Long-term Follow-up of Patients with Classic Fever of Unknown Origin: Prognostic Outcomes and Management Strategies

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2026
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Abstract
Abstract Background This study evaluates the long-term prognosis of patients with classic fever of unknown origin (FUO) who are discharged without a definitive diagnosis, enhances the understanding of FUO, and provides evidence-based guidance for its diagnosis and management. Methods A retrospective analysis was conducted on hospitalized patients at the Department of Infectious Diseases, Peking Union Medical College Hospital, who met the diagnostic criteria for classic FUO. Clinical characteristics and diagnostic outcomes were summarized, and patients without a definitive diagnosis (including those classified as clinical and indeterminate diagnoses) were examined longitudinally to determine their prognostic outcomes. Results Overall, 739 patients with classic FUO were included. At discharge, 36.8% (n=272) received a definitive etiologic diagnosis, 48.8% (n=361) had a clinical diagnosis, and 14.3% (n=106) remained indeterminate. Median hospitalization cost was significantly higher in the definitive diagnosis than in the clinical diagnosis group [22,000 RMB (IQR 14,000–37,000) vs. 17,000 RMB (IQR 11,000–29,000); P< 0.001]. Among 396 successfully followed up patients discharged without a definitive diagnosis, mortality rate was 3.3% (13/396). During follow-up, 289 patients (73.0%) received a definitive diagnosis. The concordance rate between discharge and follow-up diagnoses was 93.0% and the success rate of diagnostic anti-tuberculosis therapy was 79.1% (53/67). Among the undiagnosed patients, 31.8% (34/107) experienced spontaneous remission and 36.4% (39/107) achieved remission after short-term anti-inflammatory therapy. Conclusions Most patients with classic FUO without a definitive diagnosis have a favorable prognosis, suggesting avoiding overtreatment. This study underscores the value of diagnostic therapies and close follow-up as key strategies in clinical management.
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Authors Li Zhang, Xiaotong Tian, Baotong Zhou, Ying Ge, 范洪伟, Taisheng Li, Zhengyin LIU
Journal Open forum infectious diseases
Year 2026
DOI
10.1093/ofid/ofag372
URL
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