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

Epidemiology

• The true prevalence of chronic fatigue syndrome (CFS) is unknown. It has been estimated that in the USA approximately 2 per 1,000 suffer with the condition.^1,2 The National Institute for Clinical Excellence (NICE) suggests 4 per 1,000 in the UK.³
• Women appear to be affected more than men with the ratio reported as being female:male 2:1.
• The average age at onset is 30 years and, although CFS has been diagnosed in adolescents,⁴ it is not generally seen in children under the age of 12 or adults over the age of 65.

Aetiology

• Chronic fatigue syndrome (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.⁵ It is a chronic debilitating disorder in which chronic fatigue is the primary symptom.
• 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.
• 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.⁶
• 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.

Diagnostic criteria

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 chronic fatigue syndrome (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.

Presentation

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: patient is mobile, can care for themself and do light housework with difficulty
• Moderate: patient has reduced mobility and is restricted in all activities of daily living. They have usually stopped work or education. Poor sleep quality and duration.
• Severe: 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.

Differential diagnosis

The differential diagnoses are many and varied, and will vary from patient to patient depending on the initial presentation:

• Hypothyroidism, diabetes and anaemia should be considered as causes of fatigue
• Systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel disease as causes of arthralgia
• Underlying neoplasia as a cause of lymphadenopathy
• Metabolic muscle disorders and myopathies as a cause of muscle pain and weakness
• Psychiatric illness as a cause of depression and anxiety
• Cardiological or respiratory causes for shortness of breath and chest pain, and many other illnesses depending on the specific symptoms

Investigations

There is no currently available biomedical test which can be used to diagnose chronic fatigue syndrome (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
• Liver function tests
• U&Es and creatinine
• FBC
• Serum ferritin (in children only)
• ESR or plasma viscosity
• Random blood glucose
• Thyroid function
• 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 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.³
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).

Management

Main points from the new NICE guidance are:³

• 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 coexisting morbidity

General measures

• The natural history of the disease will mean that long-term emotional support will be required by patients with chronic fatigue syndrome (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 cognitive behavioural therapy appear to reduce symptoms and improve function based on evidence from RCTs.⁹ Most other interventions show little evidence of effectiveness. NICE suggests they be offered to patients with mild-to-moderate CFS, who choose these approaches.³ Detailed advice and plans are available within the guidance:
• 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.

Pharmacological

• 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.¹⁰
• The use of non-sedating antidepressive agents such as fluoxetine for the treatment of depression, or the early assessment by the psychiatric services 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 re-uptake inhibitor.
• Melatonin may be used in children with sleep difficulties, under specialist supervision.

Referral

This should be offered if:³

• 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.

Prognosis

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 chronic fatigue syndrome (CFS) symptoms (approximately 50%). Lower recovery rates and higher relapse rates are associated with those that have had CFS for many years.

Document references

1. Cunha BA; Chronic Fatigue syndrome. eMedicine, October 2009.
2. Prins JB, van der Meer JW, Bleijenberg G; Chronic fatigue syndrome. Lancet. 2006 Jan 28;367(9507):346-55. [abstract]
3. Chronic fatigue syndrome / Myalgic encephalomyelitis (or encephalopathy); diagnosis and management, NICE Clinical Guideline (2007); CG53
4. Tolan RW, Stewart JM; Chronic Fatigue syndrome. eMedicine, January 2009; (paediatrics).
5. Medical Research Council; CFS Research Strategy; 2003
6. 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. [abstract]
7. Carruthers BM, Jain AK, De Meirleir KL, Peterson DL, Klimas NG, Lerner AM et al. Myalgic encephalomyelitis/chronic fatigue syndrome: clinical working case definition, diagnostic and treatment protocols. Journal of Chronic Fatigue Syndrome 2003; 11(1):7-115.
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. [abstract]
9. 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. [abstract]
10. Kroenke K; Chronic fatigue syndrome: is it real? Postgrad Med. 1991 Feb 1;89(2):44-6, 49-50, 53-5. [abstract]

Internet and further reading

• Chronic Fatigue Syndrome/Myalgic Encephalopathy (CFS/ME), Department of Health (2004)
• Occupational aspects of the management of chronic fatigue syndrome: a national guideline, Department of Health (2006)
• Tiredness/fatigue in adults, Clinical Knowledge Summaries (October 2009)
• Chronic fatigue syndrome. Annette has had chronic fatigue syndrome, also known as ME, for over 25 years. She talks about how the condition affects her life and the things that have helped her to stay happy. Short video from NHS Choices (March 2009)
• Chronic fatigue syndrome (CFS). Dr Charles Shepherd, medical adviser to the ME Association, and who has ME, describes the symptoms, diagnosis and treatments for chronic fatigue syndrome. A short video from NHS Choices. (March 2009)

Acknowledgements