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Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is not a straightforward illness. It is defined by symptoms, with no diagnostic test to prove or refute the condition definitively. Medication does not seem to bring about any improvement, even though many drugs, and several unconventional therapies, have been researched, often in an imperfect way.

In order to establish an idea of prevalence of CFS/ME in the UK, the guideline based population estimates on extrapolations from other countries, which suggested a prevalence of at least 0.2–0.4%. For a GP practice with 10,000 patients, this would mean up to 40 people with CFS/ME, half of whom would require some form of specialist care.1

Although it is not possible to say exactly to what extent, CFS/ME appears to be a common condition and causes considerable suffering, with some mortality having been associated with it. At the same time, a sizeable proportion of the medical community doubts whether it exists at all.

Against that backdrop the guideline development group (GDG) had a mammoth task.1,2 However, the resulting new guideline from NICE is of landmark importance and should finally end any existing uncertainties about the impact of this often debilitating condition.

The major areas dealt with by the guideline fall into three main areas:

• recognition
• diagnosis
• management.

Recognition

One of the first difficulties in diagnosing a case of CFS/ME is scepticism about the illness itself. Doctors, researchers, and patients can, and do, have very different views about the subject. This is made worse by the many labels that have been attached to patients suffering similar illnesses. Each of the labels has connotations, with some, such as ME, preferred by patients but rarely used by doctors. Scepticism about this condition has caused real problems in the past for patients with CFS/ME, many of whom have felt their distress has been ignored.

For this reason, one of the most important parts of the guideline is the opening section. Four key priorities are taken from it and discussed below.

1) ‘Acknowledge the reality and impact of the condition and the symptoms.’1

It is hard to call to mind any other condition that would actually require such a heading. Personally, I see no conflict between recognising my patient has a problem that requires management, and maintaining an open mind about what the precise pathophysiology is. Doctors do not need to subscribe to any particular explanation for the patient’s suffering in order for them to attempt to relieve it.

The issue of aetiology was not within the remit of the guideline, but the fact that it was not the job of the guideline to deliberate this point does not impact on its value. In the words of the British Medical Journal editorial that discussed the guideline:3 ‘It serves no purpose to disbelieve the patient, who may be severely disabled as a consequence of the illness and handicapped by the lack of medical support or understanding.’

2) ‘Provide information about the range of interventions and management strategies and … on returning to work or education.’1

The hardest task for the GDG (and therefore for the GP) in establishing this recommendation was to find a source of reliable information. The guideline itself deals very well with the interventions and management strategies (see later), but there is less reliable information on the impact of CFS/ME on the patient’s work or education.

3) ‘Offer information about local and national self-help groups.’1

This recommendation from the NICE guideline should not be controversial, but it is. There are many of these groups (with over 20 registered as stakeholders), and one concern of the GDG was that a blanket recommendation would indicate it was giving its ‘seal of approval’ to all support groups. In reality, there was little or no knowledge about the quality of information and/or support many of the groups were offering, and one research paper had even found members of a support group with a worse prognosis than sufferers who had not joined a group.4 Of course, it may simply be that those patients who do not experience an improvement in their condition choose to join these groups, which would explain the findings.

In order for GPs to act on this recommendation wisely, they need to have local knowledge about the support groups in their area. They should try to ascertain which local sources of self-help are available for their patients, and how good they are.

4) ‘People with CFS/ME have the right to refuse or withdraw from any component of their care plan without this affecting other aspects of their care, or future choices about care.’1

This recommendation reflects the political reality of CFS/ME. The only therapies for which evidence of effectiveness was available were cognitive behavioural therapy (CBT) or graded exercise therapy (GET),1 although some patients describe their condition worsening with these treatments. Indeed, some patient groups are extremely wary of these therapies for fear of ill-effects. That does not detract from their overall value, but GPs have to recognise that patients may elect to avoid them. This should not compromise care (although it may remove the best hope of improving the condition). The guideline makes it clear that there are options that people with mild or moderate CFS/ME should be offered to manage their condition, and if they choose to try these options, they should be provided for them.

Diagnosis

There are two stages to diagnosing CFS/ME. These involve:

• identifying it as a possibility
• ensuring no other condition could be causing the symptoms.

Signs and symptoms

There are several clinical and research definitions. The GDG could find no good research evidence favouring one or the other, although each definition had strong adherents. The NICE guideline attempted to draw together the best of the currently available definitions (although, of course, that means it has no research pedigree either). It is clear that fatigue has to be the ‘core’ symptom. It should be:1

• new, or of specific onset (that is, it is not lifelong)
• persistent and/or recurrent
• unexplained by other conditions
• accompanied by 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).

A list of supporting symptoms can be found in Box 1, and many CFS/ME sufferers have multiple additional symptoms.

Differential diagnosis

Although CFS/ME is diagnosed on clinical grounds alone, it is important to exclude some key differential diagnoses. Box 2 (below) lists features that may be indicative of other serious conditions and should not automatically be ascribed to CFS/ME. A fairly standard battery of tests is recommended. These include:

• urinalysis
• full blood count
• renal and liver function tests
• thyroid function
• plasma viscosity or erythrocyte sedimentation rate, depending on your local laboratory’s preference
• C-reactive protein.

Less obvious investigations include tests for:

• coeliac disease—screening blood tests for gluten sensitivity
• serum calcium
• creatine kinase and ferritin (in children and young people only).

Although this may seem a lengthy list, the argument is that once the patient has experienced months of fatigue, it is probably wise to do comprehensive testing reasonably early, to avoid any risk of missed alternative diagnoses. It is probable that many of the tests will be required at some stage. In contrast, several tests for infection that have been used in fatigued patients were deemed to be only of value when there was a clear clinical pointer. For this reason the GDG did not recommend routine serological testing for Lyme disease (borelliosis), HIV, hepatitis, glandular fever, toxoplasmosis, or cytomegalovirus.

The diagnosis should be reconsidered if none of the following key features are present:1

• post-exertional fatigue or malaise
• cognitive difficulties
• sleep disturbance
• chronic pain.

Box 1: Additional symptoms that can indicate a diagnosis of CFS/ME

One or more of the following symptoms may be present: difficulty with sleeping—insomnia, hypersomnia, unrefreshing sleep, disturbed sleep–wake cycle muscle and/or joint pain at more than one location without apparent inflammation headaches painful lymph nodes without pathological enlargement sore throat cognitive dysfunction—difficulty thinking; inability to concentrate; impairment of short-term memory; and difficulties with word-finding, planning/organising thoughts, and information processing worsening symptoms following physical or mental exertion general malaise or ‘flu-like’ symptoms dizziness and/or nausea palpitations in the absence of identified cardiac pathology

CFS=chronic fatigue syndrome; ME=myalgic encephalomyelitis

Box 2: Features that can be caused by other serious conditions

‘Red flag’ signs that should not be attributed to CFS/ME without consideration of alternative diagnoses or co-morbidities. These include: localising/focal neurological signs signs and symptoms of inflammatory arthritis or connective tissue disease signs and symptoms of cardiorespiratory disease significant weight loss sleep apnoea clinically significant lymphadenopathy

CFS=chronic fatigue syndrome; ME=myalgic encephalomyelitis

Management

The guideline from NICE recommends that the patient with CFS/ME should be offered a treatment programme designed for their individual needs. It should be based on the patient’s:1

• age, preferences, and needs
• skills and ability to manage their condition, and whether they are aiming to improve or stop deterioration of their symptoms, or maintain their current state of health or prevent relapse
• symptoms according to their severity and complexity
• physical and cognitive functioning.

The potential benefits and risks of therapy should be clearly explained, and patients should also be informed that one strategy is not successful for all patients. The aims of the programme should be to maintain or improve on the patient’s physical, emotional, and cognitive capacity, and manage the impact of their symptoms.1

‘Cognitive behavioural therapy and/or graded exercise therapy should be offered to people with mild or moderate CFS/ME’1

In essence, the main management recommendations in the NICE guideline are for GET or CBT, which were the only therapies that had been found to be successful in an adequate number of trials.1 As is the case with many interventions for different illnesses, some patients’ condition will improve, and for others it will worsen. Patients who have increased symptoms after starting the specialised programme should be advised to contact their healthcare professional.

Overall, however, the trial results were favourable, with significantly more participants showing an improvement rather than deterioration of their condition. There is a broad overlap between these two therapies, with programmes for each containing many similar elements. This recommendation will have the largest resource implication as both GET and CBT require supervision by trained professionals.

It is essential to be clear that CBT or psychological approaches to CFS/ME do not imply that symptoms are psychological, ‘made up’ or in the patient’s head. Cognitive behavioural therapy is an evidence-based treatment for CFS/ME. It is a psychological therapy that involves a collaborative approach and is used in many health settings, including cardiac rehabilitation and diabetes management. When it is used for CFS/ME, the aim is to reduce the levels of symptoms, disability, and distress associated with the condition, and its use does not assume or imply any view of the nature of the underlying disease process. A course of CBT is usually 12–16 sessions.

It is also important to recognise that the recommendation for these therapies, particularly GET, is not simply a message saying ‘Go down to the gym, that will get you better’. A real concern (expressed mostly by patient groups but accepted by all) was that too much unsupervised exercise was more likely to be harmful than helpful.1

Symptom control

Healthcare professionals can consider referring patients with chronic pain to a pain management clinic. However, prescription of low-dose tricyclic antidepressants, specifically amitriptyline, may be considered for patients with CFS/ME who are in pain or who have difficulty sleeping. Exceptions to this are people already taking selective serotonin reuptake inhibitors, where there is a potential for serious adverse interactions.

Treatments not recommended

The NICE guideline recommends that some therapies should not be offered, such as monoamine oxidase inhibitors, steroids, dexamphetamine, methylphenidate, thyroxine, and antiviral agents.

The concept of ‘pacing’, a popular regimen with patient groups, suggests that the patient with CFS/ME should maintain activity at below their full capacity so they can keep some energy in reserve. There is no research evidence to support this theory,1 although a large trial is currently underway,5 so no recommendation either way could be given in the guideline.

Referral

Individual assessment should be taken into account when deciding whether to refer a patient for specialist care; the patient’s needs, their symptoms, and the presence of co-morbidities should be noted. Referral should be a joint decision between the patient and their healthcare professional. Timing of referral should be as follows:1

• mild CFS/ME—within 6 months of presentation
• moderate CFS/ME—within 3–4 months of presentation
• severe symptoms of CFS/ME —immediately.

Setback or relapse

Setbacks or relapses are an expected part of CFS/ME, and patients should be advised to expect this. Both the patient and their healthcare professional should have a plan in place to deal with management of setback/relapse so that it is readily available when needed.

Unexpected or unplanned activity, poor sleep, infection, or periods of stress can all trigger a setback/relapse. As part of the management of the event, the healthcare professional should try to discover the cause, if possible.

Conclusion

The subject of CFS/ME is controversial. The new guideline from NICE has tried to establish what is known about the illness, and what diagnostic and management strategies are sensible based on the available evidence. These may change over time, but most GPs should find the recommendations useful.

NICE implementation tools

NICE has developed the following tools to support implementation of its guideline on the diagnosis and management of chronic fatigue syndrome/myalgic encephalomyelitis. They are now available to download from the NICE website: www.nice.org.uk. Implementation advice The implementation advice document contains suggested actions for implementing the guideline. It aims to help implementers identify recommendations in the guideline that are not part of current practice, and should be used alongside the costing report and template. Costing tools National cost reports and local cost templates for the guideline have also been produced. Costing reports are estimates of the national cost impact arising from implementation based on assumptions about current practice, and predictions of how it might change following implementation of the guideline. Costing templates are spreadsheets that allow individual NHS organisations and local health economies to estimate the costs of implementation taking into account local variation from the national estimates, and they quickly assess the impact the guideline may have on local budgets. Audit criteria The audit criteria and audit reporting template have been developed to assist NHS trusts to determine whether the service is implementing, and is in compliance with, the clinical guideline. Users can cut and paste the criteria into their own programmes or they can use the template provided.

Key points for GPs

Recognise that the patient is suffering and treat their symptoms Build up knowledge of local support groups—find out what is available and how good they are Diagnosis involves looking for the core symptom of fatigue, which should be: new or of specific onset; persistent/recurrent; unexplained; resulting in reduced activity; characterised by post-exertional malaise/fatigue, typically delayed by 24 hours Exclude key differential diagnoses Tailor a treatment programme for the individual patient taking account of their age, ability to manage their condition, severity of symptoms, physical and cognitive functioning—explain benefits and risks of therapy The main therapies recommended by NICE are CBT and GET, but if patients decline to take part, this should not affect the quality of care offered to them. Advise patients whose symptoms increase after starting these programmes to contact their healthcare professional Patients with chronic pain may be referred to pain management clinics. Low-dose tricyclic antidepressants, unless contraindicated, may be considered for patients with pain or who are having difficulty sleeping Refer patients for specialist care as follows: mild cases—within 6 months moderate cases—within 3–4 months severe cases—immediately Expect setbacks or relapses, and advise the patient with CFS/ME accordingly

CBT=cognitive behavioural therapy; GET=graded exercise therapy; CFS=chronic fatigue syndrome; ME=myalgic encephalomyelitis

Practice-based commissioning take home messages

written by Dr David Jenner, NHS Alliance PBC Lead CBT and GET should be offered to CFS/ME patients These therapies need to be commissioned locally, if not already provided, and could easily be made available in primary care CFS/ME specialist therapies are usually provided by mental health services and are therefore not subject to a national tariff A specialist CFS/ME service could easily be set up as a new provider service under PBC An effective local care pathway for CFS/ME is likely to save money on referrals to other specialities and complex investigations

PBC=practice-based commissioning; CBT=cognitive behavioural therapy; GET=graded exercise therapy; CFS=chronic fatigue syndrome; ME=myalgic encephalomyelitis

References

1. National Institute for Health and Clinical Excellence. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management of chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy) in adults and children. Clinical guideline 53. London: NICE, 2007.
2. Turnbull N, Shaw E, Baker R et al. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management of chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy) in adults and children. London: Royal College of General Practitioners, 2007.
3. White P, Murphy M, Moss J et al. Chronic fatigue syndrome or myalgic encephalomyelitis. Br Med J 2007; 335 (7617): 411–412.
4. Sharpe M, Hawton K, Seagroatt V, Pasvol G. Follow up of patients presenting with fatigue to an infectious diseases clinic. Br Med J 1992; 305 (6846): 147–152.
5. www.pacetrial.orgG

William Hamilton, GP, Exeter
Consultant Senior Lecturer, University of Bristol
Member of the NICE CFS/ME Guideline Development Group