Summary

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, chronic, multisystem disease characterised by profound fatigue lasting at least 6 months, post-exertional malaise (PEM), unrefreshing sleep, and cognitive dysfunction ("brain fog"). It is a diagnosis of exclusion — all other causes of fatigue must be ruled out. ME/CFS can be severely disabling, with 25% of patients housebound or bedbound. The 2021 NICE guideline NG206 represented a paradigm shift: it removed graded exercise therapy (GET) as a treatment and emphasised energy management (pacing) as the core approach. There is no cure, and management focuses on symptom control, pacing within the "energy envelope," and multidisciplinary support.

Key Facts

• Definition: Chronic fatigue ≥6 months + PEM + unrefreshing sleep + cognitive difficulties
• Post-exertional malaise (PEM): Hallmark feature — worsening of symptoms after physical or cognitive exertion
• Prevalence: ~0.2-0.4% of the population; affects all ages
• Sex ratio: Female predominance (3-4:1)
• Triggers: Often follows viral infection (EBV, COVID-19) but cause unknown
• Severity: Mild (mobile, can work with difficulty) to severe (housebound/bedbound)
• NICE 2021: GET removed; energy management (pacing) is now the key strategy
• No biomarker: Diagnosis is clinical; exclude other causes
• Prognosis: Variable; many remain symptomatic for years; children have better outcomes

Clinical Pearls

"PEM Is the Cardinal Feature": Post-exertional malaise — a delayed worsening of symptoms 24-72 hours after even minor exertion — is what distinguishes ME/CFS from other fatigue conditions. Always ask about it.

"GET Is No Longer Recommended": The 2021 NICE guideline (NG206) removed graded exercise therapy as a treatment. Pushing through symptoms often causes harm. Energy management (pacing) is now emphasised.

"It's a Diagnosis of Exclusion": You must exclude organic causes before diagnosing ME/CFS: hypothyroidism, diabetes, anaemia, coeliac disease, sleep apnoea, depression, malignancy.

"The Energy Envelope": Patients should identify their energy limits and stay within them ("pacing"). Boom-bust cycles (overdoing it on good days) worsen PEM.

"Long COVID Overlap": Many patients with post-COVID syndrome have symptoms indistinguishable from ME/CFS. The same management principles apply.

Why This Matters Clinically

ME/CFS is often misunderstood and under-recognised. Patients frequently experience diagnostic delays of years and may face dismissive attitudes. Understanding the updated NICE guidance is essential — inappropriate advice to "push through" can cause significant harm. Compassionate, patient-centred care and evidence-based energy management can substantially improve quality of life.[1,2]

Approach

Examination in ME/CFS is often unremarkable but is essential to exclude other conditions.

General:

• Appears fatigued
• May appear well at rest (symptoms fluctuate)
• Pallor (exclude anaemia)
• Signs of thyroid dysfunction

Cardiovascular:

• Orthostatic vital signs (lying → standing BP/HR)
• POTS: HR increase ≥30 bpm within 10 minutes of standing (without BP drop)
• Orthostatic hypotension: BP drop ≥20/10 mmHg

Neurological:

• Usually normal
• Exclude focal signs (would suggest alternative diagnosis)

Lymph nodes:

• May have mild tenderness (common in ME/CFS)
• Significant lymphadenopathy = investigate

Musculoskeletal:

• Tenderness without swelling common
• Exclude inflammatory arthritis

Tests for Orthostatic Intolerance

Natural History

Prognostic Factors

Key Guidelines

Key Changes in NICE NG206 (2021)

PACE Trial Controversy

What is ME/CFS?

ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) is a long-term illness that causes extreme tiredness, problems with sleep, difficulty thinking clearly ("brain fog"), and something called post-exertional malaise (PEM) — where symptoms get worse after even small amounts of activity.

What causes it?

The exact cause isn't known. It often starts after a viral infection (like glandular fever or COVID-19). Researchers think it may involve the immune system and how the body produces energy.

How is it diagnosed?

There is no specific test for ME/CFS. Doctors diagnose it based on your symptoms — mainly tiredness lasting at least 6 months, post-exertional malaise, unrefreshing sleep, and brain fog — and by ruling out other conditions.

How is it treated?

There is no cure, but there are things that help:

• Energy management (pacing): Learning your limits and staying within them. This is the most important strategy.
• Rest: Allow yourself proper rest periods.
• Symptom treatment: Medicines can help with sleep and pain.
• Support: Occupational therapy, support groups, and sometimes specialist ME/CFS clinics.

Important: "Pushing through" or forcing yourself to exercise more does NOT help and can make things worse.

What to avoid

• Don't try to "fight through" the fatigue
• Avoid boom-bust cycles (overdoing it on good days)
• Graded exercise therapy (GET) is no longer recommended

Where to get support

• ME Association: meassociation.org.uk
• Action for ME: actionforme.org.uk
• NHS ME/CFS services (if available locally)

High-Yield Exam Topics

Sample Viva Questions

Q1: A 32-year-old presents with 8 months of profound fatigue, cognitive difficulties, and worsening after activity. How do you approach diagnosis?

Model Answer: This presentation is consistent with ME/CFS given symptoms of fatigue, cognitive dysfunction, and the key feature of post-exertional malaise (symptoms worse after activity). ME/CFS is a diagnosis of exclusion. I would take a detailed history including onset (often post-viral), impact on daily life, and enquire specifically about PEM. Examination is usually normal but excludes alternative diagnoses. Investigations: FBC, TFTs, glucose, coeliac serology, CRP, LFTs, U&E — to exclude anaemia, thyroid disease, diabetes, coeliac, inflammation. If investigations are normal and symptoms persist ≥6 months, the diagnosis is ME/CFS. I would explain the diagnosis sensitively and discuss energy management.

Q2: What is post-exertional malaise and why is it important?

Model Answer: Post-exertional malaise (PEM) is a hallmark feature of ME/CFS. It refers to a worsening of symptoms following physical, cognitive, or emotional exertion. Importantly, PEM is delayed — typically occurring 12-72 hours after the activity — and recovery is prolonged. Patients describe "crashes" or "payback." PEM distinguishes ME/CFS from other causes of chronic fatigue (like depression or deconditioning). Its presence is key to diagnosis and informs management — patients must stay within their "energy envelope" to avoid triggering PEM.

Q3: What changed in the NICE 2021 guideline for ME/CFS?

Model Answer: The 2021 NICE guideline (NG206) made significant changes:

1. Graded Exercise Therapy (GET) was removed — it is no longer recommended as it can cause harm by triggering PEM.
2. Energy management (pacing) is now the central strategy — helping patients identify their limits and stay within them.
3. CBT is only offered to help manage the impact of illness, NOT as a cure.
4. The Lightning Process is explicitly not recommended.
5. The guideline emphasised listening to patients, personalised care, and avoiding harm.

Common Exam Errors

Last Reviewed: 2025-12-24 | MedVellum Editorial Team

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.