3 learning resources available for this topic
Fever of Unknown Origin (FUO) is defined as a fever exceeding 38.3°C (101°F) on multiple occasions over at least 3 weeks with no identifiable cause after one week of intensive investigation. This diagnostic challenge affects patients across all age groups and requires systematic evaluation to identify underlying infectious, neoplastic, inflammatory, or miscellaneous causes.
FUO results from the body's inflammatory response to various stimuli, with fever mediated by cytokine release (particularly IL-1, TNF-α, and IL-6) that acts on the hypothalamic thermoregulatory center. The underlying pathophysiology varies widely depending on the etiology, which can include infectious agents evading detection, occult malignancies with paraneoplastic effects, autoimmune conditions causing chronic inflammation, or drug-induced hyperthermia.
The diagnostic approach to FUO requires methodical evaluation beginning with comprehensive history-taking, thorough physical examination, and basic laboratory studies including complete blood count, inflammatory markers, and cultures. Advanced imaging with CT or PET scans, specialized serologic testing, and tissue biopsies may be necessary when initial workup is unrevealing. The key is maintaining a broad differential diagnosis while systematically ruling out common causes before pursuing rare etiologies, as approximately 30% of FUO cases remain undiagnosed despite extensive investigation.