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{{Infobox disease
{{Infobox disease
|Name = [http://www.hfme.org/misdiagnosis.htm Chronic fatigue syndrome]
|Name = Chronic fatigue syndrome
|Field = [[Medical_error|Medical Error/mis-diagnosis]]
|Image =
|Caption =
|Field = [[Rheumatology]]
|DiseasesDB = 1645
|ICD10 = {{ICD10|G|93|3|g|90}}
|ICD9 = {{ICD9|323.9}} {{ICD9|780.71}}
|MedlinePlus = 001244
|eMedicineSubj = med
|eMedicineTopic = 3392
|eMedicine_mult = {{eMedicine2|ped|2795}}
|MeshID = D015673
}}
}}

<!-- Definition and symptoms -->
<!-- Definition and symptoms -->
'''Chronic fatigue syndrome''' ('''CFS''') is a complex medical condition, characterized by [[Fatigue (medical)#Chronic fatigue|long-term fatigue]] and other symptoms.<ref name="pmid 10583715"/><ref name=NICECG53/> These symptoms are to such a degree that they limit a person's ability to carry out ordinary daily activities.<ref name=NICECG53/> CFS may also be referred to as '''systemic exertion intolerance disease''' ('''SEID'''), '''myalgic encephalomyelitis''' ('''ME'''), '''post-viral fatigue syndrome''' ('''PVFS'''), '''chronic fatigue immune dysfunction syndrome''' ('''CFIDS'''), or [[alternative names for chronic fatigue syndrome|several other terms]].<ref name=IOM2015>{{cite journal|last1=Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last2=Board on the Health of Select Populations |last3=Institute of|first3=Medicine|date=10 February 2015|pages=20|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness.|pmid=25695122}}</ref> [[Quality of life]] of persons with CFS can be extremely compromised.<ref name="PMID 9205421">{{cite journal | author = Anderson JS, Ferrans CE | title = The quality of life of persons with chronic fatigue syndrome | journal = J Nerv Ment Dis | volume = 185 | issue = 6 | pages = 359–67 | date = June 1997 | pmid = 9205421 | doi = 10.1097/00005053-199706000-00001 | last2 = Ferrans }}</ref>
'''Definition and symptoms'''


<!-- Cause and diagnosis -->
[http://www.hfme.org/misdiagnosis.htm '''Chronic fatigue syndrome''' ('''CFS''')] is, by definition, a "syndrome". According to medical textbooks, a "syndrome", is, at best, merely a single step along the way towards reaching a correct ''diagnosis'' <ref>[[Medical diagnosis|Definition: Medical diagnosis]]</ref>. A "syndrome", by definition <ref>[[Syndrome#Medicine]]</ref>, is charactarized by a collection of symptoms which frequently occur at the same time, but can be caused by a number of different ''diseases'' <ref>[[Disease#Concepts|Diseases]]</ref>.
Biological, genetic, infectious, and psychological mechanisms have been proposed, but the cause is not understood.<ref name="pmid:12562565"/><ref name="CDCCauses">{{cite web |title= Chronic Fatigue Syndrome Causes |publisher= Centers for Disease Control and Prevention |date= October 15, 2010 |url= http://www.cdc.gov/cfs/causes/index.html |accessdate= 2012-12-20}}</ref> The fatigue of CFS is not due to ongoing exertion, is not much relieved by rest, and is not due to any other medical condition.<ref name=CDCdefinition>{{cite web |url= http://www.cdc.gov/cfs/case-definition/index.html |title= Chronic Fatigue Syndrome: Case Definition |accessdate= 2009-01-22 |date= 2006-05-03 |publisher= [[Centers for Disease Control and Prevention|CDC]] }}</ref> Diagnosis is based on a patient's signs and symptoms.<ref name=Smith2015>{{cite journal |vauthors=Smith ME, Haney E, McDonagh M, Pappas M, Daeges M, Wasson N, Fu R, Nelson HD |title=Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop |journal=Ann. Intern. Med. |volume=162 |issue=12 |pages=841–50 |year=2015 |pmid=26075755 |doi=10.7326/M15-0114 |type=Systematic review}}</ref>


<!-- Prevention and treatment -->
Evidence suggests that [[cognitive behavioral therapy]] and a gradual increase in activity suited to individual capacity can be beneficial in some cases. The medication [[rintatolimod]] may be be helpful to certain patients.<ref name=Smith2015/>.

<!-- Epidemiology -->
Estimates of the number of people with the condition vary from 7 to 3,000 per 100,000 adults.<ref name="pmid:12562565"/><ref name="PMID_15699086"/> About one million Americans and a quarter of a million people in the UK have CFS.<ref name="CDCBasic"/><ref name="NHS_CFS"/> [[Fatigue (medical)|Fatigue]] is a common symptom in many illnesses, but the fatigue experienced by persons with CFS is comparatively rare.<ref name="PMID_15699086">{{cite journal | author = Ranjith G | title = Epidemiology of chronic fatigue syndrome | journal = Occup Med (Lond) | volume = 55 | issue = 1 | pages = 13–29 | year = 2005 | pmid = 15699086 | doi = 10.1093/occmed/kqi012 }}</ref> CFS occurs more often in women than men,<ref name="PMID_15574853">{{cite journal | author = Gallagher AM, Thomas JM, Hamilton WT, White PD | title = Incidence of fatigue symptoms and diagnoses presenting in UK primary care from 1990 to 2001 | journal = J R Soc Med | volume = 97 | issue = 12 | pages = 571–5 | year = 2004 | pmid = 15574853 | pmc = 1079668 | doi = 10.1258/jrsm.97.12.571 | last2 = Thomas | last3 = Hamilton | last4 = White }}</ref> and is less common among children and adolescents.<ref name="CDCRisk">{{cite web |title= Chronic Fatigue Syndrome Who's at risk? |publisher= Centers for Disease Control and Prevention |date= February 14, 2013 |url= http://www.cdc.gov/cfs/causes/risk-groups.html |accessdate= 2013-09-25}}</ref>


<!-- Controversy -->
<!-- Controversy -->
There is agreement that CFS has a negative effect on health, happiness and productivity. However, various physicians' groups, researchers and patient advocates promote differing terminology, diagnostic criteria, proposed causes and treatments, resulting in [[Controversies related to chronic fatigue syndrome|controversy about many aspects]] of the disorder. The name "chronic fatigue syndrome" is controversial; many patients and advocacy groups, as well as some experts, believe the name trivializes the medical condition and they promote a name change.<ref name=Ottati>{{cite book |author=Ottati, Victor C. |title=The social psychology of politics |publisher=Kluwer Academic/Plenum |location=New York |year=2002 |pages=159–160 |isbn=0-306-46723-2 |accessdate= 2009-08-11 |url= http://books.google.com/?id=OYrErhPFFLwC&dq=+The+social+psychology+of+politics+By+Victor+C.+Ottati&printsec=frontcover&q=name%20change%20survey%20results}}</ref>
'''Controversy'''

== Signs and symptoms ==
Symptoms of CFS include [[malaise]] after exertion; unrefreshing sleep, widespread [[myalgia|muscle]] and [[arthralgia|joint pain]], [[sore throat]], [[headaches]] of a type not previously experienced, [[cognitive]] difficulties, chronic and severe mental and physical [[exhaustion]]. Additional symptoms may be reported, including [[muscle weakness]], increased sensitivity to light, sounds and smells, [[orthostatic intolerance|problems standing upright]], digestive disturbances, [[Depression (mood)|depression]], painful and often slightly swollen lymph nodes, [[cardiac]] and [[Respiratory system|respiratory]] problems.<ref name = Wyller>{{cite journal | author = Wyller VB | title = The chronic fatigue syndrome--an update | journal = Acta neurologica Scandinavica. Supplementum | volume = 187 | issue = | pages = 7–14 | year = 2007 | pmid = 17419822 | doi = 10.1111/j.1600-0404.2007.00840.x }}</ref> It is unclear if these symptoms represent other associated conditions or if they are produced by CFS itself.<ref name="pmid:12562565">{{cite journal | author = Afari N, Buchwald D | title = Chronic fatigue syndrome: a review | journal = Am J Psychiatr | volume = 160 | issue = 2 | pages = 221–36 | year = 2003 | pmid = 12562565 | doi = 10.1176/appi.ajp.160.2.221 | url = http://ajp.psychiatryonline.org/article.aspx?articleID=176018 | last2 = Buchwald }}</ref> Symptoms vary in number, type, and severity from person to person.<ref name="CDCSymptoms">{{cite web|url=http://www.cdc.gov/cfs/symptoms/index.html |title=Chronic Fatigue Syndrome (CFS), Symptoms |publisher=[[Centers for Disease Control and Prevention]] |date=2012-05-14 |accessdate=2012-09-23}}</ref>

=== Onset ===
The majority of CFS cases start suddenly,<ref name="PMID_9201648"/> usually accompanied by a "[[flu-like illness]]"<ref name="pmid:12562565"/> while a significant proportion of cases begin within several months of severe adverse stress.<ref name="PMID_9201648">{{cite journal | author = Salit IE | title = Precipitating factors for the chronic fatigue syndrome | journal = J Psychiatr Res | volume = 31 | issue = 1 | pages = 59–65 | year = 1997 | pmid = 9201648 | doi = 10.1016/S0022-3956(96)00050-7 }}</ref><ref>{{cite journal | author = Hatcher S, House A | title = Life events, difficulties and dilemmas in the onset of chronic fatigue syndrome: a case-control study | journal = Psychol Med | volume = 33 | issue = 7 | pages = 1185–92 | year = 2003 | pmid = 14580073 | doi = 10.1017/S0033291703008274 | url = http://eprints.whiterose.ac.uk/1226/1/house3.pdf | format = PDF | last2 = House }}</ref><ref name="PMID_10367610">{{cite journal | author = Theorell T, Blomkvist V, Lindh G, Evengård B | title = Critical life events, infections, and symptoms during the year preceding chronic fatigue syndrome (CFS): an examination of CFS patients and subjects with a nonspecific life crisis | journal = Psychosom Med. | volume = 61 | issue = 3 | pages = 304–10 | year = 1999 | pmid = 10367610 | doi=10.1097/00006842-199905000-00009| last2 = Blomkvist | last3 = Lindh | last4 = Evengård }}</ref> An Australian prospective study found that after infection by viral and non-viral [[pathogen]]s, a subset of individuals met the criteria for CFS, with the researchers concluding that "post-infective fatigue syndrome is a valid illness model for investigating one pathophysiological pathway to CFS".<ref name="pmid16950834">{{cite journal | author = Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A | title = Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study | journal = BMJ | volume = 333 | issue = 7568 | page = 575 | year = 2006 | pmid = 16950834 | pmc = 1569956 | doi = 10.1136/bmj.38933.585764.AE | last2 = Davenport | last3 = Wakefield | last4 = Vollmer-Conna | last5 = Cameron | last6 = Vernon | last7 = Reeves | last8 = Lloyd | author9 = Dubbo Infection Outcomes Study Group }}</ref> However, accurate prevalence and exact roles of infection and stress in the development of CFS are currently unknown.

=== Symptoms ===
The most commonly used [[medical diagnosis|diagnostic criteria]] and definition of CFS for research and clinical purposes were published by the United States [[Centers for Disease Control and Prevention]] (CDC).<ref name="pmid:12562565"/> The CDC recommends the following three criteria be fulfilled:<ref name=CDCdiagnosis>{{cite web |url=http://www.cdc.gov/cfs/diagnosis/index.html|title=CDC - Chronic Fatigue Syndrome (CFS) - Diagnosis| publisher=Cdc.gov |accessdate=2012-07-22}}</ref>
# A new onset (not lifelong) of severe [[Fatigue (physical)|fatigue]] for six consecutive months or greater duration which is unrelated to exertion, is not substantially relieved by rest, and is not a result of other medical conditions.
# The fatigue causes a significant reduction of previous activity levels.
# Four or more of the following symptoms that concurrently last six months or longer:
#* impaired [[memory]] or concentration
#* post-exertional [[malaise]], where physical or mental exertions bring on "extreme, prolonged exhaustion and sickness"
#* unrefreshing sleep
#* muscle [[pain]] ([[myalgia]])
#* pain in multiple joints ([[arthralgia]])
#* [[headache]]s of a new kind or greater severity
#* sore throat, frequent or recurring
#* tender [[lymph node]]s ([[Cervical lymph nodes|cervical]] or [[Axillary lymph nodes|axillary]])

The CDC states other common symptoms include the following:<ref name="CDCSymptoms" />
* [[brain fog]] (feeling like one is in a mental fog)
* difficulty maintaining an upright position, dizziness, balance problems or fainting
* [[allergies]] or sensitivities to foods, odors, chemicals, medications, or noise
* [[irritable bowel syndrome]]-like symptoms such as bloating, stomach pain, [[constipation]], [[diarrhoea]] and nausea
* [[chills]] and [[night sweats]]
* visual disturbances ([[photophobia|sensitivity to light]], blurring, eye pain)
* [[Depression (mood)|depression]] or mood problems (irritability, mood swings, anxiety, panic attacks)

The CDC proposes that persons with symptoms resembling those of CFS consult a physician to rule out several treatable illnesses: [[Lyme disease]],<ref name=CDCdiagnosis/> "[[sleep disorder]]s, [[major depressive disorder]], [[alcohol abuse|alcohol]]/[[substance abuse|substance]] abuse, [[diabetes]], [[hypothyroidism]], [[EBV infectious mononucleosis|mononucleosis]] (mono), [[Systemic lupus erythematosus|lupus]], [[multiple sclerosis]] (MS), [[chronic hepatitis]] and various [[malignancies]]."<ref>{{cite web |url=http://www.cdc.gov/cfs/pdf/cfs-resource-guide.pdf |title=CDC, Chronic Fatigue Syndrome (CFS), Making a Diagnosis |publisher=Cdc.gov |accessdate=2011-01-28}}</ref> Medications can also cause side effects that mimic symptoms of CFS.<ref name=CDCdiagnosis/>

Unlike the CDC's diagnostic criteria for CFS, the International Consensus Criteria for ME do not require the 6-month waiting period before diagnosis, noting that "No other disease criteria require that diagnoses be withheld until after the patient has suffered with the affliction for 6 months."<ref>{{Cite journal| journal = Journal of Internal Medicine | volume = 270 | issue = 4 | pages = 327–338 | date = Aug 2011 | doi = 10.1111/j.1365-2796.2011.02428.x | pmid = 21777306 | url=http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02428.x/pdf |title=Myalgic encephalomyelitis: International Consensus Criteria| last1 = Carruthers | first1 = B. M. | last2 = Van De Sande | first2 = M. I. | last3 = De Meirleir | first3 = K. L. | last4 = Klimas | first4 = N. G. | last5 = Broderick | first5 = G. | last6 = Mitchell | first6 = T. | last7 = Staines | first7 = D. | last8 = Powles | first8 = A. C. P. | last9 = Speight | first9 = N. | last10 = Vallings | first10 = R. | last11 = Bateman | first11 = L. | last12 = Baumgarten-Austrheim | first12 = B. | last13 = Bell | first13 = D. S. | last14 = Carlo-Stella | first14 = N. | last15 = Chia | first15 = J. | last16 = Darragh | first16 = A. | last17 = Jo | first17 = D. | last18 = Lewis | first18 = D. | last19 = Light | first19 = A. R. | last20 = Marshall-Gradisbik | first20 = S. | last21 = Mena | first21 = I. | last22 = Mikovits | first22 = J. A. | last23 = Miwa | first23 = K. | last24 = Murovska | first24 = M. | last25 = Pall | first25 = M. L. | last26 = Stevens | first26 = S. | pmc=3427890}}</ref>

=== Functioning ===
Despite a common diagnosis the functional capacity of individuals with CFS varies greatly.<ref name="PMID_12783037">{{cite journal | author = Vanness JM, Snell CR, Strayer DR, Dempsey L, Stevens SR | title = Subclassifying chronic fatigue syndrome through exercise testing | journal = Med Sci Sports Exerc | volume = 35 | issue = 6 | pages = 908–13 | year = 2003 | pmid = 12783037 | doi = 10.1249/01.MSS.0000069510.58763.E8 | last2 = Snell | last3 = Strayer | last4 = Dempsey l | last5 = Stevens }}</ref> Some persons with CFS lead relatively normal lives; others are totally bed-ridden and unable to care for themselves.<ref name=Ross/> For the majority of persons with CFS, work, school, and family activities are significantly reduced for extended periods of time.<ref name="CDCSymptoms" /> The severity of symptoms and disability is the same in both genders,<ref>{{cite journal | author = Ho-Yen DO, McNamara I | title = General practitioners' experience of the chronic fatigue syndrome | journal = Br J Gen Pract | volume = 41 | issue = 349 | pages = 324–6 | year = 1991 | pmid = 1777276 | pmc = 1371754 | last2 = McNamara }}</ref> and many experience strongly disabling [[chronic pain]].<ref name="PMID_16843021">{{cite journal | author = Meeus M, Nijs J, Meirleir KD | title = Chronic musculoskeletal pain in patients with the chronic fatigue syndrome: A systematic review | journal = Eur J Pain | volume = 11 | issue = 4 | pages = 377–386 | year = 2007 | pmid = 16843021 | doi = 10.1016/j.ejpain.2006.06.005 | last2 = Nijs | last3 = Meirleir }}</ref> Persons report critical reductions in levels of physical activity.<ref name="PMID_8771284">{{cite journal | author = McCully KK, Sisto SA, Natelson BH | title = Use of exercise for treatment of chronic fatigue syndrome | journal = Sports Med | volume = 21 | issue = 1 | pages = 35–48 | year = 1996 | pmid = 8771284 | doi = 10.2165/00007256-199621010-00004 | last2 = Sisto | last3 = Natelson }}</ref> Also, a reduction in the complexity of activity has been observed.<ref>{{cite journal | author = Burton C, Knoop H, Popovic N, Sharpe M, Bleijenberg G | title = Reduced complexity of activity patterns in patients with Chronic Fatigue Syndrome: a case control study | journal = Biopsychosoc Med | volume = 3 | issue = 1 | page = 7 | date = June 2009 | pmid = 19490619 | pmc = 2697171 | doi = 10.1186/1751-0759-3-7 | url = http://www.bpsmedicine.com/content/3/1/7 | last2 = Knoop | last3 = Popovic | last4 = Sharpe | last5 = Bleijenberg }}</ref> Reported impairment is comparable to other fatiguing medical conditions<ref name="PMID_14577835">{{cite journal | author = Solomon L, Nisenbaum R, Reyes M, Papanicolaou DA, Reeves WC | title = Functional status of persons with chronic fatigue syndrome in the Wichita, Kansas, population | journal = Health Qual Life Outcomes | volume = 1 | issue = 1 | pages = 48–58 | year = 2003 | pmid = 14577835 | pmc = 239865 | doi = 10.1186/1477-7525-1-48 | last2 = Nisenbaum | last3 = Reyes | last4 = Papanicolaou | last5 = Reeves }}</ref> including late-stage [[AIDS]],<ref>Mark, Loveless, MD, congressional testimony of, May 12, 1995, as reported in Hillary Johnson. (1996). Osler's Web: Inside the Labyrinth of the Chronic Fatigue Syndrome Epidemic. Crown Publishers, New York. ISBN 0-517-70353-X. pp.364-365</ref> [[Lupus erythematosus|lupus]], [[rheumatoid arthritis]], [[chronic obstructive pulmonary disease]] (COPD), and [[end-stage renal disease]].<ref name="CDCSymptoms" /> CFS affects a person's functional status and well-being more than major medical conditions such as multiple sclerosis, congestive heart failure, or type II diabetes mellitus.<ref name="PMID 9205421"/><ref name="PMID_8873490">{{cite journal | author = Komaroff AL, Fagioli LR, Doolittle TH, Gandek B, Gleit MA, Guerriero RT, Kornish RJ, Ware NC, Ware JE, Bates DW | title = Health status in patients with chronic fatigue syndrome and in general population and disease comparison groups | journal = Am. J. Med. | volume = 101 | issue = 3 | pages = 281–90 | date = September 1996 | pmid = 8873490 | doi = 10.1016/S0002-9343(96)00174-X | last2 = Fagioli | last3 = Doolittle | last4 = Gandek | last5 = Gleit | last6 = Guerriero | last7 = Kornish Rj | last8 = Ware | last9 = Ware Jr | last10 = Bates }}</ref>

Often, there are courses of remission and relapse of symptoms which make the illness difficult to manage. Persons who feel better for a period may overextend their activities, and the result can be a worsening of their symptoms with a relapse of the illness.<ref name="CDCSymptoms" />

Employment rates vary with over half unable to work and nearly two-thirds limited in their work because of their illness. More than half were on disability benefits or temporary sick leave, and less than a fifth worked full-time.<ref name=Ross>{{cite journal | author = Ross SD, Estok RP, Frame D, Stone LR, Ludensky V, Levine CB | title = Disability and chronic fatigue syndrome: a focus on function | journal = Arch Intern Med | volume = 164 | issue = 10 | pages = 1098–107 | year = 2004 | pmid = 15159267 | doi = 10.1001/archinte.164.10.1098 | url = http://archinte.ama-assn.org/cgi/content/full/164/10/1098 | last2 = Estok | last3 = Frame | last4 = Stone | last5 = Ludensky | last6 = Levine }}</ref>

=== Cognitive functioning ===
Cognitive symptoms are mainly from deficits in attention, memory, and reaction time. The deficits are in the range of 0.5 to 1.0 standard deviations below expected and are likely to affect day-to-day activities. Simple and complex information processing speed and functions entailing working memory over long time periods were moderately to extensively impaired. These deficits are generally consistent with those reported by patients. Perceptual abilities, motor speed, language, reasoning, and intelligence did not appear to be significantly altered.<ref name="PMID 20047703">{{cite journal | author = Cockshell SJ, Mathias JL | title = Cognitive functioning in chronic fatigue syndrome: a meta-analysis | journal = Psychol Med | volume = 40 | issue = 8 | pages = 1–15 | date = January 2010 | pmid = 20047703 | doi = 10.1017/S0033291709992054 | url = | last2 = Mathias }}</ref>

=== Comorbidity ===
Many CFS patients will also have, or appear to have, other medical problems or related diagnoses. [[Fibromyalgia]] occurs in a large percentage of CFS patients between onset and the second year, and some researchers suggest fibromyalgia and CFS are related.<ref>{{cite journal | author = Friedberg F, Jason LA | title = Chronic fatigue syndrome and fibromyalgia: clinical assessment and treatment | journal = J Clin Psychol. | volume = 57 | issue = 4 | pages = 433–55 | year = 2001 | pmid = 11255201 | doi = 10.1002/jclp.1040 | last2 = Jason }}</ref> As previously mentioned, many CFS sufferers also experience symptoms of [[irritable bowel syndrome]], [[temporomandibular joint]] pain, [[headache]] including [[migraine]]s, and other forms of [[myalgia]]. CFS patients have significantly higher rates of current mood disorders than the general population.<ref>{{cite journal | author = Prins J, Bleijenberg G, Rouweler EK, van der Meer J | title = Effect of psychiatric disorders on outcome of cognitive-behavioural therapy for chronic fatigue syndrome | journal = Br J Psychiatry | volume = 187 | issue = 2 | pages = 184–5 | year = 2005 | pmid = 16055833 | doi = 10.1192/bjp.187.2.184 | last2 = Bleijenberg | last3 = Rouweler | last4 = Van Der Meer }}</ref> Compared with the non-fatigued population, male CFS patients are more likely to experience [[Prostatitis#Category III: CP/CPPS, pelvic myoneuropathy|chronic pelvic pain syndrome (CP/CPPS)]], and female CFS patients are also more likely to experience [[chronic pelvic pain]].<ref>{{cite journal | author = Aaron LA, Herrell R, Ashton S, Belcourt M, Schmaling K, Goldberg J, Buchwald D | title = Comorbid Clinical Conditions in Chronic Fatigue: A Co-Twin Control Study | journal = Journal of general internal medicine | volume = 16 | issue = 1 | pages = 24–31 | year = 2001 | pmid = 11251747 | pmc = 1495162 | doi = 10.1111/j.1525-1497.2001.03419.x | last2 = Herrell | last3 = Ashton | last4 = Belcourt | last5 = Schmaling | last6 = Goldberg | last7 = Buchwald }}</ref> CFS is significantly more common in women with [[endometriosis]] compared with women in the general USA population.<ref>{{cite journal | author = Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P | title = High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis | journal = Hum Reprod | volume = 17 | issue = 10 | pages = 2715–24 | year = 2002 | pmid = 12351553 | doi = 10.1093/humrep/17.10.2715 | url = http://humrep.oxfordjournals.org/cgi/content/full/17/10/2715 | last2 = Cleary | last3 = Ballweg | last4 = Nieman | last5 = Stratton }}</ref>

== Risk factors ==
All ethnic groups and income levels are susceptible to the illness. The CDC states that ME/CFS is "at least as common" in African Americans and [[Hispanic]]s as Caucasians. A 2009 meta-analysis, however, showed that compared with the White American majority, African Americans and Native Americans have a higher risk of CFS, though it acknowledged that studies and data were limited.<ref>{{cite journal | title = A systematic review of chronic fatigue, its syndromes and ethnicity: prevalence, severity, co-morbidity and coping | journal = International Journal of Epidemiology | volume = 38 | issue = 6 | pages = 1554–70 | year = 2009 | pmid = 19349479 | doi = 10.1093/ije/dyp147 | last1 = Dinos | first1 = S | last2 = Khoshaba | first2 = B | last3 = Ashby | first3 = D | last4 = White | first4 = PD | last5 = Nazroo |first5 = J | last6 = Wessely | first6 = S | last7 = Bhui | first7 = KS}}</ref> More women than men get CFS — between 60 and 85% of cases are women; however, there is some indication that the prevalence among men is underreported. The illness is reported to occur more frequently in people between the ages of 40 and 59.<ref name="PMID_15574853"/> CFS is less prevalent among children and adolescents than adults.<ref name="CDCBasic"/> Blood relatives of people who have CFS appear to be more predisposed.<ref>{{cite journal | author = Walsh CM, Zainal NZ, Middleton SJ, Paykel ES | title = A family history study of chronic fatigue syndrome | journal = Psychiatr Genet | volume = 11 | issue = 3 | pages = 123–8 | year = 2001 | pmid = 11702053 | doi = 10.1097/00041444-200109000-00003 | last2 = Zainal | last3 = Middleton | last4 = Paykel }}</ref> There is no direct evidence that CFS is [[Contagious disease|contagious]].<ref name="CDCRisk"/>

A systematic review in 2008 included eleven primary studies that had assessed various demographic, medical, psychological, social and environmental factors to predict the development of CFS, and found many had reported significant associations to CFS.<ref name="PMID_17892624">{{cite journal | author = Hempel S, Chambers D, Bagnall AM, Forbes C | title = Risk factors for chronic fatigue syndrome/myalgic encephalomyelitis: a systematic scoping review of multiple predictor studies | journal = Psychol Med | volume = 38 | issue = 7 | pages = 915–26 | date = July 2008 | pmid = 17892624 | doi = 10.1017/S0033291707001602 | last2 = Chambers | last3 = Bagnall | last4 = Forbes }}</ref> The reviewers concluded that the lack of generalizability and replication between studies meant that "none of the identified factors appear suitable for the timely identification of patients at risk of developing CFS/ME within clinical practice."

== Pathophysiology ==
{{Main|Pathophysiology of chronic fatigue syndrome}}

The causes and mechanisms of chronic fatigue syndrome are currently unknown, despite extensive research.<ref name="CDCBasic">{{cite web |title= Chronic Fatigue Syndrome Basic Facts |publisher= Centers for Disease Control and Prevention |date= May 9, 2006 |url= http://www.cdc.gov/cfs/general/index.html |accessdate= 2008-02-07}}</ref> Research studies have developed and explored etiological hypotheses regarding a variety of factors, including [[oxidative stress]], [[genetic predisposition]],<ref name="pmid17853290">{{cite journal | author = Sanders P, Korf J | title = Neuroaetiology of chronic fatigue syndrome: an overview | journal = World Journal of Biological Psychiatry | volume = 9 | issue = 3 | pages = 165–71 | year = 2008 | pmid = 17853290 | doi = 10.1080/15622970701310971 | last2 = Korf }}</ref> [[infection]] by [[virus]]es and [[pathogenic bacteria]], [[hypothalamic-pituitary-adrenal axis]] abnormalities, [[autoimmunity|immune dysfunction]] as well as psychological and [[psychosocial]] factors. Although it is unclear whether such factors are causes or consequences of CFS (or both), various models have been proposed.<ref name="pmid11388124">{{cite journal | author = Patarca-Montero R, Antoni M, Fletcher MA, Klimas NG | title = Cytokine and other immunologic markers in chronic fatigue syndrome and their relation to neuropsychological factors | journal = Appl Neuropsychol | volume = 8 | issue = 1 | pages = 51–64 | year = 2001 | pmid = 11388124 | doi = 10.1207/S15324826AN0801_7 | url = | last2 = Antoni | last3 = Fletcher | last4 = Klimas }}</ref><ref name="pmid17561686">{{cite journal | author = Kuratsune H | title = [Overview of chronic fatigue syndrome focusing on prevalence and diagnostic criteria] | language = Japanese | journal = Nippon Rinsho | volume = 65 | issue = 6 | pages = 983–90 | date = June 2007 | pmid = 17561686 | doi = | url = }}</ref><ref name="pmid9859853">{{cite journal | author = Vercoulen JH, Swanink CM, Galama JM, Fennis JF, Jongen PJ, Hommes OR, van der Meer JW, Bleijenberg G | title = The persistence of fatigue in chronic fatigue syndrome and multiple sclerosis: development of a model | journal = J Psychosom Res | volume = 45 | issue = 6 | pages = 507–17 | year = 1998 | pmid = 9859853 | doi = 10.1016/S0022-3999(98)00023-3 | last2 = Swanink | last3 = Galama | last4 = Fennis | last5 = Jongen | last6 = Hommes | last7 = Van Der Meer | last8 = Bleijenberg }}</ref>

A substantial body of evidence points to the following abnormalities in the [[hypothalamic-pituitary-adrenal axis]] (HPA axis) in CFS patients: mild [[adrenal insufficiency|hypocortisolism]], an attenuated diurnal variation in [[cortisol]], enhanced cortisol negative feedback, and a blunted HPA axis responsiveness. It is unclear whether or not these disturbances play a primary role in the pathogenesis of CFS.<ref>{{cite journal|last=Papadopoulos|first=Andrew S.|author2=Cleare, Anthony J. |title=Hypothalamic–pituitary–adrenal axis dysfunction in chronic fatigue syndrome|journal=Nature Reviews Endocrinology|date=27 September 2011|volume=8|issue=1|pages=22–32|doi=10.1038/nrendo.2011.153|pmid=21946893}}</ref>

Persons diagnosed with the illness appear to have an abnormal immune response to exercise. Specifically, complement products are increased, larger oxidative stress is generated along with reduced anti-oxidant immune response, and larger interleukin-10 and toll-like receptor 4 gene expression are seen versus healthy controls. Many of these immune responses correlate with the symptom of post-exertional malaise.<ref name="pmid 24974723">{{cite journal |authors=Nijs J, Nees A, Paul L, De Kooning M, Ickmans K, Meeus M, Van Oosterwijck J |title=Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review |journal=Exerc Immunol Rev |volume=20 |issue= |pages=94–116 |year=2014 |url = http://www.medizin.uni-tuebingen.de/transfusionsmedizin/institut/eir/content/2014/94/article.pdf |pmid=24974723 |doi= | accessdate = 2015-06-19}}</ref>

==Diagnosis==
There are no characteristic laboratory abnormalities to diagnose CFS,<ref name="pmid 14702202"/> so testing is used to rule out other potential causes for symptoms.<ref name="CDC1994"/> When symptoms are attributable to certain other conditions, the diagnosis of CFS is excluded. Important conditions and disorders to exclude are current/active [[major depression]], [[schizophrenia]], eating disorders such as [[anorexia nervosa]] and [[bulimia]], [[bipolar disorder]], [[alcohol abuse]] or other [[substance abuse]]. Current [[morbid obesity]] and active medical diseases need to be resolved and excluded before a diagnosis of chronic fatigue syndrome can be made.<ref name="Avellaneda Fernández-2009">{{cite journal | author = Avellaneda Fernández A, Pérez Martín A, Izquierdo Martínez M, Arruti Bustillo M, Barbado Hernández FJ, de la Cruz Labrado J, Díaz-Delgado Peñas R, Gutiérrez Rivas E, Palacín Delgado C, Rivera Redondo J, Ramón Giménez JR | title = Chronic fatigue syndrome: aetiology, diagnosis and treatment | journal = BMC Psychiatry | volume = 9 Suppl 1 | pages = S1 | year = 2009 | pmid = 19857242 | pmc = 2766938 | doi = 10.1186/1471-244X-9-S1-S1 | last2 = Pérez Martín | last3 = Izquierdo Martínez | last4 = Arruti Bustillo | last5 = Barbado Hernández | author6 = de la Cruz Labrado J | last7 = Díaz-Delgado Peñas | last8 = Gutiérrez Rivas | last9 = Palacín Delgado | last10 = Rivera Redondo | last11 = Ramón Giménez }} {{open access}}</ref>

=== Definitions ===
{{Main|Clinical descriptions of chronic fatigue syndrome}}
Notable definitions include:<ref name = Wyller />
* [[Clinical descriptions of chronic fatigue syndrome#CDC 1994 criteria|Centers for Disease Control and Prevention (CDC) definition]] (1994),<ref name="CDC1994">{{cite journal | author = Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A | title = The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group | journal = Ann Intern Med | volume = 121 | issue = 12 | pages = 953–9 | date = 15 Dec 1994 | pmid = 7978722 | doi = 10.1059/0003-4819-121-12-199412150-00009 | url = http://www.annals.org/cgi/content/full/121/12/953 | doi_brokendate = 2015-01-11 | last2 = Straus | last3 = Hickie | last4 = Sharpe | last5 = Dobbins | last6 = Komaroff }}</ref> the most widely used clinical and research description of CFS,<ref name="pmid:12562565"/> is also called the [[Keiji Fukuda|Fukuda]] definition and is a revision of the ''Holmes'' or ''CDC 1988'' scoring system.<ref name=Holmes1988>{{cite journal | author = Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, Jones JF, Dubois RE, Cunningham-Rundles C, Pahwa S | title = Chronic fatigue syndrome: a working case definition | journal = Ann Intern Med | volume = 108 | issue = 3 | pages = 387–9 | year = 1988 | pmid = 2829679 | doi = 10.7326/0003-4819-108-3-387 | last2 = Kaplan | last3 = Gantz | last4 = Komaroff | last5 = Schonberger | last6 = Straus | last7 = Jones | last8 = Dubois | last9 = Cunningham-Rundles | last10 = Pahwa }}</ref> The 1994 criteria require the presence of four or more symptoms beyond fatigue, while the 1988 criteria require six to eight.<ref name=NICECG53/>
*[[Clinical descriptions of chronic fatigue syndrome#Canadian 2003 criteria|The ME/CFS 2003 Canadian Clinical working definition]]<ref name="carr">{{cite journal | author = Carruthers BM, Jain AK, De Meirleir KL, Peterson DL, Klimas NG |title= Myalgic encephalomyalitis/chronic fatigue syndrome: Clinical working definition, diagnostic and treatment protocols |journal= Journal of Chronic Fatigue Syndrome |volume= 11 |issue= 1 |pages= 7–97 |year= 2003 |url= http://www.cfids-cab.org/cfs-inform/CFS.case.def/carruthers.etal03.pdf |format=PDF |doi= 10.1300/J092v11n01_02|author2= and others |displayauthors= 1 }}</ref> states: "A patient with ME/CFS will meet the criteria for fatigue, post-exertional malaise and/or fatigue, sleep dysfunction, and pain; have two or more neurological/cognitive manifestations and one or more symptoms from two of the categories of autonomic, neuroendocrine, and immune manifestations; and the illness persists for at least 6 months".
[[Clinical practice guidelines]] are generally based on case descriptions with the aim of improving diagnosis, management, and treatment. An example is the CFS/ME guideline for the [[National Health Service]] in England and Wales, produced in 2007 by the [[National Institute for Health and Clinical Excellence]] (NICE).<ref name=NICECG53>{{cite book |publisher= [[National Institute for Health and Clinical Excellence]] |title= Guideline 53: Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy) |location= London |year= 2007 |isbn= 1-84629-453-3 |url= http://guidance.nice.org.uk/CG53 }}</ref>

=== Differential diagnoses ===
Certain medical conditions can cause chronic fatigue and must be ruled out before a diagnosis of CFS can be given. [[Hypothyroidism]], [[anemia]],<ref name="pmid_11925084" /> [[coeliac disease]] (that can occur without gastrointestinal symptoms),<ref name=LoganWong2001>{{cite journal | vauthors = Logan AC, Wong C| title = Chronic fatigue syndrome: oxidative stress and dietary modifications | journal = Altern Med Rev | volume = 6| issue = 5| pages = 450–9| date = Oct 2001| pmid = 11703165|url= http://www.altmedrev.com/publications/6/5/450.pdf | quote= Finally, recent evidence suggests celiac disease can present with neurological symptoms in the absence of gastrointestinal symptoms; therefore, celiac disease should be included in the differential diagnosis of CFS.}}</ref> [[diabetes]] and certain [[mental disorder|psychiatric disorders]] are a few of the diseases that must be ruled out if the patient presents with appropriate symptoms.<ref name=NICECG53/><ref name="CDC1994"/><ref name="pmid_11925084">{{cite journal | author = Craig T, Kakumanu S | title = Chronic fatigue syndrome: evaluation and treatment | journal = Am Fam Physician. | volume = 65 | issue = 6 | pages = 1083–90 | date = Mar 2002 | pmid = 11925084 | url = http://www.aafp.org/afp/20020315/1083.html | last2 = Kakumanu }}</ref> Other diseases, listed by the [[Centers for Disease Control and Prevention]], include [[Infection|infectious diseases]] (such as [[Epstein–Barr virus]], [[influenza]], [[HIV/AIDS|HIV infection]], [[tuberculosis]], [[Lyme disease]]), neuroendocrine diseases (such as [[thyroiditis]], [[Addison's disease]], [[adrenal insufficiency]], [[Cushing's disease]]), [[hematologic diseases]] (such as occult malignancy, [[lymphoma]]), rheumatologic diseases (such as [[fibromyalgia]], [[polymyalgia rheumatica]], [[Sjögren's syndrome]], [[giant-cell arteritis]], [[polymyositis]], [[dermatomyositis]]), [[mental disorder|psychiatric diseases]] (such as [[bipolar disorder]], [[schizophrenia]], [[delusional disorder]]s, [[dementia]], [[anorexia nervosa|anorexia]]/[[bulimia nervosa]]), neuropsychologic diseases (such as [[obstructive sleep apnea]], [[parkinsonism]], [[multiple sclerosis]]), and others (such as nasal obstruction from [[allergy|allergies]], [[sinusitis]], anatomic obstruction, [[autoimmune disease]]s, some [[chronic condition|chronic illness]], alcohol or [[substance abuse]], pharmacologic [[side effect]]s, [[toxic heavy metal|heavy metal exposure and toxicity]], marked body weight fluctuation).<ref name="pmid_11925084" />

People with [[fibromyalgia]] (FM, or fibromyalgia syndrome, FMS), like those with CFS, have muscle pain, severe fatigue and sleep disturbances. The presence of [[allodynia]] (abnormal pain responses to mild stimulation) and of extensive tender points in specific locations differentiates FM from CFS, though the two diseases often co-occur.<ref>{{cite journal | author = Bradley LA, McKendree-Smith NL, Alarcón GS | title = Pain complaints in patients with fibromyalgia versus chronic fatigue syndrome | journal = Curr Rev Pain | volume = 4 | issue = 2 | pages = 148–57 | year = 2000 | pmid = 10998728 | doi = 10.1007/s11916-000-0050-2 | last2 = McKendree-Smith | last3 = Alarcón }}</ref> Fatigue and muscle pain occurs frequently in the initial phase of various hereditary muscle disorders and in several autoimmune, endocrine and metabolic syndromes; and are frequently labelled as CFS or fibromyalgia in the absence of obvious biochemical/metabolic abnormalities and neurological symptoms.{{Citation needed|date=December 2008}}

[[Multiple chemical sensitivity]], [[Gulf War syndrome]] and [[post-polio syndrome]] have symptoms similar to those of CFS,<ref>{{cite journal | author = Vojdani A, Thrasher JD | title = Cellular and humoral immune abnormalities in Gulf War veterans | journal = Environ Health Perspect | volume = 112 | issue = 8 | pages = 840–6 | year = 2004 | pmid = 15175170 | pmc = 1242010 | doi = 10.1289/ehp.6881 | last2 = Thrasher }}</ref><ref name="polio">{{cite journal | author = Bruno RL, Creange SJ, Frick NM | title = Parallels between post-polio fatigue and chronic fatigue syndrome: a common pathophysiology? | journal = Am J Med. | volume = 105 | issue = 3A | pages = 66S–73S | year = 1998 | pmid = 9790485 | doi = 10.1016/S0002-9343(98)00161-2 | last2 = Creange | last3 = Frick }}</ref> and the last is also theorized to have a common pathophysiology.<ref name="polio"/>

Depressive symptoms, if seen in CFS, may be [[Differential diagnosis|differentially diagnosed]] from primary depression due to the absence of [[anhedonia]], decreased motivation, and guilt; and the presence of somatic symptoms such as sore throat, swollen lymph nodes, and exercise intolerance with postexertional exacerbation of symptoms.<ref name="pmid_11925084"/>

== Management==
{{Main|Chronic fatigue syndrome treatment}}

Many people do not fully recover from CFS even with treatment.<ref>{{cite journal | author = Rimes KA, Chalder T | title = Treatments for chronic fatigue syndrome | journal = Occupational Medicine | volume = 55 | issue = 1 | pages = 32–39 | year = 2005 | pmid = 15699088 | doi = 10.1093/occmed/kqi015 | last2 = Chalder }}</ref> [[Cognitive behavioural therapy]] (CBT) and [[graded exercise therapy]] (GET) have shown moderate effectiveness in a number of [[randomized controlled trial]]s.<ref name=Whiting/><ref name="cbt_systematic_review">{{cite journal | author = Chambers D, Bagnall AM, Hempel S, Forbes C | title = Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review | journal = Journal of the Royal Society of Medicine | volume = 99 | issue = 10 | pages = 506–20 | year = 2006 | pmid = 17021301 | pmc = 1592057 | doi = 10.1258/jrsm.99.10.506 | last2 = Bagnall | last3 = Hempel | last4 = Forbes }}</ref><ref name=Raine2002>{{cite journal | author = Raine R, Haines A, Sensky T, Hutchings A, Larkin K, Black N | title = Systematic review of mental health interventions for patients with common somatic symptoms: can research evidence from secondary care be extrapolated to primary care? | journal = BMJ | volume = 325 | issue = 7372 | page = 1082 | year = 2002 | pmid = 12424170 | pmc = 131187 | doi = 10.1136/bmj.325.7372.1082 | last2 = Haines | last3 = Sensky | last4 = Hutchings | last5 = Larkin | last6 = Black }}</ref><ref name=Reid2000>{{cite journal | author = Reid S, Chalder T, Cleare A, Hotopf M, Wessely S | title = Chronic fatigue syndrome | journal = BMJ | volume = 320 | issue = 7230 | pages = 292–6 | year = 2000 | pmid = 10650029 | pmc = 1117488 | doi = 10.1136/bmj.320.7230.292 | last2 = Chalder | last3 = Cleare | last4 = Hotopf | last5 = Wessely }}</ref> As many of the CBT and GET studies required visits to a clinic, those severely affected may not have been included.<ref name="cbt_systematic_review"/>
Two large surveys of patients indicated that [[Chronic fatigue syndrome treatment#Pacing|pacing]] is a helpful intervention, or is considered useful by 82-96% of participants.<ref name="afme_2008_survey">{{cite web | title = Survey Summary Report 2008 | url = http://www.actionforme.org.uk/Resources/Action%20for%20ME/Documents/get-informed/ME%202008%20%20What%20progress.pdf | publisher = Action for ME | page = 13 | format = PDF | year = 2008 | accessdate= 12 October 2013}}</ref><ref>{{cite journal | author = Bjørkum T, Wang CE, Waterloo K | title = Pasienterfaringer med ulike tiltak ved kronisk utmattelsessyndrom | language = Norwegian | journal = Tidsskrift for Den norske legeforening | volume = 129 | issue = 12 | pages = 1214–6 | date = June 2009 | pmid = 19521443 | doi = 10.4045/tidsskr.09.35791 | trans_title = Patients' experience with treatment of chronic fatigue syndrome | last2 = Wang | last3 = Waterloo }}</ref> A comprehensive rehabilitation programme only rarely results in full recovery.<ref name="PMID 22725992">{{cite journal | author = Van Cauwenbergh D, De Kooning M, Ickmans K, Nijs J | title = How to exercise people with chronic fatigue syndrome: evidence-based practice guidelines | journal = Eur J Clin Invest | volume = 42 | issue = 10 | pages = 1136–4 | year = 2012 | pmid = 22725992 | doi = 10.1111/j.1365-2362.2012.02701.x | url = http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2362.2012.02701.x/full | last2 = De Kooning | last3 = Ickmans | last4 = Nijs }}</ref> Medication plays a minor role in management.<ref>{{cite journal | author = Van Houdenhove B, Pae CU, Luyten P | title = Chronic fatigue syndrome: is there a role for non-antidepressant pharmacotherapy? | journal = Expert opinion on pharmacotherapy | volume = 11 | issue = 2 | pages = 215–23 | date = February 2010 | pmid = 20088743 | doi = 10.1517/14656560903487744 | last2 = Pae | last3 = Luyten }}</ref> No intervention has been proven effective in restoring the ability to work.<ref name="cbt_systematic_review"/>

=== Cognitive behavioral therapy ===
[[Cognitive behavioral therapy]] is a moderately effective psychological therapy<ref name=Whiting>{{cite journal | author = Whiting P, Bagnall AM, Sowden AJ, Cornell JE, Mulrow CD, Ramírez G | title = Interventions for the treatment and management of chronic fatigue syndrome: a systematic review | journal = JAMA | volume = 286 | issue = 11 | pages = 1360–8 | date = September 2001 | pmid = 11560542 | doi = 10.1001/jama.286.11.1360 | url = http://jama.ama-assn.org/cgi/content/full/286/11/1360 | last2 = Bagnall | last3 = Sowden | last4 = Cornell | last5 = Mulrow | last6 = Ramírez }}</ref><ref name="cbt_systematic_review"/> when used to treat CFS. It is often used alone or with other therapies to "manage activity levels, stress, and symptoms."<ref name="NCID_treatment">{{cite web |title= Improving Health and Quality of Life |publisher= [[Centers for Disease Control and Prevention]] |date= February 14, 2013 |url= http://www.cdc.gov/cfs/management/quality-of-life.html |accessdate= 12 October 2013}}</ref> CBT tries to help patients understand their individual symptoms and beliefs and develop strategies to improve day-to-day functioning. CBT is thought to help patients by eliminating unhelpful illness beliefs which may perpetuate the illness.<ref>{{cite book |author=Wolfe F; Chalmers A; Littlejohn GO & Salit I |title=Fibromyalgia, Chronic Fatigue Syndrome, and Repetitive Strain Injury: Current Concepts in Diagnosis, Management, Disability, and Health Economics |publisher= [[Haworth Press|Haworth Medical Press]] |location=New York |year=1995 |page=142 |isbn=1-56024-744-4 |url= http://books.google.com/?id=Da0jf7agNvgC&pg=PA142}}</ref>

A ''[[Cochrane Library|Cochrane Review]]'' meta-analysis of 15 randomized, controlled cognitive behavioral therapy trials with 1043 participants concluded that CBT reduced the symptom of fatigue. Four studies showed that CBT resulted in a clinical response for 40% of participants vs 26% treated with "usual care". Similarly, in 3 studies CBT worked better than other types of psychological therapies (48% vs 27%). The effects of CBT may diminish after therapy is completed; the reviewers write that "the evidence base at follow-up is limited to a small group of studies with inconsistent findings" and encourage further studies.<ref name="CochraneCBT">{{cite journal | author = Price JR, Mitchell E, Tidy E, Hunot V | title = Cognitive behaviour therapy for chronic fatigue syndrome in adults | journal = Cochrane Database Syst Rev | volume = | issue = 3 | pages = CD001027 | year = 2008 | pmid = 18646067 | doi = 10.1002/14651858.CD001027.pub2 | url = | editor1-last = Price | editor1-first = Jonathan R | last2 = Mitchell | last3 = Tidy | last4 = Hunot }}</ref> A 2007 meta-analysis of 5 CBT randomized controlled trials of chronic fatigue and chronic fatigue syndrome reported 33-73% of the patients improved to the point of no longer being clinically fatigued.<ref name=pmid_18060672>{{cite journal | author = Malouff JM, Thorsteinsson EB, Rooke SE, Bhullar N, Schutte NS | title = Efficacy of cognitive behavioral therapy for chronic fatigue syndrome: a meta-analysis | journal = Clin Psychol Rev | volume = 28 | issue = 5 | pages = 736–45 | date = June 2008 | pmid = 18060672 | doi = 10.1016/j.cpr.2007.10.004 | last2 = Thorsteinsson | last3 = Rooke | last4 = Bhullar | last5 = Schutte }}</ref>

A 2010 meta-analysis of trials that measured physical activity before and after CBT reported that although CBT effectively reduced fatigue, activity levels were not affected by CBT and changes in physical activity were not related to changes in fatigue. They conclude that the effect of CBT on fatigue is not influenced by a change in physical activity.<ref>{{cite journal | author = Wiborg JF, Knoop H, Stulemeijer M, Prins JB, Bleijenberg G | title = How does cognitive behaviour therapy reduce fatigue in patients with chronic fatigue syndrome? The role of physical activity | journal = Psychol Med | volume = 40 | issue = 8 | pages = 1–7 | date = January 2010 | pmid = 20047707 | doi = 10.1017/S0033291709992212 | last2 = Knoop | last3 = Stulemeijer | last4 = Prins | last5 = Bleijenberg }}</ref> According to a 2014 systematic review on recovery, the lack of changes to objectively measured physical activity after intervention is contrary to the cognitive behavioural model of CFS and suggests that patients still avoided postexertional symptom exacerbations and adapted to the illness rather than recovered from it.<ref name="{{DOI|10.1007/s11136-014-0705-9}} PMID 24791749">{{cite journal | author = Adamowicz JL, Caikauskaite I, Friedberg F | title = Defining recovery in chronic fatigue syndrome: a critical review | url = | journal = Qual Life Res. | issue = 9| page = | doi = 10.1007/s11136-014-0705-9 | pmid = 24791749 | date=Nov 2014 | volume=23 | pages=2407–16| last2 = Caikauskaite| last3 = Friedberg}}</ref>

CBT has been criticised by patients' organisations because multiple patient surveys of their members<ref name="PMID_11809249"/> have indicated that CBT can make people worse. Some dispute the validity of the evidence base behind CBT as well as graded exercise therapy (below), and conclude that it would be unethical to use these treatments.<ref>{{cite journal | author = Twisk FN, Maes M | title = A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS | journal = Neuro Endocrinol. Lett. | volume = 30 | issue = 3 | pages = 284–99 | year = 2009 | pmid = 19855350 | last2 = Maes }}</ref>

=== Exercise ===
[[Graded exercise therapy]] is a form of [[physical therapy]]. A meta-analysis published in 2004 of five randomized trials found that patients who received exercise therapy were less fatigued after 12 weeks than the control participants, and the authors cautiously conclude that GET shows promise as a treatment. However, after 6 months the benefit became non-significant compared to the control group who did not receive GET, and functional work capacity was not significantly improved after therapy.<ref name = Edmonds>{{cite journal | author = Edmonds M, McGuire H, Price J | title = Exercise therapy for chronic fatigue syndrome | journal = Cochrane Database Syst Rev | volume = | issue = 3 | pages = CD003200 | year = 2004 | pmid = 15266475 | doi = 10.1002/14651858.CD003200.pub2 | url = | editor1-last = Price | editor1-first = Jonathan R | last2 = McGuire | last3 = Price }}</ref> A systematic review published in 2006 included the same five RCTs, noting that "no severely affected patients were included in the studies of GET".<ref name="cbt_systematic_review"/> A 2012 systematic review concluded that despite the consistent positive outcomes of exercise therapy studies for CFS, "exercise therapy is not a cure for CFS", and "a comprehensive rehabilitation programme only rarely results in full recovery".<ref name="PMID 22725992"/>

Surveys conducted on behalf of patient organizations find adverse effects to be very common.<ref name=autogenerated2>{{cite journal | author = Clark C, Buchwald D, MacIntyre A, Sharpe M, Wessely S | title = Chronic fatigue syndrome: a step towards agreement | journal = Lancet | volume = 359 | issue = 9301 | pages = 97–8 | year = 2002 | pmid = 11809249 | doi = 10.1016/S0140-6736(02)07336-1 | last2 = Buchwald | last3 = MacIntyre | last4 = Sharpe | last5 = Wessely }}</ref><ref name = PMID_19521443>{{cite journal | author = Bjørkum T, Wang CE, Waterloo K | title = Patients' experience with treatment of chronic fatigue syndrome | journal = Tidsskr nor Laegeforen | volume = 129 | issue = 12 | pages = 1214–6 | date = June 2009 | pmid = 19521443 | doi = 10.4045/tidsskr.09.35791 | last2 = Wang | last3 = Waterloo }}</ref><ref name="CMO_report">{{cite web |author=Working Party on CFS/ME |title= Report of the Working Party on CFS/ME to the Chief Medical Officer for England and Wales |publisher= Department of Health |date=January 2002 |url= http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4064840 |archiveurl=http://webarchive.nationalarchives.gov.uk/20130107105354/http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4064840 |archivedate=2012-01-07}}</ref> To avoid detrimental effects from GET, care must be taken to avoid the exacerbation of symptoms while catering the program to individual capabilities and the fluctuating nature of symptoms.<ref name="PMID_18382818">{{cite journal | author = Nijs J, Paul L, Wallman K | title = Chronic fatigue syndrome: an approach combining self-management with graded exercise to avoid exacerbations | journal = J Rehabil Med | volume = 40 | issue = 4 | pages = 241–7 | date = April 2008 | pmid = 18382818 | doi = 10.2340/16501977-0185 | last2 = Paul | last3 = Wallman }}</ref> A 2015 Cochrane review found that exercise therapy may reduce fatigue among people with CFS, and concluded that the effects of exercise therapy were comparable to those of cognitive-behavioral therapy.<ref>{{cite journal|last1=Larun|first1=L|last2=Brurberg|first2=KG|last3=Odgaard-Jensen|first3=J|last4=Price|first4=JR|title=Exercise therapy for chronic fatigue syndrome.|journal=The Cochrane database of systematic reviews|date=10 February 2015|volume=2|pages=CD003200|doi=10.1002/14651858.CD003200.pub3|pmid=25674924}}</ref>

=== Pacing ===
Pacing is an energy management strategy based on the observation that symptoms of the illness tend to increase following minimal exertion. There are two forms: symptom-contingent pacing, where the decision to stop (and rest or change an activity) is determined by an awareness of an exacerbation of symptoms; and time-contingent pacing, which is determined by a set schedule of activities which a patient estimates he or she is able to complete without triggering post-exertional malaise (PEM).<ref>{{cite journal | author = Goudsmit EM, Nijs J, Jason LA, Wallman KE | title = Pacing as a strategy to improve energy management in myalgic encephalomyelitis/chronic fatigue syndrome: a consensus document | journal = Disability and Rehabilitation | volume = Early Online | issue = 13 | pages = 1–8 | date = 19 December 2011 | pmid = 22181560 | doi = 10.3109/09638288.2011.635746 | last2 = Nijs | last3 = Jason | last4 = Wallman }}</ref> Thus the principle behind pacing for CFS is to avoid over-exertion and an exacerbation of symptoms. It is not aimed at treating the illness as a whole. Those whose illness appears stable may gradually increase activity and exercise levels but according to the principle of pacing, must rest if it becomes clear that they have exceeded their limits. Some programmes combine symptom and time-contingent approaches. A trial of one such programme reported limited benefits.<ref name="PMID_18382818"/> A larger, randomised controlled trial found that pacing had statistically better results than relaxation/flexibility therapy.<ref name="PMID_15115421">{{cite journal | author = Wallman KE, Morton AR, Goodman C, Grove R, Guilfoyle AM | title = Randomised controlled trial of graded exercise in chronic fatigue syndrome | journal = Med. J. Aust. | volume = 180 | issue = 9 | pages = 444–8 | date = May 2004 | pmid = 15115421 | url = http://www.mja.com.au/public/issues/180_09_030504/wal10613_fm.html | last2 = Morton | last3 = Goodman | last4 = Grove | last5 = Guilfoyle }}</ref><ref name="PMID 16781183">{{cite journal | author = Nijs J, Meeus M, De Meirleir K | title = Chronic musculoskeletal pain in chronic fatigue syndrome: recent developments and therapeutic implications | journal = Man Ther. | volume = 11 | issue = 3 | pages = 187–91 | date = August 2006 | pmid = 16781183 | doi = 10.1016/j.math.2006.03.008 | url = | last2 = Meeus | last3 = De Meirleir }}</ref> A 2009 survey of 828 Norwegian CFS patients found that pacing was evaluated as useful by 96% of the participants.<ref name = PMID_19521443/>

=== Other ===
Evidence suggests that the medication [[rintatolimod]] may be useful in some people.<ref name=Smith2015/> In 2012, however, the [[FDA]] considered the evidence for the safety or benefit of rintatolimod to be insufficient to approve its use.<ref name=FDA2013>{{cite web|title=Drug Development for Myalgic Encephalomyelitis and Chronic Fatigue Syndrome (ME and CFS): Questions and Answers|url=http://www.fda.gov/Drugs/NewsEvents/ucm337759.htm|website=FDA|accessdate=25 September 2015|date=5 February 2013}}</ref> Other treatments of CFS have been proposed but their effectiveness has not been confirmed.<ref name=Prins2006>{{cite journal | author = Prins JB, van der Meer JW, Bleijenberg G | title = Chronic fatigue syndrome | journal = Lancet | volume = 367 | issue = 9507 | pages = 346–55 | year = 2006 | pmid = 16443043 | doi = 10.1016/S0140-6736(06)68073-2 | last2 = Van Der Meer | last3 = Bleijenberg }}</ref> Medications thought to have promise in alleviating symptoms include antidepressant and [[immunomodulator]]y agents.<ref name="pmid16029148">{{cite journal | author = Covelli V, Passeri ME, Leogrande D, Jirillo E, Amati L | title = Drug targets in stress-related disorders | journal = Curr. Med. Chem. | volume = 12 | issue = 15 | pages = 1801–9 | year = 2005 | pmid = 16029148 | doi = 10.2174/0929867054367202 | last2 = Passeri | last3 = Leogrande | last4 = Jirillo | last5 = Amati }}</ref> The evidence for antidepressants is mixed,<ref name="PMID 16575378">{{cite journal | author = Jackson JL, O'Malley PG, Kroenke K | title = Antidepressants and cognitive-behavioral therapy for symptom syndromes | journal = CNS Spectr | volume = 11 | issue = 3 | pages = 212–22 | date = January 30, 2006 | pmid = 16575378 | url = http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=417 | last2 = O'Malley | last3 = Kroenke }}</ref> and their use remains controversial.<ref name="PMID 19514866">{{cite journal | author = Pae CU, Marks DM, Patkar AA, Masand PS, Luyten P, Serretti A | title = Pharmacological treatment of chronic fatigue syndrome: focusing on the role of antidepressants | journal = Expert Opin Pharmacother | volume = 10 | issue = 10 | pages = 1561–70 | date = July 2009 | pmid = 19514866 | doi = 10.1517/14656560902988510 | last2 = Marks | last3 = Patkar | last4 = Masand | last5 = Luyten | last6 = Serretti }}</ref> Many CFS patients are sensitive to medications, particularly [[sedative]]s, and some patients report chemical and [[Food intolerance|food sensitivities]].<ref name="CDCSymptoms" /> CFS patients have a low [[placebo]] response, especially to psychological-psychiatric interventions, perhaps due to patient expectations.<ref name=Cho2005>{{cite journal | author = Cho HJ, Hotopf M, Wessely S | title = The placebo response in the treatment of chronic fatigue syndrome: A systematic review and meta-analysis | journal = Psychosom Med | volume = 67 | issue = 2 | pages = 301–13 | year = 2005 | pmid = 15784798 | doi = 10.1097/01.psy.0000156969.76986.e0 | url = http://www.psychosomaticmedicine.org/cgi/content/full/67/2/301 | accessdate = 2008-12-12 | last2 = Hotopf | last3 = Wessely }}</ref>

== Prognosis ==
A systematic review of 14 studies that described improvement and occupational outcomes of people with CFS found that "the median full recovery rate was 5% (range 0–31%) and the median proportion of patients who improved during follow-up was 39.5% (range 8–63%). Return to work at follow-up ranged from 8 to 30% in the three studies that considered this outcome." .... "In five studies, a worsening of symptoms during the period of follow-up was reported in between 5 and 20% of patients." A good outcome was associated with less fatigue severity at baseline. Other factors were occasionally, but not consistently, related to outcome, including age at onset (5 of 16 studies), and attributing illness to a psychological cause and/or having a sense of control over symptoms (4 of 16 studies).<ref name=Cairns2005>{{cite journal | author = Cairns R, Hotopf M | title = A systematic review describing the prognosis of chronic fatigue syndrome | journal = Occupational medicine (Oxford, England) | volume = 55 | issue = 1 | pages = 20–31 | year = 2005 | pmid = 15699087 | doi = 10.1093/occmed/kqi013 | url = http://occmed.oxfordjournals.org/cgi/reprint/55/1/20 | last2 = Hotopf }}</ref> Another review found that children have a better prognosis than adults, with 54–94% having recovered by follow-up compared to less than 10% of adults returning to pre-illness levels of functioning.<ref name=Joyce1997>{{cite journal | author = Joyce J, Hotopf M, Wessely S | title = The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review | journal = QJM | volume = 90 | issue = 3 | pages = 223–33 | year = 1997 | pmid = 9093600 | doi = 10.1093/qjmed/90.3.223 | url = | last2 = Hotopf | last3 = Wessely }}</ref>

A 2014 systematic review reported that estimates of recovery from CFS ranged between 0 to 66% in intervention studies and 2.6 to 62% in naturalistic studies. There was a lack of consensus in the literature on how recovery should be defined. "Recovery" was often based on limited assessments, less than a full restoration of health, and self-reports with a general lack of more objective measures, which when used, did not find significant changes in physical activity. The authors suggested that patients were still avoiding post-exertion symptom exacerbation, and could be clinically improving to a limited extent or adapting to ongoing illness rather than recovering. It was recommended using stricter and more comprehensive definitions of recovery which capture fatigue, function, patient perceptions, and recovery time following physical and mental exertion.<ref name="PMID 24791749">{{cite journal | pmid = 24791749 | doi=10.1007/s11136-014-0705-9 | volume=23 | title=Defining recovery in chronic fatigue syndrome: a critical review. | date=Nov 2014 | pages=2407–16 | journal=Quality of Life Research}}</ref>

== Epidemiology ==

A 2003 review states that studies have reported between 7 and 3,000 cases of CFS for every 100,000 adults.<ref name="pmid:12562565"/> Ranjith reviewed the epidemiological literature on CFS and suggested that the wide variance of the [[prevalence]] estimates may be due to the different definitions of CFS in use, the settings in which patients were selected, and the methodology used to exclude study participants with possible alternative diagnoses.<ref name="PMID_15699086"/> The [[Centers for Disease Control]] reports that more than 1 million Americans have CFS and approximately 80% of the cases are undiagnosed.<ref name="CDCBasic"/> Approximately 250,000 people in the UK are affected with the illness according to the [[National Health Service]].<ref name="NHS_CFS">{{cite web |title= Chronic fatigue syndrome |publisher= The National Health Service |date= 2009-06-29 |url= http://www.nhs.uk/me/introduction.aspx |accessdate= 2010-05-14}}</ref>

== History ==
{{Main|History of chronic fatigue syndrome}}
In 1934, an outbreak then referred to as ''atypical poliomyelitis'' (at the time it was considered a form of [[polio]]) occurred at the [[Los Angeles County-USC Medical Center|Los Angeles County Hospital]]. It strongly resembled what Ramsay and Acheson would later describe as ME (in 1934, there were no follow-up data to indicate chronicity and it is not known how many of those affected remained ill). Of note are the neurological symptoms, the link with a polio outbreak and the fact that most of the patients were hospital staff.<ref>Ramsay AM. Myalgic encephalomyelitis and postviral fatigue states. Second Ed. 1988</ref> During 1955, there were many similar outbreaks, the best known of which affected several hospitals that formed part of the Royal Free group in London. It also featured neurological signs and affected mostly the hospital staff.<ref name="pmid13637100">{{cite journal | author = Acheson ED | title = The clinical syndrome variously called benign myalgic encephalomyelitis, Iceland disease and epidemic neuromyasthenia | journal = The American Journal of Medicine | volume = 26 | issue = 4 | pages = 569–95 | year = 1959 | pmid = 13637100 | doi = 10.1016/0002-9343(59)90280-3 }}</ref> CFS excludes these outbreaks by definition, though many patients have a post-viral onset and the literature relating to ME is considered relevant to the study of CFS. In 1969, benign myalgic encephalomyelitis was first classified into the [[ICD|International Classification of Diseases]] under ''Diseases of the nervous system''.<ref name="ICD_8_ME">{{Cite book |title= International Classification of Diseases |publisher= World Health Organization |year= 1969 |volume= I |pages= 158, (vol 2, pp. 173) }}</ref>

The name ''chronic fatigue syndrome'' was used in the medical literature in 1987<ref name=PMID_3033338>{{cite journal | author = Buchwald D, Sullivan JL, Komaroff AL | title = Frequency of 'chronic active Epstein-Barr virus infection' in a general medical practice | journal = JAMA: the Journal of the American Medical Association | volume = 257 | issue = 17 | pages = 2303–7 | year = 1987 | pmid = 3033338 | doi = 10.1001/jama.257.17.2303 | last2 = Sullivan | last3 = Komaroff }}</ref> to describe a condition resembling "chronic active Epstein-Barr virus (EBV) infection" but which presented no evidence of active EBV as its cause. The initial case definition of CFS was published in 1988, "Chronic fatigue syndrome: a working case definition", (the [[Clinical descriptions of chronic fatigue syndrome#Holmes|Holmes definition]]), and displaced the name [[Chronic Epstein-Barr virus|''chronic Epstein-Barr virus syndrome'']]. This research case definition was published after US [[Centers for Disease Control and Prevention]] epidemiologists examined the Lake Tahoe outbreak.<ref name=autogenerated1>{{cite journal | author = Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, Jones JF, Dubois RE, Cunningham-Rundles C, Pahwa S | title = Chronic fatigue syndrome: A working case definition | journal = Annals of internal medicine | volume = 108 | issue = 3 | pages = 387–9 | year = 1988 | pmid = 2829679 | doi = 10.7326/0003-4819-108-3-387 | last2 = Kaplan | last3 = Gantz | last4 = Komaroff | last5 = Schonberger | last6 = Straus | last7 = Jones | last8 = Dubois | last9 = Cunningham-Rundles | last10 = Pahwa }}</ref><ref name="isbn0-19-263049-0">{{cite book |author=Sharpe M & Campling F |title=Chronic Fatigue Syndrome (CFS/ME): TheFacts |publisher=Oxford Press |location=Oxford |year=2000 |pages = 14, 15 | url = http://books.google.com/?id=_LqAIK616lgC&pg=PA14 |isbn=0-19-263049-0 |accessdate= 2008-04-02}}</ref><ref name="isbn0801879426">{{cite book |author=Packard RM, Berkelman RL, Brown PJ, Frumkin H |title=Emerging Illnesses and Society |publisher=JHU Press |year= 2004 |page= 156 |url= http://books.google.com/?id=EGNFPZrKIKMC&pg=PA156 |isbn=0-8018-7942-6 |accessdate= 2008-04-02}}</ref> In 2006, the CDC commenced a national program to educate the American public and health care professionals about CFS.<ref name="CDCmission">{{cite web |title= Press Briefing Transcripts |publisher= Centers for Disease Control and Prevention |date= November 3, 2006 |url= http://www.cdc.gov/media/transcripts/t061103.htm |accessdate= 2013-10-12}}</ref>

In 2009 the journal ''Science''<ref>
{{cite journal |author=Lombardi VC |title=Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome |journal=Science |volume=326 |issue=5952 |pages=585–9 |date=October 2009 |pmid=19815723 |doi=10.1126/science.1179052 |bibcode=2009Sci...326..585L |name-list-format=vanc|author2=Ruscetti FW |author3=Das Gupta J |display-authors=3 |last4=Pfost |first4=MA |last5=Hagen |first5=KS |last6=Peterson |first6=DL |last7=Ruscetti |first7=SK |last8=Bagni |first8=RK |last9=Petrow-Sadowski |first9=C
}}{{Retracted paper|{{DOI|10.1126/science.334.6063.1636-a}}|intentional=yes}}
</ref> published a study that identified the [[XMRV|XMRV retrovirus]] in a population of people with CFS. Other studies failed to reproduce this finding,<ref name=PLoSOne>{{cite journal |author=Erlwein O |title=Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome |journal=PLoS ONE |volume=5|issue= 1|pages= e8519|year=2010 |pmid= 20066031|pmc= 2795199|doi=10.1371/journal.pone.0008519 |url=http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008519|bibcode = 2010PLoSO...5.8519E |display-authors=1 |editor1-last=Nixon |editor1-first=Douglas F |last2=Kaye |first2=Steve |last3=McClure |first3=Myra O. |last4=Weber |first4=Jonathan |last5=Wills |first5=Gillian |last6=Collier |first6=David |last7=Wessely |first7=Simon |last8=Cleare |first8=Anthony }}</ref><ref>{{cite journal |author=Harriet C T Groom, Virginie C Boucherit, Kerry Makinson, Edward Randal, Sarah Baptista, Suzanne Hagan, John W Gow, Frank M Mattes, Judith Breuer, Jonathan R Kerr, Jonathan P Stoye, Kate N Bishop |title=Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome |journal=Retrovirology |volume=7 |issue=1 |year=2010 |pmid=20156349 |doi=10.1186/1742-4690-7-10 |url=http://www.retrovirology.com/content/7/1/10/abstract |pages=10 |pmc=2839973}}</ref><ref name=van_Kuppeveld>{{cite journal |author=van Kuppeveld FJ |title=Prevalence of xenotropic murine leukaemia virus-related virus in patients with chronic fatigue syndrome in the Netherlands: retrospective analysis of samples from an established cohort |journal=BMJ |volume=340 |pages=c1018 |year=2010 |pmid=20185493 |pmc=2829122 |doi=10.1136/bmj.c1018|url=http://www.bmj.com/cgi/content/full/340/feb25_1/c1018 |name-list-format=vanc|author2=Jong AS |author3=Lanke KH |display-authors=3 |last4=Verhaegh |first4=GW |last5=Melchers |first5=WJG |last6=Swanink |first6=CMA |last7=Bleijenberg |first7=G |last8=Netea |first8=MG |last9=Galama |first9=JMD}}</ref> and in 2011 the editor of Science formally retracted its XMRV paper<ref>{{cite journal |author=Alberts B |title=Retraction |journal=Science |date=December 2011 |volume=334 |issue=6063 |page=1636 |doi=10.1126/science.334.6063.1636-a |pmid=22194552|bibcode = 2011Sci...334.1636A }}</ref> while the ''Proceedings of the National Academy of Sciences'' similarly retracted a 2010 paper which had appeared to support the finding of a connection between XMRV and CFS.<ref>{{cite journal |title=Retraction for Lo et al., Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=109 |issue=1 |pages=346 |date=January 2012 |pmid=22203980 |doi=10.1073/pnas.1119641109 |pmc=3252929 |vauthors=Lo SC, Pripuzova N, Li B, etal |bibcode = 2012PNAS..109..346. }}</ref>

== Society and culture ==
[[File:Cfs woman sketch.jpg|thumb|right|A depiction of CFS]]

===Naming===
{{Main|Alternative names for chronic fatigue syndrome}}

Chronic fatigue syndrome is the most commonly used designation,<ref name="pmid 10583715"/> but widespread approval of a name is lacking.<ref name="PMID_11809249"/> Different authorities on the illness view CFS as a central nervous system, metabolic, infectious or post-infectious, cardiovascular, immune system or psychiatric disorder, and different symptom profiles may be caused by various disorders.<ref name="pmid 15929497" />

Over time and in different countries, many names have been associated with the condition(s). Aside from CFS, some other names used include Akureyri disease, benign myalgic encephalomyelitis, chronic fatigue immune dysfunction syndrome, chronic infectious mononucleosis, epidemic myalgic encephalomyelitis, epidemic neuromyasthenia, Iceland disease, myalgic encephalomyelitis, myalgic encephalitis, myalgic encephalopathy, post-viral fatigue syndrome, raphe nucleus encephalopathy, [[Royal Free Hospital|Royal Free]] disease, [[Tapanui]] flu, and yuppie flu (the last considered pejorative).<ref name = NORD>{{cite web |author= NORD |title= Chronic Fatigue Syndrome/Myalgic Encephalomyelitis |publisher= National Organization for Rare Disorders, Inc. |date= June 23, 2008 |url= http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Chronic%20Fatigue%20Syndrome/Myalgic%20Encephalomyelitis |accessdate= 2008-07-01}}</ref><ref>{{cite book |isbn= 0-393-03408-9 |last= Donoghue |first= PJ |author2=Siegel ME |url= http://books.google.com/?id=8r1dnOxPwdEC&pg=PA15 |accessdate= 2008-09-17 |title= Sick And Tired Of Feeling Sick And Tired: Living with Invisible Chronic Illness |publisher= [[W. W. Norton & Company]] |year= 1992 |page= 15}}</ref> Many patients would prefer a different name such as "myalgic encephalomyelitis", believing the name "chronic fatigue syndrome" trivializes the condition, prevents it from being seen as a serious health problem, and discourages research.<ref name=Ottati/><ref name=pmid12448589 >{{cite journal | author = Sharpe M | title = The report of the Chief Medical Officer's CFS/ME working group: what does it say and will it help? | journal = Clin Med | volume = 2 | issue = 5 | pages = 427–9 | year = 2002 | pmid = 12448589 | doi = 10.7861/clinmedicine.2-5-427 }}</ref><ref name="NYTNotYuppieFlu">{{cite news |url= http://www.nytimes.com/ref/health/healthguide/esn-chronicfatigue-ess.html |work= [[The New York Times]] |last= Tuller |first= David |title= Chronic Fatigue Syndrome No Longer Seen as 'Yuppie Flu' |date= 2008-05-30 |accessdate= 2015-06-29 }}</ref>

A 2001 review referenced myalgic encephalomyelitis symptoms in a 1959 article by [[Donald Acheson|Acheson]], stating ME could be a distinct syndrome from CFS. A 1999 review explained that the Royal Colleges of Physicians, Psychiatrists, and General Practitioners in 1996 advocated the use of chronic fatigue syndrome instead of myalgic encephalomyelitis or ME, which was in wide use in the United Kingdom, "because there is, so far, no recognized pathology in muscles and in the central nervous system as is implied by the term ME".<ref name="pmid 10583715">{{cite journal | author = Evengård B, Schacterle RS, Komaroff AL | title = Chronic fatigue syndrome: new insights and old ignorance | journal = Journal of Internal Medicine | volume = 246 | issue = 5 | pages = 455–469 | date = Nov 1999 | pmid = 10583715 | doi = 10.1046/j.1365-2796.1999.00513.x | url = http://www3.interscience.wiley.com/cgi-bin/fulltext/119095441/PDFSTART | accessdate = 2009-10-21 | last2 = Schacterle | last3 = Komaroff }}</ref><ref name="isbn 1-86016-046-8">{{cite book |author=Royal Colleges of Physicians, Psychiatrists and General Practitioners |title=Chronic fatigue syndrome; Report of a joint working group of the Royal Colleges of Physicians, Psychiatrists and General Practitioners |year= 1996|publisher=Royal College of Physicians of London |location=London, UK |isbn=1-86016-046-8 }}</ref> An editorial noted that the 1996 report received some acceptance, but also criticism from those advocating the use of different naming conventions, suggesting the report was biased, dominated by psychiatrists, and that dissenting voices were excluded.<ref>{{cite journal | title = Frustrating survey of chronic fatigue | journal = Lancet | volume = 348 | issue = 9033 | page = 971 | date = Oct 1996 | pmid = 8855845 | doi = 10.1016/S0140-6736(05)64917-3 | url = http://www.lancet.com/journals/lancet/article/PIIS0140-6736%2805%2964917-3/fulltext | last1 = The Lancet }}</ref> In 2002, a [[The Lancet|''Lancet'']] commentary noted the recent report by the "Working Group on CFS/ME"<ref name="group cfs/me 2002 ">{{cite web |author=Working Party on CSF/ME |title=Report of the Working Party on CSF/ME to the Chief Medical Officer for England and Wales |publisher=Department of Health |date=January 2002 |url=http://www.doh.gov.uk/cmo/cfsmereport/cfsmereport.pdf |format=PDF |accessdate=2009-01-25 |archiveurl= http://web.archive.org/web/20030322075848/http://www.doh.gov.uk/cmo/cfsmereport/cfsmereport.pdf |archivedate= 2003-03-22}}</ref> used the compromise name CFS/ME stating, "The fact that both names for the illness were used symbolises respect for different viewpoints whilst acknowledging the continuing lack of consensus on a universally acceptable name."<ref name="PMID_11809249">{{cite journal | author = Clark C, Buchwald D, MacIntyre A, Sharpe M, Wessely S | title = Chronic fatigue syndrome: a step towards agreement | journal = Lancet | volume = 359 | issue = 9301 | pages = 97–8 | date = January 2002 | pmid = 11809249 | doi = 10.1016/S0140-6736(02)07336-1 | url = http://linkinghub.elsevier.com/retrieve/pii/S0140673602073361 | last2 = Buchwald | last3 = MacIntyre | last4 = Sharpe | last5 = Wessely }}</ref>

A 2015 report from the [[Institute of Medicine]] proposes the illness be renamed "systemic exertion intolerance disease" and suggests new diagnostic criteria for it. Many patients, clinicians and researchers believe lengthy disproportionate exhaustion after physical or mental exertion is a core symptom (also known as post-exertional malaise).<ref name=IOM2015/><ref name="Tullar_NYT_2015">[http://well.blogs.nytimes.com/2015/02/10/chronic-fatigue-syndrome-gets-a-new-name/ Chronic Fatigue Syndrome Gets a New Name By David Tuller February 10, 2015 11:01 am New York Times]</ref>

=== Economic impact ===
Reynolds ''et al.'' (2004)<ref name="pmid 15210053">{{cite journal | author = Reynolds KJ, Vernon SD, Bouchery E, Reeves WC | title = The economic impact of chronic fatigue syndrome | journal = Cost effectiveness and resource allocation : C/E | volume = 2 | issue = 1 | page = 4 | year = 2004 | pmid = 15210053 | pmc = 449736 | doi = 10.1186/1478-7547-2-4 | last2 = Vernon | last3 = Bouchery | last4 = Reeves }} {{open access}}</ref> estimated that the illness caused about $20,000 per person with CFS in lost productivity which totals to $9.1 billion per year in the United States.<ref name="pmid 15929497">{{cite journal | author = Jason LA, Corradi K, Torres-Harding S, Taylor RR, King C | title = Chronic fatigue syndrome: the need for subtypes | journal = Neuropsychol Rev | volume = 15 | issue = 1 | pages = 29–58 | date = March 2005 | pmid = 15929497 | doi = 10.1007/s11065-005-3588-2 | last2 = Corradi | last3 = Torres-Harding | last4 = Taylor | last5 = King }}</ref> This is comparable to other chronic illnesses that extract some of the biggest medical and socioeconomic costs.<ref name="Avellaneda Fernández-2009"/> A 2008 study<ref name="pmid 2324078">{{cite journal | author = Jason LA, Benton MC, Valentine L, Johnson A, Torres-Harding S | title = The Economic impact of ME/CFS: Individual and societal costs | journal = Dyn Med | volume = 7 | page = 6 | year = 2008 | pmid = 18397528 | pmc = 2324078 | doi = 10.1186/1476-5918-7-6 | last2 = Benton | last3 = Valentine | last4 = Johnson | last5 = Torres-Harding }}</ref> calculated that the total annual cost burden of ME/CFS to society in the US was extensive, and could approach $24.0 billion.<ref name="pmid 23022717">{{cite journal | author = Broderick G, Craddock TJ | title = Systems biology of complex symptom profiles: Capturing interactivity across behavior, brain and immune regulation | journal = Brain, Behavior, and Immunity | volume = 29 | pages = 1–8 | year = 2013 | pmid = 23022717 | pmc = 3554865 | doi = 10.1016/j.bbi.2012.09.008 | last2 = Craddock }}</ref>

=== Social issues ===
A study found that CFS patients report a heavy [[psychosocial]] burden.<ref name="PMID_12097786">{{cite journal | author = Van Houdenhove B, Neerinckx E, Onghena P, Vingerhoets A, Lysens R, Vertommen H | title = Daily hassles reported by chronic fatigue syndrome and fibromyalgia patients in tertiary care: a controlled quantitative and qualitative study | journal = Psychother Psychosom | volume = 71 | issue = 4 | pages = 207–13 | year = 2002 | pmid = 12097786 | doi = 10.1159/000063646 | last2 = Neerinckx | last3 = Onghena | last4 = Vingerhoets | last5 = Lysens | last6 = Vertommen }}</ref> A survey by the Tymes Trust reported that children with CFS often state that they struggle for recognition of their needs or they feel bullied by medical and educational professionals.<ref name="colby_special">{{cite journal | author = Colby J | title = Special problems of children with myalgic encephalomyelitis/chronic fatigue syndrome and the enteroviral link | journal = J Clin Pathol | volume = 60 | issue = 2 | pages = 125–8 | year = 2007 | pmid = 16935964 | pmc = 1860612 | doi = 10.1136/jcp.2006.042606 | id = 16935964 }}</ref>

=== Social support ===
Individuals with CFS may receive a poorer quality of social support than in those with other illnesses. One study found that CFS patients reported an increased incidence of negative/unsatisfying interactions with family, friends, colleagues and doctors, when compared with healthy controls and breast cancer patients currently in remission.<ref name="nosupport">{{cite journal | author = Prins JB, Bos E, Huibers MJ, Servaes P, van der Werf SP, van der Meer JW, Bleijenberg G | title = Social support and the persistence of complaints in chronic fatigue syndrome | journal = Psychother Psychosom | volume = 73 | issue = 3 | pages = 174–82 | year = 2004 | pmid = 15031590 | doi = 10.1159/000076455 | last2 = Bos | last3 = Huibers | last4 = Servaes | last5 = Van Der Werf | last6 = Van Der Meer | last7 = Bleijenberg }}</ref>

=== Awareness day ===
May 12 is designated as International Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Awareness Day (ME/CFS). The day is observed so that stakeholders have an occasion to improve the knowledge of "the public, policymakers, and healthcare professionals about the symptoms, diagnosis, and treatment of ME/CFS, as well as the need for a better understanding of this complex illness."<ref name="NIH_Awareness">{{cite web |last= Lee |first= Nancy |title= Dr. Nancy Lee on International Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Awareness Day |publisher= U.S. Department of Health & Human Services |url=http://web.archive.org/web/20120708024540/http://www.hhs.gov/advcomcfs/cfsac-cfsa-day.html|accessdate= 2013-10-12}}</ref>

=== Doctor–patient relations ===
[[File:Petition presentation by M.E Support in Glamorgan.jpg|thumb|right|Presentation of a petition to the [[National Assembly for Wales]] relating to M.E. support in South East Wales.]]
Some in the medical community do not recognize CFS as a real condition, nor is there agreement on its prevalence.<ref name=BBCToday>{{cite web |url= http://www.bbc.co.uk/news/science-environment-14326514 |title= 'Torrent of abuse' hindering ME research |accessdate= 2011-07-31 |date= 2011-07-29 |publisher= [[Today (BBC Radio 4)|BBC]]}}</ref><ref name="pmid1794092">{{cite journal | author = Wallace PG, Sharpe M | title = Post-viral fatigue syndrome. Epidemiology: a critical review | journal = Br Med Bull. | volume = 47 | issue = 4 | pages = 942–951 | date = October 1991 | pmid = 1794092 | url = http://bmb.oxfordjournals.org/content/47/4/942.full.pdf | format = PDF }}</ref><ref name="pmid9231495">{{cite journal | author = Mounstephen A, Sharpe M | title = Chronic fatigue syndrome and occupational health | journal = Occupational Medicine | volume = 47 | issue = 4 | pages = 217–27 | year = 1997 | pmid = 9231495 | doi = 10.1093/occmed/47.4.217 | last2 = Sharpe }}</ref> There has been much disagreement over proposed causes, diagnosis, and treatment of the illness.<ref name="pmid11446147">{{cite journal | author = Hooge J | title = Chronic fatigue syndrome: cause, controversy and care | journal = Br J Nurs | volume = 1 | issue = 9 | pages = 440–1, 443, 445–6 | year = 1992 | pmid = 1446147 | doi = }}</ref><ref name="pmid8856816">{{cite journal | author = Sharpe M | title = Chronic fatigue syndrome | journal = Psychiatr. Clin. North Am. | volume = 19 | issue = 3 | pages = 549–73 | year = 1996 | pmid = 8856816 | doi = 10.1016/S0193-953X(05)70305-1 }}</ref><ref name="pmid8474729">{{cite journal | author = Denz-Penhey H, Murdoch JC | title = General practitioners acceptance of the validity of chronic fatigue syndrome as a diagnosis | journal = N. Z. Med. J. | volume = 106 | issue = 953 | pages = 122–4 | year = 1993 | pmid = 8474729 | doi = | last2 = Murdoch }}</ref><ref name="pmid11051301">{{cite journal | author = Greenlee JE, Rose JW | title = Controversies in neurological infectious diseases | journal = Semin Neurol | volume = 20 | issue = 3 | pages = 375–86 | year = 2000 | pmid = 11051301 | doi = 10.1055/s-2000-9429 | last2 = Rose }}</ref><ref name="pmid17535450">{{cite journal | author = Horton-Salway M | title = The ME Bandwagon and other labels: constructing the genuine case in talk about a controversial illness | journal = Br J Soc Psychol | volume = 46 | issue = Pt 4 | pages = 895–914 | year = 2007 | pmid = 17535450 | doi = 10.1348/014466607X173456 }}</ref> This uncertainty can significantly affect doctor-patient relations. A 2006 survey of general medical practitioners in southwest England found that despite more than two thirds accepting CFS/ME as a recognizable clinical entity, nearly half did not feel confident with making the diagnosis and/or treating the disease. Three other key factors that were significantly, positively associated with GPs' attitudes were knowing someone socially with CFS/ME, being male and seeing more patients with the condition in the last year.<ref>{{cite journal|last1=Bowen|first1=J|last2=Pheby|first2=D|last3=Charlett|first3=A|last4=McNulty|first4=C|title=Chronic Fatigue Syndrome: a survey of GPs' attitudes and knowledge.|journal=Family practice|date=August 2005|volume=22|issue=4|pages=389–93|pmid=15805128|doi=10.1093/fampra/cmi019}}</ref>

From the patient perspective, one 1997 study found that 77% of individuals with ME/CFS reported negative experiences with health care providers.<ref>{{cite journal|last1=Anderson|first1=JS|last2=Ferrans|first2=CE|title=The quality of life of persons with chronic fatigue syndrome.|journal=The Journal of Nervous and Mental Disease|date=June 1997|volume=185|issue=6|pages=359–67|pmid=9205421|doi=10.1097/00005053-199706000-00001}}</ref> In a more recent metanalysis of qualitative studies, a major theme identified in patient discourses was that they felt severely ill, yet blamed and dismissed.<ref>{{cite journal|last1=Larun|first1=L|last2=Malterud|first2=K|title=Identity and coping experiences in Chronic Fatigue Syndrome: a synthesis of qualitative studies.|journal=Patient education and counseling|date=December 2007|volume=69|issue=1-3|pages=20–8|pmid=17698311|doi=10.1016/j.pec.2007.06.008}}</ref> Another recent study of themes in patient newsgroup postings noted key themes relating to denial of social recognition of suffering and feelings of being accused of "simply faking it". Another theme that emerged strongly was that achieving diagnosis and acknowledgement requires tremendous amounts of "hard work" by patients.<ref name="pmid9231495"/><ref name="pmid16085344">{{cite journal | author = Dumit J | title = Illnesses you have to fight to get: facts as forces in uncertain, emergent illnesses | journal = Soc Sci Med. | volume = Feb;62 | issue = 3 | pages = 577–90 | date = 2005-08-08 | pmid = 16085344 | doi = 10.1016/j.socscimed.2005.06.018 }}</ref>

=== Blood donation ===
Based on the possible link between CFS and XMRV, in 2010 a variety of [[Blood donation|national blood banks]] adopted measures to discourage or prohibit individuals diagnosed with CFS from donating blood. Organizations adopting these or similar measures included the [[Canadian Blood Services]],<ref>{{cite news |url=http://www.cbc.ca/health/story/2010/04/07/blood-donations-chronic-fatigue-virus.html |title=No blood from chronic fatigue donors: agency |date=2010-04-07 |publisher= [[Canadian Broadcasting Corporation|CBC]] |accessdate= 2010-06-25 }}</ref> the [[New Zealand Blood Service]],<ref>{{cite web |url= http://www.voxy.co.nz/national/chronic-fatigue-set-disqualify-blood-donors/5/45805 |title= Chronic Fatigue Set To Disqualify Blood Donors |accessdate= 2010-06-25 |date= 2010-04-21 |last= Atkinson |first= K |publisher= Voxy.co.nz }}</ref> the [[Australian Red Cross Blood Service]]<ref>{{cite web |url=http://www.donateblood.com.au/media-centre/latest-national-news/blood-service-updates-cfs-donor-policy |title=Blood Service updates CFS donor policy |publisher= [[Australian Red Cross Blood Service]] |accessdate= 2013-07-07 }}</ref> and the [[American Association of Blood Banks]],<ref>{{cite web |url= http://www.aabb.org/pressroom/Pages/cfsrecommendation.aspx |title= Recommendation on Chronic Fatigue Syndrome and Blood Donation |publisher= [[American Association of Blood Banks]] |date= 2010-06-18 |accessdate= 2010-06-25 }}</ref>
In November 2010, the UK National Blood Service introduced a permanent deferral of donation from ME/CFS patients based on the potential harm to those patients that may result from their giving blood.<ref>{{cite web |author=NHS Blood and Transplant |url=http://www.nhsbt.nhs.uk/news-and-media/news-archive/news_2010_10_07.asp |title=ME/CFS sufferers permanently deferred from giving blood |date=2010-11-05 |accessdate=2011-10-09}}</ref> Donation policy in the UK now states, "CFS is generally diagnosed by excluding other conditions and may follow an infection that may or may not have been viral and which may be carried by the affected individual."<ref>{{cite web |author=NHS Blood and Transplant |url=http://www.transfusionguidelines.org.uk/dsg/wb/guidelines/ch013-chronic-fatigue-syndrome |title=Chronic Fatigue Syndrome |accessdate=2015-02-11}}</ref>

===Controversy===
{{Main|Controversies related to chronic fatigue syndrome}}


There has been much contention over the etiology, pathophysiology,<ref name="PMID_17892624"/> nomenclature,<ref name="NYTNotYuppieFlu" /> and diagnostic criteria of chronic fatigue syndrome.<ref name="pmid11446147" /><ref name="pmid8856816" /> Historically, many professionals within the medical community were unfamiliar with CFS, or did not recognize it as a real condition; nor was there agreement on its prevalence or seriousness.<ref name = "pmid1794092" /><ref name = "pmid9231495" /><ref>{{cite journal | author = Jason LA, Richman JA, Friedberg F, Wagner L, Taylor R, Jordan KM | title = Politics, science, and the emergence of a new disease. The case of chronic fatigue syndrome | journal = [[The American Psychologist|Am Psychol]] | volume = 52 | issue = 9 | pages = 973–83 | year = 1997 | pmid = 9301342 | doi = 10.1037/0003-066X.52.9.973 | last2 = Richman | last3 = Friedberg | last4 = Wagner | last5 = Taylor | last6 = Jordan }}</ref> Controversies still exist over funding for research and treatment of [[physiology|physiological]] versus [[psychology|psychological]]/[[psychosocial]] aspects of the illness.<ref name = "pmid11037362">{{cite journal | author = Couper J | title = Chronic fatigue syndrome and Australian psychiatry: lessons from the UK experience | journal = Aust N Z J Psychiatry | volume = 34 | issue = 5 | pages = 762–9 | year = 2000 | pmid = 11037362 | doi = 10.1046/j.1440-1614.2000.00810.x }}</ref>
Any controversy surrounding this terminology results from confusion related to the distinction between the term and definition of a ''disease'', versus the term and definition of a ''syndrome''. (See above).


==Research==
The different case definitions used to research the illness influence the types of patients selected for studies,<ref name="pmid 14702202">{{cite journal | author = Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER | title = Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution | journal = BMC Health Serv Res | volume = 3 | issue = 1 | page = 25 | year = 2003 | pmid = 14702202 | pmc = 317472 | doi = 10.1186/1472-6963-3-25 | last2 = Lloyd | last3 = Vernon | last4 = Klimas | last5 = Jason | last6 = Bleijenberg | last7 = Evengard | last8 = White | last9 = Nisenbaum | last10 = Unger | author11 = International Chronic Fatigue Syndrome Study Group }} {{open access}}</ref> and research also suggests subtypes of patients may exist within a heterogeneous population.<ref name="pmid 15929497" /><ref>{{cite journal | author = Whistler T, Unger ER, Nisenbaum R, Vernon SD | title = Integration of gene expression, clinical, and epidemiologic data to characterize Chronic Fatigue Syndrome | journal = J Transl Med | volume = 1 | issue = 1 | page = 10 | date = December 2003 | pmid = 14641939 | pmc = 305360 | doi = 10.1186/1479-5876-1-10 | url = | last2 = Unger | last3 = Nisenbaum | last4 = Vernon }}</ref><ref>{{cite journal | author = Kennedy G, Abbot NC, Spence V, Underwood C, Belch JJ | title = The specificity of the CDC-1994 criteria for chronic fatigue syndrome: comparison of health status in three groups of patients who fulfill the criteria | journal = Ann Epidemiol | volume = 14 | issue = 2 | pages = 95–100 | date = February 2004 | pmid = 15018881 | doi = 10.1016/j.annepidem.2003.10.004 | url = | last2 = Abbot | last3 = Spence | last4 = Underwood | last5 = Belch }}</ref><ref>{{cite journal | author = Aslakson E, Vollmer-Conna U, White PD | title = The validity of an empirical delineation of heterogeneity in chronic unexplained fatigue | journal = Pharmacogenomics | volume = 7 | issue = 3 | pages = 365–73 | date = April 2006 | pmid = 16610947 | doi = 10.2217/14622416.7.3.365 | last2 = Vollmer-Conna | last3 = White }}</ref> In one of the definitions, symptoms are accepted that may suggest a psychiatric disorder while others specifically exclude primary psychiatric disorders.<ref name = Wyller /> The lack of a single, unifying case definition was criticized in the Institute of Medicine's 2015 report for "creating an unclear picture of the symptoms and signs of the disorder" and "complicating comparisons of the results".<ref name="jama.jamanetwork.com">{{cite web|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=http://jama.jamanetwork.com/article.aspx?articleid=2118591|website=JAMA|publisher=IOM|accessdate=12 November 2015}}</ref>


===United Kingdom===
<!-- The Facts -->
In November 2006, an unofficial inquiry by an ad hoc group of parliamentarians in the United Kingdom, set up and chaired by former MP, Dr Ian Gibson, called the Group on Scientific Research into ME,<ref>{{cite web|url=http://www.erythos.com/gibsonenquiry/Docs/ME_Inquiry_Report.pdf |title=Erythos.com |format=PDF |accessdate=2011-01-28}}</ref> was addressed by a government minister claiming that few good biomedical research proposals have been submitted to the Medical Research Council (MRC) in contrast to those for psychosocial research. They were also told by other scientists of proposals that have been rejected, with claims of bias against biomedical research.
'''The Facts'''


The MRC confirmed to the Group that, from April 2003 to November 2006, it has turned down 10 biomedical applications relating to CFS/ME and funded five applications relating to CFS/ME, mostly in the psychiatric/psychosocial domain.
There are many different diseases and conditions which can cause some of the various symptoms that have been inappropriately placed under the umbrella of the term 'CFS'. Many people with a variety of different illnesses, diseases, ailments, and conditions have been mis-diagnosed with 'CFS', leading to failure to reach a correct diagnosis, and to inappropriate (or lack of) treatment. <ref>[[http://nightingale.ca Nightingale Research Foundation]]</ref> <ref>[[http://www.hfme.org/misdiagnosis.htm 'CFS' - always a mis-diagnosis]]</ref>.


In 2008, the MRC set up an expert group to consider how the MRC might encourage new high-quality research into CFS/ME and partnerships between researchers already working on CFS/ME and those in associated areas. It currently lists CFS/ME with a highlight notice, inviting researchers to develop high-quality research proposals for funding.<ref>{{cite web|url=http://www.mrc.ac.uk/Ourresearch/ResearchInitiatives/CFSME/index.htm |title=Chronic Fatigue Syndrome/Myalgic Encephalomyelitis |publisher=MRC.ac.uk |accessdate=2011-01-28}}</ref> In February 2010, the All-Party Parliamentary Group on ME (APPG on ME) produced a legacy paper, which welcomed the recent MRC initiative, but felt that there has been far too much emphasis in the past on psychological research with insufficient attention to biomedical research and that it is vital that further biomedical research be undertaken to help discover a cause and more effective forms of management for this disease.<ref>{{cite web|url=http://appgme.org.uk/Downloads/appg_interim_report_v2.pdf |title=APPGME.org.uk |format=PDF |accessdate=2011-01-28}}</ref>


Looking at psychologically-oriented models of the disease and behavioral treatments has been criticised by some patients and patient support groups.<ref>"IACFS/ME Statement on the PACE Trial: The Issue of Illness 'Reversal'", 24 February 2011, The International Association for Chronic Fatigue Syndrome/ME (IACFS/ME), http://www.iacfsme.org/PACETrial/tabid/450/Default.aspx</ref><ref>"PACE: 'surprising and disappointing'", 18 February 2011, Action for ME, http://www.afme.org.uk/news.asp?newsid=1047</ref><ref>"ME Association press statement about the results of the PACE study", Tony Britton for the ME Association, 18 February 2011, http://www.meassociation.org.uk/?p=4607</ref><ref>"Falling off the PACE", Kimberly McCleary, [undated (Retrieved 26 July 2011)], The CAA (CFIDS Association of America), http://www.cfids.org/pdf/lancet-analysis.pdf</ref> In 2011, it was reported that several UK researchers investigating CFS from this perspective had been subjected to verbal abuse, death threats and other harassment.<ref name="hawkes">{{cite journal|last1=Hawkes|first1=N.|title=Dangers of research into chronic fatigue syndrome|journal=BMJ|date=22 June 2011|volume=342|issue=jun22 1|pages=d3780–d3780|doi=10.1136/bmj.d3780}}</ref><ref>{{cite web | url=http://www.guardian.co.uk/society/2011/aug/21/chronic-fatigue-syndrome-myalgic-encephalomyelitis | title=Chronic fatigue syndrome researchers face death threats from militants| newspaper=The Guardian | date=2011-08-21 | accessdate=2015-08-25}}</ref>
<!-- Inappropriate association -->
'''Inappropriate association'''


===United States===
Since the late 1980s, the term 'CFS' has been particularly associated with a disease known as Myalgic Encephalomyelitis <ref>[[http://www.hfme.org Hummingbird's Foundation for Myalgic Encephalomyelitis]]</ref>. According to inaccurate information that can be found proliferating all over the internet, these two distinct definitions and terms are often used as though they were interchangeable. However, patients who suffer from Myalgic Encephalomyelitis do not qualify under the diagnostic criteria for 'CFS'.
On 29 October 2015 the National Institutes of Health declared its intent to increase research on ME/CFS. The NIH Clinical Center will study individuals with ME/CFS, and the National Institute of Neurological Disorders and Stroke (NINDS) will lead the Trans-NIH ME/CFS Research Working Group as part of a multi-institute research effort.<ref>http://www.nih.gov/news/health/oct2015/od-29.htm</ref>


== References ==
'CFS' is a term that was not even in existence until the late 1980s. 'CFS' is a term that was invented nearly two decades after the disease Myalgic Encephalomyelitis had been registered with the [[World_Health_Organization|World Health Organization]], and more than thirty years after it had been named:''
{{Reflist|30em}}


== Further reading ==
''"In 1956 the name Myalgic Encephalomyelitis was created. The term was invented jointly by Dr A Melvin Ramsay who coined this name in relation to the Royal Free Hospital epidemics that occurred in London in 1955 - 1957 and by Dr John Richardson who observed the same type of illness in his rural practice in Newcastle-upon-Tyne area during the same period. It was obvious to these physicians that they were dealing with the consequences of an epidemic and endemic infectious neurological disease (Hyde 1998, [Online]) (Hyde 2006, [Online])."'' <ref>[[http://www.hfme.org/methemedicalfacts.htm M.E. - The Medical Facts]]</ref>
* {{cite book |title= Handbook of Chronic Fatigue Syndrome |editors= [[Leonard A. Jason|Jason LA]]; [[Patricia Fennell|Fennell PA]] & Taylor RR |year= 2003 |publisher= [[John Wiley & Sons]] |isbn= 978-0-471-41512-1}}
* {{cite book |author=Sharpe, Michael; Frankie Campling |title=Chronic fatigue syndrome (CFS/ME) |publisher=[[Oxford University Press]] |location=Oxford [Oxfordshire] |year=2000 |isbn=0-19-263049-0}}
* {{cite book |editors=Jenkins, Rachel; Mowbray, James F. |title=Post-viral Fatigue Syndrome (Myalgic Encephalomyelitis) |publisher=[[John Wiley & Sons]] |year=1992 |isbn=978-0471938798}}
* {{cite book |editors=Hyde, Byron M.; Goldstein, Jay A.; Levine, Paul H. |title=The Clinical and Scientific Basis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome |publisher=Nightingale Research Foundation |year=1992 |isbn=978-0969566205}}


== External links ==
Myalgic Encephalomyelitis is a disease about which there is no mystery. Myalgic Encephalomyelitis is a clearly-deliniated disease has been well-understood by science and medicine since the mid-1950s. M.E. has been registered with the [[World_Health_Organization|World Health Organization]] as a distinct, organic (physical) neurological disease, since 1969 (see below).
<!-- BEFORE inserting new links here you should first post it to the talk page, otherwise your edit is likely to be reverted-->
* {{cite web |url=http://www.cdc.gov/cfs |title=CDC - Chronic Fatigue Syndrome (CFS) |publisher=Centers for Disease Control |work= |accessdate=2011-12-09}}
* {{cite web |url=http://www.meresearch.org.uk/information/research-database/|title=ME Research UK — Research database |work= |accessdate=2013-08-03}}


{{chronic fatigue syndrome}}


{{Authority control}}
'''As Professor Malcolm Hooper explains:'''


{{DEFAULTSORT:Chronic Fatigue Syndrome}}
''"The term myalgic encephalomyelitis has been included by the World Health Organisation (WHO) in their International Classification of Diseases (ICD), since 1969. The currently version ICD-10 lists M.E. under G.93.3 - neurological conditions. It cannot be emphasised too strongly that this recognition emerged from meticulous clinical observation and examination (2006)."'' <ref>[[http://www.hfme.org/methemedicalfacts.htm M.E. - The Medical Facts]]</ref>
[[Category:Chronic fatigue syndrome| ]]
[[Category:Ailments of unknown etiology]]
[[Category:Immune system disorders]]
[[Category:Neurological disorders]]
[[Category:Syndromes]]
[[Category:Medical controversies]]

Revision as of 17:43, 18 November 2015

Myalgic encephalomyelitis/chronic fatigue syndrome
SpecialtyNeurology, rheumatology Edit this on Wikidata

Chronic fatigue syndrome (CFS) is a complex medical condition, characterized by long-term fatigue and other symptoms.[1][2] These symptoms are to such a degree that they limit a person's ability to carry out ordinary daily activities.[2] CFS may also be referred to as systemic exertion intolerance disease (SEID), myalgic encephalomyelitis (ME), post-viral fatigue syndrome (PVFS), chronic fatigue immune dysfunction syndrome (CFIDS), or several other terms.[3] Quality of life of persons with CFS can be extremely compromised.[4]

Biological, genetic, infectious, and psychological mechanisms have been proposed, but the cause is not understood.[5][6] The fatigue of CFS is not due to ongoing exertion, is not much relieved by rest, and is not due to any other medical condition.[7] Diagnosis is based on a patient's signs and symptoms.[8]

Evidence suggests that cognitive behavioral therapy and a gradual increase in activity suited to individual capacity can be beneficial in some cases. The medication rintatolimod may be be helpful to certain patients.[8].

Estimates of the number of people with the condition vary from 7 to 3,000 per 100,000 adults.[5][9] About one million Americans and a quarter of a million people in the UK have CFS.[10][11] Fatigue is a common symptom in many illnesses, but the fatigue experienced by persons with CFS is comparatively rare.[9] CFS occurs more often in women than men,[12] and is less common among children and adolescents.[13]

There is agreement that CFS has a negative effect on health, happiness and productivity. However, various physicians' groups, researchers and patient advocates promote differing terminology, diagnostic criteria, proposed causes and treatments, resulting in controversy about many aspects of the disorder. The name "chronic fatigue syndrome" is controversial; many patients and advocacy groups, as well as some experts, believe the name trivializes the medical condition and they promote a name change.[14]

Signs and symptoms

Symptoms of CFS include malaise after exertion; unrefreshing sleep, widespread muscle and joint pain, sore throat, headaches of a type not previously experienced, cognitive difficulties, chronic and severe mental and physical exhaustion. Additional symptoms may be reported, including muscle weakness, increased sensitivity to light, sounds and smells, problems standing upright, digestive disturbances, depression, painful and often slightly swollen lymph nodes, cardiac and respiratory problems.[15] It is unclear if these symptoms represent other associated conditions or if they are produced by CFS itself.[5] Symptoms vary in number, type, and severity from person to person.[16]

Onset

The majority of CFS cases start suddenly,[17] usually accompanied by a "flu-like illness"[5] while a significant proportion of cases begin within several months of severe adverse stress.[17][18][19] An Australian prospective study found that after infection by viral and non-viral pathogens, a subset of individuals met the criteria for CFS, with the researchers concluding that "post-infective fatigue syndrome is a valid illness model for investigating one pathophysiological pathway to CFS".[20] However, accurate prevalence and exact roles of infection and stress in the development of CFS are currently unknown.

Symptoms

The most commonly used diagnostic criteria and definition of CFS for research and clinical purposes were published by the United States Centers for Disease Control and Prevention (CDC).[5] The CDC recommends the following three criteria be fulfilled:[21]

  1. A new onset (not lifelong) of severe fatigue for six consecutive months or greater duration which is unrelated to exertion, is not substantially relieved by rest, and is not a result of other medical conditions.
  2. The fatigue causes a significant reduction of previous activity levels.
  3. Four or more of the following symptoms that concurrently last six months or longer:

The CDC states other common symptoms include the following:[16]

The CDC proposes that persons with symptoms resembling those of CFS consult a physician to rule out several treatable illnesses: Lyme disease,[21] "sleep disorders, major depressive disorder, alcohol/substance abuse, diabetes, hypothyroidism, mononucleosis (mono), lupus, multiple sclerosis (MS), chronic hepatitis and various malignancies."[22] Medications can also cause side effects that mimic symptoms of CFS.[21]

Unlike the CDC's diagnostic criteria for CFS, the International Consensus Criteria for ME do not require the 6-month waiting period before diagnosis, noting that "No other disease criteria require that diagnoses be withheld until after the patient has suffered with the affliction for 6 months."[23]

Functioning

Despite a common diagnosis the functional capacity of individuals with CFS varies greatly.[24] Some persons with CFS lead relatively normal lives; others are totally bed-ridden and unable to care for themselves.[25] For the majority of persons with CFS, work, school, and family activities are significantly reduced for extended periods of time.[16] The severity of symptoms and disability is the same in both genders,[26] and many experience strongly disabling chronic pain.[27] Persons report critical reductions in levels of physical activity.[28] Also, a reduction in the complexity of activity has been observed.[29] Reported impairment is comparable to other fatiguing medical conditions[30] including late-stage AIDS,[31] lupus, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), and end-stage renal disease.[16] CFS affects a person's functional status and well-being more than major medical conditions such as multiple sclerosis, congestive heart failure, or type II diabetes mellitus.[4][32]

Often, there are courses of remission and relapse of symptoms which make the illness difficult to manage. Persons who feel better for a period may overextend their activities, and the result can be a worsening of their symptoms with a relapse of the illness.[16]

Employment rates vary with over half unable to work and nearly two-thirds limited in their work because of their illness. More than half were on disability benefits or temporary sick leave, and less than a fifth worked full-time.[25]

Cognitive functioning

Cognitive symptoms are mainly from deficits in attention, memory, and reaction time. The deficits are in the range of 0.5 to 1.0 standard deviations below expected and are likely to affect day-to-day activities. Simple and complex information processing speed and functions entailing working memory over long time periods were moderately to extensively impaired. These deficits are generally consistent with those reported by patients. Perceptual abilities, motor speed, language, reasoning, and intelligence did not appear to be significantly altered.[33]

Comorbidity

Many CFS patients will also have, or appear to have, other medical problems or related diagnoses. Fibromyalgia occurs in a large percentage of CFS patients between onset and the second year, and some researchers suggest fibromyalgia and CFS are related.[34] As previously mentioned, many CFS sufferers also experience symptoms of irritable bowel syndrome, temporomandibular joint pain, headache including migraines, and other forms of myalgia. CFS patients have significantly higher rates of current mood disorders than the general population.[35] Compared with the non-fatigued population, male CFS patients are more likely to experience chronic pelvic pain syndrome (CP/CPPS), and female CFS patients are also more likely to experience chronic pelvic pain.[36] CFS is significantly more common in women with endometriosis compared with women in the general USA population.[37]

Risk factors

All ethnic groups and income levels are susceptible to the illness. The CDC states that ME/CFS is "at least as common" in African Americans and Hispanics as Caucasians. A 2009 meta-analysis, however, showed that compared with the White American majority, African Americans and Native Americans have a higher risk of CFS, though it acknowledged that studies and data were limited.[38] More women than men get CFS — between 60 and 85% of cases are women; however, there is some indication that the prevalence among men is underreported. The illness is reported to occur more frequently in people between the ages of 40 and 59.[12] CFS is less prevalent among children and adolescents than adults.[10] Blood relatives of people who have CFS appear to be more predisposed.[39] There is no direct evidence that CFS is contagious.[13]

A systematic review in 2008 included eleven primary studies that had assessed various demographic, medical, psychological, social and environmental factors to predict the development of CFS, and found many had reported significant associations to CFS.[40] The reviewers concluded that the lack of generalizability and replication between studies meant that "none of the identified factors appear suitable for the timely identification of patients at risk of developing CFS/ME within clinical practice."

Pathophysiology

The causes and mechanisms of chronic fatigue syndrome are currently unknown, despite extensive research.[10] Research studies have developed and explored etiological hypotheses regarding a variety of factors, including oxidative stress, genetic predisposition,[41] infection by viruses and pathogenic bacteria, hypothalamic-pituitary-adrenal axis abnormalities, immune dysfunction as well as psychological and psychosocial factors. Although it is unclear whether such factors are causes or consequences of CFS (or both), various models have been proposed.[42][43][44]

A substantial body of evidence points to the following abnormalities in the hypothalamic-pituitary-adrenal axis (HPA axis) in CFS patients: mild hypocortisolism, an attenuated diurnal variation in cortisol, enhanced cortisol negative feedback, and a blunted HPA axis responsiveness. It is unclear whether or not these disturbances play a primary role in the pathogenesis of CFS.[45]

Persons diagnosed with the illness appear to have an abnormal immune response to exercise. Specifically, complement products are increased, larger oxidative stress is generated along with reduced anti-oxidant immune response, and larger interleukin-10 and toll-like receptor 4 gene expression are seen versus healthy controls. Many of these immune responses correlate with the symptom of post-exertional malaise.[46]

Diagnosis

There are no characteristic laboratory abnormalities to diagnose CFS,[47] so testing is used to rule out other potential causes for symptoms.[48] When symptoms are attributable to certain other conditions, the diagnosis of CFS is excluded. Important conditions and disorders to exclude are current/active major depression, schizophrenia, eating disorders such as anorexia nervosa and bulimia, bipolar disorder, alcohol abuse or other substance abuse. Current morbid obesity and active medical diseases need to be resolved and excluded before a diagnosis of chronic fatigue syndrome can be made.[49]

Definitions

Notable definitions include:[15]

  • Centers for Disease Control and Prevention (CDC) definition (1994),[48] the most widely used clinical and research description of CFS,[5] is also called the Fukuda definition and is a revision of the Holmes or CDC 1988 scoring system.[50] The 1994 criteria require the presence of four or more symptoms beyond fatigue, while the 1988 criteria require six to eight.[2]
  • The ME/CFS 2003 Canadian Clinical working definition[51] states: "A patient with ME/CFS will meet the criteria for fatigue, post-exertional malaise and/or fatigue, sleep dysfunction, and pain; have two or more neurological/cognitive manifestations and one or more symptoms from two of the categories of autonomic, neuroendocrine, and immune manifestations; and the illness persists for at least 6 months".

Clinical practice guidelines are generally based on case descriptions with the aim of improving diagnosis, management, and treatment. An example is the CFS/ME guideline for the National Health Service in England and Wales, produced in 2007 by the National Institute for Health and Clinical Excellence (NICE).[2]

Differential diagnoses

Certain medical conditions can cause chronic fatigue and must be ruled out before a diagnosis of CFS can be given. Hypothyroidism, anemia,[52] coeliac disease (that can occur without gastrointestinal symptoms),[53] diabetes and certain psychiatric disorders are a few of the diseases that must be ruled out if the patient presents with appropriate symptoms.[2][48][52] Other diseases, listed by the Centers for Disease Control and Prevention, include infectious diseases (such as Epstein–Barr virus, influenza, HIV infection, tuberculosis, Lyme disease), neuroendocrine diseases (such as thyroiditis, Addison's disease, adrenal insufficiency, Cushing's disease), hematologic diseases (such as occult malignancy, lymphoma), rheumatologic diseases (such as fibromyalgia, polymyalgia rheumatica, Sjögren's syndrome, giant-cell arteritis, polymyositis, dermatomyositis), psychiatric diseases (such as bipolar disorder, schizophrenia, delusional disorders, dementia, anorexia/bulimia nervosa), neuropsychologic diseases (such as obstructive sleep apnea, parkinsonism, multiple sclerosis), and others (such as nasal obstruction from allergies, sinusitis, anatomic obstruction, autoimmune diseases, some chronic illness, alcohol or substance abuse, pharmacologic side effects, heavy metal exposure and toxicity, marked body weight fluctuation).[52]

People with fibromyalgia (FM, or fibromyalgia syndrome, FMS), like those with CFS, have muscle pain, severe fatigue and sleep disturbances. The presence of allodynia (abnormal pain responses to mild stimulation) and of extensive tender points in specific locations differentiates FM from CFS, though the two diseases often co-occur.[54] Fatigue and muscle pain occurs frequently in the initial phase of various hereditary muscle disorders and in several autoimmune, endocrine and metabolic syndromes; and are frequently labelled as CFS or fibromyalgia in the absence of obvious biochemical/metabolic abnormalities and neurological symptoms.[citation needed]

Multiple chemical sensitivity, Gulf War syndrome and post-polio syndrome have symptoms similar to those of CFS,[55][56] and the last is also theorized to have a common pathophysiology.[56]

Depressive symptoms, if seen in CFS, may be differentially diagnosed from primary depression due to the absence of anhedonia, decreased motivation, and guilt; and the presence of somatic symptoms such as sore throat, swollen lymph nodes, and exercise intolerance with postexertional exacerbation of symptoms.[52]

Management

Many people do not fully recover from CFS even with treatment.[57] Cognitive behavioural therapy (CBT) and graded exercise therapy (GET) have shown moderate effectiveness in a number of randomized controlled trials.[58][59][60][61] As many of the CBT and GET studies required visits to a clinic, those severely affected may not have been included.[59] Two large surveys of patients indicated that pacing is a helpful intervention, or is considered useful by 82-96% of participants.[62][63] A comprehensive rehabilitation programme only rarely results in full recovery.[64] Medication plays a minor role in management.[65] No intervention has been proven effective in restoring the ability to work.[59]

Cognitive behavioral therapy

Cognitive behavioral therapy is a moderately effective psychological therapy[58][59] when used to treat CFS. It is often used alone or with other therapies to "manage activity levels, stress, and symptoms."[66] CBT tries to help patients understand their individual symptoms and beliefs and develop strategies to improve day-to-day functioning. CBT is thought to help patients by eliminating unhelpful illness beliefs which may perpetuate the illness.[67]

A Cochrane Review meta-analysis of 15 randomized, controlled cognitive behavioral therapy trials with 1043 participants concluded that CBT reduced the symptom of fatigue. Four studies showed that CBT resulted in a clinical response for 40% of participants vs 26% treated with "usual care". Similarly, in 3 studies CBT worked better than other types of psychological therapies (48% vs 27%). The effects of CBT may diminish after therapy is completed; the reviewers write that "the evidence base at follow-up is limited to a small group of studies with inconsistent findings" and encourage further studies.[68] A 2007 meta-analysis of 5 CBT randomized controlled trials of chronic fatigue and chronic fatigue syndrome reported 33-73% of the patients improved to the point of no longer being clinically fatigued.[69]

A 2010 meta-analysis of trials that measured physical activity before and after CBT reported that although CBT effectively reduced fatigue, activity levels were not affected by CBT and changes in physical activity were not related to changes in fatigue. They conclude that the effect of CBT on fatigue is not influenced by a change in physical activity.[70] According to a 2014 systematic review on recovery, the lack of changes to objectively measured physical activity after intervention is contrary to the cognitive behavioural model of CFS and suggests that patients still avoided postexertional symptom exacerbations and adapted to the illness rather than recovered from it.[71]

CBT has been criticised by patients' organisations because multiple patient surveys of their members[72] have indicated that CBT can make people worse. Some dispute the validity of the evidence base behind CBT as well as graded exercise therapy (below), and conclude that it would be unethical to use these treatments.[73]

Exercise

Graded exercise therapy is a form of physical therapy. A meta-analysis published in 2004 of five randomized trials found that patients who received exercise therapy were less fatigued after 12 weeks than the control participants, and the authors cautiously conclude that GET shows promise as a treatment. However, after 6 months the benefit became non-significant compared to the control group who did not receive GET, and functional work capacity was not significantly improved after therapy.[74] A systematic review published in 2006 included the same five RCTs, noting that "no severely affected patients were included in the studies of GET".[59] A 2012 systematic review concluded that despite the consistent positive outcomes of exercise therapy studies for CFS, "exercise therapy is not a cure for CFS", and "a comprehensive rehabilitation programme only rarely results in full recovery".[64]

Surveys conducted on behalf of patient organizations find adverse effects to be very common.[75][76][77] To avoid detrimental effects from GET, care must be taken to avoid the exacerbation of symptoms while catering the program to individual capabilities and the fluctuating nature of symptoms.[78] A 2015 Cochrane review found that exercise therapy may reduce fatigue among people with CFS, and concluded that the effects of exercise therapy were comparable to those of cognitive-behavioral therapy.[79]

Pacing

Pacing is an energy management strategy based on the observation that symptoms of the illness tend to increase following minimal exertion. There are two forms: symptom-contingent pacing, where the decision to stop (and rest or change an activity) is determined by an awareness of an exacerbation of symptoms; and time-contingent pacing, which is determined by a set schedule of activities which a patient estimates he or she is able to complete without triggering post-exertional malaise (PEM).[80] Thus the principle behind pacing for CFS is to avoid over-exertion and an exacerbation of symptoms. It is not aimed at treating the illness as a whole. Those whose illness appears stable may gradually increase activity and exercise levels but according to the principle of pacing, must rest if it becomes clear that they have exceeded their limits. Some programmes combine symptom and time-contingent approaches. A trial of one such programme reported limited benefits.[78] A larger, randomised controlled trial found that pacing had statistically better results than relaxation/flexibility therapy.[81][82] A 2009 survey of 828 Norwegian CFS patients found that pacing was evaluated as useful by 96% of the participants.[76]

Other

Evidence suggests that the medication rintatolimod may be useful in some people.[8] In 2012, however, the FDA considered the evidence for the safety or benefit of rintatolimod to be insufficient to approve its use.[83] Other treatments of CFS have been proposed but their effectiveness has not been confirmed.[84] Medications thought to have promise in alleviating symptoms include antidepressant and immunomodulatory agents.[85] The evidence for antidepressants is mixed,[86] and their use remains controversial.[87] Many CFS patients are sensitive to medications, particularly sedatives, and some patients report chemical and food sensitivities.[16] CFS patients have a low placebo response, especially to psychological-psychiatric interventions, perhaps due to patient expectations.[88]

Prognosis

A systematic review of 14 studies that described improvement and occupational outcomes of people with CFS found that "the median full recovery rate was 5% (range 0–31%) and the median proportion of patients who improved during follow-up was 39.5% (range 8–63%). Return to work at follow-up ranged from 8 to 30% in the three studies that considered this outcome." .... "In five studies, a worsening of symptoms during the period of follow-up was reported in between 5 and 20% of patients." A good outcome was associated with less fatigue severity at baseline. Other factors were occasionally, but not consistently, related to outcome, including age at onset (5 of 16 studies), and attributing illness to a psychological cause and/or having a sense of control over symptoms (4 of 16 studies).[89] Another review found that children have a better prognosis than adults, with 54–94% having recovered by follow-up compared to less than 10% of adults returning to pre-illness levels of functioning.[90]

A 2014 systematic review reported that estimates of recovery from CFS ranged between 0 to 66% in intervention studies and 2.6 to 62% in naturalistic studies. There was a lack of consensus in the literature on how recovery should be defined. "Recovery" was often based on limited assessments, less than a full restoration of health, and self-reports with a general lack of more objective measures, which when used, did not find significant changes in physical activity. The authors suggested that patients were still avoiding post-exertion symptom exacerbation, and could be clinically improving to a limited extent or adapting to ongoing illness rather than recovering. It was recommended using stricter and more comprehensive definitions of recovery which capture fatigue, function, patient perceptions, and recovery time following physical and mental exertion.[91]

Epidemiology

A 2003 review states that studies have reported between 7 and 3,000 cases of CFS for every 100,000 adults.[5] Ranjith reviewed the epidemiological literature on CFS and suggested that the wide variance of the prevalence estimates may be due to the different definitions of CFS in use, the settings in which patients were selected, and the methodology used to exclude study participants with possible alternative diagnoses.[9] The Centers for Disease Control reports that more than 1 million Americans have CFS and approximately 80% of the cases are undiagnosed.[10] Approximately 250,000 people in the UK are affected with the illness according to the National Health Service.[11]

History

In 1934, an outbreak then referred to as atypical poliomyelitis (at the time it was considered a form of polio) occurred at the Los Angeles County Hospital. It strongly resembled what Ramsay and Acheson would later describe as ME (in 1934, there were no follow-up data to indicate chronicity and it is not known how many of those affected remained ill). Of note are the neurological symptoms, the link with a polio outbreak and the fact that most of the patients were hospital staff.[92] During 1955, there were many similar outbreaks, the best known of which affected several hospitals that formed part of the Royal Free group in London. It also featured neurological signs and affected mostly the hospital staff.[93] CFS excludes these outbreaks by definition, though many patients have a post-viral onset and the literature relating to ME is considered relevant to the study of CFS. In 1969, benign myalgic encephalomyelitis was first classified into the International Classification of Diseases under Diseases of the nervous system.[94]

The name chronic fatigue syndrome was used in the medical literature in 1987[95] to describe a condition resembling "chronic active Epstein-Barr virus (EBV) infection" but which presented no evidence of active EBV as its cause. The initial case definition of CFS was published in 1988, "Chronic fatigue syndrome: a working case definition", (the Holmes definition), and displaced the name chronic Epstein-Barr virus syndrome. This research case definition was published after US Centers for Disease Control and Prevention epidemiologists examined the Lake Tahoe outbreak.[96][97][98] In 2006, the CDC commenced a national program to educate the American public and health care professionals about CFS.[99]

In 2009 the journal Science[100] published a study that identified the XMRV retrovirus in a population of people with CFS. Other studies failed to reproduce this finding,[101][102][103] and in 2011 the editor of Science formally retracted its XMRV paper[104] while the Proceedings of the National Academy of Sciences similarly retracted a 2010 paper which had appeared to support the finding of a connection between XMRV and CFS.[105]

Society and culture

A depiction of CFS

Naming

Chronic fatigue syndrome is the most commonly used designation,[1] but widespread approval of a name is lacking.[72] Different authorities on the illness view CFS as a central nervous system, metabolic, infectious or post-infectious, cardiovascular, immune system or psychiatric disorder, and different symptom profiles may be caused by various disorders.[106]

Over time and in different countries, many names have been associated with the condition(s). Aside from CFS, some other names used include Akureyri disease, benign myalgic encephalomyelitis, chronic fatigue immune dysfunction syndrome, chronic infectious mononucleosis, epidemic myalgic encephalomyelitis, epidemic neuromyasthenia, Iceland disease, myalgic encephalomyelitis, myalgic encephalitis, myalgic encephalopathy, post-viral fatigue syndrome, raphe nucleus encephalopathy, Royal Free disease, Tapanui flu, and yuppie flu (the last considered pejorative).[107][108] Many patients would prefer a different name such as "myalgic encephalomyelitis", believing the name "chronic fatigue syndrome" trivializes the condition, prevents it from being seen as a serious health problem, and discourages research.[14][109][110]

A 2001 review referenced myalgic encephalomyelitis symptoms in a 1959 article by Acheson, stating ME could be a distinct syndrome from CFS. A 1999 review explained that the Royal Colleges of Physicians, Psychiatrists, and General Practitioners in 1996 advocated the use of chronic fatigue syndrome instead of myalgic encephalomyelitis or ME, which was in wide use in the United Kingdom, "because there is, so far, no recognized pathology in muscles and in the central nervous system as is implied by the term ME".[1][111] An editorial noted that the 1996 report received some acceptance, but also criticism from those advocating the use of different naming conventions, suggesting the report was biased, dominated by psychiatrists, and that dissenting voices were excluded.[112] In 2002, a Lancet commentary noted the recent report by the "Working Group on CFS/ME"[113] used the compromise name CFS/ME stating, "The fact that both names for the illness were used symbolises respect for different viewpoints whilst acknowledging the continuing lack of consensus on a universally acceptable name."[72]

A 2015 report from the Institute of Medicine proposes the illness be renamed "systemic exertion intolerance disease" and suggests new diagnostic criteria for it. Many patients, clinicians and researchers believe lengthy disproportionate exhaustion after physical or mental exertion is a core symptom (also known as post-exertional malaise).[3][114]

Economic impact

Reynolds et al. (2004)[115] estimated that the illness caused about $20,000 per person with CFS in lost productivity which totals to $9.1 billion per year in the United States.[106] This is comparable to other chronic illnesses that extract some of the biggest medical and socioeconomic costs.[49] A 2008 study[116] calculated that the total annual cost burden of ME/CFS to society in the US was extensive, and could approach $24.0 billion.[117]

Social issues

A study found that CFS patients report a heavy psychosocial burden.[118] A survey by the Tymes Trust reported that children with CFS often state that they struggle for recognition of their needs or they feel bullied by medical and educational professionals.[119]

Social support

Individuals with CFS may receive a poorer quality of social support than in those with other illnesses. One study found that CFS patients reported an increased incidence of negative/unsatisfying interactions with family, friends, colleagues and doctors, when compared with healthy controls and breast cancer patients currently in remission.[120]

Awareness day

May 12 is designated as International Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Awareness Day (ME/CFS). The day is observed so that stakeholders have an occasion to improve the knowledge of "the public, policymakers, and healthcare professionals about the symptoms, diagnosis, and treatment of ME/CFS, as well as the need for a better understanding of this complex illness."[121]

Doctor–patient relations

Presentation of a petition to the National Assembly for Wales relating to M.E. support in South East Wales.

Some in the medical community do not recognize CFS as a real condition, nor is there agreement on its prevalence.[122][123][124] There has been much disagreement over proposed causes, diagnosis, and treatment of the illness.[125][126][127][128][129] This uncertainty can significantly affect doctor-patient relations. A 2006 survey of general medical practitioners in southwest England found that despite more than two thirds accepting CFS/ME as a recognizable clinical entity, nearly half did not feel confident with making the diagnosis and/or treating the disease. Three other key factors that were significantly, positively associated with GPs' attitudes were knowing someone socially with CFS/ME, being male and seeing more patients with the condition in the last year.[130]

From the patient perspective, one 1997 study found that 77% of individuals with ME/CFS reported negative experiences with health care providers.[131] In a more recent metanalysis of qualitative studies, a major theme identified in patient discourses was that they felt severely ill, yet blamed and dismissed.[132] Another recent study of themes in patient newsgroup postings noted key themes relating to denial of social recognition of suffering and feelings of being accused of "simply faking it". Another theme that emerged strongly was that achieving diagnosis and acknowledgement requires tremendous amounts of "hard work" by patients.[124][133]

Blood donation

Based on the possible link between CFS and XMRV, in 2010 a variety of national blood banks adopted measures to discourage or prohibit individuals diagnosed with CFS from donating blood. Organizations adopting these or similar measures included the Canadian Blood Services,[134] the New Zealand Blood Service,[135] the Australian Red Cross Blood Service[136] and the American Association of Blood Banks,[137] In November 2010, the UK National Blood Service introduced a permanent deferral of donation from ME/CFS patients based on the potential harm to those patients that may result from their giving blood.[138] Donation policy in the UK now states, "CFS is generally diagnosed by excluding other conditions and may follow an infection that may or may not have been viral and which may be carried by the affected individual."[139]

Controversy

There has been much contention over the etiology, pathophysiology,[40] nomenclature,[110] and diagnostic criteria of chronic fatigue syndrome.[125][126] Historically, many professionals within the medical community were unfamiliar with CFS, or did not recognize it as a real condition; nor was there agreement on its prevalence or seriousness.[123][124][140] Controversies still exist over funding for research and treatment of physiological versus psychological/psychosocial aspects of the illness.[141]

Research

The different case definitions used to research the illness influence the types of patients selected for studies,[47] and research also suggests subtypes of patients may exist within a heterogeneous population.[106][142][143][144] In one of the definitions, symptoms are accepted that may suggest a psychiatric disorder while others specifically exclude primary psychiatric disorders.[15] The lack of a single, unifying case definition was criticized in the Institute of Medicine's 2015 report for "creating an unclear picture of the symptoms and signs of the disorder" and "complicating comparisons of the results".[145]

United Kingdom

In November 2006, an unofficial inquiry by an ad hoc group of parliamentarians in the United Kingdom, set up and chaired by former MP, Dr Ian Gibson, called the Group on Scientific Research into ME,[146] was addressed by a government minister claiming that few good biomedical research proposals have been submitted to the Medical Research Council (MRC) in contrast to those for psychosocial research. They were also told by other scientists of proposals that have been rejected, with claims of bias against biomedical research.

The MRC confirmed to the Group that, from April 2003 to November 2006, it has turned down 10 biomedical applications relating to CFS/ME and funded five applications relating to CFS/ME, mostly in the psychiatric/psychosocial domain.

In 2008, the MRC set up an expert group to consider how the MRC might encourage new high-quality research into CFS/ME and partnerships between researchers already working on CFS/ME and those in associated areas. It currently lists CFS/ME with a highlight notice, inviting researchers to develop high-quality research proposals for funding.[147] In February 2010, the All-Party Parliamentary Group on ME (APPG on ME) produced a legacy paper, which welcomed the recent MRC initiative, but felt that there has been far too much emphasis in the past on psychological research with insufficient attention to biomedical research and that it is vital that further biomedical research be undertaken to help discover a cause and more effective forms of management for this disease.[148]

Looking at psychologically-oriented models of the disease and behavioral treatments has been criticised by some patients and patient support groups.[149][150][151][152] In 2011, it was reported that several UK researchers investigating CFS from this perspective had been subjected to verbal abuse, death threats and other harassment.[153][154]

United States

On 29 October 2015 the National Institutes of Health declared its intent to increase research on ME/CFS. The NIH Clinical Center will study individuals with ME/CFS, and the National Institute of Neurological Disorders and Stroke (NINDS) will lead the Trans-NIH ME/CFS Research Working Group as part of a multi-institute research effort.[155]

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