What is the definition of Fever of Unknown Origin (FUO)?

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From the Guidelines

Fever of unknown origin (FUO) is defined as 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 guideline from the European Journal of Nuclear Medicine and Molecular Imaging 1. The etiology of FUO includes various causes such as infectious, inflammatory, malignant, and miscellaneous conditions.

Key Characteristics of FUO

  • The fever should be higher than 38.3°C (100.9°F)
  • The fever should persist for at least 3 weeks
  • No diagnosis should be made despite 3 outpatient visits or in-patient days
  • FUO is divided into four different subcategories: classical, nosocomial, neutropenic, and Human Immunodeficiency Virus (HIV) – related

Diagnostic Approach

The diagnostic approach to FUO typically involves a thorough history, physical examination, and systematic testing, starting with non-invasive methods and progressing to more specialized tests as needed, such as [*18F]FDG PET/CT which has a high diagnostic yield in both FUO and inflammation of unknown origin (IUO) 1.

Management

Management of FUO focuses on identifying and treating the underlying cause while providing supportive care for symptom relief. It is essential to consider the different subcategories of FUO and the varying distributions of etiologies according to the subcategory and geographical location 1.

From the Research

Definition of Fever of Unknown Origin (FUO)

  • Fever of unknown origin (FUO) is defined as a temperature higher than 38.3 degrees C (100.9 degrees F) that lasts for more than three weeks with no obvious source despite appropriate investigation 2.
  • FUO is characterized as a disease condition of temperature exceeding 38.3°C on at least three occasions over a period of at least three weeks, with no diagnosis made despite one week of inpatient investigation 3.
  • It is also defined as persistent fevers without an identifiable cause despite extensive medical workup 4.

Categories of FUO

  • FUO can be categorized into classic FUO, nosocomial FUO, neutropenic FUO, and HIV-associated FUO based on the clinical setting and patient's underlying immune status 5.
  • The four categories of potential etiology of FUO are classic, nosocomial, immune deficient, and human immunodeficiency virus-related 2.

Diagnostic Approach

  • A thorough history, physical examination, and standard laboratory testing remain the basis of the initial evaluation of the patient with FUO 2.
  • Newer diagnostic modalities, including updated serology, viral cultures, computed tomography, and magnetic resonance imaging, have important roles in the assessment of these patients 2.
  • A serum ferritin level can be useful in the workup of a patient with prolonged febrile illness and can facilitate early diagnosis and prompt treatment of hyperferritinemic syndromes 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: an evidence-based review.

The American journal of the medical sciences, 2012

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.

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