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Etiological spectrum and outcome of fever and inflammation of unknown origin. Does symptom duration matter?

  • A. Betrains
    Correspondence
    Correspondence author at: General Internal Medicine department, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
    Affiliations
    Department of general internal medicine, University Hospitals Leuven, Leuven, Belgium

    Department of Microbiology, Immunology, and Transplantation, Laboratory of clinical infectious and inflammatory disorders, KU Leuven, Leuven, Belgium
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  • W.F. Wright
    Affiliations
    Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine Baltimore, Maryland, USA.
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  • L. Moreel
    Affiliations
    Department of general internal medicine, University Hospitals Leuven, Leuven, Belgium

    Department of Microbiology, Immunology, and Transplantation, Laboratory of clinical infectious and inflammatory disorders, KU Leuven, Leuven, Belgium
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  • F. Staels
    Affiliations
    KU Leuven, Department of Microbiology, Immunology and Transplantation, Immunogenetics Research Group, Leuven, Belgium

    KU Leuven, Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, Leuven, Belgium
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  • D. Blockmans
    Affiliations
    Department of general internal medicine, University Hospitals Leuven, Leuven, Belgium

    Department of Microbiology, Immunology, and Transplantation, Laboratory of clinical infectious and inflammatory disorders, KU Leuven, Leuven, Belgium

    European Reference Network for Immunodeficiency, Autoinflammatory, Autoimmune and Pediatric Rheumatic disease (ERN-RITA)
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  • S. Vanderschueren
    Affiliations
    Department of general internal medicine, University Hospitals Leuven, Leuven, Belgium

    Department of Microbiology, Immunology, and Transplantation, Laboratory of clinical infectious and inflammatory disorders, KU Leuven, Leuven, Belgium

    European Reference Network for Immunodeficiency, Autoinflammatory, Autoimmune and Pediatric Rheumatic disease (ERN-RITA)

    ImmunAID (Immunome project for Autoinflammatory Disorders) consortium
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Published:October 16, 2022DOI:https://doi.org/10.1016/j.ejim.2022.10.002

      Abstract

      Objective

      Evidence suggests that the symptom duration may affect the occurrence of certain fever (FUO) and inflammation (IUO) of unknown origin associated conditions. It is unclear if this could potentially guide diagnostic evaluations. We examined the association between symptom duration and diagnostic and prognostic outcomes in FUO/IUO.

      Methods

      We retrospectively analyzed a cohort of adult patients meeting criteria for FUO/IUO from a tertiary care center in Belgium between 2000 and 2019. The association between symptom duration and outcomes of interest were estimated by Cox proportional hazards models.

      Results

      Among 602 patients who met criteria for FUO/IUO (mean age 54 years, 43% female), 132 (22%) and 68 (11%) had symptoms for 3–12 months and >12 months, respectively. There were no significant differences in diagnosis or all-cause mortality between a symptom duration of <3 months and 3–12 months. In contrast, those who had a symptom duration of >12 months were less likely to receive a final diagnosis (aHR 0.42, 95% CI 0.30–0.60), in particular a diagnosis of infectious disorders (aHR 0.29, 95% CI 0.12–0.74), malignancies (aHR 0.11, 95% CI 0.03–0.46), and miscellaneous conditions (aHR 0.22, 95% CI 0.07–0.71), but no significant differences were seen in noninfectious inflammatory disorders (aHR 0.74, 95% CI 0.48–1.15) or all-cause mortality (aHR 0.55, 95% CI 0.19–1.54).

      Conclusions

      The symptom duration may be used to guide the diagnostic workup among patients with FUO and IUO, in particular those with longstanding symptoms.

      Keywords

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