The study illustrates the complexity that exclusionary conditions introduce into both research and clinical considerations of subjects potentially classified as CFS. The exclusionary diagnoses are common; 28% of subjects in a population-based sample had exclusions identified during a personal history telephone interview. Exclusionary conditions/diseases were subsequently recognized in an additional 36% of subjects undergoing a full clinical examination. It appears that during the telephone interview subjects did not know of or did not remember all of their exclusionary diagnoses. This discrepancy could be due to: (1) greater accuracy and specificity of information obtained by clinical examination compared to telephone interview; (2) variable access to healthcare which, in turn, means variable access to diagnostic means [16
]; (3) asymptomatic status contributing to unrecognized conditions; or (4) a lack of perception of bodily feelings as being abnormal. The types of diseases identified in the clinic are recognized to be important in the differential diagnosis of CFS and emphasize the need for clinicians to evaluate patients with appropriate history taking, physical examination and laboratory tests. The finding that Black people and residents of rural and urban areas were more likely to have exclusionary conditions diagnosed at a clinic suggests that access to healthcare may be a contributing factor, as limited access to quality healthcare has been documented among these subgroups [16
The finding that increased BMI was independently associated with having an exclusionary condition among CFS patients, suggests that the condition may be 'silent' as in some correlates of elevated BMI, including metabolic conditions, sleep disorders and hypothyroidism. This interpretation is supported by the finding of exclusionary conditions in 26 people who, in the telephone interview, had considered themselves 'well'.
The diagnoses considered exclusionary for CFS were originally selected because they frequently result in symptoms similar, if not identical, to those characteristic of CFS subjects. As might be expected, differences between subjects with and without exclusionary diagnoses were not universally present. For example, general fatigue and reduced activity scores of the MFI and physical function, role physical, social function and role emotional scores of the SF-36 were equivalent. Likewise, CFS and non-CFS symptom scores were not significantly different. Thus, in terms of level of overall 'sickness' [17
] and impairment, included and excluded subjects were comparable. It is not surprising that subjects with both medical and psychiatric diagnoses have more fatigue and impairment, as well as higher symptom scores, than those with only medical or psychiatric conditions. However, greater impairment in selected parameters in those subjects with only psychiatric exclusions versus those with only medical exclusions reflects a true difference or bias introduced by the self-report procedure.
Although not emphasizing the differences between subjects who fulfill defined requirements for exclusionary diagnoses and those who do not, previous studies of chronic fatigue and CFS have shown high rates of psychiatric morbidity and functional morbidity and have documented these outcomes as important public health burdens [18
]. Another study, which included 98 subjects with chronic fatigue and compared disability and psychosocial distress in those that met criteria for CFS and those who had medical or psychiatric exclusions, failed to meet the definition or were using medications specific to the study [20
]. The study results showed that the CFS subjects could not be differentiated from those who were excluded based on the study variables that addressed symptoms of depression, general health, impairment, symptom perception and somatic and psychological stress.
In principle, the results of this study, and of previous observations, support the original decision to exclude subjects with fatigue and selected concurrent identifiable illnesses/diseases from the research diagnosis of CFS as the latter shares illness characteristics and consequences with the syndrome [1
]. The excluded group may have exposures or disease components that would confound efforts to address the incidence, prevalence or pathophysiology of an otherwise unexplained condition such as CFS if it were unique [21
]. We did not address the question of subject competency to complete the in the psychiatric exclusions. Thus, considering CFS as a diagnostic possibility and pursuing a differential diagnostic process should allow identification of patients who need careful evaluations as is recommended in the 1994 definition. In particular, obesity, anaemia, thyroid disease, diabetes and heart disease are common in fatigued as well as non-fatigued subjects (Table and ).
It is equally clear that subjects with exclusionary diagnoses are at least as comparably functionally impaired as the included subjects. The chronically unwell population, identified here with a fatiguing illness, is likely to have a medical disease and/or a psychiatric disease. However, these conditions may go undiagnosed. Since subjects with and without identifiable exclusionary disease processes share many symptoms, clinical management requires careful attention in order to correctly identify and treat the medical and psychiatric illnesses. It is clear that treatment of the underlying diseases will not resolve fatigue and symptoms in all instances and it is possible that illnesses/diseases with chronic fatigue share a common underlying pathophysiologic mechanism. In order to examine this possibility, subjects with exclusionary conditions could be included with CSF cases for comparison.
The primary limitation of this study is the inclusion of subjects who have been ill for an average of 6-7 years. The majority of the subjects had experienced a gradual onset of their illness. Thus the exclusion of subjects fulfilling CFS criteria and having medical and/or psychiatric illnesses may be observed more frequently in the population under study than in the younger individuals with an acute onset. Likewise, the levels of impairment may also be more applicable to this population. Replication of these observations will be possible in future follow-up studies.
As those with CFS suffer from personal, social, workplace [1
] and observed financial losses [23
], should not all individuals fulfilling CFS inclusion criteria, with or without exclusionary diagnoses, be considered in future public health planning? For instance, would both groups benefit from prevention and intervention efforts such as cognitive behavioral therapy and graded exercise therapy [24
]? A similar question could be asked of those who are unwell but who do not reach the diagnostic threshold.