Klonoff, D C · Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 1992 · DOI
ME/CFS is a complex illness characterized by persistent fatigue and other symptoms, but doctors currently have no blood test or scan to diagnose it—they rely instead on what patients report. Research has identified that several factors may increase risk of developing ME/CFS, including viral infections, mental health conditions, and allergies, and studies show problems across multiple body systems including immune, nervous, hormone, and muscle function. While there is no cure yet, treatments like exercise, counseling, and medications can help manage some symptoms.
This foundational review synthesizes understanding of ME/CFS as a multisystem disorder and acknowledges the absence of definitive diagnostic tests, validating the diagnostic challenges patients and clinicians face. By documenting dysfunction across multiple organ systems rather than attributing symptoms to a single cause, it supports a biologically-informed view of ME/CFS and highlights the need for further research into underlying mechanisms.
This review does not establish causation for any identified risk factors—it describes associations and potential contributors without proving which factors directly cause ME/CFS. The identification of modest multisystem dysfunction does not prove these abnormalities are the primary drivers of illness rather than secondary consequences. The review also does not demonstrate the efficacy of listed treatments, only that they may provide symptomatic relief.
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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