History of chronic fatigue syndrome

Short description: Review of the topic

Royal Free Hospital in London, where Myalgic Encephalomyelitis came to prominent attention in 1955

The history of chronic fatigue syndrome (CFS; also known as Myalgic encephalomyelitis (ME) and by several other names) is thought to date back to the 19th century and before.

## Contents

* 1 Timeline
* 2 International classifications
* 2.1 ICD-8
* 2.2 ICD-9
* 2.2.1 ICD-9-CM
* 2.3 ICD-10
* 2.3.1 ICD-10-CM
* 3 References

## Timeline

Several descriptions of illness resembling those of chronic fatigue syndrome have been reported for at least 200 years.[1]

In the 19th century, neurologist George Miller Beard popularised the concept of neurasthenia, with symptoms including fatigue, anxiety, headache, impotence, neuralgia and depression.[2] This concept remained popular well into the 20th century, eventually coming to be seen as a behavioural rather than physical condition, with a diagnosis that excluded postviral syndromes. Neurasthenia has largely been abandoned as a medical diagnosis.[3] The ICD-10 system of the World Health Organization categorized neurasthenia under (F48 Other neurotic disorders) which specifically excluded chronic fatigue syndrome.[4] The current version of ICD, ICD-11, does not include neurasthenia and “deprecates” its use.

A United States Public Health Service (USPHS) official, Alexander Gilliam, described an illness that resembled poliomyelitis, after interviewing patients and reviewing records of one of several clusters which had occurred in Los Angeles , during 1934.[5] The Los Angeles County Hospital outbreak included all or most of its nurses and doctors.[6] Gilliam called the outbreak "atypical poliomyelitis" and described the symptoms as: rapid muscle weakness, vasomotor instability, clonic twitches and cramps, ataxia, severe pain (usually aggravated by exercise), neck and back stiffness, menstrual disturbance and dominant sensory involvement.[citation needed]

There was a cluster of "encephalitis" cases in 1936, at a convent in Wisconsin, amongst novices and convent candidates. The following year two towns in Switzerland had outbreaks of "abortive poliomyelitis" , and 73 Swiss soldiers were given the same diagnosis in 1939. Outbreaks in Iceland were called "Akureyri disease" or "simulating poliomyelitis" and were later called "Iceland disease."[6] 800 people in Adelaide, Australia became ill during 1949–1951 with a disease "resembling poliomyelitis." Two smaller clusters in the United States during 1950 were diagnosed as "Epidemic neuromyasthenia" and "resembling Iceland disease simulating acute anterior poliomyelitis." Additional outbreaks of poliomyelitis-like "mystery diseases" occurred from the 1950s through the 1980s, in Denmark , the United States, South Africa, and Australia, among others.[6]

Several outbreaks of a polio-resembling illness occurred in Britain in the 1950s.[7] A 1955 outbreak at the Royal Free Hospital Group was later called "Royal Free disease" or "benign myalgic encephalomyelitis".[8][9] After the Royal Free Hospital outbreak, a disorder with similar symptoms was found among the general population and the epidemic form came to be considered the exception.[citation needed] Pathology findings, both in monkeys[10] and in rare human casualties,[11] led to the conclusion that the disorder was caused by inflammation of the brain and the spinal cord, particularly the afferent nerve roots, perhaps with neuroimmune etiology.[12]

In the 1960s and 1970s, chronic fatigue symptoms were often attributed to chronic brucellosis, but typically people were seen as having psychiatric disorders, in particular depression.[6] Epidemic cases of benign myalgic encephalomyelitis were called mass hysteria by psychiatrists McEvedy and Beard in 1970,[13] provoking criticism in letters to the editor of the British Medical Journal by outbreak researchers, attending physicians, and physicians who fell ill.[14][15][16][17][18][19][20][21][22] The psychiatrists were faulted for not adequately investigating the patients they described,[23] and their conclusions have been refuted.[3][24][25] In 1978 a symposium held at the Royal Society of Medicine (RSM) concluded that "epidemic myalgic encephalomyelitis" was a distinct disease entity with a clear organic basis.[26]

The illness gained national attention in the United States when the popular magazine Hippocrates ran a cover story of an epidemic at Lake Tahoe, Nevada, in the mid-1980s.[27] The designation Chronic Epstein-Barr Virus was in use in the U.S.,[28][29] but the magazine used the term "Raggedy Ann Syndrome" to note the fatigue and loss of muscle power patients felt.[30]

Researchers investigating the Lake Tahoe cluster did not find evidence that EBV was involved, and they proposed the name "chronic fatigue syndrome", describing the main symptom of the illness.[31][32] They published the first working case definition for CFS in 1988.[33] Research increased considerably, and more so after the criteria were relaxed in 1994.[34]

In 1990, researchers presented evidence they found DNA sequences very similar to the human HTLV-II retrovirus in some CFS patients, at a conference in Kyoto, Japan.[35][36] Their study was later published in the Proceedings of the National Academy of Sciences.[37] A reporter on Prime Time Live stated the announcement made headlines all over the world. The CDC first ignored their findings,[38] then later conducted a study and published a paper that refuted the hypothesis.[39]

In the United Kingdom, the Chief Medical Officer Kenneth Calman requested a report from the medical Royal Colleges in 1996. This led to the publication of a joint report in which the term "chronic fatigue syndrome" was found to be most representative.[40] This was followed in 2002 by a further report by the new CMO, Liam Donaldson.[41]

The U.S. Centers for Disease Control & Prevention (CDC) recognize CFS as a serious illness, and launched a campaign in June 2006 to raise public and medical awareness about it.[42][43]

A 2009 study published in the journal Science reported an association between a retrovirus xenotropic murine leukemia virus-related virus (XMRV) and CFS. The editors of Science subsequently attached an "Editorial Expression of Concern" to the report, to the effect that the validity of the study "is now seriously in question".[44] and in September 2011, the authors published a "Partial Retraction" of their 2009 findings;[45] this was followed by a full retraction by the magazine's Editor in Chief, after the authors failed to agree on a full retraction statement.[46] Also in September 2011, the Blood XMRV Scientific Research Working Group published a report, which concluded "that currently available XMRV/P-MLV assays, including the assays employed by the three participating laboratories that previously reported positive results on samples from CFS patients and controls (2, 4), cannot reproducibly detect direct virus markers (RNA, DNA, or culture) or specific antibodies in blood samples from subjects previously characterized as XMRV/P-MLV positive (all but one with a diagnosis of CFS) or healthy blood donors."[47] In December 2011, the Proceedings of the National Academy of Sciences published a similar retraction for an August 2010 paper.[48] Some members of the patient community, who had viewed the XMRV findings as a source of hope for a possible cure, initially reacted negatively when the papers were called into question. One UK researcher reported verbal abuse after publishing an early paper indicating that the XMRV studies were flawed.[49]

## International classifications

The World Health Organization's (WHO) International Classification of Diseases (ICD), mandates the international classifications of diseases to allow comparison of health and health fields across countries and throughout the world.[50] Not all terms appear in the tabular list (Volume 1), and many more terms are listed in the alphabetic index (Volume 3) of the ICD.[51]

### ICD-8

Since its introduction into the eighth edition of the WHO ICD-8 in 1969 (code 323), (Benign) myalgic encephalomyelitis has been classified as a disease of the central nervous system.[52]

### ICD-9

The term "benign myalgic encephalomyelitis" appears in the 1975 ICD-9 alphabetic index, and references code 323.9, Encephalitis of unspecified cause.[53] The code 323.9 did not include reference to postviral syndrome. The term “postviral syndrome” was classified to code 780.7, Malaise and fatigue, in Chapter 16, Symptoms, signs and ill-defined conditions.[51]

The name Chronic Fatigue Syndrome has been attributed to the US Centers for Disease Control 1988 research case definition for the illness, "Chronic fatigue syndrome: a working case definition".[31][33] Chronic Fatigue Syndrome (CFS) was added to ICD-9 after 1988 and listed under code 780.71, Symptoms Signs and Ill-defined Conditions.[citation needed]

#### ICD-9-CM

Since 1979 the U.S. has used a clinical modification of WHO's ICD 9th revision (ICD-9-CM),[51] and ME is under index: "Encephalomyelitis (chronic) (granulomatous) (hemorrhagic necrotizing, acute) (myalgic, benign) (see also Encephalitis) 323.9."[54]

For CFS, a modification to the alphabetic index was made, effective on October 1, 1991, to direct users to code 780.7, Malaise and fatigue, the same code used to identify cases of postviral syndrome. In 1998, a new five-digit code included 780.71, Chronic fatigue syndrome, consistent with the WHO version of ICD-9.[51] Chronic fatigue syndrome is classified in tabular list: "Symptoms, Signs and Ill-Defined Conditions," under the sub-heading of "General Symptoms".[55]

### ICD-10

CFS is not included as a coded term in the 1992 ICD-10, WHO created a new category G93, Other disorders of brain, in Chapter VI, Diseases of the Nervous System, and created a new code G93.3, post-viral fatigue syndrome (PVFS), a condition which was previously in the symptom chapter of ICD-9. WHO also moved benign myalgic encephalomyelitis to G93.3, subordinate to PVFS. The alphabetic index contains other terms, such as chronic fatigue syndrome, to which WHO assigned the same code.[51][56]

#### ICD-10-CM

The 2010 version of the ICD-10-CM separates CFS and Postviral fatigue syndrome into mutually exclusive categories. "Chronic fatigue, unspecified | Chronic fatigue syndrome not otherwise specified" appears in Chapter XVIII under R53.82. "Postviral fatigue syndrome | benign myalgic encephalomyelitis" appears in Chapter VI under G93.3.[57] The Chronic Fatigue Syndrome Advisory Committee (CFSAC) had previously recommended CFS to be placed under the same neurological code as ME and PVFS, G93.3.[58]

The 2023 update to the ICD-10-CM added a specific code for ME/CFS, G93.32, giving CFS a code separate from unspecified chronic fatigue.[59]

## References

1. ↑ "Immunological aspects of chronic fatigue syndrome". Autoimmun Rev 8 (4): 287–91. February 2009. doi:10.1016/j.autrev.2008.08.003. PMID 18801465.
2. ↑ Beard, G (1869). "Neurasthenia, or nervous exhaustion". The Boston Medical and Surgical Journal 80 (13): 217–21. doi:10.1056/NEJM186904290801301. https://zenodo.org/record/2086793.
3. ↑ 3.0 3.1 "Chronic fatigue syndrome: new insights and old ignorance". Journal of Internal Medicine 246 (5): 455–69. Nov 1999. doi:10.1046/j.1365-2796.1999.00513.x. PMID 10583715. http://www3.interscience.wiley.com/cgi-bin/fulltext/119095441/PDFSTART. Retrieved June 25, 2009. [|permanent dead link|dead link}}]
4. ↑ WHO (2007), "Chapter V Mental and behavioural disorders (F00-F99)", ICD-10, http://apps.who.int/classifications/apps/icd/icd10online/index.htm?gf40.htm, retrieved October 9, 2009
5. ↑ Gilliam, AG (1938). "Epidemiological study on an epidemic, diagnosed as poliomyelitis, occurring among the personnel of Los Angeles County General Hospital during the summer of 1934". United States Treasury Department Public Health Service Public Health Bulletin (Washington, DC: United States Government Printing Office) 240: 1–90.
6. ↑ 6.0 6.1 6.2 6.3 Roberto Patarca-Montero (2004). Medical Etiology, Assessment, and Treatment of Chronic Fatigue and Malaise. Haworth Press. pp. 6–7. ISBN 0-7890-2196-X.
7. ↑ A. Melvin Ramsay (1986). Postviral Fatigue Syndrome. The saga of Royal Free disease. London: Gower. ISBN 0-906923-96-4.
8. ↑ The Medical Staff Of The Royal Free Hospital (1957). "An outbreak of encephalomyelitis in the Royal Free Hospital Group, London, in 1955". Br Med J 2 (5050): 895–904. doi:10.1136/bmj.2.5050.895. PMID 13472002.
9. ↑ (No authors listed) (1956). "A new clinical entity?". Lancet 270 (6926): 789–90. doi:10.1016/S0140-6736(56)91252-1. PMID 13320887.
10. ↑ "Further investigations on a disease resembling poliomyelitis seen in Adelaide". Med. J. Aust. 2 (13): 480–82. September 1955. doi:10.5694/j.1326-5377.1955.tb48805.x. PMID 13272481.
11. ↑ Wallis AL (1957). An investigation into an unusual illness seen in epidemic and sporadic form in a general practice in Cumberland in 1955 and subsequent years (M.D. thesis). Edinburgh University.
12. ↑ Richardson, J (2002). "Myalgic encephalomyelitis: guidelines for doctors". Journal of Chronic Fatigue Syndrome 10 (1): 65–80. doi:10.1300/j092v10n01_06. http://www.prohealth.com/library/showarticle.cfm?libid=9926.
13. ↑ "Concept of Benign Myalgic Encephalomyelitis". British Medical Journal 1 (5687): 11–15. 1970. doi:10.1136/bmj.1.5687.11. PMID 5411596.
14. ↑ Scott BD (January 1970). "Epidemic malaise". Br Med J 1 (5689): 170–75. doi:10.1136/bmj.1.111.170. PMID 5370039.
15. ↑ N. D. Compston; H. E. Dimsdale; A. M. Ramsay; A. T. Richardson (February 1970). "Epidemic malaise". Br Med J 1 (5692): 362–63. doi:10.1136/bmj.1.5692.362-a.
16. ↑ E. D. Acheson (February 1970). "Epidemic Malaise". Br Med J 1 (5692): 363–34. doi:10.1136/bmj.1.5692.363-b.
17. ↑ Gosling PH (February 1970). "Epidemic malaise". Br Med J 1 (5694): 499–500. doi:10.1136/bmj.1.5694.499-b. PMID 5435167.
18. ↑ Purke GJ (February 1970). "Epidemic malaise". Br Med J 1 (5694): 500. doi:10.1136/bmj.1.5694.500. PMID 5435168.
19. ↑ Hopkins EJ (February 1970). "Epidemic malaise". Br Med J 1 (5694): 500–01. doi:10.1136/bmj.1.5694.500-a. PMID 5435169.
20. ↑ Galpine JF (February 1970). "Epidemic malaise". Br Med J 1 (5694): 501. doi:10.1136/bmj.1.5694.501. PMID 5435170.
21. ↑ Poskanzer DC (May 1970). "Epidemic malaise". Br Med J 2 (5706): 420–21. doi:10.1136/bmj.2.5706.420-b. PMID 5420612.
22. ↑ Parish JG (July 1970). "Epidemic malaise". Br Med J 3 (5713): 47–48. doi:10.1136/bmj.3.5713.47-c. PMID 4316803.
23. ↑ Hooper M (2006). "Myalgic encephalomyelitis: a review with emphasis on key findings in biomedical research". J Clin Pathol 60 (5): 466–71. doi:10.1136/jcp.2006.042408. PMID 16935967. [1]
24. ↑ "Postviral fatigue syndrome: time for a new approach". Br Med J (Clin Res Ed) 296 (6623): 696–99. March 1988. doi:10.1136/bmj.296.6623.696. PMID 3128374.
25. ↑ "Objective measurement of personality variables in epidemic neuromyasthenia patients". S. Afr. Med. J. 77 (1): 31–34. January 1990. PMID 2294610.
26. ↑ [No authors listed] (June 3, 1978). "Epidemic myalgic encephalomyelitis". Br Med J 1 (6125): 1436–37. doi:10.1136/bmj.1.2791.1436-a. PMID 647324.
27. ↑ Johnson, Hilary (1996). Osler's Web: inside the labyrinth of the chronic fatigue syndrome epidemic. New York: Penguin Books. p. 24. ISBN 0-595-34874-2.
28. ↑ "Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies". Ann Intern Med 102 (1): 1–7. 1985. doi:10.7326/0003-4819-102-1-. PMID 2578266.
29. ↑ "Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection". Ann Intern Med 102 (1): 7–16. 1985. doi:10.7326/0003-4819-102-1-7. PMID 2578268.
30. ↑ Day W (1987). "Raggedy Ann syndrome". Hippocrates: July/August, cover story.
31. ↑ 31.0 31.1 Sharpe, Michael; Frankie Campling (2000). Chronic Fatigue Syndrome (CFS/ME): TheFacts. Oxford: Oxford Press. pp. 14, 15. ISBN 0-19-263049-0. https://books.google.com/books?id=_LqAIK616lgC&q=chronic+fatigue+syndrome+was+coined+in+1988+by+the+centers+for+disease+control&pg=PA14. Retrieved April 2, 2008.
32. ↑ Emerging Illnesses and Society. JHU Press. 2004. pp. 156. ISBN 0-8018-7942-6.
33. ↑ 33.0 33.1 "Chronic fatigue syndrome: a working case definition". Ann Intern Med 108 (3): 387–89. 1988. doi:10.7326/0003-4819-108-3-387. PMID 2829679.
34. ↑ "The chronic fatigue syndrome: a comprehensive approach to its definition and study". Ann. Intern. Med. 121 (12): 953–59. 1994. doi:10.7326/0003-4819-121-12-199412150-00009. PMID 7978722.
35. ↑ Palca J (September 14, 1990). "Does a retrovirus explain fatigue syndrome puzzle?". Science 249 (4974): 1240–12. doi:10.1126/science.2399461. PMID 2399461. Bibcode: 1990Sci...249.1240P. http://www.sciencemag.org/cgi/pdf_extract/249/4974/1240.
36. ↑ Altman, Lawrence K. (September 5, 1990). "Virus found that may be linked to a debilitating fatigue ailment". The New York Times. https://query.nytimes.com/gst/fullpage.html?sec=health&res=9C0CE3DD1430F936A3575AC0A966958260.
37. ↑ DeFreitas E; Hilliard B; Cheney PR et al. (April 1991). "Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome". Proc. Natl. Acad. Sci. U.S.A. 88 (7): 2922–26. doi:10.1073/pnas.88.7.2922. PMID 1672770. Bibcode: 1991PNAS...88.2922D.
38. ↑ Sam Donaldson, Nancy Snyderman, Paul Cheney, David Bell, Elaine DeFreitas, Hillary Johnson, PWC's, Paul Pollard, Mrs. Dailor, Philip Lee (March 27, 1996). Sick & Tired (Television). ABC News.
39. ↑ Centers for Disease Control Prevention (CDC) (March 1993). "Inability of retroviral tests to identify persons with chronic fatigue syndrome, 1992". Morbidity and Mortality Weekly Report (U.S. Centers for Disease Control and Prevention (CDC)) 42 (10): 183, 189–90. PMID 8446093. https://www.cdc.gov/mmwr/preview/mmwrhtml/00019881.htm. Retrieved February 23, 2009.
40. ↑ Royal Colleges of Physicians, Psychiatrists and General Practitioners (1996). Chronic fatigue syndrome; Report of a joint working group of the Royal Colleges of Physicians, Psychiatrists and General Practitioners. London: Royal College of Physicians of London. ISBN 1-86016-046-8.
41. ↑ CFS/ME Working Group (2002). "A report of the CFS/ME working group: report to the chief medical officer of an independent working group.". London: Department of Health. http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4064840.
42. ↑ "Chronic fatigue syndrome basic facts". Centers for Disease Control and Prevention. May 9, 2006. https://www.cdc.gov/cfs/cfsbasicfacts.htm.
43. ↑ Gerberding (June 7, 2008). "Address at CFS awareness campaign launch". Department of Health and Human Services. Centers for Disease Control and Prevention. https://www.cdc.gov/cfs/PSAs/Gerberding-launch.pdf.
44. ↑ Alberts B (2011). "Editorial Expression of Concern". Science 333 (6038): 35. doi:10.1126/science.1208542. PMID 21628391. Bibcode: 2011Sci...333...35A.
45. ↑ "Partial Retraction". Science 334 (6053): 176. September 2011. doi:10.1126/science.1212182. PMID 21940859. Bibcode: 2011Sci...334..176S.
46. ↑ Alberts B (2011). "Retraction". Science 334 (6063): 1636. doi:10.1126/science.334.6063.1636-a. PMID 22194552. Bibcode: 2011Sci...334.1636A.
47. ↑ "Failure to Confirm XMRV/MLVs in the Blood of Patients with Chronic Fatigue Syndrome: A Multi-Laboratory Study". Science 334 (6057): 814–17. 2011. doi:10.1126/science.1213841. PMID 21940862. Bibcode: 2011Sci...334..814S.
48. ↑ "Retraction for Lo et al., Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors". Proceedings of the National Academy of Sciences 109 (1): 346. 2011. doi:10.1073/pnas.1119641109. PMID 22203980. Bibcode: 2012PNAS..109..346..
49. ↑ "Chronic fatigue syndrome researchers face death threats from militants". 2011-08-21. https://www.theguardian.com/society/2011/aug/21/chronic-fatigue-syndrome-myalgic-encephalomyelitis.
50. ↑ World Health Organization. "The WHO Family of International Classifications". World Health Organization. https://www.who.int/classifications/en/.
51. ↑ 51.0 51.1 51.2 51.3 51.4 Centers for Disease Control and Prevention, National Center for Health Statistics, Office of the Center Director, Data Policy and Standards (March 2001). A Summary of Chronic Fatigue Syndrome and Its Classification in the International Classification of Diseases. Centers for disease Control. http://www.co-cure.org/ICD_code.pdf. Retrieved April 29, 2008.
52. ↑ International Classification of Diseases. I. World Health Organization. 1969. pp. 158, (vol 2, pp. 173).
53. ↑ International Classification of Diseases. II. World Health Organization. 1975. pp. 182. http://www.icd9data.com/2008/Volume1/320-389/320-326/323/323.61.htm. Retrieved April 30, 2008.
54. ↑ Centers for Disease Control (2006). "International Classification of Diseases 9th Revision Clinical Modification". National Center for Health Statistics. pp. g 516. http://ftp.cdc.gov/pub/Health_Statistics/NCHS/Publications/ICD9-CM/2006/. Index to Diseases ftp://ftp.cdc.gov/pub/Health_Statistics/NCHS/Publications/ICD9-CM/2006/Dindex07.zip
55. ↑ Centers for Disease Control (2006). "International Classification of Diseases 9th Revision Clinical Modification". National Center for Health Statistics. pp. g 532. http://ftp.cdc.gov/pub/Health_Statistics/NCHS/Publications/ICD9-CM/2006/. Tabular List ftp://ftp.cdc.gov/pub/Health_Statistics/NCHS/Publications/ICD9-CM/2006/Dtab07.zip
56. ↑ International Classification of Diseases (Tabular List ed.). World Health Organization. 2007. https://www.who.int/classifications/apps/icd/icd10online/?gg90.htm+g93.
57. ↑ https://www.cdc.gov/nchs/icd/icd10cm.htm International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), 2010 Update. Retrieved 2010-05-21.
58. ↑ Jarman, John (January 25, 2006). "Chronic Fatigue Syndrome Advisory Committee Sixth Meeting". U.S. Department of Health & Human Services. https://www.hhs.gov/advcomcfs/cfsac050912_min.html.
59. ↑ "ICD-10-CM Codes | Diagnosis | Healthcare Providers | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | CDC" (in en-us). 2022-12-22. https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/icd-10.html.

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