Role of FDG-PET/CT in children with fever of unknown origin

Abstract

Purpose To determine the role of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)/computed tomography (CT) in children with fever of unknown origin (FUO). Methods This retrospective single-center study included 110 children (0–18 years) with FUO who underwent FDG-PET/CT between 2010 and 2019. The diagnostic value of FDG-PET/CT for identifying cause of fever was calculated, treatment modifications after FDG-PET/CT were assessed, and logistic regression analyses were performed to identify clinical and biochemical factors associated with FDG-PET/CT outcome. Results In 53 out of 110 patients (48%), FDG-PET/CT identified a (true positive) cause of fever. Endocarditis (11%), systemic juvenile idiopathic arthritis (5%), and inflammatory bowel disorder (5%) were the most common causes of FUO. In 42 patients (38%), no cause of fever was found on FDG-PET/CT. In 58 out of 110 patients (53%), treatment modifications were made after FDG-PET/CT. FDG-PET/CT achieved a sensitivity of 85.5%, specificity of 79.2%, positive predictive value of 84.1%, and negative predictive value of 80.9%. On multivariate logistic regression, C-reactive protein was positively associated with finding a true positive focus of fever on FDG-PET/CT (OR = 1.01 (95% CI 1.00–1.02) per mg/L increase in CRP), while leukocyte count was negatively associated with finding a true positive focus of fever (OR = 0.91 (95% CI 0.85–0.97) per 109 leukocytes/L increase). Conclusion FDG-PET/CT is a valuable diagnostic tool in the evaluation of children with FUO, since it may detect a true underlying cause in almost half (48%) of all cases where none was found otherwise. It allows full-body evaluation in patients without disease-specific symptoms on one examination. CRP and leukocyte count were significantly associated with FDG-PET/CT results, which may contribute to a priori assessment on the outcome of FDG-PET/CT. Future research could be aimed at evaluating more patient-specific factors to prospectively estimate the added value of FDG-PET/CT in children with FUO.

Evaluation of FDG-PET/CT Use in Children with Suspected Infection or Inflammation

“…Elevated CRP level correlated with a positive FDG-PET/CT finding, although low CRP did not preclude positive findings. In a large cohort of children with FUO, Pijl et al also found that CRP level was positively associated with true positive FDG-PET/CT [ 8 ].…”

“…However, 47 scans were performed on stand-alone PET scanners without CT (with 40% helpful scans versus 53% helpful scans in PET scans with CT). A recent study including the largest cohort of pediatric patients with FUO thus far ( n = 110) reported that in 68/110 (62%) patients, a definite cause of fever was identified, where in 53 of 68 (78%), this cause was detected by FDG-PET/CT (53 of a total of 110 scans, 48%) [ 8 ].…”

“…In children with a provisional diagnosis before scanning, 50% of negative scans contributed to a final diagnosis versus 22% in patients with a broad differential and no provisional diagnosis before scanning. Most studies on FUO only classify positive scans as contributory due to the nature of the diagnostic question in FUO, i.e., what is the source of fever [ 6 , 7 , 8 , 18 , 19 ]. Children with a broad differential and high diagnostic uncertainty before FDG-PET/CT are more comparable to FUO and only 2/9 negative scans in this category contributed to the final diagnosis.…”

“…Literature reporting test performance in children with infection or inflammation comprises mainly retrospective studies based on data from health records of children with fever of unknown origin (FUO) [ 5 , 6 , 7 , 8 ]. In adults, the literature also includes prospective studies on the performance of FDG-PET/CT for various inflammatory or infectious diseases, such as FUO, gram-positive bacteremia and vasculitis [ 9 ].…”

Incidental PET/CT Findings of Suspected COVID-19 in a Region of High Prevalence

“…It is well known that fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) imaging demonstrates increased uptake across a variety of pathological etiologies including infections, inflammatory processes, and neoplasms. For example, FDG PET-CT imaging has been demonstrated to be useful in localizing foci of infection and inflammation in patients with fever of unknown origin [13]. In cases of COVID-19 infection documented on whole-body PET/CT, interstitial pneumonia is the predominant imaging manifestation, with multifocal bibasilar predominant ground glass opacities demonstrating increased FDG uptake in the lung parenchyma [14][15].…”