What laboratory tests are recommended for a patient with prolonged chronic fever?

Laboratory Tests for Prolonged Chronic Fever

For patients with prolonged chronic fever, a comprehensive diagnostic approach should include blood cultures, complete blood count with differential, inflammatory markers, liver function tests, and chest radiography as the initial investigations. 1

Initial Laboratory Investigations

• Blood Cultures:

  • Collect at least two sets (60 mL total) from different anatomical sites
  • Should be obtained before antibiotic administration
  • Essential for identifying bacteremia, especially in suspected endocarditis or vascular infections 1

• Complete Blood Count (CBC) with Differential:

  • Evaluates for leukocytosis, lymphopenia, thrombocytopenia, or eosinophilia
  • Abnormal white blood cell count and distribution can help distinguish infectious causes 1, 2
  • Note that up to 25% of patients with specific infections like Q fever may have increased leukocyte counts, while most maintain normal white blood cell counts 3

• Inflammatory Markers:

  • C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)
  • Particularly useful when bacterial infection probability is low to intermediate 1
  • Elevated levels suggest inflammatory processes but lack specificity 4

• Liver Function Tests:

  • Essential as hepatic involvement occurs in up to 85% of cases with certain infections like Q fever 3
  • May reveal increased liver enzyme levels, hyperbilirubinemia, or other abnormalities 1

Additional Testing

• Procalcitonin (PCT):

  • Consider when bacterial infection probability is low to intermediate and no clear focus is identified 1
  • More specific than CRP for bacterial infections

• Serology:

  • Store serum samples for potential later testing based on clinical evolution 1
  • For suspected chronic infections like Q fever, test phase I and II IgG and IgM antibodies 3
  • Consider paired samples (acute and convalescent) to demonstrate rising titers 3

• Nucleic Acid Detection:

  • PCR testing of whole blood for suspected pathogens
  • Particularly valuable early in the course of infection before antibody response develops 3

Imaging Studies

• Chest Radiography:

  • Standard investigation for all patients with fever 1
  • Rules out pneumonia and other thoracic pathologies

• Abdominal Ultrasound:

  • Consider if abdominal symptoms or abnormal liver function tests are present 1
  • Can identify hepatomegaly, splenomegaly, or other abdominal pathology

• Advanced Imaging:

  • CT scan for patients who have recently undergone thoracic, abdominal, or pelvic surgery 1
  • 18F-FDG PET/CT if initial evaluation is unrevealing and inflammatory markers remain elevated 4

Special Considerations

• Travel History:

  • For patients with recent travel to tropical regions, perform malaria testing (thick and thin blood films plus rapid diagnostic test) 1

• Invasive Testing:

  • If noninvasive tests are unrevealing, consider tissue biopsy (liver, lymph node, temporal artery, bone marrow) 4
  • Immunohistochemistry can detect pathogens in tissues even after antibiotic therapy 3

• Immunocompromised Patients:

  • More extensive workup may be needed
  • Consider specialized testing for opportunistic infections

Clinical Pitfalls to Avoid

• Relying solely on temperature patterns: Fever may not always be present in true infection, especially in elderly and immunocompromised patients 5

• Premature empiric antimicrobial therapy: This has not been shown effective for fever of unknown origin and may mask the underlying diagnosis 4

• Overlooking non-infectious causes: Up to 20% of prolonged fevers are due to non-infectious inflammatory diseases, malignancies, or miscellaneous causes 4, 2

• Inadequate follow-up: For patients with persistent fever, serologic monitoring at intervals of 3,6,12,18, and 24 months may be necessary, especially for those at risk of developing chronic infections 3

Remember that most cases of prolonged fever in adults occur because of uncommon presentations of common diseases, and up to 75% of cases will resolve spontaneously without reaching a definitive diagnosis 4. However, a systematic approach to laboratory testing is essential to identify potentially serious underlying conditions.