Page 554 - Clinical Immunology_ Principles and Practice ( PDFDrive )

532 Part four Immunological Deficiencies

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of the gut. CMV viremia is common during this period. However, In high-risk solid-organ recipients (D /R ), in particular recipients
routine use of preemptive or prophylactic therapy has been of lung and small bowel, although preemptive therapy is an
effective in preventing life-threatening CMV disease. The risk accepted alternative, universal prophylaxis is preferred. It has
of Pneumocystis pneumonia (PCP) has also decreased since the the theoretical advantage of preventing reactivation of other
introduction of PCP prophylaxis. 47 herpes viruses and may be more likely to prevent the indirect
effects of CMV. 48,50 Recently, the development of commercially
Late Postengraftment Period available CMV- specific IFN-γ release assays, which detect CMV-
This is the period of late immune recovery and ends when the specific T cells in whole blood, may allow for more precise target-
patient regains normal immunity. In the absence of chronic ing of prophylactic strategies, beyond those currently used. 55
GvHD, this period can last up to 2 years. Viral and bacterial
infections of the respiratory tract are common during this period. Other Herpes Viruses
The development of chronic GvHD delays immune restoration HSV infection is common in both SOT and HSCT recipients
and can extend this period for many years (as long as immunosup- during the first month after transplantation. Routine use of
pressive drugs are required). Infections with encapsulated bacteria antiviral prophylaxis has successfully decreased the incidence of
are common in patients with chronic GvHD, as well as oppor- severe HSV infection. However, breakthrough mucocutaneous
tunistic viral and fungal infections, including VZV and CMV HSV infection and even disseminated disease can still occur.
infections, invasive aspergillosis and non-Aspergillus mold Reactivation of VZV infection is also common; however, acyclovir
infections, and PJP, among others. 47 prophylaxis has decreased the incidence of disseminated VZV
infection significantly. Both severe VZV and HSV infections are
INFECTIONS OF PARTICULAR IMPORTANCE IN typically treated with intravenous acyclovir. 45,46
TRANSPLANT RECIPIENTS Although EBV can cause a wide spectrum of disease, EBV-
associated PTLD is the most feared complication. The term
Cytomegalovirus Infection EBV-associated PTLD is generally used to describe a heterogeneous
CMV is one of the most important pathogens affecting transplant group of clinical syndromes associated with uncontrolled
recipients. It is widely distributed in the general population; lymphoproliferation, which can result in true malignancies
seropositivity for CMV varies in different geographical regions containing clonal chromosomal abnormalities. Early diagnosis
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and ranges from 30% to 97%. Before widespread use of interven- requires a high index of suspicion. EBV viral load monitoring
tions aimed at reducing the incidence of CMV disease (i.e., and radiological evaluation can assist in early diagnosis. Reduction
pneumonitis, gastroenteritis, hepatitis, etc.), it occurred frequently of immunosuppression should be the initial strategy in managing
during the first 3 months after transplantation. In SOT, the highest the disease. Timing of additional therapies, such as treatment
risk for CMV disease is in patients in whom the donor is seroposi- with antivirals and rituximab and chemotherapy, remains
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tive and the recipient is seronegative for CMV (D /R ). CMV controversial. 45,47
has a predilection to invade the allograft, possibly as a result of HHV-6 has been associated with disease after transplantation,
an aberrant immune response within the graft. The risk of and although a variety of clinical manifestations have been
infection varies also with the type of transplantation; recipients described, the more convincing association is with encephalitis.
of lung, small intestine, and pancreas transplants have a higher The initial presentation may be subtle with memory loss or
risk, whereas the risk in liver and kidney recipients is lower. In disorientation. However, it may progress to severe mental status
SOT, CMV infection has been found consistently to be an abnormalities and seizures. The diagnosis is established with a
independent risk factor for other infectious complications as positive PCR in the CSF, and absence of other infectious agents.
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well as graft rejection. In HSCT, infection is usually the result Treatment is with ganciclovir or foscarnet. 47
of reactivation of endogenous virus; hence the highest risk is in
seropositive recipients. Without prophylaxis, up to 80% of Invasive Filamentous Fungal Infections
seropositive recipients will experience CMV infection after HSCT. Invasive pulmonary aspergillosis is the most common invasive
Seronegative individuals have a 30–40% chance of becoming filamentous fungal infection. Dissemination, including to the
infected when receiving unfiltered blood products or stem cells brain, can occur and should be ruled out in all transplant
from a seropositive donor. Risk factors for CMV disease are recipients. Risk factors are prolonged neutropenia, high-dose
acute and chronic GvHD, use of high-dose corticosteroids, use corticosteroids, cord blood transplantation, CMV disease, GvHD,
of cord blood, T-cell depletion, and use of mismatched or graft rejection, and lung transplantation. Manifestations of fila-
unrelated donors. 49 mentous fungi that are almost exclusively seen in lung transplant
Typically, CMV viremia precedes CMV disease by 1–2 weeks; recipients are tracheobronchitis, characterized by ulceration and
therefore close monitoring of CMV reactivation by polymerase cartilage invasion, and bronchial anastomotic infections. 51
chain reaction (PCR) assays or pp65 antigenemia allows the Monitoring serum Aspergillus galactomannan in high-risk
detection of early replication, and therefore institution of patients, as well as computed tomography (CT) imaging, can
appropriate antiviral therapy (ganciclovir, valganciclovir, or assist in the early diagnosis of invasive aspergillosis. Despite early
foscarnet) before the development of end organ disease. This diagnosis and treatment, the mortality associated with invasive
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approach, termed preemptive therapy, has the advantage of aspergillosis, in particular in HSCT, is still high. Antifungal
effectively decreasing the incidence of early CMV disease and prophylaxis should be considered in patients in whom prolonged
limiting drug-related toxicities. In addition, a limited amount neutropenia is expected, in patients with chronic GvHD receiving
of viral replication may allow for the development of CMV-specific high-dose corticosteroids, and in lung transplant recipients.
immune reconstitution. Preemptive therapy is the preferred Voriconazole is considered the drug of choice for invasive
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method for preventing CMV disease in HSCT and is widely aspergillosis, but newer-generation azoles, such as posaconazole
used in SOT in patients with intermediate risk for CMV disease. and isavuconazole, are good alternatives.