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Are chronic fatigue and chronic fatigue syndrome valid clinical entities across countries and healthcare settings?

Hickie I, Davenport T, Vernon SD, Nisenbaum R, Reeves WC, Hadzi-Pavlovic D, Lloyd A.
Australian and New Zealand Journal of Psychiatry; 43:25-35, 2009.

Summary

CFS represents a diagnostic and management challenge for health care providers because there are no characteristic clinical signs or laboratory markers so diagnosis depends on self reported symptoms and ruling out other possible medical/psychiatric causes of the illness. Research to identify diagnostic markers and therapeutic targets is also difficult because the current research case definition was based on expert clinical-consensus rather than empirical data. We conducted this study in response to a recommendation of the 2003 International CFS Study Group to conduct a study of patients with chronic unexplained fatigue, representing different regions and cultures, from which a definition of CFS could be empirically derived. The present study was based on analysis of pre-existing data from population-based studies, as well as studies in primary, secondary or specialized tertiary care clinics. We collected the data from a range of international settings. These included English-speaking countries (Australia, Canada, UK, US n=36,326 patients) and non-English-speaking countries (n=1,398) in Africa (Nigeria), Asia (China, Hong Kong, India, Japan, Turkey, United Arab Emirates, Vietnam), continental Europe (France, Germany, Greece, Ireland, Italy, Spain, Sweden, The Netherlands), and South America (Brazil). All studies contained data collected from patients with prolonged fatigue (1-6 months duration), chronic fatigue (>6 months duration), or CFS. Data sets included demographic details, measures of fatigue duration and severity, and information as to the setting in which the data were collected. We used multivariate statistical modeling to test the construct validity of chronic fatigue and CFS, as defined by the 1994 case definition. Analysis revealed 5 domains of illness experience: 1) prolonged fatigue and musculoskeletal pain; 2) impaired neurocognitive function; 3) symptoms of inflammation; 4) disturbed sleep; 5) disturbed mood. These domains were robust across cultures and health-care settings and, with the exception of mood disturbance, are consistent with the key criteria described in the 1994 international CFS case definition. There has been a strong tendency in the medical and lay literature on CFS to suggest that depressive symptoms are simply an understandable psychological response to the severity or duration of disability. These data argue that mood disturbance is a core component of CFS. Also, conceptually, the present findings are consistent with the notion that the key symptom phenomena of chronic fatigue states are likely to share common central nervous system mechanisms, independent of any other precipitating illness (e.g., infection) or risk factors (e.g., prior mood disturbance).

Abstract

Objective: The validity of the diagnosis of chronic fatigue syndrome and related chronic fatigue states remains controversial, particularly in psychiatry. This project utilized international epidemiological and clinical research data to test construct validity across diagnostic categories, health-care settings and countries. Relevant demographic, symptom and diagnostic data were obtained from 33 studies in 21 countries. The subjects had fatigue lasting 1- 6 months (prolonged fatigue), or > 6 months (chronic fatigue), or met diagnostic criteria for chronic fatigue syndrome.

Method: Common symptom domains were derived by factor analytic techniques. Mean scores on each symptom factor were compared across diagnostic categories, health-care settings and countries.

Results: Data were obtained on 37 724 subjects (n=20,845 female, 57%), including from population-based studies (n=15,749, 42%), studies in primary care (n=19,472, 52%), and secondary or specialist tertiary referral clinics (n=2,503, 7%). The sample included 2,013 subjects with chronic fatigue, and 1,958 with chronic fatigue syndrome. A five-factor model of the key symptom domains was preferred (‘musculoskeletal pain/fatigue’, ‘neurocognitive difficulties’, ‘inflammation’, ‘sleep disturbance/fatigue’ and ‘mood disturbance’) and was comparable across subject groups and settings. Although the core symptom profiles were similar, some differences in symptoms were observed across diagnostic categories, health-care settings and between countries.

Conclusions: The construct validity of chronic fatigue and chronic fatigue syndrome is supported by an empirically derived factor structure from existing international datasets.

Page last modified on January 5, 2009

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