Chronic Fatigue Syndrome

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PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

See also: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (ME) written for patients

Synonyms: myalgic encephalomyelitis (ME), postviral fatigue syndrome, chronic fatigue and immune dysfunction, 'yuppie flu'

Chronic fatigue syndrome (CFS) is an illness characterised by disabling fatigue of at least six months.[1]CFS is a complex disorder of unknown aetiology. Until relatively recently, many clinicians had remained sceptical over its existence as a disease entity; however, it has now gained acceptance in most circles and much research is currently underway in an attempt to learn more about the disorder.[2]

At present there are no diagnostic laboratory investigations that can be performed for CFS, and it remains a diagnosis of exclusion founded on the pattern of symptoms and signs.

  • CFS is not uncommon but the true prevalence is unknown and depends on the criteria used for diagnosis.[3]
  • It has been estimated that in the USA approximately 2 per 1,000 suffer with the condition.[4]The National Institute for Health and Care Excellence (NICE) suggests 4 per 1,000 in the UK.[5]
  • Women appear to be affected more than men with the ratio reported as being female:male 2:1.
  • CFS can affect children and recent research has shown a higher incidence in socially deprived families.[6]

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  • Numerous factors including previous psychiatric disorder, stressful events, high academic achievement, infections and many others have been suggested as having a role to play in the aetiology of the disease, but there is little firm evidence available.
  • A recent study (using longitudinal data over a period of 30 years) has found little evidence to implicate any of these as risk factors, but did suggest that sedentary children are more at risk of developing the disease in later life than children who exercise regularly.[7]
  • Epidemics of CFS have been reported in several areas, but no causative organism has been found, and there is some debate as to whether the chronic fatigue associated with these outbreaks may be a different form of disorder from CFS.

Sometimes reaching a diagnosis can be problematic for a number of reasons:

  • The onset may be relatively sudden or gradual, following a physical illness or stressful event, or apparently out of the blue.
  • The range of presenting symptoms is wide, and fatigue and pain may not always be the prominent disabling features at initial presentation.
  • Patients may have been investigated extensively, without positive findings, for varied physical symptoms and may feel frustrated by the lack of help received from the medical profession by the time the diagnosis is made.
  • Symptoms tend to vary in intensity and type over a period of weeks or months (and evolve into what is more clearly CFS with time), leading to uncertainty for both the patient and clinician about the course and nature of the underlying problem.
  • CFS cannot be diagnosed by any test currently available.
In order to make a diagnosis of CFS, it is usual for a patient to satisfy the following diagnostic criteria:[4]
  • Fatigue with all of the following features:
    • New or had a specific onset.
    • 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).
  • 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 making symptoms worse.
    • General malaise or flu-like symptoms.
    • Dizziness and/or nausea.
    • Palpitations in the absence of identified cardiac pathology.

In addition to the symptoms used to define the disorder, several other symptoms have been described:

  • General:
    • Night sweats
    • Weight loss
    • Alcohol intolerance
  • Gastrointestinal:
    • Abdominal pain
    • Bloating
    • Diarrhoea
  • Respiratory/cardiovascular:
    • Chronic cough
    • Chest pain
    • Neurally mediated hypotension on tilting (see 'Investigations', below)
    • Shortness of breath
  • Psychological:
    • Anxiety
    • Panic attacks
    • Depression
    • Irritability

Describing severity

  • Mild CFS: the patient is mobile, can care for themself and do light housework with difficulty
  • Moderate: the patient has reduced mobility and is restricted in all activities of daily living. They have usually stopped work or education. There is poor sleep quality and duration.
  • Severe: the patient is unable to do anything for themself. They suffer severe cognitive difficulties and depend on a wheelchair. They spend most of their time in bed and are sensitive to light and noise.

The differential diagnoses are many and varied, and will vary from patient to patient depending on the initial presentation. See also the separate article on Fatigue and TATT.

NICE notes these particular RED FLAG features, as worthy of investigation:[5]
  • Localising/focal neurological signs
  • Signs of inflammatory arthritis or connective tissue disease
  • Signs of cardiorespiratory disease
  • Significant weight loss
  • Sleep apnoea
  • Significant lymphadenopathy

There is no currently available biomedical test which can be used to diagnose CFS, and it remains a diagnosis of exclusion. In a patient in whom the diagnosis is suspected, the laboratory investigations performed are those required to rule out other causes of illnesses which may mimic CFS:

  • Full medical history
  • Full medical examination
  • Mental status examination
  • LFTs
  • U&Es and creatinine
  • FBC
  • Serum ferritin (in children only)
  • ESR or plasma viscosity
  • Random blood glucose
  • TFTs
  • Test for gluten sensitivity
  • Urinalysis for protein, blood and glucose
  • ± Anti-nuclear antibodies and rheumatoid factor
  • Creatine kinase

NICE recommends that the 'tilt table test' (laying the patient horizontally on a table, then tilting the table upright to 70° for 45 mins while measuring pulse and blood pressure) should NOT be routinely performed.

Patients with CFS have been found to have disordered autonomic regulation and develop hypotension during this procedure.[8]They also advise that auditory brainstem response and electrodermal conductivity tests should NOT be routinely performed.[5]The diagnosis is made when other possible diagnoses have been excluded and symptoms have persisted for four months in an adult, or three months in a child (this should be made by a paediatrician).

Reconsider the diagnosis if the patient does not suffer from:
  • Post-exercise fatigue
  • Cognitive problems
  • Sleep disturbance
  • Chronic pain

People with CFS should be evaluated for concurrent depression, pain, and sleep disturbances. Treatment options include cognitive behavioral therapy (CBT) and graded exercise therapy, both of which have been shown to moderately improve fatigue levels, work and social adjustment, anxiety, and post-exertional malaise. No pharmacological or complementary therapy has been proven to be effective.[9, 10]

The main points from the NICE guidance are:[5]

  • Shared decision making with the patient and their carers.
  • Identifying and managing symptoms early on, in ways that are suitable for that particular patient.
  • Making an accurate diagnosis and considering differential diagnoses and co-existing morbidity.

General measures

  • The natural history of the disease will mean that long-term emotional support will be required by patients with CFS, and doctors adopting an optimistic outlook can be helpful to the patient's morale.
  • Rest combined with a programme of gentle exercise can help in keeping patients mobile and motivated.
  • Graded exercise therapy and CBT appear to reduce symptoms and improve function based on evidence from randomised controlled trials (RCTs).[9, 11, 12]
  • Most other interventions show little evidence of effectiveness. NICE suggests they be offered to patients with mild-to-moderate CFS, who choose these approaches. Detailed advice and plans are available within the guidance:[5]
    • Provide information on management strategies - pros and cons, returning to work or school, natural history of illness and local or national support and self-help groups. It may be useful to liaise with occupational health services, disability services (Jobcentre Plus), schools and disability advisers in university or college.
    • Referral to a pain management clinic may be appropriate if pain is a predominant finding.


  • Although there is no evidence to support the use of any therapeutic regime to modify the course of the disorder, individual symptoms may be helped by appropriate therapy.
  • The use of non-sedating antidepressive agents such as fluoxetine may be beneficial for the treatment of depression. An early assessment by the psychiatric services may also be required in severe cases.
  • Non-steroidal anti-inflammatory agents such as ibuprofen may be helpful in the treatment of myalgias and arthralgias.
  • Consider a low-dose tricyclic antidepressant for poor sleep or pain, but NOT if the patient is already taking a selective serotonin reuptake inhibitor.
  • Melatonin may be used in children with sleep difficulties, under specialist supervision.


This should be offered if:[5]

  • The patient is a child within six weeks of presentation.
  • The patient has severe CFS symptoms.

It may also be considered after six months in mild CFS, or 3-4 months in moderate CFS, depending on symptoms and comorbidity.

  • The prognosis and clinical course of the disorder varies considerably. Some patients recover to the extent that they are able to continue virtually normal activities, with periodic CFS symptoms.
  • Lower recovery rates and higher relapse rates are associated with those who have had CFS for many years.
  • Children can be very severely afflicted but those whose symptoms are of mild-to-moderate severity are generally more likely than adults to go into remission.[13]

Further reading & references

  1. Moss-Morris R, Deary V, Castell B; Chronic fatigue syndrome. Handb Clin Neurol. 2013;110:303-14. doi: 10.1016/B978-0-444-52901-5.00025-3.
  2. CFS/ME Research Strategy; Medical Research Council, 2003
  3. Nacul LC, Lacerda EM, Pheby D, et al; Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care. BMC Med. 2011 Jul 28;9:91. doi: 10.1186/1741-7015-9-91.
  4. Prins JB, van der Meer JW, Bleijenberg G; Chronic fatigue syndrome. Lancet. 2006 Jan 28;367(9507):346-55.
  5. Chronic fatigue syndrome/Myalgic encephalomyelitis (or encephalopathy) diagnosis and management; NICE Clinical Guideline (August 2007)
  6. Crawley E; The epidemiology of chronic fatigue syndrome/myalgic encephalitis in children. Arch Dis Child. 2014 Feb;99(2):171-4. doi: 10.1136/archdischild-2012-302156. Epub 2013 Oct 21.
  7. Viner R, Hotopf M; Childhood predictors of self reported chronic fatigue syndrome/myalgic encephalomyelitis in adults: national birth cohort study. BMJ. 2004 Oct 23;329(7472):941. Epub 2004 Oct 6.
  8. Naschitz JE, Rosner I, Rozenbaum M, et al; The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome. QJM. 2003 Feb;96(2):133-42.
  9. White PD, Goldsmith KA, Johnson AL, et al; Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded Lancet. 2011 Mar 5;377(9768):823-36. Epub 2011 Feb 18.
  10. Yancey JR, Thomas SM; Chronic fatigue syndrome: diagnosis and treatment. Am Fam Physician. 2012 Oct 15;86(8):741-6.
  11. Price JR, Mitchell E, Tidy E, et al; Cognitive behaviour therapy for chronic fatigue syndrome in adults. Cochrane Database Syst Rev. 2008 Jul 16;(3):CD001027.
  12. Chambers D, Bagnall AM, Hempel S, et al; Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review. J R Soc Med. 2006 Oct;99(10):506-20.
  13. Carruthers BM, van de Sande MI, De Meirleir KL, et al; Myalgic encephalomyelitis: International Consensus Criteria. J Intern Med. 2011 Oct;270(4):327-38. doi: 10.1111/j.1365-2796.2011.02428.x. Epub 2011 Aug 22.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but makes no warranty as to its accuracy. Consult a doctor or other healthcare professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Hayley Willacy
Current Version:
Peer Reviewer:
Dr John Cox
Document ID:
1954 (v23)
Last Checked:
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