Prolonged Fevers of Unknown Origin in Children Which Defy Diagnosis

Abstract & Commentary

Synopsis: Children with prolonged FUOs in whom no etiologic diagnosis is made after extensive evaluation have a generally good prognosis.

Source: Miller LC, et al. Prolonged fevers of unknown origin in children: Patterns of presentation and outcome. J Pediatr 1996;12:419-423.

Miller et al performed a retrospective analysis of 40 children, ages 9 months to 14.6 years, with documented fever of more than four weeks duration who had been referred for evaluation to the Pediatric Rheumatology Clinic at The Floating Hospital for Children in Boston and in whom the evaluation failed to lead to a diagnosis. In 29 children, the fever was periodic, while it was daily in the remainder. The median duration of illness was 12 months in the former group and two months in the latter.

Follow-up information covering a mean of 60.2 ± 5 months after referral to the clinic was available for 37 of the 40 patients. The fever had completely resolved in 34 of the 37, while periodic fever persisted in three children for as long as five years. Two children with daily fever were subsequently found to have inflammatory bowel disease, while a third developed uveitis. Almost one-third of the children were subsequently found to have neurological problems, most commonly attention-deficit disorder.


Studies of fever of unknown origin (FUO) in adults suggest that there is a similar generally good prognosis of patients whose fever remains of unknown etiology despite extensive evaluation.1 A key predictor of the ultimate outcome of such patients is the presence or absence of significant weight loss. Those patients who do not lose weight during their illness almost invariably have resolution of their fever without a diagnosis ever being made or, in a few cases, have persistence of fever without emergence of a life-threatening disease.

The distribution of etiologies of FUOs in children differs from that in adults by virtue of a lesser incidence of malignancies, which is largely made up for by a greater proportion due to infections. In addition, Still’s disease is much more commonly encountered in children than in adults.

Despite all the tools available to the modern clinician, some cases of FUO defy etiologic explanation. This is most frustrating to both the clinician and the patient or, in the cases discussed here, the parents of the patient. In such cases, the patient and/or parents should be reassured. They should be instructed to report any significant change in the patient’s condition, and, if the fever persists, consideration should be given at 3-6 month intervals to repetition of at least a portion of the appropriate diagnostic evaluation. This study suggests that particular attention should be paid to bowel evaluation because of the occasional case of inflammatory bowel disease in such patients.


1. Kerttula Y, et al. Fever of unknown origin: A follow-up investigation of 34 patients. Scand J Infect Dis 1983; 15:185-187.