Evaluating fever of unknown origin definitions in a tertiary care setting: Implications for diagnostic criteria revision.

Abstract

Background: Fever of unknown origin (FUO) remains a diagnostic challenge and was originally defined in 1961. Its classic criteria include fever ≥ 38.3 °C (≥ 101 °F) on multiple occasions, fever lasting three weeks or longer, and a diagnosis after one week of inpatient evaluation. However, these criteria may not fully encompass the varied clinical presentations seen in resource-limited settings such as India. The adaptation of FUO definitions to local healthcare contexts is crucial for enhancing diagnostic accuracy and optimizing patient outcomes.

Aim: To investigate the applicability of revised FUO criteria in a tertiary care setting in India.

Methods: This longitudinal-exploratory study at All India Institute of Medical Sciences Rishikesh (January 2018-December 2022) analyzed 228 adult patients with fever ≥ 99.1 °F lasting over three days. Patients diagnosed within three days of admission were excluded. Data were collected retrospectively and prospectively using predefined FUO definitions based on durations of nondiagnosis (3-21 days, > 21 days), temperature ranges (99.1 °F-100.9 °F, ≥ 101 °F), and hospitalization durations (3-7 days, > 7 days). Descriptive statistics and comparative tests (Fisher's exact test, χ ² test) evaluated outcomes across definitions.

Results: Among the proposed FUO definitions, Definition B (fever lasting 3-21 days, temperatures between 99.1 °F-100.9 °F, hospitalization > 7 days) predominated (40.8%), while only 2.2% met the classical criteria. Notably, 36.5% of Definition B patients remained undiagnosed after 7-10 days, despite 94% undergoing diagnostic workups within 21 days. Infection emerged as the leading etiology across definitions, without significant variation in outcomes or mortality during hospitalization (χ ² = 27.937, P = 0.142).

Conclusion: Adapting FUO criteria to local contexts improves diagnostic accuracy and treatment. Definition B (40.8% prevalence) showed practical utility, with higher mortality in patients discharged on empirical 'Anti-tuberculosis therapy'.