PET/CT Improves Diagnosis and Management of Fever of Unknown Origin

Fever of unknown origin (FUO) is persistent fever without an identifiable cause and remains difficult to diagnose because potential etiologies are broad and no single gold-standard pathway exists. Evaluation typically begins with history, examination, and first-line tests before advanced imaging is considered. A new multicenter study indicates that molecular imaging with 18F-FDG positron emission tomography/computed tomography (PET/CT) can substantially aid diagnosis and guide management.

The investigation assessed ¹⁸F-FDG PET/CT in FUO across 12 centers in Italy and was published in the June issue of The Journal of Nuclear Medicine. The work drew on expertise from multiple institutions; among those represented were the Università degli Studi of Brescia and ASST Spedali Civili di Brescia. The study was retrospective and designed to quantify diagnostic performance and clinical impact of PET/CT in routine FUO workups.

Researchers analyzed 929 patients who underwent ¹⁸F-FDG PET/CT for FUO. Final diagnoses—infectious disease, noninfectious inflammatory disease, malignancy, or unknown cause—were established using laboratory, imaging, histopathologic or pathologic examinations, and at least six months of clinical follow-up. The evaluation examined how PET/CT findings affected diagnostic conclusions and management decisions, and how results related to clinical, epidemiologic, and biochemical parameters.

PET/CT results were positive in 549 patients and negative in 380 patients. Imaging directly influenced clinical management in approximately 75% of cases through initiation of new therapies, modification of existing treatments, or recommendations for specific invasive procedures. According to the report, this influence contributed to improved patient outcomes, increased patient safety, and reduced health care costs.

The analysis also identified predictors of a positive PET/CT scan in FUO: elevated C-reactive protein, a high neutrophil-to-lymphocyte ratio, the presence of fever at the time of imaging, and a short duration of prior antibiotic therapy. These parameters may help clinicians anticipate the yield of PET/CT and plan diagnostic sequences more efficiently.

“Based on these findings, [18F]FDG PET/CT has the potential to be a first-line tool in the workup of FUO, rather than a second- or third-line test. In addition, the integration of clinical and biochemical parameters may help improve the performance of [18F]FDG PET/CT, reducing the time to diagnosis and preventing unnecessary treatments and investigations,” said Domenico Albano, MD, nuclear medicine physician at the Università degli Studi of Brescia and ASST Spedali Civili di Brescia, Italy.