Case Control Study of Chronic Fatigue in Pediatric Patients
Authors: Carter Bryan D. , Edwards Joseph F. , Kronenberger William G. , Michalczyk Louise , Marshall Gary S. 
Published: December 2021

Objective. To determine the demographic characteristics, medical features, psychological profile, and natural history of children with chronic fatigue.
Design. Case control study.
Setting. Pediatric Infectious Diseases Clinic of Kosair Children's Hospital, 1990 to 1992.
Participants. Forty-four patients referred for persistent fatigue were evaluated. Twenty patients participated in a psychological study; 20 healthy controls of similar age and gender were recruited from community pediatric practices and 20 matched depressed controls were recruited from university psychiatry services (subjects were treated as groups in the analyses).
Measures. Demographic data were obtained for all referred patients. Those with fatigue for at least 2 months and no alternative diagnosis received a detailed history, physical, and battery of laboratory tests (complete blood count, sedimentation rate, chemistry panel, chest X-ray, thyroid stimulating hormone, thyroxine, anti-nuclear antibodies, urinalysis, immunoglobulins, and Epstein-Barr virus (EBV), toxoplasma, and cytomegalovirus serologies). Psychological study participants completed the following: background structured interview; Kaufman Brief Intelligence Test; Children's Depression Inventory; Child Behavior Checklist; Youth Self Report; Diagnostic Interview for Children and Adolescents-Revised; mail-in follow-up survey.
Results. The median age of fatigue patients was 14.3 years; 60% were female, 96% white, and 87% from the mid/upper socioeconomic status (SES). Fatigue patients were demographically similar to 21 patients referred for infectious mononucleosis (IM) but were older than other clinic patients (P &lt; .0001). White race (P = .0568) and mid/upper SES (P = .0403) were over-represented among fatigue patients compared to patients referred for other diagnoses. Of 36 patients meeting criteria for further study, 5 had an IM-like illness including evidence of recent EBV infection. For the remaining 31 patients, clinical and laboratory evaluations were unrevealing. Psychological study subjects reported marked declines in quality-of-life and scored high on measures of internalizing withdrawal, and social isolation. Nine met diagnostic criteria for depression, although depressive symptoms were not as prominent as those reported by depressed controls. Fatigue subjects scored higher on somatization than both control groups. The follow-up survey indicated symptomatic improvement in most patients.
Conclusions. Chronic fatigue was a common reason for referral, with over-representation of white children from mid/upper SES. After exclusion of EBV-associated IM, screening laboratory tests were not helpful in establishing specific organic diagnoses. Whereas the natural history was favorable, chronic fatigue resulted in major quality-of-life changes and was associated with significant levels of psychosocial distress.
Implications. Psychological evaluation is warranted in these patients, as some may have treatable psychological conditions. Given the absence of proved medical therapies, psychosocial interventions to improve quality-of-life should be studied.