Chronic fatigue syndrome
|Chronic fatigue syndrome|
|Classification and external resources|
|Patient UK||Chronic fatigue syndrome|
Chronic fatigue syndrome (CFS) is a complex medical condition, characterized by long-term fatigue and other symptoms. These symptoms are to such a degree that they limit a person's ability to carry out ordinary daily activities. CFS may also be referred to as systemic exertion intolerance disease (SEID), myalgic encephalomyelitis (ME), post-viral fatigue syndrome (PVFS), chronic fatigue immune dysfunction syndrome (CFIDS), or several other terms. Quality of life of persons with CFS can be extremely compromised.
Biological, genetic, infectious, and psychological mechanisms have been proposed, but the cause is not understood. Diagnosis is based on a person's signs and symptoms. The fatigue is not due to ongoing exertion, not relieved much by rest, and is not caused by other medical conditions. Evidence suggests that counseling, a gradual increase in exercise, and the medication rintatolimod is useful in some people. In 2012 the FDA considered that evidence for the safety or benefit of rintatolimod to be insufficient to approve its use in the United States.
Estimates of the number of people with the condition vary from 7 to 3,000 per 100,000 adults. About one million Americans and a quarter of a million people in the UK have CFS. Fatigue is a common symptom in many illnesses, but the fatigue experienced by persons with CFS is comparatively rare. CFS occurs more often in women than men, and is less common among children and adolescents.
There is agreement that CFS has a negative effect on health, happiness and productivity. However, various physicians' groups, researchers and patient advocates promote differing terminology, diagnostic criteria, proposed causes and treatments, resulting in controversy about many aspects of the disorder. The name "chronic fatigue syndrome" is controversial; many patients and advocacy groups, as well as some experts, believe the name trivializes the medical condition and they promote a name change.
- 1 Signs and symptoms
- 2 Risk factors
- 3 Pathophysiology
- 4 Diagnosis
- 5 Management
- 6 Prognosis
- 7 Epidemiology
- 8 History
- 9 Society and culture
- 10 Research
- 11 References
- 12 Further reading
- 13 External links
Signs and symptoms
Symptoms of CFS include malaise after exertion; unrefreshing sleep, widespread muscle and joint pain, sore throat, headaches of a type not previously experienced, cognitive difficulties, chronic and severe mental and physical exhaustion. Additional symptoms may be reported, including muscle weakness, increased sensitivity to light, sounds and smells, problems standing upright, digestive disturbances, depression, painful and often slightly swollen lymph nodes, cardiac and respiratory problems. It is unclear if these symptoms represent other associated conditions or if they are produced by CFS itself. Symptoms vary in number, type, and severity from person to person.
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 subset of individuals met the criteria for CFS, with the researchers concluding that "post-infective fatigue syndrome is a valid illness model for investigating one pathophysiological pathway to CFS". 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 concurrently last six months or longer:
- impaired memory or concentration
- post-exertional malaise, where physical or mental exertions bring on "extreme, prolonged exhaustion and sickness"
- unrefreshing sleep
- muscle pain (myalgia)
- pain in multiple joints (arthralgia)
- 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 for CFS, the International Consensus Criteria for ME do not require the 6-month waiting period before diagnosis, noting that "No other disease criteria require that diagnoses be withheld until after the patient has suffered with the affliction for 6 months."
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.
Many CFS patients will also have, or appear to have, other medical problems or related diagnoses. Fibromyalgia occurs in a large percentage of CFS patients between onset and the second year, and some researchers suggest fibromyalgia and CFS are related. 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.
All ethnic groups and income levels are susceptible to the illness. The CDC states that ME/CFS is "at least as common" in African Americans and Hispanics as Caucasians. A 2009 meta-analysis, however, showed that compared with the White American majority, African Americans and Native Americans have a higher risk of CFS, though it acknowledged that studies and data were limited. 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."
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.
Persons diagnosed with the illness appear to have an abnormal immune response to exercise. Specifically, complement products are increased, larger oxidative stress is generated along with reduced anti-oxidant immune response, and larger interleukin-10 and toll-like receptor 4 gene expression are seen versus healthy controls. Many of these immune responses correlate with the symptom of post-exertional malaise.
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.
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 a revision of 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 ME/CFS 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 persists for at least 6 months".
Clinical practice guidelines are generally based on case descriptions with the aim of improving diagnosis, management, and treatment. An example is the CFS/ME guideline for the National Health Service in England and Wales, produced in 2007 by the National Institute for Health and Clinical Excellence (NICE).
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 people do not fully recover from CFS even with treatment. Cognitive behavioural therapy (CBT) and graded exercise therapy (GET) have shown moderate effectiveness in a number of 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 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. A 2015 Cochrane review found that exercise therapy may reduce fatigue among people with CFS, and concluded that the effects of exercise therapy were comparable to those of cognitive-behavioral therapy.
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.
Evidence suggests that the medication rintatolimod may be useful in some people. In 2012, however, the FDA considered the evidence for the safety or benefit of rintatolimod to be insufficient to approve its use. 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. 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). 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.
In 1934, an outbreak then referred to as atypical poliomyelitis (at the time it was considered a form of polio) occurred at the Los Angeles County Hospital. It strongly resembled what Ramsay and Acheson would later describe as ME (in 1934, there were no follow-up data to indicate chronicity and it is not known how many of those affected remained ill). Of note are the neurological symptoms, the link with a polio outbreak and the fact that most of the patients were hospital staff. 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 active EBV as its cause. The initial case definition of CFS was published in 1988, "Chronic fatigue syndrome: a working case definition", (the Holmes definition), and displaced the name chronic Epstein-Barr virus syndrome. This research case definition was published after US Centers for Disease Control and Prevention epidemiologists examined the Lake Tahoe outbreak. In 2006, the CDC commenced a national program to educate the American public and health care professionals about CFS.
In 2009 the journal Science published a study that identified the XMRV retrovirus in a population of people with CFS. Other studies failed to reproduce this finding, and in 2011 the editor of Science formally retracted its XMRV paper 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.
Society and culture
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. 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."
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).
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.
Individuals with CFS may receive a poorer quality of social support than in those with other illnesses. One study found that CFS patients reported an increased incidence of negative/unsatisfying interactions with family, friends, colleagues and doctors, when compared with healthy controls and breast cancer patients currently in remission.
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. 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.
From the patient perspective, one 1997 study found that 77% of individuals with ME/CFS reported negative experiences with health care providers. 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. 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.
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 ME/CFS patients based on the potential harm to those patients that may result from their giving blood. 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."
There has been much contention over the etiology, pathophysiology, nomenclature, and diagnostic criteria of chronic fatigue syndrome. 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. Controversies still exist over funding for research and treatment of physiological versus psychological/psychosocial aspects of the illness.
The different case definitions used to research the illness influence the types of patients selected for studies, and research also suggests subtypes of patients may exist within a heterogeneous population. In one of the definitions, symptoms are accepted that may suggest a psychiatric disorder while others specifically exclude primary psychiatric disorders.
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. 
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 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.
Looking at psychologically-oriented models of the disease and behavioral treatments has been criticised by some patients and patient support groups. In 2011, it was reported that several UK researchers investigating CFS from this perspective had been subjected to verbal abuse, death threats and other harassment.
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