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Monday, August 11, 2025

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS)


Introduction
Myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS), is a chronic, complex, and debilitating disorder characterized primarily by profound fatigue not relieved by rest and accompanied by a range of physical, cognitive, and neuroimmune symptoms. The fatigue is severe enough to significantly impair daily functioning and persists for at least 6 months.
The exact cause is unknown, but it is thought to involve immune system dysregulation, neuroendocrine abnormalities, and impaired energy metabolism.

Epidemiology

  • Prevalence: Estimated at 0.2–0.4% of the population.

  • Age of onset: Commonly between 20 and 50 years but can occur at any age, including in children.

  • Female-to-male ratio: Approximately 2–3:1.

Etiology and Risk Factors

Proposed Triggers

  • Viral infections: e.g., Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), enteroviruses.

  • Bacterial infections: e.g., Coxiella burnetii (Q fever).

  • Other stressors: surgery, trauma, major psychological stress.

Risk Factors

  • Family history of ME/CFS or autoimmune diseases.

  • Female sex.

  • Previous history of allergies or asthma.

Pathophysiology

The exact mechanism remains unclear, but evidence suggests:

  • Immune dysfunction: Altered cytokine profiles, reduced natural killer (NK) cell function.

  • Neuroendocrine disturbances: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation.

  • Autonomic nervous system abnormalities: Orthostatic intolerance, postural tachycardia.

  • Mitochondrial dysfunction: Impaired oxidative metabolism and reduced energy production.

Clinical Features

Core Symptom

  • Post-exertional malaise (PEM): Worsening of symptoms after minimal physical or mental activity, lasting 24 hours or more.

Other Common Symptoms

  • Persistent fatigue lasting ≥6 months.

  • Cognitive impairment (“brain fog”): poor concentration, memory problems.

  • Unrefreshing sleep.

  • Orthostatic intolerance (lightheadedness, palpitations, dizziness when upright).

  • Muscle pain (myalgia) and joint pain without swelling.

  • Headaches of new type or severity.

  • Sore throat and tender cervical/axillary lymph nodes.

  • Hypersensitivity to light, sound, and odors.

Diagnostic Criteria

Diagnosis is clinical and based on exclusion of other causes. Commonly used criteria include:

Institute of Medicine (IOM) 2015 Criteria – All required:

  1. Substantial reduction/impairment in activity level for >6 months with fatigue not relieved by rest.

  2. Post-exertional malaise.

  3. Unrefreshing sleep.

  4. Plus ≥1 of the following:

    • Cognitive impairment.

    • Orthostatic intolerance.

Investigations

  • Routine labs (CBC, ESR/CRP, thyroid function, liver/kidney function, glucose, vitamin B12, folate) to exclude other conditions.

  • Additional tests if indicated to rule out other causes of fatigue.

Management

There is no curative treatment; management aims to relieve symptoms, improve quality of life, and prevent exacerbations. Treatment is individualized.

1. Non-Pharmacologic Strategies

  • Activity pacing: Avoid overexertion and balance rest with gentle activity to prevent PEM.

  • Sleep hygiene: Regular sleep schedule, quiet/dark sleeping environment.

  • Dietary adjustments: Balanced nutrition, small frequent meals for orthostatic intolerance.

  • Psychological support: Counseling or CBT for coping strategies (not as a cure).

  • Physical therapy: Gentle stretching or low-intensity exercise, only as tolerated.

2. Pharmacologic Symptom Management

For Pain and Muscle Aches

  • Paracetamol: 500–1000 mg every 4–6 hours as needed (max 4 g/day).

  • Ibuprofen: 200–400 mg every 6–8 hours as needed (max 1200 mg/day OTC; higher doses under medical supervision).

For Sleep Disturbance

  • Low-dose amitriptyline: 10–25 mg orally at bedtime.

  • Trazodone: 25–50 mg orally at bedtime.

  • Melatonin: 2–5 mg orally at bedtime.

For Orthostatic Intolerance

  • Fludrocortisone: 0.1–0.2 mg daily.

  • Midodrine: 2.5–10 mg orally three times daily during waking hours.

For Cognitive Symptoms (limited evidence)

  • Modafinil: 100–200 mg orally in the morning for severe daytime sleepiness (off-label).

Prognosis

  • Course is variable: some patients experience partial improvement, while others remain significantly impaired for years.

  • Early diagnosis and management may improve outcomes.

  • Complete recovery is rare, but many achieve symptom control sufficient for improved function.




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