Nuclear Imaging for Classic Fever of Unknown Origin: Meta-Analysis

Several studies have assessed nuclear imaging tests for localizing the source of fever in patients with classic fever of unknown origin (FUO); however, the role of these tests in clinical practice remains unclear. We systematically reviewed the test performance, diagnostic yield, and management decision impact of nuclear imaging tests in patients with classic FUO.

We searched PubMed, Scopus, and other databases through October 31, 2015, to identify studies reporting on the diagnostic accuracy or impact on diagnosis and management decisions of ¹⁸F-FDG PET alone or integrated with CT (¹⁸F-FDG PET/CT), gallium scintigraphy, or leukocyte scintigraphy. Two reviewers extracted data. We quantitatively synthesized test performance and diagnostic yield and descriptively analyzed evidence about the impact on management decisions.

We included 42 studies with 2,058 patients. Studies were heterogeneous and had methodologic limitations. Diagnostic yield was higher in studies with higher prevalence of neoplasms and infections. Nonneoplastic causes, such as adult-onset Still's disease and polymyalgia rheumatica, were less successfully localized. Indirect evidence suggested that ¹⁸F-FDG PET/CT had the best test performance and diagnostic yield among the 4 imaging tests; summary sensitivity was 0.86 (95% confidence interval [CI], 0.81-0.90), specificity 0.52 (95% CI, 0.36-0.67), and diagnostic yield 0.58 (95% CI, 0.51-0.64). Evidence on direct comparisons of alternative imaging modalities or on the impact of tests on management decisions was limited.

Nuclear imaging tests, particularly ¹⁸F-FDG PET/CT, can be useful in identifying the source of fever in patients with classic FUO. The contribution of nuclear imaging may be limited in clinical settings in which infective and neoplastic causes are less common. Studies using standardized diagnostic algorithms are needed to determine the optimal timing for testing and to assess the impact of tests on management decisions and patient-relevant outcomes.