Persistent High-Grade Fever in a 10-Year-Old Girl with EBV
A 10-year-old girl with persistent high-grade fever 10 days after EBV diagnosis should be evaluated for chronic active EBV infection (CAEBV) or other EBV-associated complications such as hemophagocytic lymphohistiocytosis (HLH). 1
Possible Causes of Persistent Fever
- Chronic Active EBV Infection (CAEBV): Characterized by persistent or recurrent infectious mononucleosis-like symptoms, unusual patterns of anti-EBV antibodies, and increased EBV genomes in affected tissues 1, 2
- Hemophagocytic Lymphohistiocytosis (HLH): An EBV-triggered hyperinflammatory syndrome with persistent fever, cytopenias, and extremely elevated ferritin levels (>1000 ng/mL) 1, 2
- Secondary bacterial infection: Can occur during recovery from primary EBV infection 1
- EBV meningoencephalitis: Though relatively rare in immunocompetent children, can present with high-grade fever and neurological symptoms 3
- EBV reactivation: Can occur under conditions of psychological stress with weakened cellular immunity 4
Diagnostic Approach
Initial Laboratory Tests
- Complete EBV serologic panel: Check VCA IgM, VCA IgG, and EBNA antibodies to distinguish between primary acute infection and reactivation 5
- Quantitative EBV PCR: Viral loads of more than 10^2.5 copies/μg DNA in peripheral blood mononuclear cells suggest CAEBV 1
- Ferritin level: Significantly elevated ferritin (>1000 ng/mL) is a key marker for EBV-associated HLH 2
- Complete blood count: To assess for cytopenias (particularly thrombocytopenia) 6
- Liver function tests: To evaluate for hepatitis, which can have a prolonged course in EBV infection 6
Additional Evaluations
- Immunological studies: Including lymphocyte subset analysis (B cells, CD8+ T cells) to assess immune response 7
- Cytokine analysis: Elevated inflammatory cytokines may indicate HLH or CAEBV 1
- Bone marrow examination: If HLH is suspected, to look for hemophagocytosis 1
Management Considerations
- For CAEBV: Patients often have poor prognosis and may require aggressive immunomodulatory therapy 1
- For HLH: Requires prompt recognition and treatment with immunosuppressive therapy, potentially including corticosteroids 1, 2
- For persistent EBV with autoimmune manifestations: Consider the connection between chronic EBV and autoimmune disease development 8
Important Clinical Pearls
- Persistent fever beyond 10 days after EBV diagnosis is not typical of uncomplicated primary EBV infection and warrants further investigation 1
- Children with reactivated EBV infection are more prone to multi-systemic damage compared to those with primary infection 7
- EBV can trigger autoimmune-like conditions that may present with persistent fever 2, 8
- The combination of persistent fever, lymphadenopathy, and hepatosplenomegaly is particularly concerning for CAEBV 1
Common Pitfalls to Avoid
- Assuming all EBV infections are self-limiting: While most primary EBV infections resolve without complications, persistent symptoms require thorough evaluation 1
- Missing neurological involvement: EBV can cause meningoencephalitis even in immunocompetent children 3
- Overlooking HLH: This life-threatening complication requires prompt diagnosis and treatment 1, 2
- Failing to consider chronic active EBV: This condition is rare but serious and should be considered in cases of persistent symptoms 1