(Infectious Mononucleosis)

Infectious mononucleosis manifests typically as fever, exudative pharyngitis, lymphadenopathy, hepatosplenomegaly, and atypical lymphocytosis. The spectrum of diseases is wide, ranging from asymptomatic to fatal infection. Infections commonly are unrecognized in infants and young children. Rash can occur and is more common in patients treated with ampicillin as well as with other penicillins. Central nervous system (CNS) complications include aseptic meningitis, encephalitis, myelitis, optic neuritis, cranial nerve palsies, transverse myelitis, and Guillain-Barré syndrome. Hematologic complications include splenic rupture, thrombocytopenia, agranulocytosis, hemolytic anemia, and hemophagocytic lymphohistiocytosis (HLH, or hemophagocytic syndrome). Pneumonia, orchitis, and myocarditis are observed infrequently. Replication of Epstein-Barr virus (EBV) in B lymphocytes and the resulting lymphoproliferation usually is inhibited by natural killer cells, antibody-dependent cell cytotoxicity, and T-lymphocyte cytotoxic responses. Fatal disseminated infection or B-lymphocyte or T-lymphocyte lymphomas can occur in children with no detectable immunologic abnormality as well as in children with congenital or acquired cellular immune deficiencies.

EBV is associated with several other distinct disorders, including X-linked lymphoproliferative syndrome, post-transplantation lymphoproliferative disorders, Burkitt lymphoma, nasopharyngeal carcinoma, and undifferentiated B- or T-lymphocyte lymphomas of the CNS. X-linked lymphoproliferative syndrome occurs in people with an inherited, maternally derived, recessive genetic defect in signaling lymphocytic activation molecule-associated protein (SAP) and is characterized by several phenotypic expressions, including occurrence of infectious mononucleosis early in life among boys, nodular B-lymphocyte lymphomas often with CNS involvement, and profound hypogammaglobulinemia.

EBV-associated lymphoproliferative disorders result in a number of complex syndromes in patients who are immunocompromised, such as transplant recipients or people infected with human immunodeficiency virus (HIV). The highest incidence of these disorders occurs in liver and heart transplant recipients, in whom the proliferative states range from benign lymph node hypertrophy to monoclonal lymphomas. Other EBV syndromes are of greater importance outside the United States, including Burkitt lymphoma (a B-lymphocyte tumor), found primarily in Central Africa, and nasopharyngeal carcinoma, found in Southeast Asia and the Inuit population. EBV also has been associated with Hodgkin disease (B-lymphocyte tumor), non-Hodgkin lymphomas (B- and T-lymphocyte), gastric carcinoma "lymphoepitheliomas," and a variety of common epithelial malignancies.

Chronic fatigue syndrome is not related specifically to EBV infection; however, fatigue lasting weeks to a few months may follow less than 10% of cases of classic infectious mononucleosis.