Results of a heterophile antibody screen were normal. Serological testing revealed an elevated level of IgM antibody to viral capsid antigen (VCA), consistent with a diagnosis of Epstein-Barr virus (EBV) infectious mononucleosis.
INCIDENCE AND ETIOLOGY
Infectious mononucleosis causes viral pharyngitis through proliferation of EBV in the nasopharynx, frequently producing asymptomatic infection in children (50% seroconversion by age 5 years).1,2 Infected college-aged adults usually are symptomatic with fever, sore throat, lymphadenopathy, and fatigue—12% of them seroconvert each year.1-3 EBV proliferates in the nasopharynx, is shed in oropharyngeal and other secretions (including those from the uterine cervix), and is highly contagious. Infected B-cell blasts produce acute heterophile antibodies that are diagnostic in 90% of cases; this IgM response includes antibodies to VCA. The humoral response switches over 3 to 6 weeks to IgG antibodies that target viral proteins or nuclear antigens; these antibodies persist as evidence of past infection and are found in the majority of adults.1-3
Countering the spread of EBV-infected B cells are the CD8+ cytotoxic T lymphocytes with atypical morphology.2 An efficient T-cell response suppresses the primary EBV infection and enforces transition of B-cell blasts to B memory cells that persist in the oropharyngeal saliva and are detectable in 15% to 25% of healthy adults. Failure of the T-cell response allows uncontrolled B-cell proliferation that can lead to B-cell lymphomas and other EBV-associated conditions (see below).4-8
DIFFERENTIAL DIAGNOSIS
Cytomegalovirus, herpesvirus, adenovirus, HIV, hepatitis B virus, and rubella virus infections can produce fever, pharyngitis, and lymphadenopathy similar to that of infectious mononucleosis; group A streptococcal pharyngitis and even parasitic disease, such as Toxoplasma gondii infection, can also produce these findings.1-8 EBV infection can present with other clinical findings that may include the peripheral rash of Gianotti-Crosti syndrome; the fever, lymphadenopathy, and maculopapular rash of hemophagocytic syndrome; and the fever, cervical lymphadenopathy, and fatigue of Kikuchi necrotizing lymphadenitis.4-8
DIAGNOSIS
Infectious mononucleosis is diagnosed primarily on the basis of the clinical presentation of fever, sore throat, tonsillar enlargement/exudates, generalized lymphadenopathy, erythematous maculopapular rash, and—in teens or adults—a palpable spleen.1,2 Fatigue lasting weeks to months differentiates mononucleosis from streptococcal pharyngitis.2,6
Diagnostic laboratory results may include leukocytosis of 70% or more with lymphocytes of atypical morphology in the peripheral blood smear.3 Elevated liver enzyme levels, mild to moderate thrombocytopenia without purpura, and hemolytic anemia may also be found. Results of the monospot test are unreliable in children younger than 4 years, necessitating a test panel including quantitative heterophile and IgM antibody to VCA, as in this patient.1-3 EBV nuclear antigens appear later and, along with IgG antibodies, may reflect past seroconversion rather than acute infection.2,3
Serological studies help distinguish infectious mononucleosis from other illnesses in the differential diagnosis. However, bone marrow and other studies to rule out leukemia or lymphoma may be considered in the presence of severe thrombocytopenia, hemolytic anemia, persisting unusual lymphocytes, and/or lymphadenopathy.5-8
Newer diagnostic technologies include quantitative measure of EBV viral load in blood or tissues using the polymerase chain reaction assay.2,3 This is helpful in patients with immune suppression, such as those with EBV-associated cancers (eg, Hodgkin disease, nasopharyngeal carcinoma) and AIDS patients with brain lymphomas.7 Detection of EBV-encoded RNA or proteins in tissues by in situ hybridization can complement viral load studies and is particularly useful in patients with posttransplant lymphoproliferative disorder.3
COMPLICATIONS
Airway compromise and breathing difficulties from swollen tonsils and lymphadenopathy may necessitate hospitalization during the acute phase of illness. Administration of a corticosteroid burst (eg, 1 mg/kg of prednisolone(Drug information on prednisolone) every 12 hours for 5 days) may be considered to minimize the hospital stay.9,10
Subcapsular splenic hemorrhage or splenic rupture can occur during the second week of infection. Fortunately, these are rare in children and can be managed conservatively in hemodynamically stable patients using activity limitations, serial CT scans, and monitoring in the pediatric ICU.11
Chronic fatigue syndrome—a complication more common and severe in adolescent girls—may develop within 24 months of EBV infection.6 EBV-related malignancies, including B-cell lymphomas and B-cell lymphoproliferative syndromes (in patients with poor T-cell response), Burkitt lymphoma, nasopharyngeal carcinoma, Hodgkin disease, T-cell lymphomas, and gastric carcinoma, usually occur several years after infection.7 No prophylactic or therapeutic vaccine is yet available for EBV-related malignancies.7
A transient erythematous maculopapular rash located mainly on the torso and upper extremities may occur after amoxicillin administration.12 This rash may unmask the diagnosis, as was the case in this infant (Figure). Her rash was probably associated with the EBV infection and exacerbated by the amoxicillin; her caregivers insisted that the rash was present before amoxicillin administration. She was given symptomatic therapy with analgesics and hydration after discontinuation of the amoxicillin. A call to the parents the next day confirmed that the rash and fever had begun to resolve.
