What is the preferred initial imaging modality, Positron Emission Tomography (PET) Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), for a child with Pyrexia of Unknown Origin (PUO)?

PET-CT vs MRI in Pediatric Pyrexia of Unknown Origin

FDG-PET/CT is the preferred advanced imaging modality for children with pyrexia of unknown origin when initial evaluation fails to identify the cause, demonstrating superior diagnostic performance with 85.5% sensitivity and high clinical impact in 79% of cases, while whole-body MRI has insufficient evidence to support routine use in this population. 1

Evidence-Based Imaging Algorithm

Initial Approach: Clinical Assessment First

• Begin with chest radiography only if pulmonary symptoms are present or concern exists for atypical bacterial infection, tuberculosis, or oncologic processes 1
• For febrile infants >3 months without respiratory signs, medical management without imaging is usually appropriate 1

When Advanced Imaging is Indicated

FDG-PET/CT should be considered as the second-line imaging modality when:

• Initial clinical evaluation and basic laboratory testing fail to identify fever source after 72-96 hours 2
• The child has undergone prior diagnostic studies (radiography, ultrasound) without definitive diagnosis 1

Performance Characteristics of FDG-PET/CT in Pediatric PUO

The 2025 ACR Appropriateness Criteria provides the strongest evidence for FDG-PET/CT:

• Diagnostic yield: Identifies fever source in 48% of pediatric patients 1
• Sensitivity: 85.5% with specificity of 79.2% 1
• Clinical impact: High in 79% of cases, prompting specialist referrals or changes to antimicrobial/antifungal therapy 1
• Common diagnoses identified: Endocarditis (11%), systemic juvenile idiopathic arthritis (5%), inflammatory bowel disease (5%) 1

In immunosuppressed pediatric patients specifically, FDG-PET/CT correctly identified the fever source in 88% of cases 1

MRI Performance in Pediatric PUO: Limited Evidence

Whole-body MRI has insufficient evidence to support routine use in pediatric PUO evaluation:

• No relevant literature supports MRI chest (with or without contrast) for initial PUO evaluation 1
• Whole-body MRI studies in children are rare, with only small case series available 1
• In one retrospective study of 3 pediatric PUO patients, whole-body MRI identified septic arthritis in one case and pneumonia with pleural effusion in another 1
• A larger series used whole-body MRI in 61 pediatric PUO patients primarily to rule out oncologic disease and occult abscesses, but diagnostic performance metrics were not reported 1

Special Population: Neutropenic Fever

For immunosuppressed and neutropenic children, the Children's Oncology Group specifically recommends FDG-PET/CT due to high sensitivity and specificity for infections in chest, abdomen, and pelvis 1

Critical Timing Considerations

• Perform FDG-PET/CT within 3 days of initiating oral glucocorticoid therapy if steroids are necessary, as early steroid use suppresses inflammatory activity and leads to false-negative results 2, 3
• Most children in successful diagnostic series had undergone prior basic imaging (radiography, ultrasound) before PET/CT 1

Common Pitfalls to Avoid

• Do not order whole-body MRI as first-line advanced imaging in pediatric PUO—the evidence base is insufficient and diagnostic yield is poorly characterized 1
• Avoid empiric imaging without clinical indication in well-appearing febrile children >3 months without respiratory signs 1
• Do not delay FDG-PET/CT if steroids are clinically necessary—perform imaging within 3 days of steroid initiation 2
• Remember radiation exposure concerns in children, but recognize that FDG-PET/CT's high diagnostic yield (48% identification rate) and clinical impact (79% of cases) justify its use when indicated 1

FDG-PET/MRI: Emerging but Not Ready

While FDG-PET/MRI has been suggested as potentially useful, there is insufficient data to support its use in initial pediatric PUO evaluation, and further prospective studies are needed 1