Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (CFS)
Basics
Description
- 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 impaired memory or concentration, joint/muscle pain, nonrestorative sleep, postexertional malaise (PEM), orthostatic intolerance.
- Synonyms: myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS), chronic Epstein-Barr virus syndrome, postviral fatigue syndrome, chronic fatigue immune dysfunction, systemic exertion intolerance disease
Epidemiology
- Can affect all ages; incidence peaks at 10 to 19 years and 30 to 39 years.
- Females are twice as likely to be affected.
Prevalence
- Affects all racial and ethnic groups; more prevalent in minority and low socioeconomic
- Estimated at 519 to 1,038 diagnosed per 100,000; 1.7 to 3.4 million patients may have ME/CFS.
- Up to 90% of cases may stay undiagnosed (1).
Etiology and Pathophysiology
The cause is unknown and likely multifactorial.
- Suspected initiating stressors:
- Viral, bacterial, or parasitic infection: Epstein-Barr virus, retroviruses, Lyme disease, Q fever, human herpesvirus type 6 (HHV6), enteroviruses, Ross River virus, Borna disease virus
- Recent vaccination; overexertion, chronic sleep deprivation; toxin exposure (e.g., organophosphate pesticides) or an atypical adverse reaction to a medication; significant physical or emotional trauma
- Hypothesized contributing factors:
- 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)
Genetics
- Higher concordance in monozygotic twins
- Genetic polymorphisms in several neuroimmunoendocrine-related genes may contribute to developing disease.
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
- 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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Citation
Domino, Frank J., et al., editors. "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (CFS)." 5-Minute Clinical Consult, 33rd ed., Wolters Kluwer, 2025. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688663/all/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome__CFS_.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (CFS). In: Domino FJF, Baldor RAR, Golding JJ, et al, eds. 5-Minute Clinical Consult. Wolters Kluwer; 2025. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688663/all/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome__CFS_. Accessed October 15, 2024.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (CFS). (2025). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (33rd ed.). Wolters Kluwer. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688663/all/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome__CFS_
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (CFS) [Internet]. In: Domino FJF, Baldor RAR, Golding JJ, Stephens MBM, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2025. [cited 2024 October 15]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688663/all/Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome__CFS_.
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