Holmes, G P, Kaplan, J E, Gantz, N M et al. · Annals of internal medicine · 1988 · DOI
This landmark 1988 paper proposed a new name and formal definition for what was previously called 'chronic Epstein-Barr virus syndrome.' The authors recognized that the condition was poorly understood and inconsistently diagnosed, so they renamed it 'chronic fatigue syndrome' (ME/CFS) and created a working definition to help doctors identify and study it more consistently. This definition focused on severe, ongoing fatigue along with other symptoms like sore throat, headaches, and muscle pain.
This paper established the first standardized diagnostic framework for ME/CFS, enabling consistent case identification across research studies and clinical practice. Without this definition, the condition remained fragmented and poorly recognized, hindering research progress and patient diagnosis. This work laid the foundation for decades of subsequent ME/CFS research and remains foundational to how the disease is understood today.
This study does not prove what causes ME/CFS or establish Epstein-Barr virus as a causal agent—in fact, the authors explicitly rejected the assumed EBV connection. The definition proposed is a clinical case definition for research purposes and does not constitute a validated diagnostic test or etiological explanation. It does not provide epidemiologic data on prevalence, incidence, or natural history of the condition.
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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