbidity associated with CFS, there is no evidence of an increased risk of mortality.


Patient Education

For patient education resources, see the Back, Ribs, Neck, and Head Center, as well as Chronic Fatigue Syndrome, Fibromyalgia, and Fatigue.