From the Guidelines
The diagnostic workup for Pyrexia (fever) of Unknown Origin (FUO) should begin with a thorough history and physical examination, followed by basic laboratory tests including complete blood count, comprehensive metabolic panel, urinalysis, blood cultures, and inflammatory markers (ESR, CRP), as recommended by recent guidelines 1. The initial evaluation should prioritize identifying potential sources of infection, malignancy, or autoimmune disorders.
- Basic laboratory tests should include:
- Complete blood count
- Comprehensive metabolic panel
- Urinalysis
- Blood cultures
- Inflammatory markers (ESR, CRP)
- Initial imaging should include:
- Chest X-ray
- Abdominal ultrasound or CT scan If these initial tests are inconclusive, more specialized testing is warranted based on clinical suspicion.
- This may include:
- Specialized blood cultures for fastidious organisms
- Serologic testing for specific infections (like tuberculosis, HIV, endocarditis)
- Autoimmune panels
- Advanced imaging such as CT scans of chest/abdomen/pelvis, MRI, or PET-CT scans
- Bone marrow biopsy may be considered for suspected hematologic malignancies or certain infections.
- Tissue biopsies of lymph nodes or other suspicious areas might be necessary. Throughout this process, empiric antibiotic therapy should generally be avoided unless the patient is clinically unstable, as it may mask the underlying cause 1. The workup should be systematic and guided by the patient's risk factors, travel history, occupational exposures, and predominant symptoms, as FUO can result from infections, malignancies, autoimmune disorders, or miscellaneous causes like drug fever or factitious fever. Recent studies have shown that FDG-PET/CT can be a useful tool in identifying the source of infection in patients with FUO, especially when other diagnostic tests have failed to establish an etiology 1. However, it is essential to note that FDG-PET/CT should only be considered for use after source localization with CT has failed. In patients who develop a fever during ICU stay, performing a chest radiograph is recommended as part of the initial workup 1. Additionally, CT imaging of the operative area should be performed in collaboration with the surgical service for patients who have recently undergone thoracic, abdominal, or pelvic surgery 1.
From the Research
Diagnostic Workup for Pyrexia (Fever) of Unknown Origin (FUO)
The diagnostic workup for FUO involves a thorough history, physical examination, and standard laboratory testing 2, 3, 4, 5.
- A comprehensive history and physical examination are the keys to establishing a diagnosis in patients with FUO 4.
- The four categories of potential etiology of FUO are classic, nosocomial, immune deficient, and human immunodeficiency virus-related 2, 3.
- The four subgroups of the differential diagnosis of FUO are infections, malignancies, autoimmune conditions, and miscellaneous 2.
Key Diagnostic Features
Key diagnostic features of FUO include:
- Arthritis
- Cervical lymphadenopathy
- Dyspnea (with hypoxia)
- Ocular symptoms 6 These features can improve diagnostic efficiency in patients with FUO.
Diagnostic Approach
A clinical approach to FUO involves:
- Characteristic history and physical examination findings
- Key nonspecific test abnormalities
- A focused clue-directed FUO work-up 5 Newer diagnostic modalities, including updated serology, viral cultures, computed tomography, and magnetic resonance imaging, have important roles in the assessment of these patients 2.