Chronic fatigue syndrome

Chronic fatigue syndrome
systemic exertion intolerance disease (SEID), myalgic encephalomyelitis (ME), post-viral fatigue syndrome (PVFS), chronic fatigue immune dysfunction syndrome (CFIDS), others[1]:20
Classification and external resources
Specialty Rheumatology
ICD-10 G93.3
ICD-9-CM 323.9 780.71
DiseasesDB 1645
MedlinePlus 001244
eMedicine med/3392 ped/2795
Patient UK Chronic fatigue syndrome
MeSH D015673

Chronic fatigue syndrome (CFS) is a medical condition characterized by long-term fatigue and other symptoms that limit a person's ability to carry out ordinary daily activities.[2][3] Quality of life of persons with CFS can be 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 person'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.[8][9] The medication rintatolimod may be useful for certain people.[8]

Estimates of the number of people with the condition vary from 7 to 3,000 per 100,000 adults.[5][10] About one million Americans and a quarter of a million people in the UK have CFS.[11][12] Fatigue is a common symptom in many illnesses, but the fatigue experienced by persons with CFS is comparatively rare.[10] CFS occurs more often in women than men,[13] and is less common among children and adolescents.[14] There is agreement that CFS has a negative effect on health, happiness and productivity but there is also controversy over many aspects of the disorder. Physicians, researchers and patient advocates promote different names[15] and diagnostic criteria, while evidence for proposed causes and treatments is often contradictory or of low quality.[16]

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, and heart and breathing problems.[17] 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.[18]


Gradual onset has been found to be most common, although large numbers of people self-report that onset was sudden.[1]:158 Studies suggest that critical life events, severe physical stressors, and perceived life difficulties may precipitate CFS.[17]


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:[19]

  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:[18]

The CDC proposes that persons with symptoms resembling those of CFS consult a physician to rule out several treatable illnesses: Lyme disease,[19] "sleep disorders, major depressive disorder, alcohol/substance abuse, diabetes, hypothyroidism, mononucleosis (mono), lupus, multiple sclerosis (MS), chronic hepatitis and various malignancies."[20] Medications can also cause side effects that mimic symptoms of CFS.[19]


Despite a common diagnosis the functional capacity of individuals with CFS varies greatly.[21] Some persons with CFS lead relatively normal lives; others are totally bed-ridden and unable to care for themselves.[22] For the majority of persons with CFS, work, school, and family activities are significantly reduced for extended periods of time.[18] The severity of symptoms and disability is the same in both genders,[23] and many experience strongly disabling chronic pain.[24] Persons report critical reductions in levels of physical activity.[25] Also, a reduction in the complexity of activity has been observed.[26] Reported impairment is comparable to other fatiguing medical conditions[27] including late-stage AIDS,[28] lupus, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), and end-stage renal disease.[18] 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][29]

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.[18]

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.[22]

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.[30]

Risk factors

All ethnic groups and income levels are susceptible to the illness. The CDC states that CFS is "at least as common" in African Americans and Hispanics as Caucasians.[31] 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.[32] 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.[13] CFS is less prevalent among children and adolescents than adults.[11] Blood relatives of people who have CFS appear to be more predisposed.[33] There is no direct evidence that CFS is contagious.[31]

A 2016 review proposed intestinal microbes as potential triggers of CFS.[34]


The pathophysiology of chronic fatigue syndrome is unknown. Potential causes have been proposed, including neurological factors, psychological or psychosocial factors or influences, infections, immunological factors, endocrine factors and genetic factors. No clinically meaningful risk factor has yet been identified.[35] CFS is associated with abnormal immunological response to exertion, reduced ability to recover from exertion,[1]:83 neuroendocrine abnormalities, reduced natural killer cell function,[1]:149 and forms of orthostatic intolerance including postural orthostatic tachycardia syndrome, neurally mediated hypotension, and orthostatic hypotension.[1]:107[36]

Autonomic nervous system

A 2014 review found a tentative association between autonomic nervous system dysfunction and CFS, fibromyalgia, irritable bowel syndrome, and interstitial cystitis.[37] It is unclear if their is a cause-effect relationship.[37]

One review found evidence of increased sleep latency, decreased sleep efficiency and decreased slow wave sleep in those with chronic fatigue syndrome, however the studies were not entirely consistent in their results.[38] The authors also suggested that the autonomic nervous system may play a role in disturbances.


Roles for viral and bacterial infections have been suggested for CFS and although CFS type symptoms can occur following severe infections, current data does not support the presence of an infectious process in maintaining the disease;[39] however, one of the most consistent findings in persons diagnosed with the illness is poor natural killer cell function. The reduction in natural killer cell function correlates with illness severity.[1]:149[40] Immunological factors including a chronic activation or suppression of the immune system may contribute to symptoms of CFS,[41] but they may not represent the entire picture.[42]

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 symptoms of post-exertional malaise.[43] Various cytokines have also been proposed to account for the abnormal response to exercise seen in those with CFS, such as increased lactate, decreased ATP and slower recovery.[44] Elevated levels of cytokines involved in generating sickness behavior have been found in those with CFS, however the results have not been consistent.[1][45]

Exercise recovery

Several studies have found that, despite meeting objective indicators of maximal effort during two cardiopulmonary exercise tests (CPET) 24 hours apart, patients with the illness have significantly lower results on CPET 2 than on CPET 1 on one or more of the following parameters: VO2 max, VO2 at ventilatory threshold, and maximal workload or workload at ventilatory threshold. In contrast, a single CPET may yield normal results. These findings appear to be specific to ME/CFS and provide objective evidence for the reduced ability to recover from exertion commonly reported by patients.[1]:83


Although there is a frequent comorbidity with psychiatric disorders, some evidence suggests that CFS is not a simple manifestation of an underlying psychiatric condition, but a multifactorial disease. Current data suggests that genetic, physiological and psychological factors work together to precipitate and perpetuate the illness.[5] People with CFS and their relatives tend to attribute their illness to physical causes (such as a virus or pollution) rather than to psychological causes.[5][46] Such attributions do not seem a risk factor for the development of CFS, but probably are associated with increased symptoms and worse outcomes over time.[5] Uncertainties about the causes, prognosis, diagnosis and treatment, and the lack of clinical guidance for healthcare professionals, aggravate the impact of the disease both in those affected and their caregivers.[47]


Evidence points to problems in the hypothalamic-pituitary-adrenal axis (HPA axis) that may include mild low cortisol levels, decrease in the variation of cortisol throughout the day, decreased responsiveness of the HPA axis, and a high serotonergic state. It is unclear whether or not this play a primary role in the cause of CFS[42][48][49] or has a secondary role in wosening or perpetuating symptoms later in the course of the illness.[50]


There are no characteristic laboratory abnormalities to diagnose CFS,[51] so testing is used to rule out other potential causes for symptoms.[52] 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.[53]


Notable definitions include:[17]

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).[3]

Differential diagnoses

Certain medical conditions can cause chronic fatigue and must be ruled out before a diagnosis of CFS can be given. Hypothyroidism, anemia,[56] coeliac disease (that can occur without gastrointestinal symptoms),[57] diabetes and certain psychiatric disorders are a few of the diseases that must be ruled out if the patient presents with appropriate symptoms.[3][52][56] 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).[56]

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.[58]

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 post exertional exacerbation of symptoms.[56]


There is no certain pharmacological treatment or cure for CFS[3] although various drugs have been or are being investigated.[59] A 2014 report prepared by the Agency for Healthcare Research and Quality stated that there are wide variations in the management of people, that many people receive a multifaceted approach to treatment and that no medications have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of ME/CFS, although several have been used off label. The report concluded that although counseling and graded exercise therapy (GET) have shown some benefits, these interventions have not been studied fully enough to recommend them for all people affected. The report expressed concern that GET appears to be associated with worsening symptoms in some.[60]

The United States Centres for Disease Control and Prevention(CDC) has a published guide for the management of CFS, the United Kingdom's National Institute for Health and Clinical Excellence(NICE) has a clinical guideline for the delivery of NHS care to people with CFS. The CDC guide covers treatment of symptoms, diet, activity management, counselling and exercise therapies, ongoing care and disability caused by CFS.[61] The NICE guideline is directed toward clinicians and specifies the need for shared decision-making between the patient and healthcare professionals with acknowledgement of the reality and impact of the condition and the symptoms. The NICE guideline covers illness management aspects of diet, sleep and sleep disorders, rest, relaxation, and pacing. Referral to specialist care for cognitive behavioural therapy, graded exercise therapy and activity management programmes is recommended to be offered as a choice to patients with mild or moderate CFS.[62]

Cognitive behavioral therapy

A 2014 National Institutes of Health report concluded that while counseling and behavior therapies could produce benefits for patients they may not yield improvement in quality of life and because of this limitation such therapies should not be considered as a primary treatment but rather should be used only as one component of a broader approach.[63] This same report stated that although counseling approaches have shown benefit in some measures of fatigue, function and overall improvement, these approaches have been inadequately studied in subgroups of the wider CFS patient population. Further concern was expressed that reporting of negative effects experienced by patients receiving counseling and behavior therapies had been poor.[60] A report by the Institute of Medicine published in 2015 states that it is unclear whether CBT helps to improve cognitive impairments experienced by patients.[1]:265

A 2008 Cochrane Review concluded that CBT did reduce the symptom of fatigue but noted that the benefits of CBT may diminish after the therapy is completed and that due to study limitations "the significance of these findings should be interpreted with caution".[16] A 2014 systematic review reported that there was only limited evidence that patients increased levels of physical activity after receiving CBT. The authors concluded that, as this finding is contrary to the cognitive behavioural model of CFS, patients receiving CBT were adapting to the illness rather than recovering from it.[64]

Patient organisations have long criticised the use of CBT as a treatment for CFS.[65] In 2012 the MEA commenced an extensive opinion survey of patients who had received a CBT treatment. Based on the finding of this survey, in 2015 the MEA concluded that CBT in its current form should not be recommended as a primary intervention for people with CFS[66] In a letter published online in the Lancet in 2016 Dr Charles Shepherd, medical advisor to the MEA expressed the view that the contention between patients and researchers lay in "a flawed model of causation that takes no account of the heterogeneity of both clinical presentations and disease pathways that come under the umbrella diagnosis of ME/CFS".[67]

Exercise therapy

A 2014 National Institutes of Health report concluded that while exercise therapy of the type known as graded exercise therapy (GET), could produce benefits, it may not yield improvement in quality of life and that because of this limitation GET should not be considered as a primary treatment but instead be used only as one component of a broader approach. The report also noted that a focus on exercise programs had discouraged patient participation in other types of physical activity due to concerns of precipitating increased symptoms.[63]

A 2016 Cochrane review, stated that exercise therapy could contribute to alleviation of some symptoms of CFS, especially fatigue. The Cochrane review also noted that research was inconclusive as to which, if any, type of exercise therapy was superior and concluded that no evidence had been found suggesting that exercise therapy worsened outcomes.[9]

As with CBT, patient organisations have long criticised the use of exercise therapy, most notably GET, as a treatment for CFS.[65] In 2012 the MEA commenced an extensive opinion survey of patients who had received GET. Based on the finding of this survey, in 2015 the MEA concluded that GET in its current delivered form should not be recommended as a primary intervention for people with CFS.[66]


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).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.[68]


People with CFS benefit from a well-balanced diet and eating regularly (eating little and often), including slow-release starchy foods in meals and snacks. Although elimination diets are not generally recommended, many people experience relief of CFS symptoms with these diets, including gastrointestinal complaints. To avoid the risk of malnutrition, they should be supervised by a dietitian.[62]


Antidepressants are mostly ineffective in treating CFS. Antiviral and immunological therapies provided some benefit but are limited by their side effects. Alternative treatments such as carnitine and and essential fatty acids show promising results.[69][70]


A systematic review 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).[71] 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.[72]


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.[10] The Centers for Disease Control reports that more than 1 million Americans have CFS and approximately 80% of the cases are undiagnosed.[11] Approximately 250,000 people in the UK are affected with the illness according to the National Health Service.[12]


Myalgic encephalomyelitis

From 1934 onwards, outbreaks of a previously unknown illness began to be recorded by doctors.[73][74] Initially considered to be occurrences of poliomyelitis, the illness was subsequently referred to as "epidemic neuromyasthenia".[74] In the 1950s, the term "benign myalgic encephalomyelitis" was used in relation to a comparable outbreak at the Royal Free Hospital in London.[75] The descriptions of each outbreak were varied but included symptoms of malaise, tender lymph nodes, sore throat, pain, and signs of encephalomyelitis.[76] The cause of the condition was not identified although it appeared to be infectious, and the term "benign myalgic encephalomyelitis" was chosen to reflect the lack of mortality, the severe muscular pains, evidence of damage to the nervous system, and to the presumed inflammatory nature of the disorder.[73] The syndrome appeared in sporadic as well as epidemic cases[77] and in 1969, benign myalgic encephalomyelitis appeared as an entry to the International Classification of Diseases under Diseases of the nervous system.[78]

The authors of a review of 15 outbreaks of benign myalgic encephalomyelitis, carried out in 1970, concluded that these were psychosocial phenomena caused by either mass hysteria on the part of the patients or altered medical perception of the community.[79] These conclusions were based on the higher prevalence of the disease in females in whom there was a lack of physical signs. On that basis, the authors recommended that the disease should be renamed "myalgia nervosa". Despite strong refutation by Dr. Melvin Ramsay, the proposed psychological etiology created great controversy and convinced health professionals that this was a plausible explanation for the condition.[80]

The continued work of Ramsay demonstrated that, although the disease rarely resulted in mortality, it was often severely disabling.[1]:28–29 Because of this, Ramsay proposed that the prefix "benign" be dropped.[75][81][82] In 1986, Ramsay published the first diagnostic criteria for ME, in which the condition was characterized by:

Chronic fatigue syndrome

In the mid-1980s, two large outbreaks of an illness which resembled mononucleosis drew national attention in the United States. Located in Nevada and New York, the outbreaks involved an illness which was characterized by "chronic or recurrent debilitating fatigue and various combinations of other symptoms, including a sore throat, lymph node pain and tenderness, headache, myalgia, and arthralgias". An initial link to the Epstein-Barr virus saw the illness acquire the name "chronic Epstein-Barr virus syndrome".[1]:29[54]

The United States Centers for Disease Control and Prevention convened a working group tasked with reaching a consensus on the clinical features of the illness. Meeting in 1987, the working group concluded that CFS was not new and that the many different names given to it previously reflected widely differing concepts of the illness's etiology and epidemiology.[84] The CDC working group chose "chronic fatigue syndrome" as a more neutral and inclusive name for the illness but noted that "myalgic encephalomyelitis" was widely accepted in other parts of the world.[54] The first definition of CFS was published in 1988 and although the cause of the illness remained unknown, there were several attempts to update this definition, most notably in 1994.[52] In 2006, the CDC commenced a national program to educate the American public and health care professionals about CFS.[85]

Other medical terms

A range of both theorised and confirmed medical entities and naming conventions have appeared historically in the medical literature dealing with ME and CFS, these include:

Society and culture


Many names have been proposed for the illness, currently, the most commonly used are "chronic fatigue syndrome", "myalgic encephalomyelitis", and the umbrella term "ME/CFS". Reaching consensus on a name is challenging because the etiology and pathology remain unknown.[1]:29–30

The term "chronic fatigue syndrome" has been criticized by patients as being both stigmatizing and trivializing, and which in turn prevents the illness from being seen as a serious health problem that deserves appropriate research.[93] While many patients prefer "myalgic encephalomyelitis", which they believe better reflects the medical nature of the illness,[83][94] there is resistance amongst clinicians toward the use of myalgic encephalomyelitis on the grounds that the inflammation of the central nervous system (myelitis) implied by the term has not been demonstrated.[2][95]

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).[1][96]

Economic impact

Reynolds et al. (2004)[97] 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.[98] This is comparable to other chronic illnesses that extract some of the biggest medical and socioeconomic costs.[53] A 2008 study[99] calculated that the total annual cost burden of ME/CFS to society in the US was extensive, and could approach $24.0 billion.[100]

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."[101]

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.[102][103][104] There has been much disagreement over proposed causes, diagnosis, and treatment of the illness.[105][106][107][108][109] 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.[110]

From the patient perspective, one 1997 study found that 77% of individuals with CFS reported negative experiences with health care providers.[4] 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.[111] 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.[104][112]

Blood donation

Based on concern following claims of a link,[113] subsequently shown to be unfounded, between CFS and a retrovirus, 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,[114] the New Zealand Blood Service,[115] the Australian Red Cross Blood Service[116] and the American Association of Blood Banks,[117] 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.[118] 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."[119]


There has been much contention over the etiology, pathophysiology,[35] nomenclature,[120] and diagnostic criteria of chronic fatigue syndrome.[105][106] 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.[103][104][121] Controversies still exist about whether funding should be directed towards biomedical or psychological/psychosocial research.[122]

In 2009, the journal Science[113] published a study that identified the XMRV retrovirus in a population of people with CFS. Other studies failed to reproduce this finding,[123][124][125] and in 2011, the editor of Science formally retracted its XMRV paper[126] 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.[127]

Media treatment of CFS has often been controversial; in November 1990 the magazine Newsweek ran a cover story on CFS which although supportive of an organic cause of the illness also featured the term Yuppie Flu. Reflecting a stereotype that CFS mainly affected yuppies, the implication was that CFS was a form of burnout.[128] Use of the term Yuppie flu is considered offensive both by patients and clinicians.[31][129]

Research funding

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,[130] 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.[131] 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.[132]

In the UK, there has been controversy surrounding psychologically-oriented models of the disease and behavioral treatments.[133][134][135][136]

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.[137]


The different case definitions used to research the illness influence the types of patients selected for studies,[51] and research also suggests subtypes of patients may exist within a heterogeneous population.[98][138][139][140] In one of the definitions, symptoms are accepted that may suggest a psychiatric disorder while others specifically exclude primary psychiatric disorders.[17] 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".[1]:72


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