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

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.

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

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

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.

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.