Infectious Mononucleosis: Clinical Features, Management, and Prevention

Infectious mononucleosis (IM) is a clinical syndrome caused primarily by Epstein-Barr virus (EBV) (90% of cases), a herpesvirus transmitted via saliva ("kissing disease"). Peak incidence: adolescents/young adults.

Clinical Presentation

• Classic triad: Fever, pharyngitis (exudative tonsillitis), cervical lymphadenopathy (posterior > anterior).
• Fatigue: Profound, often disproportionate; may persist weeks–months.
• Splenomegaly: 50% (palpable); risk of rupture (rare, ~0.1–0.5%).
• Hepatitis: Mild transaminitis (AST/ALT 2–3× ULN) in 80–90%; jaundice <5%.
• Rash: Maculopapular (5–15%); ampicillin/amoxicillin-induced rash in 80–100% if given (not allergy).
• Atypical lymphocytes: >10% on peripheral smear (activated CD8+ T cells).

Diagnosis

• Heterophile antibody test (Monospot®): Rapid, specific (~85%), insensitive early (<70% week 1). False + in lymphoma, other infections.
• EBV-specific serology: VCA-IgM (acute), VCA-IgG (past/acute), EBNA-IgG (past, appears 2–4 months). Definitive.
• CBC: Lymphocytosis with atypical lymphs; mild thrombocytopenia.

Management (Supportive)

• No antiviral (acyclovir reduces shedding but not clinical course).
• Rest: As needed; strict bed rest not required.
• Hydration, analgesia: Acetaminophen/NSAIDs for fever/pain.
• Corticosteroids (prednisone): Only for airway obstruction (massive tonsillar hypertrophy), severe hemolytic anemia, thrombocytopenia, neurologic complications.
• Activity restriction: No contact sports / heavy lifting × 3–4 weeks (splenic rupture risk). Gradual return.

Complications

• Splenic rupture (emergency).
• Airway obstruction.
• Neurologic: encephalitis, meningitis, Guillain-Barré, transverse myelitis.
• Hematologic: autoimmune hemolytic anemia, ITP, DIC.
• X-linked lymphoproliferative syndrome (SH2D1A mutation) — fatal IM in males.

Prevention

• No vaccine (EBV vaccine in trials).
• Avoid sharing saliva-contaminated items (drinks, utensils, toothbrushes).
• Hand hygiene.

Return to Play/Activity

• Asymptomatic + afebrile × 48h + no splenomegaly on US (or 3–4 weeks if no US).
• Gradual progression over 7–10 days.

Most recover fully in 2–4 weeks; fatigue may linger 2–3 months. Chronic fatigue syndrome develops in ~10%.