EANM consensus document on the use of [18F]FDG PET/CT in fever and inflammation of unknown origin

Abstract

Purpose: Patients with fever and inflammation of unknown origin (FUO/IUO) are clinically challenging due to variable clinical presentations with nonspecific symptoms and many differential diagnoses. Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) is increasingly used in FUO and IUO, but the optimal diagnostic strategy remains controversial. This consensus document aims to assist clinicians and nuclear medicine specialists in the appropriate use of [¹⁸F]FDG-PET/CT in FUO and IUO based on current evidence.

Methods: A working group created by the EANM infection and inflammation committee performed a systematic literature search based on PICOs with "patients with FUO/IUO" as population, "[¹⁸F]FDG-PET/CT" as intervention, and several outcomes including pre-scan characteristics, scan protocol, diagnostic yield, impact on management, prognosis, and cost-effectiveness.

Results: We included 68 articles published from 2001 to 2023: 9 systematic reviews, 49 original papers on general adult populations, and 10 original papers on specific populations. All papers were analysed and included in the evidence-based recommendations.

Conclusion: FUO and IUO remains a clinical challenge and [¹⁸F]FDG PET/CT has a definite role in the diagnostic pathway with an overall diagnostic yield or helpfulness in 50-60% of patients. A positive scan is often contributory by directly guiding treatment or subsequent diagnostic procedure. However, a negative scan may be equally important by excluding focal disease and predicting a favorable prognosis. Similar results are obtained in specific populations such as ICU-patients, children and HIV-patients.

Keywords: FDG; FUO; Fever of unknown origin; IUO; Infection; Inflammation; Inflammation of unknown origin; PET/CT.

Fig. 1

Suggested flowchart for the diagnostic strategy of fever of unknown origin (FUO), inflammation of unknown origin (IUO), and equivalent cases with nonspecific suspicion systemic infection or inflammation. *As discussed in the section on pre-scan work-up, there is no consensus on basic investigations. Most recommend at least some inflammatory markers, but any subsequent step(s) are often left at the discretion of the treating physician and may be as much based on local tradition as on evidence FUO: fever of unknown origin; IUO: inflammation of unknown origin; CRP: c-reactive protein; ESR: erythrocyte sedimentation rate; WBC: white blood cells; CXR: chest x-ray; HFLC: high-fat low-carbohydrate; LMWH: low molecular-weight heparin