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This study suggests that FDG-PET/CT can be a useful diagnostic tool in children with fever of unknown origin (FUO) when standard investigations have not identified a cause.
Key Findings
Population: 112 children (0–18 years) with FUO who underwent PET/CT at three Israeli medical centers between 2010 and 2022.
Diagnostic yield: PET/CT contributed to establishing the diagnosis in 51 of 112 patients (45.5%).
Most common diagnoses when PET/CT was helpful:
Infectious diseases: 54.9%
Most common diagnoses when PET/CT was not helpful:
Rheumatologic diseases: 66.6%
Factors associated with a higher likelihood that PET/CT would be diagnostic:
Immunodeficiency
Low hemoglobin (anemia)
Elevated lactate dehydrogenase (LDH)
Low serum albumin
Factors associated with a lower likelihood of PET/CT being diagnostic:
Rash
Arthritis
Impact on management: PET/CT influenced treatment decisions in 35.7% of patients.
Traditional inflammatory markers (CRP, ESR, ferritin) did not distinguish between diagnostic and nondiagnostic PET/CT studies.
Clinical Interpretation
The study supports using PET/CT as a second-line or advanced diagnostic test in pediatric FUO, particularly when:
Conventional laboratory tests and imaging have been unrevealing.
There is concern for occult infection, malignancy, or another metabolically active inflammatory process.
The child has features associated with higher PET/CT yield (e.g., immunodeficiency, anemia, elevated LDH, hypoalbuminemia).
The finding that PET/CT was less useful in children with rash or arthritis may reflect the fact that many pediatric rheumatologic conditions can often be diagnosed through clinical evaluation, laboratory testing, and targeted imaging rather than whole-body metabolic imaging.
Strengths
Multicenter study.
Relatively large pediatric FUO cohort.
Evaluated both diagnostic yield and impact on treatment decisions.
Limitations
Retrospective design (susceptible to selection bias).
No control group.
PET/CT use was based on clinician judgment, which may affect generalizability.
Radiation exposure remains an important consideration in children.
Bottom Line
In this cohort, PET/CT provided clinically useful diagnostic information in nearly half of pediatric FUO cases and altered management in over one-third of patients. The results support considering PET/CT in children with persistent FUO after standard investigations have failed, particularly when clinical and laboratory features suggest a higher probability of diagnostic benefit.
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