Recommendations for Updating Fever and Inflammation of Unknown Origin From a Modified Delphi Consensus Panel

William F Wright; Lauren Stelmash; Albrecht Betrains; Catharina M Mulders-Manders; Chantal P Rovers; Steven Vanderschueren; Paul G Auwaerter; International Fever and Inflammation of Unknown Origin Research Working Group

doi:10.1093/ofid/ofae298

Recommendations for Updating Fever and Inflammation of Unknown Origin From a Modified Delphi Consensus Panel

Open Forum Infect Dis. 2024 Jun 10;11(7):ofae298. doi: 10.1093/ofid/ofae298. eCollection 2024 Jul.

Authors

William F Wright¹, Lauren Stelmash², Albrecht Betrains³, Catharina M Mulders-Manders⁴, Chantal P Rovers⁴, Steven Vanderschueren⁵, Paul G Auwaerter⁶; International Fever and Inflammation of Unknown Origin Research Working Group

Collaborators

International Fever and Inflammation of Unknown Origin Research Working Group:
Cristian Baicus, Tehmina Bharucha, David Bor, Mile Bosilkovski, Michael Brown, Karen Carroll, Francesco Maria Fusco, Gavin Harris, Toshio Naito, Wim Jg Oyen, Seve Pascal, Steven Rowe, Priscilla Rupali, Lynora Saxinger, Terasawa Teruhiko, Ercan Yenilmez, Thierry Zenone

Affiliations

¹ Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² Division of Infectious Diseases, Department of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland, USA.
³ General Internal Medicine department, University Hospitals Leuven, Leuven, Belgium.
⁴ Division of Infectious Diseases, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
⁵ General Internal Medicine Department, Department of Microbiology, Immunology, and Transplantation, Laboratory of Clinical Infectious and Inflammatory Disorders, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
⁶ The Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Abstract

Background: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are syndromes commonly used as medical diagnoses. Since the existing literature has a mixture of diagnostic approaches, developing consensus-based recommendations would be helpful for clinicians, researchers, and patients.

Methods: A modified Delphi process was performed from October 2022 to July 2023, involving 4 rounds of online surveys and 2 live video conferences. The panel comprised international experts recruited based on peer-reviewed published publications and studies.

Results: Among 50 invited experts, 26 (52.0%) agreed to participate. Twenty-three panelists completed round 1 of the survey, 21 completed rounds 2 and 3, 20 completed round 4, and 7 participated in round 5 live video discussions. Of the participants, 18 (78.3%) were academic-based clinicians and researchers, 5 (21.7%) practiced in a community-based hospital, and 6 (26.1%) were female. Consensus was reached on 5 themes: (1) incorporating epidemiologic factors, such as geographic location and travel history; (2) updated criteria for classifying FUO or IUO; (3) initial evaluation approaches; (4) a classification system for diagnoses; and (5) recommendations for judicious limitation of empiric therapies. Experts strongly disagreed with using 2-deoxy-2-[¹⁸F] fluoro-D-glucose positron emission tomography/computed tomography as part of the diagnostic criteria for FUO. There were mixed opinions about the importance of the temperature measurement site, the 3-week minimum illness criterion, the need for a standard definition of relapsing fevers, and the use of similar evaluation strategies for FUO and IUO.

Conclusions: These Delphi-generated consensus-based recommendations offer potential improvements compared with earlier definitions and a guide for clinical practice and future research.

Keywords: fever; fever of unknown origin; inflammation of unknown origin; pyrexia; pyrexia of unknown origin.