Steroid Therapy in EBV Infection
Primary Indication: EBV-Associated Hemophagocytic Lymphohistiocytosis (HLH)
Corticosteroids are indicated for EBV infection primarily when it triggers hemophagocytic lymphohistiocytosis (HLH), not for uncomplicated infectious mononucleosis. 1, 2
Dosing for EBV-HLH
For less severe or improving EBV-HLH:
- Prednisolone 1-2 mg/kg/day OR
- Dexamethasone 5-10 mg/m²/day 1, 2
- Consider adding IVIG 1.6 g/kg over 2-3 days 1, 2
- This conservative approach is justified when clinical manifestations are improving 1
For rapidly deteriorating EBV-HLH:
- Initiate dexamethasone 5-10 mg/m²/day immediately 2
- Add etoposide according to HLH-94 protocol without delay 1, 2
- Add rituximab 375 mg/m² weekly for 2-4 doses to clear B-cell EBV reservoir 1, 2
- Mortality ranges from 20-88% without prompt treatment 1, 3
Critical Diagnostic Threshold
- EBV DNA levels >10³ copies/mL are clinically relevant for EBV-HLH development 1, 3
- Monitor ferritin, soluble CD25, cell counts, and EBV DNA to guide treatment intensity 1, 2
Secondary Indications: Specific EBV Complications
Severe Thrombocytopenia
- Methylprednisolone (dose not specified in guidelines, but case reports used IV formulation) 4
- Reserved for platelet counts causing bleeding diathesis 4
EBV-Associated CNS Vasculopathy
- Corticosteroids are recommended for stroke-like episodes following VZV infection with vasculopathy 1
- Example regimen: prednisolone 60-80 mg daily for 3-5 days 1
- Note: This recommendation is for VZV vasculopathy, but the principle may apply to EBV-associated CNS vasculitis 5
Chronic Active EBV (CAEBV) with Granulomatous Hepatitis
- Prednisone may provide symptomatic relief 6
- However, hematopoietic stem cell transplantation is the only curative treatment for severe CAEBV 7
When Steroids Are NOT Indicated
Uncomplicated infectious mononucleosis does NOT require corticosteroids. 8, 9
Common Pitfalls to Avoid:
- Do not use steroids for routine pharyngitis, fever, or lymphadenopathy from EBV 8
- NSAIDs (tiaramide, loxoprofen) may be more appropriate for symptomatic relief in uncomplicated cases 9
- Antivirals (acyclovir, ganciclovir) are NOT effective for EBV and should not be used 2, 7
- In immunocompromised patients on steroids/MTX, EBV reactivation may worsen, requiring reduction of immunosuppression rather than escalation 7, 5
Treatment Algorithm
Step 1: Identify the clinical syndrome
- HLH features (fever, cytopenias, hepatosplenomegaly, ferritin >500, low fibrinogen)? → Proceed to Step 2 1
- Isolated severe complication (thrombocytopenia, CNS vasculitis)? → Consider targeted steroid therapy 1, 4
- Uncomplicated mononucleosis? → Supportive care only, no steroids 8, 9
Step 2: Assess EBV-HLH severity
- Rapidly deteriorating or treatment-naive with severe disease? → Dexamethasone 5-10 mg/m² + etoposide + rituximab 1, 2
- Less severe or improving? → Prednisolone 1-2 mg/kg or dexamethasone 5-10 mg/m² ± IVIG 1, 2
Step 3: Monitor response
- Track ferritin, soluble CD25, cell counts, EBV DNA weekly 1, 2
- EBV DNA decrease of ≥1 log₁₀ in first week indicates response 2
- Adjust rituximab doses (1-4 total) based on EBV DNA clearance 2
Key Warnings
- Never delay HLH treatment while awaiting viral test results - mortality is 20-88% without prompt therapy 1, 3
- 40-70% of adult HLH is malignancy-associated (especially lymphoma), not viral - maintain high suspicion and pursue tissue diagnosis if unclear 3
- Immunosuppressive therapy (steroids, MTX) may paradoxically worsen EBV reactivation in some contexts 7, 5
- Contact an HLH reference center for refractory or complex cases 1, 2