dr.Mohsen Meidani

EPSTEIN-BARR VIRUS INFECTIONS

INFECTIOUS MONONUCLEOSIS

INCLUDING

Dr.Meidani

dr.Mohsen Meidani

DEFINITION

Epstein-Barr virus (EBV) is the cause of heterophile-positive infectious mononucleosis (IM), which is characterized by fever,sore throat, lymphadenopathy, and atypical lymphocytosis.

dr.Mohsen Meidani

EBV is also associated with several human tumors, including nasopharyngeal carcinoma, Burkitt’s lymphoma, Hodgkin’s disease, and (in patients with immunodeficiencies) B cell lymphoma.

The virus, a member of the family Herpesviridae, consists of a linear DNA core surrounded by a nucleocapsid and an envelope that contains glycoproteins.

dr.Mohsen Meidani

EPIDEMIOLOGY

EBV infections occur worldwide.

These infections are most common in early childhood, with a second peak during late adolescence.

By adulthood, more than 90% of individuals have been infected and have antibodies to the virus.

IM is usually a disease of young adults.

dr.Mohsen Meidani

EBV is spread by contact with oral secretions.

The virus is frequently transmitted from asymptomatic adults to infants and among young adults by transfer of saliva during kissing.

Transmission by less intimate contact is rare.

EBV has been transmitted by blood transfusion and by bone marrow transplantation.

More than 90% of asymptomatic seropositive individuals shed the virus in oropharyngeal secretions.

dr.Mohsen Meidani

PATHOGENESIS

EBV is transmitted by salivary secretions.

The virus infects the epithelium of the oropharynx and the salivary glands and is shed from these cells.

The virus then spreads through the bloodstream.

dr.Mohsen Meidani

Data suggest that memory B cells, not epithelial cells, are the reservoir for EBV in the body.

Cellular immunity is more important than humoral immunity in controlling EBV infection.

If T cell immunity is compromised, EBV-infected B cells may begin to proliferate.

dr.Mohsen Meidani

dr.Mohsen Meidani

CLINICAL MANIFESTATIONS

dr.Mohsen Meidani

The incubation period for IM in young adults is 4 to 6 weeks.

A prodrome of fatigue, malaise, and myalgia may last for 1 to 2 weeks before the onset of fever, sore throat, and lymphadenopathy.

Fever is usually low-grade and is most common in the first 2 weeks of the illness; however, it may persist for1 month.

dr.Mohsen Meidani

Lymphadenopathy and pharyngitis are most prominent during the first 2 weeks of the illness, while splenomegaly is more prominent during the second and third weeks.

Lymphadenopathy most often affects the posterior cervical nodes but may be generalized.

Enlarged lymph nodes are frequently tender and symmetric but are not fixed in place.

dr.Mohsen Meidani

dr.Mohsen Meidani

Pharyngitis, often the most prominent sign, can be accompanied by enlargement of the tonsils with an exudate resembling that of streptococcal pharyngitis.

A morbilliform or papular rash, usually on the arms or trunk, develops in 5% of cases.

Most patients treated with ampicillin develop a macular rash; this rash is not predictive of future adverse reactions to penicillins.

dr.Mohsen Meidani

Laboratory Findings

The white blood cell count is usually elevated and peaks at 10,000 to 20,000/L during the second or third week of illness.

Lymphocytosis is usually demonstrable, with >10% atypical lymphocytes.

atypical lymphocytes are enlarged lymphocytes that have abundant cytoplasm, vacuoles, and indentations of the cell membrane.

CD8 cells predominate among the atypical lymphocytes.

dr.Mohsen Meidani

Low-grade neutropenia and thrombocytopenia are common during the first month of illness.

Liver function is abnormal in more than 90% of cases.

Serum levels of aminotransferases and alkaline phosphatase are usually mildly elevated.

the serum concentration of bilirubin is elevated in 40% of cases.

dr.Mohsen Meidani

dr.Mohsen Meidani

Complications

Most cases of IM are self-limited.

Deaths are very rare and most often are due to central nervous system (CNS) complications, splenic rupture, upper airway obstruction, or bacterial superinfection.

dr.Mohsen Meidani

Autoimmune hemolytic anemia occurs in 2% of cases during the first 2 weeks.

Nonspecific antibody responses may also include rheumatoid factor,antinuclear antibodies, anti–smooth muscle antibodies, antiplatelet antibodies, and cryoglobulins.

IM has been associated with red-cell aplasia, severe granulocytopenia, thrombocytopenia, pancytopenia, and hemophagocytic syndrome.

Splenic rupture is more common among males than among females and may be manifest as abdominal pain, referred shoulder pain, or hemodynamic compromise.

dr.Mohsen Meidani

Hypertrophy of lymphoid tissue in the tonsils or adenoids can result in upper airway obstruction, as can inflammation and edema of the epiglottis, pharynx, or uvula.

Other rare complications associated with acute EBV infection include hepatitis (which can be fulminant), myocarditis or pericarditis with electrocardiographic changes, pneumonia with pleural effusion, interstitial nephritis, genital ulcerations, and vasculitis.

dr.Mohsen Meidani

OTHER DISEASES ASSOCIATED WITH EBV INFECTION

EBV-associated lymphoproliferative disease. The X-linked lymphoproliferative syndrome

(Duncan’s disease). Oral hairy leukoplakia. chronic fatigue syndrome. Chronic active EBV infection. Burkitt’s lymphoma. Hodgkin’s disease. CNS lymphomas in AIDS patients.

dr.Mohsen Meidani

dr.Mohsen Meidani

DIAGNOSIS

dr.Mohsen Meidani

dr.Mohsen Meidani

The heterophile test is used for the diagnosis of IM in children and adults.

A titer of 40-fold or greater is diagnostic of acute EBV infection in a patient who has symptoms compatible with IM and atypical lymphocytes.

Tests for heterophile antibodies are positive in 40% of patients with IM during the first week of illness and in 80 to 90% during the third week.

Therefore, repeated testing may be necessary, especially if the initial test is performed early.dr.Mohsen Meidani

Tests usually remain positive for 3 months after the onset of illness, but heterophile antibodies can persist for up to 1 year.

These antibodies usually are not detectable in children <5 years of age, in the elderly, or in patients presenting with symptoms not typical of IM.

False-positive monospot results are more common in persons with connective tissue disease, lymphoma, viral hepatitis, and malaria.

dr.Mohsen Meidani

Differential Diagnosis acute infection with cytomegalovirus. Toxoplasma. HIV. human herpesvirus 6. hepatitis viruses . drug hypersensitivity reactions. Rubella. acute infectious lymphocytosis in children. lymphoma or leukemia.

dr.Mohsen Meidani

TREATMENT

Therapy for IM consists of supportive measures, with rest and analgesia.

Excessive physical activity during the first month should be avoided to reduce the possibility of splenic rupture.

If splenic rupture occurs, splenectomy is required.

dr.Mohsen Meidani

Glucocorticoid therapy: Prednisone (40 to 60 mg/d for 2 to 3 days, with subsequent tapering of the dose over 1 to 2 weeks):

airway obstruction autoimmune hemolytic anemia severe thrombocytopenia.

Glucocorticoids have also been used in a few selected patients with :

severe malaise and fever severe CNS cardiac disease.

dr.Mohsen Meidani

Acyclovir, at a dosage of 400 to 800 mg five times daily, has been effective for the treatment of oral hairy leukoplakia (despite common relapses) and some cases of chronic active EBV disease.

The posttransplantation EBV lymphoproliferative syndrome generally does not respond to antiviral therapy.

When possible, therapy should be directed toward reduction of immunosuppression .

dr.Mohsen Meidani

Interferon .

antibody to CD20.

Infusions of donor lymphocytes are often effective for stem cell transplant recipients.

Infusions of EBVspecific cytotoxic T cells.

Infusion of autologous EBV-specific cytotoxic T lymphocytes

The isolation of patients with IM is unnecessary.

dr.Mohsen Meidani

dr.Mohsen Meidani