Postural Epigastric Pain as a Sign of Cytomegalovirus Gastritis in Renal Transplant Recipients: A Case-Based Review

Background

Cytomegalovirus (CMV) infection is a common cause of morbidity and mortality among patients receiving chronic maintenance immunosuppression and is often considered the most important infection in renal transplantation. CMV gastritis has been reported in transplant recipients. Symptoms are usually considered nonspecific, and gastroscopy with biopsy is usually performed to establish the diagnosis.

Methods

We report a case of primary CMV gastritis in a renal transplant recipient. A 34-year-old man presented 4 months after renal transplantation with a 1-week history of epigastric pain that decreased in supine position, increased while sitting, and further increased when standing or walking. The immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil, and prednisone. Evaluation revealed CMV viremia with a high viral load and CMV gastritis was confirmed using gastroscopy and histopathologic examination. Intravenous ganciclovir was started and continued for 3 weeks. The epigastric pain completely resolved after treatment with ganciclovir.

Conclusions

Postural epigastric pain as a sign of CMV gastritis is fairly rare in renal transplant recipients. To our knowledge this is the third article presented in the literature so far.     

Lack of cytomegalovirus and polyomavirus coexistence in Iranian kidney transplant recipients

Introduction

Maintenance of kidney graft function is essential, averting infection and coinfection. Cytomegalovirus (CMV) and BK polyomavirus (BKV) coinfection have been reported. There are a few studies of CMV and BKV infection in kidney transplant recipients in Iran, but no studies of their coinfection.

Objective

To assess the coexistence of CMV and BKV infection in renal transplant recipients.

Patients and Methods

The presence of CMV and BKV was assessed using real-time polymerase chain reaction in a cross-sectional study in 91 renal transplant recipients at 1 month posttransplantation. Assessment of CMV was performed only in blood samples, whereas BKV was assessed in both serum and urine samples.

Results

The 91 patients included 57 men (62.6%) and 34 women (37.4%), who ranged in age from 19 to 76 years. Simultaneous evaluation of CMV in plasma and BKV in urine demonstrated no significant association. Of 24 patients positive for BKV in urine, 8 (33.3%) were positive for CMV in plasma. Sixty-seven patients tested negative for BKV in urine, whereas 23 (34.4%) tested positive for CMV, which is unremarkable. Comparison of coinfection with plasma CMV and plasma BKV demonstrated no significant correlation. In 3 patients positive for BKV in plasma only, 1 (33.3%) was positive for CMV, whereas in 88 patients negative for BKV in plasma, 30 were positive for CMV.

Conclusion

No significant association was observed between CMV and BKV infections in kidney transplant recipients.     

Preemptive Therapy for the Prevention of Cytomegalovirus Disease in Renal Transplant Recipients: Our Preliminary Experience

Background

Cytomegalovirus (CMV) disease represents an important cause of morbidity in renal transplant recipients. We report our preliminary evaluation of the efficacy and security of preemptive therapy to manage renal transplant recipients with evidence of active CMV replication.

Methods

Preemptive therapy with gancyclovir and/or valgancyclovir (VGCV) was recently substituted for CMV antiviral prophylaxis at our institution. Between May 2006 and December 2007, all patients undergoing renal transplantation were included in a CMV infection surveillance program. Blood samples to determine CMV viral load were obtained weekly during the first 4 months. Asymptomatic patients, with a viral load determined using polymerase chain reaction (PCR) with CMV DNA >100,000 copies/mL, were treated with VGCV for 3 months or until resolution of viral replication. Until April 2006, patients undergoing renal transplantation received CMV prophylaxis with oral acyclovir and pp65 antigenemia was the test for CMV infection surveillance. The group on preemptive therapy was compared with a historical group on prophylaxis therapy: 100 renal patients who underwent transplantation between April 2004 and 2006.

Results

Among 96 recipients, quantitative determination of viral DNA in blood was elevated in 14 asymptomatic patients, who were treated with oral VGCV for 3 months. The patients were followed up for a median time of 13.3 months. None of the 14 patients who received VGCV developed CMV disease.

Conclusion

VGCV administered as preemptive therapy was safe and efficacious to prevent CMV disease.     

Universal prophylaxis with gancyclovir preparation is not necessary in our kidney allograft recipients

Background

Cytomegalovirus (CMV) infection is a common cause of morbidity, graft loss, and mortality among kidney recipients due to its direct and indirect influences on organs and systems. In this study, we evaluated CMV infection in transplant recipients in Iran.

Materials and methods

We performed a retrospective study of 104 renal allograft recipients and their donors transplanted between January 2005 and January 2010. We included all patients (recipients and donors) with least one valid laboratory result for CMV immunoglobulin (Ig)G and CMV IgM. We evaluated the occurrence of CMV disease in allograft recipients in at least the first 3 years after renal transplantation.

Results

Fifty-seven renal allograft recipients (54.8%) were males and 47 (45.2%) were females. The overall mean (± standard error) age was 40.32 ± 13.30 years. CMV IgG was positive in 95 cases (91.3%), negative in 9 (8.7%). Serologically, 76.9% patients were D⁺/R⁺ 14.4% D⁻/R⁺, and 8.7% D⁺R⁻. Due to the proccurrence of rejection rendering them high-risk patients for CMV infection about 15% of subjects were treated with anti thymocyte globulin (ATG) followed by prophylactic intravenous gancyclovir for 2 weeks, at doses based on allograft function. Confirmed CMV infection and CMV disease occurred in less than 5% of recipients in the first year after transplantation. About 6% of renal allograft recipients died due to infections during the first 3 years posttransplantation but CMV disease was not confirmed in these patients.

Conclusion

Due to the living donor-based renal transplantation program, the selection of low-risk patients (panel-reactive antibodies 30%), the low percent of D⁺/R⁻ patients (8.7%) and the low use of ATG for induction therapy in the Iranian model, universal prophylaxis with gancyclovir is not routinely recommended for our cases.     

Cytomegalovirus Infection and Disease Following Renal Transplantation: Preliminary Report of Incidence and Potential Risk Factors

Background

Cytomegalovirus (CMV) infection and disease are major causes of morbidity and mortality after renal transplantation. However, the incidence and potential risk factors are different in developing countries. We sought to determine the incidence and potential risk factors for CMV infection and disease in our center. We also sought to identify groups of recipients who may benefit from preemptive therapy.

Materials and methods

Forty renal transplant recipients were monitored regularly for CMV infection within 6 months after transplantation using CMV immunoglobulin (Ig) M and IgG titers, pp65 antigenemia, and CMV DNA by polymerase chain reaction (PCR). Thorough laboratory and physical examinations were performed to detect CMV disease. We evaluated the role of various factors in CMV infection and disease development using Cox regression and Kaplan-Meier statistical models.

Results

CMV infection and disease were detected in 33 (82.5%) and 10 (25%) subjects, respectively. Average time to infection and disease development was 4.7 and 11 weeks, respectively. PCR was the most accurate method of diagnosis in 22 (67%) cases. By comparison to other recipients, patients who received antithymocyte globulin (ATG) showed a significant decrease in time to disease development (P = .009). Upon multivariate survival analysis, ATG therapy remained an independent risk factor for CMV disease (odds ratio: 6.8; P = .02).

Conclusion

Due to the low rate of progression from CMV infection to disease, it does not seem reasonable to perform preemptive therapy in all infected cases. ATG therapy was an independent risk factor for CMV disease. Recipients of this treatment would be proper candidates to receive preemptive therapy.     

Cytomegalovirus viremia after kidney transplantation in Thailand: predictors of symptomatic infection and outcome

Background

While prevention of cytomegalovirus (CMV) infection after kidney transplantation (KT) has become a standard practice in Western countries, this approach is not always feasible in Thailand. In order to argue for the need for CMV prevention, the knowledge on the incidence and impact of the CMV infection following KT is highly desirable.

Methods

We retrospectively reviewed medical records of adult patients who underwent KT at our transplant center between January 2006 and December 2010. Patients who developed CMV viremia within 1 year after transplantation were studied for the incidence, risk factors, and outcome of symptomatic infection. The threshold value of blood CMV DNA load indicating symptomatic infection was also analyzed.

Results

Symptomatic CMV infection occurred in 18 (4.6%) patients within a median time of 12.1 (range, 3-30) weeks after KT. At initial presentation, coexisting opportunistic infection was common (44%) and gastrointestinal tract was the major type of organ involvement (44%). Between groups of patients with symptomatic and asymptomatic CMV infection, the mean (±standard deviation) level of blood viral load were significantly higher in the first group [4.2 (±0.5) vs 3.3 (±0.4) log copies/mL]. From multivariate analysis, associated factors of symptomatic infection included acute rejection [odds ratio (OR) 7.32, P = 0.001], and acute tubular necrosis (OR 3.44, P = .019). Death (13%) and graft failure (13%) were significantly higher among the symptomatic infection group than those in the no-infection group (P = .005 and .03, respectively).

Conclusion

Despite a low incidence rate, symptomatic CMV infection clearly resulted in significant morbidity following KT. In Thailand, the prevention of CMV infection should be prioritized among high-risk KT populations.     

Early and Delayed Onset Cytomegalovirus Infection of Liver Transplant Recipients in Endemic Areas

Background

The delayed onset of cytomegalovirus (CMV) infection after liver transplantation can place patients at risk for graft failure and mortality.

Methods

We compared early versus delayed onset of CMV infection to identify risk factors for mortality among liver transplant recipients in an endemic area.

Results

Among 710 consecutive adult liver transplant recipients, incidence of CMV infection was 47.5% (337/710). Male gender, biliary complications, acute rejection episodes, antilymphocyte antibodies high hemoglobin, and high total bilirubin were significantly different among patients with delayed versus early onset CMV infections. The overall incidence of early versus delayed CMV infections was 43.1% (306/710) versus 4.4% (31/710). Among them, 11.1% (34/306) and 25.8% (8/31) of patients developed CMV disease.

Conclusion

These results showed that a higher proportion of patients developed disease among delayed CMV infected patients (P = .039). The overall and graft survival curves for patients with early onset CMV infections were better than those of patients who had delayed onset CMV infections (P = .026 and P = .014). Recurrence of hepatitis B virus, hepatic dysfunction, and retransplantation were associated with increased mortality among patients who had a delayed CMV infection.     

The value of pre-emptive therapy for cytomegalovirus after liver transplantation

Background

Cytomegalovirus (CMV) infections are among the most common infections following liver transplantation. The main preventive methods for CMV infections are universal prophylaxis and pre-emptive therapy. In our study, we adopted a pre-emptive strategy in a higth-risk group of donor CMV-positive (D+)/recipient CMV-negative (R−) casses. We investigated whether this strategy was safe and effective to prevent CMV disease.

Methods

One hundred fifty-nine liver transplantation recipients who underwent over a 15-year period were retrospectively analyzed after follow-up for at least 6 months (mean, 63 months). Weekly quantitative polymerase chain reaction (PCR) measurements were performed to detect viral DNA. No CMV drug prophylaxis was given: antiviral CMV therapy was initiated when the PCR for CMV-DNA was >400 copies/mL.

Results

Fifty-one of 159 liver transplant recipients enrolled in the study received antiviral therapy. High-risk patients (D+/R−) developed CMV infections significantly more often than D−/R− serostatus (P = .005). CMV disease was diagnosed in 12% of CMV-positive patients. Independent of serostatus in 14 cases (27.5%) virological recurrence of CMV infection occurred after primary treatment. Survival analysis showed no significant difference between patients with versus without CMV infection (P = .950). No relationship could be found between transplant rejection and CMV infection (P = .349).

Conclusion

Our results showed that a pre-emptive strategy to prevent CMV disease was possible, even among the serological high-risk group. Only 12% of cases with CMV infection went on to manifest CMV disease with organ involvement. Survival curves were similar among patients with versus without CMV infections.     

Post-renal transplant cytomegalovirus infection: study of risk factors

Objectives

Cytomegalovirus (CMV) is a common opportunistic infection following renal transplantation (RTx). It responds promptly to antiviral treatment. The mortality rate reaches 90% if untreated. Identification of risk factors helps in the early diagnosis of CMV. We studied demographic features, risk factors, and outcomes associated with CMV infection in RTx recipients despite ganciclovir prophylaxis.

Materials and methods

We reviewed 720 RTx recipients between 2007 and 2009. We examined the serostatus of the donor and recipient before transplantation using an enzyme-linked immunosorbent assay, and diagnosed CMV infections in recipients by CMV DNA detection with a polymerase chain reaction.

Results

A total of 42 of 750 (5.6%) patients were identified to display CMV infection (69.1%) or disease (30.9%). Their mean age was 34 ± 13.5 years, with 80.9% men. CMV serologic status was D+/R− in 21.4% and D+/R+ in 59.5% patients. Fever, malaise (76.2%), and leukopenia (52.3%) were the commonest presenting symptoms; diabetes (30.9%) and hepatitis C virus (28.6%) the commonest comorbid conditions. Risk factors were triple drug immunosuppression (47.6%), antithymocyte globulin ATG induction (54.8%), and a rejection episode (26.1%) and methylprednisolone (76.2%) which were more common in CMV disease than infection. Mean CMV DNA at diagnosis was 78,803; 71.2% patients developed CMV within 6 months posttransplantation, the majority occurring after 3 months. With a mean follow-up of 4 ± 1.9 years, patient and graft survival rates were 85.7% and 81% with a mean serum creatinine value of 1.83 ± 12 mg/dL.

Conclusions

Universal CMV prophylaxis was associated with a low incidence (5.6%) and mild form of CMV disease among our patients.     

Utility of Oral Valganciclovir for Cytomegalovirus Prophylaxis: Does It Improve Treatment Compliance?

Introduction

Cytomegalovirus (CMV) infection is a significant cause of morbidity and mortality among heart transplant (HT) patients. Various prophylactic and preemptive treatment regimens have been used for its prevention. We sought to assess the impact of oral valganciclovir on CMV prophylaxis in HT patients.

Patients and Methods

A retrospective analysis of 536 consecutive HT patients at our institution allowed selection of subjects eligible for prophylaxis based on CMV serology (donor positive/recipient negative). Treatment compliance, rates of preemptive therapy and treatment for CMV disease were assessed according to prophylactic drug use. If the indication was present, treatment was considered to have been performed.

Results

Among 536 patients, 9.8% (n = 53) were eligible for prophylaxis. Seventeen patients (33%) received valganciclovir, with a compliance rate of 94.1%. The remaining 68% received prophylaxis mainly with IV. ganciclovir (5 mg/kg) during their hospital stay followed by oral ganciclovir, with a compliance rate of 57.1% (P = .01). No differences were observed when we analyzed the need for preemptive therapy (0 vs 7%; P = .28) or for treatment of systemic or organ-specific infection (6.3 vs 0%; 6.3 vs 14%, respectively; P = .8).

Conclusion

Oral valganciclovir facilitated treatment compliance in prophylaxis for CMV without being inferior to other prophylactic therapies.     

Outcome in Children Bridged and Nonbridged to Cardiac Transplantation

Background

Heart transplantation (HTx) in children with end-stage heart disease has become an accepted treatment option.

Objective

To evaluate our results of pediatric cardiac transplantation with vs without bridge methods.

Patients and Methods

The study included 31 patients (34 transplantations) younger than 18 years who underwent orthotopic HTx between March 1995 and December 2008. Ten patients were girls, and 21 were boys. Preoperative diagnoses included cardiomyopathy (n = 20), congenital heart disease (n = 7), hypertrophic cardiomyopathy (n = 2), restrictive cardiomyopathy (n = 1), and ischemic cardiomyopathy (n = 1). Mean (SD) ischemia time was 185 (72) minutes. Thirty-day mortality was 6%, and was due to primary graft failure (n = 2). Overall follow-up was 4.36 (3.93) years. Eleven patients underwent bridge techniques before HTx, and 11 patients required perioperative extracorporeal membrane oxygenation or ventricular assist device support.

Results

In the group that received extracorporeal membrane oxygenation, 8 patients (73%) were successfully weaned and discharged with excellent functional class. There were no differences in operative mortality, functional class, survival, rejection, and infection rates between the bridged and nonbridged groups. Overall actuarial 1- and 5-year survival rates were 93% and 83%, respectively. All survivors had good functional class.

Conclusion

Our findings demonstrate satisfactory medium-term outcome of HTx in selected pediatric patients with end-stage heart disease. Using bridge methods in children at high risk can increase the opportunity to receive a donor heart. These bridge methods achieve similar postoperative outcomes.     

Serological Profile of Pretransplantation Liver Patients

Introduction

A liver transplantation is the first choice of treatment for patients with hepatic insufficiency due to chronic diseases. Infections in the postoperative period represent one of the main causes of mortality in these cases. However, few articles have evaluated the predominance of certain infectious diseases and their influence on postoperative mortality.

Methods

We retrospectively evaluated the medical records of 236 patients who underwent liver transplantation from January 1997 to January 2007. In these records we checked the serological profiles for these diseases: toxoplasmosis, syphilis, human T lymphotropic virus (HTLV) I and II infection, Chagas disease, hepatitis A, hepatitis B, hepatitis C, paracoccidioidomycosis, tuberculosis, acquired immunodeficiency syndrome, cytomegalovirus (CMV), and mononucleosis (Epstein-Barr virus [EBV]). The statistical analysis was performed by table frequencies.

Results

CMV showed positivity (CMV-IgG) in 94.7% of patients, 95.8% for EBV, 33.3% for toxoplasmosis, 47.9% for hepatitis C, and 5% for hepatitis B.

Conclusion

Our analysis showed the importance of serological investigations and diagnostic examinations before the transplantation procedure, seeking to minimize possible reactivation of the disease after the use of immunosuppression drugs, particularly in the first 6 months after transplantation, or even to avoid a primary infection.     

Radionuclide imaging study of long-term pulmonary function after lobectomy in children with congenital cystic lung disease

Purpose

We evaluated the long-term pulmonary function after lobectomy for congenital cystic lung disease, in both infants and children, using radionuclide imaging (RI).

Methods

We performed a retrospective review of 93 patients who underwent resection of cystic lung lesions between 1974 and 2001. The results of postoperative lung volume/perfusion scintigraphy at 1 (n = 64), 5 (n = 32), and 10 years (n = 18) after surgery (V1, 5, 10/Q1, 5, 10) and mean transit time (MTT—a marker for air-trapping) at 1, 5, and 10 years after surgery (MTT1, 5, 10) were compared with respect to age at operation, preoperative infection, underlying disease, and type of surgery.

Results

Patients who were younger than 1 year at the time of surgery showed a significantly lower MTT5 (1.09 ± 0.08) and MTT10 (1.15 ± 0.11) than patients who were older than 1 year at the time of surgery (MTT5, 1.49 ± 0.67; MTT10, 1.54 ± 0.33). The noninfected group had significantly higher Q10 and lower MTT10 values (P < .05) compared to the infected group. No significant differences were observed between patients with single lobe vs multiple lobe resection.

Conclusions

The optimal age for surgery in patients with congenital cystic lung disease appears to be less than 1 year.     

Early and Late Virological Monitoring of Cytomegalovirus, Epstein-Barr Virus, and Human Herpes Virus 6 Infections in Small Bowel/Multivisceral Transplant Recipients

Background

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are the major causes of graft failure and posttransplantation mortality among small bowel and multivisceral transplantations (SB/MVT). Little is known about human herpes virus 6 (HHV-6) infections in transplant recipients.

Study Purpose

The purposes of this study were to analyze the clinical relevance of CMV, EBV, and HHV-6 infections after small bowel transplantation and to establish whether routine monitoring for HHV-6 infection should be recommended for the prevention of severe complications in this population.

Methods

Ten adult patients were monitored based on CMV, EBV, and HHV6 DNA quantifications in blood and biopsy tissue samples. Three patients were monitored for at least 5 months (early period) and 7 patients were monitored for 1 to 5 years after transplantation (late period).

Results

In the early period, despite prophylaxis all 3 patients developed symptomatic CMV infections: 1 fever/diarrhea, 1 enteritis and rejection, as well as 1 fever and pneumonia. Only 1 patient developed EBV and HHV-6 infections. The average time of onset of CMV infection was 3 months after transplantation and only 24 days for HHV6 infection. In the late period, of the 7 SB/MVT recipients only 1 developed an EBV infection at 2 years after transplantation. No CMV or HHV-6 infections were identified in any patient.

Conclusions

CMV infection is a major cause of organ disease and rejection in the early period after transplantation. EBV infection in adult recipients must be considered also in the late period, particularly in association with severe immunosuppression. Because HHV-6 infection occurs earlier than CMV/EBV, it may serve as an indicator for more intense virological surveillance.     

Impact of Cytomegalovirus Infection in Lung Transplant Patients Under Universal Prophylaxis: Single-Center Experience in Brazil

Introduction

Cytomegalovirus (CMV) infection, a common complication in lung transplant (LT) patients, is associated with worse outcomes. Therefore, prophylaxis and surveillance with preemptive treatment is recommended.

Objectives

Describe the epidemiology and impact on mortality of CMV infection in LT patients receiving CMV prophylaxis.

Methods

Single-center retrospective cohort of LT recipients from August 2003 to March 2008. We excluded patients with survival or follow-up shorter than 30 days. We reviewed medical charts and all CMV pp65 antigen results.

Results

Forty-seven patients met the inclusion criteria and 19 (40%) developed a CMV event: eight CMV infections, seven CMV syndromes, and 15 CMV diseases. The mean number of CMV events for each patient was 1.68 ± 0.88. Twelve patients developed CMV events during prophylaxis (5/12 had CMV serology D+/R−). Forty-six of the 47 patients had at least one episode of acute rejection (mean 2.23 ± 1.1). Median follow-up was 22 months (range = 3-50). There were seven deaths. Upon univariate analysis, CMV events were related to greater mortality (P = .04), especially if the patient experienced more than two events (P = .013) and if the first event occurred during the first 3 months after LT (P = .003). Nevertheless, a marginally significant relationship between CMV event during the first 3 months after LT and mortality was observed in the multivariate analysis (hazards ratio: 7.46; 95% confidence interval: 0.98-56.63; P = .052). Patients with CMV events more than 3 months post-LT showed the same survival as those who remained CMV-free.

Conclusion

Prophylaxis and preemptive treatment are safe and effective; however, the patients who develop CMV events during prophylaxis experience a worse prognosis.     

Prophylaxis of cytomegalovirus disease in mismatched patients after heart transplantation using combined antiviral and immunoglobulin therapy

Background

Cytomegalovirus (CMV) is a common cause of infection and morbidity after heart transplantation. Seronegative recipients (R−) of seropositive donor hearts (D+) are at high risk for CMV disease. We compared three different CMV prophylaxis regimens using combined antiviral and immunoglobulin therapy.

Methods

In 99 patients who survived more than 30 days after heart transplant, all received induction with antilymphocytic therapy and triple-drug therapy. In group A, D+R− patients received one dose of intravenous immunoglobulin (IVIG) followed by one dose of CMV-specific immunoglobulin (CMV-IVIG), and intravenous ganciclovir (GCV) for 4 weeks followed by 11 months of oral acyclovir (ACV). In group B, D+R− patients received one dose IVIG followed by five doses of CMV-IVIG and intravenous GCV for 14 weeks followed by 9 months of oral ACV. In group C, D+R− patients were treated with the same regimen as for group B, except oral ACV was replaced with oral GCV.

Results

The actuarial freedom from CMV disease for D+R− patients at 1 month, 1 year, and 2 years after transplantation in group A was 100%, 25% ± 15%, and 25% ± 15%, respectively; group B was 100%, 67% ± 27%, and 67% ± 27%; group C was 100%, 83% ± 15%, and 83% ± 15% (P < .01, groups B and C vs group A). By comparison, the actuarial freedom from CMV disease for seropositive recipients (D−R+ or D+R+) at 1 month, 1 year, and 2 years in group A was 100%, 87% ± 7%, and 82% ± 8%, respectively; group B was 100%, 88% ± 8%, and 75% ± 11%; group C was 100%, 72% ± 9%, and 72% ± 9% (P = NS among groups). Rejection rates did not differ among the three groups.

Conclusions

A longer course of intravenous GCV with multiple doses of CMV-IVIG was a more effective prophylaxis regimen against CMV disease for the high-risk group of seronegative recipients of seropositive donor hearts.     

Long-term outcome in patients with prenatally diagnosed cystic lung disease: special reference to ventilation and perfusion scan in the affected lung

Background/Purpose

The natural history of cystic lung disease (CLD) such as congenital cystic adenomatoid malformation (CCAM) and pulmonary sequestration has been altered by the advent of prenatal diagnosis. Although recent advances including fetal therapy have gradually improved outcome, the long-term course and the function of the residual lung have not been well clarified.

Methods

Twenty-two patients with CLD who had been prenatally diagnosed and treated between 1990 and 2004 were reviewed. The clinical outcome and growth measurements were established, and, where possible, all infants underwent ventilation and perfusion lung scan.

Results

Mediastinal shift was present in 14 fetuses. Fetal hydrops was present in 5 fetuses. Antenatal intervention was performed for hydrops in 2 fetuses (cyst-amniotic shunt and aspiration). Twenty-one infants underwent appropriate excisional surgery. Final diagnosis included CCAM (n = 12) and pulmonary sequestration (n = 7). No late death was observed. Common complications were failure to thrive (n = 5), frequent respiratory tract infection (n = 4), and asthmatic attack (n = 4). A significant decrease in lung ventilation and perfusion on the affected side was observed in patients with hydrops, lobectomy, and CCAM.

Conclusion

Long-term follow-up including respiratory care and growth assessment should be performed in prenatally diagnosed patients with CLD, especially those who present with hydrops.     

Histologic Features of Cytomegalovirus Enteritis in Small Bowel Allografts

Background

Cytomegalovirus (CMV) is one of the most common viral infections to affect solid organ transplant patients, most frequently owing to reactivation of a latent infection as a result of immunosuppression. CMV enteritis (CE) may enter into the differential diagnosis of acute rejection in biopsies of small bowel (SB) allografts, where differentiation is important due to disparate therapies.

Objective

The aim of this study was to identify histologic features in SB allografts that may suggest CE.

Methods

The case files for a single institution were queried for all cases of SB mucosal biopsies with cells positive by CMV immunoperoxidase staining. Morphologic and clinical information was reviewed.

Results

Six biopsies demonstrating immunoperoxidase-confirmed CE were identified in a retrospective review of the records of a single institution. A common predisposing factor was the administration of high-dose steroids within a month before CE diagnosis. Most cases (66%) displayed a demarcated area of villous/crypt loss with an abundance of plasma cells and lymphocytes and a paucity of eosinophils. One case showed an acute enteritis-like pattern of injury, corresponding with a higher number of CMV-positive cells. CMV inclusions were visible on hematoxylin-eosin stains in all but 1 case. In no case were histologic criteria for acute cellular rejection met.

Conclusions

The presence of circumscribed area of mucosal injury with few eosinophils or an acute enteritis pattern should prompt the identification of viral inclusions or the acquisition of a CMV immunostain.     

A prospective evaluation of leflunomide therapy for cytomegalovirus disease in renal transplant recipients

Aim

A preliminary observation suggests leflunomide is effective in the treatment of cytomegalovirus (CMV) disease in renal transplant recipients. A prospective evaluation was conducted in renal transplant recipients to study the efficacy of leflunomide in the treatment of CMV disease.

Patients and methods

With prior approval and informed consent for therapy and follow-up, 17 consecutive consenting renal transplant recipients with proven CMV disease were treated with leflunomide. CMV disease was defined as a clinical syndrome of fever and/or symptoms of organ involvement, leukopenia, and a positive nested CMV quantitative PCR test at 0.001 μg/5 μL template input, with or without histologic evidence of tissue invasion. Leflunomide metabolite concentrations (A77 1726) were monitored.

Results

Of the 17 patients, 14 patients were treated for 6 months for CMV disease the first time; the remaining 3 received leflunomide treatment for relapse after ganciclovir treatment, for a year. Seven patients had fever with viremia and no organ involvement, nine had viremia with involvement of gastrointestinal tract, and one had fever with CMV inclusions in the allograft, with no demonstrable viremia. The three patients with relapse treated with leflunomide responded. Overall, 15 patients (88%) clinically responded to leflunomide therapy and with viral clearance from blood and healing of involved organs. The cost of therapy with intravenous ganciclovir (Cymevene, Roche) for 2 weeks was US $721 while that of leflunomide (Cleft, Cipla Ltd) for 6 months was US $64.

Conclusion

Leflunomide treatment for CMV disease in renal transplant recipients is effective, simple, and economical.