Chronic fatigue syndrome

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In medicine, chronic fatigue syndrome is "a syndrome characterized by persistent or recurrent fatigue, diffuse musculoskeletal pain, sleep disturbances, and subjective cognitive impairment of 6 months duration or longer. Symptoms are not caused by ongoing exertion; are not relieved by rest; and result in a substantial reduction of previous levels of occupational, educational, social, or personal activities. Minor alterations of immune, neuroendocrine, and autonomic function may be associated with this syndrome. There is also considerable overlap between this condition and fibromyalgia."[1][2]


Various definitions for chronic fatigure syndrome have been proposed and they have been summarized.[3]

In 1994, the International Chronic Fatigue Syndrome Study Group proposed:[4]

"Chronic fatigue is defined as self-reported persistent or relapsing fatigue lasting 6 or more consecutive months"

"A case of idiopathic chronic fatigue is defined as clinically evaluated, unexplained chronic fatigue that fails to meet criteria for the chronic fatigue syndrome."

"A case of the chronic fatigue syndrome is defined by the presence of the following:

  • clinically evaluated, unexplained, persistent or relapsing chronic fatigue that is of new or definite onset [has not been lifelong]; is not the result of ongoing exertion; is not substantially alleviated by rest; and results in substantial reduction in previous levels of occupational, educational, social, or personal activities; and
  • the concurrent occurrence of four or more of the following symptoms, all of which must have persisted or recurred during 6 or more consecutive months of illness and must not have predated the fatigue:
    • self-reported impairment in short-term memory or concentration severe enough to cause substantial reduction in previous levels of occupational, educational, social, or personal activities;
    • sore throat;
    • tender cervical or axillary lymph nodes;
    • muscle pain, multijoint pain without joint swelling or redness;
    • headaches of a new type, pattern, or severity;
    • unrefreshing sleep; and
    • postexertional malaise lasting more than 24 hours."


An outbreak of a chronic mononucleosis-like syndrome was described in 1987.[5][6][7] Prior to this had been outbreaks of epidemic neuromyasthenia in 1959.[8][9]


Among outpatients in a health maintenance organization in the Northwestern United States of America:[4]

  • Chronic fatigue 19% of patients or 1775 to 6321 cases per 100 000 persons
    • Of the 19%, about two thirds "had a medical or psychiatric condition that could account for the fatigue"
    • Of the 19%, about 4% have chronic fatigue syndrome or 75 to 267 cases per 100 000 persons

A second cross sectional study verifies that chronic fatigue syndrome is uncommon among patients with chronic fatigue.[10]


According to twin studies, chronic fatigue syndrome may have a genetic susceptibility[11] with heritability as high as 51%[12]. This compares to a heritability for major depression of about a third.[13] Various have been single-nucleotide polymorphisms suggested.[14][15]

According to twin studies, chronic fatigue syndrome may cluster with chronic fatigue syndrome, low back pain, irritable bowel syndrome, chronic tension headache, fibromyalgia, temporomandibular joint disorder, major depression, panic attacks, and posttraumatic stress disorder suggesting a common etiology.[16]

Various retroviruses are associated with CFS.[17][18]In one study, the virus was found "in nearly 98 percent of about 300 patients with the syndrome" while only 3.7 percent of 218 healthy people were infected.[19]

Chronic fatigue syndrome may result from an interaction with organic and psychiatric factors.[20]


It has been proposed that clustered versions of CFS may increase risk of certain cancers.[21]


  1. Anonymous (2023), Chronic fatigue syndrome (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A (1994). "The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group.". Ann Intern Med 121 (12): 953-9. PMID 7978722.
  3. Anonymous. About CFS: What is Chronic Fatigue Syndrome? National Institutes of Health
  4. 4.0 4.1 Buchwald D, Umali P, Umali J, Kith P, Pearlman T, Komaroff AL (1995). "Chronic fatigue and the chronic fatigue syndrome: prevalence in a Pacific Northwest health care system.". Ann Intern Med 123 (2): 81-8. PMID 7778839.
  5. Holmes GP, Kaplan JE, Stewart JA, Hunt B, Pinsky PF, Schonberger LB (1987). "A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause?". JAMA 257 (17): 2297-302. PMID 3033337.
  6. Buchwald D, Cheney PR, Peterson DL, Henry B, Wormsley SB, Geiger A et al. (1992). "A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus type 6 infection.". Ann Intern Med 116 (2): 103-13. PMID 1309285.
  7. Levine PH, Jacobson S, Pocinki AG, Cheney P, Peterson D, Connelly RR et al. (1992). "Clinical, epidemiologic, and virologic studies in four clusters of the chronic fatigue syndrome.". Arch Intern Med 152 (8): 1611-6. PMID 1323246.
  8. HENDERSON DA, SHELOKOV A (1959). "Epidemic neuromyasthenia; clinical syndrome.". N Engl J Med 260 (15): 757-64 contd. PMID 13644582.
  9. HENDERSON DA, SHELOKOV A (1959). "Epidemic neuromyasthenia; clinical syndrome.". N Engl J Med 260 (16): 814-8 concl. PMID 13644592.
  10. Manu P, Lane TJ, Matthews DA (1988). "The frequency of the chronic fatigue syndrome in patients with symptoms of persistent fatigue.". Ann Intern Med 109 (7): 554-6. PMID 3421564.
  11. Sullivan PF, Evengård B, Jacks A, Pedersen NL (2005). "Twin analyses of chronic fatigue in a Swedish national sample.". Psychol Med 35 (9): 1327-36. DOI:10.1017/S0033291705005222. PMID 16168155. Research Blogging.
  12. Buchwald D, Herrell R, Ashton S, Belcourt M, Schmaling K, Sullivan P et al. (2001 Nov-Dec). "A twin study of chronic fatigue.". Psychosom Med 63 (6): 936-43. PMID 11719632.
  13. Sullivan PF, Neale MC, Kendler KS (2000). "Genetic epidemiology of major depression: review and meta-analysis.". Am J Psychiatry 157 (10): 1552-62. PMID 11007705.
  14. Smith AK, White PD, Aslakson E, Vollmer-Conna U, Rajeevan MS (2006). "Polymorphisms in genes regulating the HPA axis associated with empirically delineated classes of unexplained chronic fatigue.". Pharmacogenomics 7 (3): 387-94. DOI:10.2217/14622416.7.3.387. PMID 16610949. Research Blogging.
  15. Goertzel BN, Pennachin C, de Souza Coelho L, Gurbaxani B, Maloney EM, Jones JF (2006). "Combinations of single nucleotide polymorphisms in neuroendocrine effector and receptor genes predict chronic fatigue syndrome.". Pharmacogenomics 7 (3): 475-83. DOI:10.2217/14622416.7.3.475. PMID 16610957. Research Blogging.
  16. Schur EA, Afari N, Furberg H, Olarte M, Goldberg J, Sullivan PF et al. (2007). "Feeling bad in more ways than one: comorbidity patterns of medically unexplained and psychiatric conditions.". J Gen Intern Med 22 (6): 818-21. DOI:10.1007/s11606-007-0140-5. PMID 17503107. PMC PMC2219854. Research Blogging.
  17. Lo SC, Pripuzova N, Li B, Komaroff AL, Hung GC, Wang R et al. (2010). "Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors.". Proc Natl Acad Sci U S A 107 (36): 15874-9. DOI:10.1073/pnas.1006901107. PMID 20798047. Research Blogging.
  18. Lombardi, Vincent C.; Francis W. Ruscetti, Jaydip Das Gupta, Max A. Pfost, Kathryn S. Hagen, Daniel L. Peterson, Sandra K. Ruscetti, Rachel K. Bagni, Cari Petrow-Sadowski, Bert Gold, Michael Dean, Robert H. Silverman, Judy A. Mikovits (2009-10-08). "Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome". Science: 1179052. DOI:10.1126/science.1179052. Retrieved on 2009-10-09. Research Blogging.
  19. Grady, Denise. Virus Is Found in Many With Chronic Fatigue Syndrome, The New York Times, 2009-10-09. Retrieved on 2009-10-09.
  20. White PD, Thomas JM, Kangro HO, Bruce-Jones WD, Amess J, Crawford DH et al. (2001). "Predictions and associations of fatigue syndromes and mood disorders that occur after infectious mononucleosis.". Lancet 358 (9297): 1946-54. DOI:10.1016/S0140-6736(01)06961-6. PMID 11747919. Research Blogging.
  21. Levine PH, Fears TR, Cummings P, Hoover RN (1998). "Cancer and a fatiguing illness in Northern Nevada--a causal hypothesis.". Ann Epidemiol 8 (4): 245-9. PMID 9590603.