Role of PET/CT in Pyrexia of Unknown Origin (PUO)
FDG-PET/CT is a highly valuable diagnostic tool in evaluating patients with PUO, with sensitivity of 80-100% and specificity of 66.7-79.2%, capable of identifying the underlying cause in approximately 46-56% of cases. 1
Diagnostic Value of PET/CT in PUO
Diagnostic Performance
- Sensitivity: 80-100%
- Specificity: 66.7-79.2%
- Positive Predictive Value: 67-84.1%
- Negative Predictive Value: 80.9-100% 1, 2
Clinical Impact
- Identifies the underlying cause in 46-56% of PUO cases 2, 3
- Contributes to diagnosis or exclusion of focal pathology in up to 90% of patients 2
- Leads to treatment modifications in approximately 53% of cases 1
Common Etiologies Identified by PET/CT in PUO
Infectious Causes (Most Common)
- Endocarditis (11% of cases) 1
- Focal abdominal infections
- Thoracic infections
- Soft tissue infections
- Chronic osteomyelitis 4
- Splenic abscesses 1
Inflammatory/Non-infectious Causes
- Systemic juvenile idiopathic arthritis (5% of cases) 1
- Inflammatory bowel disease (5% of cases) 1
- Large vessel vasculitis (particularly aortoarteritis) 5, 4
- Sarcoidosis 4
Malignancies
- Lymphomas (Hodgkin's and aggressive non-Hodgkin's)
- Colorectal cancer
- Sarcomas 4
Timing and Positioning in Diagnostic Algorithm
When to Consider PET/CT
- After initial basic investigations have failed to identify the cause
- Before invasive diagnostic procedures
- Particularly valuable when conventional imaging is negative or inconclusive 1, 5
Factors Affecting Diagnostic Yield
- Higher yield when inflammatory markers (CRP, ESR) are elevated 3
- Prior antibiotic therapy may reduce sensitivity by suppressing inflammatory activity 1
- Early implementation in the diagnostic workup may improve outcomes by allowing timelier diagnosis 1
Advantages Over Other Imaging Modalities
- Whole-body assessment in a single examination
- Superior to labeled white blood cell scans by diagnosing a wider spectrum of diseases
- More sensitive than gallium-67 citrate scanning 4
- Can detect both focal and systemic processes
- Provides anatomical and functional information simultaneously
Limitations and Pitfalls
False positives can occur due to:
- Recent surgical procedures
- Foreign body reactions
- Inadequate suppression of myocardial FDG uptake 1
- Physiological uptake in certain organs
False negatives may occur with:
- Prior extended antibiotic therapy
- Small or mobile lesions
- Systemic diseases without focal manifestations 3
Emerging Technologies
- FDG-PET/MRI shows potential but currently has insufficient data to support routine use in PUO evaluation 1
- PET/CT technology continues to improve diagnostic impact, particularly through enhanced specificity 4
In conclusion, FDG-PET/CT represents a powerful diagnostic tool in the evaluation of PUO, particularly when initial investigations are inconclusive. Its high sensitivity and negative predictive value make it especially valuable for excluding focal pathologies as the cause of fever, while its ability to detect a wide range of infectious, inflammatory, and malignant conditions makes it an efficient second-line investigation in the diagnostic algorithm for PUO.