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For further information, see CMDT Part 32-01: 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 (Monospot)

  • Atypical large lymphocytes in blood smear; lymphocytosis

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

General Considerations

  • 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 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 of EBV 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

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

    • Transient bilateral upper lid edema (Hoagland sign)

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

  • Conjunctival hemorrhage, exudative pharyngitis, uvular edema, tonsillitis, or gingivitis may occur

  • Soft palatal petechiae may be noted

  • Other manifestations

    • Hepatitis

    • Interstitial pneumonitis (sometimes with pleural involvement)

    • Cholestasis

    • Gastritis

    • Kidney disease (mostly interstitial nephritis)

    • Epiglottitis

    • Nervous system involvement (in 1–5%)

Differential Diagnosis

  • Cytomegalovirus infection

  • Toxoplasmosis

  • Acute HIV infection

  • Secondary syphilis

  • HHV-6 infection

  • Rubella

  • Drug hypersensitivity reactions


  • Diagnosis is made based on characteristic manifestations and serologic evidence of infection (the heterophile sheep cell agglutination [HA] antibody tests or the correlated mononucleosis spot test [Monospot])

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


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

  • NSAIDs or acetaminophen and warm saline throat irrigations or gargles three or four times daily can manage symptoms

  • If a throat culture grows β-hemolytic streptococci, a 10-day course of penicillin or azithromycin is indicated

  • Corticosteroid therapy is reserved for impending airway obstruction from enlarged lymph nodes, hemolytic anemia, and severe thrombocytopenia



  • Secondary bacterial pharyngitis can occur and is often streptococcal

  • Splenic rupture (0.5–1%) is a rare but dramatic complication, and a history of preceding trauma can be elicited in 50% of the cases

  • Calculous cholecystitis, acute liver failure with massive necrosis, pericarditis and myocarditis are also infrequent complications


  • Hand washing after ...

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