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Epstein-Barr virus infections
OVERVIEW: EBV is tropic for B lymphocytes which apparently are infected in the oropharynx through salivary exchange; infected B cells then circulate in the blood and are distributed to the bone marrow and lymphoreticular system. The virus can also be found in infected epithelial cells of the buccal mucosa, salivary glands, tongue and endocervix. Within the oropharynx both parotid ductal epithelium and pharyngeal squamous epithelial cells harbor EBV DNA and are sites of viral replication and release. This suggests that chronic epithelial replication brings about continuous reinfection of B lymphoid cells. Immune T cell responses to latently infected B cells account for the clinical findings.
• Epstein-Barr virus (EBV) infections acquired early in life are asymptomatic or associated with non-specific symptoms suggesting an upper respiratory infection.
System(s) affected: Hemic/Lymphatic/Immunologic
Genetics: N/A
Incidence/Prevalence in USA:
• Incidence is about 60/100,000 persons
• College students: 5,000/100,000 persons
• Worldwide in distribution, but clinical IM is observed predominantly in countries with advanced sociohygienic conditions
Predominant age:
• Older children, adolescents and young adults
• By young adult life, 60-90% of persons are antibody positive
Predominant sex: Male = Female
SIGNS AND SYMPTOMS: • May begin abruptly or insidiously
• In adults, the temperature may rise to 103°F (39.4°C) and gradually falls over a variable period of 7-10 days; in severe cases temperature elevations of 104-105° F (40.0-40.6°C) may persist for 2 weeks
• Children usually have a low-grade fever or may be afebrile
• Diffuse hyperemia and hyperplasia of oropharyngeal lymphoid tissue
• Gelatinous, grayish-white exudative tonsillitis persists for 7-10 days in 50%
• Petechiae develop at the border of the hard and soft palates in 33%
• Tender lymphadenopathy (cervical nodes are most commonly enlarged)
• Axillary, epitrochlear, popliteal, inguinal, mediastinal and mesenteric nodes may also be affected
• Lymph node enlargement subsides over days or weeks
• Splenomegaly in 50%
• Abnormal hepatic enzymes in 80% of patients for several weeks after onset. Hepatomegaly in 15-20%.
• Pneumonitis
• Chest pain (myocarditis and pericarditis)
• Hilar adenopathy may be observed in IM cases having extensive lymphoid hyperplasia
• Neurologic (rare)
• Aseptic meningitis
• Bell's palsy
• Meningoencephalitis
• Guillain-Barre syndrome
• Transverse myelitis
• Cerebellar ataxia
• Acute psychosis
• Hematologic (rare)
• Thrombocytopenia, slight to moderate, early in illness
• Hemolytic anemia with marked neutropenia during early weeks of disease
• Aplastic anemia
• Agammaglobulinemia
• Skin manifestations (3-16%)
• Erythematous macular or maculopapular rash
• Petechial and purpuric exanthems have been reported
• Rash location - trunk and upper arms; occasionally the face and forearms involved
• Urticarial lesions on the abdomen, arms, legs
CAUSES: The Epstein-Barr virus, a member of the herpesvirus (DNA virus) group.
RISK FACTORS: • Age
• Sociohygienic level
• Geographic location
DIAGNOSIS DIFFERENTIAL DIAGNOSIS: • Streptococcal pharyngitis and tonsillitis
• Diphtheria
• Blood dyscrasias
• Rubella
• Measles
• Viral hepatitis
• Cytomegalovirus
• Toxoplasmosis
LABORATORY: • Lymphocytes and atypical lymphocytes
• Increased numbers of lymphocytes and atypical lymphocytes (may be up to 70% of leukocytes) in peripheral blood.
• In the first week after onset of illness, the white blood cell count is normal or moderately decreased. By the second week, lymphocytosis develops with more than 10% atypical lymphocytes. Such cells vary in size and shape with indented, oval or horseshoe-shaped nuclei and basophilic, vacuolated, foamy cytoplasm.
• During early illness, atypical lymphocytes are B cells transformed by EBV; later, the atypical cells are primarily T cells having immunoregulatory function
• Antibodies
• Heterophil antibodies in 80-90% of adults.
• The responsible heterophile antibody is an IgM response which appears during the first or second week of illness and persists for 3-6 months. Sheep cell agglutinins are not specific for IM and may occur in other conditions including serum sickness, infectious hepatitis, rubella, leukemia and Hodgkin's disease; low titers may also be found in normal healthy individuals.
• Differential absorption techniques distinguish these agglutinins from IM-associated heterophile antibodies. In general, the agglutinin titer is higher in IM than in other disorders; an unabsorbed heterophile titer greater than 1:128 and 1:40 or higher after absorption is significant.
• Specific antibodies to EBV-associated antigens
• Develop regularly in IM
• Viral capsid (VCA)-specific IgM and IgG are present early in illness; VCA-IgM responses disappear after several months whereas VCA-IgG antibodies persist for life.
• Antibodies to EBV early antigen (EA) complexes, associated with viral replication, are present in 70-80% of patients during acute disease and usually disappear after 6 months
• Antibodies to the EBV nuclear antigen complex (EBNA) appear slowly and develop 1-6 months after onset of illness
Drugs that may alter lab results: N/A
Disorders that may alter lab results: Atypical lymphocytes are not specific for Epstein-Barr infections and may be present in other clinical conditions including rubella, infectious hepatitis, allergic rhinitis, asthma and primary atypical pneumonia. In IM, increased numbers of atypical forms are present in peripheral blood whereas in other disorders the quantitative percentage is usually less.
PATHOLOGICAL FINDINGS: • Widespread focal and perivascular aggregates of mononuclear cells are found throughout the body
• Mononuclear infiltrations involve lymph nodes, tonsils, spleen, lungs, liver, heart, kidneys, adrenal glands, skin and central nervous system
• Bone marrow hyperplasia develops regularly and small granulomas may be present; these are non-specific and have no prognostic significance
• A polyclonal B cell proliferative response is characteristic of IM. Relatively few circulating lymphocytes are infected by EBV and represent less than 0.1% of circulating mononuclear cells in acute illness.
SPECIAL TESTS: N/A
IMAGING: Ultrasound, splenomegaly
DIAGNOSTIC PROCEDURES: See under Laboratory
TREATMENT APPROPRIATE HEALTH CARE: Outpatient usually
GENERAL MEASURES: • The treatment is chiefly supportive
• During acute stage, rest in bed
SURGICAL MEASURES: • With profound thrombocytopenia, refractory to corticosteroid therapy, splenectomy may be necessary.
ACTIVITY: • Decided on an individual basis during convalescence
• Excess exertion, heavy lifting and participation in contact sports are prohibited during acute illness and also in the presence of splenomegaly. Rupture of the spleen may be fatal if not recognized and requires blood transfusions, treatment for shock, and splenectomy.
DIET: • Maintain adequate fluid intake
• Low fat, high carbohydrate diet
• Avoid alcohol for 6-8 months
PATIENT EDUCATION: Reassurance and support
MEDICATIONS DRUG(S) OF CHOICE: • Antimicrobial agents (usually a penicillin) if throat culture is positive for Group A, beta-hemolytic streptococci. Avoid ampicillin because of rash that occurs with ampicillin in mononucleosis.
• Aspirin and warm saline gargles for the pain of pharyngeal involvement and enlarged lymph nodes
• Codeine or meperidine, for unrelieved pain
• Corticosteroids
• With severe pharyngotonsillitis with oropharyngeal edema and airway encroachment, a short course of corticosteroids may be utilized. Prednisone or its equivalent is used. Start with an initial dosage of 10-15 mg qid for 2 days. Decrease by 5 mg daily so that steroid treatment is discontinued in approximately 10 days.
• Considered for patients with marked toxicity or major complications (e.g., hemolytic anemia, thrombocytopenic purpura, neurologic sequelae, myocarditis, pericarditis and severe generalized dermatologic lesions).
Contraindications: Steroids not recommended for mild, uncomplicated IM
Precautions: Refer to manufacturer's literature
Significant possible interactions: Refer to manufacturer's literature
ALTERNATIVE DRUGS: N/A
FOLLOW UP PATIENT MONITORING: • Avoid contact sports, heavy lifting, and excess exertion until the spleen and liver have returned to normal size.
• Eliminate alcohol or exposure to other hepatotoxic drugs until liver function studies return to normal
• Monitor patients closely during the first 2-3 weeks after onset of symptoms. Thereafter follow until symptoms subside.
• Rarely, laboratory results resolve more slowly and symptoms (malaise, fatigue, intermittent sore throat, lymphadenopathy) may persist for several months
PREVENTION/AVOIDANCE: N/A
POSSIBLE COMPLICATIONS: • Airway obstruction
• Hematologic or neurologic complications
• Toxemia
• Splenic rupture (rare)
• Hypersensitivity rash
• Develops 7-10 days after initiation of ampicillin (or its analogues and other penicillins like methicillin) treatment; this generalized erythematous maculopapular eruption occurs mainly over the trunk and extremities, including palms and soles. Rash persists for a week; desquamation may continue for several days
EXPECTED COURSE AND PROGNOSIS: • IM usually mild or moderate severity
• Acute symptoms 2-3 weeks with full recovery in 4-8 weeks
MISCELLANEOUS ASSOCIATED CONDITIONS: • Infectious mononucleosis (IM): the symptomatic primary EBV infection seen in otherwise healthy older children, adolescents and young adults. Clinical features are variable in severity and duration; in children the disease is generally mild, whereas in adults it is more severe and protracted. The incubation period is 30-50 days.
• X-linked lymphoproliferative syndrome (Duncan's disease)
• Lymphoproliferative syndromes due to EBV infections in transplant patients
• Lymphomas (B cell lymphoblastic, T cell)
• Lymphocytic interstitial pneumonitis
• Hairy leukoplakia of the tongue and central nervous system lymphomas in AIDS patients
• Burkitt's lymphoma
• Nasopharyngeal carcinoma
• Parotid carcinoma
• Hodgkin's disease
AGE-RELATED FACTORS:
Pediatric:
• Infection during infancy and childhood usually subclinical and inapparent
• Clinical IM more common in older children and young adults
Geriatric: Heterophile positive IM has been reported in an elderly patient 5 weeks following blood transfusion
Others: N/A
PREGNANCY: One large prospective study of pregnant women failed to demonstrate evidence of any intrauterine EBV infection. However, rare birth defects considered to be due to congenital EBV infection have been reported; such defects include cataracts, hypotonia, cryptorchidism and micrognathia.
SYNONYMS: N/A
ICD-9-CM: 075 Infectious mononucleosis
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