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 infectious, inflammatory, malignant, and miscellaneous causes, which can be divided into four different subcategories: classical, nosocomial, neutropenic, and Human Immunodeficiency Virus (HIV) – related.
Key Points
- The definition of FUO requires a fever higher than 38.3°C (100.9°F) for at least 3 weeks
- The diagnosis should be made after at least 3 outpatient visits or in-patient days without a clear diagnosis
- FUO can be caused by various conditions, including infections, malignancies, non-infectious inflammatory disorders, and miscellaneous conditions
- The use of [18F]FDG PET/CT has a high diagnostic yield in FUO and can be helpful in identifying the underlying cause, as stated in the guideline 1.
Clinical Approach
The approach to FUO should include a thorough investigation, including:
- Detailed history
- Physical examination
- Laboratory tests
- Imaging studies This systematic approach helps clinicians identify the underlying cause of FUO, which is essential for providing appropriate treatment and improving patient outcomes. The guideline from the European Journal of Nuclear Medicine and Molecular Imaging 1 provides a framework for the diagnosis and management of FUO, emphasizing the importance of a thorough investigation and the use of [18F]FDG PET/CT in certain cases.
From the Research
Definition of Fever of Unknown Origin
- Fever of unknown origin (FUO) is defined 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 2.
- A more recent qualitative definition requires only a reasonable diagnostic evaluation 3.
- FUO is characterized as a febrile illness (temperature of 101°F [38.3°C] or higher) for three weeks or longer without an etiology despite a one-week inpatient evaluation 3.
Diagnostic Criteria
- The diagnosis of FUO requires a comprehensive history and examination to look for potentially diagnostic clues to guide the initial evaluation 3.
- Initial testing should include an evaluation for infectious etiologies, malignancies, inflammatory diseases, and miscellaneous causes 4.
- If erythrocyte sedimentation rate or C-reactive protein levels are elevated and a diagnosis has not been made after initial evaluation, 18F fluorodeoxyglucose positron emission tomography scan, with computed tomography, may be useful in reaching a diagnosis 4.
Differential Diagnosis
- More than 200 diseases can cause FUO, which are classically divided into following categories: infections, non-infectious inflammatory diseases, malignancies, and other miscellaneous disorders 5.
- The most common subgroups in the differential are infection, malignancy, noninfectious inflammatory diseases, and miscellaneous 3.
- Tuberculosis, lymphoma, and adult-onset Still's disease are the main diseases associated with FUO 6.