From the Guidelines
The initial workup for pyrexia of unknown origin (PUO) should include a comprehensive approach starting with a detailed history and physical examination, followed by basic laboratory tests and imaging studies, with the consideration of advanced tests like FDG-PET/CT if initial studies are inconclusive, as suggested by recent guidelines 1. The workup for PUO involves a step-wise approach to identify the underlying cause, which can be categorized into infections, malignancies, autoimmune disorders, or miscellaneous conditions. Initially, basic laboratory tests including complete blood count, comprehensive metabolic panel, urinalysis, blood cultures, and inflammatory markers (ESR, CRP) should be performed.
- Chest X-ray and abdominal imaging are essential initial radiographic studies.
- If these are inconclusive, more advanced testing should follow, including CT scans of chest/abdomen/pelvis, echocardiography to rule out endocarditis, and specialized serological tests for infections like tuberculosis, HIV, and autoimmune conditions. Treatment initially focuses on supportive care with antipyretics such as acetaminophen (500-1000mg every 6 hours, not exceeding 4g daily) or ibuprofen (400-600mg every 6-8 hours with food) 1.
- Empiric antibiotics are generally avoided unless there are signs of sepsis or immunocompromise, in which case broad-spectrum coverage (such as piperacillin-tazobactam 4.5g IV every 8 hours plus vancomycin dosed by weight) may be initiated after cultures are obtained. The use of FDG-PET/CT has been shown to have a high diagnostic yield in cases of fever and inflammation of unknown origin, particularly when initial studies are inconclusive, as highlighted in the EANM/SNMMI guideline for [18F]FDG hybrid PET use in infection and inflammation in adults 1.
- The diagnostic yield and helpfulness of FDG-PET/CT are usually preferred over sensitivity and specificity in these clinical settings. It is crucial to approach the workup of PUO systematically, avoiding premature treatment that may mask the underlying diagnosis and complicate management, emphasizing the importance of patience and a thorough investigation 1.
From the Research
Initial Workup for Pyrexia of Unknown Origin
The initial workup for pyrexia of unknown origin (PUO) involves a systematic clinical approach to investigation and management of patients 2. This includes:
- Taking a detailed medical history
- Conducting comprehensive physical assessments
- Performing various standard laboratory tests and imaging procedures
Causes of Pyrexia of Unknown Origin
The causes of PUO are broadly divided into four groups:
- Infective
- Inflammatory
- Neoplastic
- Miscellaneous 2
Diagnostic Strategies
Diagnostic strategies for PUO may include the use of positron emission tomography-computed tomography (PET-CT) and new molecular and serological tests for infection 2. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) is an important emerging modality in the workup of PUO, supporting the final diagnosis in 38% of patients and being diagnostic in 6.4% of patients 3.
Specific Considerations
Subacute thyroiditis should be considered in the diagnostic workup of PUO, even in the absence of overt toxic symptoms of thyroid hormone excess 4. Other rare causes of PUO, such as non-Hodgkin's lymphoma, may also present with unique and uncommon symptoms 5.
Treatment Approach
The treatment approach for PUO depends on the underlying cause, which may not always be identifiable despite extensive medical evaluation 5. In some cases, low-dose steroids may be effective, as seen in the treatment of subacute thyroiditis 4.