What viral illnesses should be tested for in a patient presenting with pancytopenia and fatigue?

Viral Testing for Pancytopenia and Fatigue

Test for Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), parvovirus B19, and HIV as the primary viral causes of pancytopenia with fatigue, with EBV-specific antibody testing (VCA IgM/IgG and EBNA) being the most important initial test in immunocompetent patients. 1

Primary Viral Testing Panel

Essential First-Line Tests

• EBV testing is the highest priority, as EBV is a well-established cause of pancytopenia and fatigue, particularly in adolescents and young adults 2, 1

  • Order EBV-specific antibody panel including VCA IgM, VCA IgG, and EBNA antibodies 1
  • VCA IgM positive with absent EBNA antibodies indicates recent primary infection 1
  • In immunocompromised patients, add quantitative EBV viral load by NAAT in peripheral blood 1

• Parvovirus B19 must be tested, as it directly causes aplastic effects on bone marrow leading to pancytopenia, especially in immunosuppressed patients 3

  • This is particularly critical as parvovirus B19 can cause severe, reversible pancytopenia 3

• CMV testing should be performed via serology and/or PCR, particularly in immunocompromised individuals 2

• HHV-6 testing requires both CSF and blood PCR to distinguish chromosomal integration from acute infection 2

• HIV testing is mandatory, as HIV-associated immunosuppression commonly causes pancytopenia 2

Geographic and Exposure-Based Testing

Travel History Considerations

• Dengue and Zika virus testing if patient has traveled to or lives in endemic areas within the past 2-3 weeks 2, 4

  • Perform both dengue and Zika NAAT on serum collected ≤7 days after symptom onset 2, 4
  • If >7 days post-symptom onset, perform IgM antibody testing followed by PRNT confirmation 2
  • Dengue commonly causes pancytopenia with leukopenia and thrombocytopenia 2

• Arbovirus testing (West Nile virus, others) based on geographic exposure and season 2

  • Serologic testing of serum and CSF preferred over molecular testing 2
  • WNV IgM in CSF has higher sensitivity (compared to 57% for CSF PCR) 2

Specific Exposure Testing

• VZV testing if vesicular rash present or history of varicella exposure 2

  • Both VZV PCR and antibody testing (IgG and IgM) from CSF and serum recommended 2

• Enterovirus testing via RT-PCR from respiratory specimens, stool, and CSF 5

  • Respiratory specimens are mandatory as certain enterovirus types are rarely detected in CSF or stool 5
  • Multiple specimens from different sites should be collected simultaneously 5

Testing Algorithm by Clinical Context

Immunocompetent Patients

1. Start with EBV-specific antibody panel (VCA IgM/IgG, EBNA) 1
2. Add parvovirus B19 serology/PCR 3
3. Test for CMV and HIV 2
4. Consider geographic/exposure-based testing (dengue, Zika, arboviruses) 2, 4

Immunocompromised Patients

1. Perform quantitative EBV viral load by NAAT in peripheral blood (not just serology) 1
2. Add CMV PCR and HHV-6/7 PCR from blood 2
3. Test for parvovirus B19 3
4. HIV testing if status unknown 2
5. Consider broader viral panel including VZV, enteroviruses 2, 5

Critical Pitfalls to Avoid

• Do not rely solely on heterophile antibody testing for EBV, as it has high false-negative rates, especially in children under 10 years 1
• Do not interpret positive enterovirus PCR from stool or throat as definitive causation, as enteroviruses colonize these sites for weeks to months after infection 5
• Do not perform arbovirus PCR alone without serology, as viremia typically peaks before symptom onset 2
• Do not delay testing for parvovirus B19 in immunosuppressed patients, as bone marrow suppression can be severe and potentially reversible 3
• Do not skip PRNT confirmation for positive flavivirus IgM results due to extensive cross-reactivity between dengue, Zika, and other flaviviruses 2, 4

Specimen Collection Priorities

• Collect serum as soon as possible after symptom onset for optimal viral detection 1, 4
• For enterovirus testing, collect respiratory specimens (nasopharyngeal aspirate or throat swab), stool, and CSF simultaneously 5
• For arbovirus testing, paired acute and convalescent sera (10-14 days apart) improve diagnostic accuracy 2
• Collect blood samples before administering any blood products or intravenous immunoglobulin 5