Epstein pear =اصابة بفيروس ابشتاين بار |
EPSTEIN-BARR VIRUS
Epidemiology
Epstein-Barr virus (EBV) is a worldwide pathogen with more than 90 percent of adults latently infected. In developed countries, most cases of primary infection occur during adolescence or early adulthood, and clinically may present as infectious mononucleosis. Primary infection may occur during childhood; however, is often sub-clinical, probably because children are better able to clear the infection. In developing countries, most of the population is infected during childhood, thus infectious mononucleosis is much less common. EBV is transmitted primarily by saliva through close contact. Viral replication occurs during primary infection, allowing infectious viral particles to be shed from the oropharynx. There are also reports of EBV acquired via blood transfusion. It is also thought that EBV may be transmitted through breast milk and genital secretions. Etiology and Pathogenesis EBV, also called human herpesvirus 4 (HHV-4), belongs to the Herpesviridae family and is approximately 180 to 200 nm in diameter. The double-stranded DNA genome encodes approximately 100 proteins and is enclosed within a capsid. The capsid is surrounded by an envelope, composed primarily of glycoprotein gp350. CD21 is present on the surface of B cells and binds with gp350, allowing entry of EBV into the cell.
EPSTEIN-BARR VIRUS AT A GLANCE
EBV infects B lymphocytes directly within the oral mucosa or infects mucosal epithelial cells, which then infect the B lymphocytes. The infected B cells are activated, and their population is expanded. These B lymphocytes allow dissemination of the virus throughout the lymphoreticular system. A clonal expansion of cytotoxic T lymphocytes allows recovery from primary infection and is the source of the atypical lymphocytes associated with EBV infection. Symptoms are likely a result of this immunologic response. EBV establishes an indefinite latent infection within the B cells, during which time low levels of the latent proteins are produced. The previously linear DNA forms a circular structure, called an episome. Thereafter, B cells may re-activate and re-infect the oropharynx; replication and shedding of the viral DNA allows transmission of the virus to new hosts.
Clinical Findings
There is an incubation period of 30 to 50 days. Primary infection with EBV in adolescents and adults typically results in infectious mononucleosis, or the “kissing disease.” The classic triad of fever, lymphadenopathy, and pharyngitis are noted in more than 50 percent of patients. The fever may range from 37.5°C (99.5°F) to 40.5°C (104.9°F) and lasts 1 to 3 weeks. Lymphadenopathy is tender and characteristically found in the posterior cervical chain. Examination of the posterior pharynx may vary from mild erythema to grossly enlarged tonsils with white exudates.87
CUTANEOUS LESIONS
Seventy percent to 100 percent of patients with infectious mononucleosis develop an eruption when antibiotics, specifically ampicillin, are administered. Similar rashes have been reported with other antibiotics, such as amoxicillin, cephalexin, erythromycin, and levofloxacin. The rash typically begins 7 to 10 days after the initial administration of antibiotics. A pruritic, erythematous, morbilliform, or scarlatiniform eruption is noted on the trunk and extremities. The rash has been described as copper-colored. Coalescence may be observed on the extensor surfaces and dependent areas. . The palms, soles, or oral mucosa may be involved. Clearance, which is usually within 7 days, is accompanied by prominent desquamation.90 The rash is thought to be a result of EBV-induced antibodies that are produced in response to the administered drug; these antibodies subsequently form immune complexes, which fix complement. This exanthem does not usually indicate a permanent allergy to the medication. An exanthem due to EBV alone may also occur in a minority of cases (approximately 5 percent to 15 percent). This rash is also morbilliform and pruritic; however, usually it commences during the first few days of illness and resolves faster, typically in 1 to 6 days. Periorbital and eyelid edema may be seen in up to 50 percent of those with infectious mononucleosis. In approximately 25 percent of cases, an enanthem is noted. Six to 20 petechiae, measuring 0.5 to 1.0 mm, may be visualized at the junction of the hard and soft palate. Lesions may coalesce forming larger lesions. Erythema multiforme, erythema nodosum, acrocyanosis, erythema annulare centrifugum, pityriasis lichenoides, palmar dermatitis, cold urticaria, and granuloma annulare have all been reported
EBV is currently the most common cause of Gianotti-Crosti syndrome (GCS; see Chap. 106). In children, primary infection with EBV is often mild or asymptomatic; as a result, typical features of infectious mononucleosis may not be observed.
RELATED PHYSICAL FINDINGS
Associated symptoms and signs may include fatigue, rigors, headache, and hepatosplenomegaly.
Laboratory Tests
Most patients with infectious mononucleosis demonstrate a lymphocytosis, often with lymphocytes accounting for more than 50 percent of the absolute white blood cell count. Atypical lymphocytes are a hallmark, typically more than 10 percent atypical lymphocytes; most of these cells represent activated T cells responding to infected B cells. Mild, transient neutropenia and thrombocytopenia are common. Transaminases are elevated in more than 80 percent of patients with infectious mononucleosis.
The presence of heterophile antibodies confirms most cases of infectious mononucleosis. Heterophile antibodies recognize antigens on the erythrocytes from a number of different species including horses, sheep, bulls, and humans; however, they do not recognize EBV. They are thought to be a result of polyclonal stimulation during the viral infection, and can occasionally be detected (false positives) in other illnesses such as lymphoma, hepatitis, or autoimmune disease. Heterophile antibodies typically appear within 1 week of the onset of symptoms, peak within 2 to 5 weeks, and may persist for up to 1 year. They are not the ideal diagnostic test in children less than 4 years old, as sensitivity is quite low.95 In the past, the Paul-Bunnell test had been used with sheep erythrocytes. Currently, the more sensitive monospot test is used, which is a latex agglutination assay with horse erythrocytes to look for heterophile antibodies. Up to 10 percent of patients with EBV mononucleosis never develop heterophile antibodies; this is referred to as heterophile-negative mononucleosis. A number of antibodies specific to EBV develop in the course of disease as well. Measurement of these specific antibodies may be warranted if infectious mononucleosis is suspected and heterophile antibodies are negative. IgM and IgG antibodies form to viral capsid antigen (VCA) and are both present at onset of disease. IgM VCA antibodies wane after approximately 3 months; IgG VCA antibodies persist for life and are a marker for previous infection. IgG antibodies to EBV nuclear antigen develop 6 to 12 weeks into the course of disease and also persist for life. IgG to early antigen develops at the onset of disease and is made up of two subsets of antibodies, anti-D and anti-R. The presence of anti-D antibodies suggests recent infection, although 30 percent of patients do not produce antibodies at all. Anti-R antibodies have no clinical significance. Thus, primary infection may be most easily diagnosed in the presence of IgM and IgG VCA antibodies as well as negative IgG EBV nuclear antigen antibodies.
Histopathology
The morbilliform exanthem associated with EBV demonstrates non-specific histopathologic findings. There is usually a mild perivascular infiltrate of inflammatory cells. Specific cutaneous manifestations may show their characteristic pathologies. Differential Diagnosis Complications Complications of infectious mononucleosis occur in approximately 20 percent of patients and include airway obstruction, autoimmune hemolytic anemia or thrombocytopenia, neutropenia,87 myocarditis, and hepatitis.80 Neurologic complications occur in approximately 5 percent
Differential Diagnosis of Infectious Mononucleosis Most Likely
Consider
Always Rule Out
Treatment for Epstein-Barr Virus Infectious Mononucleosis
Prognosis and Clinical Course Recovery from infectious mononucleosis is typically gradual over 2 to 3 weeks without specific treatment. Disease may be more protracted in older adults. Chronic active EBV infection occurs rarely.80 It begins as a primary EBV infection and persists for more than 6 months with severe illness and histologic evidence for organ disease. EBV DNA or antigens can be demonstrated from tissue, and usually EBV antibody titers are significantly elevated. Treatment Treatment for uncomplicated infectious mononucleosis is symptomatic Acetaminophen or nonsteroidal anti-inflammatory agents may be useful in treating the fever or throat discomfort. Because splenomegaly is often an associated finding, contact sports should be avoided until the spleen has returned to its normal size to avoid splenic rupture. Systemic corticosteroids may decrease the duration of fever or pharyngeal symptoms, but in general, are not recommended for uncomplicated disease. Prevention Because infectious mononucleosis is often mistaken for a bacterial infection, antibiotics may initially be used to treat. Antibiotics should be avoided in infectious mononucleosis as an exanthem is much more likely to occur in this setting. Vaccinations are currently being investigated and may prove to be helpful in preventing EBV infections in the future, particularly in high-risk patients.
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