PET/CT as a Diagnostic Tool in Pediatric Fever of Unknown Origin: A Multicenter Study

BACKGROUND: Fever of unknown origin (FUO) in pediatric patients remains a persistent diagnostic challenge, despite advances in imaging and laboratory techniques. Although positron emission tomography/computed tomography (PET/CT) has demonstrated substantial diagnostic value in adult populations, its utility in pediatric FUO is less clearly defined. This study aimed to assess the contribution of PET/CT to the diagnosis of FUO in hospitalized children and identify predictive clinical and laboratory factors for its diagnostic utility. METHODS: This retrospective cohort study reviewed medical records of pediatric patients (aged 0-18 years) diagnosed with FUO who underwent fluorodeoxyglucose PET/CT imaging between 2010 and 2022, at 3 medical centers in Israel. Clinical presentations, laboratory findings, and final diagnoses were compared between cases where PET/CT contributed to diagnosis or did not. RESULTS: A total of 112 patients were included. PET/CT contributed to diagnosis in 51 (45.5%) cases. Among these, infectious etiologies predominated (54.9%). In contrast, among noncontributory PET/CT cases, rheumatologic diseases were more common (66.6%). Factors associated with higher diagnostic yield included immunodeficiency, low hemoglobin, elevated lactate dehydrogenase, and low serum albumin. Conversely, presence of rash or arthritis was more common in nondiagnostic cases. PET/CT influenced treatment decisions in 40 (35.7%) patients. No significant differences in inflammatory markers levels (C-reactive protein, erythrocyte sedimentation rate, ferritin) were observed between the groups. CONCLUSIONS: PET/CT demonstrates a substantial diagnostic yield in pediatric FUO, particularly when certain predictive clinical and laboratory factors are present. It may represent a useful tool in the evaluation of unresolved cases after conventional investigations had failed to identify the cause of fever.