Fever of unknown origin (FUO): evolution of case definition, changing aetiological spectrum

Prolonged fever is a common problem faced by clinicians in everyday practise. Since the first description of the entity “fever of unexplained origin” by Petersdorf and Beeson in 1961, the case definition of this entity was further refined with modifications over the last 55 years. Durack and Street proposed noteworthy changes in the definition of “fever of unknown origin (FUO)”. First, they divided FUO into four groups, namely, classic, nosocomial, human immunodeficiency virus (HIV) related and neutropenic FUO. They also proposed a change in the time frame from “one week hospital study” to “three outpatient visits or three days of in-hospital investigations”. The more recent definition modified the temperature recording of above 38.3 oC (101 oF) on “several occasions” to “at least two occasions” and has listed the minimum essential laboratory testing required for diagnosis. The last five decades have also witnessed a change in the aetiological spectrum of FUO. Infectious diseases like tuberculosis are still common causes of FUO in India; an increase in non-infectious causes of FUO are increasingly being documented in studies form the west. Inspite of great advances in imaging and laboratory diagnostic methods a significant number of patients with FUO remained undiagnosed. Studies from other parts of the world have shown 9%-78% cases of FUO to remain undiagnosed while studies from India have shown this figure to be 0%-27.4%. Generating reliable epidemiological data regarding the aetiological spectrum of FUO will facilitate development of optimal work-up strategy to establish the aetiological diagnosis and facilitate the specific tests.