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MeshID = D015673 |
MeshID = D015673 |
'''Chronic fatigue syndrome''' ('''CFS''') is [[ME/CFS nomenclatures|one of several names]] given to a poorly understood, variably debilitating disorder or disorders of uncertain [[etiology|causation]]. CFS is thought, based on a 1999 study, to affect approximately 4 per 1,000 adults in the United States.<ref name=pmid10527290>{{cite journal |author=Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR, McCready W, Huang CF, Plioplys S |title=A community-based study of chronic fatigue syndrome |journal=Arch. Intern. Med. |volume=159 |issue=18 |pages=2129–37 |year=1999 | url = |pmid=10527290 | doi = 10.1001/archinte.159.18.2129 <!--Retrieved from CrossRef by DOI bot-->}}</ref>
'''Chronic fatigue syndrome''' ('''CFS''') is [[ME/CFS nomenclatures|one of several names]] given to laziness.
CFS is thought, based on a 1999 study, to affect approximately 4 per 1,000 adults in the United States.<ref name=pmid10527290>{{cite journal |author=Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR, McCready W, Huang CF, Plioplys S |title=A community-based study of chronic fatigue syndrome |journal=Arch. Intern. Med. |volume=159 |issue=18 |pages=2129–37 |year=1999 | url = |pmid=10527290 | doi = 10.1001/archinte.159.18.2129 <!--Retrieved from CrossRef by DOI bot-->}}</ref>
For unknown reasons, CFS occurs more often in women than men, and in people in their 40s and 50s.<ref>{{cite journal |author=Gallagher AM, Thomas JM, Hamilton WT, White PD |title=Incidence of fatigue symptoms and diagnoses presenting in UK primary care from 1990 to 2001 |journal=J R Soc Med |volume=97 |issue=12 |pages=571–5 |year=2004 |pmid=15574853 |doi=10.1258/jrsm.97.12.571}}</ref><ref name="CDCRisk"/> The illness is estimated to be less prevalent among children and adolescents, but studies are contradictory as to the degree.<ref name="DOI : 10.1300/J092v13n02_01">{{cite journal |author=Jason LA, Jordan K, Miike T, Bell DS, Lapp C, Torres-Harding S, Rowe K, Gurwitt A, De Meirleir K, Van Hoof ELS |title=A Pediatric Case Definition for Myalgic Encephalomyelitis and Chronic Fatigue Syndrome |journal=Journal of Chronic Fatigue Syndrome |volume=13 |issue=2-3 | pages = 1–44 |year=2006| doi = 10.1300/J092v13n02_01}}</ref>
For unknown reasons, CFS occurs more often in women than men, and in people in their 40s and 50s.<ref>{{cite journal |author=Gallagher AM, Thomas JM, Hamilton WT, White PD |title=Incidence of fatigue symptoms and diagnoses presenting in UK primary care from 1990 to 2001 |journal=J R Soc Med |volume=97 |issue=12 |pages=571–5 |year=2004 |pmid=15574853 |doi=10.1258/jrsm.97.12.571}}</ref><ref name="CDCRisk"/> The illness is estimated to be less prevalent among children and adolescents, but studies are contradictory as to the degree.<ref name="DOI : 10.1300/J092v13n02_01">{{cite journal |author=Jason LA, Jordan K, Miike T, Bell DS, Lapp C, Torres-Harding S, Rowe K, Gurwitt A, De Meirleir K, Van Hoof ELS |title=A Pediatric Case Definition for Myalgic Encephalomyelitis and Chronic Fatigue Syndrome |journal=Journal of Chronic Fatigue Syndrome |volume=13 |issue=2-3 | pages = 1–44 |year=2006| doi = 10.1300/J092v13n02_01}}</ref>

Revision as of 17:09, 8 August 2008

Chronic fatigue syndrome/ Myalgic encephalomyelitis
Classification and external resources
Specialty neurology, rheumatology
ICD-10 G93.3
ICD-9-CM 780.71
DiseasesDB 1645
MedlinePlus 001244
eMedicine med/3392 ped/2795
Patient UK Chronic fatigue syndrome
MeSH D015673

Chronic fatigue syndrome (CFS) is one of several names given to laziness. CFS is thought, based on a 1999 study, to affect approximately 4 per 1,000 adults in the United States.[1] For unknown reasons, CFS occurs more often in women than men, and in people in their 40s and 50s.[2][3] The illness is estimated to be less prevalent among children and adolescents, but studies are contradictory as to the degree.[4]

CFS often manifests with widespread myalgia and arthralgia, cognitive difficulties, chronic mental and physical exhaustion, often severe, and other characteristic symptoms in a previously healthy and active person. Despite promising avenues of research, there remains no assay or pathological finding which is widely accepted to be diagnostic of CFS. It remains a diagnosis of exclusion based largely on patient history and symptomatic criteria, although a number of tests can aid diagnosis.[5] Whereas there is agreement on the genuine threat to health, happiness, and productivity posed by CFS, various physicians' groups, researchers, and patient activists champion very different nomenclature, diagnostic criteria, etiologic hypotheses, and treatments, resulting in controversy about nearly all aspects of the disorder. Even the term chronic fatigue syndrome is controversial because a large part of the patient community believes the name trivializes the illness.[6]

Chronic fatigue syndrome is not the same as "chronic fatigue".[5] Fatigue is a common symptom in many illnesses, but CFS is a multi-systemic disease and is relatively rare by comparison.[7] Definitions (other than the 1991 UK Oxford criteria)[8] require a number of features, the most common being severe mental and physical exhaustion which is "unrelieved by rest" (1994 Fukuda definition),[9] and may be worsened by even trivial exertion (a mandatory diagnostic criterion according to some systems). Most diagnostic criteria require that symptoms must be present for at least six months, and all state the symptoms must not be caused by other medical conditions. CFS patients may report many symptoms which are not included in all diagnostic criteria, including muscle weakness, cognitive dysfunction, hypersensitivity, orthostatic intolerance, digestive disturbances, depression, poor immune response, and cardiac and respiratory problems. It is unclear if these symptoms represent co-morbid conditions or are produced by an underlying etiology of CFS.[10] Some cases improve over time, and treatments (though none are universally accepted) bring a degree of improvement to many others, though full resolution may be only 5-10% according to the United States Centers for Disease Control and Prevention (CDC).[11]


The nomenclature of the condition(s) has been challenging, since consensus is lacking within the clinical, research, and patient communities regarding its defining features and causes. Authorities on the illness do not agree if it is a central nervous system, metabolic, (post-)infectious, immune system, or neuropsychiatric disorder, nor even if it is a single homogenous disorder (with a range of possible clinical presentations), or several distinct disorders having many clinical characteristics in common.

Over time and in different countries many names have been associated with the condition(s). Some of the more common names in use include:[12][13]

Signs and symptoms


Sudden onset cases

The majority of CFS cases start suddenly,[14] usually accompanied by a "flu-like illness"[10][15][16][17] which is more likely to occur in winter,[18][19] while a significant proportion of cases begin within several months of severe adverse stress.[20][21][14] Many people report getting a case of a flu-like or other respiratory infection such as bronchitis, from which they seem never to fully recover and which evolves into CFS. The diagnosis of Post-viral fatigue syndrome is sometimes given in the early stage of the illness.[22] One study reported CFS occurred in some patients following a vaccination or a blood transfusion.[23] The accurate prevalence and exact roles of infection and stress in the development of CFS however are currently unknown.

Gradual onset cases

Other cases have a gradual onset, sometimes spread over years.[23] Patients with Lyme disease may, despite a standard course of treatment, "evolve" clinically from the symptoms of acute Lyme to those similar to CFS.[24] This has become an area of great controversy.


It can be inferred from the 2003 Canadian clinical working definition of ME/CFS[5] that there are 8 categories of symptoms:

  • Fatigue: Unexplained, persistent, or recurrent physical and mental fatigue/exhaustion that substantially reduces activity levels and is not relieved (or not completely relieved) by rest.
  • Post-exertional malaise: An inappropriate loss of physical and mental stamina, rapid muscular and cognitive fatigability, post exertional malaise and/or fatigue and/or pain and a tendency for other associated symptoms to worsen with a pathologically slow recovery period of usually 24 hours or longer. According to the authors of the Canadian clinical working definition of ME/CFS,[5] the malaise that follows exertion is often reported to be similar to the generalized pain, discomfort and fatigue associated with the acute phase of influenza. Although common in CFS, this may not be the most severe symptom in the individual case, where other symptoms (such as headaches, neurocognitive difficulties, pain and sleep disturbances) can dominate.
  • Sleep dysfunction: "Unrefreshing" sleep/rest, poor sleep quantity, insomnia or rhythm disturbances. A study found that most CFS patients have clinically significant sleep abnormalities that are potentially treatable.[25] Several studies suggest that while CFS patients may experience altered sleep architecture (such as reduced sleep efficiency, a reduction of deep sleep, prolonged sleep initiation, and alpha-wave intrusion during deep sleep) and mildly disordered breathing, overall sleep dysfunction does not seem to be a critical or causative factor in CFS.[26][27][28][29] Sleep may present with vivid disturbing dreams, and exhaustion can worsen sleep dysfunction.[30]
  • Neurological/cognitive manifestations: Common occurrences include confusion, forgetfulness, mental fatigue/brain fog, impairment of concentration and short-term memory consolidation, disorientation, difficulty with information processing, categorizing and word retrieval, and perceptual and sensory disturbances (e.g. spatial instability and disorientation and inability to focus vision), ataxia (unsteady and clumsy motion of the limbs or torso), muscle weakness and "twitches". There may also be cognitive or sensory overload (e.g. photophobia and hypersensitivity to noise and/or emotional overload, which may lead to "crash" periods and/or anxiety). A review of research relating to the neuropsychological functioning in CFS was published in 2001 and found that slowed processing speed, impaired working memory and poor learning of information are the most prominent features of cognitive dysfunctioning in patients with CFS, which couldn't be accounted solely by the severity of the depression and anxiety.[32]
  • Neuroendocrine manifestations: Common occurrences include poor temperature control or loss of thermostatic stability, subnormal body temperature and marked daily fluctuation, sweating episodes, recurrent feelings of feverishness and cold extremities, intolerance of extremes of heat and cold, digestive disturbances[33] and/or marked weight change - anorexia or abnormal appetite, loss of adaptability and worsening of symptoms with stress.
  • Immune manifestations: Common occurrences include tender lymph nodes, recurrent sore throat, recurrent flu-like symptoms, general malaise, new sensitivities to food and/or medications and/or chemicals (which may complicate treatment). At least one study has confirmed that most CFS patients reduce or cease alcohol intake, mostly due to personal experience of worsening symptoms[34] (although the cause of this is unknown and may not be strictly "immunological" as implied by the symptom list).

Activity levels

Patients report critical reductions in levels of physical activity[35] and are as impaired as persons whose fatigue can be explained by another medical or a psychiatric condition.[36] According to the CDC, studies show that the disability in CFS patients is comparable to some well-known, very severe medical conditions, such as; multiple sclerosis, AIDS, lupus, rheumatoid arthritis, heart disease, end-stage renal disease, chronic obstructive pulmonary disease (COPD) and similar chronic conditions.[37][38] The severity of symptoms and disability is the same in both genders,[39] and chronic pain is strongly disabling in CFS patients,[31] but despite a common diagnosis the functional capacity of CFS patients varies greatly.[40] While some patients are able to lead a relatively normal life, others are totally bed-bound and unable to care for themselves. A systematic review found that in a synthesis of studies, 42% of patients were employed, 54% were unemployed, 64% reported CFS-related work limitations, 55% were on disability benefits or temporary sick leave, and 19% worked full-time.[41]


The mechanisms and processes (pathogenesis) of Chronic Fatigue Syndrome are gradually being revealed through research, including physiological and epidemiological studies. In a basic overview of CFS for health professionals, the CDC states that "After more than 3,000 research studies, there is now abundant scientific evidence that CFS is a real physiological illness."[42]

Chronic fatigue syndrome (CFS) or (ME) has been described in a 2008 Toxicology journal article as, "a constellation of multi-system dysfunctions primarily involving the neurological (nervous system), endocrine (hormone system), and immune systems." The article states recent research suggests the potential that xenobiotic (chemicals), infectious agents, stress, and other insults in early life may be a component of later-life CFS.[43]

A 2007 article in the journal Autoimmunity summarised; “The current concept is that CFS pathogenesis is a multi factorial condition in which an infective agent cause an aberrant immune response characterized by a shift to Th-2 (cytokine) dominant response. When the response fails to be switched-off, a chronic immune activation occurs and is clinically expressed in the symptomatology of CFS". [44]

In a 2006 update in the journal Curr Opin Psychiatry it was said; “Recent advances in understanding the pathophysiology of chronic fatigue syndrome continue to demonstrate the involvement of the central nervous system. Hyperserotonergic state and hypoactivity of the hypothalamic-pituitary-adrenal axis (HPA axis) constitute other findings, but the question of whether these alterations are a cause or consequence of chronic fatigue syndrome still remains unanswered.” [45] Alterations in serotonin signaling can lead to physiologic and behavioral changes. A 2008 study of gene polymorphisms indicates genetic predisposition possibly resulting in enhanced activity of serotonin may be involved in the pathophysiology of CFS. [46]

Chronic fatigue is a typical symptom of neurological diseases, including chronic fatigue syndrome, is also seen in diseases that affect the central, peripheral, and autonomic nervous systems (central fatigue). Enhanced perception of effort and limited endurance of sustained physical and mental activities are the main characteristics of central fatigue. Metabolic and structural lesions can cause muscle fatigability (peripheral fatigue) also disrupt the usual process of activation in pathways interconnecting the basal ganglia (peripheral nerves), thalamus, limbic system, and higher cortical centre are implicated in the pathophysiological process of central fatigue. A state of low cortisol might sensitize the hypothalamic-pituitary-adrenal axis (HPA axis) to development of persistent central fatigue after stress. [47]

Chronic Fatigue Syndrome (CFS) is a disorder whose etiology and pathogenesis are still unknown. In this syndrome both abnormalities of nervous and immune systems have been reported. Nervous and immune systems mutually cooperate via release of mediators of both neurological and immunological derivation. Hormone (ACTH) is a product of the HPA axis which stimulates secretion of corticosteroids from adrenals. In turn, corticosteroids modulate the immune response by virtue of their anti-inflammatory activity. On the other hand, catecholamines, products of the sympathetic nervous system (SNS), regulate immune function by acting on specific beta-adrenergic receptors. Conversely, cytokines released by certain immune cells, upon stimulation, are able to cross the blood-brain-barrier, thus modulating nervous functions (e.g., thermoregulation, sleep, and appetite). However, cytokines are locally produced in the brain, especially in the hypothalamus, thus contributing to the development of appetite, thermoregulation, sleep and behavioural effects. In addition infections/pathogens and/or their products, the so-called stressors are able to activate both HPA axis and SNS, thus influencing immune responses. [48]


The etiology of CFS is unknown, and many causes have been proposed. The etiology may be different for subgroups of patients, and may result in a common clinical outcome.[42] Some plausible hypotheses are as follows. (1) CFS is often associated with viral infection. (2) Anomalies of the HPA axis are often observed in CFS, but it is not clear if they are a cause or consequence of the disorder. (3) Immune dysfunction is also found in CFS studies, and hypothesized as the cause of CFS. (4) In the psychiatric and psychosocial model, some researchers hypothesize cognitive and behavioral factors are involved in the persistence of fatigue and illness behavior.[49] Other hypotheses for the causes of CFS are (5) Oxidative stress and (6) genetic predisposition.[50]

Definitions, Guidelines, and Summaries

In 1938, Assistant Surgeon General of United States, Dr A Gilliam reported on a 1934 epidemic of what was diagnosed at the time as Poliomyelitis. He called the unusual symptoms and attack rate in adults unparalleled. His detailed description that added up to a twenty-point definition of 90 pages is considered by Byron Hyde of the Nightingale Research Foundation as the first useful description of ME/CFS. Dr Hyde in a Review of Publication of Gilliam refers to Gilliam's own communications and his claims that the publication of the report was delayed by concerned US authorities until 1938.[51]

Competing definitions, guidelines, and summary descriptions have accrued. Among them, some of the most notable are

  • The Ramsay definition (1986) [52]
  • The Holmes et al (1988) scoring system,[53] sometimes called "CDC 1988"
  • The Oxford criteria (1991)[8]
  • The "Fukuda" CDC definition (1994),[9] or "CDC 1994"
  • The Carruthers et al (2003) Canadian Case definition for ME/CFS[5]

Case definitions in CFS have largely been established to define patients for research study purposes, and have certain limitations when used for general practitioner purposes. Several studies have found that using different case definitions ( eg broad vs conservative[55] ) has major influence on the types of patients selected and have also supported the distinction between specific subgroups of CFS to be identified and/or for the case definition to be further clarified with emphasis on using empirical studies: An international CFS study group for the CDC found in 2003 that ambiguities in the CDC 1994 CFS research case definition contribute to inconsistent case identification.[56]

At this time, there is no accepted conclusive test or series of tests for ME/CFS. According to the CDC, the main purpose of performing diagnostic tests of any sort at this point in time, is to rule out other causes for fatigue and other symptoms of CFS.[9] A review published in 2006 found that the accurate diagnosis of CFS is low[57]

Clinical practice guidelines, with the aim of improving diagnosis, several countries have now produced these, which are generally based on case descriptions but these documents have the aim of guiding decisions and criteria regarding diagnosis, management, and treatment. Modern medical guidelines are based on an examination of current evidence within the paradigm of evidence-based medicine and they usually include summarized consensus statements. Guidelines are usually produced at national or international levels by medical associations or governmental bodies.


Improvement may occur with medical care and additional therapies of pacing, cognitive behavioral therapy (CBT) and graded exercise therapy (GET). The latter two therapies have been found to be efficacious in small trials, but patient organisations surveys have reported adverse effects.[58] Interventions involving rehabilitation therapies have been shown to be at least partially effective in some people with CFS. [59][60][61][62]

Some therapies recommended by different sources include:


Many patients do not fully recover from CFS, even with treatment.[68] Some management strategies are suggested to reduce the consequences of having CFS. Medications, other medical treatments, complementary and alternative medicine are considered. A systematic review has shown that CFS patients are less susceptible to placebo effects than predicted, and have a low placebo response compared to patients with other diseases.[69] CFS is associated with chemical sensitivity,[70] [71] and some patients often respond to a fraction of a therapeutic dose that is normal for other conditions.[72][73]

A 2005 review in the journal Curr Med Chem. concluded, “it seems that major drug targets in stress-related disorders are immune cells in terms of inhibition of proinflammatory cytokines and modulation of Th (cytokine pattern) responses”. In CFS, in a series of recent therapeutic trials several immunomodulating agents have been used, such as staphypan Berna, lactic acid bacteria, kuibitang and intravenous immunoglobulin. In particular, according to recent evidences, antidepressants seem to exert beneficial effects in augmenting NK cell activity in depressed patients. [48]



A systematic review of 14 studies of the outcome of untreated 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."[74] It is not known whether any patients truly "recover" entirely from the illness, or achieve remission from a relapsing, remitting illness[citation needed]. Few untreated patients report a total "cure".


CFS is unlikely to increase the risk of an early death. A systematic review of 14 studies of the outcome of CFS reported 8 deaths, but none were considered directly attributable to CFS.[74] To date there have been two studies directly addressing life expectancy in CFS. In a preliminary 2006 study of CFS self-help group members, it was reported that CFS patients were likely to die at a younger than average age for cancer, heart failure, and suicide.[75] However, a much larger study of 641 CDC criteria diagnosed patients with CFS, who were followed up for a mean of 9 years, showed no excess risk of dying from any cause.[76]

People diagnosed with CFS may die, as in the case in the UK of Sophia Mirza, where the coroner recorded a verdict of "Acute anuric renal failure due to dehydration arising as a result of CFS." According to Sophia's mother, Sophia became intolerant to water and managed only 4 fluid ounces per day.[77] The pathologist said, "ME describes inflammation of the spinal cord and muscles. My work supports the inflammation theory...The changes of dorsal root ganglionitis seen in 75% of Sophia's spinal cord were very similar to that seen during active infection by herpes viruses." This was seen as a form of recognition by the ME community.[78] Previous cases have listed CFS as the cause of death in the US and Australia[79]


Due to problems with the definition of CFS, estimates of its prevalence vary widely. Studies in the United States have previously found between 75 and 420 cases of CFS for every 100,000 adults. The CDC states that more than 1 million Americans have CFS and approximately 80% of the cases are undiagnosed.[11] All ethnic and racial groups appear susceptible to the illness, and lower income groups are slightly more likely to develop CFS.[3] 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. Blood relatives of people who have CFS appear to be more predisposed.[3][80] However, CFS does not appear directly contagious; caretakers, partners and others in close contact with persons with CFS for years do not develop CFS any more frequently (excluding relatives, as earlier).

Epidemiological research on children and adolescents has received minimal focus according to a 2006 research review. Among minors, prevalence appears to be lower than for adults and various studies have found a range of 50-80% of the cases occur in girls. The authors hypothesize the differences in estimates of ME/CFS among pediatric studies may result because of the lack of a reliable pediatric case definition.[4]

CFS generally occurs in endemic cases. In addition, over 50 instances have been documented, such as the Royal Free Hospital incident, where epidemic clusters were reported.[who?][52][51] In these instances, significant numbers of people came down with illnesses described[weasel words] as ME or CFS simultaneously, confined to a local area or even a single building. An infectious origin for these clusters was considered highly likely due to:

  • transference by inoculation to monkeys which developed symptomology and on post-mortem demonstrated neurological, vascular and cardiac damage (Fellow and Miles, 1955).
  • human post-mortems or scans demonstrating abnormalities consistent with chronic infection (Wallis 1957, Schwartz et al 1994)
  • serologic evidence of Iceland Disease blocking spread of polio type I spreading northwards (Sigurdsson et al, 1958).
  • the pattern of acute onset with pharyngitis, mild fever, muscular pain, neck stiff­ness, cervical lymphadenopathy, gastroenteric symptoms, diffuse CNS involvement and photosensitivity were consistent with viral infection with an observed incubation period of 5-7 days. The biphasic clinical picture echoes pathogenesis through the pharynx, spreading through the reticuloendothelial barrier, then the CNS, resulting in morphological changes in mature lymphocytes and antibody creation. (Acheson, Ramsay, RIchardson, Crowley, Dillon et al)
  • A predeliction for residential communities and most outbreaks occurring in summer (Acheson)
  • The isolation of the non-polio enterovirus ECHO-9 in patients (Lyle, Annals of Internal Medicine 1959; 51: 248-269)
  • psychiatric disease was a widely regarded exclusion for M.E. diagnosis (e.g. Acheson) and positive criteria for hysteria were absent (Gosling, Mayne, 1970).
  • At the 1978 RSM Symposium, new evidence was presented of increased anti-complementary activity and the ability of lymphocytes to proliferate and survive in vitro for up to 19 weeks. (Compston 1978).

Since most current definitions of CFS exclude such findings and signs, it is disputed whether they refer to a differential diagnosis (but see below).

According to the CDC, CFS itself is not contagious.[81]

Disease associations

Some diseases show a considerable overlap with CFS. According to an article in American Family Physician in 2002, Multiple Sclerosis, Thyroid disorders, anemia, and diabetes are but a few of the diseases that must be ruled out if the patient presents with appropriate symptoms.[9][82]

People with fibromyalgia (FM, or Fibromyalgia Syndrome, FMS) have muscle pain and sleep disturbances. 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.[83] Those with multiple chemical sensitivity (MCS) are sensitive to chemicals and have sleep disturbances. Many veterans with Gulf War syndrome (GWS) have symptoms almost identical to CFS.[84] One study found several parallels when relating the symptoms of Post-polio syndrome with CFS, and postulates a possible common pathophysiology for the illnesses.[85]

Although post-Lyme syndrome and CFS share many features/symptoms, a study found that patients of the former experience more cognitive impairment and the patients of the latter experience more flu-like symptoms.[86]

One review (2006) 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.[87] Hysterical diagnoses are not merely diagnoses of exclusion but require criteria to be met on the positive grounds of both primary and secondary gain.[88] Primary Depression can be excluded in the differential diagnosis due to the absence of anhedonia and la belle indifference, the variability (lability) of mood, and the presence of sensory phenomena and somatic signs such as ataxia, myclonus and most importantly, exercise intolerance with paresis, malaise and general deterioration,Cite error: A <ref> tag is missing the closing </ref> (see the help page). which can in some cases become a comorbid situational depression.


Many CFS patients will also have, or appear to have, other medical problems or related diagnoses. Co-morbid fibromyalgia is common, although there are differences in pain complaints.[89] Fibromyalgia occurs in a large percentage of CFS patients between onset and the second year, and some researchers suggest fibromyalgia and CFS are related.[90] Similarly, multiple chemical sensitivity (MCS) is reported by many CFS patients, and it is speculated that these similar conditions may be related by some underlying mechanism, such as elevated nitric oxide/peroxynitrite.[91] As previously mentioned, many CFS sufferers also experience symptoms of irritable bowel syndrome, temporomandibular joint pain, headache including migraines, and other forms of myalgia. Clinical depression and anxiety are also commonly co-morbid. 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.[92] CFS is significantly more common in women with endometriosis compared with women in the general USA population.[93]

Social issues

Many patients report that a chronic fatigue syndrome diagnosis carries a considerable stigma, and has frequently been viewed as malingering, hypochondria, phobia, "wanting attention" or "yuppie flu". As there is no objective test for the condition at this time, it has been argued that it is easy to invent or feign CFS-like symptoms for financial, social, or emotional benefits.[94][95] CFS sufferers argue in turn that the perceived "benefits" are hardly as generous as some may believe, and that CFS patients would greatly prefer to be healthy and independent. A study found that CFS patients endure a heavy psychosocial burden.[96] 2,338 respondents of a survey by a UK patient organization highlights that those with the worst symptoms often receive the least support from health and social services.[97] A study found that CFS patients receive worse social support than disease-free cancer patients or healthy controls, which may perpetuate fatigue severity and functional impairment in CFS.[98] A survey by the Thymes Trust found that children with CFS often state that they struggle for recognition of their needs and/or they feel bullied by medical and educational professionals.[99] The ambiguity of the status of CFS as a medical condition may cause higher perceived stigma.[100] A study suggests that while there are no gender differences in CFS symptoms, men and women have different perceptions of their illness and are treated differently by the medical profession.[101] Anxiety and depression often result from the emotional, social and financial crises caused by CFS. While few studies have been made, it is believed that CFS patients are at a high risk of suicide.[102]

A lack of information and awareness has led to many patients to feel stigmatized.[103] CFS patients may not receive total medical and social acceptance and they state that some people trivialise the illness.[98]


Attempts to describe conditions similar to ME/CFS date back to at least the 17th Century.[104][51]

A major outbreak in 1934 at the Los Angeles County Hospital infected all or most of its nurses and doctors. It was referred to as Atypical Poliomyelitis, and was generally believed to be a form of polio.[105]

The outbreak that gave it one of its most common names, Myalgic Encephalomyelitis, occurred at London's Royal Free Hospital in 1955, inflicting mostly the hospital staff, and formed the basis of descriptions by Achenson, Ramsay, and others.[106]

Although early reports described epidemics, and by the 1950’s at least fourteen had occurred worldwide, (see ME/CFS outbreaks) of which seven of the fourteen occurred in staffs of hospitals. By the 1990s at least 50 similar clusters or epidemics have appeared in the medical literature. "It has always been known by investigators that these epidemics of ME/CFS tended merely to highlight the same disease activity in the general public in the epidemic area". Reports of cases were fairly stable through the 70’s. But since 1979 there has been an enormous but poorly documented increase in cases of ME/CFS. These increases compounded slowly until 1984 when an exponential increase occurred. The numbers did not drop afterwards as one might expect after an epidemic but have continued to rise in increasing number. [51]

(Benign) Myalgic Encephalomyelitis was first classified into the International Classification of Diseases in 1969 under Diseases of the nervous system.[107]

The name Chronic Fatigue Syndrome has been attributed to the 1988 article, "Chronic fatigue syndrome: a working case definition", (Holmes definition). This research case definition was published after US Centers for Disease Control epidemiologists examined patients at the Lake Tahoe outbreak.[108][109][53]

In 2006 the CDC estimated there were more than 1 million cases of CFS in the US and commenced a public awareness program.[11]

Since inception, the condition has been steeped in controversy. Despite continuous research and many findings, indicating also likely subsets of patients, the present state of study on this condition is fragmented and contentious.[110]


ME/CFS is an illness with a long history of controversies, which include:

The name

Different terms to describe the condition(s) have been used over the years in different parts of the world (see ME/CFS nomenclatures). Many members of CFS advocacy groups feel the name Chronic fatigue syndrome trivializes the illness and should be changed.[6]

The cause(s), diagnosis, and treatment

For years, many professionals within the medical community did not recognize ME/CFS as a real condition, nor was there agreement on its prevalence.[111][112] There has been much disagreement over proposed cause(s), diagnosis, and treatment of the illness.[113][114][115][116][117] It may be necessary to embrace medical uncertainty, and also to accept patient experience in order to facilitate diagnosis, treatment, and recovery process. [118]

It is suggested that a context of contested causation may have serious negative effects on healthcare for individuals. An adverserial social context, may erode patient-provider trust, test the provider's self-assurance and capability to share power with the patient, and raise problematic issues of reparation, compensation, and blame. [119]

Research priorities

The etiology is still not known, and a major divide still exists over funding for research and treatment of physiological versus psychological and psychosocial aspects of the illness. The division is especially great between ME patient groups and psychological and psychosocial treatment advocates in Great Britain.[117]

Support for patients

Sufferers describe the struggle for healthcare and legitimacy due to bureaucratic denial of the condition because of its lack of a known etiology. Institutions maintain the exclusion of patient support by rhetorical arguments of the open-endedness of science to delay new findings of fact. Patient groups respond to the systematic nature of these exclusions by developing counter-arguments. This has resulted in an expensive and prolonged conflict for all involved.[120][112]

In 1998 it became known almost 13 million dollars for CFS research had been redirected or improperly accounted for by the United States CDC. The agency stated the need to respond to other public health emergencies. The director of a U.S. national patient advocacy group charged the CDC had a bias against studying the disease.[121]

See also


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