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Key Features

  • Acute infection can occur at any age but is most common at age 10–35 years

  • Epstein-Barr virus (EBV) is the causative agent

  • Similar syndromes are caused by

    • Cytomegalovirus (CMV)

    • Acute HIV infection

    • Toxoplasmosis

  • EBV shows a strong serologic association with

    • HIV-related lymphomas

    • Nasopharyngeal carcinoma

    • Burkitt lymphoma

    • Oral hairy leukoplakia

    • Posttransplant lymphoproliferative disorder

Clinical Findings

  • Fever, sore throat common

  • Malaise, anorexia, myalgia are early findings

  • Lymphadenopathy very common

  • Transient bilateral upper-lid edema (Hoagland sign)

  • Splenomegaly (50%)

  • Maculopapular rash uncommon (15%), except in patients receiving ampicillin (90%)

  • Exudative pharyngitis, uvular edema, tonsillitis, or gingivitis may occur and soft palatal petechiae may be noted

  • Other manifestations

    • Hepatitis

    • Interstitial pneumonitis

    • Cholestasis

    • Gastritis

    • Acute interstitial nephritis

    • Nervous system involvement (mononeuropathies and occasionally aseptic meningitis, encephalitis, cerebellitis, peripheral and optic neuritis, transverse myelitis, or Guillain–Barré syndrome)

    • Kidney disease (mostly interstitial nephritis)

    • Epiglottitis

    • Pneumonia

    • Pleural involvement

    • Myocarditis

  • Secondary bacterial infections of the throat

  • Splenic rupture is rare but dramatic

  • Nonspecific ECG changes (5%)


  • Combination of sore throat, fever, fatigue, adenopathy, and splenomegaly suggests the diagnosis

  • Chronicity of pharyngitis makes infectious mononucleosis more likely than bacterial pharyngitis

  • Granulocytopenia with lymphocytosis, especially large, atypical lymphocytes

  • Hemolytic anemia and thrombocytopenia

  • Heterophil antibody and Monospot tests usually positive

  • Antibody (IgM) titers to early antigens including viral capsid antigen can be useful early in disease


  • 95% of patients recover without antiviral therapy

  • Acyclovir and other antiviral drugs are without verified clinical benefit

  • Chronic EBV syndromes are increasingly recognized, especially in immunodeficient persons (Duncan syndrome)

  • Hand washing after contact and avoidance of close personal contact with active cases is prudent

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