Laboratory Findings
Histopathology
: The use of EBV-specific immunohistochemical staining to detect EBV proteins may provide improved sensitivity and specificity for establishing EBV as the specific cause of disease when the etiology of the syndrome is broad.
Serology
:
AIM is diagnosed by detection of heterophile antibodies (Paul-Bunnell test), which provide moderate to good sensitivity and high specificity for detection of AIM during the acute, symptomatic phase of disease. This “spot” test has an overall sensitivity ≤92% and specificity >96%, except in children <4 years old, where the slide test is less sensitive. Heterophile agglutination is positive in 60% of young adults by 2 weeks and 90% by 4 weeks after onset of clinical infectious mononucleosis (therefore, they may be negative when hematologic and clinical findings are present). Low titers may persist for a year. False-positive slide tests may occur in leukemia, malignant lymphoma, malaria, rubella, hepatitis, and pancreatic carcinoma, and they may be present for years in some persons with no known explanation. In adults, false positive results in approximately 2% of patients and false negative results in approximately 5%.
Specific EBV antibody tests: Specific tests are rarely required; most patients are heterophile antibody positive, and clinical illness is usually self-limited and relatively mild. Specific tests may be useful, however, in atypical mononucleosis syndromes or for very severe cases, especially in young children or immunocompromised patients. See Epstein-Barr Virus (EBV) Serology Screen Antibody Profile in Chapter
17
, Infectious Disease Assays.
Anti-EA-R is high and correlated with tumor burden in Burkitt lymphoma. Anti-EA-D is high and correlated with tumor burden in nasopharyngeal carcinoma.
Nucleic acid
–
based testing
: Qualitative or quantitative PCR may be valuable for diagnosis or disease management in EBV-associated diseases.
Core laboratory
:
In AIM, hematologic findings of absolute (>4,500/μL) and relative lymphocytosis (≥50%) in 70% of cases, with ≥10% (often ≤70%) characteristic atypical lymphocytes. Leukopenia and granulocytopenia are evident during the first week. Later, WBC is increased (usually 10,000–20,000/μL) because of increased lymphocytes; peak changes occur in 7–10 days; may persist for 1–2 months. Increased number of bands and >5% eosinophilia are frequent. Mild thrombocytopenia is seen in about 50% of early cases, and platelet dysfunction is frequent. Hemolytic anemia is rare.
Evidence of mild hepatitis (e.g., increased serum transaminases, increased urine urobilinogen) is very frequent but may be transient. Increased serum bilirubin in ≤30% of adults and <9% of children. Bilirubin/enzyme dissociation (serum bilirubin normal or <2 mg/dL with moderate increase of ALP, GGT, AST, ALT) occurs in 75% of cases. If no liver function abnormalities can be found, another diagnosis should be sought.
T-cell response: AIM is associated with an oligoclonal expansion of CD8
+
T lymphocytes.
HEPATITIS VIRUSES
See Chapter
5
, Digestive Diseases.
HERPES SIMPLEX VIRUS INFECTIONS
Definition
Herpes simplex viruses (HSV) are members of the family
Herpesviridae
, subfamily
Alphaherpesvirinae
. Humans serve as the normal reservoir for HSV infections, and HSV disease has a global distribution. The viruses are transmitted by close personal contact. There is no evidence for epidemics of HSV, although clusters of infections may occur. There is no clear seasonal pattern in the incidence of HSV disease. Genital infections are most commonly caused by HSV-2; genital infections caused by HSV-1 tend to be milder and associated with a lower rate of recurrence.
Who Should Be Suspected?
HSV infection is associated with a number of syndromes, including:
Primary oropharyngeal
: HSV disease is usually asymptomatic or associated with mild symptoms. Severe symptoms may occur, including vesicular gingivostomatitis and pharyngitis with lymphadenopathy. Nonspecific symptoms are common, including fever and malaise. Adolescents and adults may present with a mononucleosis syndrome. Specific antibodies are usually detectable within the first week following onset of infection, but virus may continue to shed for several weeks. Outbreaks of recurrent lesions, usually at the vermilion border of the lip, are usually preceded by pain, itching, or other symptoms. Lesions usually crust over within 4–5 days.
