Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): diagnosis and management.
Fan, Jin, Jiao, Jiao, Chang, Hai-Qing et al. · Journal of translational medicine · 2025 · DOI
Quick Summary
This comprehensive review examines how ME/CFS is diagnosed and treated based on current medical knowledge. The authors found that ME/CFS is caused by problems with the immune system, energy production in cells, and brain inflammation, but there are currently no definitive blood tests to confirm the disease. Treatment options include both medication approaches (targeting immune dysfunction and cell energy) and non-medication strategies like activity pacing and cognitive behavioral therapy, though doctors now recognize that exercise programs can actually harm some patients.
Why It Matters
This review provides clinicians and patients with current, evidence-based guidance on ME/CFS diagnosis and management at a time when prevalence is rising and overlap with post-COVID syndrome is increasing. The explicit recommendation against graded exercise therapy represents an important shift in clinical practice that protects patients from potentially harmful interventions. Understanding the multiple biological pathways involved (immune, mitochondrial, neuroinflammatory) supports the rationale for developing targeted, combination treatment approaches.
Observed Findings
Current ME/CFS diagnosis relies on clinical symptoms and lacks definitive biomarkers
Immune dysregulation, oxidative stress, mitochondrial dysfunction, and neuroinflammation are consistently identified in ME/CFS pathology
Graded exercise therapy (GET) is contraindicated due to potential for harm
Cognitive behavioral therapy (CBT) functions as adjunctive symptom management, not cure
Activity pacing and personalized symptom-oriented approaches are recommended as core management strategies
Inferred Conclusions
ME/CFS has multiple concurrent biological dysfunctions requiring multi-targeted treatment approaches rather than single-pathway interventions
Personalized, symptom-oriented clinical assessment is essential given individual differences in disease presentation and treatment response
Biomarker development is critical for improving diagnostic precision and enabling mechanism-based treatment selection
Current non-pharmacological interventions (CBT, activity pacing) provide symptom relief through different mechanisms than previously assumed graded exercise protocols
Remaining Questions
Which specific biomarkers or biomarker combinations would best predict ME/CFS diagnosis and treatment response in individual patients?
What This Study Does Not Prove
This review does not establish causal mechanisms—it summarizes associations between immune dysfunction, cellular energy problems, and ME/CFS symptoms without proving which mechanisms cause which symptoms. The absence of validated biomarkers means this review cannot determine how to definitively diagnose ME/CFS in individual patients or predict which treatments will work best for specific people. The review's recommendations reflect current evidence quality, which is still limited for many interventions, particularly combination therapies.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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How should pharmacological and non-pharmacological interventions be optimally combined to target multiple pathophysiological pathways simultaneously?
What mechanistic factors explain why certain patients benefit from specific interventions while others do not, and how can personalized treatment selection be improved?
How can real-world digital health technologies be effectively integrated into ME/CFS monitoring and management to track disease progression and treatment efficacy over time?