Chronic fatigue syndrome
|Chronic fatigue syndrome|
|Classification and external resources|
|NCI||Chronic fatigue syndrome|
|Patient UK||Chronic fatigue syndrome|
Chronic fatigue syndrome (CFS) is the common name for a group of significantly debilitating medical conditions characterized by persistent fatigue and other specific symptoms that lasts for a minimum of six months in adults (and 3 months in children or adolescents). The fatigue is not due to exertion, not significantly relieved by rest, and is not caused by other medical conditions. CFS may also be referred to as myalgic encephalomyelitis (ME), post-viral fatigue syndrome (PVFS), chronic fatigue immune dysfunction syndrome (CFIDS), or by several other terms. Biological, genetic, infectious and psychological mechanisms have been proposed, but the etiology of CFS is not understood and it may have multiple causes.
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, and other characteristic symptoms in a previously healthy and active person. Additional symptoms may be reported, including muscle weakness, increased sensitivity to light, sounds and smells, orthostatic intolerance, digestive disturbances, depression, painful and often slightly swollen lymph nodes, cardiac and respiratory problems. It is unclear if these symptoms represent co-morbid conditions or if they are produced by an underlying etiology of CFS. CFS symptoms vary in number, type, and severity from person to person. Quality of life of persons with CFS can be extremely compromised.
Fatigue is a common symptom in many illnesses, but CFS is comparatively rare. Estimates of prevalence vary from 7 to 3,000 cases of CFS for every 100,000 adults; national health organizations have estimated more than one million Americans and approximately a quarter of a million people in the UK have CFS. CFS occurs more often in women than men, and is less prevalent among children and adolescents.
Although there is agreement that CFS poses genuine threats to health, happiness and productivity, various physicians' groups, researchers and patient advocates promote differing nomenclatures, diagnostic criteria, etiologic hypotheses 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.
- 1 Classification
- 2 Signs and symptoms
- 3 Pathophysiology
- 4 Diagnosis
- 5 Treatment
- 6 Prognosis
- 7 Epidemiology
- 8 History
- 9 Research funding
- 10 Society and culture
- 11 References
- 12 Further reading
- 13 External links
Notable definitions include:
- Centers for Disease Control and Prevention (CDC) definition (1994), the most widely used clinical and research description of CFS, is also called the Fukuda definition and is based on the Holmes or CDC 1988 scoring system. The 1994 criteria require the presence of four or more symptoms beyond fatigue, while the 1988 criteria require six to eight.
- The Oxford criteria (1991) include CFS of unknown etiology and a subtype called post-infectious fatigue syndrome (PIFS). Important differences are that the presence of mental fatigue is necessary to fulfill the criteria and symptoms are accepted that may suggest a psychiatric disorder.
- The 2003 Canadian Clinical working definition 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 will persist for at least 6 months]".
The different case definitions used to research the illness may influence the types of patients selected for studies, and research also suggests subtypes of patients exist within the heterogeneous illness.
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).
Chronic fatigue syndrome is the most commonly used designation, but widespread approval of a name is lacking. 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.
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). 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.
A 2001 review referenced myalgic encephalomyelitis symptoms in a 1959 article by Acheson, stating ME could be a distinct syndrome from CFS, but in literature the two terms are generally seen as synonymous. 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." 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. In 2002, a Lancet commentary noted the recent report by the "Working Group on CFS/ME" 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."
Signs and symptoms
The majority of CFS cases start suddenly, usually accompanied by a "flu-like illness" while a significant proportion of cases begin within several months of severe adverse stress. An Australian prospective study found that after infection by viral and non-viral pathogens, a sub-set 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". However, accurate prevalence and exact roles of infection and stress in the development of CFS are currently unknown.
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). The CDC recommends the following three criteria be fulfilled:
- 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.
- The fatigue causes a significant reduction of previous activity levels.
- Four or more of the following symptoms that 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)
- headaches of a new kind or greater severity
- sore throat, frequent or recurring
- tender lymph nodes (cervical or axillary)
The CDC states other common symptoms include the following:
- 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 (sensitivity to light, blurring, eye pain)
- 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, "sleep disorders, major depressive disorder, alcohol/substance abuse, diabetes, hypothyroidism, mononucleosis (mono), lupus, multiple sclerosis (MS), chronic hepatitis and various malignancies." Medications can also cause side effects that mimic symptoms of CFS.
Unlike the CDC's diagnostic criteria, the International Consensus Criteria 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."
Despite a common diagnosis the functional capacity of individuals with CFS varies greatly. Some persons with CFS lead relatively normal lives; others are totally bed-ridden and unable to care for themselves. For the majority of persons with CFS, work, school, and family activities are significantly reduced for extended periods of time. The severity of symptoms and disability is the same in both genders, and many experience strongly disabling chronic pain. Persons report critical reductions in levels of physical activity. Also, a reduction in the complexity of activity has been observed. Reported impairment is comparable to other fatiguing medical conditions including late-stage AIDS, lupus, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), and end-stage renal disease. 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.
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.
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.
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.
The etiology and pathogenesis (i.e., the causes and mechanisms) of chronic fatigue syndrome are currently unknown, despite extensive research. Research studies have developed and explored etiological hypotheses regarding a variety of factors, including oxidative stress, genetic predisposition, 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.
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.
There are no characteristic laboratory abnormalities to diagnose CFS, so testing is used to rule out other potential causes for symptoms. 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.
Many people do not fully recover from CFS even with treatment. Cognitive behavioural therapy (CBT) and graded exercise therapy (GET) have shown moderate effectiveness for many people in multiple randomized controlled trials. As many of the CBT and GET studies required visits to a clinic, those severely affected may not have been included. Two large surveys of patients indicated that pacing is a helpful intervention, or is considered useful by 82-96% of participants. A comprehensive rehabilitation programme only rarely results in full recovery. Medication plays a minor role in management. No intervention has been proven effective in restoring the ability to work.
Cognitive behavioral therapy
Cognitive behavioral therapy is a moderately effective psychological therapy when used to treat CFS. It is often used alone or with other therapies to "manage activity levels, stress, and symptoms." 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.
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. 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.
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. 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.
CBT has been criticised by patients' organisations because multiple patient surveys of their members 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.
Graded exercise therapy
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. A systematic review published in 2006 included the same five RCTs, noting that "no severely affected patients were included in the studies of GET". 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".
Surveys conducted on behalf of patient organizations find adverse effects to be very common. 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.
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. Some programmes combine symptom and time-contingent approaches. A trial of one such programme reported limited benefits. A larger, randomised controlled trial found that pacing had statistically better results than relaxation/flexibility therapy. A 2009 survey of 828 Norwegian CFS patients found that pacing was evaluated as useful by 96% of the participants.
Other treatments of CFS have been proposed but their effectiveness has not been confirmed. Medications thought to have promise in alleviating symptoms include antidepressant and immunomodulatory agents. The evidence for antidepressants is mixed, and their use remains controversial. Many CFS patients are sensitive to medications, particularly sedatives, and some patients report chemical and food sensitivities. CFS patients have a low placebo response, especially to psychological-psychiatric interventions, perhaps due to patient expectations.
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, a sense of control over symptoms and not attributing illness to a physical cause. 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.
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.
A 2003 review states that studies have reported between 7 and 3,000 cases of CFS for every 100,000 adults. 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. The Centers for Disease Control reports that more than 1 million Americans have CFS and approximately 80% of the cases are undiagnosed. Approximately 250,000 people in the UK are affected with the illness according to the National Health Service.
All ethnic and racial groups appear susceptible to the illness, and lower income groups are slightly more likely to develop CFS. A 2009 meta-analysis showed that compared with the White American majority, African Americans and Native Americans have a significantly higher risk of CFS. 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. CFS is less prevalent among children and adolescents than adults. Blood relatives of people who have CFS appear to be more predisposed. There is no direct evidence that CFS is contagious.
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. 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."
Certain medical conditions can cause chronic fatigue and must be ruled out before a diagnosis of CFS can be given. Hypothyroidism, anemia, diabetes and certain psychiatric disorders are a few of the diseases that must be ruled out if the patient presents with appropriate symptoms.
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. 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.
A 2006 review found that there was a lack of literature to establish the discriminant validity of undifferentiated somatoform disorder from CFS. The author stated that there is a need for proponents of chronic fatigue syndrome to distinguish it from undifferentiated somatoform disorder. The author also mentioned that the experience of fatigue as exclusively physical and not mental is captured by the definition of somatoform disorder but not CFS. Hysterical diagnoses are not merely diagnoses of exclusion but require criteria to be met on the positive grounds of both primary and secondary gain.
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.
Many CFS patients will also have, or appear to have, other medical problems or related diagnoses. Co-morbid fibromyalgia is common. Fibromyalgia occurs in a large percentage of CFS patients between onset and the second year, and some researchers suggest fibromyalgia and CFS are related. 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. 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. CFS is significantly more common in women with endometriosis compared with women in the general USA population.
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 beyond six months.) Of note are the neurological symptoms, the link with a polio outbreak and the fact that most of the patients were hospital staff  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. 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.
The name chronic fatigue syndrome was used in the medical literature in 1987 to describe a condition resembling "chronic active Epstein-Barr virus (EBV) infection" but which presented no evidence of 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 patients at the Lake Tahoe outbreak. In 2006, the CDC commenced a national program to educate the American public and health care professionals about CFS.
A 2009 study published in the journal Science reported an association between a retrovirus xenotropic murine leukemia virus-related virus (XMRV) and CFS. The editors of Science subsequently attached an "Editorial Expression of Concern" to the report to the effect that the validity of the study "is now seriously in question". and in September 2011, the authors published a "Partial Retraction" of their 2009 findings, this was followed by a full retraction by the magazine’s Editor in Chief after the authors failed to agree on a full retraction statement. Also in September 2011, the Blood XMRV Scientific Research Working Group published a report which concluded "that currently available XMRV/P-MLV assays, including the assays employed by the three participating laboratories that previously reported positive results on samples from CFS patients and controls (2, 4), cannot reproducibly detect direct virus markers (RNA, DNA, or culture) or specific antibodies in blood samples from subjects previously characterized as XMRV/P-MLV positive (all but one with a diagnosis of CFS) or healthy blood donors." In December 2011, the Proceedings of the National Academy of Sciences published a similar retraction for an August 2010 paper.
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, 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 support for 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. 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.
Society and culture
Reynolds et al. (2004) 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. This is comparable to other chronic illnesses that extract some of the biggest medical and socioeconomic costs. A 2008 study calculated that the total annual cost burden of ME/CFS to society in the US was extensive, and could approach $24.0 billion.
A study found that CFS patients report a heavy psychosocial burden. 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.
A study found that CFS patients in support groups reported no change in negative interactions compared to an improvement in negative interactions reported by those treated with Cognitive Behavioural Therapy. Patients with greater amounts of negative interactions received worse social support on average than disease-free cancer patients or healthy controls which, in turn, led to greater fatigue severity and functional impairment than CBT-treated patients.
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."
Some in the medical community do not recognize CFS as a real condition, nor is there agreement on its prevalence. There has been much disagreement over proposed causes, diagnosis, and treatment of the illness. The context of contested causation may affect the lives of the individuals diagnosed with CFS, affecting the patient-doctor relationship, the doctor's confidence in their ability to diagnose and treat, ability to share issues and control in diagnosis with the patient, and raise problematic issues of reparation, compensation, and blame. Disagreements over how the condition is dealt with by health-care systems have resulted in an expensive and prolonged conflict for all involved.
A major divide exists over whether funding for research and treatment should focus on physiological, psychological, or psychosocial aspects of CFS. This division is especially great between patient groups and psychological and psychosocial treatment advocates in Great Britain. In 2011, it was reported by the BBC that this conflict had involved personal vilification and allegations of professional misconduct to professional societies and universities of researchers who were investigating possible psychiatric connections. One of these researchers, Simon Wessely, reported personal death threats. Virologist Myra McClure stated she was subjected to horrible abuse from extremists after publishing a paper indicating that early studies suggesting a link between CFS and the XMRV virus were flawed. As a result, she decided not to pursue any further research into CFS. Pediatrician Esther Crawley changed her phone number and talked to the police. Wellcome Trust's then director Mark Walport indicated good research is needed to understand the illness, but it would be tragic if serious researchers are dissuaded from working on it. He further stated, "But why would any scientist work on it if they know that all they're going to receive is a torrent of abuse?" The ME Association's Charles Shepherd stated the abuse of researchers was unacceptable, but that patients had a justifiable complaint that almost no UK government funds are devoted to biomedical research for the illness.
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, the New Zealand Blood Service, the Australian Red Cross Blood Service and the American Association of Blood Banks, In November 2010, the UK National Blood Service introduced a permanent deferral of donation from CFS patients based on the potential harm to those patients that may result from their giving blood.
There has been much contention over the etiology, pathophysiology, nomenclature, and diagnostic criteria of chronic fatigue syndrome. Controversies still exist over funding for research and treatment of physiological versus psychological and psychosocial aspects of the illness. 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. Contrasting viewpoints among CFS experts became apparent in 1993, when psychiatrists David and Wessely contested the WHO classification of CFS under diseases of the nervous system, arguing that it was a form of neurasthenia to be classified as a psychiatric condition.
- Evengård B, Schacterle RS, Komaroff AL (Nov 1999). "Chronic fatigue syndrome: new insights and old ignorance". Journal of Internal Medicine 246 (5): 455–469. doi:10.1046/j.1365-2796.1999.00513.x. PMID 10583715. Retrieved 2009-10-21.
- Guideline 53: Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy). London: National Institute for Health and Clinical Excellence. 2007. ISBN 1-84629-453-3.
- "Chronic Fatigue Syndrome: Case Definition". CDC. 2006-05-03. Retrieved 2009-01-22.
- Sanders P, Korf J (2008). "Neuroaetiology of chronic fatigue syndrome: an overview". World J. Biol. Psychiatry 9 (3): 165–71. doi:10.1080/15622970701310971. PMID 17853290.
- Afari N, Buchwald D (2003). "Chronic fatigue syndrome: a review". Am J Psychiatr 160 (2): 221–36. doi:10.1176/appi.ajp.160.2.221. PMID 12562565.
- "Chronic Fatigue Syndrome Causes". Centers for Disease Control and Prevention. October 15, 2010. Retrieved 2012-12-20.
- Wyller VB (2007). "The chronic fatigue syndrome--an update". Acta neurologica Scandinavica. Supplementum 187: 7–14. doi:10.1111/j.1600-0404.2007.00840.x. PMID 17419822.
- "Chronic Fatigue Syndrome (CFS), Symptoms". Centers for Disease Control and Prevention. 2012-05-14. Retrieved 2012-09-23.
- Anderson JS, Ferrans CE (June 1997). "The quality of life of persons with chronic fatigue syndrome". J Nerv Ment Dis 185 (6): 359–67. doi:10.1097/00005053-199706000-00001. PMID 9205421.
- Ranjith G (2005). "Epidemiology of chronic fatigue syndrome". Occup Med (Lond) 55 (1): 13–29. doi:10.1093/occmed/kqi012. PMID 15699086.
- "Chronic Fatigue Syndrome Basic Facts". Centers for Disease Control and Prevention. May 9, 2006. Retrieved 2008-02-07.
- "Chronic fatigue syndrome". The National Health Service. 2009-06-29. Retrieved 2010-05-14.
- Gallagher AM, Thomas JM, Hamilton WT, White PD (2004). "Incidence of fatigue symptoms and diagnoses presenting in UK primary care from 1990 to 2001". J R Soc Med 97 (12): 571–5. doi:10.1258/jrsm.97.12.571. PMC 1079668. PMID 15574853.
- "Chronic Fatigue Syndrome Who's at risk?". Centers for Disease Control and Prevention. February 14, 2013. Retrieved 2013-09-25.
- Ottati, Victor C. (2002). The social psychology of politics. New York: Kluwer Academic/Plenum. pp. 159–160. ISBN 0-306-46723-2. Retrieved 2009-08-11.
- Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A (15 Dec 1994). "The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group". Ann Intern Med 121 (12): 953–9. doi:10.1059/0003-4819-121-12-199412150-00009 (inactive 2014-03-23). PMID 7978722.
- Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, Jones JF, Dubois RE, Cunningham-Rundles C, Pahwa S (1988). "Chronic fatigue syndrome: a working case definition". Ann Intern Med 108 (3): 387–9. doi:10.7326/0003-4819-108-3-387. PMID 2829679.
- Sharpe MC, Archard LC, Banatvala JE, Borysiewicz LK, Clare AW, David A, Edwards RH, Hawton KE, Lambert HP, Lane RJ (1991). "A report- chronic fatigue syndrome: guidelines for research". J R Soc Med 84 (2): 118–21. PMC 1293107. PMID 1999813. Synopsis by Oxford criteria for the diagnosis of chronic fatigue syndrome at GPnotebook
- Carruthers BM, Jain AK, De Meirleir KL, Peterson DL, Klimas NG, et al. (2003). "Myalgic encephalomyalitis/chronic fatigue syndrome: Clinical working definition, diagnostic and treatment protocols" (PDF). Journal of Chronic Fatigue Syndrome 11 (1): 7–97. doi:10.1300/J092v11n01_02.
- Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER (2003). "Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution". BMC Health Serv Res 3 (1): 25. doi:10.1186/1472-6963-3-25. PMC 317472. PMID 14702202.
- Jason LA, Corradi K, Torres-Harding S, Taylor RR, King C (March 2005). "Chronic fatigue syndrome: the need for subtypes". Neuropsychol Rev 15 (1): 29–58. doi:10.1007/s11065-005-3588-2. PMID 15929497.
- Whistler T, Unger ER, Nisenbaum R, Vernon SD (December 2003). "Integration of gene expression, clinical, and epidemiologic data to characterize Chronic Fatigue Syndrome". J Transl Med 1 (1): 10. doi:10.1186/1479-5876-1-10. PMC 305360. PMID 14641939.
- Kennedy G, Abbot NC, Spence V, Underwood C, Belch JJ (February 2004). "The specificity of the CDC-1994 criteria for chronic fatigue syndrome: comparison of health status in three groups of patients who fulfill the criteria". Ann Epidemiol 14 (2): 95–100. doi:10.1016/j.annepidem.2003.10.004. PMID 15018881.
- Aslakson E, Vollmer-Conna U, White PD (April 2006). "The validity of an empirical delineation of heterogeneity in chronic unexplained fatigue". Pharmacogenomics 7 (3): 365–73. doi:10.2217/146224184.108.40.2065. PMID 16610947.
- Clark C, Buchwald D, MacIntyre A, Sharpe M, Wessely S (January 2002). "Chronic fatigue syndrome: a step towards agreement". Lancet 359 (9301): 97–8. doi:10.1016/S0140-6736(02)07336-1. PMID 11809249.
- NORD (June 23, 2008). "Chronic Fatigue Syndrome/Myalgic Encephalomyelitis". National Organization for Rare Disorders, Inc. Retrieved 2008-07-01.
- Donoghue, PJ; Siegel ME (1992). Sick And Tired Of Feeling Sick And Tired: Living with Invisible Chronic Illness. W. W. Norton & Company. p. 15. ISBN 0-393-03408-9. Retrieved 2008-09-17.
- Sharpe M (2002). "The report of the Chief Medical Officer's CFS/ME working group: what does it say and will it help?". Clin Med 2 (5): 427–9. doi:10.7861/clinmedicine.2-5-427. PMID 12448589.
- Tuller, David (2008-05-30). "Chronic Fatigue Syndrome No Longer Seen as 'Yuppie Flu'". The New York Times. Retrieved 2013-02-26.
- Whiting P, Bagnall AM, Sowden AJ, Cornell JE, Mulrow CD, Ramírez G (September 2001). "Interventions for the treatment and management of chronic fatigue syndrome: a systematic review". JAMA 286 (11): 1360–8. doi:10.1001/jama.286.11.1360. PMID 11560542.
- Royal Colleges of Physicians, Psychiatrists and General Practitioners (1996). Chronic fatigue syndrome; Report of a joint working group of the Royal Colleges of Physicians, Psychiatrists and General Practitioners. London, UK: Royal College of Physicians of London. ISBN 1-86016-046-8.
- "Frustrating survey of chronic fatigue". Lancet 348 (9033): 971. Oct 1996. doi:10.1016/S0140-6736(05)64917-3. PMID 8855845.
- Working Party on CSF/ME (January 2002). "Report of the Working Party on CSF/ME to the Chief Medical Officer for England and Wales" (PDF). Department of Health. Archived from the original on 2003-03-22. Retrieved 2009-01-25.
- Salit IE (1997). "Precipitating factors for the chronic fatigue syndrome". J Psychiatr Res 31 (1): 59–65. doi:10.1016/S0022-3956(96)00050-7. PMID 9201648.
- Hatcher S, House A (2003). "Life events, difficulties and dilemmas in the onset of chronic fatigue syndrome: a case-control study" (PDF). Psychol Med 33 (7): 1185–92. doi:10.1017/S0033291703008274. PMID 14580073.
- Theorell T, Blomkvist V, Lindh G, Evengård B (1999). "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". Psychosom Med. 61 (3): 304–10. doi:10.1097/00006842-199905000-00009. PMID 10367610.
- Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A (2006). "Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study". BMJ 333 (7568): 575. doi:10.1136/bmj.38933.585764.AE. PMC 1569956. PMID 16950834.
- "CDC - Chronic Fatigue Syndrome (CFS) - Diagnosis". Cdc.gov. Retrieved 2012-07-22.
- "CDC, Chronic Fatigue Syndrome (CFS), Making a Diagnosis". Cdc.gov. Retrieved 2011-01-28.
- "Myalgic encephalomyelitis: International Consensus Criteria". Journal of Internal Medicine 270 (4). Aug 2011. pp. 327–338. doi:10.1111/j.1365-2796.2011.02428.x.
- Vanness JM, Snell CR, Strayer DR, Dempsey L, Stevens SR (2003). "Subclassifying chronic fatigue syndrome through exercise testing". Med Sci Sports Exerc 35 (6): 908–13. doi:10.1249/01.MSS.0000069510.58763.E8. PMID 12783037.
- Ross SD, Estok RP, Frame D, Stone LR, Ludensky V, Levine CB (2004). "Disability and chronic fatigue syndrome: a focus on function". Arch Intern Med 164 (10): 1098–107. doi:10.1001/archinte.164.10.1098. PMID 15159267.
- Ho-Yen DO, McNamara I (1991). "General practitioners' experience of the chronic fatigue syndrome". Br J Gen Pract 41 (349): 324–6. PMC 1371754. PMID 1777276.
- Meeus M, Nijs J, Meirleir KD (2007). "Chronic musculoskeletal pain in patients with the chronic fatigue syndrome: A systematic review". Eur J Pain 11 (4): 377–386. doi:10.1016/j.ejpain.2006.06.005. PMID 16843021.
- McCully KK, Sisto SA, Natelson BH (1996). "Use of exercise for treatment of chronic fatigue syndrome". Sports Med 21 (1): 35–48. doi:10.2165/00007256-199621010-00004. PMID 8771284.
- Burton C, Knoop H, Popovic N, Sharpe M, Bleijenberg G (June 2009). "Reduced complexity of activity patterns in patients with Chronic Fatigue Syndrome: a case control study". Biopsychosoc Med 3 (1): 7. doi:10.1186/1751-0759-3-7. PMC 2697171. PMID 19490619.
- Solomon L, Nisenbaum R, Reyes M, Papanicolaou DA, Reeves WC (2003). "Functional status of persons with chronic fatigue syndrome in the Wichita, Kansas, population". Health Qual Life Outcomes 1 (1): 48–58. doi:10.1186/1477-7525-1-48. PMC 239865. PMID 14577835.
- 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
- Komaroff AL, Fagioli LR, Doolittle TH, Gandek B, Gleit MA, Guerriero RT, Kornish RJ, Ware NC, Ware JE, Bates DW (September 1996). "Health status in patients with chronic fatigue syndrome and in general population and disease comparison groups". Am. J. Med. 101 (3): 281–90. doi:10.1016/S0002-9343(96)00174-X. PMID 8873490.
- Cockshell SJ, Mathias JL (January 2010). "Cognitive functioning in chronic fatigue syndrome: a meta-analysis". Psychol Med 40 (8): 1–15. doi:10.1017/S0033291709992054. PMID 20047703.
- Sanders P, Korf J (2008). "Neuroaetiology of chronic fatigue syndrome: an overview". World Journal of Biological Psychiatry 9 (3): 165–71. doi:10.1080/15622970701310971. PMID 17853290.
- Patarca-Montero R, Antoni M, Fletcher MA, Klimas NG (2001). "Cytokine and other immunologic markers in chronic fatigue syndrome and their relation to neuropsychological factors". Appl Neuropsychol 8 (1): 51–64. doi:10.1207/S15324826AN0801_7. PMID 11388124.
- Kuratsune H (June 2007). "[Overview of chronic fatigue syndrome focusing on prevalence and diagnostic criteria]". Nippon Rinsho (in Japanese) 65 (6): 983–90. PMID 17561686.
- Vercoulen JH, Swanink CM, Galama JM, Fennis JF, Jongen PJ, Hommes OR, van der Meer JW, Bleijenberg G (1998). "The persistence of fatigue in chronic fatigue syndrome and multiple sclerosis: development of a model". J Psychosom Res 45 (6): 507–17. doi:10.1016/S0022-3999(98)00023-3. PMID 9859853.
- Papadopoulos, Andrew S.; Cleare, Anthony J. (27 September 2011). "Hypothalamic–pituitary–adrenal axis dysfunction in chronic fatigue syndrome". Nature Reviews Endocrinology 8 (1): 22–32. doi:10.1038/nrendo.2011.153.
- 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 (2009). "Chronic fatigue syndrome: aetiology, diagnosis and treatment". BMC Psychiatry. 9 Suppl 1: S1. doi:10.1186/1471-244X-9-S1-S1. PMC 2766938. PMID 19857242.
- Rimes KA, Chalder T (2005). "Treatments for chronic fatigue syndrome". Occupational Medicine 55 (1): 32–39. doi:10.1093/occmed/kqi015. PMID 15699088.
- Chambers D, Bagnall AM, Hempel S, Forbes C (2006). "Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review". Journal of the Royal Society of Medicine 99 (10): 506–20. doi:10.1258/jrsm.99.10.506. PMC 1592057. PMID 17021301.
- Raine R, Haines A, Sensky T, Hutchings A, Larkin K, Black N (2002). "Systematic review of mental health interventions for patients with common somatic symptoms: can research evidence from secondary care be extrapolated to primary care?". BMJ 325 (7372): 1082. doi:10.1136/bmj.325.7372.1082. PMC 131187. PMID 12424170.
- Reid S, Chalder T, Cleare A, Hotopf M, Wessely S (2000). "Chronic fatigue syndrome". BMJ 320 (7230): 292–6. doi:10.1136/bmj.320.7230.292. PMC 1117488. PMID 10650029.
- "Survey Summary Report 2008" (PDF). Action for ME. 2008. p. 13. Retrieved 12 October 2013.
- Bjørkum T, Wang CE, Waterloo K (June 2009). "Pasienterfaringer med ulike tiltak ved kronisk utmattelsessyndrom" [Patients' experience with treatment of chronic fatigue syndrome]. Tidsskrift for Den norske legeforening (in Norwegian) 129 (12): 1214–6. doi:10.4045/tidsskr.09.35791. PMID 19521443.
- Van Cauwenbergh D, De Kooning M, Ickmans K, Nijs J (2012). "How to exercise people with chronic fatigue syndrome: evidence-based practice guidelines.". Eur J Clin Invest 42 (10): 1136–4. doi:10.1111/j.1365-2362.2012.02701.x. PMID 22725992.
- Van Houdenhove B, Pae CU, Luyten P (February 2010). "Chronic fatigue syndrome: is there a role for non-antidepressant pharmacotherapy?". Expert opinion on pharmacotherapy 11 (2): 215–23. doi:10.1517/14656560903487744. PMID 20088743.
- "Improving Health and Quality of Life". Centers for Disease Control and Prevention. February 14, 2013. Retrieved 12 October 2013.
- Wolfe F; Chalmers A; Littlejohn GO & Salit I (1995). Fibromyalgia, Chronic Fatigue Syndrome, and Repetitive Strain Injury: Current Concepts in Diagnosis, Management, Disability, and Health Economics. New York: Haworth Medical Press. p. 142. ISBN 1-56024-744-4.
- Price JR, Mitchell E, Tidy E, Hunot V (2008). Price, Jonathan R, ed. "Cognitive behaviour therapy for chronic fatigue syndrome in adults". Cochrane Database Syst Rev (3): CD001027. doi:10.1002/14651858.CD001027.pub2. PMID 18646067.
- Malouff JM, Thorsteinsson EB, Rooke SE, Bhullar N, Schutte NS (June 2008). "Efficacy of cognitive behavioral therapy for chronic fatigue syndrome: a meta-analysis". Clin Psychol Rev 28 (5): 736–45. doi:10.1016/j.cpr.2007.10.004. PMID 18060672.
- Wiborg JF, Knoop H, Stulemeijer M, Prins JB, Bleijenberg G (January 2010). "How does cognitive behaviour therapy reduce fatigue in patients with chronic fatigue syndrome? The role of physical activity". Psychol Med 40 (8): 1–7. doi:10.1017/S0033291709992212. PMID 20047707.
- Adamowicz JL, Caikauskaite I, Friedberg F (Nov 2014). "Defining recovery in chronic fatigue syndrome: a critical review". Qual Life Res. 23 (9): 2407–16. doi:10.1007/s11136-014-0705-9. PMID 24791749.
- White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R (2007). "Protocol for the PACE trial: A randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy". BMC Neurol 7: 6. doi:10.1186/1471-2377-7-6. PMC 2147058. PMID 17397525.
- Twisk FN, Maes M (2009). "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". Neuro Endocrinol. Lett. 30 (3): 284–99. PMID 19855350.
- Edmonds M, McGuire H, Price J (2004). Price, Jonathan R, ed. "Exercise therapy for chronic fatigue syndrome". Cochrane Database Syst Rev (3): CD003200. doi:10.1002/14651858.CD003200.pub2. PMID 15266475.
- Clark C, Buchwald D, MacIntyre A, Sharpe M, Wessely S (2002). "Chronic fatigue syndrome: a step towards agreement". Lancet 359 (9301): 97–8. doi:10.1016/S0140-6736(02)07336-1. PMID 11809249.
- Bjørkum T, Wang CE, Waterloo K (June 2009). "Patients' experience with treatment of chronic fatigue syndrome". Tidsskr nor Laegeforen 129 (12): 1214–6. doi:10.4045/tidsskr.09.35791. PMID 19521443.
- Working Party on CFS/ME (January 2002). "Report of the Working Party on CFS/ME to the Chief Medical Officer for England and Wales". Department of Health. Archived from the original on 2012-01-07.
- Nijs J, Paul L, Wallman K (April 2008). "Chronic fatigue syndrome: an approach combining self-management with graded exercise to avoid exacerbations". J Rehabil Med 40 (4): 241–7. doi:10.2340/16501977-0185. PMID 18382818.
- Goudsmit EM, Nijs J, Jason LA, Wallman KE (19 December 2011). "Pacing as a strategy to improve energy management in myalgic encephalomyelitis/chronic fatigue syndrome: a consensus document". Disability and Rehabilitation. Early Online (13): 1–8. doi:10.3109/09638288.2011.635746. PMID 22181560.
- Wallman KE, Morton AR, Goodman C, Grove R, Guilfoyle AM (May 2004). "Randomised controlled trial of graded exercise in chronic fatigue syndrome". Med. J. Aust. 180 (9): 444–8. PMID 15115421.
- Nijs J, Meeus M, De Meirleir K (August 2006). "Chronic musculoskeletal pain in chronic fatigue syndrome: recent developments and therapeutic implications". Man Ther. 11 (3): 187–91. doi:10.1016/j.math.2006.03.008. PMID 16781183.
- Prins JB, van der Meer JW, Bleijenberg G (2006). "Chronic fatigue syndrome". Lancet 367 (9507): 346–55. doi:10.1016/S0140-6736(06)68073-2. PMID 16443043.
- Covelli V, Passeri ME, Leogrande D, Jirillo E, Amati L (2005). "Drug targets in stress-related disorders". Curr. Med. Chem. 12 (15): 1801–9. doi:10.2174/0929867054367202. PMID 16029148.
- Jackson JL, O'Malley PG, Kroenke K (March 200). "Antidepressants and cognitive-behavioral therapy for symptom syndromes". CNS Spectr 11 (3): 212–22. PMID 16575378. Check date values in:
- Pae CU, Marks DM, Patkar AA, Masand PS, Luyten P, Serretti A (July 2009). "Pharmacological treatment of chronic fatigue syndrome: focusing on the role of antidepressants". Expert Opin Pharmacother 10 (10): 1561–70. doi:10.1517/14656560902988510. PMID 19514866.
- Cho HJ, Hotopf M, Wessely S (2005). "The placebo response in the treatment of chronic fatigue syndrome: A systematic review and meta-analysis". Psychosom Med 67 (2): 301–13. doi:10.1097/01.psy.0000156969.76986.e0. PMID 15784798. Retrieved 2008-12-12.
- Cairns R, Hotopf M (2005). "A systematic review describing the prognosis of chronic fatigue syndrome". Occupational medicine (Oxford, England) 55 (1): 20–31. doi:10.1093/occmed/kqi013. PMID 15699087.
- Joyce J, Hotopf M, Wessely S (1997). "The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review". QJM 90 (3): 223–33. doi:10.1093/qjmed/90.3.223. PMID 9093600.
- Adamowicz JL, Caikauskaite I, Friedberg F. Defining recovery in chronic fatigue syndrome: a critical review. Qual Life Res. 2014 May 3. [Epub ahead of print] PMID 24791749.
- Dinos S, Khoshaba B, Ashby D, White PD, Nazroo J, Wessely S, Bhui KS (2009). "A systematic review of chronic fatigue, its syndromes and ethnicity: prevalence, severity, co-morbidity and coping". International Journal of Epidemiology 38 (6): 1554–70. doi:10.1093/ije/dyp147. PMID 19349479.
- Walsh CM, Zainal NZ, Middleton SJ, Paykel ES (2001). "A family history study of chronic fatigue syndrome". Psychiatr Genet 11 (3): 123–8. doi:10.1097/00041444-200109000-00003. PMID 11702053.
- "Chronic Fatigue Syndrome—Who's at Risk?". Retrieved 2014-12-12.
- Hempel S, Chambers D, Bagnall AM, Forbes C (July 2008). "Risk factors for chronic fatigue syndrome/myalgic encephalomyelitis: a systematic scoping review of multiple predictor studies". Psychol Med 38 (7): 915–26. doi:10.1017/S0033291707001602. PMID 17892624.
- Craig T, Kakumanu S (Mar 2002). "Chronic fatigue syndrome: evaluation and treatment". Am Fam Physician. 65 (6): 1083–90. PMID 11925084.
- Bradley LA, McKendree-Smith NL, Alarcón GS (2000). "Pain complaints in patients with fibromyalgia versus chronic fatigue syndrome". Curr Rev Pain 4 (2): 148–57. doi:10.1007/s11916-000-0050-2. PMID 10998728.
- van Staden WC (2006). "Conceptual issues in undifferentiated somatoform disorder and chronic fatigue syndrome". Curr Opin Psychiatry 19 (6): 613–8. doi:10.1097/01.yco.0000245753.83502.d9. PMID 17012941.
- Jenkins R, Mowbray J, ed. Post-viral Fatigue Syndrome. 1991 John Wiley & Sons Ltd
- Vojdani A, Thrasher JD (2004). "Cellular and humoral immune abnormalities in Gulf War veterans". Environ Health Perspect 112 (8): 840–6. doi:10.1289/ehp.6881. PMC 1242010. PMID 15175170.
- Bruno RL, Creange SJ, Frick NM (1998). "Parallels between post-polio fatigue and chronic fatigue syndrome: a common pathophysiology?". Am J Med. 105 (3A): 66S–73S. doi:10.1016/S0002-9343(98)00161-2. PMID 9790485.
- Friedberg F, Jason LA (2001). "Chronic fatigue syndrome and fibromyalgia: clinical assessment and treatment". J Clin Psychol. 57 (4): 433–55. doi:10.1002/jclp.1040. PMID 11255201.
- Prins J, Bleijenberg G, Rouweler EK, van der Meer J (2005). "Effect of psychiatric disorders on outcome of cognitive-behavioural therapy for chronic fatigue syndrome". Br J Psychiatry 187 (2): 184–5. doi:10.1192/bjp.187.2.184. PMID 16055833.
- Aaron LA, Herrell R, Ashton S, Belcourt M, Schmaling K, Goldberg J, Buchwald D (2001). "Comorbid Clinical Conditions in Chronic Fatigue: A Co-Twin Control Study". Journal of general internal medicine 16 (1): 24–31. doi:10.1111/j.1525-1497.2001.03419.x. PMC 1495162. PMID 11251747.
- Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P (2002). "High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis". Hum Reprod 17 (10): 2715–24. doi:10.1093/humrep/17.10.2715. PMID 12351553.
- Ramsay AM. Myalgic encephalomyelitis and postviral fatigue states. Second Ed. 1988
- Acheson ED (1959). "The clinical syndrome variously called benign myalgic encephalomyelitis, Iceland disease and epidemic neuromyasthenia". The American Journal of Medicine 26 (4): 569–95. doi:10.1016/0002-9343(59)90280-3. PMID 13637100.
- International Classification of Diseases I. World Health Organization. 1969. pp. 158, (vol 2, pp. 173).
- Buchwald D, Sullivan JL, Komaroff AL (1987). "Frequency of 'chronic active Epstein-Barr virus infection' in a general medical practice". JAMA: the Journal of the American Medical Association 257 (17): 2303–7. doi:10.1001/jama.257.17.2303. PMID 3033338.
- Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, Jones JF, Dubois RE, Cunningham-Rundles C, Pahwa S (1988). "Chronic fatigue syndrome: A working case definition". Annals of internal medicine 108 (3): 387–9. doi:10.7326/0003-4819-108-3-387. PMID 2829679.
- Sharpe M & Campling F (2000). Chronic Fatigue Syndrome (CFS/ME): TheFacts. Oxford: Oxford Press. pp. 14, 15. ISBN 0-19-263049-0. Retrieved 2008-04-02.
- Packard RM, Berkelman RL, Brown PJ, Frumkin H (2004). Emerging Illnesses and Society. JHU Press. p. 156. ISBN 0-8018-7942-6. Retrieved 2008-04-02.
- "Press Briefing Transcripts". Centers for Disease Control and Prevention. November 3, 2006. Retrieved 2013-10-12.
- Alberts B (2011). "Editorial Expression of Concern". Science 333 (6038): 35. doi:10.1126/science.1208542. PMID 21628391.
- Silverman RH, Das Gupta J, Lombardi VC, Ruscetti FW, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Mikovits JA (September 2011). "Partial Retraction". Science. doi:10.1126/science.1212182. PMID 21940859.
- Alberts B (2011). "Retraction". Science 334 (6063): 1636. doi:10.1126/science.334.6063.1636-a. PMID 22194552.
- Simmons G, Glynn SA, Komaroff AL, Mikovits JA, Tobler LH, Hackett J, Tang N, Switzer WM, Heneine W, Hewlett IK, Zhao J, Lo SC, Alter HJ, Linnen JM, Gao K, Coffin JM, Kearney MF, Ruscetti FW, Pfost MA, Bethel J, Kleinman S, Holmberg JA, Busch MP (2011). "Failure to Confirm XMRV/MLVs in the Blood of Patients with Chronic Fatigue Syndrome: A Multi-Laboratory Study". Science 334 (6057): 814–7. doi:10.1126/science.1213841. PMC 3299483. PMID 21940862.
- Lo SC, Pripuzova N, Li B, Komaroff AL, Hung GC, Wang R, Alter HJ (2011). "Retraction for Lo et al., Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors". Proceedings of the National Academy of Sciences 109 (1): 346. doi:10.1073/pnas.1119641109. PMC 3252929. PMID 22203980.
- "Erythos.com" (PDF). Retrieved 2011-01-28.
- "Chronic Fatigue Syndrome/Myalgic Encephalomyelitis". MRC.ac.uk. Retrieved 2011-01-28.
- "APPGME.org.uk" (PDF). Retrieved 2011-01-28.
- Reynolds KJ, Vernon SD, Bouchery E, Reeves WC (2004). "The economic impact of chronic fatigue syndrome". Cost effectiveness and resource allocation : C/E 2 (1): 4. doi:10.1186/1478-7547-2-4. PMC 449736. PMID 15210053.
- Jason LA, Benton MC, Valentine L, Johnson A, Torres-Harding S (2008). "The Economic impact of ME/CFS: Individual and societal costs". Dyn Med 7: 6. doi:10.1186/1476-5918-7-6. PMC 2324078. PMID 18397528.
- Broderick G, Craddock TJ (2013). "Systems biology of complex symptom profiles: Capturing interactivity across behavior, brain and immune regulation". Brain, Behavior, and Immunity 29: 1–8. doi:10.1016/j.bbi.2012.09.008. PMC 3554865. PMID 23022717.
- Van Houdenhove B, Neerinckx E, Onghena P, Vingerhoets A, Lysens R, Vertommen H (2002). "Daily hassles reported by chronic fatigue syndrome and fibromyalgia patients in tertiary care: a controlled quantitative and qualitative study". Psychother Psychosom 71 (4): 207–13. doi:10.1159/000063646. PMID 12097786.
- Colby J (2007). "Special problems of children with myalgic encephalomyelitis/chronic fatigue syndrome and the enteroviral link". J Clin Pathol 60 (2): 125–8. doi:10.1136/jcp.2006.042606. PMC 1860612. PMID 16935964. 16935964.
- Prins JB, Bos E, Huibers MJ, Servaes P, van der Werf SP, van der Meer JW, Bleijenberg G (2004). "Social support and the persistence of complaints in chronic fatigue syndrome". Psychother Psychosom 73 (3): 174–82. doi:10.1159/000076455. PMID 15031590.
- Lee, Nancy. "Dr. Nancy Lee on International Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Awareness Day". U.S. Department of Health & Human Services. Retrieved 2013-10-12.
- Poulton, Sonia (2012-05-08). "All in the mind? Why critics are wrong to deny the existence of chronic fatigue". Mail Online (Dail Mail). Retrieved 2014-02-07.
- "'Torrent of abuse' hindering ME research". BBC. 2011-07-29. Retrieved 2011-07-31.
- Wallace PG, Sharpe M (October 1991). "Post-viral fatigue syndrome. Epidemiology: a critical review" (PDF). Br Med Bull. 47 (4): 942–951. PMID 1794092.
- Mounstephen A, Sharpe M (1997). "Chronic fatigue syndrome and occupational health". Occupational Medicine 47 (4): 217–27. doi:10.1093/occmed/47.4.217. PMID 9231495.
- Hooge J (1992). "Chronic fatigue syndrome: cause, controversy and care". Br J Nurs 1 (9): 440–1, 443, 445–6. PMID 1446147.
- Sharpe M (1996). "Chronic fatigue syndrome". Psychiatr. Clin. North Am. 19 (3): 549–73. doi:10.1016/S0193-953X(05)70305-1. PMID 8856816.
- Denz-Penhey H, Murdoch JC (1993). "General practitioners acceptance of the validity of chronic fatigue syndrome as a diagnosis". N. Z. Med. J. 106 (953): 122–4. PMID 8474729.
- Greenlee JE, Rose JW (2000). "Controversies in neurological infectious diseases". Semin Neurol 20 (3): 375–86. doi:10.1055/s-2000-9429. PMID 11051301.
- Horton-Salway M (2007). "The ME Bandwagon and other labels: constructing the genuine case in talk about a controversial illness". Br J Soc Psychol 46 (Pt 4): 895–914. doi:10.1348/014466607X173456. PMID 17535450.
- Engel CC, Adkins JA, Cowan DN (2002). "Caring for medically unexplained physical symptoms after toxic environmental exposures: effects of contested causation". Environ. Health Perspect. 110 Suppl 4 (Suppl 4): 641–7. doi:10.1289/ehp.02110s4641. PMC 1241219. PMID 12194900.
- Dumit J (2005-08-08). "Illnesses you have to fight to get: facts as forces in uncertain, emergent illnesses". Soc Sci Med. Feb;62 (3): 577–90. doi:10.1016/j.socscimed.2005.06.018. PMID 16085344.
- "Chronic fatigue syndrome researchers face death threats from militants". The Guardian. 2011-08-21. Retrieved 2014-02-02.
- "Views from the front line". Science Media Centre. 2012. Retrieved 2012-12-07.
- "No blood from chronic fatigue donors: agency". CBC. 2010-04-07. Retrieved 2010-06-25.
- Atkinson, K (2010-04-21). "Chronic Fatigue Set To Disqualify Blood Donors". Voxy.co.nz. Retrieved 2010-06-25.
- "Blood Service updates CFS donor policy". Australian Red Cross Blood Service. Retrieved 2013-07-07.
- "Recommendation on Chronic Fatigue Syndrome and Blood Donation". American Association of Blood Banks. 2010-06-18. Retrieved 2010-06-25.
- NHS Blood and Transplant (2010-11-05). "ME/CFS sufferers permanently deferred from giving blood". Retrieved 2011-10-09.
- Couper J (2000). "Chronic fatigue syndrome and Australian psychiatry: lessons from the UK experience". Aust N Z J Psychiatry 34 (5): 762–9. doi:10.1046/j.1440-1614.2000.00810.x. PMID 11037362.
- Jason LA, Richman JA, Friedberg F, Wagner L, Taylor R, Jordan KM (1997). "Politics, science, and the emergence of a new disease. The case of chronic fatigue syndrome". Am Psychol 52 (9): 973–83. doi:10.1037/0003-066X.52.9.973. PMID 9301342.
- David A, Wessely S (1993). "Chronic fatigue, ME, and ICD-10". The Lancet 342 (8881): 1247–8. doi:10.1016/0140-6736(93)92234-K. PMID 7901572.
- Jason LA; Fennell PA & Taylor RR, ed. (2003). Handbook of Chronic Fatigue Syndrome. John Wiley & Sons. ISBN 978-0-471-41512-1.
- Sharpe, Michael; Frankie Campling (2000). Chronic fatigue syndrome (CFS/ME). Oxford [Oxfordshire]: Oxford University Press. ISBN 0-19-263049-0.
- "CDC - Chronic Fatigue Syndrome (CFS)". Centers for Disease Control. Retrieved 2011-12-09.
- Chronic fatigue syndrome at DMOZ
- "ME Research UK — Research database". Retrieved 2013-08-03.
- Chronic Fatigue Syndrome on patient.co.uk