Key questions answered
Chronic fatigue syndrome
Dr Abhijit Chaudhuri advises on diagnosis and management of a problem that commonly presents in primary care
How is chronic fatigue syndrome defined?
Chronic fatigue syndrome (CFS) is a common problem. It is a potentially disabling condition that predominantly affects younger people, including children. Women are more commonly affected than men, and CFS is often mistaken for depression, somatisation or, in children, school phobia.
Patients with CFS experience persistent and overwhelming fatigue and feel exhausted after minimal physical exertion. They
also have generalised muscle aches, unrefreshing sleep, impaired short-term memory, recurrent sore throat or other minor infections, daily migraine-type headache and multi-joint pain.
What is the difference between CFS, ME and PVFS?
CFS is neither a new illness nor a medicalisation of common tiredness. In fact, the first epidemic of CFS to strike England dates back to the Tudor period when Anne Boleyn fell ill during the epidemic of 'English Sweats'. Charles Darwin is believed to have suffered from the illness, as is Florence Nightingale.
The term myalgic encephalomyelitis (ME) describes outbreaks of an illness characterised by muscle pain (myalgia) with neurological and psychological symptoms
(encephalomyelitis). Analyses of 60 epidemics across the globe have demonstrated consistent clinical symptoms. ME is recognised as running a chronic course, and patients have disabilities due to persistent symptoms of pain, fatigue and loss of endurance to normal physical activities, with conspicuous deterioration after exercise. A viral infection was presumed to be a possible trigger for ME – the designation post-viral fatigue syndrome (PVFS) is also used to identify sporadic cases of similar illness.
The more recent term CFS was introduced in 1988 and the term CFS-ME is usually preferred over ME.
How should CFS be diagnosed?
The key issue is to exclude CFS from other causes of fatigue. This may not be easy in the absence of any specific or sensitive laboratory marker. Most patients with CFS do not have any history of longstanding psychiatric disorder or other ongoing systemic illness.
A diagnosis of CFS can be safely made in primary care, provided the core features of fatigue in the international criteria are recognised: that is, clinically evaluated, medically unexplained persistent or relapsing chronic fatigue of new and definite onset (that is, not lifelong 'tired all the time'), and which is not relieved by rest or sleep and results in substantial reduction of a normal level of activities.
To properly define a condition as CFS, four or more additional symptoms should be present, all of which must have persisted throughout, but not predated, the fatigue. These include: chest pain (syndrome X), gait disequilibrium (Pedersen's syndrome), appearance or exacerbation of asthma and skin allergy, irritable bowel, night sweats and alcohol intolerance. Although some postural changes in heart rate and blood pressure may be present, autonomic failure is relatively uncommon in CFS.
As always, a search should be made to exclude medical, psychiatric and iatrogenic causes of chronic fatigue (see table 1) and investigations (see table 2) should be considered if symptoms persist beyond three weeks in an adult. In children, a weight-and-height chart, school attendance report and daily sleep pattern are informative.
The international case definition requires that significant fatigue without any other cause must be present for six months. However, a provisional diagnosis may be considered as early as six weeks for adults and four for children and adolescents. Early consideration of the diagnosis of CFS is important for appropriate care pathways to be identified, especially in children and adolescents whose needs are more diverse.
What is an effective management strategy?
While a significant proportion of patients are likely to make a spontaneous recovery over 12 to 18 months, the prospect of complete recovery is less certain in patients with established disability and persistent symptoms beyond three years. With the possible exception of carnitine (N-acylcarnitine), attempts to treat CFS pharmacologically have not been successful in large trials.
Non-pharmacological interventions are essentially supportive and rehabilitative, and short-term trial results of cognitive behaviour therapy appear to be promising.
The role of exercise is another therapeutic area of controversy. Daily physical activity should be individualised for each patient with the emphasis on regularity rather than amount of activity, which should be paced throughout the day.
Pharmacological treatment of chronic pain and sleep disorder can be rewarding in CFS. Low doses of amitriptyline (10 to 25mg) or gabapentin (300 to 1200mg) may be
effective and an SSRI (such as sertraline or citalopram) in smaller doses is helpful.
Opiates, codeine-containing analgesics and long-acting benzodiazepines are not recommended and patients should be advised not to take caffeinated beverages, alcohol or tobacco. Antioxidants can be helpful and diet (fruits, vegetables and oily fish) should be reviewed.
Patients with irritable bowel symptoms should be screened for coeliac disease and could try restricting wheat intake.
Rehabilitation in adults and children should be carefully planned and gradually phased with periodic reviews of progress.
There will be cases that require specialist referrals. At an early stage, this is likely due to uncertainty in the diagnosis, and later, due to complex management issues. Specialist services for CFS patients are not widely available and in the absence of a designated local centre, referral should be made, preferably to a specialist with an interest in, or knowledge of CFS such as neurologists, infectious disease specialists, rheumatologists, general physicians, psychiatrists or psychologists. It is always helpful to discuss the nature of referral with the patient, and in case of children, a paediatrician should be consulted first.
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1 Essential exclusions
• Medical: all clinically distinct disorders, for example, anaemia, cancer, thyroid disease, liver disease, dementia, multiple sclerosis
• Psychiatric: major or psychotic depression, bipolar disorder, substance misuse, eating disorder, schizophrenia, delusional disorder, somatoform disorder
• Iatrogenic: many common medications, for example, anti-hypertensives, antidepressants, anti-epileptics, interferons, statins, ß-blockers, tranquilisers, antihistamines, sedatives and hypnotics
Recommended screening investigations for adults with suspected CFS
• FBC, red cell indices; serum ferritin in all women of childbearing age
• ESR and CRP
• U&Es, LFT, GGT, TSH, plasma glucose and serum CK
• Postural changes in blood pressure
Optional (in selected cases only)
• ECG – in patients with chest pain and orthostatic tachycardia
• Folic acid and vitamin B12 levels – in patients with sensory symptoms
• ANA (antinuclear antibody) and ENA (extractable nuclear antibody) – in patients with joint swelling, skin rash, dry eyes or dry mouth
• Epstein Barr virus serology and serum ACE – in patients with cervical lymphadenopathy
• Tissue transglutaminase antibody – in patients with irritable bowel
• Hepatitis virus serology – in patients with a history of drug misuse
• Lyme disease serology – in patients with a recent history of tick bite
• Chest X-ray – in patients with history of chronic cough, weight loss or sweating, and in new immigrants