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1268 Part IX: Lymphocytes and Plasma Cells Chapter 82: Mononucleosis Syndromes 1269

develop. In the allogeneic hematopoietic stem cell transplantation set- from that organ. When the ganciclovir is discontinued, CMV some-
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ting, if the recipient is CMV-seronegative and the donor is positive for times reactivates from that organ and primary infection can develop
CMV, infection occurs often, but not in everyone. Although pulmonary several months later. When this happens, patients present with fever and
involvement is most common, the retina and gastrointestinal tract also diarrhea and often have a negative blood CMV by PCR. CMV-induced
can be involved. Because the donor cells are not exposed to immuno- bowel disease develops because the colonic mucosal cells, as noted pre-
suppressive medication, other factors need to come into play for CMV viously, are targets for primary infection and virus replication. However,
infection to become manifest. The other possible matches with respect because the blood PCR for CMV is negative, the diagnosis eludes the
to CMV are that the recipient is CMV-seropositive and the donor is transplant clinician until colonoscopy and biopsy are carried out.
negative, or both the recipient and the donor are seropositive. If the There are other clinical settings where CMV may play a role. There
recipient is seropositive and has been repeatedly exposed to therapeutic are hints that HIV patients with pneumocystis pneumonia who also
regimens in the process of treatment for the recipient’s underlying dis- have CMV secretions do less well than those who simply have pneumo-
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ease, reactivation of CMV could occur before the recipient undergoes cystis pneumonia. In the intensive care unit, CMV reactivation may
transplantation. It would be a “self-vaccination” process for some. One occur in the very ill nonimmunosuppressed patient. It is uncertain what
needs to consider whether serious infection with CMV is a major prob- role the virus plays in this setting.
lem in allogeneic hematopoietic stem cell transplantations, or whether
it is the interaction between the virus, the pulmonary macrophage, and
the host. 117–120 CMV continues to be a problem, but there are now pre- PRIMARY HIV INFECTION
liminary studies of a CMV DNA vaccine that are promising. MONONUCLEOSIS
Two approaches have been taken to manage CMV infection for
solid-organ recipients. The first is to provide anti-CMV antiviral agents An acute syndrome develops very frequently at the time of development
when the donor, the recipient, or both are CMV-seropositive. Antiviral of primary infection with HIV. 124–127 The frequency with which the HIV
prophylaxis is initiated at transplantation and continued for up to 120 mononucleosis syndrome develops is uncertain, but for this discussion
days thereafter. The second is to provide CMV antiviral prophylaxis only the difference in features is more important. The acute retroviral syn-
for those situations where the donor is seropositive and the recipient is drome must be recognized for both the patient’s health and the public
seronegative. For other situations, weekly monitoring for CMV by PCR health. Fever is sudden in onset, followed by sore throat, lymphadenop-
is done. If that result is positive, the subject is treated for approximately athy, tonsillar hypertrophy, painful oral ulcerations, conjunctivitis, and
1 month. In those who undergo specific monitoring, fewer people receive rash. Nausea, vomiting, and diarrhea also occur. Leucopenia, throm-
anti-CMV antiviral drugs and for those who do, the duration is shorter. It bocytopenia, a relative increase in band neutrophils, and a small pro-
also makes the best sense as those recipients who were seropositive pre– portion of reactive lymphocytes usually can be identified on the blood
solid-organ transplantation have a very low frequency of disease. 116 film. Although absolute lymphocytosis is uncommon, the syndrome
For solid-organ transplantations, clinical illness caused by CMV is referred to as HIV mononucleosis. Uncommonly, patients may also
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and rejection of the transplanted organ are difficult to differentiate. develop a heterophile antibody. Among a group of 563 heterophile
Fever develops in the recipient when they begin to mount an immune antibody-positive patient samples retrospectively tested for HIV-1 RNA
response. Because the cells in the transplanted organ are now “more and p24 antigen, approximately 1 percent had evidence of primary
127
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foreign” than they were prior to virus reactivation, an immune response HIV-1 infection. In another study, none of 132 cases was positive.
occurs directed at the infected monocyte. Although both hepatic and Because in this situation, anti-HIV antibody response has not yet devel-
gastrointestinal changes occur, mononucleosis usually does not. There oped, HIV load in the blood should be measured by PCR to make a
is the potential for rejection of the donated organ. Reactivation of one’s diagnosis of HIV infection. Usually, viral load is very high (greater
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own latent CMV in a solid-organ recipient does not lead to a problem. than 50,000 viral particles per milliliter of blood). Early treatment may
On occasion, reactivation of CMV in the donor organ in a previously reduce the incidence of HIV-1 complications (Chap. 81). Acute HIV-1
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seropositive recipient can lead to illness. infection may be particularly contagious. Discussion of the findings
Other infectious problems develop in solid-organ recipients. It with the patient may prevent transmission to a sexual partner. 124,128
is proposed that reactivation of the CMV in the macrophage system
inhibits the protective function of that system. In the lung where inha-
lation of potentially infectious agents occurs continuously, new infec- OTHER AGENTS LINKED TO A
tion can develop because of impairment of the protective action of the MONONUCLEOSIS SYNDROME
macrophages or the neutrophils. 122,123 In addition, a number of organ-
isms can, in the case of renal transplantation, be transplanted with the Human herpes virus-6 occasionally has been associated with a
kidney. Besides the viruses discussed above, these can include bacteria, mononucleosis-type syndrome as has metapneumonia virus (see
yeast, and parasites, such as Strongyloides sp. Table 82–1). 129,130 Hepatitis A and rubella virus infection have produced
When fever develops there is a tendency for the transplantation the typical blood lymphocytic changes. Pharyngitis is not a prominent
physician to increase immunosuppression under the assumption that feature in patients infected with T. gondii. Lymphocytosis is mild, and
rejection is occurring. If the fever is a result of development of primary liver functions are normal even when the liver is enlarged. Usually,
infection with CMV, the immunosuppressive therapy leads to perma- toxoplasmosis presents as posterior cervical lymphadenopathy. In the
nent interference with development of posttransplantation immunity United States, exposure to oocysts from cat feces is the primary route of
to the CMV. That, in turn, leads to life-long continued problems with infection. In other countries, ingestion of partially cooked meat, espe-
CMV infection. cially from sheep, is a route of infection. The IgM immunofluorescent
One of the other confusing features for the transplantation phy- antibody test for T. gondii is useful in diagnosing the disease.
sician has stemmed from the common practice to provide ganciclovir Cat scratch disease, Corynebacterium diphtheriae pharyngitis,
prophylaxis to prevent CMV infection posttransplantation to every- infection with brucellosis, or lymphoma can be mistaken for mononu-
one (see above). Those who are seronegative, receive an organ from a cleosis. Other, as yet unidentified, agents probably produce the classic
seropositive donor, and receive ganciclovir that suppresses reactivation syndrome as laboratory studies for all of the known infectious agents,

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