Concurrent Cytomegalovirus Infection Research Articles

Neuroendocrine tumor of the rectum with concurrent cytomegalovirus infection

Neuroendocrine tumor of the rectum with concurrent cytomegalovirus infection

The Histopathology of Anorectal Neisseria gonorrhoeae Infection.

Neisseria gonorrhoeae infection of the anorectal tract is often asymptomatic and infrequently biopsied, but pathologists can be tasked with identifying the histologic features of possible infection. The study was undertaken to better characterize clinical and morphologic features of confirmed anorectal gonococcal infection. From 2011 to 2020, 201 positive gonococcal nucleic acid amplification testing samples from 174 patients collected from the distal colorectum and/or anus were matched to eight patients with concurrent biopsy specimens of the distal anorectum. Complete demographic, clinical, and infectious information was collected for each biopsied patient. The histomorphologic features of each biopsy were systematically tabulated. All eight gonococcal cases were obtained from men who have sex with men. Each case showed at least mild acute inflammation with moderate activity identified in one case with concurrent cytomegalovirus infection. Intense lymphoplasmacytic infiltration was not commonly seen (two of eight). Half of the cases showed mucosal ulceration, and seven of eight cases demonstrated lymphoid aggregates. The microscopic features are mild compared with other well-described types of infectious proctitis, with most cases displaying mild acute inflammation and scattered lymphoid aggregates. These findings highlight the importance of obtaining a complete patient history and recommending additional infectious workup even when only subtle changes are present.

Invasive pulmonary aspergillosis in heart transplant recipients: Is mortality decreasing?

IntroductionInfection remains a major complication among heart transplant (HT) recipients, causing approximately 20% of deaths in the first year after transplantation. In this population, Aspergillus species can have various clinical presentations including invasive pulmonary aspergillosis (IPA), which has high mortality (53-78%). AimsTo establish the characteristics of IPA infection in HT recipients and their outcomes in our setting. MethodsOf 328 heart transplantations performed in our center between 1998 and 2016, five cases of IPA were identified. Patient medical records were examined and clinical variables were extracted. ResultsAll cases were male, with a mean age of 62 years. The most common indication for HT was nonischemic dilated cardiomyopathy. Productive cough was reported as the main symptom. The imaging assessment was based on chest radiography and chest computed tomography. The most commonly reported radiological abnormality was multiple nodular opacities in both techniques. Bronchoscopy was performed in all patients and A. fumigatus was isolated in four cases on BAL culture. Treatment included amphotericin in four patients, subsequently changed to voriconazole in three patients, and posaconazole in one patient, with total treatment lasting an average of 12 months. Neutropenia was found in only one patient, renal failure was observed in two patients, and concurrent cytomegalovirus infection occurred in three patients. All patients survived after a mean follow-up of 18 months. ConclusionsIPA is a potentially lethal complication after HT. An early diagnosis and prompt initiation of aggressive treatment are the cornerstone for better survival.

Are CMV-predictive scores in inflammatory bowel disease useful in clinical practice?

Concurrent cytomegalovirus (CMV) in inflammatory bowel disease (IBD)-related colitis is an important scenario associated with high rates of colectomy and other morbidity. Due to the low incidence of CMV, testing of all patients is associated with an unacceptably high consumption of resources and delay in treatment. Therefore, several predictive scores have been developed to identify patients at risk for a CMV infection. We performed a retrospective single center study in a German University hospital including all IBD patients with available data on CMV-PCR analysis in whole blood between 2010 and 2018 and evaluated 2 prognostic scores for CMV infection for their diagnostic accuracy. In the study, 907 patients with IBD and CMV-PCR were identified. Of them, 21 patients (2.3 %) had a positive CMV-PCR (≥ 1000 copies/mL), 14 of them in ulcerative colitis and 7 in Crohn's disease. The Berlin Score identified 667 patients (73.1 %) as potentially CMV-positive, resulting in a positive predictive value of 2.5 % and a negative predictive value of 98.3 %. In contrast, the Münster Score identified 60 patients as potentially CMV-positive, resulting in a PPV of 20 % and an NPV of 99.4 %. Scoring systems can help to identify patients at risk for a CMV infection and minimize resource consumption and delay in treatment. Due to low incidence, a 2-step-algorithm, consisting of the Münster Score followed by a CMV-PCR if the score indicates a CMV infection, is preferable.

CYTOMEGALOVIRUS PNEUMONITIS IN A CRITICALLY ILL PATIENT WITH RHEUMATOID ARTHRITIS ON IMMUNOTHERAPY

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Cytomegalovirus (CMV) pneumonitis is an uncommon diagnosis typically seen in patients with immunosuppression. It can range in pathology from minimal interstitial pneumonitis to diffuse alveolar damage. It is associated with high morbidity and mortality in HIV patients and transplant recipients but is rare in patients with autoimmune diseases on immunotherapy. CASE PRESENTATION: A 52 year old female with previous history of rheumatoid arthritis on methotrexate and infliximab for over 1 year was transferred from outside hospital to the ICU after progressive dyspnea and tachypnea with high fever for two weeks that had not been improving on antibiotics. She was intubated for pending respiratory failure and had an urgent bronchoscopy with lavage. Sample from BAL showed histoplasmosis and amphotericin B with broad antibiotics and steroid burst was started. Her course was complicated over the first week of her stay by shock requiring pressor support, AKI, transaminitis, anemia, thrombocytopenia, and difficulty weaning from the ventilator. She was diagnosed with disseminated histoplasmosis. Other labwork for infectious and autoimmune workup at this time had been negative, including histo antigen, blastomyces, toxoplasma, HIV, hepatitis panel, ANA, and ANCA panel. Extubation was attempted on day 12 of her stay but she required reintubation the following day. Ampho B was switched to itraconazole at this time but patient still did not significantly improve after several more days. A surgical lung biopsy revealed CMV with diffuse alveolar damage in addition to histoplasmosis and the patient developed a pneumothorax. Viral load PCR for CMV was 99500 IU/ml. Ganciclovir was started. Her course would be complicated further by A-Fib with RVR and neutropenia, but over the next several weeks her oxygenation and overall clinical condition would slowly improve. She was transferred to LTACH after a 2 month long ICU stay. She was eventually extubated at LTACH and is currently doing well at home following an inpatient rehab stay. DISCUSSION: This patient developed multiple organ failure during her ICU stay and only began to clinically improve following diagnosis and treatment of her CMV infection. She did not respond well to broad spectrum antibiotics or antifungal initially. BAL has poor sensitivity and specificity for CMV and more aggressive diagnostic workup is sometimes indicated. There are no current guidelines for either antiviral prophylaxis or duration of therapy for CMV in setting of autoimmune disorder on immunotherapy. CONCLUSIONS: We strongly suggest that in patients on immunosuppressive therapy with acute respiratory failure who fail to respond to treatment with a recognized pathogen, other pathologies should be considered. Reference #1: Papazian L et al. Cytomegalovirus reactivation in ICU patients. Intensive Care Med. Jan;42(1):28-37. 2016 Reference #2: Travi G et al. Cytomegalovirus pneumonia in hematopoietic stem cell recipients. J Intensive Care Med. Jul-Aug;29(4):200-12. 2014 Reference #3: Lee KY et al. Predictors of Mortality in autoimmune disease patients with concurrent cytomegalovirus infections detected by quantitative real-time PCR. PLoS One. Jul 25;12(7). 2017 DISCLOSURES: No relevant relationships by Clifford Hecht, source=Web Response

Invasive pulmonary aspergillosis in heart transplant recipients: Is mortality decreasing?

IntroductionInfection remains a major complication among heart transplant (HT) recipients, causing approximately 20% of deaths in the first year after transplantation. In this population, Aspergillus spp. can have various clinical presentations including invasive pulmonary aspergillosis (IPA), with high mortality (53-78%). ObjectivesTo establish the characteristics of IPA infection in HT recipients and their outcomes in our center. MethodsAmong 328 HTs performed in our center between 1998 and 2016, we identified five cases of IPA. Patient medical records were examined and clinical variables were extracted. ResultsAll cases were male, and mean age was 62 years. The most common indication for HT was non-ischemic dilated cardiomyopathy. Productive cough was reported as the main symptom. The radiological assessment was based on chest X-ray and chest computed tomography. The most commonly reported radiographic abnormality was multiple nodular opacities in both techniques. Bronchoscopy was performed in all patients and Aspergillus fumigatus was isolated in four cases on bronchoalveolar lavage culture. Treatment included amphotericin in four patients, subsequently changed to voriconazole in three, and posaconazole in one patient, with total treatment lasting an average of 12 months. Neutropenia was found in only one patient, renal failure was observed in two patients, and concurrent cytomegalovirus infection in three patients. All patients were alive after a mean follow-up of 18 months. ConclusionsIPA is a potentially lethal complication after HT. Early diagnosis and prompt initiation of aggressive treatment are the cornerstone of better survival.

Predictors of mortality in autoimmune disease patients with concurrent cytomegalovirus infections detected by quantitative real-time PCR.

ObjectiveCytomegaloviruses (CMV) can have a significant impact on the prognosis of immunocompromised patients. Unlike in the transplantation and AIDS fields, only a few studies on CMV infections have been published in the field of autoimmunity. In this study, we examined the clinical outcomes of CMV infections in patients with autoimmune diseases at a single tertiary medical institution.MethodsA retrospective study was performed to identify the mortality risk factors associated with CMV infections in patients with autoimmune diseases. We reviewed the medical records of patients with autoimmune diseases who were diagnosed with CMV infections using real-time quantitative polymerase chain reaction between December 2005 and March 2016. Clinical and laboratory parameters as well as treatment outcomes were analyzed.ResultsSeventy-three CMV infected patients were separated into survivors and non-survivors. Non-survivors had significantly higher median CMV-DNA copy numbers than survivors (95,500 vs 6,700 copies/mL, p = 0.005) and demonstrated significantly more frequent incidents of CMV pneumonitis (69.2 vs 36.2%, p = 0.007). After adjusting for multiple confounding covariates, the log CMV-DNA copies/mL (hazard ratio, 1.48; 95% confidence interval, 1.14–1.92; p = 0.003) and the presence of concurrent infections (hazard ratio, 22.00; 95% confidence interval, 2.75–175.97, p = 0.004) were identified as independent mortality risk factors. Furthermore, patients with high CMV copy numbers (> 60,000 copies/mL) had higher in-hospital mortality than those with low CMV copy numbers (p < 0.05).ConclusionsCMV-DNA copy numbers and concurrent infections are predictors of in-hospital mortality in CMV-infected patients with autoimmune diseases. Therefore, serial measurements of CMV-DNA copy numbers and close observation for signs of other infections are recommended for patients with autoimmune diseases who have concurrent CMV infection.

Incidence of Pneumocystis Jiroveci Pneumonia in Patients Following Intestinal Transplantation.

Introduction: Pneumocystis jiroveci pneumonia (PJP) is a life-threatening infection, thought to occur commonly in the first 6 months following solid organ transplant.[1] Therefore anti-PJP prophylaxis is generally recommended for 6–12 months post-transplant. However, a recent study has reported that most PJP occurred several years after transplant and affected patients who were no longer taking prophylaxis.[2] This raises the question of whether anti-PJP prophylaxis needs to be considered for longer periods. Accordingly, we have conducted a retrospective review of the incidence of PJP in our intestinal transplant cohort. Methods: 61 patients’ underwent intestinal, modified multivisceral and full multivisceral transplantations at our transplant unit between February 2006 and February 2016. As per protocol, patients were started on oral Co-trimoxazole 480mg 3 times per week on day 14 post-transplant and this was discontinued after 6 months. Alternative such as nebulised Pentamidine or Atovaquone was given if patients were allergic to Co-trimoxazole or developed side effects such as leukopenia. Cases of PJP were identified through a review of case-records and microbiological samples. Demographic data and known risk factors for PJP (immunosuppression therapies, graft rejection, concurrent cytomegalovirus (CMV) infection, neutrophil and lymphocyte counts) were also collected. Results: 5 out of 61 (8.2%) patients developed PJP, diagnosed from PCR bronchial washings obtained via bronchoscopy and alveolar lavage. All cases occurred beyond 6 months (median 22; range 14–58 months) post-transplant when they were no longer taking prophylaxis. All affected patients had had intestinal rejection prior to PJP diagnosis. The median time to diagnosis was 6 months (range 2–50 months) after treatment for rejection (pulsed methylprednisolone, anti-thymocyte globulin, alemtuzumab). None of the patients were taking prophylaxis at the time of diagnosis, except for one for a short period of time. This patient was started on Atovaquone prophylaxis following intensive anti-rejection treatment and developed PJP less than a month later. Other identifiable risk factors included extra-immunosuppression (prednisolone, rituximab, concomitant tacrolimus and sirolimus), recent or recurrent CMV infection (3/5), profound lymphopenia (median 0.06; 5/5), neutropenia (1/5) and >60 years old (4/5). 2 deaths occurred following diagnosis of PJP with subsequent multi-organ failure. Conclusion: All PJP cases in our cohort occurred beyond 6 months post-transplant and seem to follow treatment for rejection. The affected patients were relatively over-immunosuppressed, lymphopenic and were not taking anti-PJP prophylaxis at the time of diagnosis. This suggests that duration of prophylaxis should be personalised based on their risk factors. Rather than stopping and restarting prophylaxis, we have elected to continue anti-PJP prophylaxis life-long in all of our cohort.

Assessment of Disease Severity and Role of Cytomegalo Virus Infection in Patients with Ulcerative Colitis.

Course of Ulcerative Colitis is characterized by intermittent flares interposed between variable periods of remission. Identification of exacerbating factors and appropriate assessment of disease activity are crucial in deciding the choice of treatment. To evaluate various clinical, endoscopic and histological parameters in assessing disease activity and to find out various risk factors involved in the exacerbation of ulcerative colitis especially the role of Cytomegalo Virus (CMV) infection. It was a prospective study of patients diagnosed as ulcerative colitis presenting with acute exacerbation of symptoms (cases) and those who were in remission (controls). A detailed evaluation of the disease history including personal history, treatment compliance and clinical disease severity were noted. Investigations including blood routine, endoscopic examination with biopsy, histopathological examination and immunohistochemistry for CMV were done on the biopsy sample. A total of 58 patients with ulcerative colitis were studied which included 37 cases and 21 controls. Out of the various clinical and demographic parameters, Good treatment compliance (p =0.0003) and Perceived Stress Scale (PSS) score (p=0.0001) showed significant difference between cases and controls. Basic laboratory parameters {Haemoglobin level, Total Leucocyte Count (TLC) and Erythrocyte Sedimentation Rate (ESR)}, clinical disease severity predictors (Truelove and Witt's criteria, Mayo score and endoscopic disease severity grade) and Geboes histological scoring showed significant difference between cases and controls. The prevalence of CMV colitis in our study was only 5.4% (two cases). Clinical and endoscopic disease severity indicators can be used as predictors of histological activity in ulcerative colitis. Poor treatment compliance and stress are important risk factors for acute exacerbation of ulcerative colitis. Clinicians should be aware of the possibility of concurrent CMV infection while treating patients with acute exacerbation of ulcerative colitis not responding to the conventional management. Reduced prevalence of CMV colitis in cases of acute exacerbation of ulcerative colitis in our study may be due to the small sample size, reduced number of steroid dependent cases or reduced severity of our cases.

What are the factors that affect hospitalization and surgery for aggravation of ulcerative colitis?

We investigated factors that may affect hospitalization and surgery in patients presenting with aggravation of ulcerative colitis (UC). This study included 222 UC patients who had visited our hospital regularly since 2000 (127 men, 95 women; mean age at onset, 34±16 years). We divided the patients into groups according to whether or not they were hospitalized for aggravation of UC (hospitalized group, n=75; nonhospitalized group, n=147), compared the clinical features and clinical courses between the two groups, and also analyzed the cumulative rates of surgery. Then, only the 75 patients of the hospitalized group were divided into two groups for a subanalysis (colectomy group, n=25; noncolectomy group, n=50). In the hospitalized group, the rates of use of steroids and thiopurine immunomodulators were significantly higher, and the rates of concurrent cytomegalovirus (CMV) infection and surgery for UC aggravation were also significantly higher. Multivariate analysis identified CMV infection [odds ratio (OR), 8.2; 95% confidence interval (CI), 1.91-35.33; P=0.0047] and steroid use (OR, 4.4; 95% CI, 1.30-14.93; P=0.0170) as risk factors for hospitalization because of UC aggravation. Moreover, the cumulative rate of surgery was significantly higher in the hospitalized group (P<0.0001). Multivariate analysis as part of the subanalysis identified the use of thiopurine immunomodulators as a factor for avoidance of surgery (OR, 0.2; 95% CI, 0.08-0.67; P=0.0072). Concurrent CMV infection was associated with an eight-fold increase in the risk of hospitalization for UC aggravation. In contrast, maintenance therapy with thiopurine immunomodulators reduced the risk of surgery by 80%.

Atypical Presentation of Exophytic Herpes Simplex Virus Type 2 With Concurrent Cytomegalovirus Infection

We report 3 unusual cases of atypical exophytic cutaneous herpes simplex virus (HSV) type 2 with concurrent cytomegalovirus (CMV) infection in immunosuppressed patients and raise awareness to the significant clinical and pathologic challenges in establishing the correct diagnosis. In all the 3 cases, the lesions presented as fungating plaques and nodules with areas of superficial erosion. Initial clinical differential included genital warts, syphilis, versus cutaneous malignancy. All the 3 patients were referred to the dermatology clinic where a combination of cutaneous biopsies, viral cultures of the lesions, polymerase chain reaction, CMV antigenemia, and immunoperoxidase stains for CMV and HSV confirmed the diagnosis of HSV type 2 with concurrent CMV infection. All the 3 patients were treated with oral valganciclovir with significant improvement noted at the follow-up visit. In addition, we review the previously reported HSV/CMV cutaneous coinfection cases.

Thrombotic Microangiopathy in Patients with Allogeneic Hematopoietic Stem Cell Transplantation

Background : Transplantation-associated thrombotic microangiopathy (TMA) is infrequent but devastating complications after allogeneic hematopoietic stem cell transplantation (HSCT). However, there were no widely accepted criteria for the definition of TMA. Recently, the Blood and Marrow Transplants Clinical Trials Network (BMT CTN) and International Working Group (IWG) proposed a definition for TMA with some differences. The BMT CTN defined TMA as an increased number of schistocytes (3 2/high power field (HPF)) and elevated lactate dehydrogenase (LDH), concurrent renal and/or neurologic dysfunction, and negative Coombs' test results. On the other hand, the IWG defined TMA by adding prolonged or progressive thrombocytopenia, a decrease in hemoglobin and serum haptoglobin concentration instead of concurrent renal and/or neurologic dysfunction and negative Coombs' test results. In addition, the value of an increased number of schistocytes (34% or 3 8/HPF) for diagnosis of TMA by IWG is higher than that by BMT CTN (3 2/HPF). Until now, there has been no report to validate both criteria for TMA.Patients and Methods : We retrospectively examined 672 consecutive patients (median age 34 years, range 15–68) who underwent allogeneic HSCT from matched sibling donor (n = 442) and alternative donor (n = 230) at Catholic HSCT Center between January 2002 and December 2006 to analyze the role of some predicting factors for the incidence and outcome of TMA after HSCT and to validate two recently proposed criteria for TMA. We defined TMA as an increased number of schistocytes (3 2/HPF), elevated LDH, prolonged or progressive thrombocytopenia, a decrease in hemoglobin and serum haptoglobin concentration, and negative Coombs' test results (O-TMA). O-TMA with renal and/or neurologic dysfunction was compatible with TMA defined by BMT CTN (B-TMA), and O-TMA with increased number of schistocytes over 8/HPF was compatible with TMA defined by IWG (I-TMA). TMA-associated death was defined as the interval from the onset of TMA to death which was associated with TMA without a relapse from underlying diseases after the onset of TMA.Results : Among 672 patients, 85 patients (13%) developed O-TMA including 41 patients (6%) with B-TMA and 17 patients (3%) with I-TMA. On multivariate analysis, TMA occurrence was higher in patients with older age (P = 0.001), mismatched human leukocyte antigen (P < 0.001), and acute graft-versus-host disease (GVHD) 3 grade II (P < 0.001) for O-TMA, in patients with older age (P = 0.002), advanced disease status at HSCT (P = 0.005), and acute GVHD 3 grade II (P < 0.001) for B-TMA, and advanced disease status at HSCT (P = 0.017) and acute GVHD 3 grade III (P < 0.001) for I-TMA. In patients with O-TMA, patients with renal dysfunction (hazard ratio 4.03, 95% CI 2.38–6.83, P < 0.001) and/or concurrent veno-occlusive disease (hazard ratio 3.16, 95% CI 1.50–6.62, P = 0.002) proved to have significantly decreased overall survival by multivariate analysis. In addition, the presence of renal dysfunction was the only significant factor associated with increased TMA-associated death (hazard ratio 11.61, 95% CI 4.79–28.16, P < 0.001). Maximal schistocytes count over 8/HPF and other factors including sex mismatch, acute GVHD 3 grade III, advanced disease status at HSCT, maximal LDH over 1298 IU/l, neurologic dysfunction, and concurrent cytomegalo virus infection that were significant on univariate analysis failed to show the significance relationship on multivariate analysis.Conclusions : This study identifies which patients are more prone to developing TMA after allogeneic HSCT according to three definitions for TMA (O-TMA, B-TMA and I-TMA). Notably, using multivariate analysis in patients with O-TMA, this retrospective study shows the importance of renal dysfunction compared to the maximal number of schistocytes count, which suggests that there are possible shortcomings of the definition by I-TMA that can miss out those with schistocytes count less than 8/HPF who may need early detection as a TMA. The proposed definitions of TMA need to be modified and be validated with prospective studies.

Congenital Cytomegalovirus Infection: A Cause of Renal Dysplasia?

Cytomegalovirus (CMV) infection is one of the most frequently encountered viral infections of the fetus and induces a wide range of histologic and clinical manifestations. Congenital abnormalities are typically restricted to the central nervous system despite evidence of CMV inclusions occurring in most epithelial cells. Although tissue injury and even glomerulonephritis have been observed in congenital CMV infections, renal multicystic dysplasia has not been reported. Herein, we describe a case of unilateral renal dysplasia in a 19-week fetus with concurrent CMV infection. We believe the present case to be the first description of a virus apparently inducing renal multicystic dysplasia.

Weekly High-Dose Cidofovir Is an Effective Treatment for Symptomatic BK Virus (BKV)-Associated Hemorrhagic Cystitis (HC) after Allogeneic Stem Cell Transplantation (Allo-SCT).

A proportion of cases of HC after allo-SCT are associated with infection from BKV. Supportive treatment is not sufficient for the relief of symptoms in many patients with BKV-associated HC. Cidofovir is an antiviral agent active against BKV. Its use is limited, however, due to the reported risk of renal failure in patients with cytomegalovirus (CMV) infection. The experience with cidofovir in BKV-associated HC is anecdotal, and the optimal dose schedule of the drug has not been determined. We administered weekly high-dose cidofovir in 5 patients for the treatment of 6 episodes of symptomatic BKV-associated HC, which were refractory to first-line therapy with hydration and continuous bladder irrigation. One patient was treated twice with cidofovir for 2 temporally separated episodes of HC, combined with papillary necrosis and ureteritis respectively. All 5 patients were males, aged 21–44 years, and had received grafts from matched related (n=2), matched unrelated (n=1) or haploidentical (n=1) donors. The median time from transplantation to diagnosis of HC was 61.5 (range, 26–303) days. In all cases, the development of HC was associated with severe immunosuppression due to profound lymphopenia or treatment with steroids or antithymocyte globulin for GVHD. BKV-associated HC was confirmed by detection of BKV in the urine by real-time PCR (1.5 × 107–5.5 × 109 copies/ml). In 2 of the 6 episodes, the patients also developed BKV viremia (5.0–9.9 × 103 copies/ml). The median time from the manifestation of symptoms to initiation of cidofovir was 12 (range, 4–53) days. Cidofovir was started at a dose of 2.5 mg/kg/week intravenously over 1 hour. If renal function remained stable, subsequent doses of 5 mg/kg were given at weekly intervals for a total of 4–6 doses. Oral probenecid and intravenous hydration were administered in combination with cidofovir. No patient developed renal toxicity (a rise in serum creatinine of at least 1.5 × baseline or proteinuria). In 5 of the 6 cases, clinical improvement of patients was observed, with a median time to response of 5 (range, 3–8) days after the first dose of cidofovir. Complete resolution of symptoms of HC was achieved in these 5 cases after 4 to 6 doses of cidofovir. BKV viral load was monitored weekly in urine (and blood) during therapy. Clinical responses did not correlate with a reduction in viral load in urine. However, in the 2 cases with BKV viremia, real-time PCR became negative after treatment with cidofovir. Concomitant CMV infection was detected in 5 of the 6 episodes of BKV-associated HC, and in all but one, complete suppression of CMV reactivation was achieved by cidofovir. Four of the 5 patients are currently alive and free of symptoms of HC. In conclusion, treatment of BKV-associated HC with cidofovir at the dose of 5 mg/kg/week seems to be safe and may result in prompt and sustained relief of the debilitating symptoms of this condition. Additional manifestations of BKV-associated disease (papillary necrosis and ureteritis) and concurrent CMV infection can be managed successfully with this dose schedule. To our knowledge, these 6 cases comprise the largest reported experience of treatment of BKV-associated HC with cidofovir, albeit the encouraging results need to be substantiated by further trials.

Cytomegalovirus Colitis Complicating Inflammatory Bowel Disease

When patients with inflammatory bowel disease (IBD) are admitted to the hospital with a flare of acute severe colitis, the possibility of a concurrent cytomegalovirus (CMV) infection causing or worsening the colitis is often considered. IBD patients are usually immunosuppressed, and therefore presumably at increased risk for active CMV infection and disease. Multiple techniques are used to diagnose CMV infection, including endoscopy, histology, serology, viral culture, CMV antigen testing, and CMV DNA testing. Immunohistochemistry (IHC) performed on colon biopsy specimens with monoclonal antibodies directed against CMV immediate early antigen is considered by most to be the current gold standard for diagnosis. The prevalence of CMV infection in acute severe colitis appears to be 21-34%, and the prevalence of CMV infection in the steroid refractory subgroup of these patients is 33-36%. After antiviral therapy, colitis remission rates in IBD patients with CMV infection range from 67% to 100%, though CMV histological infection or the presence of circulating virus alone is not always associated with steroid resistance, and may not require antiviral therapy.

Polyoma Virus-Associated Nephropathy and Concurrent Cytomegalovirus Infection in the Kidney Transplant Recipients

Introduction Cytomegalovirus (CMV) and polyoma virus BK (BKV) may both establish latency following primary infection. Frequent reactivation of these viruses can occur in the kidney transplant recipients. BKV may induce CMV gene expression by stimulating cellular regulator proteins or by its own gene regulator proteins. A high rate of concurrent CMV infections has been noted in kidney transplant recipients with polyoma virus-associated nephropathy (PVAN). Methods PVAN was identified in 10 of 191 patients who received kidney transplants between October 1998 and September 2003. PVAN was confirmed by allograft kidney biopsy. Four of the 10 patients were complicated by concurrent CMV infection. Results Two patients had only serological evidence of CMV infection and one patient had CMV gastritis. These three patients were treated with intravenous ganciclovir with good results. Disseminated ganciclovir-resistant CMV disease was demonstrated in the remaining patient. This 34-year-old kidney transplant recipient with PVAN died of multiorgan failure despite antiviral therapy with both ganciclovir and foscarnet. Conclusion PVAN with concurrent CMV infection in kidney transplant recipients showed variable clinical courses including mortality. Further studies are needed to elucidate the influence of PVAN on the pathogenesis of CMV infection.

Kaposi's Sarcoma Occurring in a Cardiac Transplant Patient on Tacrolimus

Kaposi's sarcoma is a relatively rare but potentially fatal malignancy which affects immunosuppressed individuals. It has been found to occur especially in association with cyclosporine and tacrolimus use and with concurrent cytomegalovirus infection. When detected and treated early, it usually carries a good prognosis and responds well to measures increasing immunocompetence. We report a case of cutneous Kaposi's sarcoma occurring in a cardiac transplant patient treated with tacrolimus.

Ganciclovir Is Associated with Low or Undetectable Epstein-Barr Virus DNA Load in Cerebrospinal Fluid of Patients with HIV-Related Primary Central Nervous System Lymphoma

Epstein-Barr virus (EBV) is pathogenically linked to human immunodeficiency virus (HIV)-related primary central nervous system lymphoma (PCNSL) and is found in virtually all HIV-related PCNSL cases. The objective of this study was to assess the effect of ganciclovir on EBV DNA replication in patients with HIV-related PCNSL. EBV DNA was measured by real-time polymerase chain reaction in cerebrospinal fluid and plasma samples from 25 patients with HIV-related PCNSL. Eight of these patients were receiving ganciclovir for concurrent cytomegalovirus infections. EBV DNA was detected in cerebrospinal fluid samples obtained from 15 (88%) of 17 ganciclovir-untreated patients and 4 (50%) of 8 ganciclovir-treated patients (P = .028). EBV DNA load was significantly lower for treated patients, compared with untreated patients (median value, 2.15 vs. 4.16 log copies/mL; P = .001). Analysis of sequential cerebrospinal fluid samples from 7 patients showed that EBV DNA decreased in samples obtained from 2 patients following the start of ganciclovir administration but did not decrease in samples obtained from the 5 untreated patients. In addition, patients who received ganciclovir survived longer than the untreated patients (median duration of survival, 181 vs. 72 days; P = .006). The effect of ganciclovir on EBV DNA load in cerebrospinal fluid supports the hypothesis that EBV is replicating in patients with PCNSL. This observation, together with the effect of ganciclovir therapy on patient survival, suggests that this drug might be useful for the management of PCNSL.

Cytomegalovirus-induced thrombocytopenia in an immunocompetent adult effectively treated with intravenous immunoglobulin: A case report and review

The authors report the case of an 80-year-old male patient who presented with colitis and severe thrombocytopenia. The work-up revealed concurrent cytomegalovirus infection. After failure of prednisone, a single infusion of high-dose intravenous immunoglobulin produced a rapid and sustained response. Seventeen cases from the world literature are reviewed. Corticosteroids seem effective in about one third of cases. In those who do not respond, splenectomy is relatively ineffective and more specific anti-CMV treatment with ganciclovir is of unproven efficacy and toxic, in view of the relatively favourable long term outcome the authors recommend intravenous immunoglobulin in cases of severe bleeding or when the platelet level is under 10×109 /l.

Oligo-monoclonal immunoglobulins frequently develop during concurrent cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections in patients after renal transplantation.

In the present study we report that the appearance of oligo-monoclonal immunoglobulins (oligoM-Igs) in the sera of transplanted individuals is concurrent with the detection of coincident active CMV infection and EBV replication. Eighty-four renal allograft patients were monitored with respect to CMV isolation, to CMV conventional serology and humoral response against the EBV trans-activator ZEBRA (an immediate-early antigen also called BZLF1). Titration of anti-ZEBRA antibodies (IgG and IgM) and amount of EBV DNA in serum were evaluated. Using the combination of four techniques (agarose gel electrophoresis, analytical isoelectric focusing, high resolution immunoelectrophoresis, immunofixation electrophoresis), oligoM-Igs were found in 25% of patients after allografting and significantly associated with rejection episodes (P < 0.001). Twenty out of 23 (86%) concurrent CMV/EBV infections were associated with serum oligoM-Igs (P < 0.001). One can thus reasonably assume that a sustained EBV replication following iatrogenic immunosuppression can promote the immunoglobulin heavy chain expression in EBV-infected B lymphocytes. The proliferation of immunoglobulin-secreting clones might occur after active CMV infection, through a transient over-immunosuppression or via immune subversion.