Last reviewed: July 2018
Last updated: January  2018



History and exam

Key diagnostic factors

  • persistent disabling fatigue
  • post-exertional malaise/fatigue (PEM), exertional exhaustion
  • short-term memory and/or concentration impairment
  • sore throat
  • generalised arthralgia without inflammation
  • headache/migraine with onset after the fatigue
  • unrefreshing sleep
  • orthostatic intolerance
  • diffuse muscular, tendon, fascial, and other pain
  • tender lymph nodes/glands

Other diagnostic factors

  • age of onset (adolescence and 30 to 50 years)
  • flu-like symptoms (malaise, myalgia, feverishness)
  • dizziness/lightheadedness
  • anxiety, affective disorder, atypical depression
  • sensations of altered temperature
  • exertion-induced cognitive dysfunction (affecting working memory, not persistent)
  • irritant sensitivities
  • feverishness

Risk factors

  • female sex
  • autoimmunity
  • positive family history of CFS
  • genetic factors
  • gut microbiome
  • infections
  • psychological factors
  • ancestry
  • joint hypermobility/laxity

Diagnostic investigations

1st investigations to order

  • FBC with WBC differential
  • ESR
  • CRP
  • comprehensive metabolic panel
  • TSH
  • antinuclear antibody (ANA), rheumatoid factor
  • HIV antibody test
Full details

Investigations to consider

  • heads-up tilt table test if symptomatic orthostatic intolerance
  • 2-day cardiopulmonary exercise testing
  • serum ferritin
  • HbA1c
  • urine toxicology screen
  • antibody tests for gluten sensitivity/coeliac disease
  • brain magnetic resonance imaging (MRI)
Full details

Treatment algorithm



Authors VIEW ALL

James N. Baraniuk


Division of Rheumatology, Immunology, and Allergy

Georgetown University




JNB is an author of a number of references cited in this monograph.

Dr James N. Baraniuk would like to gratefully acknowledge Dr Craig N. Sawchuk and Dr Dedra Buchwald, the previous contributors to this monograph. CNS declares that he has no competing interests. DB is an author of a number of references cited in this monograph.

Peer reviewers VIEW ALL

General Practitioner

Howick Health and Medical Centre


New Zealand


RV declares that she has no competing interests.

Consultant Neurologist and Clinical Director of Neurosciences

Department of Neurology

Queen's Hospital




AC has received honoraria, speaker fee, and sponsorship from the following pharmaceutical companies: TEVA, Novartis, Biogen, Bayer Schering, Terumo BCT, and Genzyme.

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