Chronic fatigue syndrome (
CFS) is the most common name used to designate a significantly debilitating medical 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, not substantially relieved by rest, nor caused by other medical conditions. The disorder may also be referred to as myalgic encephalomyelitis (ME),
post-viral fatigue syndromePost-viral fatigue syndrome is a condition or conditions characterized by fatigue following a viral infection. The term is not widely used, but the state of prolonged or severe fatigue after illness is not uncommon...
(PVFS), chronic fatigue immune dysfunction syndrome (CFIDS), or several other terms. Although classified by the World Health Organization under
Diseases of the nervous system, the
etiologyEtiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
(cause or origin) of CFS is unknown, and multiple psychological and physiological factors may contribute to the development and maintenance of symptoms. There is no diagnostic laboratory test or biomarker for CFS.
Symptoms of CFS include post-exertional malaise; unrefreshing sleep; widespread
muscleMyalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
and
joint painArthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
; sore throat; headaches of a type not previously experienced; cognitive difficulties; chronic, often severe, mental and physical exhaustion; and other characteristic symptoms in a previously healthy and active person. Persons with CFS may report additional symptoms including
muscle weaknessMuscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...
, increased sensitivity to light, sounds and smells,
orthostatic intoleranceOrthostatic intolerance is a subcategory of dysautonomia, a disorder of the autonomic nervous system occurring when an individual stands up....
, digestive disturbances,
depressionDepression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
, and cardiac and
respiratoryThe respiratory system is the anatomical system of an organism that introduces respiratory gases to the interior and performs gas exchange. In humans and other mammals, the anatomical features of the respiratory system include airways, lungs, and the respiratory muscles...
problems. It is unclear if these symptoms represent co-morbid conditions or are produced by an underlying etiology of CFS.
Fatigue is a common symptom in many illnesses, but CFS is comparatively rare. 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 "chronic fatigue syndrome" 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.
Classification
Notable definitions include:
- CDC definition (1994)—the most widely used clinical and research description of CFS, it is also called the Fukuda
Keiji Fukuda is an American physician with expertise in influenza epidemiology. In March 2009, Fukuda was appointed Assistant Director-General for Health, Security and Environment ad interim for the World Health Organization and as of September 2010, he holds this position permanently...
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]".
The different case definitions used to research the illness may influence the types of patients selected for studies, and research also suggests subtypes of patients exist within the heterogeneous illness. Clinical practice guidelines—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 ServiceThe National Health Service is the shared name of three of the four publicly funded healthcare systems in the United Kingdom. They provide a comprehensive range of health services, the vast majority of which are free at the point of use to residents of the United Kingdom...
in
EnglandEngland is a country that is part of the United Kingdom. It shares land borders with Scotland to the north and Wales to the west; the Irish Sea is to the north west, the Celtic Sea to the south west, with the North Sea to the east and the English Channel to the south separating it from continental...
and
WalesWales is a country that is part of the United Kingdom and the island of Great Britain, bordered by England to its east and the Atlantic Ocean and Irish Sea to its west. It has a population of three million, and a total area of 20,779 km²...
, produced in 2007 by the
National Institute for Health and Clinical ExcellenceThe National Institute for Health and Clinical Excellence is a special health authority of the English National Health Service , serving both English NHS and the Welsh NHS...
(NICE).
Naming
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 syndromePost-viral fatigue syndrome is a condition or conditions characterized by fatigue following a viral infection. The term is not widely used, but the state of prolonged or severe fatigue after illness is not uncommon...
, raphe nucleus encephalopathy,
Royal FreeThe Royal Free Hospital is a major teaching hospital in Hampstead, London, England and part of the Royal Free Hampstead NHS Trust....
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
AchesonSir Donald Acheson KBE was a British physician and epidemiologist who served as Chief Medical Officer of the United Kingdom from 1983–91...
, 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
LancetThe Lancet is a weekly peer-reviewed general medical journal. It is one of the world's best known, oldest, and most respected general medical journals...
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."
Onset
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
pathogenA pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
s, 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.
Symptoms
The most commonly used
diagnostic criteriaMedical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...
and definition of CFS for research and clinical purposes were published by the United States
Centers for Disease Control and PreventionThe Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
(CDC). The CDC definition of CFS requires the following two criteria be fulfilled:
- A new onset (not lifelong) of unexplained, persistent fatigue
Fatigue is a state of awareness describing a range of afflictions, usually associated with physical and/or mental weakness, though varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles...
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
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
or concentration
- Post-exertional malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
, where physical or mental exertions bring on "extreme, prolonged exhaustion and sickness"
- Unrefreshing sleep
- Muscle pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
(myalgiaMyalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
)
- Pain in multiple joints (arthralgia
Arthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
)
- Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
s of a new kind or greater severity
- Sore throat, frequent or recurring
- Tender lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
s (cervical or axillary)
Other common symptoms include:
- Irritable bowel, abdominal pain, nausea, diarrhea or bloating
- Chills and night sweats
- Brain fog
Cognitive dysfunction is defined as unusually poor mental function, associated with confusion, forgetfulness and difficulty concentrating...
- 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:
Lyme diseaseLyme disease, or Lyme borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia. Borrelia burgdorferi sensu stricto is the main cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii cause most...
, "
sleep disorderA sleep disorder, or somnipathy, is a medical disorder of the sleep patterns of a person or animal. Some sleep disorders are serious enough to interfere with normal physical, mental and emotional functioning...
s, depression,
alcoholAlcohol abuse, as described in the DSM-IV, is a psychiatric diagnosis describing the recurring use of alcoholic beverages despite negative consequences. Alcohol abuse eventually progresses to alcoholism, a condition in which an individual becomes dependent on alcoholic beverages in order to avoid...
/
substanceA substance-related disorder is an umbrella term used to describe several different conditions associated with several different substances .A substance related disorder is a condition in which an individual uses or abuses a...
abuse, diabetes,
hypothyroidismHypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
, mononucleosis (mono),
lupusSystemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
,
multiple sclerosisMultiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
(MS), chronic hepatitis and various malignancies." Medications can also cause side effects that mimic symptoms of CFS.
Functioning
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 including late-stage
AIDSAcquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
,
lupusLupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
,
rheumatoid arthritisRheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
,
chronic obstructive pulmonary diseaseChronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...
(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 The severity of symptoms and disability is the same in both genders with strongly disabling
chronic painChronic pain has several different meanings in medicine. Traditionally, the distinction between acute and chronic pain has relied upon an arbitrary interval of time from onset; the two most commonly used markers being 3 months and 6 months since the initiation of pain, though some theorists and...
, 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.
Cognitive functioning
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.
Pathophysiology
The mechanisms and
pathogenesisThe pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...
of chronic fatigue syndrome are unknown. Research studies have examined and hypothesized about the possible biomedical and epidemiological characteristics of the disease, including
oxidative stressOxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
,
genetic predispositionA genetic predisposition is a genetic affectation which influences the phenotype of an individual organism within a species or population but by definition that phenotype can also be modified by the environmental conditions. In the rest of the population, conditions cannot have that effect...
,
infectionAn infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
by
virusA virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es and
pathogenic bacteriaPathogenic bacteria are bacteria that cause bacterial infection. This article deals with human pathogenic bacteria.Although the vast majority of bacteria are harmless or beneficial, quite a few bacteria are pathogenic...
,
hypothalamic-pituitary-adrenal axisThe hypothalamic-pituitary-adrenal axis , also known as thelimbic-hypothalamic-pituitary-adrenal axis and, occasionally, as the hypothalamic-pituitary-adrenal-gonadotropic axis, is a complex set of direct influences and feedback interactions among the hypothalamus, the pituitary gland ,...
abnormalities ,
immune dysfunctionAutoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
as well as psychological and
psychosocialFor a concept to be psychosocial means it relates to one's psychological development in, and interaction with, a social environment. The individual needs not be fully aware of this relationship with his or her environment. It was first commonly used by psychologist Erik Erikson in his stages of...
factors. Although it is unclear which factors are a cause, or consequence, of CFS, various models are proposed.
Diagnosis
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.
Treatment
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 trialA randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
s. 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. No intervention has been proven effective in restoring the ability to work.
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 ReviewThe Cochrane Library is a collection of databases in medicine and other healthcare specialties provided by the Cochrane Collaboration and other organisations. At its core is the collection of Cochrane Reviews, a database of systematic reviews and meta-analyses which summarize and interpret the...
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 therapyGraded exercise therapy is physical activity that starts very slowly and gradually increases over time. This approach is used as part of a treatment plan for chronic fatigue syndrome and certain other conditions...
(GET) is a form of
physical therapyPhysical therapy , often abbreviated PT, is a health care profession. Physical therapy is concerned with identifying and maximizing quality of life and movement potential within the spheres of promotion, prevention, diagnosis, treatment/intervention,and rehabilitation...
. 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". 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
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
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
immunomodulatorAn immunomodulator, also known as an immunotherapy is a substance which has an effect on the immune system.- Immunosuppressants :Inhibits immune response in organ transplantation and autoimmune diseases.- Immunostimulants :...
y agents. The evidence for antidepressants is mixed and their use remains controversial. Many CFS patients are sensitive to medications, particularly
sedativeA sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
s, and some patients report chemical and
food sensitivitiesFood intolerance or non-allergic food hypersensitivity is a term used widely for varied physiological responses associated with a particular food, or compound found in a range of foods....
. CFS patients have a low
placeboA placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
response, especially to psychological-psychiatric interventions, perhaps due to patient expectations.
Recovery
A systematic review of 14 studies that described improvement and occupational outcomes of people with CFS found that "the median full recovery rate was 5% (range 0–31%) and the median proportion of patients who improved during follow-up was 39.5% (range 8–63%). Return to work at follow-up ranged from 8 to 30% in the three studies that considered this outcome." .... "In five studies, a worsening of symptoms during the period of follow-up was reported in between 5 and 20% of patients." A good outcome was associated with less fatigue severity at baseline, a sense of control over symptoms and not attributing illness to a physical cause. Another review found that children have a better prognosis than adults, with 54–94% having recovered by follow-up compared to less than 10% of adults returning to pre-morbid levels of functioning.
According to the CDC, delays in diagnosis and treatment can reduce the chance of improvement.
Mortality
Two studies were published in 2006 that directly addressed mortality in CFS. A 14 year
longitudinal studyA longitudinal study is a correlational research study that involves repeated observations of the same variables over long periods of time — often many decades. It is a type of observational study. Longitudinal studies are often used in psychology to study developmental trends across the...
of persons with CFS reported that all-cause mortality or suicide rates of individuals were not significantly different from
standardized mortality ratesThe standardized mortality ratio or SMR in epidemiology is the ratio of observed deaths to expected deaths, where expected deaths are calculated for a typical area with the same age and gender mix by looking at the death rates for different ages and genders in the larger population.The SMR may be...
(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.
Prevalence
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
prevalenceIn epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
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 ServiceThe National Health Service is the shared name of three of the four publicly funded healthcare systems in the United Kingdom. They provide a comprehensive range of health services, the vast majority of which are free at the point of use to residents of the United Kingdom...
.
Risk factors
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
contagiousA contagious disease is a subset category of infectious diseases , which are easily transmitted by physical contact with the person suffering the disease, or by their secretions or objects touched by them....
, though it is seen in members of the same family; this is believed to be a familial or
geneticGenetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
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."
Differential diagnoses
Certain medical conditions can cause chronic fatigue and must be ruled out before a diagnosis of CFS can be given.
HypothyroidismHypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
,
anemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, 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
fibromyalgiaFibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...
(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 sensitivityMultiple chemical sensitivity is a chronic medical condition characterized by symptoms the affected person attributes to exposure to low levels of chemicals. Commonly suspected substances include smoke, pesticides, plastics, synthetic fabrics, scented products, petroleum products and paints...
,
Gulf War syndromeGulf War syndrome or Gulf War illness describes a medical condition that affected veterans and civilians who were near conflicts during or downwind of chemical weapons depot demolition, after the 1991 Gulf War. A wide range of acute and chronic symptoms have included fatigue, musculoskeletal...
and
post-polio syndromePost-polio syndrome is a condition that affects approximately 25–50% of people who have previously contracted poliomyelitis—a viral infection of the nervous system—after the initial infection. Typically the symptoms appear 15–30 years after recovery from the original paralytic attack, at an age of...
have symptoms similar to those of CFS, and the last 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 validityIn psychology, discriminant validity tests whether concepts or measurements that are supposed to be unrelated are, in fact, unrelated.Campbell and Fiske introduced the concept of discriminant validity within their discussion on evaluating test validity. They stressed the importance of using both...
of undifferentiated
somatoform disorderIn psychology, a somatoform disorder is a mental disorder characterized by physical symptoms that suggest physical illness or injury - symptoms that cannot be explained fully by a general medical condition, direct effect of a substance, or attributable to another mental disorder . The symptoms that...
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 diagnosedA differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...
from primary depression due to the absence of
anhedoniaIn psychology and psychiatry, anhedonia is defined as the inability to experience pleasure from activities usually found enjoyable, e.g. hobbies, exercise, social interaction or sexual activity....
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.
Co-morbidity
Many CFS patients will also have, or appear to have, other medical problems or related diagnoses. Co-morbid
fibromyalgiaFibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...
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 syndromeIrritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...
,
temporomandibular jointThe temporomandibular joint is the joint of the jaw and is frequently referred to as TMJ. There are two TMJs, one on either side, working in unison. The name is derived from the two bones which form the joint: the upper temporal bone which is part of the cranium , and the lower jaw bone called the...
pain,
headacheA headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
including
migraineMigraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
s, and other forms of
myalgiaMyalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
. 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
endometriosisEndometriosis is a gynecological medical condition in which cells from the lining of the uterus appear and flourish outside the uterine cavity, most commonly on the ovaries. The uterine cavity is lined by endometrial cells, which are under the influence of female hormones...
compared with women in the general USA population.
History
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 HospitalLos Angeles County+USC Medical Center, also known as County/USC, by the abbreviation LAC+USC, or by the name Los Angeles County General, is a 600-bed public teaching hospital located in the Boyle Heights neighborhood of Los Angeles, California...
. 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 HospitalThe Royal Free Hospital is a major teaching hospital in Hampstead, London, England and part of the Royal Free Hampstead NHS Trust....
in
LondonLondon is the capital city of :England and the :United Kingdom, the largest metropolitan area in the United Kingdom, and the largest urban zone in the European Union by most measures. Located on the River Thames, London has been a major settlement for two millennia, its history going back to its...
,
United KingdomThe United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
, 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 DiseasesThe International Statistical Classification of Diseases and Related Health Problems is a medical classification that provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or disease...
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 PreventionThe Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
epidemiologists examined patients at the Lake Tahoe outbreak. In 2006 the CDC commenced a national program to educate the American public and health care professionals about CFS.
A 2009 study published in the journal "Science", reported an association between a retrovirus xenotropic murine leukemia virus-related virus (XMRV) and CFS. The editors of
Science, subsequently attached an "Editorial Expression of Concern" to the report to the effect that the validity of the study "
is now seriously in question". and in September 2011, the authors published a "Partial Retraction" of their 2009 findings,. Also in September 2011 the Blood XMRV Scientific Research Working Group published a report which concluded "that currently available XMRV/P-MLV assays, including the assays employed by the three participating laboratories that previously reported positive results on samples from CFS patients and controls (2, 4), cannot reproducibly detect direct virus markers (RNA, DNA, or culture) or specific antibodies in blood samples from subjects previously characterized as XMRV/P-MLV positive (all but one with a diagnosis of CFS) or healthy blood donors."
Research funding
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 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.
Economic impact
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.
Social issues
A study found that CFS patients report a heavy
psychosocialFor a concept to be psychosocial means it relates to one's psychological development in, and interaction with, a social environment. The individual needs not be fully aware of this relationship with his or her environment. It was first commonly used by psychologist Erik Erikson in his stages of...
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.
Support groups
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.
Doctor-patient relations
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. Disagreements over how the condition is dealt with by health care systems has resulted in an expensive and prolonged conflict for all involved.
A major divide exists over whether funding for research and treatment should focus on physiological, psychological or
psychosocialFor a concept to be psychosocial means it relates to one's psychological development in, and interaction with, a social environment. The individual needs not be fully aware of this relationship with his or her environment. It was first commonly used by psychologist Erik Erikson in his stages of...
aspects of CFS. This division is especially great between patient groups and psychological and psychosocial treatment advocates in Great Britain. In 2011, it was reported by the
BBCThe British Broadcasting Corporation is a British public service broadcaster. Its headquarters is at Broadcasting House in the City of Westminster, London. It is the largest broadcaster in the world, with about 23,000 staff...
this conflict had involved personal vilification and allegations of professional misconduct to professional societies and universities of researchers who were investigating possible psychiatric connections. One of these researchers,
Simon WesselySimon Wessely is a British psychiatrist. He is professor of epidemiological and liaison psychiatry at the Institute of Psychiatry, King's College London and Head of its department of psychological medicine, Vice Dean for Academic Psychiatry, Teaching and Training at the Institute of Psychiatry, as...
, reported personal death threats, and others noted such vilification would lead researchers to abandon or avoid the area of study entirely, as few would want to undergo this "torrent of abuse." Charles Shepherd from the ME Association condemned the abuse of researchers but emphasised that the underlying frustration stems from government funding of research focusing almost exclusively on psychiatric, rather than biomedical, causes.
Blood donation
Based on the possible link between CFS and XMRV, in 2010 a variety of
national blood banksA blood donation occurs when a person voluntarily has blood drawn and used for transfusions or made into medications by a process called fractionation....
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 ServicesCanadian Blood Services is a national, not-for-profit charitable organization that manages the blood supply in all provinces and territories of Canada, outside of Quebec, and oversees the OneMatch Stem Cell and Marrow Network . A separate organization, Héma-Québec, operates in the province of Quebec...
, the
New Zealand Blood ServiceThe New Zealand Blood Service is the body primarily responsible for blood donation and related services in New Zealand.Unlike its Australian counterpart, the NZBS is a service operated by the New Zealand Government, not the New Zealand Red Cross....
, the
Australian Red Cross Blood ServiceThe Australian Red Cross Blood Service is a branch of the Australian Red Cross. It is the body primarily responsible for blood donation and related services in Australia.-History:...
and the American Association of Blood Banks,
In November 2010 the UK National Blood Service introduced a permanent deferral of donation from CFS patients based on the potential harm to those patients that may result from their giving blood.
Controversy
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 exist over funding for research and treatment of
physiologicalPhysiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...
versus
psychologicalPsychology is the study of the mind and behavior. Its immediate goal is to understand individuals and groups by both establishing general principles and researching specific cases. For many, the ultimate goal of psychology is to benefit society...
and
psychosocialFor a concept to be psychosocial means it relates to one's psychological development in, and interaction with, a social environment. The individual needs not be fully aware of this relationship with his or her environment. It was first commonly used by psychologist Erik Erikson in his stages of...
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
WesselySimon Wessely is a British psychiatrist. He is professor of epidemiological and liaison psychiatry at the Institute of Psychiatry, King's College London and Head of its department of psychological medicine, Vice Dean for Academic Psychiatry, Teaching and Training at the Institute of Psychiatry, as...
contested the WHO classification of CFS under diseases of the nervous system, arguing that it was a form of
neurastheniaNeurasthenia is a psycho-pathological term first used by George Miller Beard in 1869 to denote a condition with symptoms of fatigue, anxiety, headache, neuralgia and depressed mood...
to be classified as a psychiatric condition.
External links