Holmes et al., 1998). Of the eight symptoms, the most commonly reported are headaches, postexertional malaise, impaired cognition, and muscle pain (Buchwald and Garrity, 1994).

CFS is a diagnosis of exclusion. The CDC criteria require that three elements be completed as part of a comprehensive evaluation. The first element, determining whether the symptom criteria for CFS are present, requires that a person be queried specifically about length and severity of fatigue and about eight ancillary symptoms. The second element, determining whether other medical conditions are present, mandates a complete physical examination, a battery of specified laboratory tests, and a medical history. The third element, assessing exclusionary psychiatric conditions, requires an interview by a trained professional to obtain diagnostic information.

The etiology of CFS is unknown, and there are no widely accepted laboratory tests or pathologic physical signs (Epstein, 1995). Several biologic correlates of the syndrome have emerged, including dysregulation of the hypothalamic-pituitary-adrenal axis, immune activation, and other measures (Goshorn, 1998), but they might be present in only a minority of patients; and those findings are not specific to CFS. Although infectious agents may trigger some cases of CFS, a complex, multifactorial etiology that incorporates biologic, psychological, and social factors is likely (Wessely, 1998). The degree of disability associated with CFS is striking, with high rates of unemployment (Bombardier and Buchwald, 1996; Buchwald, 1996) and poor quality of life related to health (Hardt et al., 2001; Komaroff et al., 1996).

Thus, in this report, a primary study for CFS is one in which CFS has been diagnosed. A secondary study is one in which a CFS-like condition has been documented. Both primary and secondary studies needed to include a suitable control group so that findings could be interpreted. Other studies that estimated the prevalence of symptoms of “chronic fatigue” (Gray et al., 1999a; Unwin et al., 1999), or multisymptom illness (Fukuda et al., 1998), are not considered further in this section. Likewise, studies that used scalar measures of disability and poor quality of life related to health (Reid et al., 2001) as surrogates for the CDC criteria are not included. Finally, self-reports of CFS (Unwin et al., 1999) and self-reports of a physician diagnosis of CFS (Gray et al., 2002) were not included among the secondary studies because diagnostic data obtained that way are highly inaccurate. For example, in the Eisen et al. (2005) study, which the committee considered to be the only primary study, only two or three of 38 deployed and eight nondeployed veterans who self-reported CFS received a formal diagnosis after a comprehensive examination. Others, using a method of classifying a case of CFS based on cutoff scores on a fatigue scale and a functional status instrument, found that only 11% of veterans reporting a diagnosis of CFS met operational CFS study criteria.

Summary of Volume 4
Primary Studies

CFS was one of 12 primary health outcome measures studied by Eisen et al. (2005), who conducted medical evaluations in phase III of the nationally representative, population-based VA study. In the period 1999-2001, 1061 of 11,441 deployed and 1128 of 9476 nondeployed veterans selected were evaluated. Those veterans had participated in the phase I survey study conducted in 1995 (Kang et al., 2000). The veterans were randomly selected, and the researchers were blinded to their deployment status. The diagnosis of CFS was based on in-person interviews, examinations, and the strict application of the CDC criteria (Fukuda et al., 1994). The authors concluded that the population prevalence of CFS was higher in deployed than in nondeployed veterans: 1.6% vs 0.1% (OR 40.6, 95% CI 10.2-161.15). Study strengths are its



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