What is the definition of fever of unknown origin?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: July 7, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Fever of unknown origin (FUO) is defined as a fever higher than 38.3°C (100.9°F) persisting for at least 3 weeks, with no diagnosis despite 3 outpatient visits or in-patient days. This definition is based on the most recent and highest quality study available, which emphasizes the importance of a prolonged period of fever without a clear diagnosis despite appropriate investigation 1. The condition is categorized into four main types: classical, nosocomial, neutropenic, and HIV-related, each with varying etiologies including infectious, inflammatory, malignant, and miscellaneous causes. Key points to consider in the definition and diagnosis of FUO include:

  • The duration of fever: at least 3 weeks
  • The absence of a clear diagnosis despite investigation
  • The categorization into different types based on the patient's condition and setting
  • The range of potential causes, from infections to malignancies and autoimmune disorders. The diagnostic approach to FUO involves a thorough history, physical examination, and systematic testing, with the use of tools like [18F]FDG PET/CT showing high diagnostic yield in both FUO and inflammation of unknown origin (IUO) 1.

From the Research

Definition of Fever of Unknown Origin

The definition of fever of unknown origin (FUO) is a disease condition characterized by:

  • A temperature exceeding 38.3°C (101°F) on multiple occasions
  • Duration of fever for more than three weeks
  • No diagnosis made despite a reasonable diagnostic evaluation, which may include:
    • One week of inpatient investigation 2
    • A minimum diagnostic workup, including laboratory tests and imaging studies 3, 4
  • The etiology of the fever remains unknown, despite extensive testing and evaluation 2, 3, 5, 4, 6

Key Characteristics

  • FUO is often defined as a febrile illness with no obvious source despite appropriate investigation 5
  • The differential diagnosis is broad, but typically categorized as:
    • Infection
    • Malignancy
    • Noninfectious inflammatory disease
    • Miscellaneous 3, 4
  • Most cases in adults occur due to uncommon presentations of common diseases, and up to 75% of cases may resolve spontaneously without reaching a definitive diagnosis 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Fever of unknown origin (FUO) revised.

Wiener klinische Wochenschrift, 2016

Research

Fever of Unknown Origin in Adults.

American family physician, 2022

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.