Evolution of Pyrexia of Unknown Origin (PUO) Definition
The Statement is Correct: The Definition Has Been Relaxed
The modern definition of PUO has indeed been relaxed from the original 1961 Petersdorf-Beeson criteria, now allowing for diagnosis after 3 outpatient visits, 3 inpatient days, or 1 week of intensive ambulatory investigation, rather than requiring a full week of inpatient investigation. 1, 2, 3
Classic vs. Current Definitions
Original 1961 Definition
- Temperature above 38.3°C (100.9°F) on multiple occasions 4
- Duration of at least 3 weeks 4
- No diagnosis despite 1 week of investigation in hospital 4
Relaxed Modern Definition
- Temperature exceeding 38.3°C (100.9°F) 1, 2, 3
- Persisting for at least 3 weeks 1, 2, 3
- No diagnosis despite any of the following: 1, 2, 3
- 3 outpatient visits, OR
- 3 inpatient days, OR
- 1 week of intensive ambulatory investigation
Why the Relaxation Occurred
The definition evolved to reflect modern clinical practice where:
- Outpatient diagnostic capabilities have dramatically improved, with advanced imaging (PET/CT), molecular diagnostics, and specialized serological tests now readily available without hospitalization 1, 2
- Healthcare delivery has shifted toward ambulatory care, making prolonged inpatient stays for diagnostic workup both impractical and unnecessary 4, 5
- The pace of investigations has accelerated, allowing comprehensive evaluation to occur more rapidly than in 1961 5, 6
Mandatory Classification into Subcategories
The modern approach requires classifying PUO into four distinct subcategories, as etiology distribution varies significantly by category:
- Classical PUO (immunocompetent outpatients) 1, 2, 3
- Nosocomial PUO (hospitalized patients developing fever) 1, 2, 3
- Neutropenic PUO (neutrophil count <500 cells/mm³) 1, 2, 3
- HIV-related PUO (confirmed HIV infection with fever) 1, 2, 3
Critical Caveat
Do not diagnose "PUO" prematurely in resource-limited settings or before completing appropriate initial investigations—this is a diagnosis of exclusion requiring thorough evaluation, and premature labeling may cause clinicians to miss treatable infections. 1, 2