Chronic Fatigue Syndrome: progress and possibilities, by Carolina X Sandler, Andrew R Lloyd in Medical Journal of Australia April 5, 2020


Review Summary

  • Chronic fatigue syndrome (CFS) is a prevalent condition affecting
    about one in 100 patients attending primary care.
  • There is no diagnostic test, validated biomarker, clear
    pathophysiology or curative treatment.
  • The core symptom of fatigue affects both physical and cognitive
    activities, and features a prolonged post‐activity exacerbation
    triggered by tasks previously achieved without difficulty.
  • Although several different diagnostic criteria are proposed, for
    clinical purposes only three elements are required: recognition of the
    typical fatigue; history and physical examination to exclude other
    medical or psychiatric conditions which may explain the symptoms; and a
    restricted set of laboratory investigations.
  • Studies of the underlying pathophysiology clearly implicate a range of
    different acute infections as a trigger for onset in a significant
    minority of cases, but no other medical or psychological factor has been
    reproducibly implicated.
  • There have been numerous small case-control studies seeking to
    identify the biological basis of the condition. These studies have
    largely resolved what the condition is not: ongoing infection,
    immunological disorder, endocrine disorder, primary sleep disorder, or
    simply attributable to a psychiatric condition.
  • A growing body of evidence suggests CFS arises from functional
    (non‐structural) changes in the brain, but of uncertain character and
    location. Further functional neuroimaging studies are needed.
  • There is clear evidence for a genetic contribution to CFS from family
    and twin studies, suggesting that a large scale genome‐wide association
    study is warranted.
  • Despite the many unknowns in relation to CFS, there is significant
    room for improvement in provision of the diagnosis and supportive care.
    This may be facilitated via clinician education.


Chronic fatigue syndrome (CFS) is an enigmatic clinical entity which challenges patients, health care providers and researchers alike.1 The diagnosis is sometimes avoided by medical practitioners, leaving patients in diagnostic limbo andprone to non-evidence- based labels and potentially harmful treatments. This quandary reflects the lack of a diagnostic test, validated biomarker, clear pathophysiology or curative treatment.

We retrieved publications from MEDLINE, PsycINFO, EMBASE, Cochrane and PubMed databases from 1988 to 2019 to consider aspects of clinical decision making in the diagnosis, assessment of prognosis, and management of CFS; provide an update on understanding of CFS pathophysiology; and identify priorities for improved care of patients with CFS and for future research. This review focuses on adult populations, but the condition also affects children and adolescents (reviewed elsewhere).2

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