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Chronic Fatigue Syndrome (CFS)

Chronic Fatigue Syndrome (CFS) is a topic covered in the 5-Minute Clinical Consult.

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  • A complex physical illness characterized by a new or definite onset of debilitating fatigue that persists for >6 months and significantly reduces a person’s ability to perform usual activities. Key features include:
    • Impaired memory or concentration
    • Joint and muscle pain
    • Unrefreshing sleep
    • Postexertional malaise
    • Orthostatic intolerance (i.e., dizziness and light-headedness when standing up)
  • Synonyms: myalgic encephalomyelitis, chronic Epstein-Barr virus syndrome, postviral fatigue syndrome, chronic fatigue immune dysfunction, and systemic exertion intolerance disease (1)
  • Fatigue is not relieved by rest and results in >50% reduction in previous activities (occupational, educational, social, and personal).
  • Other potential medical causes must be ruled out (2).


  • Generally occurs as sporadic or isolated cases, although cluster outbreaks have occurred in different parts of the world—Iceland (1948), London, England (1955), New Zealand (1984), and the United States (1984 and 1985)
  • Onset usually between 30 and 50 years of age, can affect all ages (1)[B]
  • Females affected 3 to 4 times more than male
  • Estimated annual cost from loss of productivity and medical bills ranges from $17 to 24 billion in the United States.

  • Affects all racial and ethnic groups; more prevalent in minority and low socioeconomic groups
  • An estimated 836,000 to 2.5 million Americans suffer from chronic fatigue syndrome (CFS) (1)[B].

Etiology and Pathophysiology

  • Unknown and likely multifactorial
    • Possible interaction between genetic predisposition, environmental factors, an initiating stressor, and perpetuating factors
  • A recent theory attributes possible neuroendocrine immunologic and biochemical effects in CFS to dysbiosis of the gut microbiome.
  • Physiologic or environmental stressors are potential precipitants.
  • Many patients with chronic fatigue recall significant stressors (e.g., major medical procedure, loss of a loved one, loss of employment) in months before symptoms began. History of childhood trauma is common.
  • Systems hypothesized to contribute to altered physiology include:
    • Neuroendocrine (e.g., diminished cortisol response to increased corticotropin concentrations)
    • Immune (e.g., increased C-reactive protein and β-2 microglobulin)
    • Neuromuscular (e.g., dysfunction of oxidative metabolism)
    • Autonomic (Orthostatic hypotension is reported in a proportion of CFS patients.)
    • Serotonergic (e.g., hyperserotonergic mechanisms or upregulation of serotonin receptors)

Higher concordance among monozygotic twins compared with dizygotic twins

Risk Factors

Possible predisposing factors include (3):

  • Personality characteristics (neuroticism and introversion)
  • Lifestyle
    • Childhood inactivity or over activity
    • Inactivity in adulthood after infectious mononucleosis
    • Familial predisposition
    • Comorbid depression or anxiety
  • Long-standing medical conditions in childhood
  • Childhood trauma (emotional, physical, sexual abuse)
  • Prolonged idiopathic chronic fatigue
  • Postinfectious fatigue and CFS have been noted to follow mononucleosis, Ross River virus, Coxiella burnetii, herpes zoster, Q fever, and Giardia lamblia.
  • Due to concern for a possible “as yet undiscovered” infectious etiology, CFS patients excluded from donating blood by the American Red Cross in 2010

Commonly Associated Conditions

Common comorbidities include:

  • Fibromyalgia (more common in women)
  • Irritable bowel syndrome
  • Gynecologic conditions (pelvic pain, endometriosis) and GYN surgeries (hysterectomy, oophorectomy) (2)
  • Anxiety disorders
  • Major depression
  • Posttraumatic stress disorder (including physical and/or past sexual abuse)
  • Domestic violence
  • Attention deficit hyperactivity disorder (ADHD)
  • Postural orthostatic tachycardia syndrome (POTS)
  • Sleep disorders, including OSA
  • Reduced left ventricular size and mass

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Stephens, Mark B., et al., editors. "Chronic Fatigue Syndrome (CFS)." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116132/all/Chronic_Fatigue_Syndrome__CFS_.
Chronic Fatigue Syndrome (CFS). In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116132/all/Chronic_Fatigue_Syndrome__CFS_. Accessed March 22, 2019.
Chronic Fatigue Syndrome (CFS). (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116132/all/Chronic_Fatigue_Syndrome__CFS_
Chronic Fatigue Syndrome (CFS) [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 March 22]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116132/all/Chronic_Fatigue_Syndrome__CFS_.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Chronic Fatigue Syndrome (CFS) ID - 116132 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116132/all/Chronic_Fatigue_Syndrome__CFS_ PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -