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Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution

William C Reeves1*, Andrew Lloyd2, Suzanne D Vernon1, Nancy Klimas3, Leonard A Jason4, Gijs Bleijenberg5, Birgitta Evengard6, Peter D White7, Rosane Nisenbaum1, Elizabeth R Unger1 and the International Chronic Fatigue Syndrome Study Group

Author affiliations

1 Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

2 Inflammation Research Unit, School of Pathology, University of New South Wales, Sydney, Australia

3 University of Miami and the Department of Veterans Affairs Medical Center, Miami, Florida, United States of America

4 DePaul University, Chicago, Illinois, United States of America

5 University Medical Center Nijmegen, Netherlands

6 Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden

7 Barts and the London School of Medicine, London, United Kingdom

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Citation and License

BMC Health Services Research 2003, 3:25  doi:10.1186/1472-6963-3-25

Published: 31 December 2003



Chronic fatigue syndrome (CFS) is defined by symptoms and disability, has no confirmatory physical signs or characteristic laboratory abnormalities, and the etiology and pathophysiology remain unknown. Difficulties with accurate case ascertainment contribute to this ignorance.


Experienced investigators from around the world who are involved in CFS research met for a series of three day workshops in 2000, 2001 and 2002 intended to identify the problems in application of the current CFS case definition. The investigators were divided into focus groups and each group was charged with a topic. The investigators in each focus group relied on their own clinical and scientific knowledge, brainstorming within each group and with all investigators when focus group summaries were presented. Relevant literature was selected and reviewed independent of the workshops. The relevant literature was circulated via list-serves and resolved as being relevant by group consensus. Focus group reports were analyzed and compiled into the recommendations presented here.


Ambiguities in the current CFS research definition that contribute to inconsistent case identification were identified. Recommendations for use of the definition, standardization of classification instruments and study design issues are presented that are intended to improve the precision of case ascertainment. The International CFS Study Group also identified ambiguities associated with exclusionary and comorbid conditions and reviewed the standardized, internationally applicable instruments used to measure symptoms, fatigue intensity and associated disability.


This paper provides an approach to guide systematic, and hopefully reproducible, application of the current case definition, so that case ascertainment would be more uniform across sites. Ultimately, an operational CFS case definition will need to be based on empirical studies designed to delineate the possibly distinct biological pathways that result in chronic fatigue.

chronic fatigue syndrome; CFS; fatigue; case definition; classification