Chronic fatigue syndrome

Last updated: July 1, 2022

Summarytoggle arrow icon

Chronic fatigue syndrome (CFS), also known as “myalgic encephalomyelitis,” is a multisystem disease characterized by severe fatigue, cognitive dysfunction, unrefreshing sleep, orthostatic intolerance, and post-exertional malaise. The etiology of CFS is not completely understood but possible factors include genetic predisposition, prior infections, and immune abnormalities to the immune system. Diagnosis is based on clinical examination (i.e., IOM diagnostic criteria for CFS) and exclusion of other causes (e.g., glucose measurement to rule out diabetes mellitus). Since there is no curative treatment, management focuses on alleviating symptoms (e.g., improving quality of sleep). In most cases, symptoms improve with treatment but complete resolution of symptoms is rare.

Epidemiologytoggle arrow icon

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

The etiology of CFS is not completely understood. Factors possibly involved include the following:

Clinical featurestoggle arrow icon

  • Most common symptoms:
    • Unexplained fatigue that is not relieved by rest
    • Post-exertional malaise (e.g., muscle/joint pain, headache)
    • Unrefreshing sleep (i.e., daytime hypersomnolence and nighttime insomnia)
    • Cognitive impairment (e.g., impaired short term memory, decreased attention span)
    • Orthostatic intolerance (e.g., dizziness, nausea, vomiting)
    • Psychiatric symptoms (e.g., anxiety, depression)
  • Symptoms are typically exacerbated by excessive physical activity or stress (e.g., infection).
  • Physical examination is typically normal.

Diagnosticstoggle arrow icon

2015 IOM diagnostic criteria for CFS [2]

  • Presence of all three of the following symptoms:
    • New-onset (not life-long) and often profound fatigue that
      • Is not alleviated by rest.
      • Is not the result of excessive exertion.
      • Substantially impairs academic, professional, leisure, or social function for > 6 months
    • Post-exertional malaise
    • Unrefreshing sleep
  • Presence of at least one of the following two symptoms:
    • Cognitive impairment
    • Orthostatic intolerance
  • Diagnosis should be reassessed if symptoms are not moderate to severe at least 50% of the time.

Rule out other causes

See also “Differential diagnoses” below.

Differential diagnosestoggle arrow icon

The differential diagnoses listed here are not exhaustive.

Treatmenttoggle arrow icon

Since there is no curative treatment, management focuses on alleviating symptoms.

Prognosistoggle arrow icon

In most patients, symptoms improve with treatment but complete resolution of symptoms is rare (∼ 2% of cases). [18]

Referencestoggle arrow icon

  1. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management. Updated: August 22, 2007. Accessed: July 1, 2022.
  2. Institute of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness.. The National Academies Press ; 2015
  3. Smith AK, White PD, Aslakson E, Vollmer-Conna U, Rajeevan MS. Polymorphisms in genes regulating the HPA axis associated with empirically delineated classes of unexplained chronic fatigue.. Pharmacogenomics. 2006; 7 (3): p.387-94.doi: 10.2217/14622416.7.3.387 . | Open in Read by QxMD
  4. Goertzel BN, Pennachin C, de Souza Coelho L, Gurbaxani B, Maloney EM, Jones JF. Combinations of single nucleotide polymorphisms in neuroendocrine effector and receptor genes predict chronic fatigue syndrome.. Pharmacogenomics. 2006; 7 (3): p.475-83.doi: 10.2217/14622416.7.3.475 . | Open in Read by QxMD
  5. Manian FA. Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response?. Clin Infect Dis. 1994; 19 (3): p.448-53.doi: 10.1093/clinids/19.3.448 . | Open in Read by QxMD
  6. Ablashi DV, Eastman HB, Owen CB, et al. Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients.. J Clin Virol. 2000; 16 (3): p.179-91.doi: 10.1016/s1386-6532(99)00079-7 . | Open in Read by QxMD
  7. Kerr JR. The role of parvovirus B19 in the pathogenesis of autoimmunity and autoimmune disease.. J Clin Pathol. 2016; 69 (4): p.279-91.doi: 10.1136/jclinpath-2015-203455 . | Open in Read by QxMD
  8. Mantovani E, Mariotto S, Gabbiani D, et al. Chronic fatigue syndrome: an emerging sequela in COVID-19 survivors?. J Neurovirol. 2021; 27 (4): p.631-637.doi: 10.1007/s13365-021-01002-x . | Open in Read by QxMD
  9. Caligiuri M, Murray C, Buchwald D, et al. Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome.. J Immunol. 1987; 139 (10): p.3306-13.
  10. Loebel M, Grabowski P, Heidecke H, et al. Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome.. Brain Behav Immun. 2016; 52: p.32-39.doi: 10.1016/j.bbi.2015.09.013 . | Open in Read by QxMD
  11. Konstantinov K, von Mikecz A, Buchwald D, Jones J, Gerace L, Tan EM. Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.. J Clin Invest. 1996; 98 (8): p.1888-96.doi: 10.1172/JCI118990 . | Open in Read by QxMD
  12. von Mikecz A, Konstantinov K, Buchwald DS, Gerace L, Tan EM. High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome.. Arthritis Rheum. 1997; 40 (2): p.295-305.doi: 10.1002/art.1780400215 . | Open in Read by QxMD
  13. Klimas NG, Salvato FR, Morgan R, Fletcher MA. Immunologic abnormalities in chronic fatigue syndrome.. J Clin Microbiol. 1990; 28 (6): p.1403-10.doi: 10.1128/jcm.28.6.1403-1410.1990 . | Open in Read by QxMD
  14. Hornig M, Gottschalk G, Peterson DL, et al. Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome.. Mol Psychiatry. 2016; 21 (2): p.261-9.doi: 10.1038/mp.2015.29 . | Open in Read by QxMD
  15. Orlandi AC, Ventura C, Gallinaro AL, Costa RA, Lage LV. Improvement in pain, fatigue, and subjective sleep quality through sleep hygiene tips in patients with fibromyalgia.. Revista brasileira de reumatologia. 2012; 52 (5): p.666-78.
  16. Castro-Marrero J, Sáez-Francàs N, Santillo D, Alegre J. Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: all roads lead to Rome.. Br J Pharmacol. 2017; 174 (5): p.345-369.doi: 10.1111/bph.13702 . | Open in Read by QxMD
  17. Jason L, Benton M, Torres-Harding S, Muldowney K. The impact of energy modulation on physical functioning and fatigue severity among patients with ME/CFS.. Patient Educ Couns. 2009; 77 (2): p.237-41.doi: 10.1016/j.pec.2009.02.015 . | Open in Read by QxMD
  18. Bombardier CH, Buchwald D. Outcome and prognosis of patients with chronic fatigue vs chronic fatigue syndrome.. Arch Intern Med. 1995; 155 (19): p.2105-10.

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