Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (CFS)



  • A chronic and complex physical illness characterized by a new or definitive onset of debilitating fatigue that persists for >6 months with moderate-to-severe intensity at least half of the time, which significantly reduces a person’s ability to perform activities, and can’t be fully explained by an underlying medical condition
  • Key features include (1):
    • Impaired memory or concentration; joint and muscle pain, nonrestorative sleep; postexertional malaise (PEM), orthostatic intolerance
  • Synonyms: myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS), chronic Epstein-Barr virus (EBV) syndrome, postviral fatigue syndrome, chronic fatigue immune dysfunction, and systemic exertion intolerance disease (SEID)


  • Can affect all ages; incidence peaks at ages 10 to 19 years and 30 to 39 years (1).
  • Females are twice as likely to be affected.
  • Up to 70% of patients are unable to return to work, and one quarter remain bedridden or housebound (2).


  • Affects all racial and ethnic groups; more prevalent in minority and low socioeconomic groups
  • Estimated at 519 to 1,038 diagnosed per 100,000; 1.7 to 3.4 million patients may suffer from ME or CFS.
  • Up to 90% of cases may remain undiagnosed (2).

Etiology and Pathophysiology

Cause is unknown and likely multifactorial

  • Suspected initiating stressors:
    • Viral, bacterial, or parasitic infection: EBV, retroviruses, Lyme disease, Q fever, human herpesvirus type 6 (HHV6), enteroviruses, Ross River virus, Borna disease virus; significant physical or emotional trauma
    • Recent vaccination; overexertion, chronic sleep deprivation; toxin exposure (e.g., organophosphate pesticides) or an atypical adverse reaction to a medication
  • Hypothesized contributing systems and factors (3):
    • Cellular metabolism (e.g., reduced oxidative phosphorylation and mitochondrial function in T cells); neuroendocrine system (e.g., diminished cortisol response to increased corticotropin); immune system (e.g., increased proinflammatory cytokines, C-reactive protein, and β2-microglobulin); muscular system (e.g., reduced oxygen uptake); autonomic system (e.g., orthostatic hypotension); serotonergic system (e.g., upregulation of serotonin receptors); gastrointestinal system (e.g., increased wall permeability, altered gut microbiota, irritable bowel syndrome [IBS] comorbidity)


  • Higher concordance in monozygotic twins
  • Genetic polymorphisms in several neuroimmunoendocrine-related genes may contribute to developing disease (3).

Risk Factors

  • Family history of ME or CFS
  • Personality characteristics (neuroticism and introversion); comorbid depression or anxiety
  • Long-standing medical and/or mental health conditions in childhood; childhood inactivity or overactivity; childhood trauma (emotional, physical, or sexual abuse)
  • Prolonged idiopathic chronic fatigue

Commonly Associated Conditions

  • Fibromyalgia (more common in women)
  • IBS
  • Gynecologic conditions (pelvic pain, endometriosis) and surgeries (hysterectomy, oophorectomy)
  • Anxiety disorders and/or major depressive disorders; posttraumatic stress disorder (PTSD), including physical and/or past sexual abuse; domestic violence; attention deficit hyperactivity disorder (ADHD)
  • Postural orthostatic tachycardia syndrome (POTS); sleep disorders, including obstructive sleep apnea (OSA)
  • Reduced left ventricular size and mass; prolapsed mitral valve; temporomandibular joint syndrome
  • Multiple chemical sensitivities; migraines, myofascial pain syndrome
  • Hashimoto thyroiditis, Raynaud phenomenon; interstitial cystitis, sicca syndrome, allergies

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