What is the role of Positron Emission Tomography (PET) scan in diagnosing Pyrexia of Unknown Origin (PUO)?

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

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

Diagnostic Performance of FDG-PET/CT in PUO

Effectiveness in Identifying Fever Source

• 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
• 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
• The most common causes of PUO identified by PET/CT include endocarditis (11%), systemic juvenile idiopathic arthritis (5%), and inflammatory bowel disorder (5%) 1
• 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

Impact on Clinical Management

• FDG-PET/CT findings led to treatment modifications in 53% of patients in a large pediatric study, demonstrating its significant clinical impact 1
• 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 1
• 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 1

Optimal Timing and Positioning in Diagnostic Algorithm

First-line vs. Second-line Testing

• There is some debate about the optimal timing of FDG-PET/CT in the diagnostic algorithm for PUO 1
• Some experts recommend FDG-PET/CT as an initial imaging modality for FUO in adults 1
• However, most guidelines suggest that FDG-PET/CT is more appropriate as a second-line test after initial imaging has been performed 1, 2
• The American College of Radiology guidelines indicate that most patients who benefit from FDG-PET/CT have already undergone prior diagnostic studies such as radiography and ultrasound 1

Advantages Over Other Imaging Modalities

• FDG-PET/CT has the potential to replace other imaging techniques in the evaluation of patients with PUO 3
• Compared to labeled white blood cell scans, FDG-PET/CT allows diagnosis of a wider spectrum of diseases 3
• Compared to gallium-67 citrate scanning, FDG-PET/CT appears to be more sensitive 3
• The integration of CT with PET (PET/CT) improves specificity by providing precise anatomical localization of hypermetabolic foci 3, 4

Disease Categories Detected by FDG-PET/CT in PUO

Infectious Causes

• FDG-PET/CT is highly effective in identifying focal abdominal, thoracic, or soft-tissue infections, as well as chronic osteomyelitis 3
• In sepsis of unknown origin, FDG-PET/CT can detect the site of infection in 56.4% of cases 1
• Negative findings on FDG-PET/CT essentially rule out orthopedic prosthetic infections 3

Non-infectious Inflammatory Disorders

• FDG-PET/CT is particularly valuable in diagnosing large-vessel vasculitis and aortoarteritis 5, 3
• In one study, FDG-PET/CT was diagnostic in 6.4% of PUO cases where other investigations including contrast-enhanced CT failed, with all these cases being aortoarteritis 5
• FDG-PET/CT is also useful in visualizing other inflammatory conditions such as inflammatory bowel disease, sarcoidosis, and thyroiditis 3, 4

Malignancies

• FDG-PET/CT is effective in detecting malignancies causing fever, particularly Hodgkin's disease, aggressive non-Hodgkin's lymphoma, colorectal cancer, and sarcoma 3
• In occult primary cancers, PET/CT has been shown to identify the primary site in 25% to 57% of patients 1

Limitations and Considerations

Technical and Interpretive Challenges

• False positives can occur due to recent valve implantation, inadequate suppression of myocardial FDG uptake, or prior use of certain surgical adhesives 1
• Extended periods of antibiotic therapy prior to PET/CT may reduce inflammatory activity and lead to false negative results 1
• Small or mobile vegetations in endocarditis may be missed by PET/CT, highlighting the need for a multimodality approach 1

Patient Selection

• The diagnostic yield of FDG-PET/CT may be higher in patients with elevated inflammatory markers such as C-reactive protein 1
• 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 1

Evidence Quality

• Most studies on FDG-PET/CT in PUO are retrospective with relatively small patient numbers 1
• The lack of a structured diagnostic workup in many studies may have led to selection bias 1
• Despite these limitations, the consistent findings across multiple studies support the utility of FDG-PET/CT in PUO evaluation 1, 3, 2