Myalgic encephalomyelitis (Chronic fatigue syndrome)

Last reviewed: 3 May 2023
Last updated: 19 Jan 2022



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
More key diagnostic factors

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
Other diagnostic factors

Risk factors

  • female sex
  • Epstein-Barr infection in adolescents
  • coronavirus disease 2019 (COVID-19)
  • positive family history of ME/CFS
  • genetic factors
  • specific infectious diseases in adults
  • autoimmunity
  • gut microbiome
  • psychological factors
  • major depressive disorder
  • ancestry
  • joint hypermobility/laxity
More risk factors

Diagnostic investigations

1st investigations to order

  • DePaul symptom questionnaire
  • FBC with WBC differential
  • erythrocyte sedimentation rate
  • CRP
  • comprehensive metabolic panel
  • thyroid-stimulating hormone
  • antinuclear antibody (ANA), rheumatoid factor
  • HIV antibody test
More 1st investigations to order

Investigations to consider

  • heads-up tilt-table test if symptomatic orthostatic intolerance
  • serum ferritin
  • HbA1c
  • urine toxicology screen
  • antibody tests for gluten sensitivity/coeliac disease
More investigations to consider

Emerging tests

  • 2-day cardiopulmonary exercise testing

Treatment algorithm


all patients



James N. Baraniuk, MD


Division of Rheumatology, Immunology, and Allergy

Georgetown University




JNB has received reimbursement for accommodation and airfare as a Visiting Professor from Griffith University, Menzies Institute, National Center for Emerging Diseases, Surfer's Paradise, Australia. He has received reimbursement for carrying out two PhD Thesis Evaluations at Griffith University. He has received a number of research grants as a consultant and/or collaborator with financial support as contracted through Georgetown University. He has been a member of the Center for Scientific Review Special Emphasis Panel for ME/CFS at the National Institutes of Health, the Department of Veterans Affairs' Health Services Research and Development Scientific Merit Review Board, and the Department of Defense Peer Reviewed Medical Research Program study section. He has served on a number of Advisory Boards (Department of Veterans Affairs, Research Advisory Committee on Persian Gulf War Illness), on one occasion with financial reimbursement. Non-reimbursed activities include a number of lectures on ME/CFS, a role as a lecturer at George Washington School of Public Health, Washington, DC. He is the author of a number of recent abstracts and presentations on ME/CFS/Gulf War Illness. JNB is the author of one reference cited in the topic.


Dr James N. Baraniuk would like to gratefully acknowledge Dr Craig N. Sawchuk and Dr Dedra Buchwald, previous contributors to this topic.


CNS declares that he has no competing interests. DB is an author of a number of references cited in this topic. This topic was reviewed in 2018 by a patient with ME/CFS, and their feedback was considered as part of the topic update. The patient peer reviewer does not wish to be named.

Peer reviewers

Alastair Santhouse, MA (Cantab), MB, B.Chir, FRCP, FRCPsych

Consultant Psychiatrist in Psychological Medicine

South London and Maudsley NHS Foundation Trust

Denmark Hill




AS declares that he was a guideline development group member for NICE ME/CFS 2007 guidelines CG53.

Ben Z. Katz, MD

Professor of Pediatrics

Division of Infectious Diseases

Northwestern University Feinberg School of Medicine

Attending Physician

Ann & Robert H. Lurie Children’s Hospital of Chicago




BZK declares that he has no competing interests.

Indre Bileviciute-Ljungar, MD, PhD

Associated Professor in Rehabilitation Medicine

Department of Clinical Sciences

Danderyd University Hospital

Karolinska Institutet




IB-L declares that he has no competing interests.

Tarek Gaber, MB, BCh, MSc, FRCP

Consultant Physician in Rehabilitation Medicine

Wrightington, Wigan and Leigh NHS Trust

Leigh Infirmary




TG declares that he has no competing interests.

Malcolm Hooper, PhD, B Pharm, MRIC, C Chem

ME patient advocate

Emeritus Professor of Medicinal Chemistry

University of Sunderland




MH has lectured on ME and made national and international presentations to groups concerned with ME in Denmark, Sweden, Australia, US, and UK. He has acted as a witness for the GMC (UK) and received payment for this (travel and subsistence). He has also received payment from a family he supported in legal proceedings relating to vaccine damage, after the case was settled in their favour. He is a founder member of the Academy Of Nutritional Medicine, which has a special interest in Lyme disease. Their guidelines mention ME/CFS several times. He has given their keynote address for 3 years. He is the author of the paper Hooper M. Myalgic encephalomyelitis: a review with emphasis on key findings in biomedical research. J Clin Pathol. 2007;60:466-71. He is a member of the trustees for the John Richardson Research Group and the ME research group. He is also a trustee of European Services for People with Autism (ESPA) and a member of ESPA-Research, which is developing techniques to help with this condition. All of this work is voluntary.

  • Differentials

    • Coronavirus disease (COVID-19)
    • Migraine
    • Anxiety
    More Differentials
  • Guidelines

    • Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management
    • Myalgic encephalomyelitis/chronic fatigue syndrome: symptoms and diagnosis of ME/CFS
    More Guidelines
  • Patient leaflets

    Depression in adults: what is it?

    Depression in adults: what treatments work?

    More Patient leaflets
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