From the Guidelines
The workup for fever of unknown origin (FUO) should prioritize the use of [18F]FDG PET/CT due to its high diagnostic yield in this clinical setting, as supported by the recent guideline from the European Journal of Nuclear Medicine and Molecular Imaging 1. When approaching a patient with FUO, it is essential to start with a thorough history and physical examination, followed by basic laboratory tests, including:
- Complete blood count
- Comprehensive metabolic panel
- Urinalysis
- Blood cultures
- Inflammatory markers like ESR and CRP Initial imaging typically includes:
- Chest X-ray
- Abdominal ultrasound or CT scan If these initial tests are inconclusive, more specialized testing should be pursued based on clinical suspicion, including:
- Specialized blood cultures
- Serologic testing for infections (like HIV, tuberculosis, endocarditis)
- Autoimmune panels
- Advanced imaging such as CT scans of chest/abdomen/pelvis, MRI, or PET-CT, with [18F]FDG PET/CT being a preferred option due to its high diagnostic yield 1. Bone marrow biopsy may be considered if hematologic malignancy is suspected. Empiric antibiotic therapy is generally not recommended unless the patient is critically ill or neutropenic. The diagnostic approach should be systematic and iterative, with careful review of all previous data at each step. FUO workup requires patience as the cause often reveals itself over time, with infections, malignancies, and autoimmune disorders being the most common etiologies, as noted in the guideline 1. Consultation with infectious disease specialists is often valuable when initial evaluations are unrevealing.
From the Research
Diagnostic Approach
The diagnostic approach for fever of unknown origin (FUO) typically involves a comprehensive history and physical examination to help narrow potential etiologies 2, 3, 4, 5, 6.
Initial Evaluation
Initial testing should include:
- Evaluation for infectious etiologies
- Malignancies
- Inflammatory diseases
- Miscellaneous causes such as venous thromboembolism and thyroiditis 2
- A minimum diagnostic workup, including:
- Complete blood count
- Chest radiography
- Urinalysis and culture
- Electrolyte panel
- Liver enzymes
- Erythrocyte sedimentation rate
- C-reactive protein level testing 3
Further Testing
Further testing may include:
- Blood cultures
- Lactate dehydrogenase
- Creatine kinase
- Rheumatoid factor
- Antinuclear antibodies
- Human immunodeficiency virus and appropriate region-specific serologic testing
- Abdominal and pelvic ultrasonography or computed tomography 3
- 18F fluorodeoxyglucose positron emission tomography plus computed tomography to guide the clinician toward tissue biopsy 2, 3
Tissue Biopsy
If noninvasive diagnostic tests are unrevealing, then the invasive test of choice is a tissue biopsy because of the relatively high diagnostic yield 2. Depending on clinical indications, this may include:
- Liver biopsy
- Lymph node biopsy
- Temporal artery biopsy
- Skin biopsy
- Skin-muscle biopsy
- Bone marrow biopsy 2
Treatment
Empiric antimicrobial therapy has not been shown to be effective in the treatment of fever of unknown origin and therefore should be avoided except in patients who are neutropenic, immunocompromised, or critically ill 2, 3.