Fever of unknown origin (FUO): which are the factors influencing the final diagnosis? A 2005-2015 systematic review

Francesco Maria Fusco, Raffaella Pisapia, Salvatore Nardiello, Stefano Domenico Cicala, Giovanni Battista Gaeta, Giuseppina Brancaccio, Francesco Maria Fusco, Raffaella Pisapia, Salvatore Nardiello, Stefano Domenico Cicala, Giovanni Battista Gaeta, Giuseppina Brancaccio

Abstract

Background: The differential diagnosis of Fever of Unknown Origin (FUO) is very extensive, and includes infectious diseases (ID), neoplasms and noninfectious inflammatory diseases (NIID). Many FUO remain undiagnosed. Factors influencing the final diagnosis of FUO are unclear.

Methods: To identify factors associated with FUO diagnostic categories, we performed a systematic review of classical FUO case-series published in 2005-2015 and including patients from 2000. Moreover, to explore changing over time, we compared these case-series with those published in 1995-2004.

Results: Eighteen case-series, including 3164 patients, were included. ID were diagnosed in 37.8% of patients, NIID in 20.9%, and neoplasm in 11.6%, FUO were undiagnosed in 23.2%. NIIDs significantly increased over time. An association exists between study country income level and ID (increasing when the income decreases) and undiagnosed FUO (increasing when the income increases); even if not significant, the use of a pre-defined Minimal Diagnostic Work-up to qualify a fever as FUO seems to correlate with a lower prevalence of infections and a higher prevalence of undiagnosed FUO. The multivariate regression analysis shows significant association between geographic area, with ID being more frequent in Asia and Europe having the higher prevalence of undiagnosed FUO. Significant associations were found with model of study and FUO defining criteria, also.

Conclusions: Despite advances in diagnostics, FUO still remains a challenge, with ID still representing the first cause. The main factors influencing the diagnostic categories are the income and the geographic position of the study country.

Keywords: Diagnostic outcomes; Fever of unknown origin; Infectious diseases; Neoplasms; Noninfectious inflammatory diseases.

Conflict of interest statement

All authors declare that they have no competing interests. One of the author (FMF) is Associated Editor for BMC Infectious Diseases.

Figures

Fig. 1
Fig. 1
Flow Chart for the selection of 2006–2014 case-series about FUO
Fig. 2
Fig. 2
Comparison of tests and procedures included in a “Minimal Diagnostic Work-up” performed before qualifying a fever as FUO in new (2006–2014) and old (1995–2004) case-series
Fig. 3
Fig. 3
a-e Distribution of diagnostic categories associated to geographic area; income level of country, criteria used for FUO definition, model of study, and use of a Minimal Diagnostic Work-up to be performed before defining a fever as FUO
Fig. 4
Fig. 4
a-d Multivariate logistic regression models for infection (a), neoplasm (b), NIID (c), undiagnosed FUO (d)

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Source: PubMed

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