Chronic Fatigue Syndrome

 

(CFS), collection of persistent, debilitating symptoms, the most notable of which is severe, lasting fatigue. In other countries it is known variously as myalgic encephalomyelitis, chronic fatigue and immune dysfunction syndrome, and postviral fatigue syndrome. It was first recognized as a syndrome in the 1860s by Dr. George Beard, who called it neurasthenia. He believed it to be a neurosis with a fatigue component. Definitions and theories of its cause have changed over the years; many cases have been misdiagnosed as imaginary because doctors could find no cause. In the mid-1980s it came to the public's attention, as affluent women in their thirties began to seek treatment. (For unknown reasons, more women than men seek treatment for the disease.)

Symptoms and Identification

As currently defined, chronic fatigue syndrome is the presence of severe, disabling fatigue lasting for six or more consecutive months. The fatigue is persistent or relapsing, and is new (i.e., not lifelong), not relieved by rest, not the result of ongoing exertion, and interferes with normal work, social, educational, or personal activities. Diagnosis also requires at least four of the following symptoms, each persistent or recurring and not present before the fatigue: impairment of short-term memory or concentration, sore throat, tender lymph nodes in the neck or axillary region, muscle pain, joint pain, headaches peculiar to the syndrome, unrefreshing sleep, and malaise of more than one day's duration following exertion. Chronic fatigue that does not meet all these criteria is termed “idiopathic fatigue.”

The course of the disease varies. Many people first experience symptoms after a cold or bout of the flu. Most people reach a plateau early on; the symptoms come and go with varying severity afterward. Some experience complete remission; others have their symptoms indefinitely.

There are no specific diagnostic tests. Diagnosis must first rule out known causes of fatigue such as hypothyroidism, cancer, multiple sclerosis, and major depression with psychotic or melancholic features (e.g., schizophrenia, bipolar disorder). Chronic fatigue syndrome and nonpsychotic, nonmelancholic depression, however, are not mutually exclusive. Substance abuse and side effects of prescribed medications must also be eliminated as possible causes.

Cause and Treatment

There is no known single cause of CFS. Some authorities believe it is a condition shared by many different underlying diseases rather than an entity unto itself; others believe it is caused by a defect of the immune system. Hormonal deficits, low blood pressure, and viral infections have been studied as possible causes or contributors. The postulated causal link with Epstein-Barr virus hypothesized in the mid-1980s has been discounted.

There is no definitive treatment for CFS, although success has been reported anecdotally with antidepressants, antianxiety medications, antivirals, and immune boosters. Symptomatic treatment for the muscle and joint pains is helpful in some cases. Counseling and peer support groups help some patients cope with the frustrating nature of the disease.

Chronic fatigue syndrome/ myalgic encephalomyelitis
Classification & external resources

ICD-10	G93.3
ICD-9	780.71
DiseasesDB	1645
MedlinePlus	001244
eMedicine	med/3392  ped/2795
MeSH	D015673

Chronic fatigue syndrome (CFS) is one of several names given to a poorly understood, highly debilitating disorder of uncertain cause/causes, which is thought to affect approximately 4 per 1,000 adults^[1] in the United States and other countries, and a smaller fraction of children.^[2]

The disorder is marked by chronic mental and physical exhaustion, often severe, and by other specific symptoms, arising in previously healthy and active persons. Despite promising avenues of research, there remains no objective assay or pathological finding which is widely accepted to be diagnostic of CFS. It remains largely a diagnosis of exclusion, made on the basis of patient history and symptomatic criteria, although a number of tests exist which can help aid diagnosis.^[3] Although there is agreement on the genuine threat to health, happiness, and productivity posed by CFS, various physicians' groups, researchers, and patient activists champion very different nomenclature, diagnostic criteria, etiologic hypotheses, and favored treatments, resulting in ongoing controversy about nearly all aspects of the disorder. The name chronic fatigue syndrome is itself controversial, with some patient advocates and other authorities preferring terms such as myalgic encephalomyelitis ("ME" or "ME/CFS") and post-viral fatigue syndrome ("PVFS"), which imply specific underlying etiologies or pathologic processes.^[4]

Chronic fatigue syndrome is not the same as "chronic fatigue”. While fatigue is a common symptom in many illnesses, CFS is a multi-symptom disease and is relatively rare by comparison.^[5] Definitions (other than the 1991 UK Oxford criteria^[6]) require a number of features, the most common being severe mental and physical exhaustion which is "unrelieved by rest" (according to the 1994 Fukuda definition),^[7] and may be worsened by even trivial exertion (a mandatory diagnostic criterion according to some systems). Most diagnostic criteria insist that the symptoms must be present for at least six months, and all insist on there being no other cause for them: i.e. the symptoms must be idiopathic, not caused by other medical conditions such as diabetes, hypothyroidism or anemia. CFS patients may report many other 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 the same underlying etiology as CFS itself.^[8] Some cases improve over time, and treatments (though none are universally accepted) bring a degree of improvement to many others, though resolution is rare.

CFS occurs more often, but not exclusively, in women, for unknown reasons. CFS is most easily diagnosed when formerly active adults become ill, and is most commonly diagnosed in young to middle aged adults, although it is also reported in children, adolescents and the elderly.^[9]

Nomenclature

The naming of chronic fatigue syndrome has been challenging, since consensus is lacking within the medical, research, and patient communities regarding the defining features of the syndrome. It may be considered by different authorities to be a central nervous system, metabolic, (post-)infectious, immune system or neuropsychiatric disorder.

There are a number of different terms which have been identified at various times with this disorder.

• Myalgic encephalomyelitis or ME translates to "inflammation of the brain and spinal cord with muscle pain" and as a disease entity has been recognized and described in the medical literature since 1938, with the seminal paper being that by Wallis in 1957; Sir Donald Acheson's (a former Chief Medical Officer) major review of ME was published in 1959.^[10] In 1962 the distinguished neurologist Lord Brain included ME in his textbook of neurology, and in 1978 the Royal Society of Medicine accepted ME as a distinct clinical entity. In 1988 both the UK Department of Health and Social Services and the British Medical Association officially recognized it as a legitimate and potentially distressing disorder.^{[citation needed]} Opponents of the term ME maintain there is no objective evidence of inflammation, although central nervous system inflammation has been documented in some patients diagnosed with CFS (e.g. the case of Sophia Mirza). Many patients, and some research and medical professionals in the United Kingdom and Canada, use this term in preference to or in conjuction with CFS (ME/CFS or CFS/ME). The international association of researchers and clinicians is named IACFS/ME.
• Myalgic encephalopathy, similar to the above, with "pathy" referring to unspecified pathology rather than inflammation; this term has some support in the UK and US.
• Chronic fatigue syndrome (CFS); this name was introduced non-unanimously in 1988 by a group of United States researchers based at the Centers for Disease Control and Prevention in response to the 1984 Lake Tahoe ME epidemic, and is used increasingly over other designations, particularly in the United States. Many patients and clinicians perceive the term as trivializing^[11] and as the 1994 Fukuda paper itself cedes, stigmatizing which has led to a campaigning movement to change the name and definition.
• Chronic fatigue immune dysfunction syndrome (CFIDS); many patients and advocacy groups in the USA use the term CFIDS, introduced by patients current with the biomedical research in an attempt to reduce the psychiatric stigma attached to "chronic fatigue," as well as the public perception of CFS as a psychiatric syndrome. The term also calls attention to the immune dysfunction in patients for which evidence has been steadily growing since the illness was first identified, and which now appears to be an integral part of this illness.^[12]
• Post-viral fatigue syndrome (PVFS); this is a related disorder. According to original ME researcher Dr. Melvin Ramsay, "The crucial differentiation between ME and other forms of post-viral fatigue syndrome lies in the striking variability of the symptoms not only in the course of a day but often within the hour^[13].
• Chronic Epstein-Barr virus (CEBV) or Chronic Mononucleosis; the term CEBV was introduced by virologists Dr. Stephen Straus^[14] and Dr. Jim Jones^[15] in the United States. The Epstein-Barr virus, a neurotropic virus that more commonly causes infectious mononucleosis, was thought by Straus and Jones to be the cause of CFS. Subsequent discovery of the closely related human herpesvirus 6 shifted the direction of biomedical studies, although a vastly expanded and substantial body of published research continues to show active viral infection or reinfection of CFS patients by these two viruses. These viruses are also found in healthy controls, lying dormant.
• Low Natural Killer cell disease; this name is used widely in Japan. It reflects research showing a reduction in the number of natural killer cells in many CFS patients. More significantly, in-vitro activity of the remaining natural killer cells is reduced, often by as much as two thirds.
• Yuppie Flu; this was a factually inaccurate term first published in a November 1990 Newsweek cover story^[specify] and never official medical terminology. It reflects a stereotypical assumption that CFS mainly affects the affluent ("yuppies"), and implies that it is a form of burnout. CFS, however, affects people of all races, genders, and social standings^[1]; and is not a form of flu. The phrase is considered offensive by patients and clinicians.^[16][17][18]
• Uncommonly used terms include Akureyri Disease, Iceland disease (in Iceland),^[19] Royal Free disease (after the location of an outbreak),^[20] atypical poliomyelitis, epidemic neuromyasthenia, epidemic vasculitis, raphe nucleus encephalopathy, and Tapanui flu (after the New Zealand town Tapanui where the first doctor in the country to investigate the disease, Dr Peter Snow, lived).

Signs and Symptoms

Onset

The majority of CFS cases begin after a period of stress in the year preceding the illness^[21][22] or after a flu-like illness^[23][24][25] and is therefore more likely to occur during winter.^[26][27] Some cases of CFS start gradually, but the majority start suddenly, usually triggered by a flu-like viral infection. The diagnosis of Post Viral Fatigue Syndrome is sometimes given in the early stage of the illness.

Sudden onset cases

Many people with CFS report a sudden, drastic start to their illness. Some people can remember a specific day or even hour when they first became ill. Often CFS starts with, or is triggered by, another illness. Many people report getting a case of a flu-like or other respiratory infection such as bronchitis, from which they seem never to fully recover and which evolves into CFS. Some patients report that it began after a vaccination or a blood transfusion^[28].

Gradual onset cases

Other cases have a gradual onset, sometimes spread over years^[28].

Patients with Lyme disease may, despite a standard course of treatment, "evolve" clinically from the symptoms of acute Lyme to those similar to CFS^[29]. This has become an area of great controversy.

Course

It can be inferred from the 2003 "Canadian" clinical working definition of ME/CFS^[3] that there are 8 categories of symptoms:

• Fatigue: Unexplained, persistent, or recurrent physical and mental fatigue/exhaustion that substantially reduces activity levels and is not relieved (or not completely relieved) by rest.

• Post-exertional malaise: An inappropriate loss of physical and mental stamina, rapid muscular and cognitive fatigability, symptom exacerbation after exertion, plus a pathologically slow recovery period usually 24 hours or longer.

• Sleep dysfunction: "Unrefreshing" sleep/rest, poor sleep quantity, insomnia or rhythm disturbances. A study found that most CFS patients have clinically significant sleep abnormalities that are potentially treatable.^[30] Several studies suggest that while CFS patients may experience altered sleep architecture (such as reduced sleep efficiency, a reduction of deep sleep, prolonged sleep initiation, and alpha-wave intrusion during deep sleep) and mildly disordered breathing, overall sleep dysfunction does not seem to be a critical or causative factor in CFS.^{[31][32][33][34]} Sleep patterns may be further interrupted by vivid "feverish" dreams^{[citation needed]}, and unlike in healthy persons, exercise can worsen the sleep dysfunction.^{[citation needed]}

• Pain: Pain is often widespread and migratory in nature, including a significant degree of muscle pain and/or joint pain (without joint swelling or redness, and may be transitory). Other symptoms include headaches (particularly of a new type, severity, or duration), lymph node pain, sore throats, and abdominal pain (often as a symptom of irritable bowel syndrome). Patients also report; bone, eye and testicular pain, nerve pain and painful skin sensitivity. Chest pain has been attributed variously to microvascular disease or cardiomyopathy by researchers, and many patients also report painful tachycardia. A systematic review assessing the studies of chronic pain in CFS found that although the exact prevalence is unknown, it is strongly disabling in patients, but unrelated to depression.^[35]

• Neurological/cognitive manifestations: Common occurrences include confusion, forgetfulness, mental fatigue/brain fog, impairment of concentration and short-term memory consolidation, disorientation, difficulty with information processing, categorizing and word retrieval, and perceptual and sensory disturbances (e.g. spatial instability and disorientation and inability to focus vision), ataxia (unsteady and clumsy motion of the limbs or torso), muscle weakness and "twitches". There may also be cognitive or sensory overload (e.g. photophobia and hypersensitivity to noise and/or emotional overload, which may lead to "crash" periods and/or anxiety).

• Autonomic manifestations: Common occurrences include orthostatic intolerance, neurally mediated hypotension (NMH), postural orthostatic tachycardia syndrome (POTS), delayed postural hypotension, lightheadedness, extreme pallor, nausea and irritable bowel syndrome, urinary frequency and bladder dysfunction, palpitations with or without cardiac arrhythmias, and exertional dyspnea (perceived difficulty breathing or pain on breathing).

• Neuroendocrine manifestations: Common occurrences include poor temperature control or loss of thermostatic stability, subnormal body temperature and marked daily fluctuation, sweating episodes, recurrent feelings of feverishness and cold extremities, intolerance of extremes of heat and cold, digestive disturbances^[36] and/or marked weight change - anorexia or abnormal appetite, loss of adaptability and worsening of symptoms with stress.

• Immune manifestations: Common occurrences include tender lymph nodes, recurrent sore throat, recurrent flu-like symptoms, general malaise, new sensitivities to food and/or medications and/or chemicals (which may complicate treatment). At least one study has confirmed that most CFS patients reduce or cease alcohol intake, mostly due to personal experience of worsening symptoms^[37] (although the cause of this is unknown and may not be strictly "immunological" as implied by the symptom list).

There may also be other psychological/psychiatric symptoms/comorbidities in some patients.^{[citation needed]} See the Proposed causes and pathophysiology section for more information about the possible causes of, and treatments for, the above listed symptoms.

Activity levels

Patients report critical reductions in levels of physical activity^[38] with the severity of symptoms and disability the same in both genders^[39]; but despite a common diagnosis, the functional capacity of CFS patients varies greatly.^[40], and chronic pain is strongly disabling in CFS patients.^[35] According to the CDC ^[41][42], studies show that the disability in CFS patients is comparable to some well-known, very severe medical conditions, such as; multiple sclerosis, AIDS, lupus, rheumatoid arthritis, heart disease, end-stage renal disease, chronic obstructive pulmonary disease (COPD) and similar chronic conditions. While some patients are able to lead a relatively normal life, others are totally bed-bound and unable to care for themselves. Almost all patients find they must drastically reduce their activity from pre-illness levels, regardless of their previous level of athleticism, and must severely modify or give up physical hobbies and exercise. Many patients find themselves unable to work full-time, or at all. A considerable number of CFS cases in many countries are on disability benefits or private insurance, or have made claims and been denied.

Post-exertion symptom exacerbation

One of the most common and recognizable aspects of CFS is what is called "post-exertional malaise". Patients also frequently experience rapid weakening and loss of muscle strength. When people with CFS exert themselves, physically or cognitively beyond their limits in either intensity or frequency, their symptoms worsen. This is to say that exertion is unsustainable. The harder the exertion and the longer it lasts, the worse the decompensation will be afterward, and with greater recovery time. Although symptoms may increase immediately and proportionally, the decompensation effects usually takes 24 hours or more to reach full extent, and can sometimes take several days or longer to gradually accumulate. This can make judging appropriate activity difficult. Time to recover strength has been described as inordinate and "pathological" and limits often change daily and from hour-to-hour, as well as through longer relapses and remissions. Severely affected patients may have "hard" limits such as severe loss of muscle power or drastic postural hypotension causing collapse or blackouts, rendering complete if usually temporary debilitation, and imposing strict, if variable, limitations. It is such limitations that usually enforce disability upon patients sooner or later, after an initial cyclical "push-crash" period, which can be prolonged through poor advice or diagnostic delay. Typically symptoms lessen or disappear with recumbency, due to othostasis as a form of exertion and neuro-vascular adaptability. Therefore patients need to intersperse any activity with rest periods, which is referred to as pacing. Muscles which are frequently used tend to be weakest.

In patients without a diagnosis of CFS, or a proper understanding of how CFS affects exertion, a "downward spiral," can occur where a sufferer will try to work harder to make up for the previous day or week's lack instead of resting. This causes further deterioration and often can trigger a relapse or worsening of their condition. It must be noted that patients may be compelled to exert themselves in a society that does not yet afford CFS total medical and social acceptance or trivialises the illness (see below).^[43][44] Sometimes acute onset cases start with severe illness imposing drastic limitations, and patients may be admitted to hospital. Complications, co-morbid illness, and unknown factors can cause exacerbation, which may not be within patients' control. Since CFS is not defined as the result of ongoing exertion, at least some patients with a relapse or progressive course cannot be explained through activity levels.

When the illness is coupled with unaccommodating family, friends, colleagues, often due to stigma, and social repercussions such as financial needs, housing problems, the struggle to obtain disability benefits or insurance, discrimination and misconception within the care sector, it can put demands on the sufferer exceeding their safe capabilities. Many sufferers describe needing to do things for themselves in the times they feel better simply because there is no-one to delegate to.^[43]

Proposed causes and pathophysiology

The cause of CFS is unknown, although a large number of causes have been proposed, and several proposed causes have very vocal and partisan advocates. In a basic overview of CFS for health professionals, the CDC states that "After more than 3,000 research studies, there is now abundant scientific evidence that CFS is a real physiological illness."^[45] The cause of CFS may be different for different patients, but if so, the various causes may result in a common clinical outcome.

Neurological abnormalities

Researchers have found evidence that CFS may involve distinct neurological abnormalities. MRI and SPECT scans show abnormalities within the brain. ^[46] Studies have shown that CFS patients have abnormalities in blood flow to the brain ^[47] possibly indicative of viral cause ^[48] and similar but not identical compared to patients with clinical depression. ^{[49] [50]} A number of studies have shown that CFS patients have abnormal levels of neurotransmitters including increased serotonin ^{[51] [52]} (the opposite of what is found in primary depression). ^[53]Reduced brain serotonin receptor sensitivity or number ^[54] , and high auto antibodies to serotonin have also been found. ^[55] Recent studies found altered gene expression in the brain’s serotonin and sympathetic nervous system pathways, ^[56] with altered responses of the HPA axis to serotonin. ^[57] Other neurotramsmitters have been found affected including glutamate, ^[58] sensitivity to acetylcholine associated with vasoconstriction ^[59], and autoantibodies to cholinergic receptors, associated with central pain. ^[60] Beta-endorphin, a natural pain killer, has been found to be low in CFS patients, the opposite of what is found in primary depression. ^{[61] [62]}

Dysautonomia

Dysautonomia is the disruption of the function of the autonomic nervous system (ANS). The ANS is tightly tied to the body's endocrine system and also directly controls some aspects of blood pressure control and metabolism. The dysautonomia that evidences itself in CFS shows up mostly in problems of orthostatic intolerance - the inability to stand up without feeling dizzy, faint, nauseated, etc. Research into the orthostatic intolerance found in CFS indicates it is very similar to that found in postural orthostatic tachycardia syndrome (POTS). POTS and CFS patients exhibit reduced blood flows to the heart upon standing that result in reduced blood flow to the brain. The reduced blood flows to the heart are believed to originate in blood pooling in the lower body upon standing. Many CFS patients report symptoms of orthostatic intolerance and low or lowered blood pressure.^[63]

Inner-ear disorders

Main article: balance disorder

Problems such as Meniere's, tumor in the inner ear, ^{[citation needed]} or Benign Paroxysmal Positional Vertigo (BPPV) can cause dizziness, vertigo, and fatigue. Recurrent ear infections are common in some CFS sufferers. Tinnitus is also quite common ^[64] Antibodies associated with hearing loss have been found in CFS and FMS patients with inner ear disorders ^[65]

Orthostatic hypotension

Syndromes of orthostatic intolerance, in particular neurally mediated hypotension (NMH) and Postural orthostatic tachycardia syndrome (POTS), have been shown to be associated with chronic fatigue syndrome.^[66][67] These conditions, which reduce blood flow to the brain after periods of standing, can be diagnosed with a tilt table test. Unfortunately, fludrocortisone, a drug sometimes used to treat low blood pressure, seems to have little or no benefit for people with CFS.^[68]

Psychiatric abnormalities

Depression

There is some overlap in symptoms between depression and CFS, and sometimes cases of CFS are mistakenly attributed to clinical depression. There are, however, many clinical differences between the two^[69].

Clinical depression often responds well to physical exercise, whereas CFS is characterised by exercise intolerance but with a willingness to be active. (See section on post-exertion symptom exacerbation.) Comorbid depression occurs in 10-15% of CFS patients and should be treated as usual, except that the patient’s energy level, cognitive dysfunction and drug sensitivity must be taken into account^[69]. Comorbid depression may be the result of living with CFS or a pre-existing condition.

Low dosages of antidepressants are sometimes prescribed to help a CFS patient sleep better.

Stress and trauma

Stress contributes to many different illnesses, and can cause a series of responses that in genetically predisposed individuals may lead to stress-related brain disease after adverse experiences.^[70] Although the majority of people who experience stress/trauma do not develop CFS, these (including infection) increase the likelihood of acquiring CFS within one year^[21][22] and a genetic disposition to CFS has been demonstrated. Other studies also suggest that childhood stress/trauma significantly increases the likelihood of acquiring CFS as an adult, with one study finding a 3 to 8 fold increase (depending on the trauma type).^[71] Another study found both stress and emotional instability to be significant risk factors, an effect which may be buffered by genetic influences, with the researchers also concluding that "emotional instability assessed 25 years earlier is associated with chronic fatigue through genetic mechanisms contributing to both personality style and expression of the disorder ... these findings suggest plausible mechanisms for chronic fatiguing illness." They also found no association between extraversion and fatigue.^[72] Anxiety disorders have also been found to be a risk factor in 5-15 year olds.^[73]

CFS has been linked to an impaired stress response (see the Post-exertion symptom exacerbation section). It has also been proposed that this was associated with dysfunction of the hypothalamus-pituitary-adrenal axis (the HPA axis helps the body remain stable under physiological and psychological stress) and some evidence for this has been found^[74]; although this may only be subtle^[75], and acquired as a result of CFS.^[76] The controversy surrounding CFS has caused some social issues for patients and may contribute to their stress (see the Social issues section).

Oxidative stress

Further information: Oxidative stress

Oxidative stress is an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates or easily repair the resulting damage. Several studies^{[77][78][79][80][81][82]} and a review^[83] have implicated oxidative stress in CFS symptoms; especially relating to fatigue, pain and postexertional malaise / exercise intolerance. According to researchers of one study, the findings on oxidative stress (and nitric oxide-related toxicity) seem consistent with their findings of the abnormal 2-5A synthetase/RNase L enzyme (antiviral) activity which has previously been implicated in the pathology of exercise intolerance in CFS.^[84]

Immune dysfunction

When compared with CFS patients with normal natural killer cell activity, those with lower levels reported less vigor, more daytime dysfunction, and more cognitive impairment; with the researchers suggesting this to be useful at subtyping.^[85] However an earlier systematic review on the immunology of CFS published in 2003 found an inverse association between study quality and findings of low levels of natural killer cells (suggesting that the association may be related to study methodology), although no such association was found with studies finding abnormalities in T cells and cytokine levels.^[86] The researchers also concluded that no consistent pattern of immunological abnormalities had been identified, however, a later updated review on the phenomenology and pathophysiology of CFS published in 2006 found that immune system involvement in the pathogenesis of CFS seems certain but the findings on the specific mechanisms are still inconsistent.^[87] There is also evidence that people with CFS have improper gene expression including both over expression and under expression of genes involved in the immune system (see the gene expression section).

RNase L deregulation

Several studies have highlighted the existence of abnormal 2-5A synthetase/RNase L enzyme (antiviral) activity in some CFS patients^{[88][89][90][91][92][93]}, with several more studies finding this to correlate with the worsening of symptoms after exercise.^{[94][95][96][84]} A review published in 2005 suggested that this impaired pathway is of clinical importance and that further studies addressing treatment of this deregulation are warranted.^[97] A study found that elevated RNase L did not correlate with alpha-delta sleep.^[98]

Hyperactive immunity

Autoimmune disorders, representing a hyperactive immune system, most likely through a cell-mediated process, have been suggested.^[99][100] In July 2005, researchers in the UK reported significant gene changes in the white blood cells in CFS patients consistent with the theory of immune system activation, possibly by an antigen triggering a constant immune fatigue state. The study, led by Dr Jonathan Kerr, discovered that 35 white blood cell genes, out of a total of 9,522 genes scanned were demonstrating differential function. There was also suggestion of neuronal and mitochondrial dysfunction as a result.^[101]

Allergies

Similarly to the theory of immune dysfunction, some doctors believe that CFS patients suffer from immune dysfunction caused by exposure to allergens, ranging from food allergies or food intolerances (see below) to pollen and dander allergies. However, this theory fails to explain the many reported and documented cluster outbreaks of CFS, and is therefore not taken seriously by leading researchers in the field. Instead, severe allergies may occasionally cause CFS-like symptoms, or patients with CFS may develop additional problems with allergies or food intolerances, which is common. ^[102]