Myalgic encephalomyelitis

What is myalgic encephalomyelitis?¹

Myalgic encephalomyelitis (ME), known more commonly as chronic fatigue syndrome (CFS), is a complex, chronic medical condition affecting multiple body systems and of unknown cause.

ME/CFS can affect different aspects of the lives of people with ME/CFS and their families and carers, including activities of daily living, family life, social life, emotional well-being, work and education. ME/CFS is also a fluctuating condition in which a person's symptoms can change unpredictably in nature and severity over a day, week or longer. ME/CFS varies in long-term prognosis from person to person.

The impacts of ME/CFS can be worsened by particular triggers (can be known or new triggers, although in many cases there is no clear trigger), can be self-managed with support and advice, and can involve flare-ups and relapses even if symptoms are well managed. Planning for these flare-ups and relapses should be part of the energy management plan.

ME/CFS is classified by the World Health Organization (WHO) as a neurological disease, and this classification is recognised by the Department of Health, the Medical Research Council and the National Institute for Health and Care Excellence (NICE).

Diagnosing ME/CFS remains a challenge. Although the clinical features of the disease have been well established within diagnostic criteria, the diagnosis of ME/CFS is still one of exclusion, meaning that other medical conditions must be ruled out. The pathophysiological mechanisms are unclear but the neuro-immuno-endocrinological pattern of ME/CFS patients gleaned from various studies indicates that these three pillars may be the key point to understand the complexity of the disease.² Patients often experience symptoms for a prolonged time before an identification is made. Once diagnosed, patients often complain of receiving hostility from their healthcare provider as well as being subjected to treatment strategies that exacerbate their symptoms.³

• ME/CFS has an estimated prevalence of 0.1-0.5%.²

• ME/CFS predominantly affects adults, with a peak age of onset of between 20 and 45 years with a female:male ratio of 3:1.⁴

• It affects all ethnicities and socioeconomic groups but there is some evidence of a higher incidence in socially deprived families.⁵

• UK prevalence is thought to be around 0.16%.¹

• White people in the UK are five times more likely to be diagnosed with ME/CFS than people of other ethnicities.¹

The underlying cause of ME/CFS is still not well understood. Prior to a ME/CFS diagnosis, patients are mostly healthy, fully functional, and have a good quality of life.

• Approximately 50-80% of people with ME/CFS start suddenly with a flu-like illness.

• ME/CFS is often found after infection by a virus, bacterium, or parasite, suggesting an immunological dysfunction, accompanied by a strong genetic predisposition, as shown in twin analysis.

• Viral involvement is a well-supported theory due to the high index of an infectious onset in at least half of the patients.

• Life stressors can cause a negative impact on the neuroendocrine circuits of stress, leading to other complications besides immunological impairment.

• In addition to immune and viral aetiology, the attenuation of the hypothalamus-pituitary-adrenal (HPA) axis is documented in adult and adolescent ME/CFS patients, with marked evidence of systemic hypocortisolism, which can influence immunological and neuronal homeostasis.

• Studies have reported enhanced sympathetic nervous activity, as well as increased levels of catecholamines in ME/CFS, providing some evidence for a neuroactive pattern in the pathophysiology of ME/CFS.

• Many clinicians now accept that ME/CFS is likely to be a neuroimmune disorder, involving interaction of neurological and immunological processes, and an overactive innate immune response.⁶⁷

• There is a suggestion that glymphatic disturbance may play a part in the development of ME/CFS. ⁶

• More recent studies have shown an increase in hippocampal grey matter in patients with ME/CFS. ⁸

• There is some suggestion that long COVID and ME/CFS have very similar underlying causes ⁸ but other specialists disagree.⁹

There is currently no diagnostic test for ME/CFS and it is recognised on clinical grounds alone.

ME/CFS may be considered if all of the following symptoms are not explained by another condition, and are persistent for a minimum of six weeks in adults, and four weeks in children and young people:

• Debilitating fatigue that is worsened by activity, is not caused by excessive cognitive, physical, emotional or social exertion, and is not significantly relieved by rest.

• Post-exertional malaise after activity in which the worsening of symptoms:

  • Is often delayed in onset by hours or days.

  • Is disproportionate to the activity.

  • Has a prolonged recovery time that may last hours, days, weeks or longer.

• Unrefreshing sleep or sleep disturbance (or both), which may include:

  • Feeling exhausted, feeling flu-like, and stiff on waking.

  • Broken or shallow sleep, altered sleep pattern, or hypersomnia.

• Cognitive difficulties (sometimes described as 'brain fog'), which may include problems finding words or numbers, difficulty in speaking, slowed responsiveness, short-term memory problems, and difficulty concentrating or multitasking.

• The person's ability to engage in occupational, educational, social, or personal activities is significantly reduced from pre-illness levels.

In addition to the symptoms outlined above, the following symptoms may also be associated with, but are not exclusive to, ME/CFS:

• Orthostatic intolerance and autonomic dysfunction, including dizziness, palpitations, fainting, nausea on standing or sitting upright from a reclining position.

• Temperature hypersensitivity resulting in profuse sweating, chills, hot flushes, or feeling very cold.

• Neuromuscular symptoms, including twitching and myoclonic jerks.

• Flu-like symptoms, including sore throat, tender glands, nausea, chills or muscle aches.

• Intolerance to alcohol, or to certain foods and chemicals.

• Heightened sensory sensitivities, including to light, sound, touch, taste, and smell.

• Pain, including pain on touch, myalgia, headaches, eye pain, abdominal pain, or joint pain without acute redness, swelling, or effusion.

Describing severity¹⁰

Definitions of severity are not clear-cut because individual symptoms vary widely in severity, and people may have some symptoms more severely than others. The following definitions are provided by NICE as a guide to the level of impact of symptoms on everyday functioning.

• Mild ME/CFS: able to care for themselves and do some light domestic tasks (sometimes needing support) but may have difficulties with mobility. Most are still working or in education, but to do this they have probably stopped all leisure and social pursuits. They often have reduced hours, take days off and use the weekend to cope with the rest of the week.

• Moderate ME/CFS: reduced mobility and are restricted in all activities of daily living, although they may have peaks and troughs in their level of symptoms and ability to do activities. They have usually stopped work or education, and need rest periods, often resting in the afternoon for one or two hours. Their sleep at night is generally of poor quality and disturbed.

• Severe ME/CFS: unable to do any activity for themselves or can carry out minimal daily tasks only (such as face washing or cleaning teeth). They have severe cognitive difficulties and may depend on a wheelchair for mobility. They are often unable to leave the house or have a severe and prolonged after effect if they do so. They may also spend most of their time in bed and are often extremely sensitive to light and sound.

• Very severe ME/CFS: remain in bed all day and dependent on care. They need help with personal hygiene and eating, and are very sensitive to sensory stimuli. Some people may not be able to swallow and may need to be tube fed.

ME/CFS is diagnosed following careful assessment of history and examination, and exclusion of other possible causes of the presenting symptoms. There are currently no blood or other diagnostic tests available.

Many people with ME/CFS experience prolonged delays before getting properly assessed and diagnosed. A number of people diagnosed as having ME/CFS do in fact have a different condition.

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

• Postural tachycardia syndrome (PoTS).

• Hypothyroidism, diabetes, and anaemia should be considered as causes of fatigue.

• Systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel disease should be considered as causes of arthralgia.

• Underlying neoplasia should be considered as a cause of lymphadenopathy.

• Metabolic muscle disorders and myopathies should be considered as a cause of muscle pain and weakness.

• Psychiatric illness should be considered as a cause of depression and anxiety.

• Cardiological or respiratory causes should be considered for shortness of breath and chest pain, and many other illnesses, depending on the specific symptoms.

If ME/CFS is suspected, carry out:

• A medical assessment (including symptoms and history, comorbidities, overall physical and mental health, and a physical examination to exclude any other possible diagnoses).

Arrange initial investigations to exclude other diagnoses, including:

• Urinalysis for protein, blood and glucose.

• FBC, ESR or plasma viscosity, CRP.

• U&Es, liver function, thyroid function, calcium and phosphate.

• HbA1c, serum ferritin, coeliac screening, creatine kinase.

• Additional investigations to exclude other diagnoses may include vitamin D, vitamin B12, and folate levels; serological tests if there is a history of infection; and 9 am cortisol for adrenal insufficiency.

• Refer adults directly to an ME/CFS specialist team to confirm their diagnosis and develop a care and support plan.

• When ME/CFS is suspected in a child or young person, refer them to a paediatrician for further assessment for ME/CFS, and investigations for other conditions.

• Children and young people who have been diagnosed with ME/CFS after assessment by a paediatrician should be referred on by the paediatrician to a paediatric ME/CFS specialist team to confirm their diagnosis and develop a care and support plan.

Although some studies have shown benefit with some interventions, no effective intervention has been definitively proven for ME/CFS.¹¹

Advice for people with suspected ME/CFS

When ME/CFS is suspected, give people personalised advice about managing their symptoms. Also advise them:

• Not to use more energy than they perceive they have. They should manage their daily activity and not 'push through' their symptoms.

• To rest and convalesce as needed (this might mean making changes to their daily routine, including work, school, and other activities).

• To maintain a healthy balanced diet, with adequate fluid intake.

Explain that their diagnosis can only be confirmed after three months of persistent symptoms.

It is important to recognise that, despite guidance stating that people with ME/CFS should have significant input from a specialist team, this is often not available in the NHS with long waits to see a ME/CFS specialist and then limited or no input following any diagnosis.

Energy management

Each person has a different and fluctuating energy limit and they are experts in judging their own limits. It uses a flexible, tailored approach so that activity is never automatically increased but is maintained or adjusted (upwards after a period of stability or downwards when symptoms are worse).

Energy management is a self-management strategy led by the person affected, with support from a healthcare professional in an ME/CFS specialist team. It should include all types of activity (cognitive, physical, emotional and social) and take into account the person's overall level of activity. It helps people learn to use the amount of energy they have while reducing their risk of post-exertional malaise or worsening their symptoms by exceeding their limits.

Energy management can take weeks, months or sometimes even years to reach stabilisation or to increase tolerance or activity. The first step is to agree a sustainable level of activity as the first step, which may mean reducing activity. The plan should include periods of rest and activity, and incorporate the need for pre-emptive rest. It is important to alternate and vary between different types of activity and to break activities into small chunks.

Do not advise exercise that is not part of a programme, such as going to the gym or to exercise more, because this may worsen their symptoms.

A personalised physical activity or exercise programme should only be considered for people with ME/CFS who feel ready to progress their physical activity beyond their current activities of daily living or who would like to incorporate physical activity or exercise into managing their ME/CFS.

Some people with ME/CFS have found that exercise can make their symptoms worse; for some people it makes no difference, and others find it very helpful. If a physical activity or exercise programme is offered, it should be overseen by a physiotherapist in an ME/CFS specialist team.

NICE recommends that graded exercise therapy (fixed incremental increases in physical activity or exercise) should not be undertaken in ME/CFS.

Flare-ups and relapse

Agree with the person how to adjust their physical activity during a flare-up or relapse. This should include providing access to review and support from a physiotherapist in an ME/CFS specialist team.

The time it takes to return to the level of physical activity they had before varies from person to person. Once symptoms stabilise and the person feels able to resume physical activity, a new physical activity baseline should be established.

Symptom management for people with ME/CFS

Rest and sleep

Rest periods are part of all management strategies for ME/CFS. Introduce rest periods into the daily routine, including how often and for how long, as appropriate for each person. Relaxation techniques at the beginning of each rest period can be helpful. Common changes in sleep patterns seen in ME/CFS include broken or shallow sleep, altered sleep pattern or hypersomnia.

Take into account the need for rest in the day, and balance this against how the person is sleeping at night. Introduce changes to sleep patterns gradually. If sleep management strategies do not improve the person's sleep and rest, think about the possibility of an underlying sleep disorder or dysfunction and whether to refer to an appropriate specialist.

Physical functioning and mobility

Strategies to maintain and prevent deterioration of physical functioning and mobility need to be carried out in small amounts and spread out throughout the day. Strategies should include joint mobility, muscle flexibility, balance, postural, and positional support, muscle function, bone health, and cardiovascular health.

People with severe or very severe ME/CFS or those with prolonged periods of immobility should be assessed for areas at risk of pressure ulcers, deep vein thrombosis, and any risk of contractures.

Care and support plans in relation to physical functioning and mobility may include bed mobility, moving from lying to sitting to standing, transferring from bed to chair, using mobility aids, walking, joint mobility, muscle stretching, muscle strength, balance, and going up and down stairs.

Orthostatic intolerance

People with ME/CFS may experience orthostatic intolerance, including postural orthostatic tachycardia syndrome (PoTS). Clear advice should be given on adequate and frequent fluid intake, including on getting up in the morning and prior to activity. They should be encouraged to use compression stockings. PoTS is manageable for most people without further input but referral to secondary care should be considered if their symptoms are severe or worsening, or if there are concerns that another condition may be the cause. However there are limited NHS services for PoTS in most of the UK.

Pain

Chronic pain is sometimes associated with ME/CFS. Consider referring the person to specialist pain services if appropriate and if available.

Medicines

People with ME/CFS may be more intolerant of drug treatment. Consider starting any medication at a lower dose, and gradually increasing the dose if tolerated.

Dietary management and strategies

Adequate fluid intake and a well-balanced diet are essential. NICE advises that referral for a dietetic assessment by a dietician with a special interest in ME/CFS shpuld be considered for people with ME/CFS if they are losing weight and at risk of malnutrition, gaining weight, or following a restrictive diet. Again, this is unlikely to be available in most parts of the UK.

Children and young people with ME/CFS who are losing weight or have faltering growth or dietary restrictions should be referred to a paediatric dietician with a special interest in ME/CFS.

People with ME/CFS may be at risk of vitamin D deficiency, especially those who are housebound or bed-bound.

There is not enough evidence to support routinely taking vitamin and mineral supplements as a cure for ME/CFS or for managing symptoms.

Cognitive behavioural therapy (CBT)

CBT for people with ME/CFS should be offered if the patient would like to use it to support symptom management, improve wellbeing, functioning, and quality of life, and reduce the distress associated with having a chronic illness.

Managing flare-ups in symptoms and relapse

Flare-ups and relapses can happen even if the person's symptoms are well managed.

• A flare-up is a worsening of their symptoms beyond normal day-to-day variation, which lasts a few days.

• A relapse is a sustained and marked exacerbation of ME/CFS symptoms lasting longer than a flare-up and needing substantial and sustained adjustment of energy management.

Self-management strategies should include:

• Flare-up: identify possible triggers, such as acute illness or overexertion (there may be no clear trigger), temporarily reduce activity levels, monitor symptoms (although flare-ups are transient, some will develop into a relapse), and do not return to usual activity levels until the flare-up has resolved.

• Relapse: identify possible causes, reduce or stop some activities, increase the frequency or duration of rest periods, and reassess energy limits to stabilise symptoms.

If a flare-up or relapse cannot be managed using the person's self-management strategies, they should be advised to contact their named contact in primary care or the ME/CFS specialist team.

Review in primary care¹

Offer adults with ME/CFS a review of their care and support plan in primary care at least once a year. Children and young people with ME/CFS should be reviewed by a specialist paediatrician.

When carrying out a review in primary care, ensure you have access to the person's care and support plan and any clinical communications from the ME/CFS specialist team (including their discharge letter, if relevant). Discuss and record as a minimum:

• Their condition, including any changes in their illness and the impact of this.

• Symptoms, including whether they have experienced new symptoms.

• Self-management - ask about their energy management plan and (if relevant) their physical activity or exercise programme.

• Who is helping them and how they provide support.

• Psychological, emotional and social well-being.

• Any future plans, such as considering any changes or if they have any challenges ahead.

Consider seeking advice from an appropriate specialist if there is uncertainty about interpreting signs and symptoms and whether a referral is needed.

Evaluate and investigate whether new symptoms, or a change in symptoms, are due to the person's ME/CFS or whether they are due to another condition.

Severe or very severe ME/CFS¹

People with severe or very severe ME/CFS may experience symptoms that significantly affect their lives, including:

• Emotional well-being and ability to interact with others and care for themselves.

• Severe and constant pain, which can have muscular, arthralgic or neuropathic features.

• Hypersensitivity to light, sound, touch, movement, temperature extremes and smells.

• Extreme weakness, with severely reduced movement and very limited mobility.

• Reduced ability or inability to speak or swallow

• Cognitive difficulties that limit the ability to communicate and take in written or verbal communication.

• Sleep disturbance such as unrefreshing sleep, hypersomnia and altered sleep pattern.

• Gastrointestinal difficulties such as nausea, incontinence, constipation and bloating.

• Neurological symptoms such as double vision and other visual disorders, dizziness.

• Orthostatic intolerance and autonomic dysfunction, such as postural orthostatic tachycardia syndrome (PoTS) and postural hypotension.

Symptoms of severe or very severe ME/CFS may mean that people:

• Need a low-stimulus environment, such as a dark quiet room, with little or no social interaction.

• Are housebound or bed-bound and may need support with all activities of daily living, including aids and adaptations.

• Need careful physical contact, taking into account possible sensitivity to touch

• Cannot communicate without support and may need to choose someone to be their advocate and communicate for them.

• Are unable to eat and digest food easily and may need support with hydration and nutrition.

• Have problems accessing information - for example, because of difficulty with screens, sound and light sensitivity, headaches affecting their ability to read, or brain fog affecting their concentration.

Refer people with severe or very severe ME/CFS to a physiotherapist or occupational therapist working in an ME/CFS specialist team for support on developing energy management plans.

Refer people with severe or very severe ME/CFS for a dietetic assessment by a dietician with a special interest in ME/CFS.

The process and pace of any CBT for people with severe or very severe ME/CFS should be adjusted to meet the person's needs. This might include shorter, less frequent sessions and longer-term goals.

The outcome is very variable. Studies suggest that children with ME/CFS have a better chance of full recovery than adults with the condition.¹² Up to 83% of children made a full recovery though studies are limited by different definitions. ¹³One study suggested that physicians use the word "recovery" to mean complete symptom remission and a return to the patient's age-adjusted pre-morbid condition which resulted in a lower success rate; the recommendation was that ME/CFS should be viewed more through the lens of significant improvements and the ability to return to a more normal life, albeit not always with complete recovery. ¹⁴ Studies suggest that up to 8% of people make a full recovery whilst between 17 and 64% have significant improvement. ¹²

There is currently no effective method for predicting how the illness will progress or whether it will improve or resolve for any individual patient.

Predictors of outcomes (though none of these have been consistent across all studies) include:¹²

• On the whole, patients who are younger when they develop ME/CFS, have a better prognosis.

• Those who presented in old age have been shown to have a worse prognosis.

• A more severe degree of fatigue at onset has been shown to have a worse prognosis.

• Patients with comorbid fibromyalgia has been shown to have a worse prognosis.

• Patients with comorbid psychiatric conditions have been shown to have a worse prognosis.

• Receipt of financial compensation has been shown to lead to significantly better outcomes.

• Other risk factors for poorer recovery include:

  • Female sex.

  • Life stressors.

  • Lower socio-economic status.

Death in people with ME/CFS is usually caused by an unrelated illness, cancer and cardiovascular abnormalities are the most common causes.