State-of-the-Art Review: Contemporary Ambulatory Approach to Adult Fever of Unknown Origin

Fever of unknown origin remains a diagnostic frontier, with research predominantly focused on the underlying disease spectrum. However, this focus largely overlooked issues between previous diagnostic criteria-the "quantitative" or "qualitative" definitions-and the critical role of evaluating the patient. This review synthesizes mounting evidence that the qualitative criteria are a central, yet underappreciated, driver of an effective and efficient clinical evaluation process for the ambulatory adult immunocompetent population. With input from infectious disease physicians, rheumatologists, and oncologists with expertise in this area, we chart the complex landscape of this widely recognized and potentially devastating condition, revealing key recommendations from a modified Delphi consensus panel and the Society of Nuclear Medicine and Molecular Imaging that offer changes beyond earlier definitions and management. By recentering the conversation around this updated approach, we argue for a paradigm shift for modern clinical practice and future research.