From the Guidelines
The diagnostic workup for Pyrexia (fever) of Unknown Origin (FUO) in a primary care setting should begin with a thorough history and physical examination, followed by initial laboratory tests including complete blood count with differential, comprehensive metabolic panel, erythrocyte sedimentation rate, C-reactive protein, urinalysis, and blood cultures (at least two sets), as recommended by recent guidelines 1. The workup for FUO in primary care is a systematic approach that aims to identify the underlying cause of the fever.
- Initial steps include:
- A thorough history and physical examination to identify potential sources of infection, inflammatory conditions, and malignancies
- Initial laboratory tests such as complete blood count with differential, comprehensive metabolic panel, erythrocyte sedimentation rate, C-reactive protein, urinalysis, and blood cultures (at least two sets)
- Imaging studies such as chest X-ray and tuberculin skin testing are important initial imaging and screening tests, as suggested by 1
- If these initial evaluations are non-diagnostic, additional testing may include HIV testing, heterophile antibody testing, liver function tests, rheumatoid factor, antinuclear antibody, and thyroid function tests
- Further imaging studies such as CT scans of the chest, abdomen, and pelvis may be necessary to identify occult infections or malignancies, as recommended by 1
- Specialized tests based on clinical suspicion might include echocardiography for endocarditis, bone marrow biopsy for hematologic malignancies, or temporal artery biopsy for giant cell arteritis in elderly patients
- The use of [18F]FDG PET/CT has a high diagnostic yield in both FUO and inflammation of unknown origin (IUO), as stated in 1 Throughout the workup, it's essential to avoid empiric antibiotics unless there is clear evidence of bacterial infection, as this can mask the underlying cause, and the approach should be guided by the patient's age, risk factors, and clinical presentation, with referral to specialists if the diagnosis remains elusive after initial evaluation.
From the Research
Diagnostic Workup for Pyrexia (Fever) of Unknown Origin (FUO)
The diagnostic workup for FUO in a primary care setting involves a comprehensive approach to identify the underlying cause of the fever. The following steps are recommended:
- A thorough history and physical examination to help narrow potential etiologies 2, 3, 4, 5
- Initial testing should include an evaluation for infectious etiologies, malignancies, inflammatory diseases, and miscellaneous causes such as venous thromboembolism and thyroiditis 2
- Laboratory tests, including erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) levels, to help identify potential causes 2
- Imaging studies, such as computed tomography (CT) or magnetic resonance imaging (MRI), may be useful in reaching a diagnosis 2, 4
- If noninvasive diagnostic tests are unrevealing, invasive tests such as tissue biopsy may be necessary to reach a diagnosis 2
- A focused, clue-directed approach to the workup, based on characteristic history and physical examination findings, as well as key nonspecific test abnormalities 5
Categories of Potential Etiology
The potential etiologies of FUO can be categorized into:
- Infections 2, 3, 4, 6
- Malignancies 2, 3, 4, 6
- Noninfectious inflammatory diseases 2, 3, 4, 6
- Miscellaneous causes, such as drug fevers and internal medicine diseases 2, 6