Update on imaging in fever and inflammation of unknown origin: focus on infectious disorders

Background: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are diagnostic challenges that often require an extensive work-up. When first-line tests do not provide any or only misleading clues, second-line investigations such as specialized imaging techniques are often warranted.

Objectives: To provide an overview of the diagnostic value of imaging techniques that are commonly used in patients with FUO/IUO.

Sources: MEDLINE database was searched to identify the most relevant studies, trials, reviews, or meta-analyses until 31 March 2023.

Content: The most important types of second-line imaging tests for FUO and IUO are outlined, including [⁶⁷Ga]-citrate single-photon emission computed tomography/computed tomography (CT), labelled leukocyte imaging, [¹⁸F]-fluorodeoxyglucose positron emission tomography CT ([¹⁸F]-FDG-PET), and whole-body magnetic resonance imaging. This review summarizes the diagnostic yield, extends on potential future imaging techniques (pathogen-specific bacterial imaging and [¹⁸F]-FDG-PET/magnetic resonance imaging), discusses cost-effectiveness, highlights practical implications and pitfalls, and addresses future perspectives. Where applicable, we provide additional data specifically for the infection subgroup.

Implications: Although many imaging examinations are proven to be useful in FUO and IUO, [¹⁸F]-FDG-PET/CT is the preferred second-line test when available as it provides a high diagnostic yield in a presumably cost-effective way.