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Slae M, Ben-Or MS, Schwell R, Pinhasov D, Averbuch D, Davidovics Z, Elia A, Or EE, Stepensky P, Zaidman I. Endoscopic findings in the evaluation of gastrointestinal symptoms in pediatric patients post hematopoietic stem cell transplantation. J Pediatr Gastroenterol Nutr 2025. [PMID: 40313112 DOI: 10.1002/jpn3.70051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 01/22/2025] [Accepted: 02/19/2025] [Indexed: 05/03/2025]
Abstract
OBJECTIVES Endoscopy plays a pivotal role in diagnosing gastrointestinal (GI) symptoms of pediatric patients post hematopoietic stem cell transplantation (HSCT). There is very little data on whether endoscopic findings can predict pathological diagnosis and treatment outcomes in the pediatric population. The primary objective was to determine the association between macroscopic and microscopic findings of endoscopies in pediatric patients post-HSCT. A secondary objective was to evaluate whether macroscopic findings can predict treatment outcomes or differentiate between causes of GI symptoms. METHODS This single-center prospective study analyzed the results of endoscopic evaluation in patients aged 18 years or younger, who developed GI symptoms during and after HSCT and required an endoscopy for diagnosis. Macroscopic and microscopic findings of upper and lower endoscopies were reviewed and compared, thus evaluating the correlation between the two. Predetermined sites throughout the GI tract were examined for their macroscopic and microscopic findings, to examine whether their results suggest graft-versus-host disease (GVHD), infection, or both. Patients' change in treatment and clinical response were also assessed. RESULTS In 22 patients, 249 tissue samples were macroscopically and microscopically evaluated. When abnormal macroscopic findings were present, microscopic findings were present in 86.2% of the cases. In 72.1% of the endoscopic sites with normal macroscopic results, abnormal microscopic findings were present (p value = 0.004, Fisher-Freeman-Halton exact test). CONCLUSION This study provides further evidence supporting the correlation between macroscopic and microscopic evaluation in the diagnosis of GVHD post-HSCT, however, normal macroscopic findings do not rule out the presence of GVHD.
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Affiliation(s)
- Mordechai Slae
- Department of Pediatrics, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
| | - Mor Segal Ben-Or
- Department of Pediatrics, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
| | - Ronit Schwell
- Department of Pediatrics, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
| | - Diana Pinhasov
- Department of General Surgery, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
| | - Diana Averbuch
- Department of Pediatrics, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
| | - Zev Davidovics
- Department of Pediatrics, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
| | - Anna Elia
- Pathology Department, Hebrew University Medical Center, Jerusalem, Israel
| | - Ehud Even Or
- Department of Bone Marrow Transplant and Cancer Immunotherapy, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
| | - Polina Stepensky
- Department of Bone Marrow Transplant and Cancer Immunotherapy, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
| | - Irina Zaidman
- Department of Bone Marrow Transplant and Cancer Immunotherapy, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
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Sanchez-Paz L, Tirado Zambrana PS, Villa Poza C, Hernández-Rivas JÁ, Landete Hernández E. Iron deficiency anemia: an early clinical presentation of cytomegalovirus-induced hemorrhagic colitis in chronic myeloid leukemia patients under dasatinib treatment. Ther Adv Hematol 2024; 15:20406207241291736. [PMID: 39494242 PMCID: PMC11528592 DOI: 10.1177/20406207241291736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Accepted: 09/25/2024] [Indexed: 11/05/2024] Open
Abstract
Dasatinib is a second-generation tyrosine kinase inhibitor employed for chronic myeloid leukemia (CML) treatment that achieves high rates of prolonged and complete molecular responses (MR). Among the adverse effects reported, it has been associated with hemorrhagic complications, mainly due to its inhibiting effects on platelet functions. In addition, immune alterations induced by dasatinib may elevate the risk of bleeding and cytomegalovirus (CMV) infection, particularly in the gastrointestinal tract, thus contributing to the development of hemorrhagic colitis. In this case report, we highlight three cases of CML receiving treatment with dasatinib where CMV hemorrhagic colitis occurred. All of them exhibited iron deficiency anemia as a premature clinical manifestation in the absence of intestinal symptoms, unlike cases previously reported in the literature. CMV infection was confirmed with stool samples or tissue quantitative polymerase chain reaction and/or immunohistochemistry staining in colon biopsies. All three cases could be managed with valganciclovir and iron supplements in an outpatient setting. Management strategies of dasatinib during and after CMV infection varied, as they are not yet established and need to be individualized based on the gravity of symptoms and disease state. Iron deficiency anemia during dasatinib treatment should raise suspicion for the potential presence of CMV colitis, prompting endoscopic studies to rule out this complication, even if intestinal symptoms are not present.
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Affiliation(s)
- Laura Sanchez-Paz
- Hematology Department, Infanta Leonor University Hospital, Avda Gran Via del Este, nº80, Vallecas, Madrid 28031, Spain
| | | | - Carlos Villa Poza
- Gastroenterology Department, Infanta Leonor University Hospital, Madrid, Spain
| | - José-Ángel Hernández-Rivas
- Hematology Department, Infanta Leonor University Hospital, Madrid, Spain
- Universidad Complutense, Madrid, Spain
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3
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Passarin O, Hoogewoud F, Manuel O, Guex-Crosier Y. Clinical manifestations and immune markers of non-HIV-related CMV retinitis. BMC Infect Dis 2024; 24:787. [PMID: 39107686 PMCID: PMC11302169 DOI: 10.1186/s12879-024-09653-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 07/23/2024] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND Since the HIV epidemic in the 1980s, CMV retinitis has been mainly reported in this context. CMV retinitis in persons living with HIV is usually observed when CD4 + cells are below 50 cells/mm3. This study aims to describe the immune markers of non-HIV-related CMV retinitis as well as to describe its clinical manifestations and outcomes. METHODS Retrospective chart review of consecutive patients with CMV retinitis not related to HIV seen at the uveitis clinic of Jules Gonin Eye Hospital between 2000 and 2023. We reported the clinical manifestations and outcomes of the patients. We additionally assessed immune markers during CMV retinitis (leukocyte, lymphocyte, CD4 + cell and CD8 + cell counts as well as immunoglobulin levels). RESULTS Fifteen patients (22 eyes) were included. Underlying disease was hematologic malignancy in 9 patients, solid organ transplant in 3 patients, rheumatic disease in 2 patients and thymoma in one patient. The median time between the onset of underlying disease and the diagnosis of retinitis was 4.8 years. Lymphopenia was observed in 8/15 patients (mild = 3, moderate = 4, severe = 1), and low CD4 counts were observed in 9/12 patients, with less than 100 cells/mm3 in 4 patients. Hypogammaglobulinemia was detected in 7/11 patients. Retinitis was bilateral in 7/15 patients, and severe visual loss was frequent (5/19 eyes). Disease recurrence was seen in 7/13 patients at a median time of 6 months after initial diagnosis. No differences in immune markers were observed in patients with vs. without recurrence. CONCLUSION CMV retinitis is a rare disorder that can affect patients suffering any kind of immunodeficiency. It is associated with a high visual morbidity despite adequate treatment. CD4 + cell counts are usually higher than those in HIV patients, but B-cell dysfunction is common.
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Affiliation(s)
- Olga Passarin
- Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, avenue de France 15, Lausanne, 1002, Switzerland
- Cabinet ophtalmologique, Av. de la Gare 52, Lausanne, 1003, Switzerland
| | - Florence Hoogewoud
- Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, avenue de France 15, Lausanne, 1002, Switzerland
| | - Oriol Manuel
- Department of Infectiology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, 1011, Switzerland
| | - Yan Guex-Crosier
- Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, avenue de France 15, Lausanne, 1002, Switzerland.
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4
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Matsunaga N, Suzuki T, Nishitarumizu N, Nakanishi Y, Kondo A, Kato Y, Ebina T, Marumo Y, Nakamura T, Nakashima T, Kinoshita S, Narita T, Ri M, Kusumoto S, Komatsu H, Iida S. Clinical Significance of Cytomegalovirus Reactivation in Patients With Plasma Cell Dyscrasia Who Were Treated With Anti-CD38 Monoclonal Antibody: A Retrospective Analysis in a Single Institution. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2024; 24:531-536.e1. [PMID: 38653670 DOI: 10.1016/j.clml.2024.03.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 03/19/2024] [Accepted: 03/28/2024] [Indexed: 04/25/2024]
Abstract
INTRODUCTION Anti-CD38 monoclonal antibodies (mAbs) have improved the prognosis of patients with plasma cell dyscrasia (PCD), but are also associated with increased infectious adverse events. Cytomegalovirus (CMV) is a common latent pathogen that is reactivated in immunocompromised individuals. Although CMV reactivation has mostly been reported after high-dose chemotherapy followed by stem cell transplantation in patients with PCD, cases of reactivation during anti-CD38 mAb therapy have been reported recently. Due to limited studies, we aimed to determine the frequency and impact of CMV reactivation during anti-CD38 mAb therapy. PATIENTS AND METHODS This retrospective analysis included 154 consecutive patients with PCD who were treated with anti-CD38 mAbs at a single institution. RESULTS Seventy-six patients were evaluated for CMV reactivation by CMV pp65 antigen testing, and 29 (38%) patients, including nine with newly diagnosed PCD, showed positive results. Patients who tested positive for the CMV pp65 antigen had substantially lower serum albumin levels than those who tested negative. However, the two groups showed no marked difference in the concurrent anti-PCD medications or baseline absolute lymphocyte count. Although most patients showing positive results in the CMV pp65 antigen test had mild or no symptoms, with fever being the most common symptom, some patients developed CMV end-organ disease. In addition, CMV reactivation interfered with the course of anti-PCD treatment in most patients, necessitating dose reductions, delays, and discontinuation of chemotherapy. CONCLUSION This study provides an overview of the clinical impact of CMV reactivation in patients with PCD treated with anti-CD38 mAb-containing regimens.
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Affiliation(s)
- Naohiro Matsunaga
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya,Aichi, Japan
| | - Tomotaka Suzuki
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya,Aichi, Japan.
| | - Nozomi Nishitarumizu
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya,Aichi, Japan
| | - Yoko Nakanishi
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya,Aichi, Japan
| | - Aki Kondo
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya,Aichi, Japan
| | - Yukiyasu Kato
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya,Aichi, Japan
| | - Toru Ebina
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya,Aichi, Japan
| | - Yoshiaki Marumo
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya,Aichi, Japan
| | - Tomoyuki Nakamura
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya,Aichi, Japan
| | - Takahiro Nakashima
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya,Aichi, Japan
| | - Shiori Kinoshita
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya,Aichi, Japan
| | - Tomoko Narita
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya,Aichi, Japan
| | - Masaki Ri
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya,Aichi, Japan
| | - Shigeru Kusumoto
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya,Aichi, Japan
| | - Hirokazu Komatsu
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya,Aichi, Japan
| | - Shinsuke Iida
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya,Aichi, Japan
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Sattayalertyanyong O, Limsrivilai J, Phaophu P, Subdee N, Horthongkham N, Pongpaibul A, Angkathunyakul N, Chayakulkeeree M, Pausawasdi N, Charatcharoenwitthaya P. Performance of Cytomegalovirus Real-Time Polymerase Chain Reaction Assays of Fecal and Plasma Specimens for Diagnosing Cytomegalovirus Colitis. Clin Transl Gastroenterol 2023; 14:e00574. [PMID: 36854054 PMCID: PMC10208703 DOI: 10.14309/ctg.0000000000000574] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 02/09/2023] [Indexed: 03/02/2023] Open
Abstract
INTRODUCTION Cytomegalovirus (CMV) viral load detected by real-time polymerase chain reaction (PCR) in plasma or stool may facilitate detection of CMV colitis. METHODS This prospective study enrolled 117 patients with clinically suspected CMV colitis. Patients presenting with gastrointestinal symptoms and having increased risk of CMV infection were eligible. All participants underwent colonoscopy with tissue biopsy. Five patients underwent colonoscopy twice because of clinical recurrence, resulting in a total of 122 colonoscopies. Stool CMV-PCR and plasma CMV-PCR were performed within 7 days before/after colonoscopy. Twenty asymptomatic volunteers also underwent the same protocol. RESULTS Twenty-seven (23.1%) of 122 colonoscopies yielded positive for CMV colitis. The sensitivity and specificity was 70.4% and 91.6% for stool CMV-PCR and 66.7% and 94.7% for plasma CMV-PCR, respectively. The sensitivity of either positive plasma or positive stool CMV-PCR was 81.5%, which is significantly higher than that of plasma CMV-PCR alone ( P = 0.045). However, positive results from both tests yielded a specificity of 95.8%, which is significantly higher than that of stool CMV-PCR alone ( P = 0.045). There was a good and significant correlation between stool CMV-PCR and plasma CMV-PCR ( r = 0.71, P < 0.01), and both tests significantly correlated with the cytomegalic cell count ( r = 0.62, P < 0.01 for stool and r = 0.64, P < 0.01 for plasma). There were no positive stool or plasma CMV-PCR assays among volunteers. DISCUSSION The results of this study strongly suggest that the combination of stool CMV-PCR and plasma CMV-PCR can be used to confidently rule in (both positive) or rule out (both negative) a diagnosis of CMV colitis.
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Affiliation(s)
- Onuma Sattayalertyanyong
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;
- Siriraj GI Endoscopy Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;
| | - Julajak Limsrivilai
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;
| | - Phutthaphorn Phaophu
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;
| | - Nichcha Subdee
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;
| | - Navin Horthongkham
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;
| | - Ananya Pongpaibul
- Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;
| | - Napat Angkathunyakul
- Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;
| | - Methee Chayakulkeeree
- Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| | - Nonthalee Pausawasdi
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;
| | - Phunchai Charatcharoenwitthaya
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;
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Ahn B, Yun KW, Hong KT, Choi JY, Kang HJ, Seong MW, Kim TS, Ahn SJ, Choi EH. Threshold of Quantitative Cytomegalovirus DNA PCR for Preemptive Treatment in Pediatric Hematopoietic Stem Cell Transplant Recipients. J Pediatr Hematol Oncol 2023; 45:e200-e207. [PMID: 35482472 DOI: 10.1097/mph.0000000000002467] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 03/22/2022] [Indexed: 01/10/2023]
Abstract
BACKGROUND Consensus cytomegalovirus (CMV) DNA viral load thresholds for intervention in hematopoietic stem cell transplant (HSCT) recipients have not been established, especially in children. This study aimed at obtaining viral load thresholds of CMV DNA to guide preemptive management in pediatric HSCT recipients. MATERIALS AND METHODS A total of 465 blood samples from 177 children who received HSCT between 2015 and 2019 were included in a single center in Korea. The samples were analyzed for CMV infection by both antigenemia assay and quantitative DNA polymerase chain reaction. The 2 assay results were compared for the 233 samples which were collected when antiviral treatment has not been initiated. We determined the viral loads corresponding to the antigenemia of 5 pp65-positive cells/2×10 5 white blood cells (WBCs) as the level for initiating preemptive therapy. RESULTS Sixty percent of the samples were collected within 100 days (39.7% in 0 to 50 d, 60.2% in 0 to 100 d) from the graft infusion. The correlation between CMV DNA viral load and CMV antigenemia level increased significantly after 50 days from the graft infusion ( r =0.71 vs. r =0.93, P <0.0001). The correlation was greater in the antiviral treatment-naive group than the treatment group ( r =0.75 vs. r =0.66, P <0.0001). Under receiver operating characteristic curve analysis of the treatment-naive group, the estimated threshold CMV DNA viral loads corresponding to 5 pp65-positive cells/2×10 5 WBCs was 898 IU/mL. CONCLUSIONS The CMV DNA levels that corresponded to 5 pp65-positive cells/2×10 5 WBCs was 900 IU/mL in the HSCT group. The proposed viral load thresholds can be used to guide preemptive therapy in pediatric HSCT recipients, especially in the preengraftment period.
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Affiliation(s)
| | | | | | | | - Hyoung Jin Kang
- Departments of Pediatrics
- Seoul National University Cancer Research Institute, Seoul
- Wide River Institute of Immunology, Hongcheon-gun
| | - Moon-Woo Seong
- Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine
| | - Taek Soo Kim
- Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine
| | - Sung Jin Ahn
- Department of Information Statistics, Gyeongsang National University, Jinju, Korea
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7
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Cytomegalovirus gastroenteritis in patients with acute graft-versus-host disease. Blood Adv 2021; 6:574-584. [PMID: 34788389 PMCID: PMC8791573 DOI: 10.1182/bloodadvances.2021005885] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 10/26/2021] [Indexed: 11/20/2022] Open
Abstract
A pre-emptive strategy has successfully decreased cytomegalovirus (CMV) disease after allogeneic hematopoietic cell transplantation (HCT). However, some recipients still develop CMV gastroenteritis, especially after acute graft-versus-host disease (aGVHD), and its incidence, risk factors, and prognostic impact remain to be elucidated. We retrospectively analyzed 3759 consecutive adult patients who developed grade II-IV aGVHD using a Japanese registry database. The cumulative incidence of CMV gastroenteritis was 5.7% by day 365 from the development of grade II-IV aGVHD. Advanced age (hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.16-2.22; P = 0.004), GVHD prophylaxis with mycophenolate mofetil and calcineurin inhibitor (HR, 1.73; 95% CI, 1.08-2.77; P = 0.024), lower-gut aGVHD (HR, 2.17; 95% CI, 1.58-2.98; P < 0.001), and the use of systemic steroids (HR, 1.78; 95% CI, 1.16-2.74; P = 0.008) were independent risk factors for CMV gastroenteritis. Development of CMV gastroenteritis was associated with an increased risk of nonrelapse mortality (HR, 1.89; 95% CI, 1.50-2.39; P < 0.001). Moreover, letermovir prophylaxis significantly reduced both the incidence of CMV gastroenteritis (HR, 0.50; 95% CI, 0.25-0.99; P = 0.047) and the risk of nonrelapse mortality (HR, 0.72; 95% CI, 0.52-0.99; P = 0.043). In summary, CMV gastroenteritis is a life-threatening complication that sets the need for preventive strategies with letermovir and targeted surveillance.
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8
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Abstract
Abdominal pain in an immunocompromised patient represents a common clinical scenario that may have uncommon causes. Evaluation relies first on identifying the immunocompromise, whether due to congenital immunodeficiencies, malignancy, hematopoietic stem cell transplant, solid organ transplant, or human immunodeficiency virus/acquired immunodeficiency syndrome. Based on this determination, the emergency physician may then build a focused differential of pathophysiologic possibilities. Careful evaluation is necessary given the absence of classic physical examination findings, and liberal use of laboratory and cross-sectional imaging is prudent. Conservative evaluation and disposition of these high-risk patients is important to consider.
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Affiliation(s)
- Carmen Wolfe
- Department of Emergency Medicine, Vanderbilt University Medical Center, 1313 21st Avenue South, Oxford House 703, Nashville, TN 37232, USA.
| | - Nicole McCoin
- Department of Emergency Medicine, Ochsner Medical Center, 1514 Jefferson Highway, New Orleans, LA 70121, USA
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9
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Limaye AP, Babu TM, Boeckh M. Progress and Challenges in the Prevention, Diagnosis, and Management of Cytomegalovirus Infection in Transplantation. Clin Microbiol Rev 2020; 34:34/1/e00043-19. [PMID: 33115722 PMCID: PMC7920732 DOI: 10.1128/cmr.00043-19] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hosts with compromised or naive immune systems, such as individuals living with HIV/AIDS, transplant recipients, and fetuses, are at the highest risk for complications from cytomegalovirus (CMV) infection. Despite substantial progress in prevention, diagnostics, and treatment, CMV continues to negatively impact both solid-organ transplant (SOT) and hematologic cell transplant (HCT) recipients. In this article, we summarize important developments in the field over the past 10 years and highlight new approaches and remaining challenges to the optimal control of CMV infection and disease in transplant settings.
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Affiliation(s)
- Ajit P Limaye
- Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA
| | - Tara M Babu
- Division of Infectious Diseases, University of Rochester Medical Center, Rochester, New York, USA
- Department of Infectious Diseases, Overlake Medical Center, Bellevue, Washington, USA
| | - Michael Boeckh
- Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
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10
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Miyao K, Terakura S, Ozawa Y, Sawa M, Kohno A, Kasahara S, Iida H, Ino K, Kusumoto S, Kasai M, Takami A, Kurahashi S, Kajiguchi T, Morishita T, Nishida T, Murata M. Comparison of Transplantation Outcomes after Foscarnet and Ganciclovir Administration as First-Line Anti-Cytomegalovirus Preemptive Therapy. Transplant Cell Ther 2020; 27:342.e1-342.e10. [PMID: 33836887 DOI: 10.1016/j.jtct.2020.12.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 11/20/2020] [Accepted: 12/08/2020] [Indexed: 11/25/2022]
Abstract
Ganciclovir (GCV) and foscarnet (FCN) are effective anti-cytomegalovirus (CMV) preemptive therapies; however, the impact of the 2 agents on various clinical outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) remains unclear. We retrospectively analyzed data on 532 patients undergoing allogeneic HSCT from unrelated donors and administered FCN (n = 86) or GCV (n = 446) as first-line anti-CMV preemptive therapy. Overall survival, relapse, and nonrelapse mortality (NRM) did not differ between the FCN and GCV groups, whereas the GCV group had a higher risk of chronic graft-versus-host disease (cGVHD) (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.28 to 4.39; P = .006) and extensive cGVHD (HR, 3.94; 95% CI, 1.43 to 10.9; P = .008). All 13 patients with cGVHD in the FCN group survived. Switching to the other agent was done mainly due to hematologic adverse events in the GCV group and mainly due to insufficient efficacy in the FCN group. The incidence of end-organ CMV disease was similar in the 2 groups. Selection of FCN or GCV as first-line preemptive anti-CMV therapy did not affect survival, relapse, or NRM. Physicians can select either of the agents, depending on the clinical situation; however, the selection may influence the cGVHD-related clinical course in HSCT recipients.
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Affiliation(s)
- Kotaro Miyao
- Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan; Department of Hematology and Oncology, Tosei General Hospital, Seto, Japan.
| | - Seitaro Terakura
- Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yukiyasu Ozawa
- Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan
| | - Masashi Sawa
- Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan
| | - Akio Kohno
- Department of Hematology and Oncology, Konan Kosei Hospital, Konan, Japan
| | - Senji Kasahara
- Division of Hematology, Gifu Municipal Hospital, Gifu, Japan
| | - Hiroatsu Iida
- Department of Hematology, National Hospital Organization Nagoya Medical Center, Nagoya, Japan
| | - Kazuko Ino
- Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Shigeru Kusumoto
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Science, Nagoya, Japan
| | - Masanobu Kasai
- Department of Hematology and Oncology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
| | - Akiyoshi Takami
- Division of Hematology, Department of Internal Medicine, School of Medicine, Aichi Medical University, Nagakute, Japan
| | - Shingo Kurahashi
- Division of Hematology and Oncology, Toyohashi Municipal Hospital, Toyohashi, Japan
| | - Tomohiro Kajiguchi
- Department of Hematology and Oncology, Tosei General Hospital, Seto, Japan
| | - Takanobu Morishita
- Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan
| | - Tetsuya Nishida
- Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Makoto Murata
- Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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11
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Cytomegalovirus retinitis after allogeneic hematopoietic stem cell transplantation under cytomegalovirus antigenemia-guided active screening. Bone Marrow Transplant 2020; 56:1266-1271. [PMID: 33311594 DOI: 10.1038/s41409-020-01176-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 10/14/2020] [Accepted: 11/25/2020] [Indexed: 11/09/2022]
Abstract
Although cytomegalovirus (CMV) remains a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT), the incidence of CMV retinitis is considered to be lower than the incidence of CMV infection in other organs following allogeneic HSCT. In this study, the incidence and characteristics of CMV retinitis were retrospectively evaluated in recipients of allogeneic HSCT. Ophthalmological screening was performed at the development of ocular symptoms or positive CMV infection using peripheral blood evaluated by pp65 antigenemia or polymerase chain reaction. Of the 514 patients, 13 patients developed CMV retinitis. The median onset of CMV retinitis was day 34 (range, 21-118) post transplant, and the cumulative incidence was 2.5% (95% CI, 1.6-4.2) at 6 months after transplantation. Five patients presented ocular symptoms at the onset. In the remaining eight asymptomatic patients, the diagnosis of CMV retinitis was made by the screening guided by positive CMV infection. All evaluable patients responded to antiviral treatment but three showed incomplete improvement with ocular sequela. Our results suggest that the incidence of CMV retinitis after allogeneic HSCT is not negligible and active ophthalmological screening based not only on symptoms but also positive CMV infection monitoring contributes to the early diagnosis of CMV retinitis.
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A Case of Cytomegalovirus-Induced Oral Ulcer in an Older Adult Patient with Nephrotic Syndrome due to Membranous Nephropathy. Case Rep Dent 2020; 2020:8843816. [PMID: 33062344 PMCID: PMC7542526 DOI: 10.1155/2020/8843816] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 09/17/2020] [Indexed: 11/21/2022] Open
Abstract
We report a case of cytomegalovirus- (CMV-) induced buccal ulcer in a patient with nephrotic syndrome. An 82-year-old man with membranous nephropathy was on immunosuppressive therapy presented with an ulcer in the oral cavity and was hospitalized. Intraoral examination revealed an inflamed and painful ulcer on the left buccal mucosa. Blood test results showed CMV positivity, and histopathological examination confirmed the diagnosis. Anti-CMV therapy (ganciclovir) was initiated from the third day of hospitalization. However, he developed dyspnea on the 14th day. Computed tomography images of the chest revealed the presence of ground-glass opacities, and noninvasive positive pressure ventilation was initiated under the provisional diagnosis of pneumocystis pneumonia caused by ganciclovir-associated myelosuppression and/or steroid-induced immunocompromised state. The patient died of pneumocystis pneumonia on the 21st day. The patient had received immunosuppressive therapy for renal dysfunction. Immunocompromised patients with CMV infection should be treated with caution, as drugs for CMV may themselves cause myelosuppression, deteriorating the prognosis of the patient.
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Bueno F, Albert E, Giménez E, Piñana JL, Pérez A, Gómez MD, Hernández‐Boluda JC, Gonzalez‐Barberá EM, Montoro J, Guerreiro M, Balaguer‐Roselló A, Hernani R, Sanz J, Solano C, Navarro D. Cytomegalovirus DNA load monitoring in stool specimens for anticipating the occurrence of intestinal acute graft‐versus‐host disease following allogeneic hematopoietic stem cell transplantation: Is it of any value? Transpl Infect Dis 2020; 22:e13440. [DOI: 10.1111/tid.13440] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 07/15/2020] [Accepted: 08/02/2020] [Indexed: 12/11/2022]
Affiliation(s)
- Felipe Bueno
- Microbiology Service Hospital Clínico UniversitarioInstitute for Research INCLIVA Valencia Spain
| | - Eliseo Albert
- Microbiology Service Hospital Clínico UniversitarioInstitute for Research INCLIVA Valencia Spain
| | - Estela Giménez
- Microbiology Service Hospital Clínico UniversitarioInstitute for Research INCLIVA Valencia Spain
| | - José Luis Piñana
- Hematology Department Hospital Universitari i Politècnic La Fe Valencia Spain
| | - Ariadna Pérez
- Hematology Service Hospital Clínico UniversitarioInstitute for Research INCLIVA Valencia Spain
| | - María Dolores Gómez
- Microbiology Service Hospital Universitari i Politècnic La Fe Valencia Spain
| | - Juan Carlos Hernández‐Boluda
- Hematology Service Hospital Clínico UniversitarioInstitute for Research INCLIVA Valencia Spain
- Department of Medicine School of Medicine University of Valencia Valencia Spain
| | | | - Juan Montoro
- Hematology Department Hospital Universitari i Politècnic La Fe Valencia Spain
| | - Manuel Guerreiro
- Hematology Department Hospital Universitari i Politècnic La Fe Valencia Spain
| | | | - Rafael Hernani
- Hematology Service Hospital Clínico UniversitarioInstitute for Research INCLIVA Valencia Spain
| | - Jaime Sanz
- Hematology Department Hospital Universitari i Politècnic La Fe Valencia Spain
| | - Carlos Solano
- Hematology Service Hospital Clínico UniversitarioInstitute for Research INCLIVA Valencia Spain
- Department of Medicine School of Medicine University of Valencia Valencia Spain
| | - David Navarro
- Microbiology Service Hospital Clínico UniversitarioInstitute for Research INCLIVA Valencia Spain
- Department of Microbiology School of Medicine University of Valencia Valencia Spain
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McDonald GB, Sarmiento JI, Rees-Lui G, Myerson D. Cytomegalovirus hepatitis after bone marrow transplantation: An autopsy study with clinical, histologic and laboratory correlates. J Viral Hepat 2019; 26:1344-1350. [PMID: 31315152 DOI: 10.1111/jvh.13176] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Revised: 06/03/2019] [Accepted: 06/13/2019] [Indexed: 02/06/2023]
Abstract
Mortality from cytomegalovirus disease after marrow transplantation can be reduced by treatment with antiviral drugs based on the detection of viremia and organ involvement. We examined autopsy liver specimens to determine the frequency, extent and outcome of cytomegalovirus hepatitis and whether cytomegalovirus hepatitis occurred in the absence of cytomegalovirus disease elsewhere. Autopsy specimens from 50 transplant patients were evaluated for cytomegalovirus-infected cells, in five groups of 10, according to extent of CMV during life and at autopsy. Liver sections were examined by routine light microscopy, immunohistochemistry and in situ DNA hybridization. Clinical and laboratory data collected during the last 30 days of life were analysed as markers of liver cytomegalovirus infection. Cytomegalovirus-infected cells were detected in the livers of 10/10 patients with cytomegalovirus infection during life and widespread cytomegalovirus at autopsy; in 3/20 livers from patients with cytomegalovirus infection during life but negative liver cultures at autopsy; and in 1/10 livers from cytomegalovirus-seropositive patients who had been without other evidence of cytomegalovirus infection. Histology detected a lower density of cytomegalovirus-bearing cells per unit area of liver, compared to immunohistochemistry and in situ hybridization. No cytomegalovirus-infected cells were detected in livers from cytomegalovirus-seronegative controls. No distinctive clinical or laboratory findings correlated with liver cytomegalovirus detection. CMV liver disease is common in allografted patients with disseminated CMV but may rarely be isolated to the liver, best demonstrated with IHC and ISH. Massive hepatic necrosis from CMV was not seen in any autopsy liver in this study.
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Affiliation(s)
- George B McDonald
- Gastroenterology/Hepatology and Pathology Sections, Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, Washington
| | | | | | - David Myerson
- Gastroenterology/Hepatology and Pathology Sections, Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, Washington
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Basílio-Queirós D, Venturini L, Laib Sampaio K, Sinzger C, Weissinger EM. Fast and Efficient Titration of Human Cytomegalovirus Stocks with a Self-Excisable Bacterial Artificial Chromosomes Cassette by Flow Cytometry. Hum Gene Ther Methods 2019; 30:122-126. [PMID: 31280610 DOI: 10.1089/hgtb.2019.084] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
The study of human cytomegalovirus (HCMV) has for long been challenging due to the inability of clinical strains to efficiently proliferate in vitro until adaptive mutations occur. These mutations lead to strains that differ considerably from clinical isolates, many of them showing altered cell tropism, a decrease in cell association and higher susceptibility to an innate immune response. These problems were recently solved by the use of bacterial artificial chromosome (BAC) vectors that allow for the conservation of an intact HCMV genome. Other characteristics that render HCMV difficult for in vitro study are related to its slow replication rate that leads to some constraints in its titration. During the cloning of HCMV into BAC vectors, many groups additionally inserted a fluorescent tag to facilitate the virus characterization. However, the methods used for titration of HCMV-BAC stocks are still relaying on the standard methods that are expensive and/or time consuming. In this study, we assessed the possibility of viral titration by fluorescence-activated cell sorting (FACS), making use of the fluorescent tags that many of the HCMV-BACs hold. We compared viral titers obtained by immunohistochemistry with FACS, a faster and inexpensive technique. We showed that viral titers are comparable using the techniques already mentioned, and that titration by FACS is an efficient, fast, and cost-effective method. The establishment of viral titration of BAC vectors by FACS can further simplify the study of HCMV.
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Affiliation(s)
- Débora Basílio-Queirós
- 1Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
| | - Letizia Venturini
- 1Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
| | | | | | - Eva M Weissinger
- 1Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
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Yokose T, Obara H, Shinoda M, Nakano Y, Kitago M, Yagi H, Abe Y, Yamada Y, Matsubara K, Oshima G, Hori S, Ibuki S, Higashi H, Masuda Y, Hayashi M, Mori T, Kawaida M, Fujimura T, Hoshino K, Kameyama K, Kuroda T, Kitagawa Y. Colon perforation due to antigenemia-negative cytomegalovirus gastroenteritis after liver transplantation: A case report and review of literature. World J Gastroenterol 2019; 25:1899-1906. [PMID: 31057303 PMCID: PMC6478612 DOI: 10.3748/wjg.v25.i15.1899] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 03/03/2019] [Accepted: 03/16/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) remains a critical complication after solid-organ transplantation. The CMV antigenemia (AG) test is useful for monitoring CMV infection. Although the AG-positivity rate in CMV gastroenteritis is known to be low at onset, almost all cases become positive during the disease course. We treated a patient with transverse colon perforation due to AG-negative CMV gastroenteritis, following a living donor liver transplantation (LDLT).
CASE SUMMARY The patient was a 52-year-old woman with decompensated liver cirrhosis as a result of autoimmune hepatitis who underwent a blood-type compatible LDLT with her second son as the donor. On day 20 after surgery, upper and lower gastrointestinal endoscopy (GE) revealed multiple gastric ulcers and transverse colon ulcers. The biopsy tissue immunostaining confirmed a diagnosis of CMV gastroenteritis. On day 28 after surgery, an abdominal computed tomography revealed transverse colon perforation, and simple lavage and drainage were performed along with an urgent ileostomy. Although the repeated remission and aggravation of CMV gastroenteritis and acute cellular rejection made the control of immunosuppression difficult, the upper GE eventually revealed an improvement in the gastric ulcers, and the biopsy samples were negative for CMV. The CMV-AG test remained negative, therefore, we had to evaluate the status of the CMV infection on the basis of the clinical symptoms and GE.
CONCLUSION This case report suggests a monitoring method that could be useful for AG-negative CMV gastroenteritis after a solid-organ transplantation.
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Affiliation(s)
- Takahiro Yokose
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Hideaki Obara
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Masahiro Shinoda
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Yutaka Nakano
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Minoru Kitago
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Hiroshi Yagi
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Yuta Abe
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Yohei Yamada
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Kentaro Matsubara
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Go Oshima
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Shutaro Hori
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Sho Ibuki
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Hisanobu Higashi
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Yuki Masuda
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Masanori Hayashi
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Takehiko Mori
- Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Miho Kawaida
- Department of Pathology, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Takumi Fujimura
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Ken Hoshino
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Kaori Kameyama
- Department of Pathology, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Tatsuo Kuroda
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo 1608582, Japan
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Real-time quantitative PCR analysis of endoscopic biopsies for diagnosing CMV gastrointestinal disease in non-HIV immunocompromised patients: a diagnostic accuracy study. Eur J Clin Microbiol Infect Dis 2018; 37:2389-2396. [PMID: 30255430 DOI: 10.1007/s10096-018-3387-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Accepted: 09/19/2018] [Indexed: 12/27/2022]
Abstract
Cytomegalovirus gastrointestinal diseases (CMV-GIDs) are end-organ diseases of the gastrointestinal (GI) tract caused by CMV in immunocompromised patients. We aimed to evaluate the performance of quantitative polymerase chain reaction (qPCR) on endoscopic biopsies. We retrospectively reviewed the qPCR data on endoscopic biopsies in nonhuman immunodeficiency virus (HIV) immunocompromised patients between January 2009 and May 2015. The performance of the qPCR for CMV-GID was evaluated with the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). A total of 195 patients were included, and 28 patients with confirmed CMV-GID were identified. The AUROC of the qPCR was 0.935 (95% confidence interval [CI], 0.885 to 0.985), the sensitivity was 89.3% (95% CI, 71.8 to 97.7%), and the specificity was 85.6% (95% CI, 79.4 to 97.6%) with a cutoff value of 180 copies/μg DNA. The proportion of patients with inflammatory bowel disease in the histopathology-negative, PCR-positive group was smaller than that in the histopathology-positive group (10.7 vs 35.0%, p = 0.026), but other characteristics were not significantly different. The use of qPCR on endoscopic biopsies demonstrated good diagnostic performance for detecting CMV in non-HIV immunocompromised patients. It may increase the diagnostic yield when combined with a conventional histopathology.
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Zavrelova A, Radocha J, Pliskova L, Paterova P, Vejrazkova E, Cyrany J, Gabalec F, Podhola M, Zak P. Detection of cytomegalovirus DNA in fecal samples in the diagnosis of enterocolitis after allogeneic stem cell transplantation. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2018; 162:227-231. [PMID: 29765165 DOI: 10.5507/bp.2018.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Accepted: 04/17/2018] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Cytomegalovirus enterocolitis is a rare but potentially life threatening complication after allogeneic stem cell transplantation. Its early diagnosis and treatment are essential for a successful outcome. OBJECTIVE To determine the potential benefit of fecal CMV DNA detection in the diagnosis of CMV colitis among stem cell transplant recipients. STUDY DESIGN Biopsies from the lower gastrointestinal tract, taken during 69 episodes of diarrhea, were compared with fecal samples previously examined for CMV DNA in 45 patients after allogeneic stem cell transplantation. RESULTS Six confirmed cases of CMV colitis were observed, with 16 out of 69 (23%) fecal samples proving positive for CMV DNA. Only one positive sample correlated with histologically confirmed CMV colitis, and 15 samples were evaluated as false positive. These results provide a 16.7% sensitivity and 76.2% specificity in the diagnosis of CMV enterocolitis. CONCLUSION The examination of fecal samples for the presence of CMV DNA has very low potential in the diagnosis of CMV enterocolitis after allogeneic stem cell transplantation; therefore, a biopsy of the gastrointestinal mucosa is still warranted for correct diagnosis.
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Affiliation(s)
- Alzbeta Zavrelova
- 4 th Department of Internal Medicine - Hematology, University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
| | - Jakub Radocha
- 4 th Department of Internal Medicine - Hematology, University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
| | - Lenka Pliskova
- Institute of Clinical Biochemistry, University Hospital Hradec Kralove Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
| | - Pavla Paterova
- Department of Clinical Microbiology, University Hospital Hradec Kralove Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
| | - Eva Vejrazkova
- 4 th Department of Internal Medicine - Hematology, University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
| | - Jiri Cyrany
- 2 nd Department of Internal Medicine - Gastroenterology, University Hospital Hradec Kralove Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
| | - Filip Gabalec
- 4 th Department of Internal Medicine - Hematology, University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
| | - Miroslav Podhola
- The Fingerland´s Department of Patology, University Hospital Hradec Kralove Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
| | - Pavel Zak
- 4 th Department of Internal Medicine - Hematology, University Hospital Hradec Kralove and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
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Matsuda K, Ono S, Ishikawa M, Miyamoto S, Abiko S, Tsuda M, Yamamoto K, Kudo T, Shimizu Y, Hayase E, Hashimoto D, Teshima T, Matsuno Y, Sakamoto N. Cecum ulcer is a reliable endoscopic finding in cytomegalovirus colitis concomitant with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Ann Hematol 2018; 97:877-883. [PMID: 29340759 DOI: 10.1007/s00277-018-3241-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 01/05/2018] [Indexed: 12/13/2022]
Abstract
Although graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), cytomegalovirus (CMV) reactivation also occurs in patients after allo-HSCT and these conditions often clinically overlap. The aim of this study was to determine reliable endoscopic findings of CMV colitis in patients with gastrointestinal graft-versus-host-disease (GI-GVHD). Patients after allo-HSCT who were histologically confirmed to have GI-GVHD with or without CMV colitis and patients with an immunosuppressive condition were retrospectively analyzed. We divided the patients into three groups: GI-GVHD with CMV colitis (group A), GI-GVHD without CMV colitis (group B), and CMV colitis without undergoing allo-HSCT (group C). From medical records, the involved colorectal areas and endoscopic findings according to the groups were compared. A total of 70 patients were divided into three groups (group A: n = 19, group B: n = 28, group C: n = 23). Mucosal injuries in groups A and C frequently occurred in the cecum including ileocecal valves. On the other hand, there were no abnormal lesions on ileocecal valves in group B. Furthermore, ulcer lesions were more frequently observed in groups A and C than in group B (p < 0.001). The sensitivity and specificity of mucosal injuries in the cecum for prediction of CMV colitis were 89.5 and 76.5%, respectively, and mucosal injuries in the cecum were more reliable findings than CMV antigenemia. Ulcer lesions in the cecum are reliable endoscopic findings for CMV colitis in patients with GI-GVHD after allo-HSCT.
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Affiliation(s)
- Kana Matsuda
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine, Nishi-7, Kita-15, Kita-ku, Sapporo, 060-8638, Japan
| | - Shoko Ono
- Division of Endoscopy, Hokkaido University Hospital, Nishi-7, Kita-15, Kita-ku, Sapporo, 060-8638, Japan.
| | - Marin Ishikawa
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine, Nishi-7, Kita-15, Kita-ku, Sapporo, 060-8638, Japan
| | - Shuichi Miyamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine, Nishi-7, Kita-15, Kita-ku, Sapporo, 060-8638, Japan
| | - Satoshi Abiko
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine, Nishi-7, Kita-15, Kita-ku, Sapporo, 060-8638, Japan
| | - Momoko Tsuda
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine, Nishi-7, Kita-15, Kita-ku, Sapporo, 060-8638, Japan
| | - Keiko Yamamoto
- Division of Endoscopy, Hokkaido University Hospital, Nishi-7, Kita-15, Kita-ku, Sapporo, 060-8638, Japan
| | - Takahiko Kudo
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine, Nishi-7, Kita-15, Kita-ku, Sapporo, 060-8638, Japan
| | - Yuichi Shimizu
- Division of Endoscopy, Hokkaido University Hospital, Nishi-7, Kita-15, Kita-ku, Sapporo, 060-8638, Japan
| | - Eiko Hayase
- Department of Hematology, Hokkaido University Faculty of Medicine, Nishi-7, Kita-15, Kita-ku, Sapporo, 060-8638, Japan
| | - Daigo Hashimoto
- Department of Hematology, Hokkaido University Faculty of Medicine, Nishi-7, Kita-15, Kita-ku, Sapporo, 060-8638, Japan
| | - Takanori Teshima
- Department of Hematology, Hokkaido University Faculty of Medicine, Nishi-7, Kita-15, Kita-ku, Sapporo, 060-8638, Japan
| | - Yoshihiro Matsuno
- Department of Pathology, Hokkaido University Hospital, Nishi-7, Kita-15, Kita-ku, Sapporo, 060-8638, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine, Nishi-7, Kita-15, Kita-ku, Sapporo, 060-8638, Japan
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20
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Narita YM, Horie C, Hirahara K, Kano Y, Shiohara T, Mizukawa Y. Bullous pemphigoid complicated by cytomegalovirus disease as a manifestation of immune reconstitution inflammatory syndrome: retrospective analyses of our institutional cases and literature review. Int J Dermatol 2017; 57:202-208. [PMID: 29197074 DOI: 10.1111/ijd.13799] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 05/12/2017] [Accepted: 09/15/2017] [Indexed: 12/01/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) disease induced by reactivation of latent CMV is a fatal viral infection that may develop in a setting of therapy with immunosuppressive agents. There is a clear need to clarify any clinical features and markers of CMV disease. OBJECTIVE We investigated which clinical markers usually available in a clinical setting can predict CMV disease occurring in bullous pemphigoid (BP) patients receiving corticosteroids. METHOD We described a BP patient with CMV disease complicated by gastrointestinal hemorrhage and liver dysfunction. Prompted by this patient, we retrospectively analyzed clinical features and laboratory findings in our institutional four BP patients and previously reported nine BP patients with CMV disease. We also compared these patients with our institutional 42 BP patients not complicated by CMV disease. RESULTS High levels of anti-BP180 antibody titers associated with resistance to corticosteroids are a risk factor for the development of CMV disease. A reduction in platelet (PLT) and white blood cell (WBC) counts and an increase in alanine aminotransferase (ALT) levels 3-4 weeks after the initiation of corticosteroids are useful predictive markers for the onset of CMV disease. CONCLUSIONS Frequent WBC, PLT, and ALT measurements may identify BP patients at a risk of subsequently developing CMV disease. Careful monitoring of CMV disease in BP refractory to systemic corticosteroids may reduce the risk of fatal outcomes.
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Affiliation(s)
- Yoko M Narita
- Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Chiho Horie
- Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Kazuhisa Hirahara
- Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Yoko Kano
- Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Tetsuo Shiohara
- Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Yoshiko Mizukawa
- Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan
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21
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Imaoka Y, Ohira M, Ishiyama K, Ide K, Kobayashi T, Tahara H, Ohdan H. Perforation of the gallbladder in a patient with acute cytomegalovirus cholecystitis shortly following renal transplantation. Transpl Infect Dis 2017; 19. [PMID: 28605108 DOI: 10.1111/tid.12733] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2016] [Revised: 03/06/2017] [Accepted: 03/25/2017] [Indexed: 11/29/2022]
Abstract
A 74-year-old man with end-stage renal failure secondary to diabetes received a living donor renal transplant (cytomegalovirus [CMV]-seropositive recipient from a CMV-seropositive donor). Computed tomography scan revealed a gallbladder with hemorrhage. On postoperative day 27, cholecystography revealed gallbladder perforation; he underwent an emergency operation. Histological examination of the gallbladder wall was positive for multiple viral inclusion bodies. We report a very rare case of both hemorrhagic and perforated CMV cholecystitis within a month following renal transplantation.
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Affiliation(s)
- Yuki Imaoka
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kohei Ishiyama
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kentaro Ide
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroyuki Tahara
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
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Aizawa R, Matsumoto S, Uneno Y, Nishikawa Y, Ozaki Y, Mori Y, Kanai M, Ishida Y, Sakanaka K, Hiraoka M, Muto M. Severe esophagitis associated with cytomegalovirus during concurrent chemoradiotherapy for esophageal cancer. Jpn J Clin Oncol 2017; 47:885-888. [PMID: 28591845 DOI: 10.1093/jjco/hyx083] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Accepted: 05/24/2017] [Indexed: 12/31/2022] Open
Abstract
Although radiation esophagitis is one of the most common adverse events that occurs during chemoradiotherapy (CRT) in patients with esophageal cancer, CRT-associated cytomegalovirus (CMV) esophagitis is rare. CMV esophagitis typically occurs in patients with an immunosuppressed status. Here we report a case of CMV esophagitis during CRT initially treated as radiation esophagitis. A 64-year-old man with mid-thoracic esophageal cancer was admitted to our hospital with clinical stage cT4bN1M1 (supraclavicular lymph node metastasis) Stage IV according to the UICC ver. 7 guidelines, and he was administered definitive concurrent CRT. From the 39th day of CRT onwards, he presented with a sustained fever and severe odynophagia that was resistant to antibiotic therapy. An esophagoscopy revealed severe esophagitis with a circumferential ulcer throughout the entire esophagus, and CMV esophagitis was clinically suspected because of positive result of CMV antigenemia. Subsequently, antiviral therapy for CMV provided dramatic relief of his symptoms. Later, CMV DNA was confirmed with a polymerase chain reaction in the biopsy specimen.The symptoms of CMV esophagitis resemble those of radiation esophagitis and can make the diagnosis difficult. Thus, CMV esophagitis associated CRT may be overlooked or masked by radiation esophagitis and can cause a delay in healing. Therefore, CMV esophagitis may be considered when severe intractable esophagitis is observed during CRT.
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Affiliation(s)
- Rihito Aizawa
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shigemi Matsumoto
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
| | - Yu Uneno
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
| | | | - Yoshinao Ozaki
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
| | - Yukiko Mori
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
| | - Masashi Kanai
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
| | - Yuichi Ishida
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Katsuyuki Sakanaka
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | | | - Manabu Muto
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
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Chiba A, Nakamura F, Nakazaki K, Kurokawa M. Cytomegalovirus antigenemia and end-organ disease in Japanese patients treated with bendamustine. Leuk Lymphoma 2017; 59:749-751. [PMID: 28697686 DOI: 10.1080/10428194.2017.1347928] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Akira Chiba
- a Department of Hematology and Oncology, Graduate School of Medicine , The University of Tokyo , Bunkyo-ku , Tokyo , Japan
| | - Fumihiko Nakamura
- a Department of Hematology and Oncology, Graduate School of Medicine , The University of Tokyo , Bunkyo-ku , Tokyo , Japan
| | - Kumi Nakazaki
- a Department of Hematology and Oncology, Graduate School of Medicine , The University of Tokyo , Bunkyo-ku , Tokyo , Japan
| | - Mineo Kurokawa
- a Department of Hematology and Oncology, Graduate School of Medicine , The University of Tokyo , Bunkyo-ku , Tokyo , Japan
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Abstract
Cytomegalovirus (CMV), the largest of the herpesviruses, causes a wide range of clinical syndromes, from asymptomatic infection to severe disease in immunocompromised hosts. Laboratory methods for diagnosis include molecular testing, antigenemia, culture, serology, and histopathology. Treatment of CMV infection and disease is indicated in selected immunocompromised hosts, and preventive approaches are indicated in high-risk groups. This chapter reviews the epidemiology, clinical aspects, and the laboratory diagnosis and management of CMV in immunocompromised hosts.
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Ogonek J, Verma K, Schultze-Florey C, Varanasi P, Luther S, Schweier P, Kühnau W, Göhring G, Dammann E, Stadler M, Ganser A, Koehl U, Koenecke C, Weissinger EM, Hambach L. Characterization of High-Avidity Cytomegalovirus-Specific T Cells with Differential Tetramer Binding Coappearing after Allogeneic Stem Cell Transplantation. THE JOURNAL OF IMMUNOLOGY 2017. [DOI: 10.4049/jimmunol.1601992] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Chan ST, Logan AC. The clinical impact of cytomegalovirus infection following allogeneic hematopoietic cell transplantation: Why the quest for meaningful prophylaxis still matters. Blood Rev 2017; 31:173-183. [DOI: 10.1016/j.blre.2017.01.002] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Revised: 12/16/2016] [Accepted: 01/31/2017] [Indexed: 11/28/2022]
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Tandon P, James P, Cordeiro E, Mallick R, Shukla T, McCurdy JD. Diagnostic Accuracy of Blood-Based Tests and Histopathology for Cytomegalovirus Reactivation in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. Inflamm Bowel Dis 2017; 23:551-560. [PMID: 28296820 DOI: 10.1097/mib.0000000000001073] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND It is unclear if traditional histopathology and noninvasive blood-based tests are sufficiently accurate to detect cytomegalovirus (CMV) reactivation in inflammatory bowel disease. Therefore, we assessed the diagnostic accuracy of these tests compared with immunohistochemistry (IHC) and tissue polymerase chain reaction (PCR). METHODS A systematic search of electronic databases was performed from inception through January 2016 for observational studies comparing diagnostic tests for CMV reactivation in inflammatory bowel disease. IHC and tissue PCR were considered reference standards and were used to evaluate the accuracy of blood-based tests and hematoxylin and eosin histopathology. Weighted summary estimates with 95% confidence intervals (CIs) were calculated using bivariate analysis. RESULTS Nine studies examined the accuracy of blood-based tests for predicting colonic CMV reactivation: 5 studies by pp65 antigenemia and 4 studies by blood PCR. The overall sensitivity was 50.8% (95% CI, 19.9-81.6), the specificity was 99.9% (95% CI, 99-100), and the positive predictive value was 83.8% (95% CI, 58.6-95.0). The sensitivities of pp65 and blood PCR were 39.7% (95% CI, 27.4-52.1) and 60.0% (95% CI, 46.5-73.5), respectively. Nine studies examined the sensitivity of histopathology. The overall sensitivity was 12.5% (95% CI, 3.6-21.4), 34.6% by IHC (95% CI, 13.8-55.4), and 4.7% by tissue PCR (95% CI, 1.2-17.1). CONCLUSIONS Although blood-based tests seem to predict colonic CMV reactivation, they are insensitive tests. Similarly, histopathology has poor sensitivity for detecting colonic CMV. In agreement with current guidelines, these tests should not replace IHC or tissue PCR for detecting CMV reactivation in inflammatory bowel disease.
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Affiliation(s)
- Parul Tandon
- *Division of Gastroenterology and Hepatology, The Ottawa Hospital, Ottawa, Ontario, Canada; †Division of General Surgery, The Ottawa Hospital, Ottawa, Ontaro, Canada; and ‡Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
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Beswick L, Ye B, van Langenberg DR. Toward an Algorithm for the Diagnosis and Management of CMV in Patients with Colitis. Inflamm Bowel Dis 2016; 22:2966-2976. [PMID: 27763950 DOI: 10.1097/mib.0000000000000958] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
INTRODUCTION Concurrent cytomegalovirus (CMV) in inflammatory bowel disease-related colitis is an important yet complex clinical scenario associated with high rates of colectomy and other morbidity. This review aimed to examine the literature to produce a comprehensive diagnostic and treatment algorithm for the management of CMV in patients with colitis. METHODS A systematic literature review was conducted via PubMed/Medline databases until August 31, 2015, using multiple keywords in English language and where original data only presented. RESULTS This review discusses the concept of CMV reactivation which frequently occurs in inflammatory bowel disease-related colitis, most commonly in those presenting with steroid-refractory colitis. In this context, although signifying a poorer prognosis, in most cases, the virus is nonpathogenic and thus antiviral treatment is unhelpful. However, when reactivation gives rise to true CMV disease (colitis) as best discriminated by histology with immunohistochemistry (and the density of such) in colonic biopsy tissue, the patient does benefit from antivirals. CONCLUSION Diagnostic-based patient selection and treatment is integral to optimal outcomes in CMV, and therefore we propose an algorithm based on these concepts that now requires prospective evaluation.
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Affiliation(s)
- Lauren Beswick
- *Department of Gastroenterology, Eastern Health, Melbourne, Victoria, Australia; and †Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
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Ogonek J, Kralj Juric M, Ghimire S, Varanasi PR, Holler E, Greinix H, Weissinger E. Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation. Front Immunol 2016; 7:507. [PMID: 27909435 PMCID: PMC5112259 DOI: 10.3389/fimmu.2016.00507] [Citation(s) in RCA: 298] [Impact Index Per Article: 33.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Accepted: 11/02/2016] [Indexed: 12/17/2022] Open
Abstract
The timely reconstitution and regain of function of a donor-derived immune system is of utmost importance for the recovery and long-term survival of patients after allogeneic hematopoietic stem cell transplantation (HSCT). Of note, new developments such as umbilical cord blood or haploidentical grafts were associated with prolonged immunodeficiency due to delayed immune reconstitution, raising the need for better understanding and enhancing the process of immune reconstitution and finding strategies to further optimize these transplant procedures. Immune reconstitution post-HSCT occurs in several phases, innate immunity being the first to regain function. The slow T cell reconstitution is regarded as primarily responsible for deleterious infections with latent viruses or fungi, occurrence of graft-versus-host disease, and relapse. Here we aim to summarize the major steps of the adaptive immune reconstitution and will discuss the importance of immune balance in patients after HSCT.
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Affiliation(s)
- Justyna Ogonek
- Transplantation Biology, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
| | - Mateja Kralj Juric
- BMT, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
| | - Sakhila Ghimire
- Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany
| | - Pavankumar Reddy Varanasi
- Transplantation Biology, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
| | - Ernst Holler
- Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany
| | | | - Eva Weissinger
- Transplantation Biology, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
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Kim T, Lee YM, Lee SO, Choi SH, Kim YS, Woo JH, Sung H, Jung JH, Shin S, Kim YH, Kang YA, Lee YS, Lee JH, Lee JH, Lee KH, Park SK, Han DJ, Kim SH. Differences of cytomegalovirus diseases between kidney and hematopoietic stem cell transplant recipients during preemptive therapy. Korean J Intern Med 2016; 31:961-70. [PMID: 27055664 PMCID: PMC5016278 DOI: 10.3904/kjim.2015.079] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Revised: 05/22/2015] [Accepted: 06/30/2015] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND/AIMS Cytomegalovirus (CMV) surveillance and preemptive therapy is a widely-used strategy for preventing CMV disease in transplant recipients. However, there are limited data on the incidence and patterns of CMV disease during the preemptive period. Thus, we investigated the incidence and pattern of tissue-invasive CMV disease in CMV seropositive kidney transplantation (KT) and hematopoietic stem cell transplantation (HCT) recipients during preemptive therapy. METHODS We prospectively identified patients with tissue-invasive CMV disease among 664 KT (90%) and 496 HCT (96%) recipients who were D+/R+ (both donor and recipient seropositive) during a 4-year period. RESULTS The incidence rates of CMV disease were 4.1/100 person-years (4%, 27/664) in KT recipients and 5.0/100 person-years (4%, 21/496) in HCT recipients. Twenty-six (96%) of the KT recipients with CMV disease had gastrointestinal CMV, whereas 17 (81%) of the HCT recipients had gastrointestinal CMV and 4 (19%) had CMV retinitis. Thus, CMV retinitis was more common among HCT recipients (p = 0.03). All 27 KT recipients with CMV disease suffered abrupt onset of CMV disease before or during preemptive therapy; 10 (48%) of the 21 HCT recipients with CMV disease were also classified in this way but the other 11 (52%) were classified as CMV disease following successful ganciclovir preemptive therapy (p < 0.001). CONCLUSIONS The incidence of CMV disease was about 4% in both KT and HCT recipients during preemptive therapy. However, CMV retinitis and CMV disease as a relapsed infection were more frequently found among HCT recipients.
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Affiliation(s)
- Tark Kim
- Division of Infectious Diseases, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yu-Mi Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Department of Infectious Diseases, Inje University Busan Paik Hospital, Busan, Korea
| | - Sang-Oh Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang-Ho Choi
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yang Soo Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jun Hee Woo
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Heungsup Sung
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Joo Hee Jung
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Shin
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young Hoon Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Ah Kang
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Shin Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jung-Hee Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Je-Hwan Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyoo-Hyung Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Su-Kil Park
- Department of Nephrology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Duck Jong Han
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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CMV in Hematopoietic Stem Cell Transplantation. Mediterr J Hematol Infect Dis 2016; 8:e2016031. [PMID: 27413524 PMCID: PMC4928522 DOI: 10.4084/mjhid.2016.031] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Accepted: 06/06/2016] [Indexed: 12/12/2022] Open
Abstract
Due to its negative impact on the outcome of stem cell transplant (SCT) and solid organ transplant patients (SOT) CMV has been called “the troll of transplantation”. One of the greatest advances in the management of SCT has been the introduction of the preemptive strategy. Since its introduction, the incidence of the viremia, as expected, remains unchanged but there has been a marked decline in the incidence of early CMV disease. However, in spite of the advances in prevention of CMV disease, CMV is still today an important cause of morbidity and mortality. Late CMV disease is still occurring in a significant proportion of patients and the so-called indirect effects of CMV are causing significant morbidity and mortality. Fortunately there have been several advances in the development of new antivirals, adoptive immunotherapy and DNA-CMV vaccines that might transform the management of CMV in the near future.
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Fisher C, Alexander J, Bhattacharya R, Rakita R, Kirby K, Boeckh M, Limaye A. Sensitivity of blood and tissue diagnostics for gastrointestinal cytomegalovirus disease in solid organ transplant recipients. Transpl Infect Dis 2016; 18:372-80. [DOI: 10.1111/tid.12531] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Revised: 12/17/2015] [Accepted: 01/21/2016] [Indexed: 12/12/2022]
Affiliation(s)
- C.E. Fisher
- Divisions of Allergy & Infectious Disease; Department of Medicine; University of Washington; Seattle Washington USA
- Vaccine and Infectious Disease Division; Fred Hutchinson Cancer Research Center; Seattle Washington USA
| | - J. Alexander
- Gastroenterology; Department of Medicine; University of Washington; Seattle Washington USA
| | - R. Bhattacharya
- Gastroenterology; Department of Medicine; University of Washington; Seattle Washington USA
| | - R.M. Rakita
- Divisions of Allergy & Infectious Disease; Department of Medicine; University of Washington; Seattle Washington USA
| | - K.A. Kirby
- Division of Geriatrics; San Francisco VA Medical Center and University of California; San Francisco California USA
| | - M. Boeckh
- Divisions of Allergy & Infectious Disease; Department of Medicine; University of Washington; Seattle Washington USA
- Vaccine and Infectious Disease Division; Fred Hutchinson Cancer Research Center; Seattle Washington USA
| | - A.P. Limaye
- Divisions of Allergy & Infectious Disease; Department of Medicine; University of Washington; Seattle Washington USA
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Hirayama Y, Ando T, Hirooka Y, Watanabe O, Miyahara R, Nakamura M, Yamamura T, Goto H. Characteristic endoscopic findings and risk factors for cytomegalovirus-associated colitis in patients with active ulcerative colitis. World J Gastrointest Endosc 2016; 8:301-309. [PMID: 27014426 PMCID: PMC4804188 DOI: 10.4253/wjge.v8.i6.301] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2015] [Revised: 09/11/2015] [Accepted: 01/19/2016] [Indexed: 02/05/2023] Open
Abstract
AIM: To identify characteristic endoscopic findings and risk factors for cytomegalovirus (CMV)-associated colitis in patients with active ulcerative colitis (UC).
METHODS: A total of 149 UC patients admitted to the Department of Gastroenterology, Nagoya University Hospital, from January 2004 to December 2013 with exacerbation of UC symptoms were enrolled in this retrospective study. All medical records, including colonoscopy results, were reviewed. CMV infection was determined by the presence of CMV antigen, CMV inclusion bodies in biopsy specimens, or positive specific immunohistochemical staining for CMV. Multivariate analysis was used to identify independent risk factors for CMV colitis.
RESULTS: Multivariate analysis indicated independent associations with the extent of disease (pancolitis) and use of > 400 mg corticosteroids for the previous 4 wk. In contrast, no association was seen with sex, age at UC diagnosis, immunomodulator use, or infliximab use. Punched-out ulceration was also significantly associated with CMV infection in patients with active UC (odds ratio = 12.672, 95%CI: 4.210-38.143).
CONCLUSION: Identification of a total corticosteroid dose > 400 mg for 4 wk, extensive colitis and a specific endoscopic finding of punched-out ulcer might facilitate the more rapid diagnosis and timely initiation of antiviral therapy for CMV-associated colitis in patients with active UC.
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Kaul A, Bhadauria D, Agarwal V, Ruhela V, Kumar A, Mohendra S, Barai S, Prasad N, Gupta A, Sharma RK. Seronegative invasive gastro-intestinal cytomegalovirus disease in renal allograft recipients a diagnostic dilemma! - Tissue PCR the saviour? Indian J Med Microbiol 2016; 33:447-52. [PMID: 26068358 DOI: 10.4103/0255-0857.158596] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Seronegative Invasive Gastro-intestinal cytomegalovirus disease in renal allograft recipients Background -CMV as oppurtunistic infection affecting the gastrointerstinal tract is the most common cause for tissue invasive CMV disease occuring in 10-30% of organ transplant recepients. Gastrointerstinal CMV disease can be diagnosed in presence of clinical suspecion along with histopathological findings (CMV inclusions) and presence of mucosal lesion(s) on endoscopic examination with collaborative evidences via molecular technique. Aims-Few cases of CMV infection affecting the gastrointerstinal tract show no evidences of dissemintion despite use of highly sensitive molecular techniques. We encountered 6 cases where in despite strong clinical suspecion of Gastrointerstinal CMV disease there were seronegative and endoscopic negative evidences for CMV, blind tissue biopsy yeilded positive results for CMV disease with excellent improvement with antiviral therapy. Conclusions-Blind biopsy specimen for tissue PCR could serve as saviour in an immunocompromised individiual who has a strong clinical symptomatology for GI-CMV disease in absence of viremia, normal endoscopy and histopathology, so that the early therapeutic interventions could help in excellent patient and graft survival.
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Affiliation(s)
- A Kaul
- Department of Nephrology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
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Sun YQ, Xu LP, Han TT, Zhang XH, Wang Y, Han W, Wang FR, Wang JZ, Chen H, Chen YH, Yan CH, Chen Y, Liu KY, Huang XJ. Detection of human cytomegalovirus (CMV) DNA in feces has limited value in predicting CMV enteritis in patients with intestinal graft-versus-host disease after allogeneic stem cell transplantation. Transpl Infect Dis 2015; 17:655-61. [PMID: 26275161 DOI: 10.1111/tid.12420] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Revised: 06/24/2015] [Accepted: 07/05/2015] [Indexed: 11/26/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) enteritis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is difficult to diagnose. We aimed to evaluate the sensitivity and specificity of the detection of CMV DNA in feces for predicting CMV enteritis. METHODS HSCT patients with intestinal graft-versus-host disease (GVHD) were enrolled if they met the following criteria: (i) underwent a colonoscopy and (ii) peripheral blood and feces specimens were available for CMV DNA detection within 24 h of colonoscopy. The colonoscopy histology was used as the gold standard for diagnosing CMV enteritis. RESULTS Fifty-six patients underwent 58 colonoscopy examinations, and 7 were diagnosed as having CMV enteritis. Within 24 h of colonoscopy, 9 patients had detectable CMV in the feces and 19 patients had detectable CMV in the plasma, respectively. In the 7 patients with CMV enteritis, only 2 had detectable CMV in the stool, resulting in a sensitivity of 28.6%. In the 51 patients without CMV enteritis, 44 had no detectable CMV in the stool, with a specificity of 86.3%. CONCLUSION We concluded that CMV detection in the feces was not a good predictor of CMV enteritis in patients with intestinal GVHD after allo-HSCT.
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Affiliation(s)
- Y-Q Sun
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Diseases, Beijing, China
| | - L-P Xu
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Diseases, Beijing, China
| | - T-T Han
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Diseases, Beijing, China
| | - X-H Zhang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Diseases, Beijing, China
| | - Y Wang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Diseases, Beijing, China
| | - W Han
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Diseases, Beijing, China
| | - F-R Wang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Diseases, Beijing, China
| | - J-Z Wang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Diseases, Beijing, China
| | - H Chen
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Diseases, Beijing, China
| | - Y-H Chen
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Diseases, Beijing, China
| | - C-H Yan
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Diseases, Beijing, China
| | - Y Chen
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Diseases, Beijing, China
| | - K-Y Liu
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Diseases, Beijing, China
| | - X-J Huang
- Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Diseases, Beijing, China
- Peking-Tsinghua Center for Life Sciences, Beijing, China
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Azevedo* LS, Pierrotti LC, Abdala E, Costa SF, Strabelli TMV, Campos SV, Ramos JF, Latif AZA, Litvinov N, Maluf NZ, Filho HHC, Pannuti CS, Lopes MH, dos Santos VA, da Cruz Gouveia Linardi C, Yasuda MAS, de Sousa Marques HH. Cytomegalovirus infection in transplant recipients. Clinics (Sao Paulo) 2015; 70:515-23. [PMID: 26222822 PMCID: PMC4496754 DOI: 10.6061/clinics/2015(07)09] [Citation(s) in RCA: 199] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2015] [Revised: 03/31/2015] [Accepted: 03/31/2015] [Indexed: 12/12/2022] Open
Abstract
Cytomegalovirus infection is a frequent complication after transplantation. This infection occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative patients and can be defined as follows: latent infection, active infection, viral syndrome or invasive disease. This condition occurs mainly between 30 and 90 days after transplantation. In hematopoietic stem cell transplantation in particular, infection usually occurs within the first 30 days after transplantation and in the presence of graft-versus-host disease. The major risk factors are when the recipient is cytomegalovirus seronegative and the donor is seropositive as well as when lymphocyte-depleting antibodies are used. There are two methods for the diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase chain reaction. Serology has no value for the diagnosis of active disease, whereas histology of the affected tissue and bronchoalveolar lavage analysis are useful in the diagnosis of invasive disease. Cytomegalovirus disease can be prevented by prophylaxis (the administration of antiviral drugs to all or to a subgroup of patients who are at higher risk of viral replication) or by preemptive therapy (the early diagnosis of viral replication before development of the disease and prescription of antiviral treatment to prevent the appearance of clinical disease). The drug used is intravenous or oral ganciclovir; oral valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and the gold-standard drug is intravenous ganciclovir. Treatment should be given for 2 to 3 weeks and should be continued for an additional 7 days after the first negative result for viremia.
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Affiliation(s)
- Luiz Sergio Azevedo*
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Committee for Infection in Immunosuppressed Patients, São Paulo/SP, Brazil
| | - Lígia Camera Pierrotti
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Committee for Infection in Immunosuppressed Patients, São Paulo/SP, Brazil
| | - Edson Abdala
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Committee for Infection in Immunosuppressed Patients, São Paulo/SP, Brazil
| | - Silvia Figueiredo Costa
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Committee for Infection in Immunosuppressed Patients, São Paulo/SP, Brazil
| | - Tânia Mara Varejão Strabelli
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Committee for Infection in Immunosuppressed Patients, São Paulo/SP, Brazil
| | - Silvia Vidal Campos
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Committee for Infection in Immunosuppressed Patients, São Paulo/SP, Brazil
| | - Jéssica Fernandes Ramos
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Committee for Infection in Immunosuppressed Patients, São Paulo/SP, Brazil
| | - Acram Zahredine Abdul Latif
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Committee for Infection in Immunosuppressed Patients, São Paulo/SP, Brazil
| | - Nadia Litvinov
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Committee for Infection in Immunosuppressed Patients, São Paulo/SP, Brazil
| | - Natalya Zaidan Maluf
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Committee for Infection in Immunosuppressed Patients, São Paulo/SP, Brazil
| | - Helio Hehl Caiaffa Filho
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Committee for Infection in Immunosuppressed Patients, São Paulo/SP, Brazil
| | - Claudio Sergio Pannuti
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Committee for Infection in Immunosuppressed Patients, São Paulo/SP, Brazil
| | - Marta Heloisa Lopes
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Committee for Infection in Immunosuppressed Patients, São Paulo/SP, Brazil
| | - Vera Aparecida dos Santos
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Committee for Infection in Immunosuppressed Patients, São Paulo/SP, Brazil
| | - Camila da Cruz Gouveia Linardi
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Committee for Infection in Immunosuppressed Patients, São Paulo/SP, Brazil
| | - Maria Aparecida Shikanai Yasuda
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Committee for Infection in Immunosuppressed Patients, São Paulo/SP, Brazil
| | - Heloisa Helena de Sousa Marques
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Committee for Infection in Immunosuppressed Patients, São Paulo/SP, Brazil
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Chun J, Lee C, Kwon JE, Hwang SW, Kim SG, Kim JS, Jung HC, Im JP. Usefulness of the cytomegalovirus antigenemia assay in patients with ulcerative colitis. Intest Res 2015; 13:50-9. [PMID: 25691843 PMCID: PMC4316222 DOI: 10.5217/ir.2015.13.1.50] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2014] [Revised: 05/28/2014] [Accepted: 06/30/2014] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Patients with ulcerative colitis (UC) are at high risk for cytomegalovirus (CMV) reactivation. The usefulness of the CMV antigenemia assay in active UC patients has rarely been studied. We assessed whether the assay detects CMV colitis and predicts clinical outcomes in patients with UC. Methods We retrospectively reviewed the medical records of patients hospitalized for moderate-to-severe UC from 2003 to 2012. Positive CMV antigenemia was defined as ≥1 pp65-positive cell per 2×105 polymorphonuclear neutrophils. CMV colitis was defined as the presence of inclusion bodies and/or positive immunohistochemistry in the colonic mucosa. The primary outcome was steroid refractoriness, defined as the absence of clinical improvement after intravenous high-dose steroid administration. Results A total of 43 patients were enrolled. CMV antigenemia was detected in 12 (27.9%) patients. Positive CMV antigenemia was significantly associated with CMV colitis (P =0.001). The sensitivity and specificity of positive CMV antigenemia for diagnosing CMV colitis were 66.7% and 87.1%, respectively. Steroid refractoriness was found in 11 of 12 (91.7%) and 12 of 31 (38.7%) patients with positive and negative CMV antigenemia, respectively (P =0.002). The independent predictors for steroid refractoriness were positive CMV antigenemia (adjusted odds ratio [OR], 7.73; 95% confidence interval [CI], 1.22-49.19; P =0.030) and a shorter duration from the diagnosis of UC (adjusted OR, 0.99; 95% CI, 0.98-0.99; P =0.025). Conclusions The CMV antigenemia assay shows low sensitivity but high specificity for detecting CMV colitis and may predict steroid-refractory UC. Early rescue therapy might be considered in UC patients positive for CMV antigenemia.
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Affiliation(s)
- Jaeyoung Chun
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Changhyun Lee
- Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - Ji-Eun Kwon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Sung Wook Hwang
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Sang Gyun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Joo Sung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyun Chae Jung
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jong Pil Im
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Naseem Z, Hendahewa R, Mustaev M, Premaratne G. Cytomegalovirus enteritis with ischemia in an immunocompetent patient: A rare case report. Int J Surg Case Rep 2015; 15:146-8. [PMID: 26363106 PMCID: PMC4601982 DOI: 10.1016/j.ijscr.2015.08.040] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Revised: 08/03/2015] [Accepted: 08/27/2015] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Cytomegalovirus (CMV) is predominantly an opportunistic infection in the immunocompromised patients. Though, there are few cases of CMV colitis being reported in the immunocompetent individuals, CMV enteritis is exceedingly rare and enteritis leading into small bowel ischemia has never been reported yet. PRESENTATION OF CASE A-78-year-old male patient presented with distal small obstruction for 4 days duration. Clinical examination revealed a distended abdomen and localised peritonism in right iliac fossa. An initial computed tomography (CT) scan revealed distended small bowel loops up to the thickened inflammed terminal illeum with no free fluid or gas and a normal appendix. No immunosuppressive risk factors such as human immunodeficiency virus, transplant procedures, or steroid therapy were present. Hematologic investigations showed leucocytosis with neutrophilia. Diagnostic laparoscopy confirmed a thickened terminal ileum causing small bowel obstruction. Laparoscopy converted to laparotomy and right hemicolectomy was performed. Histology showed isolated small bowel ischemia with ulcerative changes and cytomegalovirus inclusions. The patient was started on ganciclovir therapy and subsequently had an uneventful recovery and discharged after 16 days. DISCUSSION Cytomegalovirus enteritis was initially not suspected in our patient. In this case CMV caused ischemia of the small bowel without evidence of colonic involvement. Even in elderly patients, the small bowel remains resilient to the ischemic changes because of the copious blood supply. CONCLUSION We report possibly the first case of isolated small bowel ischaemia caused by cytomegalovirus in immunocompetent individuals, needed surgical resection.
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Affiliation(s)
- Zainab Naseem
- Department of General Surgery, Caboolture Hospital, QLD 4510, Australia.
| | - Rasika Hendahewa
- Department of General Surgery, Caboolture Hospital, QLD 4510, Australia
| | - Muslim Mustaev
- Department of General Surgery, Caboolture Hospital, QLD 4510, Australia
| | - Gamini Premaratne
- Department of General Surgery, Caboolture Hospital, QLD 4510, Australia
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Kharfan-Dabaja MA, Nishihori T. Vaccine therapy for cytomegalovirus in the setting of allogeneic hematopoietic cell transplantation. Expert Rev Vaccines 2014; 14:341-50. [PMID: 25468066 DOI: 10.1586/14760584.2015.989990] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Passive immunization against CMV is desirable to minimize or perhaps eliminate complications related to CMV disease. In allogeneic hematopoietic cell transplantation (allo-HCT), the major challenge facing a successful anti-CMV vaccine is inducing immunity in an immunocompromised host. To date, only one CMV vaccine, ASP0113, has been evaluated in a randomized, placebo-controlled Phase II study. ASP0113 is a bivalent product containing two plasmids that encode CMV glycoprotein B and tegument phosphoprotein 65, respectively. Although there was no significant difference in rate of initiation of anti-CMV therapy, rates of CMV viremia were lower in the ASP0113 group when measured by a central laboratory. Also, time-to-first episode of viremia was longer in subjects receiving ASP0113. These findings paved the way for an ongoing placebo-controlled Phase III study aiming at enrolling 500 subjects. Results of this Phase III trial, especially if it meets clinically meaningful endpoints, will ultimately determine the role of anti-CMV vaccine strategies in allo-HCT.
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Affiliation(s)
- Mohamed A Kharfan-Dabaja
- Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, FOB-3, Tampa, FL, USA
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Ko JH, Peck KR, Lee WJ, Lee JY, Cho SY, Ha YE, Kang CI, Chung DR, Kim YH, Lee NY, Kim KM, Song JH. Clinical presentation and risk factors for cytomegalovirus colitis in immunocompetent adult patients. Clin Infect Dis 2014; 60:e20-6. [PMID: 25452594 DOI: 10.1093/cid/ciu969] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) colitis is a common manifestation of CMV end-organ disease, which has typically been described in immunocompromised hosts. Recently, it has been noted that this also occurs in immunocompetent patients. To gather relevant data about clinical presentation, prognosis, and risk factors for development of CMV colitis in immunocompetent hosts, we analyzed all cases that occurred during a 19-year period at our institution. METHODS A case-control study was performed to identify risk factors for CMV colitis in immunocompetent hosts. Electronic medical records of individuals who were admitted and diagnosed with CMV colitis between January 1995 and February 2014 at a tertiary care university hospital were reviewed. Two non-CMV colitis patients who were age- and sex-matched were selected as controls for each case. RESULTS A total of 51 patients with CMV colitis were included in this study along with 102 control patients. Certain conditions including renal disease on hemodialysis, neurologic disease, rheumatologic disease, intensive care unit admission, and exposure to antibiotics, antacids, steroids, or red blood cell (RBC) transfusions within 1 month of diagnosis of colitis were associated with CMV colitis on univariate analysis. Among these, steroid use and RBC transfusion within 1 month were identified as independent risk factors for developing CMV colitis on multivariate analysis. The 30-day mortality rate was 7.8% without any attributable mortality. CONCLUSIONS Steroid use and RBC transfusion within 1 month of the diagnosis of colitis were independent risk factors for development of CMV colitis in immunocompetent hosts.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Kyoung-Mee Kim
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Ganzenmueller T, Kluba J, Becker JU, Bachmann O, Heim A. Detection of cytomegalovirus (CMV) by real-time PCR in fecal samples for the non-invasive diagnosis of CMV intestinal disease. J Clin Virol 2014; 61:517-22. [PMID: 25453330 DOI: 10.1016/j.jcv.2014.10.009] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Revised: 10/09/2014] [Accepted: 10/14/2014] [Indexed: 12/18/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) infection of the gastrointestinal tract can cause CMV intestinal disease (CMV-ID), a severe complication in immunocompromised patients. Current gold standard for diagnosing CMV-ID requires the analysis of colon biopsies. Testing of fecal samples by CMV PCR might be a non-invasive diagnostic alternative, but data on this method is scarce. OBJECTIVES To evaluate the use of quantitative CMV real-time PCR in fecal samples for diagnosing CMV-ID. STUDY DESIGN Fecal samples and lower intestinal tract biopsies from 66 patients were analyzed by quantitative CMV PCR. To evaluate the diagnostic significance of CMV detection by PCR in fecal samples, patients were classified according to the etiology of their intestinal disease (based on results of endoscopy, histopathology and quantitative CMV DNA detection in biopsies) into three groups: "CMV-ID", "non-CMV-ID", and "equivocal". RESULTS 10/66 fecal samples were tested positive by quantitative CMV PCR, but CMV DNA loads were low (range <1000-11,000copies/ml). CMV detection by PCR in fecal samples was positive in 8/12 patients of the CMV-ID group, resulting in a sensitivity of 67% for diagnosing CMV-ID. With two exceptions, fecal CMV PCR was negative in the non-CMV-ID group (45/47) indicating a good specificity (96%). Moreover, CMV DNA detection in feces was associated with high CMV DNA levels in intestinal biopsies. CONCLUSIONS Negative CMV PCR results from fecal samples cannot exclude CMV-ID and thus have to be confirmed by analyzing intestinal biopsies. However, positive fecal PCR results are diagnostically useful and might help to circumvent invasive diagnostic procedures as endoscopy.
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Affiliation(s)
- Tina Ganzenmueller
- Institute of Virology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
| | - Jeanette Kluba
- Institute of Virology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany
| | - Jan Ulrich Becker
- Institute of Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany
| | - Oliver Bachmann
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany; German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Germany
| | - Albert Heim
- Institute of Virology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany
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Bhutani D, Dyson G, Manasa R, Deol A, Ratanatharathorn V, Ayash L, Abidi M, Lum LG, Al-Kadhimi Z, Uberti JP. Incidence, risk factors, and outcome of cytomegalovirus viremia and gastroenteritis in patients with gastrointestinal graft-versus-host disease. Biol Blood Marrow Transplant 2014; 21:159-64. [PMID: 25445637 DOI: 10.1016/j.bbmt.2014.10.004] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2014] [Accepted: 10/06/2014] [Indexed: 11/26/2022]
Abstract
Gastrointestinal (GI) graft-versus-host disease (GVHD) is one of the most common causes of morbidity and mortality after allogeneic stem cell transplantation. In addition, cytomegalovirus (CMV) infection of the gastrointestinal tract can complicate the post-transplantation course of these patients and it can be difficult to differentiate the 2 diagnoses given that they can present with similar symptoms. We retrospectively analyzed 252 patients who were diagnosed with GI GVHD to evaluate the incidence, risk factors, and outcomes of CMV viremia and CMV gastroenteritis in these patients. The median age at the time of transplantation was 51 years, 35% were related donor transplantations, and 65% were unrelated donor transplantations. A total of 114 (45%) patients developed CMV viremia at a median of 34 days (range, 14 to 236 days) after transplantation. Only recipient CMV IgG serostatus was significantly associated with development of CMV viremia (P < .001). The incidence of CMV viremia with relation to donor (D) and recipient (R) CMV serostatus subgroups was as follows: D+/R+, 73%; D-/R+, 67%; D+/R-, 19%; and D-/R-, 0. A total of 31 patients were diagnosed with a biopsy-proven CMV gastroenteritis; 2 patients had evidence of CMV gastroenteritis and GVHD on the first biopsy and 29 on the second biopsy. Median time to development of CMV gastroenteritis was 52 days (range, 19 to 236 days) after transplantation. Using death as a competing risk, the cumulative incidence of CMV gastroenteritis at 1 year was 16.4%. The incidence of CMV gastroenteritis in relation to the donor/recipient serostatus was as follows: D+/R+, 22%; D-/R+, 31%; D+/R-, 12%; and D-/R-, 0. Median follow-up time for the 252 patients was 35.4 (95% CI 23.8 to 44.8) months. The estimated overall survival rate at 1 and 2 years was .45 (95% confidence interval [CI], .39 to .52) and .39 (95% CI, .33 to .46), respectively. Of the examined variables, those related to the overall survival were maximal clinical GVHD grade (P < .001) and development of CMV gastroenteritis (P = .008). Development of CMV viremia was not associated with increased mortality. In conclusion, CMV gastroenteritis is common complication in patients with GI GVHD and can adversely affect the prognosis.
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Affiliation(s)
- Divaya Bhutani
- Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
| | - Gregory Dyson
- Karmanos Cancer Institute, Wayne State University, Detroit, Michigan; Department of Oncology, Wayne State University, Detroit, Michigan
| | - Richard Manasa
- Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
| | - Abhinav Deol
- Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
| | | | - Lois Ayash
- Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
| | - Muneer Abidi
- Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
| | - Lawrence G Lum
- Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
| | - Zaid Al-Kadhimi
- Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Joseph P Uberti
- Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
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Kim JW, Boo SJ, Ye BD, Kim CL, Yang SK, Kim J, Kim SA, Park SH, Park SK, Yang DH, Jung KW, Kim KJ, Byeon JS, Myung SJ, Kim JH. Clinical utility of cytomegalovirus antigenemia assay and blood cytomegalovirus DNA PCR for cytomegaloviral colitis patients with moderate to severe ulcerative colitis. J Crohns Colitis 2014; 8:693-701. [PMID: 24405983 DOI: 10.1016/j.crohns.2013.12.014] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Revised: 12/16/2013] [Accepted: 12/17/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Clinical usefulness of cytomegalovirus (CMV) antigenemia assay and blood CMV polymerase chain reaction (PCR) in patients with ulcerative colitis (UC) needs to be evaluated. METHODS Medical records of moderate to severe UC patients between January 2001 and December 2012 were reviewed retrospectively. Diagnostic performances of CMV antigenemia assay and blood PCR to predict CMV colitis, and clinical outcome according to the results were analyzed. CMV colitis was diagnosed by H&E staining and/or CMV immunohistochemistry. RESULTS Of the 229 study subjects, 83 patients (36.2%) had CMV colitis. The sensitivity and specificity of CMV antigenemia assay were 47.0% and 81.7%, and those of blood CMV DNA PCR were 44.3% and 87.9%, respectively. If either CMV antigenemia or PCR was positive in the presence of significant ulcers, the sensitivity and specificity of having CMV colitis were 67.3% and 75.7%, respectively, with the area under the receiver operating characteristic curve value of 0.717. Among patients with significant ulcers, positive CMV antigenemia (33/50 [66.0%] vs. 31/102 [30.4%]; p<0.001) and positive blood CMV PCR (25/37 [67.6%] vs. 24/86 [27.9%]; p<0.001) showed significantly higher probability of CMV colitis than blood test-negative patients. UC-CMV colitis patients with positive CMV antigenemia showed significantly higher rate of colectomy than those with negative antigenemia (13/39 [33.3%] vs. 5/44 [11.4%]; p=0.015). CONCLUSIONS Although CMV antigenemia and blood CMV PCR showed low sensitivity for diagnosing CMV colitis, the specificity values were high. Among UC-CMV colitis patients, CMV antigenemia showed significant association with subsequent colectomy.
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Affiliation(s)
- Jong Wook Kim
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Republic of Korea
| | - Sun-Jin Boo
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Republic of Korea
| | - Byong Duk Ye
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
| | - Chang Lae Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jihun Kim
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Sun A Kim
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Sang Hyoung Park
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Soo-Kyung Park
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Dong-Hoon Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Kee Wook Jung
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Kyung-Jo Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jeong-Sik Byeon
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Seung-Jae Myung
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jin-Ho Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
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Risk factors for cytomegalovirus gastrointestinal diseases in adult patients with cancer. Eur J Clin Microbiol Infect Dis 2014; 33:1847-53. [DOI: 10.1007/s10096-014-2107-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Accepted: 04/02/2014] [Indexed: 10/25/2022]
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Gotoh M, Yoshizawa S, Katagiri S, Suguro T, Asano M, Kitahara T, Akahane D, Okabe S, Tauchi T, Ito Y, Ohyashiki K. Human herpesvirus 6 reactivation on the 30th day after allogeneic hematopoietic stem cell transplantation can predict grade 2-4 acute graft-versus-host disease. Transpl Infect Dis 2014; 16:440-9. [DOI: 10.1111/tid.12229] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2013] [Revised: 12/04/2013] [Accepted: 01/30/2014] [Indexed: 11/30/2022]
Affiliation(s)
- M. Gotoh
- First Department of Internal Medicine; Tokyo Medical University; Tokyo Japan
| | - S. Yoshizawa
- First Department of Internal Medicine; Tokyo Medical University; Tokyo Japan
| | - S. Katagiri
- First Department of Internal Medicine; Tokyo Medical University; Tokyo Japan
| | - T. Suguro
- First Department of Internal Medicine; Tokyo Medical University; Tokyo Japan
| | - M. Asano
- First Department of Internal Medicine; Tokyo Medical University; Tokyo Japan
| | - T. Kitahara
- First Department of Internal Medicine; Tokyo Medical University; Tokyo Japan
| | - D. Akahane
- First Department of Internal Medicine; Tokyo Medical University; Tokyo Japan
| | - S. Okabe
- First Department of Internal Medicine; Tokyo Medical University; Tokyo Japan
| | - T. Tauchi
- First Department of Internal Medicine; Tokyo Medical University; Tokyo Japan
| | - Y. Ito
- First Department of Internal Medicine; Tokyo Medical University; Tokyo Japan
| | - K. Ohyashiki
- First Department of Internal Medicine; Tokyo Medical University; Tokyo Japan
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Cytomegalovirus enteritis in immunocompetent subjects: A case report and review of the literature. J Infect Chemother 2014; 20:325-9. [DOI: 10.1016/j.jiac.2013.12.004] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Revised: 10/25/2013] [Accepted: 12/01/2013] [Indexed: 11/19/2022]
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Inokuchi T, Kato J, Hiraoka S, Suzuki H, Nakarai A, Hirakawa T, Akita M, Takahashi S, Harada K, Okada H, Yamamoto K. Long-term follow-up of ulcerative colitis patients treated on the basis of their cytomegalovirus antigen status. World J Gastroenterol 2014; 20:509-517. [PMID: 24574719 PMCID: PMC3923025 DOI: 10.3748/wjg.v20.i2.509] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2013] [Revised: 09/15/2013] [Accepted: 10/22/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To clarify the impact of cytomegalovirus (CMV) activation and antiviral therapy based on CMV antigen status on the long-term clinical course of ulcerative colitis (UC) patients.
METHODS: UC patients with flare-up were divided into CMV-positive and -negative groups according to the CMV antigenemia assay. The main treatment strategy provided for the patients in the CMV-positive group comprised a dose reduction of corticosteroids and administration of ganciclovir.
RESULTS: The median number of days to initial remission was significantly greater for the patients in the CMV-positive group (21 d vs 16 d, P = 0.009). However, the relapse rate after remission and colectomy rate during more than 30 mo of observation did not differ between the two groups. Multivariate analysis revealed that administration of ganciclovir was the only independent factor for avoiding colectomy in patients of the CMV-positive group.
CONCLUSION: CMV antigen status did not significantly affect the long-term prognosis in UC patients under treatment with appropriate antiviral therapy.
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Fujimoto D, Matsushima A, Nagao M, Takakura S, Ichiyama S. Risk factors associated with elevated blood cytomegalovirus pp65 antigen levels in patients with autoimmune diseases. Mod Rheumatol 2014. [DOI: 10.3109/s10165-012-0651-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Ariza-Heredia EJ, Nesher L, Chemaly RF. Cytomegalovirus diseases after hematopoietic stem cell transplantation: a mini-review. Cancer Lett 2014; 342:1-8. [PMID: 24041869 DOI: 10.1016/j.canlet.2013.09.004] [Citation(s) in RCA: 131] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2013] [Accepted: 09/08/2013] [Indexed: 02/03/2023]
Abstract
Cytomegalovirus (CMV) infection remains a significant complication after hematopoietic stem cell transplantation (HSCT) and may have a deleterious impact on the overall outcome after transplantation. In addition to the direct effects of CMV infection, tissue-invasive CMV diseases may be associated with increased risk of graft versus host disease, myelosuppression, and invasive bacterial and fungal infections. Because of these direct and indirect adverse effects, prevention of CMV infection, mostly through pre-emptive therapy, is one of the essential strategies that may improve outcomes of HSCT recipients. Management of CMV infection relies mainly on intravenous (IV) antiviral therapy with ganciclovir and foscarnet, with or without IV polyclonal immunoglobulins. Although viral resistance remains rare, better tolerated antiviral agents with less serious side effects are needed, and a few will be evaluated in phase III clinical trials in the near future.
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Affiliation(s)
- Ella J Ariza-Heredia
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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Lin J, Chen S, Zhao Z, Cummings OW, Fan R. CD123 is a useful immunohistochemical marker to facilitate diagnosis of acute graft-versus-host disease in colon. Hum Pathol 2013; 44:2075-80. [DOI: 10.1016/j.humpath.2013.02.023] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2012] [Revised: 02/05/2013] [Accepted: 02/06/2013] [Indexed: 01/26/2023]
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