Symptoms of CFS include widespread muscle and joint pain, cognitive difficulties, chronic, often severe mental and physical exhaustion and other characteristic symptoms in a previously healthy and active person. Fatigue is a common symptom in many illnesses, but CFS is a multi-systemic disease and is relatively rare by comparison. Diagnosis (other than the 1991 UK Oxford criteria) require a number of features, the most common being severe mental and physical exhaustion which is "unrelieved by rest" (1994 Fukuda definition), 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. The condition may be managed rather than treated, with full resolution in only 5-10% of cases.
CFS is thought to have an incidence of 4 adults per 1,000 in the United States. For unknown reasons, CFS occurs more often in women than men, and in people in their 40s and 50s. The illness is estimated to be less prevalent among children and adolescents, but studies are contradictory as to the degree. Despite promising avenues of research there remains no medical test 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.
Whereas there is agreement on the genuine threat to health, happiness, and productivity posed by CFS, various physicians groups, researchers, and patient activists promote different nomenclature, diagnostic criteria, etiologic hypotheses, and treatments, resulting in controversy about nearly all aspects of the disorder. The name CFS itself is controversial, as advocacy groups as well as some experts feel it trivializes the illness and have supported efforts to change it. The World Health Organization's ICD uses the terms post-viral fatigue syndrome and benign myalgic encephalomyelitis. Another alternative name for CFS is chronic fatigue immune dysfunction syndrome.
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 look upon the condition as a central nervous system, metabolic, (post-)infectious, cardiovascular, immune system or psychiatric disorder, and consider the possibility that it is not a single homogenous disorder (with a range of possible clinical presentations), but a group of several distinct disorders with many clinical characteristics in common.
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 (ME, particularly in the United Kingdom, Canada, New Zealand and Australia), myalgic encephalitis, myalgic encephalopathy, post-viral fatigue syndrome, raphe nucleus encephalopathy, Royal Free disease, Tapanui flu and yuppie flu (now considered pejorative).
The mechanisms and processes (pathogenesis) of Chronic Fatigue Syndrome are unknown, but are the subjects of many research studies, including physiological and epidemiological studies. Searching for the etiology and pathological pathways of CFS is complicated since sub-groups of patients may have different causes for a convergent set of symptoms of CFS that produces a common clinical outcome. Hypotheses being researched include viral infection, hypothalamic-pituitary-adrenal axis abnormalities (though it is unclear if this is a cause, or consequence, of CFS), immune dysfunction, mental and psychosocial factors causing or contributing towards CFS. Because of social prejudices assuming that psychological disorders are not biological or "real", many patients object to the idea that the CFS is a mental disorder. Other hypotheses include oxidative stress and genetic predisposition.
Some researchers say that exposure to chemicals, infectious agents, stress, and other insults in early life may be a component of later-life CFS. Another idea is that a virus or another infectious agent might provoke an abnormal immune response in some people that does not get switched off and becomes chronic.
The central nervous system is important in CFS. Research has been reported on a "Hyperserotonergic state and hypoactivity of the hypothalamic-pituitary-adrenal axis (HPA axis)" in CFS. Genetic factors may be the basis for some of these changes. A 2008 study of gene polymorphisms indicates genetic predisposition possibly resulting in enhanced activity of serotonin. Another report says that low cortisol levels can be responsible: "hypocortisolaemia might sensitize the hypothalamic-pituitary-adrenal axis to development of persistent central fatigue after stress."
Some researchers conclude from these reports that nervous and immune system involvements are not separate. "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. Besides pathogens and/or their products, the so-called stressors are able to activate both HPA axis and SNS, thus influencing immune responses."
Among several competing clinical descriptions of CFS, some of the most notable are:
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 ) 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.
There is no conclusive diagnostic test for CFS, and testing is generally used to rule out other potential causes for symptoms.
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.
Many patients do not fully recover from CFS, even with treatment. Some management strategies are suggested to reduce the consequences of having CFS. Medications, other medical treatments, and complementary and alternative medicine are considered.
Medications thought to have promise in alleviating stress-related disorders include antidepressant and immunomodulatory agents "such as staphypan Berna, lactic acid bacteria, kuibitang and intravenous immunoglobulin. CFS patients are less susceptible to placebo effects than predicted, and have a low placebo response compared to patients with other diseases. CFS is associated with chemical sensitivity, and some patients often respond to a fraction of a therapeutic dose that is normal for other conditions.
Cognitive behavioral therapy (CBT), a form of psychological therapy, is reported as an effective therapy in many studies including a meta-analysis of 15 randomized, controlled trials with 1043 participants saying psychological therapy had significantly better results than standard therapies of CFS. In this analysis, CBT also appeared to work better than other types of psychological therapies. CBT has value for treating medically unexplained symptoms (MUS) like CFS according to Deary et al. who write, "a broadly conceptualized cognitive behavioural model of MUS suggests a novel and plausible mechanism of symptom generation and has heuristic value."
Interventions involving rehabilitation therapies have also been shown to be at least partially effective in some people with CFS. Analysis of multiple randomized, controlled trials of exercise therapy of patients diagnosed with CFS shows improvements in fatigue symptoms over controls.
Some patient organisations dispute the results of the CBT and exercise therapies.
Additional therapies recommended by different sources include adaptive pacing, therapies based on the "envelope theory", and yogaYoga.
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. 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. Previous cases have listed CFS as the cause of death in the US and Australia
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.
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. In these instances, significant numbers of people came down with illnesses described 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:
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.
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. 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. One study found several parallels when relating the symptoms of Post-polio syndrome with CFS, and postulates a possible common pathophysiology for the illnesses.
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.
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. Hysterical diagnoses are not merely diagnoses of exclusion but require criteria to be met on the positive grounds of both primary and secondary gain. 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,. Feeling depressed is also a commonplace reaction to the losses caused by chronic illness which can in some cases become a comorbid situational depression.
A lack of information and awareness has led to many patients to feel stigmatized. CFS patients may not receive total medical and social acceptance and they state that some people trivialise the illness.
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.
The outbreak that gave rise to the name Myalgic Encephalomyelitis (see Chronic fatigue syndrome outbreaks) 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.
(Benign) Myalgic Encephalomyelitis was first classified into the International Classification of Diseases in 1969 under Diseases of the nervous system.
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.
In 2006 the CDC estimated there were more than 1 million cases of CFS in the US and commenced a public awareness program.
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.
For years, many professionals within the medical community did not recognize CFS as a real condition, nor was 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. The etiology is unknown and a major divide exists over whether funding for research and treatment should focus on physiological, psychological or psychosocial aspects of CFS. The division is especially great between patient groups and psychological and psychosocial treatment advocates in Great Britain. Sufferers describe the struggle for healthcare and legitimacy due to bureaucratic denial of the condition because of its lack of a known etiology. Disagreements over how the condition is dealt with by health care systems has resulted in an expensive and prolonged conflict for all involved.
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