Fever of unknown origin in children: a systematic review.

BACKGROUND: there are no previous systematic reviews of published pediatric case series describing the etiology of fever of unknown origin (FUO). The purpose of collecting these data is to determine the etiologies for children with FUO in both developing and developed countries.

METHODS: the database Ovid Medline R (1950 to August 2009 week 4) and Ovid Embase (1980 to 2010 week 2) were used to conduct the search. Studies in any language were included if they provided the diagnosis in a series of 10 or more children with FUO. The diagnosis of each child at the time of publication of the study was recorded.

RESULTS: there were 18 studies that met the inclusion criteria, describing 1638 children. The diagnosis at the time of publication was malignancy for 93 children (6%), collagen vascular disease for 150 (9%), miscellaneous non-infectious conditions for 179 (11%), infection for 832 (51%), and no diagnosis for 384 (23%). There were 491 bacterial infections (59% of all infections) with common diagnoses being brucellosis, tuberculosis, and typhoid fever in developing countries, osteomyelitis, tuberculosis, and Bartonellosis in developed countries, and urinary tract infections in both. For children with no diagnosis after investigations, most had fever that ultimately resolved with no sequelae.

CONCLUSIONS: about half of FUOs in published case series are ultimately shown to be due to infections with collagen vascular disease and malignancy also being common diagnoses. However, there is such a wide variety of possibilities that investigations should primarily be driven by the clinical story.