Prolonged Fevers of Unknown Origin in Children
ABSTRACT & COMMENTARY
Synopsis: Children presenting to a rheumatology clinic for evaluation of prolonged (> 1 month) fever without an obvious source usually have a benign course, although some may later have neurological problems.
Source: Miller LC, et al. Prolonged fevers of unknown origin in children: Patterns of presentation and outcome. J Pediatr 1996;12:419-423.
Retrospective review was made of 40 children, 9 months-14.6 years of age, presenting to the Pediatric Rheumatology Clinic at the Boston Floating Hospital for Children with prolonged (> 1 month) fevers of unknown origin. Twenty-nine of the children had intermittent (periodic) fevers, and 11 had daily fevers. At extended follow-up, most had completely recovered. Underlying disease was found in very few of the children with periodic fevers, but 29% were later found to have neurological problems.
COMMENT BY PAUL L. McCARTHY, MD, FAAP
This is a report of 40 children referred to a pediatric rheumatology clinic over a 10-year period for evaluation of prolonged, daily occurring (n = 11) or prolonged, periodic (n = 29) fevers. The authors recognize the limitations of this report: the population was highly selected, the study is retrospective, no standardized evaluations were done, and, finally, long-term outcome data were gathered from parents by phone. The proportion of patients with periodic fevers, nearly three of four, is much greater than in other reports of prolonged fever in children. It demonstrates the selection bias inherent in studying a population of patients referred for evaluation of prolonged fever to a rheumatology clinic. Because of this selection bias, one is less ready to accept the authors’ conclusion that "for the majority of children, fevers without obvious source usually have a benign outcome." This conclusion may apply to children with periodic fever. In fact, it has been reported previously that, once cyclic neutropenia and familial Mediterranean fever have been excluded, children with periodic fever generally do not have an occult underlying illness. In the present report, only one child with periodic fever had an underlying illnessinflammatory bowel disease; the patient developed prominent abdominal findings.
Long-term follow-up data gathered from parents by phone indicated that 8 of 27 patients with periodic fevers for whom outcome data were available had neurological complications, most often attention-deficit hyperactivity disorder (n = 4) and developmental delay (n = 2). This reported relationship between prolonged periodic fevers and adverse CNS outcome must be interpreted with caution. The documentation of these outcome diagnoses was based on parental report by phone. Moreover, no comparison group data were presented that would allow the reader to assess the occurrence of these outcome diagnoses in other populations matched by age and selected socio-demographic characteristics. Because of these limitations of the study’s research design, one can conclude that the reported relationship between prolonged periodic fever and neurologic complications is of interest but requires further confirmation. (Dr. McCarthy is Professor of Pediatrics and Director of the Rheumatology Clinic at Yale University School of Medicine.)
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