Superiority of 18F-FDG PET compared to 111In-labelled leucocyte scintigraphy in the evaluation of fever of unknown origin.
Seshadri, N, Sonoda, L I, Lever, A M et al. · The Journal of infection · 2012 · DOI
Quick Summary
This study compared two imaging tests for finding the cause of fever that doctors can't explain. One test (PET) was much better at detecting problems—finding a cause in 86% of patients—compared to the other test (leucocyte scintigraphy), which only found a cause in 20% of patients. PET scans successfully identified infections, inflammation, and other conditions causing unexplained fevers.
Why It Matters
ME/CFS patients often present with unexplained fever and persistent symptoms that can resemble fever of unknown origin. This study demonstrates that PET imaging is superior for identifying inflammatory and infectious causes of prolonged fevers, which could help clinicians better differentiate ME/CFS from other treatable conditions causing similar presentations. The finding that three patients were subsequently diagnosed with ME/CFS after extensive investigation highlights the diagnostic challenge of this condition.
Observed Findings
PET detected abnormal tracer uptake in 14/23 patients (61%) compared to 3/23 (13%) on leucocyte scintigraphy (p<0.01)
PET sensitivity for identifying FUO etiology was 86% versus 20% for leucocyte scintigraphy
All leucocyte scintigraphy-positive cases (n=3) were confirmed on PET as infections
PET identified diverse etiologies: infections, vasculitis, non-infectious inflammatory conditions, and cancer
Three patients were ultimately diagnosed with ME/CFS during follow-up investigation
Inferred Conclusions
18F-FDG PET has superior sensitivity compared to 111In-labelled leucocyte scintigraphy for identifying the etiology of fever of unknown origin
PET/PET-CT should be the preferred non-invasive investigation in assessing patients with unexplained prolonged fever
Lower specificity of PET reflects its ability to detect general inflammatory processes rather than specific diagnoses, requiring clinical correlation
Remaining Questions
What is the optimal timing and protocols for PET imaging in evaluating prolonged fever?
How does PET performance differ across specific inflammatory and infectious etiologies in larger prospective cohorts?
What This Study Does Not Prove
This study does not prove that PET can definitively diagnose ME/CFS itself, nor does it establish the underlying cause of ME/CFS. The study is primarily about identifying causes of fever of unknown origin—a different clinical presentation than typical ME/CFS. The small sample size (23 patients) and inclusion of ME/CFS as an outcome only in three follow-up cases limits generalizability to the broader ME/CFS population.