From the Guidelines
The management of pyrexia of unknown origin (PUO) should start with a thorough history and physical examination, followed by comprehensive laboratory testing and imaging, with a consideration for the use of [18F]FDG PET/CT scans for diagnostic purposes, as recommended by the most recent guideline 1. The approach to managing a case of pyrexia of unknown origin (PUO) involves a systematic and iterative process. Key steps include:
- A thorough history and physical examination to identify potential causes and guide further investigations
- Comprehensive laboratory testing, including complete blood count, liver function tests, blood cultures, urinalysis, and inflammatory markers like ESR and CRP
- Initial imaging with chest X-ray, abdominal ultrasound, and possibly CT scans of the chest, abdomen, and pelvis
- Consideration of more specialized tests if initial investigations are inconclusive, such as echocardiography, bone marrow examination, serological tests for autoimmune conditions and specific infections, and [18F]FDG PET/CT scans, which have been shown to have a high diagnostic yield in cases of fever and inflammation of unknown origin 1
- Empiric antibiotic therapy is generally not recommended unless there are signs of sepsis or immunocompromise, as suggested by earlier guidelines 1, 1
- Antipyretics like acetaminophen or ibuprofen can be used for symptomatic relief while investigations are ongoing The diagnostic approach should be iterative, with regular reassessment of the patient's condition and response to any interventions, considering that PUO can result from a wide range of conditions, including infectious, inflammatory, neoplastic, and miscellaneous categories 1.
From the Research
Approach to Managing Pyrexia of Unknown Origin (PUO)
The approach to managing a case of pyrexia (fever) of unknown origin (PUO) involves a systematic clinical approach to investigation and management of patients. The following steps can be taken:
- Identify the subgroup of PUO, which can be classical, nosocomial, neutropenic, HIV-related, or elderly, as each subgroup requires different investigative strategies 2
- Divide the causes of PUO into four groups: infective, inflammatory, neoplastic, and miscellaneous 2
- Use early positron emission tomography-computed tomography (PET-CT) and new molecular and serological tests for infection to improve diagnostic capability 2, 3
- Consider potential second-line investigations when the aetiology is unclear, such as thyroid function tests to rule out subacute thyroiditis 4
- Be aware of the diverse etiology and diagnostic challenges of PUO, and consider unique presentations and diagnostic dilemmas 5
Diagnostic Challenges
Despite adequate investigations, up to 50% of patients with PUO may still have no cause found for their fever 2. However, the cohort of undiagnosed patients has a good prognosis 2. A structured approach to investigation and management, including the use of complex modern techniques such as PET-CT, can help to provide a diagnosis for patients with PUO 3.
Investigation and Management
The investigation and management of PUO should be tailored to the individual patient, taking into account their medical history, physical assessment, and laboratory test results. Immunocompromised individuals, those with HIV infection, and patients admitted to hospital for other reasons with persistent or unexplained fever represent distinct subgroups that require different approaches to investigation and management 6.