Fever of Unknown Origin (FUO) Criteria Influences Diagnostic Outcomes: A Systematic Review and Meta-Analysis

Criteria classifying fever of unknown origin (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). A systematic review of studies would help physicians anticipate the frequency of illness types that could influence management.

Prospective studies published in Medline (PubMed), Embase, Scopus, and Web of Science databases from January 1, 1997 to July 31, 2022, were included. A meta-analysis estimated associated pooled proportions between these criteria and diagnostic outcomes adjusted to the International Classification of Diseases, 10th edition (ICD-10) definitions.

Five qualitative studies corresponded to an increase of 15.3% (95% CI: 2.3%-28.3%, P = .021) in undiagnosed FUO proportions compared to eleven quantitative studies. Quantitative studies had 19.7% (95% CI: 6.0%-33.4%, P = .005) more in adjusted infectious disease proportions than qualitative studies. No significant differences in proportions between FUO defining criteria were noted for adjusted noninfectious inflammatory disorders (P = .318), oncology (P = .901), non-inflammatory miscellaneous disorders (P = .321), diagnostic evaluation process, gross national income (GNI), or World Health Organization (WHO) geographic region.

Use of either qualitative or quantitative FUO criteria was associated with a statistically significant risk of over- or under-estimating infectious diseases and undiagnosed illnesses when using an ICD-10 adjusted FUO five-category system. Clinicians should anticipate differences depending on which criteria are used. While further research is warranted, qualitative criteria provide the best framework for study comparisons.