Chronic Fatigue and the Chronic Fatigue Syndrome: Prevalence in a Pacific Northwest Health Care System

Fatigue is a common symptom in primary care settings [1-10]; it is reported by at least 20% of patients seeking medical care. Similarly, large community surveys indicate that up to half of the general population reports having unusual fatigue, usually of limited duration [11-18]. In most cases, the fatigue is transient and is explained by prevailing circumstances, relieved by rest, and of little cause for concern. Fatigue can, however, be chronic and debilitating. Chronic fatigue may be associated with many well-known medical and psychological conditions and is the hallmark of the chronic fatigue syndrome, which is characterized by profound fatigue that is often accompanied by sleep disturbances, myalgias, pharyngitis, and depression [19]. The chronic fatigue syndrome has been reported worldwide, and case definitions have been developed by the Centers for Disease Control and Prevention (CDC) (see Appendix) and British and Australian researchers [19-21]. Recently, the CDC directed the formulation of a new international case definition that incorporates the major components of the original criteria [22]. We report the results of the first study of the chronic fatigue syndrome in the community. Previous population-based surveys have examined the prevalence of fatigue [11-18], but none have directly ascertained the prevalence of the chronic fatigue syndrome itself. Studies in the United States [23], Australia [21], and Scotland [24] have indirectly estimated the prevalence of the chronic fatigue syndrome in the community by identifying persons seeking care for fatigue through sentinel physicians. Another study in the United Kingdom used self-report on a mailed questionnaire to determine the diagnosis of the chronic fatigue syndrome [18]. In these investigations, the frequency of the chronic fatigue syndrome ranged from 3.4 to 249 cases per 100 000 persons. Other approximations of prevalence have used data from an epidemiologic study of psychiatric illness [25] or information from viral serology request forms [26]; these sources did not provide the specific information required to assess whether persons met any case definition for the chronic fatigue syndrome [19-21]. To determine the prevalence of the chronic fatigue syndrome and chronic, unexplained, debilitating fatigue in the community, we surveyed 4000 members of a large health maintenance organization. Another of our objectives was to compare the results of systematic physical and laboratory examinations and assessments of psychological distress and functional status in persons with chronic fatigue (including those with the chronic fatigue syndrome) with the results of these tests in healthy, nonfatigued, age- and sex-matched controls drawn from the same population. Methods The study setting was Group Health Cooperative of Puget Sound, a staff-model, nonprofit, prepaid health maintenance organization that serves 388 000 persons in Washington State. Group Health Cooperative medical records reflect essentially all medical care received by the organization's members, regardless of service site. Facilities include two hospitals, 23 medical centers, three specialty centers, and a progressive care facility. Group Health Cooperative serves a heterogeneous socioeconomic population, the age and sex of which closely resemble the age and sex of the general population of the Puget Sound region. Group Health Cooperative maintains computerized clinical information systems and supports the Center for Health Studies, a research unit experienced in conducting epidemiologic studies. Study participants were drawn from the Group Health Cooperative central region, which administratively includes five clinic sites and 84 primary care physicians and geographically contains much of the greater Seattle area. At study commencement, approximately 108 000 persons were enrolled in this region. Selection of Potential Cases and Controls A screening survey was mailed to 4000 randomly selected Group Health Cooperative members, regardless of whether they had sought medical care for any reason. The survey was re-mailed to nonrespondents; those who did not respond to the second mailing were telephoned and interviewed directly by research assistants. The screening survey included the following two queries, which were intended to assess the presence of two major criteria for the chronic fatigue syndrome that were established by the original CDC case definition [19] (see Appendix): Have you felt unusual fatigue or loss of energy, either constantly or repeatedly, for at least the past 6 months? and Does this state of fatigue interfere with your work or responsibilities at home such that you have had to reduce your level of activity by at least one-half? Enrollees answering no to one or both queries were excluded from further consideration as cases. Those answering yes to both questions reviewed a list of medical and psychiatric conditions that can produce fatigue. If any of these conditions were present, members were considered ineligible for further study. The Group Health Cooperative records of persons answering yes to the above questions and explicitly denying any potential cause of fatigue were abstracted and reviewed. If the medical record showed any previously unreported, unrecognized, or incompletely evaluated medical or psychiatric conditions, or regular use of medications or other substances that could result in chronic fatigue, persons were not evaluated further. Persons were not excluded for a history of a grief reaction (for example, depression after the death of a spouse). When this screening process produced a potential case, approval for study participation was sought from that person's primary care physician. After receipt of approval, eligible cases were invited to participate in the study. Controls were chosen from among those answering no to both of the two major screening questions. The Group Health Cooperative records of controls were reviewed to confirm the absence of medical and psychiatric illnesses associated with fatigue. If they were eligible, potential controls were invited to participate after receipt of approval from their primary care physicians. Controls were age-matched (within 5 years) and sex-matched to the cases; 80% were also matched for clinic location. Cases and controls gave written informed consent. Index Visit Evaluation All 74 cases and 74 controls had a medical evaluation consisting of a questionnaire (148 items for cases; 124 items for controls) about past and current medical problems; the questionnaire included items that would elicit the information required to diagnose the chronic fatigue syndrome. Cases and controls also had a standardized physical examination and a battery of blood tests directed toward detecting causes of fatigue. The physical examiner was blinded to whether a person was a case or a control. Routine tests included a complete blood count with manual differential; a test for erythrocyte sedimentation rate; SMA-24 (to assess electrolyte concentrations and levels of blood urea nitrogen, creatinine, glucose, uric acid, phosphate, calcium, magnesium, cholesterol, triglycerides, total protein, globulin, albumin, total and direct bilirubin, alkaline phosphatase, -glutamyl transpeptidase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and iron); and tests for thyroid function and antinuclear antibodies. Additional laboratory testing was done on the basis of the medical history, the physical examination, and the laboratory results, according to an explicit, previously developed algorithm. Functional status and psychological status were assessed by the Medical Outcomes Study Short-Form Health Survey (SF-36) and the Hopkins Symptom Checklist-90 (SCL-90). The SF-36 assesses physical and mental health, role and social functioning, pain, and health perception [27]. The SCL-90 was used to determine current psychological distress by measuring the presence and severity of specific symptoms [16]. Of particular interest were the dimensions of depression, anxiety, and somatization. Psychiatric diagnoses among persons meeting the criteria for the chronic fatigue syndrome were determined using the National Institute of Mental Health (NIMH) Diagnostic Interview Schedule Version III-A [28], a structured interview administered by a trained research assistant that assigns current and lifetime diagnoses on the basis of DSM-III-R criteria [29]. Additional information was obtained during the administration of the Diagnostic Interview Schedule to determine the onset and resolution of psychiatric disorders relative to the onset of chronic fatigue. The Diagnostic Interview Schedule was not given to all persons because structured psychiatric interviews in the assessment of the chronic fatigue syndrome were not formally recommended by the National Institutes of Health (NIH), the NIMH, or the CDC until 2 to 4 years after study commencement. Follow-up Evaluations At 12 and 24 months, cases and controls completed the SCL-90, the SF-36, and a brief fatigue inventory that explicitly inquired about the presence of chronic, debilitating fatigue during the follow-up period. Cases were also seen in person at 1 year and reassessed using a questionnaire (which included questions about symptoms required by the original CDC criteria for the chronic fatigue syndrome) and repeated laboratory and physical examinations identical to those done at the index visit. The physical and laboratory examinations were not repeated for controls. Lastly, the medical records of the 74 cases and the 74 controls were reviewed approximately 1 year after enrollment and at completion of the study protocol to record information collected by Group Health Cooperative providers during regular visits. Definitions of Chronic Fatigue, Chronic Fatigue Alone, and the Chronic Fatigue Syndrome Cases who met the two major criteria from the original CDC case definition [19, 30] on th