Definition of Pyrexia of Unknown Origin (PUO) in Children
In pediatric patients, PUO is defined as fever ≥38.3°C (101°F) persisting for at least 3 weeks with no diagnosis despite 3 outpatient visits or 3 inpatient days of investigation. 1, 2
Core Diagnostic Criteria
The definition requires three essential components:
- Temperature threshold: Fever must be ≥38.3°C (101°F), though some pediatricians use >38°C as their cutoff in practice 1, 3
- Duration requirement: Fever must persist for at least 3 weeks, distinguishing PUO from acute fever without source (FWS), which is an acute illness with no apparent source after initial evaluation 4
- Investigation requirement: No diagnosis should be apparent despite 3 outpatient visits or 3 inpatient days of investigation 1, 2
Important Distinction: Prolonged FUO vs. Classical PUO
Prolonged FUO represents a separate clinical entity in children, defined as documented fever lasting more than 7 to 10 days with no apparent source and no diagnosis after 1 week of clinical investigations. 5 This shorter timeframe (7-10 days vs. 3 weeks) reflects the practical reality that children with persistent unexplained fever often require earlier intervention than the classical 3-week definition would suggest.
Age-Specific Considerations
- Neonates and infants (<3 months): Have the highest risk for invasive bacterial infections, with 8-13% having bacterial infections (predominantly urinary tract infections), and infants <28 days are at highest risk 1
- Young children (>3 months to 36 months): Require exclusion of congenital or cardiac disease in those who are febrile and ill-appearing, and 25% may show pneumonia on chest radiograph despite no obvious respiratory source 1
Classification System
PUO should be classified into four subcategories to guide workup, as etiology distribution varies significantly:
- Classical PUO (community-acquired)
- Nosocomial PUO
- Neutropenic PUO (defined as single oral temperature ≥38.3°C OR ≥38.0°C sustained over at least 1 hour in neutropenic patients) 2, 4
- HIV-related PUO 2, 4
Critical Pitfall to Avoid
Do not confuse PUO with "fever without source" (FWS)—FWS is an acute illness with no apparent source after initial evaluation, while PUO requires prolonged fever >3 weeks with no identifiable source. 4 This distinction is crucial because the diagnostic approach, differential diagnosis, and urgency of intervention differ substantially between these two entities.
Temperature Measurement Standards
- Central temperature monitoring (pulmonary artery catheter, bladder catheters, or esophageal balloon thermistors) is preferred for accurate diagnosis in inpatient settings 4
- Oral or rectal temperatures are reliable alternatives when central monitoring is unavailable 4
- Avoid axillary, tympanic membrane, temporal artery thermometers, or chemical dot thermometers for diagnostic purposes due to unreliability 4