What is the diagnostic workup for Pyrexia (Fever) of Unknown Origin (FUO)?

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From the Guidelines

Fever of Unknown Origin (FUO) diagnostic workup should start with a chest radiograph.

Initial Evaluation

  • A chest radiograph is recommended as the initial imaging test for patients who develop a fever during ICU stay 1.
  • This is because pneumonia is a common cause of fever in ICU patients, and bedside chest radiography is a low-cost, noninvasive test.

Further Evaluation

  • If an etiology is not readily identified by the initial workup, CT imaging of the operative area is recommended for patients who have recently undergone thoracic, abdominal, or pelvic surgery 1.
  • For critically ill patients with fever in whom other diagnostic tests have failed to establish an etiology, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT may be considered if the risk of transport is deemed acceptable 1.
  • CT imaging is usually the first-line modality in patients with fever of unknown origin, especially when pneumonia is suspected 1.

Special Considerations

  • Bronchoscopy and bronchoalveolar lavage (BAL) should be carried out using a standardized protocol in patients with fever of unknown origin not responding to an appropriate first-line therapy after 72–96 h 1.
  • Galactomannan (GM) screening or an intensive work-up with GM for 3 days after 4 days persisting fever together with clinical and radiological examinations may be effective in detecting invasive aspergillosis 1.
  • 1,3-β-D-glucan (BG) measurement may also be useful in detecting invasive fungal infections, but its limitations and potential interferences should be considered 1.

From the Research

Diagnostic Workup for Pyrexia (Fever) of Unknown Origin (FUO)

The diagnostic workup for FUO involves a comprehensive approach to identify the underlying cause of the fever. The following steps are involved in the diagnostic workup:

  • Initial evaluation: A comprehensive history and physical examination to help narrow potential etiologies 2
  • Laboratory tests: Evaluation for infectious etiologies, malignancies, inflammatory diseases, and miscellaneous causes such as venous thromboembolism and thyroiditis 2
  • Imaging studies:
    • Radionuclide imaging, such as Gallium-67 citrate, has been used in the past, but has several disadvantages, including a high radiation dose and suboptimal image quality 3
    • Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) and PET/computed tomography (CT) have become increasingly important in the diagnostic workup of patients with FUO, as they can localize lesions and areas of interest for further evaluation 3, 4
    • FDG PET-CT is considered the imaging technique of first choice in the diagnostic workup of FUO 4
  • Invasive tests: Tissue biopsy, such as liver, lymph node, temporal artery, skin, skin-muscle, or bone marrow biopsy, may be necessary if noninvasive diagnostic tests are unrevealing 2
  • Classification: FUO can be classified into different categories, including classic FUO, nosocomial FUO, neutropenic FUO, and HIV-associated FUO, based on the clinical setting and patient's underlying immune status 5, 6

Special Considerations

  • In older patients, the diagnostic workup for FUO may need to be tailored to their specific needs and underlying health conditions 5
  • In patients with no localizing signs and symptoms, the workup should begin with a comprehensive history and physical examination to help narrow potential etiologies 2
  • Empiric antimicrobial therapy should be avoided except in patients who are neutropenic, immunocompromised, or critically ill 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Fever of Unknown Origin in Adults.

American family physician, 2022

Research

Fever of unknown origin.

Clinical medicine (London, England), 2015

Research

Fever of unknown origin: an evidence-based review.

The American journal of the medical sciences, 2012

Research

[Fever of unknown origin].

Zeitschrift fur Rheumatologie, 2013

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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