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

CLINICAL MANIFESTATIONS COMPLICATIONS
In most cases, the new infection with CMV is clinically silent. However, Hemolytic anemia and thrombocytopenia occur in primary CMV infec-
some newly infected individuals will develop high fever (40°C often), tion and are other findings that may lead the clinician initially to con-
weight loss, and associated malaise and myalgia. Abnormal liver func- sider a diagnosis of lymphoma. There are a variety of pathogenic factors,
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tion and a palpable spleen similar to that seen with EBV occur. A left which explain these hematologic changes. The most prominent neuro-
shift in the differential white count may occur initially, evidenced by logic complication is Guillain-Barré syndrome and, less commonly,
a higher proportion of band neutrophils. The incidence of lymphade- transverse myelitis and aseptic meningitis (see Table 82–3). Antibody
nopathy is much higher in the young then in the older person with pri- that develops to CMV-infected cells cross reacts with GM antigen that
2
mary CMV. Infection occurs in the older individual because they have may explain the development of Guillain-Barré syndrome. 66,67 This anti-
not been infected during their younger years (Tables 82–2 and 82–3 list body can be absorbed with CMV-infected fibroblasts but not by unin-
additional clinical and laboratory findings). Because no classic mani- fected fibroblasts.
festation, such as severe exudative pharyngitis, develops, CMV is not Because it is not the B cell that is the target of infection, but the
considered in the differential diagnosis. Instead, it is assumed that the monocyte–macrophage lineage, 112,113 evolution to unrestrained B-cell
patient has a bacterial infection and antibiotics are administered. How replication, lymphoma, and PTLD do not occur.
frequently this occurs is uncertain but administration of a β-lactam
antibiotic may be associated with development of a rash and the mis- CYTOMEGALOVIRUS IN TRANSPLANTATION
taken impression that the recipient is allergic to penicillin. Because the
disease occurs in the older population, including those older than age CMV does not predispose to hematologic malignancy. However, it plays
50 years, the causes of fever of unknown origin often are pursued in an a critical role in all of the transplantation settings, with some very sim-
expensive evaluation prior to the diagnosis. A number of the laboratory ilar findings in lung and allogeneic hematopoietic stem cell transplants.
and physical findings raise many diagnostic possibilities. Development It is rare in autologous hematopoietic stem cell transplantations, but can
of antinuclear factor and thrombocytopenia (Table 82–5) often errone- occur and be a serious infection (Chap. 23 discusses CMV infection in
ously leads to the diagnosis of a collagen vascular disease. The presence allogeneic hematopoietic stem cell transplantation).
of splenomegaly raises the question of lymphoma. In all solid-organ transplantations, there are three potential types
of infection that can occur because of CMV. 114–116 The monocyte–
macrophage cells in all solid organs, for example, heart, kidney, pan-
LABORATORY FINDINGS creas, and liver of CMV-seropositive individuals, harbor CMV that can
The cell that becomes infected initially is not the B lymphocyte but be reactivated. The CMV-seronegative recipient who receives an organ
from a CMV-positive donor can develop a primary infection when the
a cell in the monocyte–macrophage lineage and it is that cell or cells CMV reactivates from the donor organ. Because this occurs when the
to which the T-lymphocyte responds. 112,113 Lymphocytosis that devel- recipient is receiving immunosuppression, this is the most serious clin-
ops is indistinguishable from that of EBV-induced disease. In some ical problem. 115,116 The classic situation occurs when a parent, who is
patients, neutrophilia with band forms occurs early in the infection. older and has developed infection in the past, donates a kidney or a
In addition, because the incubation period is 30 to 40 days, IgG and segment of their liver containing CMV to their child. A second pos-
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IgM antibodies to CMV have already developed when the disease first sibility is that the CMV in the seropositive recipient, even when the
becomes manifest. The PCR of a blood sample for CMV usually is pos- donor is CMV-seronegative, can be reactivated. Because it is the recip-
itive, and CMV can be isolated from specimens of urine or saliva. Liver ient’s own latent CMV that is reactivated, the clinical manifestations of
function abnormalities (see Tables 82–2 and 82–3) include bilirubin infection usually are mild or absent. The third occurs when both the
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elevation. Jaundice may occur in up to 25 percent of these ill patients. donor and the recipient are both CMV-seropositive. Clinical disease can
Prolonged illness and severe fatigue is quite common in this subset of sometimes occur, but its severity is difficult to predict. Clinical disease
ill individuals. consists of fever, liver function abnormalities, and inflammatory bowel
changes. Prior to the availability of antiviral agents, most patients who
developed primary CMV infection did well. In solid-organ transplan-
116
tation patients, in the majority of situations, immunosuppressive ther-
apy starts with the transplantation and then is maintained for prolonged
TABLE 82–5. Laboratory Findings in Mononucleosis periods.
Complication Epstein-Barr Virus Cytomegalovirus CMV pulmonary problems occur mainly in lung and allogeneic
Heterophile +++ – hematopoietic stem cell transplantations. One contributing factor is
antibody that an ideal in vitro growth system for CMV is pulmonary macro-
phages obtained by bronchoalveolar lavage (BAL) from humans.
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Lymphocytosis +++ ++
That raises the question, does the CMV grow well in the pulmonary
Reactive +++ ++ macrophage in vivo? Does latency in the macrophage–monocyte cellu-
lymphocytes lar system from which it reactivates play an important role in lung and
Abnormal liver ++ ++ allogeneic hematopoietic stem cell transplant patient populations? 118–120
function It is in that setting that the infected macrophage is either occurring in
Antinuclear factor + + a foreign tissue, the lung transplant, or is being seen as foreign by the
allogeneic hematopoietic stem cell cellular derivatives.
Cold agglutinins + + In patients receiving an allogeneic hematopoietic stem cell trans-
Cryoglobulins + + plant, the immunosuppressive regimen is of relatively short dura-
Decreased platelets ++ + tion, unless the patient develops graft-versus-host disease compared
to that for solid-organ recipients. If both the recipient and the donor
+++, Characteristic; ++, common; +, occurs. are CMV-seronegative, posttransplantation, CMV infection does not

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