What is the recommended management for a young adult or adolescent diagnosed with Epstein Barr virus (EBV) infection, presenting with symptoms such as fever, sore throat, and lymphadenopathy?

Management of Epstein-Barr Virus Infection in Adolescents and Young Adults

For immunocompetent adolescents and young adults with typical EBV infectious mononucleosis (fever, sore throat, lymphadenopathy), provide symptomatic treatment only—no antivirals, no antibiotics, and no corticosteroids are indicated for uncomplicated cases. 1, 2

Initial Clinical Assessment

Key Diagnostic Features to Identify

• Classic triad: Fever, pharyngitis with tonsillar enlargement, and cervical lymphadenopathy 1
• Additional findings: Fatigue, palatal petechiae, hepatosplenomegaly 1, 2
• Laboratory confirmation: Heterophile antibody test (71-90% accuracy, but 25% false-negative in first week) 1
• Supporting lab finding: Lymphocyte count >4,000/mm³ makes IM likely; <4,000/mm³ makes it unlikely 1

Critical Red Flags Requiring Further Evaluation

• Persistent high-grade fever beyond 10 days warrants evaluation for chronic active EBV (CAEBV) or hemophagocytic lymphohistiocytosis (HLH) 3, 4
• Immunocompromised status (transplant recipients, HIV, immunosuppressive therapy) requires aggressive workup for EBV-associated post-transplant lymphoproliferative disorder (PTLD) 5, 6
• Severe gastrointestinal symptoms in immunocompromised patients mandate urgent endoscopy with biopsy 6

Standard Management for Uncomplicated Cases

Symptomatic Treatment Only

• Pain and fever control: Acetaminophen or NSAIDs 1
• Adequate hydration and rest 1, 2
• Avoid antibiotics: Do not prescribe antibiotics empirically, as they provide no benefit and amoxicillin specifically causes severe rash in 80-90% of EBV patients 5, 1
• No antivirals: Acyclovir, ganciclovir, and foscarnet have no proven efficacy in primary EBV infection 6, 1
• No corticosteroids: Glucocorticoids do not reduce length or severity of illness in uncomplicated cases 1

Activity Restrictions

• Restrict physical activity for 3 weeks from symptom onset to reduce risk of splenic rupture 1
• No contact sports or heavy lifting during this period 1

Management of Complicated or Atypical Presentations

When Fever Persists Beyond 10 Days

Order the following diagnostic workup immediately: 3, 4

• Quantitative EBV PCR on whole blood (>10^2.5 copies/μg DNA in peripheral blood mononuclear cells suggests CAEBV) 3, 4
• EBV-specific antibody patterns: VCA-IgG ≥1:640 AND EA-IgG ≥1:160 characteristic of CAEBV 3, 4
• Ferritin level: >1,000 ng/mL suggests HLH 3
• Cytokine analysis if HLH suspected 3
• Bone marrow examination may be necessary if HLH suspected to look for hemophagocytosis 3

Immunocompromised Patients

These patients require fundamentally different management: 5, 6

• Immediate reduction or discontinuation of immunosuppression if clinically feasible 6
• Prospective weekly EBV DNA monitoring starting within first month and continuing for at least 4 months post-transplant 5, 4
• Urgent endoscopy with biopsy if gastrointestinal symptoms present (histology with EBER in situ hybridization mandatory) 5, 6
• Rituximab 375 mg/m² once weekly is first-line therapy for proven or probable EBV-PTLD 6
• Pre-emptive rituximab may be considered for rising viral loads before clinical disease develops 4

Critical Pitfalls to Avoid

Medication Errors

• Never prescribe amoxicillin or ampicillin to patients with suspected EBV—this causes severe rash in the majority of patients 5
• Do not use antivirals for primary EBV infection in immunocompetent patients, as they have no proven benefit 6, 1
• Avoid routine corticosteroids, as they do not improve outcomes and may increase infection risk 1

Diagnostic Errors

• Do not assume all EBV infections are self-limiting—persistent symptoms beyond 3 months require formal evaluation for CAEBV 3, 4
• Do not misinterpret serology: Positive VCA-IgG, EBNA-IgG, and EA antibodies together represent resolved infection with possible non-specific immune activation, NOT reactivation 4
• Do not overlook HLH, which is rare but life-threatening and requires prompt immunosuppressive therapy 3

Special Population Considerations

• EBV-seronegative adolescents and young adults on thiopurines: While there is insufficient evidence to absolutely avoid thiopurines, be aware of increased risk of hemophagocytic lymphohistiocytosis (80% of pediatric HLH cases are EBV-related with thiopurine exposure) 5
• Children have highest risk of airway obstruction, which is the most common cause of hospitalization from IM 1

When to Hospitalize

• Severe airway compromise from tonsillar enlargement (most common in children) 1
• Inability to maintain oral hydration 1
• Suspected splenic rupture (abdominal pain, hypotension, tachycardia) 1
• Suspected HLH or CAEBV requiring aggressive immunomodulatory therapy 3
• Immunocompromised patients with suspected PTLD 5, 6

Prognosis and Long-Term Considerations

• Most immunocompetent patients recover completely within weeks to months without sequelae 1, 2
• CAEBV carries poor prognosis and can progress to T-cell or NK-cell malignant lymphomas 3, 4
• Long-term EBV infection is associated with nasopharyngeal carcinoma and lymphomas in general population 2