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1996; Komaroff and Buchwald 1998). Other studies have noted that 60% to 70% of CFS patients reported allergies, compared to 20% of the general population, and CFS has been associated with heightened reactivity to allergens (Straus et al. 1988). Since allergies are immunological phenomena, scientists have examined other immunological parameters and found decreased natural killer cell number and activity, altered lymphocyte sub-set numbers and percentage, and increased expression of activation markers on lymphocyte subsets (Buchwald and Komaroff 1991; Straus et al. 1993; Komaroff and Buchwald 1998). Other areas have also been investigated, including neuroendocrine, especially hypothalamic-pituitary-adrenal abnormalities and psychiatric illness (Demitrack et al. 1991; Manu et al. 1988). More recently, autonomic nervous system dysfunction has been hypothesized to be associated with CFS because the symptoms of neurally mediated hypotension can overlap with those of CFS (Bou-Holaigah et al. 1995). However, no finding was ultimately found to be adequately reproducible and reliable to warrant its use as a diagnostic marker. Although many abnormalities exist in CFS, they are not observed in many patients and may not correlate with clinical status, leading to disagreement over their etiological relevance.


In 1994 the Centers for Disease Control and Prevention convened the International Chronic Fatigue Syndrome Study Group to develop a conceptual framework and a set of research guidelines for use in studies of CFS (Fukuda et al. 1994). This group developed diagnostic criteria for CFS (see Table 5-1).

TABLE 5-1 Diagnostic Criteria for Chronic Fatigue Syndrome

A person must meet both of the following criteria in order to be diagnosed with CFS:

1. Clinically evaluated, unexplained, persistent, or relapsing fatigue of new or definite onset that is not due to ongoing exertion, is not substantially relieved by rest, and results in a substantial reduction in previous levels of occupational, educational, social, or personal activities; and

2. Concurrent occurrence of four or more of the following symptoms, all of which must have persisted or recurred for at least six months:

• Impaired short-term memory or concentration severe enough to cause substantial reduction in previous levels of activity;

• Sore throat;

• Tender cervical or axillary lymph nodes;

• Muscle pain, multijoint pain without joint swelling or redness;

• Headaches of a new type or severity;

• Unrefreshing sleep;

• Postexertional malaise lasting more than 24 hours.

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