What is the clinical definition of fever of unknown origin (FUO) in the inpatient setting?

Clinical Definition of Fever of Unknown Origin in the Inpatient Setting

Fever of unknown origin (FUO) in the inpatient setting is defined as fever exceeding 38.3°C (100.9°F) persisting for at least 3 weeks without diagnosis despite 3 inpatient days of investigation. 1, 2, 3

Core Diagnostic Criteria

The definition requires three essential components that must all be present:

• Temperature threshold: Single measurement ≥38.3°C (100.9°F) 4, 5
• Duration requirement: Fever persisting for at least 3 weeks 1, 2, 3, 5
• Investigation requirement: No diagnosis despite 3 inpatient days of evaluation (or 3 outpatient visits in the original definition) 1, 2, 3

Temperature Measurement Standards

For accurate diagnosis in the inpatient setting, temperature measurement method matters significantly:

• Preferred methods: Central temperature monitoring via pulmonary artery catheter thermistors, bladder catheters, or esophageal balloon thermistors when these devices are already in place 4
• Alternative reliable methods: Oral or rectal temperatures when central monitoring is unavailable 4
• Avoid unreliable methods: Axillary, tympanic membrane, temporal artery thermometers, or chemical dot thermometers should not be used for diagnostic purposes 4

Classification Categories

FUO must be classified into one of four subcategories, as etiology and management differ substantially:

• Classical FUO: Community-dwelling immunocompetent patients 1, 2, 3
• Nosocomial FUO: Hospitalized patients developing fever after admission 1, 2, 3
• Neutropenic FUO: Patients with neutropenia (typically <500 cells/mm³) 1, 2, 3
• HIV-related FUO: Patients with known HIV infection 1, 2, 3

Critical Distinctions

ICU-Specific Fever Definition

In critically ill ICU patients, the Society of Critical Care Medicine and IDSA define "new fever" more simply as a single temperature ≥38.3°C, without the 3-week duration requirement, as this represents a different clinical entity requiring immediate evaluation 4

Neutropenic Patients

For neutropenic patients due to chemotherapy, fever is defined as either a single oral temperature ≥38.3°C OR ≥38.0°C sustained over at least 1 hour, which is a lower threshold than classical FUO 4

Pediatric Considerations

In pediatric patients, fever without source (FWS) differs from FUO—FWS is acute illness with no apparent source after initial evaluation, while FUO requires prolonged fever >3 weeks with no identifiable source 4

Important Caveats

Not all infected patients manifest fever, and absence of fever in patients with infection is associated with worse outcomes, so the diagnostic approach may apply to suspected infection regardless of temperature elevation 4

The definition represents a diagnosis of exclusion requiring thorough evaluation before application—premature diagnosis of FUO should be avoided, particularly in resource-limited settings where treatable infections must be ruled out first 1, 2