Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (CFS)

Myalgic Encephalomyelitis/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 definitive 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).


  • Usually 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 from age 30 to 50 years; 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 symptom onset.
  • History of childhood trauma is common.
  • Systems hypothesized to contribute include:
    • Neuroendocrine (e.g., diminished cortisol response to increased corticotropin concentrations)
    • Immune (e.g., increased C-reactive protein and β2-microglobulin)
    • Neuromuscular (e.g., dysfunction of oxidative metabolism)
    • Autonomic (orthostatic hypotension)
    • Serotonergic (e.g., hyperserotonergic mechanisms or upregulation of serotonin receptors)

Higher concordance among monozygotic twins compared with dizygotic twins

Risk Factors

Possible predisposing factors:

  • Personality characteristics (neuroticism and introversion)
  • Lifestyle
    • Childhood inactivity or overactivity
    • 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 possible 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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