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, χ² 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 (χ² = 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'.

Keywords: Empirical therapy; New definition; Pyrexia of unknown origin; Tuberculosis

Core Tip: This study evaluates the feasibility of revising fever of unknown origin (FUO) diagnostic criteria in a tertiary care setting in North India. It proposes a new definition (Definition B), which includes fever lasting 3-21 days, temperatures between 99.1 °F-100.9 °F, and hospitalization for over 7 days. The findings highlight the predominance of infections as the leading etiology, the low applicability of classical FUO criteria, and the importance of adapting diagnostic frameworks to local epidemiology. This approach aims to enhance early diagnosis, optimize resource use, and improve patient outcomes in resource-limited settings.