Definition & Key Features

Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome (ME/CFS) is a complex, chronic, fluctuating, multi-system medical condition. Its pathophysiology is still under investigation. It affects individuals differently, with impacts ranging from mild limitation to profound incapacity.

Hallmark Features:

• Debilitating Fatigue: Worsened by activity, not caused by excessive exertion, and not relieved by rest. It is often described as feeling ‘flu-like’ or being ‘physically drained’.
• Post-Exertional Malaise (PEM): A disproportionate worsening of symptoms following minimal physical, cognitive, emotional, or social activity. The onset is often delayed by hours or days, with a prolonged recovery that may last for days, weeks, or even longer. This is a core feature.
• Unrefreshing Sleep: Sleep disturbance is common, including feeling exhausted upon waking, broken or shallow sleep, altered sleep patterns, or hypersomnia.
• Cognitive Difficulties (‘Brain Fog’): Problems with word-finding, slowed responsiveness, short-term memory deficits, and difficulty with concentration or multitasking.

Severity Levels:

• Mild: Able to care for themselves and perform light domestic tasks. Most are in work or education but have likely ceased all leisure and social activities and may require reduced hours or days off to cope.
• Moderate: Mobility is reduced, and they are restricted in all activities of daily living. They have usually stopped work or education and require regular rest periods.
• Severe: Unable to perform any activity for themselves or only minimal tasks (e.g., washing face). They have severe cognitive difficulties, may depend on a wheelchair, are often unable to leave the house, and are extremely sensitive to light and sound.
• Very Severe: Bed-bound all day and dependent on care for all needs, including personal hygiene and eating. They experience extreme sensitivity to sensory stimuli. Some may require tube feeding.

Complications: If unmanaged, ME/CFS leads to significant functional decline. Prolonged immobility, especially in severe cases, increases the risk of pressure ulcers, deep vein thrombosis (DVT), and muscle contractures. There is also a substantial impact on psychological, emotional, and social wellbeing.

Epidemiology & Risk Factors

• Prevalence: It is estimated that approximately 0.5% to 0.9% of the UK population has ME/CFS, potentially affecting around 400,000 people. Many cases are believed to be undiagnosed.
• Age Patterns: It can affect people of all ages, including children. In adults, it is most common between the ages of 30 and 50. In children, a common age for development is 13-15 years.
• Gender Patterns: ME/CFS is diagnosed significantly more often in women than in men, with ratios estimated at approximately 4:1. The disparity can be as high as 6:1 for women in their 30s and 40s.
• Non-Modifiable Risk Factors:
  • Genetics: The condition can run in families, suggesting a genetic predisposition.
  • Female Sex: Women are at a significantly higher risk.
• Modifiable/Triggering Factors:
  • Infections: Onset often follows an acute viral or bacterial infection (e.g., Epstein-Barr virus, Coxiella burnetii, COVID-19). Approximately 1 in 10 people with certain infections may develop an ME/CFS-like illness.
  • Physical or Emotional Trauma: Some individuals report an injury, surgery, or significant emotional stress shortly before symptom onset.

Clinical Presentation & Diagnosis

Typical Symptoms: In addition to the four core features, the following are also common:

• Orthostatic Intolerance: Dizziness, palpitations, fainting, or nausea upon moving to an upright position (e.g., Postural Orthostatic Tachycardia Syndrome – POTS).
• Pain: Widespread muscle pain (myalgia), joint pain (without swelling), headaches, or pain on touch.
• Neuromuscular Symptoms: Twitching, myoclonic jerks.
• Flu-like Symptoms: Sore throat, tender lymph nodes, chills, muscle aches.
• Heightened Sensory Sensitivities: Intolerance to light, sound, touch, taste, and smell.
• Gastrointestinal Issues: Nausea, bloating, constipation.
• Temperature Hypersensitivity: Profuse sweating, chills, hot flushes.
• Intolerance: To alcohol, or certain foods and chemicals.

Diagnostic Criteria (NICE NG206): A diagnosis can be made when:

1. All four core symptoms (debilitating fatigue, post-exertional malaise, unrefreshing sleep, cognitive difficulties) have persisted for a minimum of 3 months.
2. The person’s ability to engage in occupational, educational, social, or personal activities is significantly reduced from pre-illness levels.
3. The symptoms are not explained by another condition.

Suspecting ME/CFS: Suspect ME/CFS if the four core symptoms have been present for a minimum of 6 weeks in adults or 4 weeks in children and young people, alongside a significant reduction in functioning.

Investigations (to exclude other diagnoses): Perform the following at initial presentation:

• Urine: Urinalysis for protein, blood, and glucose.
• Blood Tests:
  • Full blood count
  • Urea and electrolytes
  • Liver function tests
  • Thyroid function tests
  • Erythrocyte sedimentation rate (ESR) or plasma viscosity
  • C-reactive protein (CRP)
  • Calcium and phosphate
  • HbA1c
  • Serum ferritin
  • Coeliac screening (tissue transglutaminase antibodies)
  • Creatine kinase

Use clinical judgement for additional tests, such as Vitamin D, B12, folate, and 9 am cortisol for adrenal insufficiency.

Red Flags for Referral or Action:

• Consider seeking advice from an appropriate specialist if there is diagnostic uncertainty.
• For children and young people: Refer to a paediatrician for further assessment as soon as ME/CFS is suspected.

Differential Diagnoses: The investigation panel aims to rule out conditions such as: Anaemia, thyroid disease, diabetes, adrenal insufficiency, coeliac disease, liver disease, autoimmune conditions, primary sleep disorders, and mood disorders.

Initial Management

First-line approach is non-pharmacological. There is no curative pharmacological treatment for ME/CFS.

Non-Pharmacological Measures (Core of Management):

1. Energy Management:
   • Indication: For all patients with suspected or diagnosed ME/CFS. This is the central self-management strategy.
   • Approach:
     • Advise the patient not to push through symptoms.
     • Work with the patient to establish their current energy limits for all types of activity (physical, cognitive, emotional).
     • The initial step is often to reduce activity to a sustainable level that does not trigger post-exertional malaise.
     • Plan daily routines with pre-emptive rest, alternating and breaking down activities into manageable chunks.
     • Use tools like activity diaries or phone monitors to track activity and symptoms.
     • This is a long-term strategy; stabilisation can take months or years.
2. Rest and Sleep:
   • Advise on the importance of structured rest periods during the day.
   • Provide personalised sleep management advice (e.g., good sleep habits, managing daytime rest against night-time sleep).
3. Dietary Advice:
   • Emphasise the importance of a healthy balanced diet (NHS Eat Well Guide) and adequate fluid intake.
   • Advise eating small, regular meals to manage nausea.
   • Consider Vitamin D deficiency risk, especially in housebound patients.

Patient Education (from initial suspicion):

• Explain that diagnosis is confirmed at 3 months.
• Advise them to manage energy, rest as needed, and maintain a balanced diet.
• Reassure them they can return for review if symptoms worsen.

Pharmacological Measures (for Symptom Control ONLY):

• DO NOT offer any medicine or supplement to CURE ME/CFS.
• When prescribing for associated symptoms (e.g., pain, orthostatic intolerance):
  • Start at a lower dose than in usual clinical practice.
  • Increase the dose gradually and monitor for tolerance and side effects, as people with ME/CFS can be intolerant to medicines.
  • Pain management should follow relevant NICE guidelines (e.g., for neuropathic pain).
  • Medicines for orthostatic intolerance should only be prescribed or overseen by a specialist.
  • In children and young people, drug treatment must be started under paediatric supervision.

Initial Monitoring:

• Regularly review the patient’s self-management strategies.
• Monitor symptoms and their impact on daily life.
• For children, begin liaison with their school to support flexible adjustments.

Further Management & Escalation

Referral Indications:

• Adults: Refer to an ME/CFS specialist team once the diagnostic criteria are met at 3 months to confirm the diagnosis and develop a holistic care and support plan.
• Children and Young People: Refer to a paediatrician as soon as ME/CFS is suspected. Following assessment by the paediatrician, refer to a paediatric ME/CFS specialist team.
• Specialist Referrals for Specific Symptoms:
  • Dietitian with ME/CFS interest: If there is weight loss/gain or a restrictive diet.
  • Secondary Care Specialist: For severe or worsening orthostatic intolerance.
  • Specialist Pain Service: For complex pain management.
  • Physiotherapist/Occupational Therapist in an ME/CFS team: For support with energy management, mobility issues, or if the patient is ready to consider a physical activity programme.

Specialist Interventions (if first-line symptom management is insufficient):

• Personalised Physical Activity Programme:
  • This is NOT Graded Exercise Therapy (GET). DO NOT offer GET (defined as fixed incremental increases in physical activity based on deconditioning theories).
  • Only consider for patients who feel ready to progress beyond daily activities.
  • Must be overseen by a physiotherapist in an ME/CFS specialist team.
  • The programme involves establishing a stable baseline below their energy limit, maintaining it, and only then making very slow, flexible adjustments, with a clear plan for managing flare-ups.
• Cognitive Behavioural Therapy (CBT):
  • This is NOT a cure. It is offered to help patients manage symptoms, improve functioning, and reduce the distress of living with a chronic illness.
  • It should only be offered if the patient wishes to use it as a supportive tool.
  • Must be delivered by a therapist with expertise in ME/CFS.
  • The approach is collaborative, non-judgemental, and adapted to the patient’s fluctuating symptoms and energy levels.
• DO NOT OFFER the Lightning Process.

Red Flags for Urgent Escalation/Reassessment:

• A relapse (sustained and marked exacerbation of symptoms) that cannot be managed with the existing care plan.
• The appearance of any new symptoms or a significant deterioration in existing ones. These must be evaluated and investigated, not assumed to be part of ME/CFS.

Surgical Options:

• There are no surgical options for the treatment of ME/CFS itself.

Follow-up & Safety Netting

• Frequency of Follow-up:
  • Adults: A review in primary care at least once a year.
  • Children and Young People: A review at least every 6 months.
  • More frequent reviews are necessary depending on symptom severity and complexity.
• Monitoring Requirements at Review:
  • Discuss changes in the condition and symptoms.
  • Review the energy management plan.
  • Assess psychological, emotional, and social wellbeing.
  • Investigate any new symptoms to rule out other conditions.
• Patient Advice on Self-Management:
  • Flare-ups vs. Relapses: Educate the patient on the difference. A flare-up is a temporary worsening of symptoms for a few days. A relapse is a sustained and marked exacerbation requiring a substantial adjustment to energy management.
  • Flare-up Plan: Temporarily reduce activity, identify triggers if possible, and do not return to usual activity until it resolves.
  • Relapse Plan: Substantially reduce or stop activities, increase rest, and reassess energy limits to stabilise.
  • Information and Support: actionforme.org.uk, meassociation.org.uk
• Health Promotion:
  • Ensure vaccinations are up to date.
  • Advise on Vitamin D supplementation for those who are housebound.
  • Discuss social care needs assessments and financial support/benefits where applicable.
• Warning Signs Prompting Urgent Reassessment:
  • Contact their named primary care or specialist team contact if a flare-up or relapse cannot be managed with their agreed plan.
  • Any new symptom or a significant change in symptoms warrants a full clinical evaluation.
  • For people with severe ME/CFS, assess regularly for complications of immobility (pressure ulcers, DVT risk).

Key Points to Remember

1. Believe the Patient: Acknowledge the reality and impact of their symptoms. ME/CFS is a recognised, complex medical condition.
2. Core Symptoms are Key: Diagnosis requires all four: Debilitating fatigue, Post-Exertional Malaise (PEM), unrefreshing sleep, and cognitive difficulties, present for at least 3 months. PEM is a hallmark feature.
3. Investigate and Refer: Perform baseline bloods to exclude other causes. Refer adults to a specialist team at 3 months. Refer children to a paediatrician on suspicion.
4. Energy Management is Central: The core of management is helping patients stay within their energy limits. Advise them not to ‘push through’.
5. No Cure, Manage Symptoms: There is no curative drug. Use medication cautiously at low starting doses for symptom control only.
6. DO NOT Offer Graded Exercise Therapy (GET): Generalised or fixed incremental exercise programmes are harmful. Personalised activity programmes must be specialist-led, cautious, and flexible.
7. DO NOT Offer the Lightning Process.
8. Plan for Flare-ups and Relapses: A written plan for managing symptom exacerbations is essential for every patient.
9. Investigate New Symptoms: Do not assume a new symptom is part of ME/CFS. It requires fresh clinical assessment.
10. Acknowledge Severity: The impact ranges from mild to very severe, where patients can be totally bed-bound and dependent on others for all care. Adapt care delivery accordingly (e.g., home visits).

This MedDigest summary is intended for educational purposes only and should not be used for clinical purposes. It is an independent resource, prepared by MedDigest, to offer an accessible overview of information drawn from the NICE guidelines. The original NICE content is © Crown copyright and is used under the Open Government Licence v3.0. While MedDigest strives for accuracy in its educational summaries, this content has not been reviewed or produced by NICE. For comprehensive and definitive recommendations, please always refer to the complete NICE guidelines.

References

NICE (29 October 2021) Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. https://www.nice.org.uk/guidance/ng206