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For further information, see CMDT Part 34-02: Human Herpesviruses

KEY FEATURES

Essentials of Diagnosis

  • Malaise, fever, and (exudative) sore throat

  • Palatal petechiae, lymphadenopathy, splenomegaly, and, occasionally, a maculopapular rash

  • Positive heterophile agglutination test or mononucleosis spot test (Monospot)

  • Atypical large lymphocytes on peripheral blood smear; lymphocytosis

  • Complications: hepatitis, myocarditis, neuropathy, encephalitis, airway obstruction from adenitis, hemolytic anemia, thrombocytopenia

General Considerations

  • Epstein-Barr virus (EBV) is ubiquitous; infects > 95% of the adult population worldwide and persists for the person's lifetime

  • Infectious mononucleosis is a common manifestation of EBV infection and may occur at any age

  • EBV is largely transmitted by saliva but can also be recovered from genital secretions

  • Saliva may remain infectious during convalescence, for 6 months or longer after symptom onset

  • The incubation period lasts several weeks (30–50 days)

  • In the United States, the incidence of EBV infection is declining, although prevalence remains high for those aged 12–19 years

CLINICAL FINDINGS

Symptoms and Signs

  • Fever, sore throat, fatigue, malaise, anorexia, and myalgia typically occur in the early phase of the illness

  • Physical findings include

    • Petechiae on soft palate

    • Exudative pharyngitis, uvular edema, tonsillitis, or gingivitis

    • Lymphadenopathy (discrete, nonsuppurative, slightly painful, especially along the posterior cervical chain)

    • Transient bilateral upper lid edema (Hoagland sign); conjunctival hemorrhage

    • Splenomegaly (in up to 50% of patients, sometimes massive)

  • Other manifestations

    • Hepatitis

    • Interstitial pneumonitis (sometimes with pleural involvement)

    • Cholestasis

    • Gastritis

    • Kidney disease (most often, interstitial nephritis)

    • Epiglottitis

    • Nervous system involvement (in 1–5%)

Differential Diagnosis

  • Cytomegalovirus infection

  • Toxoplasmosis

  • Acute HIV infection

  • Secondary syphilis

  • Human herpes virus 6 (HHV-6) infection

  • Rubella

  • Drug hypersensitivity reactions

DIAGNOSIS

Laboratory Tests

  • Initial granulocytopenia followed within 1 week by lymphocytic leukocytosis with > 10% atypical lymphocytes

  • Hemolytic anemia (with antibodies) and thrombocytopenia occur occasionally

  • Serologic evidence of infection

    • Heterophile sheep cell agglutination (HA) antibody tests or the correlated Monospot test

    • Usually becomes positive within 4 weeks after onset of illness

    • Specific but often insensitive in early illness; may be absent in 20% of adults

    • Immunoglobulins

      • Immunoglobulin M (IgM) antibody to EB virus capsid antigen (VCA) rises and falls during acute illness

      • Immunoglobulin G (IgG) antibody to VCA rises and persists for life

      • IgG antibodies to EBV nuclear antigen (EBNA) appear after 4 weeks of onset and persist

  • Polymerase chain reaction (PCR) for EBV DNA is useful in the evaluation of malignancies associated with EBV

TREATMENT

  • No specific antiviral therapy is needed in more than 95% of patients with acute EBV-associated infectious mononucleosis

  • Non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen and warm saline gargles or throat irrigations three or four times daily can manage symptoms

  • If a throat culture also grows β-hemolytic streptococci, a 10-day course of penicillin or ...

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