Chronic Fatigue Syndrome (CFS)/ ME

Chronic fatigue syndrome (CFS) is a serious disorder characterised by persistent post-exertional fatigue and substantial symptoms related to cognitive, immune and autonomous dysfunction. Disease mechanisms are complex with no single causal factor identified. Yet there are indications that infections and immunological dysfunction contribute to development and maintenance of symptoms, probably interacting with genetic and psychosocial factors.

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Chronic Fatigue Syndrome (CFS)/ ME Summary

Chronic fatigue syndrome (CFS) is characterised by a sudden or gradual onset of persistent disabling fatigue, post-exertional malaise (PEM, exertional exhaustion), unrefreshing sleep, cognitive and autonomic dysfunction, myalgia, arthralgia, headache, and sore throat and lymph nodes, with symptoms lasting at least 6 months. Exertional exhaustion is the critical aspect that distinguishes myalgic encephalomyelitis/CFS from other nociceptive, interoceptive, and fatiguing illnesses. The primary goals of management are to provide a supportive healthcare environment with a team of occupational, physiotherapy, and other appropriate therapists who will manage symptoms and improve functional capacity. The chronic but fluctuating disabilities require substantial lifestyle changes to plan each day’s activities carefully, conserve energy resources for the most important tasks, schedule rest periods to avoid individuals overtaxing themselves, and to improve the quality of sleep.

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The Cdc-1988/holmes Criteria

Holmes et al coined the term ‘chronic fatigue syndrome’ in 1988, as an alternative to ‘The chronic Epstein-Barr virus syndrome’. Since this case definition—the CDC-1988/Holmes Criteria—was presented in 1988, numerous revisions have been developed, aiming for distinctive and reliable identification of individuals who represent a homogenous and consistent phenotype of the hypothesised disease entity, consistent with pathophysiological and psychosocial findings. Currently, the term ‘myalgic encephalomyelitis’ (ME) is commonly used to conceptualise a specific neuroimmunological condition, assumed to be more severe and less psychologically attributed than CFS. In 2003, Carruthers et al presented the Canadian-2003 Criteria for diagnosis of ME/CFS. A revised version was presented as International Consensus Criteria (the ICC-2011 Criteria) for ME, claiming to be a selective case definition for identification of patients with neuroimmune exhaustion with a pathologically low threshold of fatigability and symptom flare after exertion. The assertion that CFS and ME are different clinical entities is disputed.


Myalgic Encephalomyelitis (ME) and chronic fatigue syndrome (CFS) were names given to two well-documented cluster outbreaks of a clinically similar illness in London, UK in 1955 and in NV, USA in 1984. Several different but overlapping case definitions have been published for ME and for CFS to aid in diagnosing sporadic cases. Research studies tend to use the term CFS because a case definition was written for this purpose. The name CFS has been criticized for trivializing the illness and it can be confused with the non-specific term chronic fatigue, which is a common symptom in other illnesses. The World Health Organization classifies ME as a disease of the central nervous system.

Less common names for the illness include chronic fatigue immune dysfunction syndrome, myalgic encephalopathy, and neuro-endocrine-immune dysfunction syndrome. In 2015 a new name, systemic exertion intolerance disease (SEID) and a new case definition were suggested. Currently, the new name is under discussion and the new case definition has not yet been clinically validated. This publication will use the acronym ME/CFS.

Symptoms of ME/CFS sometimes follow an acute illness, such as influenza or infectious mononucleosis. If symptoms resolve within 6 months, the term post-infectious fatigue syndrome is used to describe the illness.


Myalgic encephalomyelitis/chronic fatigue syndrome can begin suddenly, gradually, or with an abrupt increase in the intensity and frequency of milder chronic symptoms. There can be a history of repeated minor relapsing and remitting prodromal illnesses over the months or years preceding the onset. An acute onset of fever and viral-like symptoms is common, and the onset also can be marked by severe orthostatic symptoms. ME/CFS can follow a known illness such as infectious mononucleosis. A gradual onset is more common in younger children and can occur over months or years.

While all patients experience a substantial loss of physical and cognitive functioning, there is a wide spectrum of severity. Mildly affected young people might be able to attend school full-time or part-time, but they might have to limit sport and after-school activities and have frequent school absences. ME/CFS has been found to be the most common cause of long-term absence from school. More severely affected young people can be wheelchair dependent, housebound, or bedbound. The more impaired might even have difficulty participating in-home tutoring sessions. In young persons with ME/CFS, overall self-reported quality of life is often lower than in other illnesses such as diabetes, epilepsy, and cystic fibrosis.

Symptoms often fluctuate significantly during the day and from day-to-day. Commonly, patients are slow to get moving upon awakening, with somewhat better function later in the day. Reduced ability to function after activity (physical, cognitive, emotional, orthostatic stress, or academic pressure)—often referred to as “a crash” by patients—with prolonged recovery is a feature. In females, ME/CFS symptoms are often worse at or just before the menstrual period. The unpredictable level of function from day-to-day can interfere with planning ahead for school attendance, social outings, or family obligations.


The possibility of CFS/ME if a person hasfatigue with all of the following features:

  • new or had a specific onset (that is, it is not lifelong)
  • persistent and/or recurrent
  • unexplained by other conditions
  • has resulted in a substantial reduction in activity level
  • characterised by post-exertional malaise and/or fatigue (typically delayed, for example by at least 24 hours, with slow recovery over several days)

and one or more of the following symptoms

    • difficulty with sleeping, such as insomnia, hypersomnia, unrefreshing sleep, a disturbed sleep-wake cycle
    • muscle and/or joint pain that is multi-site and without evidence of inflammation
    • headaches
    • painful lymph nodes without pathological enlargement
    • sore throat
    • cognitive dysfunction, such as difficulty thinking, inability to concentrate, impairment of short-term memory, and difficulties with word-finding, planning/organising thoughts and information processing
    • physical or mental exertion makes symptoms worse
    • general malaise or ‘flu-like’ symptoms
    • dizziness and/or nausea
    • palpitations in the absence of identified cardiac pathology


No valid, reliable, laboratory test that confirms the diagnosis is currently available. The diagnosis of ME/CFS is purely clinical and is based on the history and the exclusion of other fatiguing illnesses by physical examination and medical testing. Routine blood tests are usually normal. If the typical symptom pattern is not recognized, the diagnosis will be overlooked. The diagnosis depends on the patient’s symptoms meeting the criteria of one of several overlapping case definitions. Most of the case definitions were developed for adults and they can exclude some young people with ME/CFS. Some case definitions are also quite complex to use in primary care and some do not require the cardinal symptom of post-exertional exacerbation of symptoms to be present.

A diagnosis should be made after other possible diagnoses have been excluded and the symptoms have persisted for:

  • 4 months in an adult
  • 3 months in a child or young person; the diagnosis should be made or confirmed by a paediatrician.

Tests For Cfs/me

The following tests should usually be done:

  • urinalysis for protein, blood and glucose
  • full blood count
  • urea and electrolytes
  • liver function tests
  • thyroid function tests
  • erythrocyte sedimentation rate or plasma viscosity
  • C-reactive protein
  • random blood glucose
  • serum creatinine
  • screening blood tests for gluten sensitivity
  • serum calcium
  • creatine kinase
  • assessment of serum ferritin levels (children and young people only).

If any of the above test results are abnormal, it is important to rule out other causes of chronic fatigue.


The course of ME/CFS is very unpredictable but must often be measured in years, not weeks or months. Remissions and relapses are common. Relapses can be caused by overexertion, infectious illnesses or failure to recover from a “crash”. Dramatic improvement sometimes occurs in the first 4 years, but a slow improvement over time is more likely.

It is generally accepted that young people with ME/CFS have a more favourable prognosis than adults. There have been few studies with sufficient numbers and duration of follow-up to be confident of the findings, but factors such as severity of symptoms or age at onset have not been shown to be reliable predictors of long-term outcomes. In a follow-up study of nearly 700 young people the average duration of illness of those who report having “recovered” was 4–5 years with a range from 1 to 15 years. By 5 years, 60% reported recovery, and by 12 years, 88% reported recovery. Of those who reported recovery, about one-third admitted to modifying their activities to remain feeling well. Several other studies found that although many patients improved, 20–48% showed no improvement or actually had worse fatigue and physical impairment at follow-up times ranging from 2 to 13 years. Even among those who report having completely recovered, many describe persistent symptoms that are not reported by healthy individuals.

\Feedback from young people indicated that an important determinant of their functioning as adults was the effort made to enable them to remain engaged in education. This might have followed relatively unconventional pathways but it enabled them to remain socially connected and to feel they were able to achieve their aspirations fully or in part. From this group, more than 95% were either studying or working part or fulltime.

Management Of Cfs/me

Pharmacological interventions for symptom control

There is no known pharmacological treatment or cure for CFS/ME. However, symptoms of CFS/ME should be managed as in usual clinical practice. If chronic pain is a predominant feature, healthcare professionals should consider referral to a pain management clinic. Prescribing of low-dose tricyclic antidepressants,

Prescribing of low-dose tricyclic antidepressants, specifically, amitriptyline should be considered for people with CFS/ME who have poor sleep or pain. Tricyclic antidepressants should not be offered to people who are already taking selective serotonin reuptake inhibitors (SSRIs) because of the potential for serious adverse interactions.

Melatonin may be considered for children and young people with CFS/ME who have sleep difficulties.


Although exclusion diets are not generally recommended for managing CFS/ME, many people find them helpful in managing symptoms, including bowel symptoms. If a person with CFS/ME undertakes an exclusion diet or dietary manipulation, healthcare professionals should seek advice from a dietitian because of the risk of malnutrition.

Function And Quality-of-life Management

Sleep management

Healthcare professionals should provide tailored sleep management advice that includes:

  • Explaining the role and effect of disordered sleep or sleep dysfunction in CFS/ME
  • Identifying the common changes in sleep patterns seen in CFS/ME that may exacerbate fatigue symptoms (such as insomnia, hypersomnia, sleep reversal, altered sleep-wake cycle and non-refreshing sleep)
  • Providing general advice on good sleep hygiene
  • Introducing changes to sleep patterns gradually

Sleep management strategies should not include encouraging daytime sleeping and naps. People with CFS/ME should be advised that excessive sleep does not generally improve physical or mental functioning, and excessive periods of daytime sleep or frequent napping may further disrupt the sleep-wake cycle.

Rest periods

Rest periods are a component of all management strategies for CFS/ME. Healthcare professionals should advise people with CFS/ME on the role of rest, how to introduce rest periods into their daily routine, and the frequency and length appropriate for each person. This may include:

  • Limiting the length of rest periods to 30 minutes at a time.
  • Introducing ‘low level’ physical and cognitive activities (depending on the severity of symptoms).
  • Using relaxation techniques


Relaxation techniques appropriate to the person with CFS/ME should be offered for the management of pain, sleep problems and comorbid stress or anxiety. There are a number of different relaxation techniques (such as guided visualisation or breathing techniques) that can be incorporated into rest periods.


People with CFS/ME have reported pacing to be helpful in self-managing CFS/ME. However, healthcare professionals should advise people with CFS/ME that, at present, there is insufficient research evidence on the benefits or harm of pacing.

Referral to specialist CFS/ME 

Any decision to refer a person to specialist CFS/ME care should be based on their needs, the type, duration, complexity and severity of their symptoms, and the presence of comorbidities.

Cognitive behavioural therapy (CBT) and/or graded exercise therapy (GET) should be offered to people with mild or moderate CFS/ME and provided to those who choose these approaches because currently, these are the interventions for which there is the clearest research evidence of benefit.

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Dr Murli Krishna

Consultant Pain Medicine