Fever of Unknown Origin

Excerpt

Fever of unknown origin (FUO) was first described by Dr. Petersdorf and Dr. Beesom in 1961. FUO was defined as a temperature of 101 degrees Fahrenheit (38.3 degrees Centigrade) or higher with a minimum duration of three weeks without an established diagnosis despite at least one week's investigation in the hospital. This definition was later changed to accommodate technological advances allowing for sophisticated outpatient evaluations, increasing numbers of immunocompromised individuals including those with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), and more complex treatment options becoming available. The revised definition proposed by Durack and Street in 1991 divided cases into four distinct subclasses: classic FUO, nosocomial FUO, neutropenic FUO, and HIV-related FUO.

A comprehensive history and physical examination can aid in diagnosis and direct diagnostic testing. Recommended investigations for work-up include complete blood count (CBC) with differential, three sets of blood cultures (from different sites, several hours apart, and before initiation of antibiotic therapy, if indicated), chest radiograph, complete metabolic panel (including hepatitis serologies if liver function tests are abnormal), urinalysis with microscopy and urine culture, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibodies (ANA), rheumatoid factor (RA), cytomegalovirus IgM antibodies or virus detection in blood, heterophile antibody test, tuberculin skin test, HIV testing and computed tomography (CT) scan of the abdomen.

Over 200 malignant/neoplastic, infectious, rheumatic/inflammatory, and miscellaneous disorders can cause FUO. Providers often order non-clue-based imaging and specific testing early in the FUO workup, which may be misleading and is certainly not economical. Despite extensive workup and diagnostic advances, up to 51% of FUO cases remain undiagnosed. In modern medicine, FUO remains one of the most challenging diagnoses.

It is important to note that immunocompromised and HIV patients may require an entirely different approach in diagnosing and treatment of recurrent fevers. This article focuses on FUO in immunocompetent adult patients.