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1266 Part IX: Lymphocytes and Plasma Cells Chapter 82: Mononucleosis Syndromes 1267

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TABLE 82–4. Special Problems with Epstein-Barr Virus or vaccine, adoptive transfer of activated cytotoxic T cells, and the
development of peptides that inhibit viral replication.
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Cytomegalovirus Infection
Epstein-Barr Virus Cytomegalovirus
Rare congenital infection 129,130 Congenital infection 110 CYTOMEGALOVIRUS
Chronic progressive Posttransplant primary MONONUCLEOSIS
mononucleosis 65–67,72–74 infection 114,115
Hemophagocytic syndrome 77,78 Graft-versus-host disease HISTORY
association 143 The early description of CMV-related disease was that of an uncommon
XX-linked B cell lymphoma 92 Transfusion-related infection 144 congenital syndrome with abnormal liver function and thrombocytope-
nia leading to petechiae. Subsequently, it was recognized that previ-
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Posttransplant lymphoprolifera- Aspergillus and/or Pneumocystis ously healthy young children with a primary infection with CMV had
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tive disease 88–91 infection 122,123
prolonged abnormal liver function, hepatosplenomegaly, lymphocyto-
T or NK lymphoproliferative sis, and thrombocytopenia. Later, primary CMV infection was linked to
disease 94,95 a febrile mononucleosis syndrome. 108
African Burkitt lymphoma 5
Approximately 20% of Burkitt EPIDEMIOLOGY
lymphoma in the United States 5 In the developing world, CMV infects the majority of individuals by
Approximately 35% of Hodgkin the age of 5 or 6 years. Three factors contribute to this. In those soci-
lymphoma 84–87 eties, mothers are still in their teen years when they deliver their chil-
dren. These young women have active CMV virus in their cervix that
Nasopharyngeal carcinoma 96,97
has persisted since they were younger. The cervical virus is aspirated
Approximately 5% of gastric by the child during the birthing process. Transmission to the newborn
carcinoma 99 also occurs through breast milk. In addition, all of these young children
Leiomyoma and leiomyosar- play together when they are young and virus is transmitted readily to
coma in HIV or immunosup- those who have avoided earlier infection. Infection at the time of birth
pressed patients 98 from the cervical virus or shortly after birth from breast milk or another
Oral hairy leukoplakia 102 child does not lead to any known consequences. However, congenital
infection occurs in all populations. For less-than-clear reasons, a sero-
positive mother may deliver a child who has become infected in utero.
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In the developing world, most often it occurs in the babies whose moth-
ers are seropositive before they become pregnant and the disease in the
and often within the first few months. The abnormally proliferating new born is not clinically obvious at birth. These children, who have
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cell almost always is a B cell and the process at an early stage may be asymptomatic congenital infection, may develop unilateral or bilateral
monoclonal. In the initial states, the disease may respond to lowering hearing deficits later. Congenital CMV infection in the babies of sero-
of immunosuppressive medications. Although administration of anti- positive women and may account for a significant number of people
viral prophylaxis seems to lower the frequency of development of the with hearing loss. 109
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disease, once the disease develops, antiviral agents are ineffective. In the developed world, first children often have parents who have
When disease develops, in addition to reduction in immunosuppres- not had CMV infection. If primary infection occurs in the mother at or
sion, administration of anti-CD20 therapy with rituximab is used. near the time of impregnation in anticipation of the second child, severe
Occasionally, PTLD occurs in a person who is EBV antibody-positive congenital infection may develop. It is not clear which of the several
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pretransplantation. When this occurs, the onset is usually greater than possible factors contribute to why that child acquires congenital CMV
1 year posttransplantation. infection and more study is required to lead to intelligent management
In young males with an X-linked lymphoproliferative syndrome, decisions.
primary EBV infection leads to unabated B-cell proliferation and evo- Presence of CMV in oral secretions and in urine in children living
lution into a frank B-cell lymphoma, the so-called Duncan syndrome. together in families where there is known CMV has been recognized for
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These young males do not develop a T-cell response and hence do not many years. The source of the virus is not entirely clear. It is not always
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develop mononucleosis. Although control of this effect of EBV infec- certain whether these children acquired infection at birth or from breast
tion by treatment with antiviral agents and/or chemotherapy has been milk and they continue to have active infection or whether it is resulting
attempted, the Duncan syndrome usually is fatal. from transmission among children. The latter is suspected but not proven.
Oral hairy leukoplakia, a characteristic white lingual lesion with It is strongly suspected that when a CMV-infected child comes in
hairy projections, occurs in patients with HIV infection. It is caused by contact with a CMV-seronegative grandparent, primary infection in
EBV infection of the lingual epithelium. 102 that grandparent may occur. This can be associated with CMV disease
in the older person, although the development of disease associated
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with the infection is uncommon. Very little is known about the risk
FUTURE THERAPEUTIC APPROACHES of CMV-infected semen in those undergoing heterosexual intercourse.
TO EPSTEIN-BARR VIRUS INFECTION However, there is a very high frequency of CMV infection in young
AND NEOPLASIA homosexual males. Almost all active homosexual young men are sero-
positive to CMV by age 20 years, which contrasts to only 20 percent of
Because of the severe consequences of EBV infection, several approaches heterosexual young men. Presumably that 20 percent of heterosexual
to preventing or treating these disorders are underway, such as an EBV men were infected as children.

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