What initial investigations should be done for a patient presenting with fever and lymphadenopathy?

Initial Investigations for Fever and Lymphadenopathy

The initial investigations for a patient presenting with fever and lymphadenopathy should include complete blood count with differential, blood cultures, comprehensive metabolic panel, chest X-ray, and appropriate serological testing based on epidemiological risk factors. 1

Basic Laboratory Investigations

First-line Tests

• Complete blood count (CBC) with differential
  • Look for: lymphopenia (viral infections, HIV, typhoid), eosinophilia (parasitic infections), thrombocytopenia (malaria, dengue, acute HIV) 1
• Blood cultures (two sets)
  • Essential to identify bacteremia, particularly important if typhoid is suspected (sensitivity up to 80%) 1
• Comprehensive metabolic panel
  • Liver function tests to assess for hepatitis or liver involvement 1
  • Renal function tests to evaluate kidney function
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
  • Elevated in inflammatory and infectious conditions 1
• Lactate dehydrogenase (LDH)
  • May be elevated in malignancies, particularly lymphomas 1

Serological Testing

• HIV testing
  • Should be offered to all patients with unexplained lymphadenopathy and fever 1, 2
• EBV serology (monospot test and/or EBV-specific antibodies)
  • Particularly important in patients with prominent pharyngitis and posterior cervical lymphadenopathy 2
• CMV serology
  • Consider in mononucleosis-like syndrome with negative EBV testing 2
• Additional serological tests based on epidemiological risk:
  • Brucella serology for those with animal exposure or consumption of unpasteurized dairy 1
  • Dengue serology for travelers to endemic areas 1
  • Toxoplasmosis serology

Imaging Studies

• Chest X-ray
  • Indicated for all patients with fever and lymphadenopathy to evaluate for hilar/mediastinal lymphadenopathy, pulmonary infiltrates, or masses 1
• Ultrasound of affected lymph node regions
  • Helpful to characterize lymphadenopathy and guide potential biopsy 1
• CT scan of neck, chest, abdomen, and pelvis with contrast
  • Consider when lymphoma or disseminated infection is suspected 1
• PET/CT scan
  • Consider when malignancy is suspected, particularly lymphoma 1

Specialized Testing

Lymph Node Evaluation

• Excisional lymph node biopsy
  • Gold standard for diagnosis of lymphoma and other causes of persistent lymphadenopathy 1
  • Core needle biopsy may be adequate in some cases 1
  • Fine-needle aspiration is generally insufficient except in specific circumstances 1

Microbiological Testing

• Tuberculosis testing
  • Tuberculin skin test or interferon-gamma release assay
  • Consider in patients with risk factors or from endemic areas 1
• Malaria testing
  • Blood films and rapid diagnostic tests for patients with travel to endemic areas 1

Algorithm Based on Clinical Presentation

For Acute Presentation (<2 weeks)

1. CBC, blood cultures, basic metabolics, LFTs, ESR/CRP
2. Chest X-ray
3. Monospot test/EBV serology
4. HIV testing
5. Consider empiric treatment for bacterial infection if clinically indicated

For Subacute/Chronic Presentation (>2 weeks)

1. All tests from acute presentation
2. CT scan of affected regions
3. Additional serologies based on exposure history
4. Consider lymph node biopsy if diagnosis remains unclear after initial testing

Special Considerations

Travel History

• For returning travelers, include specific testing based on geographic exposure:
  • Malaria testing for travelers to endemic areas
  • Dengue, chikungunya for appropriate travel history
  • Parasitic infections (filariasis, schistosomiasis) based on exposure 1

Immunocompromised Patients

• More aggressive initial workup including:
  • Blood cultures from all central venous catheter lumens 1
  • Consider fungal cultures and serology
  • Lower threshold for CT imaging and biopsy

Common Pitfalls to Avoid

1. Premature diagnosis of viral syndrome - Always consider serious bacterial infections and malignancies
2. Failure to obtain adequate blood cultures - Ensure proper volume and timing
3. Missing travel and exposure history - Critical for identifying tropical and zoonotic infections
4. Delaying lymph node biopsy - Consider early in cases of persistent unexplained lymphadenopathy
5. Overlooking HIV - Test all patients with unexplained fever and lymphadenopathy

By following this systematic approach to investigating fever and lymphadenopathy, clinicians can efficiently identify the underlying cause and initiate appropriate management to improve patient outcomes.