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Fever of unknown origin (FUO): which are the factors influencing the final diagnosis? A 2005-2015 systematic review
Francesco Maria Fusco1, Raffaella Pisapia2, Salvatore Nardiello3
1Infectious Diseases Unit 1, S. Maria Annunziata Hospital, Central Tuscany Health Unit, Via dell'Antella 54, 50012, Bagno a Ripoli, FI, Italy. francescomaria.fusco@uslcentro.toscana.it.
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.
Insights
Fever of Unknown Origin (FUO) diagnosis is influenced by country income and geography. Infectious diseases (ID) are common, but undiagnosed cases increase in higher-income nations, highlighting diagnostic challenges.
Area of Science:
- Internal Medicine
- Infectious Diseases
- Diagnostics
Background:
- Fever of Unknown Origin (FUO) presents a broad differential diagnosis including infectious diseases (ID), neoplasms, and noninfectious inflammatory diseases (NIID).
- A significant proportion of FUO cases remain undiagnosed, and the factors influencing diagnostic outcomes are not well understood.
- Understanding these factors is crucial for improving diagnostic yield in FUO.
Purpose of the Study:
- To identify factors associated with the diagnostic categories of FUO.
- To explore temporal trends in FUO diagnoses by comparing recent case-series with older ones.
- To analyze the impact of study country characteristics on FUO diagnosis.
Main Methods:
- Systematic review of classical FUO case-series published between 2005-2015, including patients from 2000 onwards.
- Comparison of findings with case-series published between 1995-2004 to assess changes over time.
- Multivariate regression analysis to identify significant associations between study factors and FUO diagnostic categories.
Main Results:
- Eighteen case-series encompassing 3164 patients were analyzed.
- Infectious diseases (ID) were diagnosed in 37.8%, NIID in 20.9%, and neoplasms in 11.6%, with 23.2% remaining undiagnosed.
- NIIDs showed a significant increase over time. Lower country income correlated with higher ID rates, while higher income correlated with more undiagnosed FUO. Geographic location, particularly Asia and Europe, showed significant associations with specific diagnostic categories.
Conclusions:
- Infectious diseases remain the leading cause of FUO, despite diagnostic advancements.
- Country income level and geographic location are key determinants influencing FUO diagnostic categories.
- FUO continues to pose a diagnostic challenge, emphasizing the need for further research into influencing factors.
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