Role of PET Scan in Diagnosing Pyrexia of Unknown Origin (PUO)

Diagnostic Performance of FDG-PET/CT in PUO

The American College of Radiology suggests that FDG-PET/CT is a valuable second-line imaging modality in the diagnostic workup of pyrexia of unknown origin with high sensitivity (80-100%) and specificity (66.7-79.2%) that can identify the source of fever in approximately 48% of cases and lead to treatment modifications in up to 53% of patients 1, 2
FDG-PET/CT whole body has demonstrated significant utility in identifying the source of fever in patients with PUO, with multiple studies confirming its effectiveness in both pediatric and adult populations 1, 2, 3
In a large retrospective review of 110 pediatric patients with PUO, FDG-PET/CT identified the source of fever (true-positive result) in 48% of patients 1, 2
The most common causes of PUO identified by PET/CT include endocarditis (11%), systemic juvenile idiopathic arthritis (5%), and inflammatory bowel disorder (5%) 2
FDG-PET/CT has shown high diagnostic performance with sensitivity ranging from 80% to 100% and specificity from 66.7% to 79.2% in pediatric patients 1, 2

FDG-PET/CT findings led to treatment modifications in 53% of patients in a large pediatric study, demonstrating its significant clinical impact 2, 3
In adult patients with bacteremia of unknown origin, FDG-PET/CT had a high clinical impact in 47.3% of cases, independent of the duration of preceding antimicrobial treatment 4
FDG-PET/CT was the first modality to identify the site of infection in 41.1% of cases in patients with bacteremia of unknown origin 4

In sepsis of unknown origin, FDG-PET/CT can detect the site of infection in 56.4% of cases 4, 5

In occult primary cancers, PET/CT has been shown to identify the primary site in 25% to 57% of patients 6

False positives can occur due to recent valve implantation, inadequate suppression of myocardial FDG uptake, or prior use of certain surgical adhesives 7
Extended periods of antibiotic therapy prior to PET/CT may reduce inflammatory activity and lead to false negative results 7
Small or mobile vegetations in endocarditis may be missed by PET/CT, highlighting the need for a multimodality approach 7

The diagnostic yield of FDG-PET/CT may be higher in patients with elevated inflammatory markers such as C-reactive protein 7
Early implementation of PET/CT in the diagnostic workup may improve outcomes by allowing for timelier diagnosis and preventing missed diagnoses due to extended periods of antibiotic therapy 7

Most studies on FDG-PET/CT in PUO are retrospective with relatively small patient numbers 1, 2
The lack of a structured diagnostic workup in many studies may have led to selection bias 1, 2
Despite these limitations, the consistent findings across multiple studies support the utility of FDG-PET/CT in PUO evaluation 1, 2

The European Journal of Nuclear Medicine and Molecular Imaging recommends FDG-PET/CT for patients with fever persisting for at least 3 weeks with temperature higher than 38.3°C (100.9°F) after standard initial workup fails to identify the cause, and ideally within 3 days of initiation of oral glucocorticoid therapy to prevent suppression of inflammatory activity 8
FDG-PET/CT has higher diagnostic yield in patients with elevated inflammatory markers (such as CRP, ESR) 8
A negative FDG-PET/CT can predict favorable prognosis through spontaneous remission of fever and potentially allows a watchful waiting approach, with cost-effectiveness demonstrated in both FUO and inflammation of unknown origin 8

Patients should fast for at least 4-6 hours prior to FDG injection to minimize physiologic glucose uptake, and adequate hydration should be maintained before and after FDG injection, with blood glucose levels checked before FDG administration, and optimal levels below 150-180 mg/dL 9
Consider myocardial suppression preparation (high-fat, low-carbohydrate diet for 24 hours before the scan, plus prolonged fasting) when there is potential cardiac etiology to reduce physiological myocardial uptake 8

Whole-body imaging from skull base to mid-thigh is standard, with extension to include the brain and lower extremities when clinically indicated, and low-dose CT should be performed for attenuation correction and anatomical correlation 10
Image acquisition typically begins 60 minutes after FDG injection 9

Physiologic FDG uptake in brain, heart, urinary tract, and bowel must be distinguished from pathologic uptake 9