Do you routinely consider FDG PET/CT imaging for workup of fever of unknown origin?

The landscape of FUO and IUO and our clinical approach to diagnosing its cause has changed significantly over the past several decades. More sensitive microbiologic screening for infectious etiologies, including syndromic molecular panels and next-generation sequencing are now clinically available and have enhanced our capacity to diagnose occult infections and are increasingly within the standard of care.

When the likelihood of infection diminishes, the potential for fever and/or inflammation to be driven by immune-mediated diseases or occult malignancy increases. Clinical options include pan CT chest, abdomen, and pelvis, which is readily available and cost-effective, as well as FDG PET/CT, which is less readily available and more expensive. Given my choice, I prefer first-line PET-CT if possible. While no direct comparisons are available regarding the sensitivity and diagnostic accuracy of these modalities, a recent meta-analysis (Buchrits et al., PMID 38499136) suggests that PET-CT is numerically more sensitive, especially for occult malignancy. It is also highly efficient for detecting large vessel vasculitis (occult GCA, Takayasu's, IgG4, or even infectious aortitis), which epidemiologically is increasingly encountered. Having said that, the aggressive use of pan CT is also efficient and valuable.