Article Text

Case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review
  1. Kjetil Gundro Brurberg1,
  2. Marita Sporstøl Fønhus1,
  3. Lillebeth Larun1,
  4. Signe Flottorp1,2,
  5. Kirsti Malterud3,4,5
  1. 1Norwegian Knowledge Centre for the Health Services, Oslo, Norway
  2. 2Institute of Health and Society, University of Oslo, Oslo, Norway
  3. 3Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
  4. 4Research Unit for General Practice, Uni Health, Uni Research, Bergen, Norway
  5. 5Research Unit for General Practice in Copenhagen, Copenhagen K, Denmark
  1. Correspondence to Dr Kjetil Gundro Brurberg; kgb{at}


Objective To identify case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), and explore how the validity of case definitions can be evaluated in the absence of a reference standard.

Design Systematic review.

Setting International.

Participants A literature search, updated as of November 2013, led to the identification of 20 case definitions and inclusion of 38 validation studies.

Primary and secondary outcome measure Validation studies were assessed for risk of bias and categorised according to three validation models: (1) independent application of several case definitions on the same population, (2) sequential application of different case definitions on patients diagnosed with CFS/ME with one set of diagnostic criteria or (3) comparison of prevalence estimates from different case definitions applied on different populations.

Results A total of 38 studies contributed data of sufficient quality and consistency for evaluation of validity, with CDC-1994/Fukuda as the most frequently applied case definition. No study rigorously assessed the reproducibility or feasibility of case definitions. Validation studies were small with methodological weaknesses and inconsistent results. No empirical data indicated that any case definition specifically identified patients with a neuroimmunological condition.

Conclusions Classification of patients according to severity and symptom patterns, aiming to predict prognosis or effectiveness of therapy, seems useful. Development of further case definitions of CFS/ME should be given a low priority. Consistency in research can be achieved by applying diagnostic criteria that have been subjected to systematic evaluation.

  • Epidemiology
  • Primary Care
  • Statistics & Research Methods

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

View Full Text

Statistics from

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Files in this Data Supplement:

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.