Petersdorf and Beeson10 defined fever of unknown origin (FUO) as fever persisting for longer than 3 weeks, a documented temperature of greater than 101° F (38.3° C) on several occasions, and an uncertain diagnosis after intensive study for at least 1 week. Subsequently, in 1968 Dechovitz and Moffet2 defined FUO in children as fever lasting longer than 2 weeks for which no diagnosis could be made. With the advent of more advanced diagnostic modalities, a more contemporary definition in children is a minimum of 14 days of daily documented temperature of 38.3° C or greater without apparent cause, after performance of repeated physical examinations and screening laboratory tests.
The list of possible causes of FUO is extensive and is outlined below. Although the incidence of the causes of FUO in children may change, most investigators have found that infections predominate. New infectious disease etiologies continue to be added to the list of causes of FUO in children: Epstein-Barr virus (EBV), Lyme disease, hepatitis viruses, and human immunodeficiency virus (HIV). Reported cases demonstrate an increase in cases of osteomyelitis of the axial skeleton and infections resulting from different presentations of Bartonella henselae infections.
The approach to a patient with unexplained fever begins with a detailed history and physical examination. The history should review general complaints, not discounting seemingly benign symptoms. Additionally, careful attention must be given to an inventory of recent travel history, living environment, diet, pet and animal exposure, and recent medications. Organ involvement may not always be apparent by history or physical examination when a child first presents with prolonged fever. Physical findings may take weeks to develop, and repeated questioning and physical examinations are critical in the management of any child with prolonged fever.
No algorithms for the evaluation of FUO have been established because the differential diagnosis is so extensive. We have listed tests that can be considered in the evaluation of FUO. The tests should be used based on findings from the history and physical examination. As time passes and the fever persists, the evaluation should become more extensive because common causes of fever become less likely. The child with fever of more than 2 weeks’ duration often needs to be admitted to the hospital after the initial outpatient evaluation. The pattern of fever can be assessed, the work-up can be expedited, and the possibility of factitious fever can be eliminated.
