Chronic fatigue syndrome
|Chronic fatigue syndrome|
|Classification and external resources|
Chronic fatigue syndrome (CFS) is the most common name used to specify a disorder or group of disorders generally defined by persistent fatigue accompanied by other specific symptoms for a minimum of six months, not due to ongoing exertion and not substantially relieved by rest. The disorder may also be referred to as myalgic encephalomyelitis (ME), post-viral fatigue syndrome (PVFS), or several other terms. Although classified by the World Health Organization under Diseases of the nervous system, the etiology (cause or origin) of CFS is currently unknown and there is no diagnostic laboratory test or biomarker.
Fatigue is a common symptom in many illnesses, but CFS is a multi-systemic disease and is relatively rare by comparison. Symptoms of CFS include post-exertional malaise; unrefreshing sleep; widespread muscle and joint pain; sore throat; cognitive difficulties; chronic, often severe, mental and physical exhaustion; and other characteristic symptoms in a previously healthy and active person. CFS patients may report additional symptoms including muscle weakness, increased sensitivity to light, sounds and smells, orthostatic intolerance, digestive disturbances, depression, and cardiac and respiratory problems. It is unclear if these symptoms represent co-morbid conditions or are produced by an underlying etiology of CFS. All diagnostic criteria require that the symptoms must not be caused by other medical conditions.
Estimates of CFS prevalence vary widely, from 7 to 3,000 cases of CFS for every 100,000 adults, but national health organizations have estimated more than 1 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. The quality of life is "particularly and uniquely disrupted" in CFS.
There is agreement on the genuine threat to health, happiness and productivity posed by CFS, but various physicians' groups, researchers and patient advocates promote different nomenclature, diagnostic criteria, etiologic hypotheses and treatments, resulting in controversy about many aspects of the disorder. The name CFS itself is controversial as many patients and advocacy groups, as well as some experts, want the name changed as they believe that it stigmatizes by not conveying the seriousness of the illness.
Notable definitions include:
- CDC definition (1994)—the most widely used clinical and research description of CFS, it is also called the Fukuda definition and was based on the Holmes or CDC 1988 scoring system. The 1994 criteria require the presence of four or more symptoms beyond fatigue, where the 1988 criteria require six to eight.
- The Oxford criteria (1991)—includes 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 that "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]".
Using different case definitions may influence the types of patients selected for studies, and there is research to suggest subtypes of patients or disease exist. Clinical practice guidelines—with the aim of improving diagnosis, management, and treatment—are generally based on case descriptions. 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 (CFS) 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 that different symptom profiles may be caused by a number of 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 (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 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." The 1996 report received some acceptance, but also harsh criticism that patients' views had been 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 definition of CFS requires the following two criteria be fulfilled:
- A new onset (not lifelong) of unexplained, persistent fatigue unrelated to exertion and not substantially relieved by rest, that causes a significant reduction in 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)
Other common symptoms include:
- Irritable bowel, abdominal pain, nausea, diarrhea or bloating
- Chills and night sweats
- Brain fog
- Chest pain
- Shortness of breath
- Chronic cough
- Visual disturbances (blurring, sensitivity to light, eye pain or dry eyes)
- Allergies or sensitivities to foods, alcohol, odors, chemicals, medications or noise
- Difficulty maintaining upright position (orthostatic instability, irregular heartbeat, dizziness, balance problems or fainting)
- Psychological problems (depression, irritability, mood swings, anxiety, panic attacks)
The CDC recommends that persons with symptoms resembling those of CFS consult a physician to rule out several treatable illnesses: "sleep disorders, depression, 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.
People report critical reductions in levels of physical activity and a reduction in the complexity of activity has been observed, with reported impairment comparable to other fatiguing medical conditions such as late-stage AIDS, lupus, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), and the effects of chemotherapy. 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 The severity of symptoms and disability is the same in both genders with strongly disabling chronic pain, but despite a common diagnosis the functional capacity of individuals with CFS varies greatly. While some lead relatively normal lives, others are totally bed-ridden and unable to care for themselves. 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.
A 2010 meta-analysis concluded cognitive symptoms were principally resultants of decreased attention, memory, and reaction time. The deficits were in the range of 0.5 to 1.0 standard deviations below expected and were judged 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 mechanisms and pathogenesis of chronic fatigue syndrome are unknown. Research studies have examined and hypothesized about the possible biomedical and epidemiological characteristics of the disease, 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 which factors are a cause, or consequence, of CFS, various models are proposed.
A 2009 study reported an association of the retrovirus xenotropic murine leukemia virus-related virus (XMRV) and CFS, but many independent laboratories have detected no XMRV in CFS patient samples. Researchers suspect that contamination was responsible for the initial positive results, a hypothesis supported by several independent studies.
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.
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 patient surveys indicated that pacing is the most helpful intervention, or is considered useful by 96% of participants. Medication plays a minor role in management.
Cognitive behavioral therapy
Cognitive behavioral therapy (CBT), a form of psychological therapy often used to treat chronically ill patients, is a moderately effective treatment for CFS  that "can be useful in treating some CFS patients." Since the cause or causes of CFS are unknown, CBT tries to help patients understand their individual symptoms and beliefs and develop strategies to improve day-to-day functioning.
A Cochrane Review meta-analysis of 15 randomized, controlled cognitive behavioral therapy trials with 1043 participants concluded that CBT was an effective treatment to reduce the symptom of fatigue. Four reviewed studies showed that CBT resulted in a clinical response for 40% of participants vs 26% of those treated with "usual care". Similarly, in three studies CBT worked better than other types of psychological therapies (48% vs 27%). The effects may diminish after a course of 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 showed 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 mediated by a change in physical activity.
CBT has been criticised by patients' organisations because of negative reports from some of their members that have indicated that CBT can sometimes make people worse, a common result across multiple patient surveys.
Graded exercise therapy
Graded exercise therapy (GET) 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. A systematic review published in 2006 included the same five RCTs, noting that "no severely affected patients were included in the studies of GET". Surveys conducted on behalf of patient organizations commonly report adverse effects.
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 which encourages behavioral change while acknowledging patient fluctuations in symptom severity and delayed exercise recovery. Patients are advised to set manageable daily activity/exercise goals and balance activity and rest to avoid over-exertion which may worsen symptoms. Those able to function within their individual limits are encouraged to gradually increase activity and exercise levels while maintaining established energy management techniques. The goal is to gradually increase the level of routine functioning of the individual. A small randomised controlled trial concluded 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 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." 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-morbid levels of functioning. According to the CDC, delays in diagnosis and treatment can reduce the chance of improvement.
Two studies were published in 2006 that directly addressed mortality in CFS. A 14 year longitudinal study of persons with CFS reported that all-cause mortality or suicide rates of individuals were not significantly different from standardized mortality rates (SMRs). A smaller retrospective study in individuals with CFS reported the leading causes of death were heart failure, suicide, and cancer. The ages of death for these three conditions were significantly younger than in the general population respectively. Significant limitations of the study were the inability to check the accuracy of the CFS diagnosis of the individuals or causes of death, and the inability to generalize the data to the overall population of patients with CFS due to the data collection methods.
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, though it is seen in members of the same family; this is believed to be a familial or genetic link but more research is required for a definitive answer.
A systematic review in 2008 included 11 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) 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. Multiple chemical sensitivity, Gulf War syndrome and post-polio syndrome have symptoms similar to those of CFS, and the latter is also theorized to have a common pathophysiology.
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.
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 seen in CFS may be differentially diagnosed from primary depression due to the absence of anhedonia and la belle indifference, 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, where only patients with fibromyalgia show abnormal pain responses. 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. Feeling depressed is also a commonplace reaction to the losses caused by chronic illness which can in some cases become a comorbid situational depression. 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 is now called chronic fatigue syndrome and affected a large number of nurses and doctors. In 1955 at the Royal Free Hospital in London, United Kingdom, another outbreak occurred that also affected mostly the hospital staff. Also resembling CFS, it was called both Royal Free disease and benign myalgic encephalomyelitis and formed the basis of descriptions by Acheson, Ramsay, and others. 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 (CFS) 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.
In November 2006, an unofficial inquiry by an ad hoc group of parliamentarians, set up and chaired by former MP, Dr Ian Gibson, called the Group on Scientific Research into ME was informed by a government minister 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 this type of 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. A 2008 study estimated that the total annual cost burden of ME/CFS to society in the US was approximately $18.7 to $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 and/or they feel bullied by medical and educational professionals. The ambiguity of the status of CFS as a medical condition may cause higher perceived stigma.
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.
Some in the medical community did not at first 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. 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. 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.
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, and decline donations when aware the potential donor had been diagnosed. Organizations adopting these or similar measures included the Canadian Blood Services, the New Zealand Blood Service, the Australian Red Cross Blood Service, the American Association of Blood Banks, and the NHS Blood and Transplant.
Chronic fatigue syndrome (CFS) is an illness with a long history of controversies. There has been much contention over the etiology, pathophysiology, nomenclature and diagnostic criteria. Controversies still exists 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.
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- ed. by (2003). Jason LA; Fennell PA & Taylor RR. ed. Handbook of Chronic Fatigue Syndrome. John Wiley & Sons. ISBN 978-0471415121.
- Sharpe, Michael; Frankie Campling (2000). Chronic fatigue syndrome (CFS/ME). Oxford [Oxfordshire]: Oxford University Press. ISBN 0-19-263049-0.
- Chronic Fatigue Syndrome at the US Centers for Disease Control and Prevention
- Chronic fatigue syndrome at the Open Directory Project
- Research database at ME Research UK