Chronic fatigue syndrome

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 in adults (and 3 months in children/adolescents), 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 syndrome (PVFS), chronic fatigue immune dysfunction syndrome (CFIDS), or several other terms. Biological, genetic, infectious and psychological mechanisms have been proposed for the development and persistence of symptoms but the etiology of CFS is not understood and may have multiple causes. There is no diagnostic laboratory test or biomarker for CFS.

Symptoms of CFS include post-exertional malaise; unrefreshing sleep; widespread muscle and joint pain; 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 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. CFS symptoms vary from person to person in number, type, and severity.

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, believe the name trivializes the medical condition and want the name changed.

Classification

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]".

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 Service in England and Wales, produced in 2007 by the National Institute for Health and Clinical Excellence (NICE).

Naming

Chronic fatigue syndrome 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 different symptom profiles may be caused by 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." An editorial noted that the 1996 report received some acceptance, but also criticism from those advocating the use of different naming conventions, suggesting the report was biased, dominated by psychiatrists, and that dissenting voices were 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

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 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.

Symptoms

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 recommends the following three criteria be fulfilled:

1. A new onset (not lifelong) of severe fatigue for six consecutive months or greater duration which is unrelated to exertion, is not substantially relieved by rest, and is not a result of other medical conditions.
2. The fatigue causes a significant reduction of previous activity levels.
3. 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 proposes that persons with symptoms resembling those of CFS consult a physician to rule out several treatable illnesses: Lyme disease, "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.

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 AIDS, lupus, rheumatoid arthritis, chronic obstructive pulmonary disease (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 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.


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.

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 trials. As many of the CBT and GET studies required visits to a clinic, those severely affected may not have been included. Two large surveys of patients 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, 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 whatever the cause of the symptoms. CBT is also thought to help patients by removing unhelpful illness beliefs which may perpetuate the illness.

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 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. 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 based on the observation that symptoms of the illness tend to increase following minimal exertion. There are two forms: symptom-contingent pacing, where the decision to stop (and rest or change an activity) is determined by an awareness of an exacerbation of symptoms; and time-contingent pacing, which is determined by a set schedule of activities which a patient estimates he or she is able to complete without triggering post-exertional malaise (PEM). Thus the principle behind pacing for CFS is to avoid over-exertion and an exacerbation of symptoms. It is not aimed at treating the illness as a whole. Those whose illness appears stable may gradually increase activity and exercise levels but according to the principle of pacing, must rest if it becomes clear that they have exceeded their limits. Some programmes combine symptom and time-contingent approaches. A trial of one such programme reported limited benefits. A larger, randomised controlled trial found 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.