6/22/2023 0 Comments Fever of unknown originThe different methodologies among case-series (definition of FUO, retrospective or prospective model, use and composition of a minimal diagnostic work-up), may contribute to determine the final distribution of various causes of fever and the prevalence of FUO remaining without a diagnosis. ![]() Clinical profile of FUO could have changed over time, in consideration of advances in diagnostic techniques, evolving socioeconomic status of the countries, development of new broad-spectrum pharmaceuticals, the emergence of new diseases and the attitude of physicians. Among these factors, geographic prevalence patterns, the patient’s age, and the gap between the investigative resources of developing and developed countries may have a great significance. In published case-series, the spectrum of diseases causing FUO is very different, due to several factors still poorly explored. However, despite recent advances in medicine, about a quarter of FUO remains undiagnosed. Infectious diseases (ID), neoplasms and non-infectious inflammatory diseases (NIID) are the main categories of diseases causing FUO. ![]() The differential diagnosis of FUO is the most wide-ranging in medicine, since more than 200 conditions have been identified as the cause of FUO. In recent years, some authors proposed to change the quantitative criterion (diagnosis uncertain after 1 week or 3 days of investigation) with the qualitative requirement that fever remained undiagnosed after a minimal diagnostic work-up had been performed however, investigations that should be included in the work-up remain a matter of debate. To meet the evolution of diagnostic capabilities, some modifications in the definition of FUO occurred through the years: in 1991, Durak and Street proposed that there be a distinction between classical FUO and three other types, namely nosocomial, neutropenic and HIV-associated FUO moreover, they reduced the duration of investigation, before defining a FUO, to at least 3 days in hospital or at least 3 outpatient visits. The main factors influencing the diagnostic categories are the income and the geographic position of the study country.įever of unknown origin (FUO) was originally defined by Petersdorf and Beeson as an illness of more than 3 weeks’ duration, with fever greater than 38.3 ☌ (101 ☏) on several occasions, the cause of which is uncertain after 1 week of in-hospital investigations. Conclusionsĭespite advances in diagnostics, FUO still remains a challenge, with ID still representing the first cause. Significant associations were found with model of study and FUO defining criteria, also. 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. 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. ID were diagnosed in 37.8% of patients, NIID in 20.9%, and neoplasm in 11.6%, FUO were undiagnosed in 23.2%. ![]() ResultsĮighteen case-series, including 3164 patients, were included. Moreover, to explore changing over time, we compared these case-series with those published in 1995–2004. 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. Factors influencing the final diagnosis of FUO are unclear. The differential diagnosis of Fever of Unknown Origin (FUO) is very extensive, and includes infectious diseases (ID), neoplasms and noninfectious inflammatory diseases (NIID).
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