University of Louisville

Older case series established diagnostic considerations for children meeting a priori definitions of fever of unknown origin (FUO). No recent study has examined the final diagnoses of children referred for unexplained fever. This study was conducted with a retrospective chart review of patients referred to a pediatric infectious diseases clinic from 2008 to 2012 for unexplained fever. Sixty-nine of 221 patients were referred for "prolonged" unexplained fever. Ten of these were not actually having fever, and 11 had diagnoses that were readily apparent at the initial visit. The remaining 48 were classified as having FUO. The median duration of reported fever for these patients was 30 days; 15 had a diagnosis made, 5 of which were serious. None of the serious FUO diagnoses were infections. Of 152 patients with "recurrent" unexplained fever, 92 had an "intermittent" fever pattern, and most of these had sequential, self-limited viral illnesses or no definitive diagnosis made. Twenty of the 60 patients with a "periodic" fever pattern were diagnosed with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. Overall, 166 patients either were not having fever, had self-limited illnesses, or ultimately had no cause of fever discovered. Only 12 had a serious illness, 2 of which were infections (malaria and typhoid fever). Most children referred with unexplained fever had either self-limited illnesses or no specific diagnosis established. Serious diagnoses were unusual, suggesting that these diagnoses rarely present with unexplained fever alone, or that, when they do, the diagnoses are made by primary care providers or other subspecialists.

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Prolonged and recurrent fevers in children.

Marshall GS

The Journal of infection • 2014-Jan-01

Some children referred for prolonged fever are actually not having elevated temperatures; the approach here requires dissection of the history and correction of health misperceptions. Others have well-documented fevers associated with clinical, laboratory, or epidemiologic findings that should point to a specific diagnosis. "Fever-of-Unknown-Origin" (FUO) is the clinical scenario of daily fever for ≥ 14 days that defies explanation after a careful history, physical examination, and basic laboratory tests. The diagnostic approach requires a meticulous fever diary, serial clinical and laboratory evaluations, vigilance for the appearance of new signs and symptoms, and targeted investigations; the pace of the work-up is determined by the severity of the illness. Approximately half of children with FUO will have a self-limited illness and will never have a specific diagnosis made; the other half will ultimately be found to have, in order, infectious, inflammatory, or neoplastic conditions. Irregular, intermittent, recurrent fevers in the well-appearing child are likely to be sequential viral illnesses. Monogenic autoinflammatory diseases should be considered in those who do not fit the picture of recurrent infections and who do not have hallmarks of immune deficiency. Stereotypical febrile illnesses that recur with clockwork periodicity should raise the possibilities of cyclic neutropenia, if the cycle is approximately 21 days, or periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, the most common periodic fever in childhood.

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