What is the typical symptom progression of Epstein-Barr Virus (EBV) infection?

Typical Symptom Progression of Epstein-Barr Virus (EBV) Infection

EBV infection typically begins with a 6-week incubation period followed by fever, sore throat, fatigue, lymphadenopathy, and atypical lymphocytosis, with symptoms gradually resolving over 2-4 weeks in most immunocompetent individuals. 1

Initial Phase and Incubation Period

• Unlike most viral illnesses, EBV has an unusually long incubation period of approximately 6 weeks 2
• During this time, patients are typically asymptomatic while the virus establishes itself
• Viral shedding in oral secretions begins during late incubation period, often before symptoms appear

Prodromal and Acute Phase Symptoms

The classic symptom progression follows this pattern:

1. Early symptoms (Days 1-5):

   • Low-grade fever
   • Malaise and fatigue
   • Headache
   • Myalgia (muscle pain)

2. Peak symptoms (Days 5-14):

   • High fever (often persistent)
   • Severe sore throat with exudative pharyngitis/tonsillitis
   • Significant lymphadenopathy (particularly cervical)
   • Extreme fatigue and weakness
   • Development of atypical lymphocytosis in peripheral blood
   • Hepatosplenomegaly in many cases 3

3. Laboratory changes:

   • Heterophile antibodies become detectable 6-10 days after symptom onset
   • Peak antibody levels occur during 2nd-3rd week of illness 1
   • VCA IgM appears early in infection
   • VCA IgG may be positive in acute phase
   • EBNA antibodies appear weeks to months after initial infection 1

Resolution Phase

• Fever typically resolves within 10-14 days
• Lymphadenopathy and pharyngitis improve within 2-3 weeks
• Fatigue and malaise may persist for several weeks to months
• Splenomegaly gradually resolves over 3-4 weeks

Potential Complications

While most EBV infections resolve without complications, be alert for:

• Hematological complications:

  • Atypical lymphocytosis
  • Hemolytic anemia
  • Thrombocytopenia
  • Rarely, disseminated intravascular coagulation 4

• Hepatic involvement:

  • Mild to moderate elevation of liver enzymes is common
  • Rarely, cholestatic hepatitis 5

• Neurological complications:

  • Encephalitis
  • Meningitis
  • Guillain-Barré syndrome

• Other rare complications:

  • Splenic rupture (risk highest 2-3 weeks after symptom onset)
  • Acute acalculous cholecystitis 6
  • Hemophagocytic lymphohistiocytosis (HLH) 5
  • Airway obstruction from severe tonsillar hypertrophy

Chronic Active EBV Infection

In rare cases, patients may develop chronic active EBV infection (CAEBV), characterized by:

• Persistent or recurrent infectious mononucleosis-like symptoms for >6 months
• Elevated EBV antibody titers (VCA IgG ≥1:640, EA IgG ≥1:160)
• Persistent fever, lymphadenopathy, hepatosplenomegaly
• Debilitating fatigue, sore throat, headache, myalgia, arthralgia
• Potential development of serious complications including hematological disorders and lymphoproliferative diseases 3

Important Clinical Considerations

• Activity restrictions (especially avoiding contact sports) are recommended for at least 3-4 weeks from symptom onset to prevent splenic rupture 1
• No specific antiviral treatment is indicated for immunocompetent individuals with uncomplicated EBV infection 1
• Supportive care with adequate hydration, rest, antipyretics, and analgesics is the mainstay of treatment 1
• Monitoring for rare but serious complications is essential, particularly in patients with severe or prolonged symptoms

The typical EBV infection is self-limited in immunocompetent hosts, but recognizing the characteristic symptom progression helps identify atypical presentations that may require further evaluation and management.