Key Learning Points: Revised NICE Guidance on ME/CFS

Dr David Strain Defines Best Practice Management of the Chronic, Poorly Understood Condition ME in Six Key Learning Points

Myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS), is a complex, chronic medical condition affecting multiple body systems.¹ At least a quarter of a million people are living with the condition in England and Wales alone.¹ However, this number may underestimate the true prevalence of the condition, which is under-reported as a result of the prejudice, disbelief, and stigmatisation that people with ME/CFS often experience from people who do not understand their illness (including family, friends, health and social care professionals, and teachers).¹

This scepticism about ME/CFS is the result of insufficient understanding of the underlying pathophysiology of the disease.² The lack of a diagnostic test for ME/CFS has led it to be regarded as a ‘hysterical’ or ‘functional’ condition, similarly to how conditions such as multiple sclerosis were viewed before the advent of technology to identify them.³ In the case of multiple sclerosis, magnetic resonance imaging (MRI) enabled the routine visualisation of sclerotic plaques in a population previously labelled as functional, and helped the biological mechanisms of the condition to gain acceptance.⁴  The absence of measurable pathology, the disbelief around ME/CFS has persisted. Another significant contributor is the label ‘chronic fatigue syndrome’, coined by Dr Anthony Komaroff of the US Centers for Disease Control and Prevention when describing an outbreak of a chronic, flu-like illness at Incline Village (Lake Tahoe, Nevada, USA) in 1984.⁵ Subsequently, Dr Komaroff described the terminology as ‘a big mistake because the name, in my opinion and the opinion of a lot of people … both trivializes and stigmatizes the illness. It makes it seem unimportant. Maybe not even real.’⁶

Before the COVID-19 pandemic, ME/CFS was increasingly being viewed as a postviral syndrome, with Epstein–Barr virus the most commonly implicated trigger.⁷ However, the recognition of long COVID as a condition has led to widespread acceptance that postacute viral syndromes can cause significant physical manifestations.⁷ Beyond the similarities in presentation, patients with ME/CFS exhibit a distinct plasma immune signature (lower levels of interleukin [IL]-16, IL-7, and Vascular endothelial growth factor A),⁸ dissociation of intercytokine regulatory networks,^9,10 and cerebral changes on MRI,¹¹ reminiscent of patients with long COVID,^12–14 suggesting that these are similar diseases—if not the same disease—with different triggers.

The revision of NICE Guideline (NG) 206, Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management,¹ has been welcomed by physicians, therapists, and the ME/CFS community alike. It has highlighted the diagnostic uncertainty regarding the condition, the need for personalised goals and, importantly, the need for further research. However, the recommendations in NG206 should not be assumed to apply to people with post-COVID-19 syndrome, as the evidence for the guideline was reviewed before the COVID-19 pandemic.¹  This article provides six key learning points from the guidance that explain how it can be implemented in primary care.

1. Learn How to Recognise ME/CFS

Although distinct abnormalities can be detected in some people with ME/CFS, there is currently no diagnostic test; a clinical diagnosis is made based on the presence of a collection of symptoms (see Box 1). Four key symptoms are required to make a diagnosis of ME/CFS:¹

• fatigue
• postexertional malaise (PEM)
• unrefreshing sleep
• cognitive impairment.

To fulfil the diagnostic criteria of ME/CFS, symptoms must have persisted for at least 3 months, and have no other explanation.¹ Thus, the first stage of assessment for any patient with suspected ME/CFS is to exclude alternative causes of fatigue.¹ This should be done through a routine physical examination and medical history taking, alongside blood tests and urinalysis to exclude alternative diagnoses such as chronic kidney disease, diabetes, autoimmune diseases, or anaemia (see Table 1 for a full list of recommended tests).^1,15  

It is often worth explaining to the patient before performing these investigations that there is no diagnostic test for ME/CFS; therefore, we would not expect any abnormal results from the tests. In my experience, a series of negative or ‘normal’ results can be distressing to an individual if they are not aware that this is the expectation. Indeed, for many, their interpretation of ‘everything is normal’ is that their healthcare practitioner does not believe that they are experiencing these symptoms, or believes that they are all psychosomatic.

2. Understand How to Counsel a Patient With Suspected ME/CFS

When advising people on how to manage their symptoms, it is important to focus on providing personalised coping strategies.¹ A key element is to advise them not to use more energy than they perceive they have,¹ often described as an ‘energy envelope’.¹⁶ They should aim to manage their daily activity, and not ‘push through’ their symptoms.¹ GPs should emphasise the need to rest and convalesce after any sort of exertion.¹ This may require planning and scheduling, particularly when considering routine activities such as school or work.¹ NICE also advises that maintaining a healthy balanced diet, with adequate fluid intake, can help patients to manage their symptoms.¹ It may be important to add the caveat that this approach does not work for all, and is unlikely to cause a complete resolution even in those who are responsive to dietary manipulation.¹⁷

When possible, individuals should be referred to a specialist ME/CFS service; however, NICE acknowledges that this service is not available in every region of the UK.¹ These specialist teams commonly comprise clinicians from a range of specialisms (including rheumatology, rehabilitation medicine, endocrinology, infectious diseases, neurology, immunology, general practice, and paediatrics)—as well as physiotherapists, exercise physiologists, occupational therapists, dietitians, and psychologists—with experience in diagnosing and managing this complex disease.¹ The role of the specialist team is to develop a personalised care and support plan with the patient and their family or carers.¹ By holistically assessing the person’s functional capacity and the impact of the symptoms on their psychological, emotional, and social wellbeing, a care plan can be agreed upon that meets the patient’s needs.¹ The aim is to facilitate as normal a life as possible. It is important to remind the person experiencing the symptoms that, currently, there is no proven cure for ME/CFS, and although many patients recover or experience long periods of remission, they are still prone to flare-ups and relapses.¹

3. Appreciate the Roles of Physical Activity and Rest

The role of graded exercise therapy in ME/CFS remain a controversial. Several individuals have reported benefitting from progressive escalation of exercise in postacute viral fatigue syndromes; some have even suggested that graded exercise therapy has offered them a cure.¹⁸ By definition, however, these individuals do not have ME/CFS, as they do not experience PEM. People experiencing PEM should not be advised to undertake exercise outside of their programme of activity.¹ Indeed, telling them to ‘exercise more’ is likely to worsen their symptoms.¹ Similarly, when an activity programme is offered, the risks and benefits should be discussed with patients, and it should be reinforced that it is not a curative treatment.¹ NICE states that patients with ME/CFS should not be offered any therapy based on fixed incremental increases in exercise.¹

That is not to say that people with ME/CFS should not undertake any exercise; however, it is important to ensure that any physical activity is bracketed well within their energy envelope, and does not result in a worsening of symptoms.¹ Their level of physical activity should be maintained for a period of time before making any attempt to increase it, and adjusted either up or down as needed to help them improve their physical abilities while staying within their energy limits.¹ It should also be acknowledged that these exercise programmes may cause a relapse of symptoms; if this occurs, they should immediately return to lower levels of physical activity until their condition stabilises.¹

Rest is an essential part of the management strategy for ME/CFS.¹ Rest periods should be incorporated into the daily routines of people with ME/CFS, and parameters such as how often and for how long should be tailored to the needs of each person.¹ For many, however, rest alone is insufficient, and the use of relaxation techniques at the beginning of a rest period may be helpful.¹

People with ME/CFS should also be counselled on the importance of sleep for the management of their condition.¹ Personalised sleep management plans should be established, including explanations of the effects of sleep disturbance in ME/CFS, and information on how to recognise common sleep problems in ME/CFS (such as broken or shallow sleep, altered sleep pattern, or hypersomnia).¹ Attempting to improve these may take some time, and sleep patterns should be modified gradually.¹

4. Achieve Symptomatic Control of Aligned Conditions

Pain is a very common symptom experienced by people with ME/CFS.¹ If pain in a person with ME/CFS does not respond to simple analgesics, NICE recommends that they should be referred to a specialist pain service, and treated in accordance with NICE Clinical Guideline (CG) 173 and CG150 on neuropathic pain and headache in over 12s, respectively.^1,19,20 Patients with ME/CFS may be more intolerant of drug treatment; therefore, clinicians are advised to consider commencing medicines at lower doses than in usual clinical practice, and increasing the dose gradually if tolerated.¹

People with ME/CFS may also experience orthostatic intolerance, including postural orthostatic tachycardia syndrome.¹ NICE recommends that patients who experience orthostatic intolerance should be referred to secondary care if their symptoms worsen, or if there are concerns that another condition may be responsible.¹

A dietary evaluation is essential for patients with ME/CFS.¹ In my experience, the natural response of many people experiencing fatigue is to reach for high-energy, high-carbohydrate, or caffeine-based supplements. These are likely to cause dynamic peaks and troughs in energy levels, and some ‘trigger’ foods and drinks—such as alcohol, caffeine, fat, milk and dairy, and gluten—may actually exacerbate symptoms.¹⁷ Nutritional choices are also known to impact the gut microbiome;²¹ alteration of the gut microbiome is thought to contribute to the pathogenesis of ME/CFS,¹⁷ and may explain the vitamin deficiencies common in these patients. The new NICE guidance reminds clinicians that patients with ME/CFS may be at risk of vitamin D deficiency—particularly those who are housebound or bedbound.¹ However, there is insufficient evidence to support routine vitamin and mineral supplementation, either as a cure or for symptomatic relief, in people living with ME/CFS.¹ People with ME/CFS may experience unplanned weight loss or weight gain, or follow a very restrictive diet—a dietetic assessment by a dietitian with a special interest in ME/CFS is useful in these circumstances.¹

5. Be Aware of the Place of Cognitive Behavioural Therapy

For many people living with ME/CFS, the condition has a significant impact on their psychological, emotional, and social wellbeing.¹ Cognitive behavioural therapy (CBT) may be of benefit to help these individuals manage their symptoms.^22,23 CBT should only be delivered to people with ME/CFS by healthcare professionals with training and experience in CBT for ME/CFS, and under the clinical supervision of someone with expertise in CBT for ME/CFS.¹ It is important to highlight to patients that CBT is not a cure for ME/CFS; indeed, this assumption may be detrimental to the relationship between patient and healthcare practitioner, as it implies that abnormal beliefs and behaviours are an underlying cause of ME/CFS.¹ Rather, its purpose is to improve their quality of life and functioning and to help them deal with the distress associated with having a chronic disease, and should recognise that the feelings they are experiencing are to be expected given the physiological impact of the disease.¹

Exploration of the challenges that people with ME/CFS face through CBT may help healthcare professionals to develop a shared understanding with the person with ME/CFS and their family and carers.¹ It also offers an opportunity to review their individualised care plan and self-management strategy in order to make appropriate adaptations if their symptoms and functioning change.¹

6. Learn How to Support People With Severe ME/CFS

As with any chronic disease, there is a gradation of severity of ME/CFS. The symptoms experienced by people with severe or very severe ME/CFS are summarised in Box 2.¹

People with severe or very severe ME/CFS may need:¹

• a low-stimulus environment, with little or no social interaction
• careful support with all activities of daily living that takes into account possible sensitivity to touch
• assistance with communication and accessing information, such as an advocate who can communicate on their behalf.

Therefore, NICE advises that, where possible, support for people with severe or very severe ME/CFS should be delivered by health and social care practitioners who are known to the person and their family or carers, and aware of the person’s needs.¹ Consultations may need to occur in short sessions online, over the phone, or in the patient’s home, and a risk assessment should be conducted for each interaction with the person to ensure that the benefits outweigh the risks.¹  

The aim of consultations should be to agree a personalised care plan.¹ Development of this plan should be a collaborative process between the person with ME/CFS and their specialist team, informed by a holistic assessment.¹ It is the basis for other assessments, and incorporates all aspects of care, including social care, energy management, physical activity, physical functioning and mobility, CBT, and dietary management.¹ These care plans are, by necessity, adaptable. As the patient’s condition improves, physical activity can be increased, energy expenditure may be reviewed, and dietary regimens may become more flexible. However, it must be explained to the patient that any inflammatory stimulus may exacerbate symptoms and cause a deterioration in overall wellbeing; therefore, guidance on managing flare-ups and relapses should also be included in the personalised care plan.¹ A record of interventions that have been successful previously may help to guide the response to relapses. It is important to appreciate that a person with ME/CFS is unlikely to be seen at their worst—the severity of their disease means that it is unlikely that they would leave their home to attend an appointment or have the mental capacity to engage with services. In my experience, this is reflected in a high rate of nonattendance of patients with ME/CFS in clinics or primary care surgeries. Indeed, missing an appointment may be an indicator of the start of a relapse; thus, rather than consider discharging these patients from the service, this should be a trigger to determine whether greater input from the multidisciplinary team is required.

Hospital care is occasionally required to manage the symptoms of severe or very severe ME/CFS.¹ Stimuli such as bright lights, background noise, or strong smells, which may trigger further relapses, should be minimised during transfer and admission.¹ Maintaining good hydration and nutritional support is essential, as some people with ME/CFS experience difficulty eating and drinking.¹ Nourishing drinks and snacks with soft-texture food should be offered little and often.¹ In acute settings, parenteral nutrition may be offered.¹

Summary

ME/CFS is a complex, chronic disease of uncertain pathogenesis. It is a clinical diagnosis based on a collection of symptoms and the exclusion of alternative causes; however, there is no diagnostic test. This diagnostic uncertainty has led to significant stigma over the past 40 years. In addition, because no underlying mechanism for ME/CFS has been discovered to date, there is no proven curative therapy. Thus, the current management of ME/CFS involves agreeing an individualised care plan with patients and their families and carers that defines an appropriate amount of physical activity, provides a nutritional plan, and offers the necessary psychological support. One of the most important steps in the management of people living with ME/CFS is accepting the patient’s description of their symptoms, and providing reassurance that any ‘normal’ test results do not imply an absence of disease—just an absence of the appropriate technology to confirm the diagnosis.

Dr David Strain

Clinical Senior Lecturer, Diabetes and Vascular Research Centre, University of Exeter Medical School; Medical Advisor to Action for ME