Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (497 page)

Serology
: Not useful for diagnosis.

Typical core laboratory
: CBC and WBC counts are typically normal or show only mild, nonspecific abnormalities.

CSF findings
: Enteroviral meningitis shows moderate pleocytosis (<1,000 mononuclear cells; may see PMN predominance early), normal or slightly reduced glucose, normal or slightly increased protein.

EPSTEIN-BARR VIRUS INFECTIONS

   Definition

Epstein-Barr virus (EBV) is a lymphocryptovirus in the
Herpesviridae
family. EBV infections are widespread and occur worldwide. In developing regions, primary EBV infections usually occur in younger children. In developed countries, primary infections usually occur in adolescents and young adults. The rate of seropositivity is high (>90%) by middle age. Infections are primarily transmitted by oropharyngeal secretions. After exposure, oropharyngeal epithelial cells and tonsillar B lymphocytes are thought to be the first cells infected. Infection is spread to lymphoid cells throughout the body by memory B cells.

   Who Should Be Suspected?

Most primary EBV infections are asymptomatic, but EBV infection may cause a variety of mild to severe diseases:

   
Acute infectious mononucleosis (AIM)
: AIM is the most common manifestation of primary EBV infection, usually occurring in adolescents. Patients commonly present with fever, pharyngitis, posterior lymphadenopathy, and lethargy. Headache and malaise are also common, and rash, anorexia, nausea, and other nonspecific “viral” symptoms occur less frequently. A palpable spleen may be present in a significant proportion of patients, and splenic rupture, although uncommon, is a serious potential complication of AIM. The development of a morbilliform rash following amoxicillin or ampicillin treatment is highly suggestive of EBV AIM in patients with febrile pharyngitis syndromes.

Acute symptoms usually resolve within 2 weeks, but fatigue may persist for months. Note that mononucleosis syndromes are not agent specific for EBV. Heterophile-negative mononucleosis syndrome may be found in other infectious diseases, especially CMV, toxoplasmosis, and HSV. Atypical lymphocytes may be seen in other acute illnesses (e.g., rubella, roseola, mumps, acute viral hepatitis, acute HIV, drug reactions).

   
Nasopharyngeal carcinoma
: EBV DNA is consistently detected in nasopharyngeal carcinoma cells.

   
Lymphoproliferative diseases
: EBV infection is associated with a number of lymphoproliferative diseases, including:

   
Burkitt lymphoma
: EBV has been implicated as a cause of endemic Burkitt lymphoma in equatorial Africa. EBV is seen less frequently in sporadic cases outside of endemic areas.

   
Hodgkin disease
: EBV DNA may be detected in malignant cells of Hodgkin disease. The frequency of detection varies in different geographic regions but is almost universal in Hodgkin disease associated with AIDS.

   
Lymphomas associated with HIV infection
: The incidence of non-Hodgkin lymphoma is markedly increased compared to nonimmunocompromised patients, and EBV is associated with a majority of these malignancies. Most EBV-related non-Hodgkin lymphomas in HIV-infected patients present in the CNS.

   
Posttransplant lymphoproliferative disease (PTLD)
: The severity of PTLD after allograft transplantation may range from benign B-cell proliferation to aggressive B-cell lymphoma. The severity of disease is related to the degree of immunosuppression. Fever, pharyngitis, and nonspecific symptoms may occur during the development of PTLD.

   
X-linked lymphoproliferative syndrome (XLP)
: XLP, manifested by a severe or fatal mononucleosis or immunodeficiency syndrome, is essentially a selective defect in immunity to EBV infection. Mutation in the gene implicated in XLP,
SH2D1A
, results in defective activation–induced cell death in CD8 T lymphocytes, with subsequent uncontrolled proliferation.