Fever of unknown origin (FUO) is a relatively uncommon condition in United States children. Nevertheless, FUO remains a challenging clinical problem for even the most astute clinician that requires excellent history taking and physical examination skills. In the more elusive cases, repeated history and physical examination are the hallmarks of evaluation. Although diagnostic testing has been extremely valuable, a Sherlock Holmes-like attention to clues and details is key (being that Sir Arthur Conan Doyle was also a physician).

Infections remain the most common cause of fever in general and of FUO in particular. In the past, infections obviously not only contributed to confirmed causes of FUO but also perhaps to many cases in the unknown cause categories. However, more advanced and rapid diagnostic techniques now allow clinicians to diagnose more infectious causes sooner. Accordingly, compared to the past, infections now constitute the cause of a relatively smaller number of cases...

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