What are the diagnostic criteria for chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME)?

Diagnostic Criteria for Chronic Fatigue Syndrome (ME/CFS)

The diagnostic criteria for chronic fatigue syndrome (ME/CFS) include a substantial reduction in activity levels for at least 6 months, profound fatigue not alleviated by rest, postexertional malaise, unrefreshing sleep, and either cognitive impairment or orthostatic intolerance. 1

Core Diagnostic Requirements

• Substantial impairment: Significant reduction in ability to engage in pre-illness occupational, educational, social, or personal activities lasting for at least 6 months 1
• Profound fatigue: New or definite onset (not lifelong) fatigue that is not substantially alleviated by rest 1
• Postexertional malaise: Worsening of symptoms following physical or cognitive exertion, often delayed by hours or days 1
• Unrefreshing sleep: Sleep that does not restore normal energy or function 1

Plus at least one of the following:

• Cognitive impairment: Problems with memory, concentration, information processing ("brain fog") 1
• Orthostatic intolerance: Symptoms that worsen upon assuming and maintaining upright posture 1

Clinical Evaluation Process

• Exclusion of alternative diagnoses: ME/CFS is a diagnosis of exclusion requiring thorough evaluation to rule out other conditions that could explain symptoms 1
• Duration requirement: Symptoms must persist for at least 6 months to meet diagnostic criteria 1
• Symptom pattern: Symptoms typically follow a viral or bacterial infection in many cases 1
• Severity assessment: 25% of patients have severe ME/CFS, often meaning they are bed-bound with extreme sensory sensitivity 1

Associated Findings

• Immune system abnormalities: Diminished natural killer cell function, T cell exhaustion, and other immune dysregulation 1
• Mitochondrial dysfunction: Impaired energy production and metabolic abnormalities 1
• Vascular and endothelial abnormalities: Including deformed red blood cells and reduced blood volume 1
• Neurological abnormalities: Neuroinflammation, reduced cerebral blood flow, and brainstem abnormalities 1
• Endocrine abnormalities: Hypothalamus-pituitary-adrenal axis dysfunction, including low cortisol levels 1

Diagnostic Pitfalls to Avoid

• Misattribution to deconditioning: ME/CFS involves complex pathophysiology beyond simple deconditioning 2
• Overlooking postexertional malaise: This cardinal symptom distinguishes ME/CFS from other fatigue conditions 1
• Misdiagnosis as psychiatric disorder: ME/CFS is a biological illness with neurological and immunological components, not primarily a psychiatric condition 1
• Reliance on laboratory tests: No definitive biomarkers exist; diagnosis remains clinical 3, 4
• Inadequate exclusion of other conditions: Thorough evaluation needed to rule out other causes of chronic fatigue 5, 4

Differential Diagnosis Considerations

• Postural Orthostatic Tachycardia Syndrome (POTS): Heart rate increase ≥30 bpm within 10 minutes of standing without hypotension 1, 2
• Long COVID: About half of long COVID patients meet criteria for ME/CFS, with similar pathophysiological mechanisms 1, 2
• Primary sleep disorders: Can cause fatigue but typically don't include postexertional malaise 5
• Endocrine disorders: Thyroid dysfunction, adrenal insufficiency 5
• Autoimmune conditions: Such as systemic lupus erythematosus, rheumatoid arthritis 5

ME/CFS remains a challenging diagnosis requiring careful clinical assessment. The absence of a definitive biomarker necessitates thorough evaluation and application of established clinical criteria to identify affected patients and provide appropriate management.