#2-74E. Leveraging Consensus: Updated Diagnostic Criteria and Evaluation Strategy for Fever of Unknown Origin (BMJ, 2025)

Are you facing diagnostic uncertainty in patients with prolonged, unexplained fever? This paper addresses Fever of Unknown Origin (FUO), a complex clinical syndrome defined by a prolonged febrile illness (≥3 weeks of fever ≥38.3°C on ≥3 occasions) in an immunocompetent patient despite completion of a standard set of minimal investigations. The article outlines the current international consensus-based defining criteria, reviews the differential diagnoses—classified into infections, non-infection inflammatory disorders, and neoplasms—and emphasizes how causes vary geographically. A key clinical update from the 2024 Delphi consensus is the recommendation for the early use of 18FDG-PET/CT in FUO patients lacking obvious diagnostic clues, which promises high diagnostic yields. However, clinicians must be mindful of a notable limitation: the difficulty in distinguishing pathological uptake from normal physiological activity in organs such as the brain, liver, and bowel. As most FUO cases are atypical presentations of common diseases rather than rare conditions, this review provides essential guidance, offering a structured, systematic evaluation protocol that helps non-specialists efficiently navigate complex diagnostic pathways and make timely specialist referrals.

Citation: William F Wright, Samuel C Durso, Colleen Forry, Chantal P Rovers. Fever of unknown origin. BMJ. 2025. DOI: 10.1136/bmj-2024-080847

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