What is fever of unknown origin (FUO)?

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 condition is characterized by a prolonged and unexplained elevation of body temperature, and it can be divided into four different subcategories: classical, nosocomial, neutropenic, and Human Immunodeficiency Virus (HIV) – related 1. The etiology of FUO includes infectious, inflammatory, malignant, and miscellaneous causes, and the distribution of these causes varies according to the FUO subcategory and geographical location.

Some key points to consider when evaluating FUO include:

• The definition of FUO, which requires a fever persisting for at least 3 weeks with no diagnosis despite multiple outpatient visits or in-patient days 1
• The different subcategories of FUO, which can help guide the diagnostic approach and management
• The various etiologies of FUO, including infectious, inflammatory, malignant, and miscellaneous causes
• The use of [18F]FDG PET/CT, which has a high diagnostic yield in both FUO and inflammation of unknown origin (IUO) 1

In terms of diagnosis and management, [18F]FDG PET/CT is usually preferred over sensitivity and specificity due to its high diagnostic yield and helpfulness in both FUO and IUO. This imaging modality can help identify the underlying cause of the fever and guide further management. It is essential to note that some patients with FUO may never have a final causative diagnosis, highlighting the importance of a thorough diagnostic approach and ongoing monitoring 1.

From the Research

Definition of Fever of Unknown Origin (FUO)

• Fever of unknown origin (FUO) is defined as a clinically documented temperature of 101°F or higher on several occasions, coupled with an unrevealing diagnostic workup 2.
• FUO is recognized as sustained, unexplained fever despite a comprehensive workup 3.
• It is defined as a temperature elevation of 101 degrees F (38.3 degrees C) or higher for 3 weeks or longer, the cause of which is not diagnosed after 1 week of intensive in-hospital investigation 4.

Etiologies of FUO

• The differential diagnosis of FUO is broad but is typically categorized as infection, malignancy, noninfectious inflammatory disease, or miscellaneous 2.
• In children, the most common cause of FUO is represented by infections, followed by inflammatory conditions and neoplastic causes 5.
• More than 200 diseases can cause FUO, including tuberculosis, lymphoma, and adult-onset Still's disease 6.

Diagnostic Approach

• The diagnostic approach to FUO should begin with a comprehensive history and physical examination to help narrow potential etiologies 2.
• Initial testing should include an evaluation for infectious etiologies, malignancies, inflammatory diseases, and miscellaneous causes 2.
• Fluorodeoxyglucose PET is a promising imaging modality in FUO 6.
• Invasive testing, such as tissue biopsy, may be useful in reaching a diagnosis if noninvasive diagnostic tests are unrevealing 2.