Criteria used affects diagnostic outcome in fevers of unknown origin

Applying either the qualitative or the quantitative criteria of fever of unknown origin (FUO) appears to over- or underestimate infectious diseases and undiagnosed illnesses when using an International Classification of Diseases, 10th edition (ICD-10)-adjusted FUO five-category system.

“Criteria classifying FUO patients remains subject to discrepancies. A minimal standardized set of investigative tests serves as the foundation for the qualitative criteria, whereas quantitative incorporates the length of evaluation (7 or 3 days),” according to the authors. 

This systematic review and meta-analysis identified prospective studies using the databases of Medline, Embase, Scopus, and Web of Science from 1 January 1997 to 31 July 2022. The authors estimated the associated pooled proportions between the criteria used and the diagnostic outcomes adjusted to the ICD-10 definitions.

Five qualitative studies demonstrated a 15.3-percent increase (95 percent confidence interval [CI], 2.3–28.3; p=0.021) in undiagnosed FUO proportions relative to 11 quantitative studies. On the other hand, quantitative studies showed 19.7 percent (95 percent CI, 6.0–33.4; p=0.005) more in adjusted infectious disease proportions than qualitative studies.

No significant differences were seen in the proportions between FUO defining criteria for adjusted noninfectious inflammatory disorders (p=0.318), oncology (p=0.901), noninflammatory miscellaneous disorders (p=0.321), diagnostic evaluation process, gross national income (GNI), or World Health Organization (WHO) geographic region.

“Clinicians should anticipate differences depending on which criteria are used. While further research is warranted, qualitative criteria provide the best framework for study comparisons,” the authors said.