|
1
|
Onisor D, Brusnic O, Mocan S, Stoian M, Avram C, Boicean A, Dobru D. Cytomegalovirus in Ulcerative Colitis: An Unwanted "Guest". Pathogens 2024; 13:650. [PMID: 39204250 PMCID: PMC11356953 DOI: 10.3390/pathogens13080650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Revised: 07/23/2024] [Accepted: 07/30/2024] [Indexed: 09/03/2024] Open
Abstract
The role of cytomegalovirus (CMV) in the flare-up of ulcerative colitis (UC) is not clearly understood. CMV can cause similar symptoms in different clinical contexts, which may be attributed to the natural evolution of the viral infection, the patient's immune status, or its association with inflammatory bowel disease (IBD). This study aims to delineate the diverse manifestations of CMV-related lesions from clinical, endoscopic, and histopathological perspectives, alongside a brief narrative review of the literature. In managing IBD patients, it is crucial to be vigilant for signs of CMV reactivation, especially before the initiation of more intensive therapies.
Collapse
Affiliation(s)
- Danusia Onisor
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540139 Targu Mures, Romania; (D.O.); (D.D.)
- Gastroenterology Department, Mureș County Clinical Hospital, 540103 Targu Mures, Romania
| | - Olga Brusnic
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540139 Targu Mures, Romania; (D.O.); (D.D.)
- Gastroenterology Department, Mureș County Clinical Hospital, 540103 Targu Mures, Romania
| | - Simona Mocan
- Pathology Department, Emergency County Hospital, 540136 Targu Mures, Romania;
| | - Mircea Stoian
- Department of Anesthesiology and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania;
| | - Calin Avram
- Department of Medical Informatics and Biostatistics, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540139 Targu Mures, Romania
| | - Adrian Boicean
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania;
| | - Daniela Dobru
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540139 Targu Mures, Romania; (D.O.); (D.D.)
- Gastroenterology Department, Mureș County Clinical Hospital, 540103 Targu Mures, Romania
| |
Collapse
|
|
2
|
Ozdemir B, Atay A, Kayhan MA, Ozin YO, Gokce DT, Altunsoy A, Guner R. Tissue quantitative RT-PCR test for diagnostic significance of cytomegalovirus infection in patients with inflammatory bowel disease and treatment response: Cytomegalovirus infection in patients with inflammatory bowel disease. Medicine (Baltimore) 2023; 102:e34463. [PMID: 37543790 PMCID: PMC10402982 DOI: 10.1097/md.0000000000034463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/28/2023] [Accepted: 07/03/2023] [Indexed: 08/07/2023] Open
Abstract
Cytomegalovirus (CMV) is an opportunistic pathogen that exacerbates inflammatory bowel disease (IBD). There are no clear diagnostic criteria for CMV infection in IBD patients. The aim of this study was to evaluate the importance of the diagnosis of CMV infection with CMV-DNA polymerase chain reaction (PCR) in the colonic mucosa and the response to antiviral treatment. We retrospectively analyzed the clinical data of 30 patients with IBD (24 men, 6 women; median age: 42 years) who were hospitalized because of IBD exacerbation and whose samples were assessed by tissue CMV-DNA PCR positivity. Most of the IBD patients had ulcerative colitis (90%). The CMV-DNA PCR median value was 8848 copies/mL of tissue (range 90-242,936 copies/mL). Blood CMV-DNA PCR was found to be positive in a small group (33.3%, 10/30) of tissue CMV-DNA PCR-positive cases. immunohistochemistry tests were positive in only 5 of the 23 patients positive for CMV-DNA PCR in the colonic mucosa, and high remission (25/30, 83.3%) was detected with antiviral therapy. Recurrence of CMV colitis infection was observed in 9 of 25 patients who had remission with antiviral therapy. The tissue CMV-DNA PCR test was found to be more useful than blood CMV-DNA PCR and immunohistochemistry tests for diagnosing CMV colitis, and the tissue CMV-DNA PCR test enabled rapid and appropriate treatment.
Collapse
Affiliation(s)
- Burcu Ozdemir
- Department of Infectious Diseases and Clinical Microbiology Clinic, Ankara City Hospital, Ankara, Turkey
| | - Ali Atay
- Department of Gastroenterology, Ankara City Hospital, Ankara, Turkey
| | | | | | | | - Adalet Altunsoy
- Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences Ankara City Hospital, Ankara, Turkey
| | - Rahmet Guner
- Department of Infectious Diseases and Clinical Microbiology Clinic, Ankara Yildirim Beyazit University, Ankara City Hospital, Ankara, Turkey
| |
Collapse
|
|
3
|
Maeda T, Sakai H, Ozawa N, Sugiyama T, Takada J, Kubota M, Ibuka T, Shirakami Y, Araki H, Shimizu M. Acute cytomegalovirus infection in an immunocompetent patient with ulcerative colitis: A case report. Exp Ther Med 2019; 18:2271-2277. [PMID: 31452714 DOI: 10.3892/etm.2019.7823] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 07/18/2019] [Indexed: 11/06/2022] Open
Abstract
Cytomegalovirus (CMV) is a ubiquitous member of the Herpesviridae family that can present with a variety of clinical manifestations, including encephalitis, retinitis, interstitial pneumonia and colitis. These serious symptoms are generally observed as opportunistic infections in immunocompromised hosts, including patients with acquired immunodeficiency syndrome and those receiving steroids and/or immunosuppressants. Symptomatic CMV infections in patients with ulcerative colitis are found in patients treated with steroids and/or immunosuppressants but rarely affect those who are not taking these agents. The present study reported the case of a young patient without concurrent use of immunosuppressive agents for the treatment of ulcerative colitis. The patient presented with acute mononucleosis and colitis caused by primary CMV infection. This was characterized by the presence of atypical lymphocytes and hepatosplenomegaly, elevation of transaminase levels, serology-positive anti-CMV IgM, and CMV antigenemia. Additionally, CMV-positive cells were histologically detected in colonic biopsy specimens. The patient's symptoms and clinical parameters improved following initiation of intravenous ganciclovir. It was concluded that even if patients with ulcerative colitis are not treated with steroids and/or immunosuppressants, significant attention should be paid to acute CMV infections in the context of severe or persistent colonic inflammation.
Collapse
Affiliation(s)
- Toshihide Maeda
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Hiroyasu Sakai
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Noritaka Ozawa
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Tomohiko Sugiyama
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Jun Takada
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Masaya Kubota
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Takashi Ibuka
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Yohei Shirakami
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Hiroshi Araki
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Masahito Shimizu
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| |
Collapse
|
|
4
|
Weng MT, Tung CC, Lee YS, Leong YL, Shieh MJ, Shun CT, Wang CY, Wong JM, Wei SC. Cytomegalovirus colitis in hospitalized inflammatory bowel disease patients in Taiwan: a referral center study. BMC Gastroenterol 2017; 17:28. [PMID: 28193173 PMCID: PMC5307794 DOI: 10.1186/s12876-017-0586-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Accepted: 02/09/2017] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Colitis is exacerbated in patients with concurrent cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). We assessed the prevalence and clinical features of CMV colitis in hospitalized IBD patients. METHODS A retrospective study reviewed the data from January 1, 1998 through December 31, 2013 compiled at the National Taiwan University Hospital. The CMV colitis patients' demographic data, clinical information, treatment regimens, pathologic findings, and outcome were analyzed. RESULTS A total of 673 IBD patients were hospitalized during the study period. There were 312 patients diagnosed with Crohn's disease (CD) and 361 with ulcerative colitis (UC). CMV colitis was diagnosed as having positive inclusion bodies in colonic tissue. Six of the 312 CD patients (1.9%) and five of the 361 UC patients (1.4%) were diagnosed with CMV colitis. Compared to CD patients without CMV colitis, patients with CMV colitis were more often older (p < 0.005). Higher steroid usage was noted in the CMV positive group compared to age and gender matched CMV negative IBD patients (81.8% vs. 51.5%). Eight patients received ganciclovir treatment. Three patients who did not receive antiviral treatment had colitis flare-ups after the index admission. CONCLUSIONS The prevalence of CMV colitis in hospitalized IBD inpatients was 1.6% in Taiwan. Two associated factors for CMV colitis in hospitalized IBD patients were that they were elderly in CD and were on higher doses of steroids. Routine histopathology studies and/or PCR for refractory colitis patients are suggested to diagnose CMV colitis. Once the diagnosis is made, antiviral treatment is recommended to decrease the colitis relapse rate.
Collapse
Affiliation(s)
- Meng-Tzu Weng
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, No. 7 Chung-Shan South Road, Taipei City, Taiwan
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- Department of Chemical Engineering & Materials Science, Yuan-Ze University, Taoyuan, Taiwan
| | - Chien-Chih Tung
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, No. 7 Chung-Shan South Road, Taipei City, Taiwan
| | - Yi-Shuan Lee
- Department of Pathology and Forensic Medicine, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
| | - Yew-Loong Leong
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, No. 7 Chung-Shan South Road, Taipei City, Taiwan
- Department of Internal Medicine, West Garden Hospital, Taipei City, Taiwan
| | - Ming-Jium Shieh
- Department of Oncology, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
| | - Chia-Tung Shun
- Department of Pathology and Forensic Medicine, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
| | - Cheng-Yi Wang
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, No. 7 Chung-Shan South Road, Taipei City, Taiwan
| | - Jau-Min Wong
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, No. 7 Chung-Shan South Road, Taipei City, Taiwan
| | - Shu-Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, No. 7 Chung-Shan South Road, Taipei City, Taiwan.
| |
Collapse
|
|
5
|
Thörn M, Rorsman F, Rönnblom A, Sangfelt P, Wanders A, Eriksson BM, Bondeson K. Active cytomegalovirus infection diagnosed by real-time PCR in patients with inflammatory bowel disease: a prospective, controlled observational study (.). Scand J Gastroenterol 2016; 51:1075-80. [PMID: 27142339 DOI: 10.3109/00365521.2016.1156154] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE It is assumed that cytomegaloviral (CMV) infection in inflammatory bowel disease (IBD) is caused by reactivation due to the immunosuppressive therapy, but the role of CMV as a pathophysiological factor and prognostic marker in IBD is unclear. The aim of this study was to investigate CMV infection in IBD, with real-time polymerase chain reaction (PCR) and immunohistochemistry, with emphasis on newly diagnosed disease. MATERIALS AND METHODS In this prospective, controlled study, 67 patients with IBD and 34 control patients with irritable bowel syndrome (IBS) or rectal bleeding were included. Serology for CMV was analysed along with CMV DNA in plasma, mucosal biopsies, and faeces. Mucosal biopsies were further analysed with histopathology and CMV immunohistochemistry. RESULTS Detection of CMV IgM was more common in patients with IBD, compared to controls, 21% versus 3%. CMV DNA was found in 16% of patients with newly diagnosed, untreated IBD and in 38% of steroid-treated patients. Four of the five patients that needed urgent surgery were CMV-DNA positive in at least one of three sample types. None of the controls had detectable CMV DNA. CONCLUSIONS Active CMV infection was found in high proportions of newly diagnosed untreated patients with IBD, in patients on immunosuppression and in patients in the need of surgery. Low CMV-DNA levels in non-immunosuppressed patients were not a risk factor for the development of more severe IBD, while the detection of CMV DNA in patients on immunosuppressive therapy may foresee disease progression.
Collapse
Affiliation(s)
- Mari Thörn
- a Department of Medical Sciences, Section of Gastroenterology and Hepatology , Uppsala University , Uppsala , Sweden
| | - Fredrik Rorsman
- a Department of Medical Sciences, Section of Gastroenterology and Hepatology , Uppsala University , Uppsala , Sweden
| | - Anders Rönnblom
- a Department of Medical Sciences, Section of Gastroenterology and Hepatology , Uppsala University , Uppsala , Sweden
| | - Per Sangfelt
- a Department of Medical Sciences, Section of Gastroenterology and Hepatology , Uppsala University , Uppsala , Sweden
| | - Alkwin Wanders
- b Department of Immunology, Genetics and Pathology , Uppsala University , Uppsala , Sweden
| | - Britt-Marie Eriksson
- c Department of Medical Sciences, Section of Infectious Diseases , Uppsala University , Uppsala , Sweden
| | - Kåre Bondeson
- d Department of Medical Sciences, Clinical Microbiology and Infectious Medicine , Uppsala University , Uppsala , Sweden
| |
Collapse
|
|
6
|
Khan TV, Toms C. Cytomegalovirus Colitis and Subsequent New Diagnosis of Inflammatory Bowel Disease in an Immunocompetent Host: A Case Study and Literature Review. AMERICAN JOURNAL OF CASE REPORTS 2016; 17:538-43. [PMID: 27460032 PMCID: PMC4968430 DOI: 10.12659/ajcr.898005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Patient: Male, 40 Final Diagnosis: CMV colitis Symptoms: Abdominal pain • diarrhea • jaundice Medication: — Clinical Procedure: Flexible sigmoidoscopy • colonoscopy Specialty: Family Medicine
Collapse
Affiliation(s)
- Tipu V Khan
- Ventura County Medical Center, Family Medicine Residency Program, University of California, Los Angeles David Geffen School of Medicine, Ventura, CA, USA
| | | |
Collapse
|
|
7
|
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.
Collapse
|
|
8
|
Gauss A, Rosenstiel S, Schnitzler P, Hinz U, Rehlen T, Kadmon M, Ehehalt R, Stremmel W, Zawierucha A. Intestinal cytomegalovirus infection in patients hospitalized for exacerbation of inflammatory bowel disease: a 10-year tertiary referral center experience. Eur J Gastroenterol Hepatol 2015; 27:712-20. [PMID: 25919654 DOI: 10.1097/meg.0000000000000361] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
OBJECTIVES This 10-year retrospective cohort study aims to determine the prevalence and risk factors of cytomegalovirus (CMV) infection in inpatients with exacerbated inflammatory bowel disease (IBD). METHODS All patients admitted to the Department of Gastroenterology of the University Hospital Heidelberg for IBD exacerbation between January 2004 and June 2013 were enrolled. To identify the risk factors of CMV infection, infected individuals were compared with those with excluded infection. RESULTS Among 297 patients with exacerbated IBD, 21 had confirmed CMV infection and 79 had excluded CMV infection, whereas the remaining patients had not been sufficiently tested for CMV. Taking into account only sufficiently tested individuals, the prevalence of CMV infection was 22.7% in ulcerative colitis and 16.0% in Crohn's disease. The occurrence of CMV infection was associated with the following variables at admission: age of 30 years or more [odds ratio (OR) 14.29; P=0.004], disease duration less than 60 months (OR 7.69; P=0.011), a blood leukocyte count less than 11/nl (OR 4.49; P=0.041), and immunosuppressive therapy (OR 6.73; P=0.0129). CMV-positive patients remained in the hospital longer than noninfected patients (P=0.0009). In the CMV-positive cohort, a 66-year-old woman died of CMV pneumonia and sepsis, whereas there was no death in the CMV-negative cohort. CONCLUSION Immunuosuppressive therapy and age older than 30 years were identified as the main risk factors for the development of CMV infection in exacerbated IBD. Because of the risk of death, diagnostics of CMV infection should especially be initiated in older patients on immunosuppressive therapy.
Collapse
Affiliation(s)
- Annika Gauss
- Departments of aGastroenterology bInfectious Diseases, Virology cSurgery, University Hospital Heidelberg dOutpatient Clinic of Gastroenterology, Heidelberg, Germany
| | | | | | | | | | | | | | | | | |
Collapse
|
|
9
|
Liu CC, Zhang ZY. Relationship between cytomegalovirus infection and inflammatory bowel disease. Shijie Huaren Xiaohua Zazhi 2015; 23:1784-1790. [DOI: 10.11569/wcjd.v23.i11.1784] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Human cytomegalovirus (HCMV) is a common opportunistic pathogenic virus, which causes dormant or latent infection following primary infection in immunocompetent individuals and overt infection in immunocompromised patients. Inflammatory bowel disease (IBD) is a chronic, recurrent inflammatory illness and patients with IBD are often immunosuppressed, through combined action of potentially malnutrition, use of immunosuppressants, etc. These factors predispose patients with IBD to an increased risk of developing HCMV infection. The number of IBD patients with concomitant HCMV infection is increasing and the adverse role of HCMV in IBD has drawn much attention from clinicians. Recent evidence suggests that HCMV may play an essential role in the progression of IBD, and elucidating the possible association between HCMV infection and IBD as well as the underlying mechanisms has great diagnostic and therapeutic implications. Here we review the possible relationship between HCMV and IBD.
Collapse
|
|
10
|
Cakir M, Ersoz S, Akbulut UE. Disseminated cytomegalovirus infection and protein losing enteropathy as presenting feature of pediatric patient with Crohn's disease. Pediatr Gastroenterol Hepatol Nutr 2015; 18:60-5. [PMID: 25866735 PMCID: PMC4392002 DOI: 10.5223/pghn.2015.18.1.60] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Revised: 12/25/2014] [Accepted: 01/09/2015] [Indexed: 01/21/2023] Open
Abstract
We report a pediatric patient admitted with abdominal pain, diffuse lower extremity edema and watery diarrhea for two months. Laboratory findings including complete blood count, serum albumin, lipid and immunoglobulin levels were compatible with protein losing enteropathy. Colonoscopic examination revealed diffuse ulcers with smooth raised edge (like "punched out holes") in the colon and terminal ileum. Histopathological examination showed active colitis, ulcerations and inclusion bodies. Immunostaining for cytomegalovirus was positive. Despite supportive management, antiviral therapy, the clinical condition of the patient worsened and developed disseminated cytomegalovirus infection and the patient died. Protein losing enteropathy and disseminated cytomegalovirus infection a presenting of feature in steroid-naive patient with inflammatory bowel disease is very rare. Hypogammaglobulinemia associated with protein losing enteropathy in Crohn's disease may predispose the cytomegalovirus infection in previously healthy children.
Collapse
Affiliation(s)
- Murat Cakir
- Department of Pediatric Gastroenterology Hepatology and Nutrition, Karadeniz Technical University, Trabzon, Turkey
| | - Safak Ersoz
- Department of Pathology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Ulas Emre Akbulut
- Department of Pediatric Gastroenterology Hepatology and Nutrition, Karadeniz Technical University, Trabzon, Turkey
| |
Collapse
|
|
11
|
Kim YS, Kim YH, Kim JS, Jeong SY, Park SJ, Cheon JH, Ye BD, Jung SA, Park YS, Choi CH, Kim KO, Jang BI, Han DS, Yang SK, Kim WH. Long-term outcomes of cytomegalovirus reactivation in patients with moderate to severe ulcerative colitis: a multicenter study. Gut Liver 2014; 8:643-7. [PMID: 25368753 PMCID: PMC4215451 DOI: 10.5009/gnl13427] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2013] [Revised: 12/17/2013] [Accepted: 12/20/2013] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Cytomegalovirus (CMV) reactivations are frequently observed in patients with active ulcerative colitis (UC), and ganciclovir therapy is effective in patients with steroid-refractory UC. This study aimed to determine the long-term outcomes of CMV reactivation and the long-term therapeutic efficacy of ganciclovir treatment. Methods This retrospective multicenter study included a cohort of 72 patients with moderate-to-severe UC who were evaluated for CMV reactivation at the time of their initial UC flare. Colectomy, disease relapse, and the recurrence rate of CMV reactivation were investigated. Results The mean duration of follow-up for the 72 patients was 43.16±19.78 months (range, 1 to 67 months). The cumulative colectomy (log-rank, p=0.025) and disease flare-up rates (log-rank, p=0.048) were significantly higher in the CMV-positive group. Of the 11 patients who were successfully treated with ganciclovir in the initial treatment, three patients (27.3%) experienced CMV reactivation, and six patients (54.5%) experienced poor outcomes, such as the need for colectomy or a steroid-dependent state. Conclusions The patients who had CMV-reactivated UC showed poor outcomes at the long-term follow-up, and the long-term efficacy of ganciclovir therapy was marginal. Careful assessment is necessary for patients who exhibit evidence of CMV reactivation.
Collapse
Affiliation(s)
- You Sun Kim
- Department of Internal Medicine, Inje University College of Medicine, Seoul, Korea ; IBD Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul, Korea
| | - Young-Ho Kim
- Sungkyunkwan University School of Medicine, Seoul, Korea ; IBD Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul, Korea
| | - Joo Sung Kim
- Seoul National University College of Medicine, Seoul, Korea ; IBD Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul, Korea
| | - Seong Yeon Jeong
- Department of Internal Medicine, Inje University College of Medicine, Seoul, Korea
| | - Soo Jeong Park
- Yonsei University College of Medicine, Seoul, Korea ; IBD Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul, Korea
| | - Jae Hee Cheon
- Yonsei University College of Medicine, Seoul, Korea ; IBD Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul, Korea
| | - Byong Duk Ye
- University of Ulsan College of Medicine, Seoul, Korea ; IBD Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul, Korea
| | - Sung-Ae Jung
- Ewha Womans University School of Medicine, Seoul, Korea ; IBD Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul, Korea
| | - Young Sook Park
- Eulji University College of Medicine, Seoul, Korea ; IBD Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul, Korea
| | - Chang Hwan Choi
- Chung-Ang University College of Medicine, Seoul, Korea ; IBD Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul, Korea
| | - Kyeung Ok Kim
- Yeungnam University College of Medicine, Daegu, Korea ; IBD Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul, Korea
| | - Byung Ik Jang
- Yeungnam University College of Medicine, Daegu, Korea ; IBD Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul, Korea
| | - Dong Soo Han
- Hanyang University College of Medicine, Guri, Korea ; IBD Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul, Korea
| | - Suk-Kyun Yang
- University of Ulsan College of Medicine, Seoul, Korea ; IBD Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul, Korea
| | - Won Ho Kim
- Yonsei University College of Medicine, Seoul, Korea ; IBD Study Group of the Korean Association for the Study of Intestinal Diseases, Seoul, Korea
| |
Collapse
|
|
12
|
Delvincourt M, Lopez A, Pillet S, Bourrier A, Seksik P, Cosnes J, Carrat F, Gozlan J, Beaugerie L, Roblin X, Peyrin-Biroulet L, Sokol H. The impact of cytomegalovirus reactivation and its treatment on the course of inflammatory bowel disease. Aliment Pharmacol Ther 2014; 39:712-20. [PMID: 24506221 DOI: 10.1111/apt.12650] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Revised: 01/03/2014] [Accepted: 01/15/2014] [Indexed: 12/18/2022]
Abstract
BACKGROUND Consequences of latent cytomegalovirus (CMV) infection reactivation on inflammatory bowel disease (IBD) flare, as a flare-worsening factor or simple bystander, are debated. Impact of anti-viral treatment on IBD course is poorly known. AIM To assess the impact of CMV reactivation on patients hospitalised for IBD flare and the effect of anti-viral treatment on IBD flare in patients with CMV reactivation. METHODS First, a population of UC patients from Saint-Antoine hospital, in flare with positive blood CMV PCR without anti-viral treatment (n = 26), were compared to matched patients with negative blood CMV PCR in a case-control study. Secondly, a total of 110 hospitalisations between October 2003 and May 2012 for IBD flare-up with CMV reactivation (80 diagnosed on blood PCR, 33 on tissue PCR) were identified in three French referral centres. Evolution following CMV reactivation diagnosis was compared between patients receiving anti-viral treatment and those who did not. RESULTS In the case-control study, no differences were observed between the two groups regarding length of hospital stay and colectomy rate. Comparing treated and untreated patients, no differences were observed at inclusion regarding age, gender, IBD type, immunosuppressant, CRP and haemoglobin level. No differences were observed regarding CRP level decrease at 10 days and colectomy rate at 3 months. Anti-viral treatment was associated with lower serum albumin level at inclusion and longer hospitalisation. CONCLUSIONS CMV reactivation does not appear to alter the course of IBD flare. CMV treatment does not seem to impact the course of IBD. These results should be confirmed prospectively.
Collapse
Affiliation(s)
- M Delvincourt
- Department of Gastroenterology, Saint Antoine Hospital, Assistance Publique Hôpitaux de Paris and Paris VI University, Paris, France
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
13
|
Albenberg LG, Mamula P, Brown K, Baldassano RN, Russo P. Colitis in Infancy and Childhood. PATHOLOGY OF PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2014:197-248. [DOI: 10.1007/978-3-642-54053-0_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
14
|
Looking for endoscopic features of cytomegalovirus colitis: a study of 187 patients with active ulcerative colitis, positive and negative for cytomegalovirus. Inflamm Bowel Dis 2013; 19:1156-63. [PMID: 23619714 DOI: 10.1097/mib.0b013e31828075ce] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) is frequently detected in ulcerative colitis (UC) lesions of steroid-refractory patients. This has led to the suspicion that CMV might cause colitis and steroid refractoriness. METHODS During 2003 and 2011, 187 consecutive patients were divided into group I (n = 105), corticosteroid-free and thiopurine-free in the past 6 months, and group II (n = 82), all corticosteroid refractory. The combination of serum CMV immunoglobulin (Ig)M, CMV IgG, CMV antigenemia (Ag), and real-time polymerase chain reaction assays were performed to identify CMV(+) patients. RESULTS In group I, 79 patients were CMV IgG(+) and 26 patients were CMV IgG(-) and CMV IgM(-). In group II, 61 patients were CMV IgG(+), 1 CMV IgM(+), and 20 CMV IgG(-) and CMV IgM(-). All CMV IgG(+) patients were screened for CMV Ag. In group I, 6 of the 79 CMV IgG(+) patients were CMV Ag(+). In group II, 27 patients were CMV Ag(+). Colonoscopy was performed in all patients before screening for CMV. Similar colonoscopic features including punched out ulcers, geographic ulcers, and irregular ulcers were found in both CMV(+) and CMV(-) patients, without any striking difference between the 2 groups. CONCLUSIONS CMV reactivation might be encouraged by immunosuppressive drugs, like corticosteroids, immunomodulators, and therefore, patients with UC are at a high risk of CMV reactivation, potentially exacerbating UC. However, this study of 187 patients, CMV(+) and CMV(-), could not find colonoscopic features unique to CMV, except that CMV might be one factor for steroid refractoriness, and UC exacerbation.
Collapse
|
|
15
|
|
|
16
|
Nielsen OH, Bjerrum JT, Herfarth H, Rogler G. Recent advances using immunomodulators for inflammatory bowel disease. J Clin Pharmacol 2013; 53:575-88. [PMID: 23408468 DOI: 10.1002/jcph.2] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2012] [Accepted: 11/12/2012] [Indexed: 12/14/2022]
Abstract
Use of the immunomodulators thiopurines and methotrexate (MTX) in the treatment of inflammatory bowel disease (IBD), i.e., Crohn's disease and ulcerative colitis (UC), is considered to be good clinical practice. However, despite being administered to a considerable number of IBD patients over the years, questions remain about the most rational treatment regimens of azathioprine (AZA), 6-mercaptopurine (6-MP), and MTX, and results from a range of recent studies necessitate increased attention to how to optimize the use of these immunomodulators. First and foremost, it is of utmost importance to define the subgroup of IBD patients in need of immunomodulators, including those in need of combination therapy with biologic agents, especially because some side effects may be rather severe. Second, colorectal cancer is observed more often in IBD patients than in the background population. However, a recent nationwide Dutch study pointed to a preventive effect of thiopurines. Finally, the need for an appropriate approach to the discontinuation of immunomodulators is emphasized. Since controversy continues regarding the most appropriate use of immunomodulators, this paper is focusing on pharmacokinetics, pharmacogenetics, and therapeutic blood testing, as well as the occurrence of adverse events, when using AZA, 6-MP, and MTX in an attempt to determine a more up-to-date and rational treatment regimen in IBD.
Collapse
Affiliation(s)
- Ole Haagen Nielsen
- Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Denmark.
| | | | | | | |
Collapse
|
|
17
|
Yi F, Zhao J, Luckheeram RV, Lei Y, Wang C, Huang S, Song L, Wang W, Xia B. The prevalence and risk factors of cytomegalovirus infection in inflammatory bowel disease in Wuhan, Central China. Virol J 2013; 10:43. [PMID: 23374225 PMCID: PMC3573922 DOI: 10.1186/1743-422x-10-43] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2012] [Accepted: 11/27/2012] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The etiology of inflammatory bowel disease (IBD) is not clear and cytomegalovirus (CMV) infection is often associated with IBD patients. The etiologic link between IBD and CMV infection needs to be studied. The objective of the present study is to investigate the prevalence and risk factors of CMV in a cohort of IBD patients from Central China. METHODS Two hundred and twenty six IBD patients (189 ulcerative colitis (UC) and 37 patients with Crohn's disease (CD)), and 290 age and sex matched healthy controls were recruited. CMV DNA was detected by nested PCR, while serum anti-CMV IgG and anti-CMV IgM was determined by ELISAs. Colonoscopy/enteroscopy with biopsy of diseased tissues and subsequent H&E stain were then conducted in IBD patients with positive anti-CMV IgM. Finally, we analyzed the prevalence and clinical risk factors of CMV infection in IBD patients. RESULTS The prevalence of CMV DNA and anti-CMV IgG positive rate in IBD patients were 84.07% and 76.11%, respectively, higher than those in healthy controls (59.66% and 50.69%, respectively, P < 0.05), However, anti-CMV IgM positive rate was no different with healthy controls (1.77% vs 0.34%, P = 0.235). In univariate analysis of risk factors, the recent use of corticosteroid was associated with increase of CMV DNA and IgM positive rate in UC (P = 0.035 and P = 0.015, respectively), aminosalicylic acid drug therapy was correlated with positivity of CMV DNA and IgG in UC and CMV DNA in CD (P = 0.041, P < 0.001 and P = 0.014, respectively), the treatment of immunosuppresent was correlated with CMV IgM (P < 0.001). Furthermore, patients with severe UC were significantly associated with CMV DNA and IgM (P = 0.048 and P = 0.031, respectively). Malnutrition (albumin < 35 G/L) was also found to be related with CMV recent infection (P = 0.031). In multivariate analysis of risk factors in UC, pancolitis was significantly associated with CMV DNA positivity (P = 0.001). Severe UC and pancolitis seemed to be related with IgG positivity. For CD, there was just single factor associated with CMV positive in each group, multivariate analysis was unnecessary. CONCLUSIONS CMV positive rate in IBD patients was significantly higher, than in healthy controls. The use of aminosalicylic acid, corticosteroid, immunosuppressants, pancolitis and severe IBD patients seemed to be more susceptible to CMV infection in univariate analysis of risk factors. However, no risk factor was found to be significantly correlated with CMV infection in multivariate analysis of risk factors.
Collapse
Affiliation(s)
- Fengming Yi
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University School of Medicine, Donghu Road 169, Wuhan 430071, P.R. of China
| | - Jie Zhao
- The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, P.R. of China
| | - Rishi Vishal Luckheeram
- The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, P.R. of China
| | - Yuan Lei
- The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, P.R. of China
| | - Changgao Wang
- The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, P.R. of China
| | - Sha Huang
- The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, P.R. of China
| | - Lu Song
- The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, P.R. of China
| | - Wei Wang
- The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, P.R. of China
| | - Bing Xia
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University School of Medicine, Donghu Road 169, Wuhan 430071, P.R. of China
- The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan 430071, P.R. of China
| |
Collapse
|
|
18
|
Yamamoto-Furusho JK, de León-Rendón JL, Rodas L. [Infection frequency in patients with chronic idiopathic ulcerative colitis]. REVISTA DE GASTROENTEROLOGIA DE MEXICO 2012; 77:186-192. [PMID: 23159238 DOI: 10.1016/j.rgmx.2012.07.042] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/11/2012] [Revised: 07/02/2012] [Accepted: 07/10/2012] [Indexed: 02/08/2023]
Abstract
BACKGROUND Ulcerative Colitis (UC) is a chronic inflammatory bowel disease characterized by diffuse inflammation of the mucosa of the colon. Up to now, diverse observational studies have implicated a wide variety of pathogenic microorganisms as causal and exacerbating factors in UC. Clostridium difficile (C. difficile) infection has been associated with recurrence and treatment failure and its incidence in patients with UC has been on the rise in the last few years. AIMS To determine the frequency of infection by different microorganisms in Mexican UC patients. PATIENTS AND METHODS A total of 150 patients with definitive UC diagnosis were studied. All the stool tests for parasites and ova, stool cultures, tests for the C. difficile toxins A and B, and immunohistochemistry for Cytomegalovirus in colon segment biopsies were analyzed. Other demographic and clinical variables of the disease were recorded for their correlation with infection frequency. RESULTS Infection frequency in UC patients was 28.00%. C. difficile infection was present in 0.013%. Other pathogens were found, such as Endolimax nana (9.00%), Entamoeba histolytica (3.00%), Cytomegalovirus (2.00%), Salmonella (2.00%), Shigella (0.70%), Toxoplasma gondii (0.70%) and Iodamoeba bütschlii (0.70%). CONCLUSIONS Infection frequency was 28.00% in our study and C. difficile infection represented only 0.013%.
Collapse
Affiliation(s)
- J K Yamamoto-Furusho
- Clínica de Enfermedad Inflamatoria Intestinal, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", México D.F., México.
| | | | | |
Collapse
|
|
19
|
Shahani L. CMV infection complicating the diagnosis of Crohn's disease in an immunocompetent patient. BMJ Case Rep 2012; 2012:bcr.11.2011.5254. [PMID: 22605861 DOI: 10.1136/bcr.11.2011.5254] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Cytomegalovirus (CMV) affects the gastrointestinal tract commonly; however CMV colitis is uncommon in patients who are not severely immunocompromised. The author reports a 51-year-old Caucasian female who was admitted to the hospital with exacerbation of her chronic diarrhoea. CAT scan of the abdomen and pelvis showed thickening of the wall of the terminal ileum with inflammatory stranding and follow-up colonoscopy showed extensive circumferential ulceration in the terminal ileum. Biopsies confirmed diagnosis of CMV infection and the patient was started on appropriate antimicrobial agents. CMV viremia showed response to the medication; however the patient's intestinal symptoms failed to improve. Nodular lesions consistent with erythema nodusum were noticed and promethus test was consistent with Crohn's disease. The patient showed good response to immunosuppressive therapy. CMV infections are known to exacerbate symptoms of inflammatory bowel disease and hence Crohn's disease should be suspected in an immunocompetent patient presenting with CMV ileitis.
Collapse
Affiliation(s)
- Lokesh Shahani
- Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
| |
Collapse
|
|
20
|
Nowacki TM, Bettenworth D, Ross M, Heidemann J, Lehmann PV, Lügering A. Cytomegalovirus (CMV)-Specific Perforin and Granzyme B ELISPOT Assays Detect Reactivation of CMV Infection in Inflammatory Bowel Disease. Cells 2012; 1:35-50. [PMID: 24710412 PMCID: PMC3901090 DOI: 10.3390/cells1020035] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2012] [Revised: 04/12/2012] [Accepted: 04/16/2012] [Indexed: 12/19/2022] Open
Abstract
The role of cytomegalovirus (CMV) infection in the pathogenesis and exacerbation of Inflammatory Bowel Disease (IBD) has been unresolved. Typically, the CMV genome remains dormant in infected cells, but a breakdown of immune surveillance can lead to re-activation of viral replication in the gut mucosa, which is not necessarily associated with viremia or changes in antibody titers. We hypothesized that the detection of CMV-specific CD8 effector T cells should permit the distinction between dormant and active CMV infection. As CD8 effector T cells, unlike memory CD8 T cells, have perforin (PFN) and granzyme B (GzB) preformed in their cytoplasmic granules, we employed single cell resolution ELISPOT assays to measure the CMV antigen-triggered release of these molecules by CD8 T cells isolated from subjects with IBD, and age-matched healthy controls. The frequencies of CMV-specific (GzB) and PFN-producing CD8 T cells were increased in IBD patients compared to healthy controls. Furthermore, the increased CMV reactivity was associated with active IBD disease and with longer disease duration. Notably, PCR on serum frequently failed to detect CMV DNA during flares. The data show that during active IBD there is a flare of CD8 T cell activity against CMV in a substantial proportion of IBD patients, suggesting CMV reactivation that serum PCR does not detect. While it remains open whether CMV reactivation is a cause or consequence of IBD, our data suggest that monitoring CMV antigen-specific effector CD8 T cells with GzB and PFN ELISPOT analysis can provide novel insights into the role of CMV infection in IBD. Additionally, our data have implications for the fields of transplantation, HIV, cancer, and autoimmune diseases, in all of which patient care critically depends on sensitive and reliable detection of a reactivation of CMV infection.
Collapse
Affiliation(s)
- Tobias M Nowacki
- Department of Medicine B, University of Münster, Münster 48149, Germany.
| | | | - Matthias Ross
- Department of Medicine B, University of Münster, Münster 48149, Germany.
| | - Jan Heidemann
- Department of Medicine B, University of Münster, Münster 48149, Germany.
| | - Paul V Lehmann
- Cellular Technology Limited, Shaker Heights, OH 44122-5350, USA.
| | | |
Collapse
|
|
21
|
Antonelli E, Baldoni M, Giovenali P, Villanacci V, Essatari M, Bassotti G. Intestinal superinfections in patients with inflammatory bowel diseases. J Crohns Colitis 2012; 6:154-159. [PMID: 22325169 DOI: 10.1016/j.crohns.2011.07.012] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2011] [Revised: 07/13/2011] [Accepted: 07/20/2011] [Indexed: 02/08/2023]
Abstract
BACKGROUND Intestinal superinfections may occur in the setting of inflammatory bowel diseases (IBD), complicating the clinical picture and triggering flares of disease. AIMS To report our experience with intestinal superinfections in IBD patients over a three-year period. METHODS Charts of patients hospitalized for moderate-to-severe active disease during the observation period were reviewed, and data of patients with flares due to infections collected and analyzed. RESULTS Overall, 15 out of 113 IBD patients (13.3%) had flare-ups related to intestinal infections; 143 acute flare-ups were thus documented, with 17 episodes (12%) related to infective agents, represented by Campylobacter jejuni (3 infections), Clostridium difficile (7 infections), and Cytomegalovirus (7 infections). All but two infections occurred in ulcerative colitis patients, and all responded to appropriate treatment. CONCLUSIONS Intestinal superinfections may complicate the clinical picture of IBD patients, increasing the diagnostic and therapeutic burden. Appropriate early diagnostic and therapeutic measures are thus needed in these patients.
Collapse
Affiliation(s)
- Elisabetta Antonelli
- Gastroenterology and Hepatology Section, Department of Clinical and Experimental Medicine, University of Perugia, Italy
| | | | | | | | | | | |
Collapse
|
|
22
|
Turner D, Travis SPL, Griffiths AM, Ruemmele FM, Levine A, Benchimol EI, Dubinsky M, Alex G, Baldassano RN, Langer JC, Shamberger R, Hyams JS, Cucchiara S, Bousvaros A, Escher JC, Markowitz J, Wilson DC, van Assche G, Russell RK. Consensus for managing acute severe ulcerative colitis in children: a systematic review and joint statement from ECCO, ESPGHAN, and the Porto IBD Working Group of ESPGHAN. Am J Gastroenterol 2011; 106:574-88. [PMID: 21224839 DOI: 10.1038/ajg.2010.481] [Citation(s) in RCA: 144] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Acute severe ulcerative colitis (ASC) is a potentially life-threatening disease. We aimed to formulate guidelines for managing ASC in children based on systematic review of the literature and robust consensus process. This manuscript is a product of a joint effort of the ECCO (European Crohn's and Colitis Organization), the Pediatric Porto Inflammatory Bowel Disease (IBD) Working group of ESPGHAN (European Society of Pediatric Gastroenterology, Hepatology, and Nutrition) and ESPGHAN. METHODS A group of 19 experts in pediatric IBD participated in an iterative consensus process including two face-to-face meetings. A total of 17 predefined questions were addressed by working subgroups based on a systematic review of the literature. RESULTS The recommendations and practice points were eventually endorsed with a consensus rate of at least 95% regarding: definitions, initial evaluation, standard therapy, timing of second-line therapy, the role of endoscopic evaluation and heparin prophylaxis, how to administer second-line medical therapy, how to assess response, surgical considerations, and discharge recommendations. A management flowchart is presented based on daily scoring of the Pediatric Ulcerative Colitis Activity Index (PUCAI), along with 28 formal recommendations and 34 practice points. CONCLUSIONS These guidelines provide clinically useful points to guide the management of ASC in children. Taken together, the recommendations offer a standardized protocol that allows effective monitoring of disease progress and timely treatment escalation when needed.
Collapse
Affiliation(s)
- Dan Turner
- Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
23
|
Abstract
Ulcerative colitis (UC) patients are believed to have an increased risk for the colonic reactivation of cytomegalovirus (CMV) infection due to both inherent and iatrogenic factors. Numerous studies and case reports have described CMV infection as complicating the disease course of ulcerative colitis patients; the existing evidence suggests an association between the presence of CMV infection and increased colectomy and mortality rates in UC patients. Whether CMV is nonpathogenic with a tropism towards areas of dysplasia and inflammation in the colon of UC or plays an active role in pathogenesis is still debated. In this paper, we examine the existing evidence for the diagnosis and management of CMV infection in UC patients.
Collapse
|
|
24
|
Lévêque N, Brixi-Benmansour H, Reig T, Renois F, Talmud D, Brodard V, Coste JF, De Champs C, Andréoletti L, Diebold MD. Low frequency of cytomegalovirus infection during exacerbations of inflammatory bowel diseases. J Med Virol 2010; 82:1694-700. [DOI: 10.1002/jmv.21877] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
|
|
25
|
Subramanian V, Finlayson C, Harrison T, Rice P, Pollok R. Primary cytomegalovirus infectious colitis complicating Crohn's disease successfully treated with oral valganciclovir. J Crohns Colitis 2010; 4:199-202. [PMID: 21122506 DOI: 10.1016/j.crohns.2009.11.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2008] [Revised: 10/09/2009] [Accepted: 11/10/2009] [Indexed: 02/08/2023]
Abstract
Most cases of cytomegalovirus (CMV) colitis that develop in patients with inflammatory bowel disease (IBD) are caused by reactivation of a latent virus. Primary CMV infections are rare in adult patients. Treatment with immunosuppressive agents increases the infection risk in patients with IBD. We present a 26 year old lady with primary CMV colitis, superimposed on underlying Crohn's colitis. The diagnosis was confirmed by a viral-like prodrome, a positive CMV IgM titer, presence of low avidity IgG antibodies to CMV, high CMV DNA titers in the plasma, and immunohistological detection of CMV positive cells in her colonic mucosa. The patient responded to initial treatment with intravenous ganciclovir with a fall in plasma levels of CMV DNA, treatment was completed with oral valganciclovir until plasma CMV DNA levels became undetectable.
Collapse
Affiliation(s)
- Venkataraman Subramanian
- Department of Gastroenterology, St George's Healthcare NHS Trust, Blackshaw Road, London SW17 0QT, United Kingdom.
| | | | | | | | | |
Collapse
|
|
26
|
New pathophysiological insights and modern treatment of IBD. J Gastroenterol 2010; 45:571-83. [PMID: 20213337 DOI: 10.1007/s00535-010-0219-3] [Citation(s) in RCA: 142] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2010] [Accepted: 02/03/2010] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel disease (IBD), which comprises two main types, namely, Crohn's disease and ulcerative colitis, affects approximately 3.6 million people in the USA and Europe, and an alarming rise in low-incidence areas, such as Asia, is currently being observed. In the last decade, spontaneous mutations in a diversity of genes have been identified, and these have helped to elucidate pathways that can lead to IBD. Animal studies have also increased our knowledge of the pathological dialogue between the intestinal microbiota and components of the innate and adaptive immune systems misdirecting the immune system to attack the colon. Present-day medical therapy of IBD consists of salicylates, corticosteroids, immunosuppressants and immunomodulators. However, their use may result in severe side effects and complications, such as an increased rate of malignancies or infectious diseases. In clinical practice, there is still a high frequency of incomplete or absent response to medical therapy, indicating a compelling need for new therapeutic strategies. This review summarizes current epidemiology, pathogenesis and diagnostic strategies in IBD. It also provides insight in today's differentiated clinical therapy and describes mechanisms of promising future medicinal approaches.
Collapse
|
|
27
|
He X, Bennett AE, Lian L, Shen B. Recurrent cytomegalovirus infection in ileal pouch-anal anastomosis for ulcerative colitis. Inflamm Bowel Dis 2010; 16:903-4. [PMID: 19821508 DOI: 10.1002/ibd.21121] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
|
|
28
|
Cytomegalovirus infection in patients with active inflammatory bowel disease. Dig Dis Sci 2010; 55:1059-65. [PMID: 20112061 DOI: 10.1007/s10620-010-1126-4] [Citation(s) in RCA: 83] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2009] [Accepted: 01/11/2010] [Indexed: 02/07/2023]
Abstract
BACKGROUND The reported prevalence of cytomegalovirus (CMV) infection with active inflammatory bowel disease (IBD) is highly variable, and whether CMV negatively impacts the clinical course is controversial. AIMS The aim of this study was to determine the prevalence of CMV in patients with active ulcerative colitis (UC) or Crohn's disease (CD) and compare the course of disease in patients with and without CMV. METHODS Consecutive patients with acute exacerbations of active IBD colitis had immunohistochemistry staining for CMV antigen performed on archived specimens. Clinical features were retrospectively reviewed. RESULTS Twelve (10%) of 122 UC patients had CMV, and 0/20 patients with CD had CMV. Of 12 UC patients with CMV infection, seven were not taking steroids or immunosuppressives at their index flare. UC patients with CMV were more likely to have leukocytosis (OR = 5.3, 95% CI 1.5-18.2), require hospitalization (OR = 4.9, 95% CI 1.2-19.0), and be hospitalized > or =7 days (OR = 5.0, 95% CI 1.6-21.3) compared to patients without CMV. Of 12 UC patients with CMV, ten (83%) were treated for their index flare with steroids or 6-mercaptopurine. Only one patient (8%) was treated for CMV infection which occurred 14 months after index endoscopy. Over the 6 months after the index flare, UC patients with CMV had a higher frequency of IBD-related hospitalizations compared to patients without CMV (50 vs. 24%, P = 0.021), but none required surgery or died. CONCLUSIONS The prevalence of CMV with active UC was 10%. Although CMV infection may be a marker of disease severity, our results suggest it does not cause severe morbidity or mortality in a general population of patients with a UC flare.
Collapse
|
|
29
|
Suzuki H, Kato J, Kuriyama M, Hiraoka S, Kuwaki K, Yamamoto K. Specific endoscopic features of ulcerative colitis complicated by cytomegalovirus infection. World J Gastroenterol 2010; 16:1245-51. [PMID: 20222169 PMCID: PMC2839178 DOI: 10.3748/wjg.v16.i10.1245] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify specific colonoscopic findings in patients with ulcerative colitis (UC) complicated by cytomegalovirus (CMV) infection.
METHODS: Among UC patients who were hospitalized due to exacerbation of symptoms, colonoscopic findings were compared between 15 CMV-positive patients and 58 CMV-negative patients. CMV infection was determined by blood test for CMV antigenemia. Five aspects of mucosal changes were analyzed (loss of vascular pattern, erythema, mucosal edema, easy bleeding, and mucinous exudates) as well as five aspects of ulcerative change (wide mucosal defect, punched-out ulceration, longitudinal ulceration, irregular ulceration, and cobblestone-like appearance). Sensitivity, specificity, positive predictive value, and negative predictive value of each finding for CMV positivity were determined.
RESULTS: The sensitivity of irregular ulceration for positive CMV was 100%. The specificity of wide mucosal defect was 95%. Punched-out ulceration and longitudinal ulceration exhibited relatively high sensitivity and specificity (more than 70% for each).
CONCLUSION: Specific colonoscopic findings in patients with UC complicated by CMV infection were identified. These findings may facilitate the early diagnosis of CMV infection in UC patients.
Collapse
|
|
30
|
Cha JM, Lee JI, Choe JW, Joo KR, Jung SW, Shin HP, Choi SI. Cytomegalovirus enteritis causing ileal perforation in an elderly immunocompetent individual. Yonsei Med J 2010; 51:279-83. [PMID: 20191024 PMCID: PMC2824877 DOI: 10.3349/ymj.2010.51.2.279] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2008] [Revised: 07/01/2008] [Accepted: 07/01/2008] [Indexed: 01/21/2023] Open
Abstract
Cytomegalovirus (CMV) infection is usually subclinical in immunocompetent individuals, however it can be life threatening in an elderly immunocompetent individual. We report a case of CMV enteritis causing ileal perforation in a physically active elderly man. An 88-year-old healthy man presented with abdominal pain and diarrhea. After initial conservative treatment, emergency laparotomy was performed for ileal perforation. The diagnosis of CMV enteritis was based on histological findings revealing many large cells with CMV inclusion bodies in the surgical specimen. In elderly individuals, even though they are immunocompetent, CMV enteritis may result in major complications such as bowel perforation, and it should be included in the differential diagnosis of diarrhea if it is resistant to conventional treatment.
Collapse
Affiliation(s)
- Jae Myung Cha
- Department of Internal Medicine, East-West Neo Medical Center, Kyung Hee University College of Medicine, Seoul, Korea.
| | | | | | | | | | | | | |
Collapse
|
|
31
|
Maher MM, Nassar MI. Acute cytomegalovirus infection is a risk factor in refractory and complicated inflammatory bowel disease. Dig Dis Sci 2009; 54:2456-62. [PMID: 19093204 DOI: 10.1007/s10620-008-0639-6] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2008] [Accepted: 11/12/2008] [Indexed: 12/12/2022]
Abstract
The role of cytomegalovirus (CMV) infection in patients with inflammatory bowel disease (IBD) is controversial. Although CMV has been specifically associated with refractory disease, the strength and nature of this association have been a subject of debate. The aim of this study was to evaluate the prevalence and outcome of acute cytomegalovirus infection in patients with severe refractory and complicated inflammatory bowel disease. Seventy-two patients with active IBD (both ulcerative colitis [UC] and Crohn's diseases [CD]) were included in this study. Thorough history taking and physical examination of all patients was made with special emphasis on symptoms and signs of CMV disease. Colonoscopic assessment was made for the extent and activity of IBD and collection of specimen. Prevalence of CMV infection was estimated by serology; anti-CMV IgM and IgG antibodies, and pathologic studies of colonic biopsies used conventional haematoxylin and eosin (H & E) and immunohistochemistry (IHC) with monoclonal antibodies. Complete blood count and liver function tests were done for all patients. Among 72 patients with active inflammatory bowel disease, 23 (31.9%) were resistant to intravenous steroids. CMV was detected in eight (six with UC and two with CD) of the 23 (34.8%) steroid-resistant patients and in only one (3.2%) patient in the remaining 31 patients under steroid treatment and was not detected in 18 IBD patients not using steroids. Among nine CMV-positive IBD patients, six (66.6%) were female and six had fever; cervical lymphadenopathy was found in five patients and splenomegaly in two, compared to no patients in the CMV-negative group (P = 0.01 and 0.03, respectively). Leucopenia and thrombocytopenia were predominantly seen in the CMV-positive versus CMV-negative patients (2.1+/-0.3 vs. 5.9+/-3.4 and 98+/-34 vs. 165+/-101, respectively). Pancolitis was found in five of nine CMV-positive IBD patients whereas in only two patients out of 63 in the CMV-negative group (P = 0.005). Acute CMV infection in patients with IBD is not rare and is often underestimated. CMV infection in patients with refractory or complicated IBD should be ruled out before aggressive immunosuppressive therapy. High clinical index of suspicion for the association of CMV infection with IBD should be directed towards female IBD patients presenting with fever, lymphadenopathy, splenomegaly, leucopenia, and mild hepatitis. CMV IHC is significantly more sensitive than routine H & E stain and should be considered as part of the routine evaluation of IBD patients with severe exacerbation or steroid-refractory disease before proceeding with other medical or surgical therapy that may not be necessary once the CMV is treated.
Collapse
Affiliation(s)
- Maha M Maher
- Department of Internal Medicine, Mansoura University, Mansoura, Egypt,
| | | |
Collapse
|
|
32
|
Onyeagocha C, Hossain MS, Kumar A, Jones RM, Roback J, Gewirtz AT. Latent cytomegalovirus infection exacerbates experimental colitis. THE AMERICAN JOURNAL OF PATHOLOGY 2009; 175:2034-42. [PMID: 19815702 DOI: 10.2353/ajpath.2009.090471] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Inflammatory bowel disease (IBD) severity is positively correlated with cytomegalovirus (CMV) infection. This may reflect CMV triggering and/or exacerbating flares of IBD and/or IBD or immunosuppressive drugs administered to patients with IBD increasing susceptibility to CMV infection. Herein, we performed studies in mice to investigate these possibilities. Mice administered murine CMV (MCMV) developed signs of acute viral infection (malaise and weight loss) and had MCMV loads that were readily detected in numerous organs including the intestine. By 4 weeks, these mice manifested a "latent" infection in which MCMV levels were low but detectable by PCR. Such MCMV infection did not induce acute colitis in either wild-type mice or IL-10(-/-) mice, which are highly prone to developing colitis. However, underlying MCMV infection in an acute or latent state exacerbated the severity of colitis induced by dextran sodium sulfate (DSS). Such potentiation of DSS colitis by latent MCMV infection seemed to occur without viral reactivation. Whereas initial MCMV infection induced acute alterations in serum and intestinal cytokines, such cytokine levels returned to baseline before administration of DSS. However, the initial infection resulted in lasting elevation of antibodies to commensal bacterial antigens, suggesting that MCMV infection may have potentiated colitis via priming of the intestinal immune response to gut microbiota. Thus, underlying CMV infection can alter mucosal immunity, potentially increasing the tendency of CMV-infected hosts to develop colitis.
Collapse
|
|
33
|
|
|
34
|
Ayre K, Warren BF, Jeffery K, Travis SPL. The role of CMV in steroid-resistant ulcerative colitis: A systematic review. J Crohns Colitis 2009; 3:141-8. [PMID: 21172262 DOI: 10.1016/j.crohns.2009.03.002] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2008] [Revised: 03/02/2009] [Accepted: 03/03/2009] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Steroid-resistance presents a management challenge in ulcerative colitis. How steroid-resistance occurs is unknown, but cytomegalovirus infection, often unrecognised, may be the cause in some patients. Current evidence and therapeutic recommendations are examined. METHODS A systematic review of PubMed and EMBASE databases was performed. Search and exclusion criteria are defined in the text. RESULTS Heterogeneity of experimental design and definitions of key terms were notable. Criteria for cytomegalovirus disease, infection or detection varied, as did definitions of steroid-resistance. CMV infection defined by antigenaemia or serology was common in patients on steroids and associated with a higher rate of steroid-resistance (41.66-61% versus 0-68% in steroid-responsive patients). Colonic mucosal cytomegalovirus disease detected by histopathology was associated with intravenous steroid-resistance in 5-36%, compared to 0-10% of steroid-responsive patients. CMV colitis has rarely been reported in association with ulcerative colitis without steroids or other immunomodulators. CMV colitis in healthy individuals is so exceptional as to be the topic of case reports. CONCLUSION Ulcerative colitis and its treatment put patients at risk of CMV infection or reactivation. A distinction is necessary between CMV disease (colitis) and CMV infection. Only colonic mucosal CMV infection detected by histopathology appears clinically relevant and appropriate for antiviral therapy. CMV antigenaemia may be associated with steroid-resistance, but may also be a self-limiting marker of viral reactivation. The impact of CMV on steroid-resistance is complicated by inconsistencies in the literature. Coherent definitions of clinically relevant CMV infection and steroid-resistance are needed.
Collapse
Affiliation(s)
- Karyn Ayre
- Department of Surgery, Queen Margaret Hospital, Dunfermline, United Kingdom
| | | | | | | |
Collapse
|
|
35
|
Criscuoli V, Mocciaro F, Orlando A, Rizzuto MR, Renda MC, Cottone M. Cytomegalovirus disappearance after treatment for refractory ulcerative colitis in 2 patients treated with infliximab and 1 patient with leukapheresis. Inflamm Bowel Dis 2009; 15:810-1. [PMID: 18839422 DOI: 10.1002/ibd.20742] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
|
|
36
|
Systematic review: cytomegalovirus infection in inflammatory bowel disease. J Gastroenterol 2009; 43:735-40. [PMID: 18958541 DOI: 10.1007/s00535-008-2246-x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2008] [Accepted: 07/01/2008] [Indexed: 02/04/2023]
|
|
37
|
Mariguela VC, Chacha SGF, Cunha ADA, Troncon LEDA, Zucoloto S, Figueiredo LTM. Cytomegalovirus in colorectal cancer and idiopathic ulcerative colitis. Rev Inst Med Trop Sao Paulo 2008; 50:83-7. [PMID: 18488086 DOI: 10.1590/s0036-46652008000200004] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2007] [Accepted: 01/29/2008] [Indexed: 11/22/2022] Open
Abstract
Cytomegalovirus (CMV) is a genus in the family Herpesviridae that has been associated with gastrointestinal syndromes. In this work we looked for a possible association of CMV infection with colorectal cancer and ulcerative colitis (UC). Blood and enteric tissue samples of 14 patients with colorectal cancer and of 21 with UC were subjected to a nested-PCR that amplifies part of the gB gene of CMV and also to immunohistochemistry using a specific monoclonal antibody to IE 76 kDa protein of CMV. CMV was detected by nested-PCR in the blood and/or the enteric tissue of nine (64.3%) colorectal cancer and 16 (76.2%) ulcerative colitis patients. In the immunohistochemistry it was observed that 12 (12/21, 57.1%) positive enteric tissue samples of patients with UC and none from patients with colorectal cancer (0/14) were positive to CMV. The positivity of CMV infections in the UC patient group (12/21, 57.1%) showed by both techniques, was significantly higher (p = 0.015) than that observed for colorectal cancer patients (2/14, 14.3%). These results suggest an association of ulcerative colitis with CMV infection of the enteric tissue.
Collapse
|
|
38
|
Abstract
Cytomegalovirus (CMV) infection of the GI tract is a common problem in patients immunosuppressed by HIV or organ transplantation. The esophagus and colon are the most common sites of involvement. Recent developments in diagnosis, such as immunohistochemical staining, shell vial assay and PCR, aid in early detection and predicting the prognosis of CMV disease in susceptible individuals. Although current drugs have limitations in terms of toxicity, drug interactions and resistance, newer drugs appear promising.
Collapse
Affiliation(s)
- Neelima Reddy
- University of Alabama at Birmingham, Division of Gastroenterology and Hepatology, Birmingham, AL 35294-0007, USA
| | | |
Collapse
|
|
39
|
Berkelhammer C. Cytomegalovirus (CMV)-negative blood transfusions in CMV-negative inflammatory bowel disease patients. Inflamm Bowel Dis 2007; 13:1184. [PMID: 17387678 DOI: 10.1002/ibd.20136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
|
|
40
|
Gisbert JP, Gomollón F. [Common errors in the management of the seriously ill patient with inflammatory bowel disease]. GASTROENTEROLOGIA Y HEPATOLOGIA 2007; 30:294-314. [PMID: 17493441 DOI: 10.1157/13101982] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Javier P Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Universidad Autónoma, Madrid, Spain.
| | | |
Collapse
|
|
41
|
Mikami S, Nakase H, Ueno S, Matsuura M, Sakurai T, Chiba T. Involvement of cytomegalovirus infection in the ileal lesions of the patient with Behçet's disease. Inflamm Bowel Dis 2007; 13:802-3. [PMID: 17253611 DOI: 10.1002/ibd.20105] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
|
|
42
|
Nakase H, Yoshino T, Ueno S, Uza N, Mikami S, Matsuura M, Chiba T. Importance of early detection of cytomegalovirus infection in refractory inflammatory bowel disease. Inflamm Bowel Dis 2007; 13:364. [PMID: 17206718 DOI: 10.1002/ibd.20033] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
|
|
43
|
Casadesus D, Tani T, Wakai T, Maruyama S, Iiai T, Okamoto H, Hatakeyama K. Possible role of human cytomegalovirus in pouchitis after proctocolectomy with ileal pouch-anal anastomosis in patients with ulcerative colitis. World J Gastroenterol 2007; 13:1085-9. [PMID: 17373744 PMCID: PMC4146872 DOI: 10.3748/wjg.v13.i7.1085] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To detect the presence of human cytomegalovirus (HCMV) proteins and genes on the ileal pouch of patients with ulcerative colitis who have undergone proctocolectomy with ileal pouch-anal anastomosis (IPAA).
METHODS: Immunohistochemistry, polymerase chain reaction (PCR) and PCR sequencing methods were utilized to test the presence of HCMV in pouch specimens taken from 34 patients in 86 endoscopies.
RESULTS: HCMV genes and proteins were detected in samples from 12 (35.2%) patients. The rate of detection was significant in the endoscopies from patients diagnosed with pouchitis (5 of 12, 41.6%), according to the Japanese classification of pouchitis, in comparison to patients with normal pouch (7 of 62, 11.2%; P = 0.021). In all patients with pouchitis in which the HCMV was detected, it was the first episode of pouchitis. The virus was not detected in previous biopsies taken in normal endoscopies of these patients. During the follow-up, HCMV was detected in one patient with recurrent pouchitis and in 3 patients whose pouchitis episodes improved but whose positive endoscopic findings persisted.
CONCLUSION: HCMV can take part in the inflammatory process of the pouch in some patients with ulcerative colitis who have undergone proctocolectomy with IPAA.
Collapse
Affiliation(s)
- Damian Casadesus
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata City 951-8510, Japan
| | | | | | | | | | | | | |
Collapse
|
|
44
|
Rezania D, Ouban A, Marcet J, Kelley S, Coppola D. CMV Colitis Mimicking Recurrent Inflammatory Bowel Disease: Report of Three Cases. Am Surg 2007. [DOI: 10.1177/000313480707300113] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The association between cytomegalovirus infection and inflammatory bowel disease challenges both the clinician and the pathologist to establish the correct diagnosis and to prescribe the most appropriate form of therapy. To understand this association the authors report three patients who presented with signs and symptoms mimicking reactivated inflammatory bowel disease who responded poorly to aggressive treatment of inflammatory bowel disease. Microscopic examination, in all three cases revealed numerous nuclear and cytoplasmic viral inclusions, as demonstrated by cytomegalovirus immunohistochemistry, as well as histologic findings consistent with inflammatory bowel disease (ulcerative colitis and/or Crohn's disease). Because the clinical pathologic features of cytomegalovirus colitis and inflammatory bowel disease often overlap, and because of the possible coexistence of cytomegalovirus colitis with idiopathic colitis, the possibility of cytomegalovirus infection should be always considered, so that the most appropriate therapy can be instituted for these patients.
Collapse
Affiliation(s)
- Dorna Rezania
- Departments of Pathology, College of Medicine, Tampa, Florida
| | | | - Jorge Marcet
- Surgery, University of South Florida, College of Medicine, Tampa, Florida
| | - Scott Kelley
- Surgery, University of South Florida, College of Medicine, Tampa, Florida
| | - Domenico Coppola
- Departments of Pathology, College of Medicine, Tampa, Florida
- Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| |
Collapse
|
|
45
|
Abstract
When patients with inflammatory bowel disease (IBD) are admitted to the hospital with a flare of acute severe colitis, the possibility of a concurrent cytomegalovirus (CMV) infection causing or worsening the colitis is often considered. IBD patients are usually immunosuppressed, and therefore presumably at increased risk for active CMV infection and disease. Multiple techniques are used to diagnose CMV infection, including endoscopy, histology, serology, viral culture, CMV antigen testing, and CMV DNA testing. Immunohistochemistry (IHC) performed on colon biopsy specimens with monoclonal antibodies directed against CMV immediate early antigen is considered by most to be the current gold standard for diagnosis. The prevalence of CMV infection in acute severe colitis appears to be 21-34%, and the prevalence of CMV infection in the steroid refractory subgroup of these patients is 33-36%. After antiviral therapy, colitis remission rates in IBD patients with CMV infection range from 67% to 100%, though CMV histological infection or the presence of circulating virus alone is not always associated with steroid resistance, and may not require antiviral therapy.
Collapse
Affiliation(s)
- Ahmed Kandiel
- Center for Inflammatory Bowel Disease, Department of Gastroenterology/Hepatology, Cleveland Clinic, Cleveland, Ohio 44195, USA
| | | |
Collapse
|
|
46
|
Martin SI, Sepehr A, Fishman JA. Primary infection with cytomegalovirus in ulcerative colitis. Dig Dis Sci 2006; 51:2184-7. [PMID: 17120145 DOI: 10.1007/s10620-006-9474-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2006] [Accepted: 05/31/2006] [Indexed: 12/13/2022]
Affiliation(s)
- Stanley I Martin
- Infectious Disease Division, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
| | | | | |
Collapse
|
|
47
|
Cytomegalovirus ileitis associated with goblet cell carcinoid tumour of the appendix. J Infect 2006; 54:e153-6. [PMID: 17049463 DOI: 10.1016/j.jinf.2006.09.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2006] [Revised: 08/19/2006] [Accepted: 09/09/2006] [Indexed: 10/24/2022]
Abstract
We report a female patient with cytomegalovirus (CMV) terminal ileitis and CMV viraemia, associated with a metastatic goblet cell carcinoid (GCC) tumour of the appendix. She was treated with ileocaecal resection followed by ganciclovir. We highlight the importance of vigilant histopathological assessment and discuss the existing literature on gastrointestinal CMV infection in immunocompetent patients.
Collapse
|
|
48
|
Kou T, Nakase H, Tamaki H, Kudo T, Nishio A, Chiba T. Cytomegalovirus infection in patients with ulcerative colitis diagnosed by quantitative real-time PCR analysis. Dig Dis Sci 2006; 51:1052-5. [PMID: 16865568 DOI: 10.1007/s10620-006-8006-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2005] [Accepted: 07/27/2005] [Indexed: 12/13/2022]
Affiliation(s)
- Tadayuki Kou
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Shogoin, Kyoto, 606-8507, Japan
| | | | | | | | | | | |
Collapse
|
|
49
|
Kojima T, Watanabe T, Hata K, Shinozaki M, Yokoyama T, Nagawa H. Cytomegalovirus infection in ulcerative colitis. Scand J Gastroenterol 2006; 41:706-11. [PMID: 16716970 DOI: 10.1080/00365520500408584] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Cytomegalovirus (CMV) infection has been reported as an exacerbating factor in inflammatory bowel disease but the relationship between CMV infection and ulcerative colitis (UC) remains unclear. There has been no detailed research to elucidate the clinicopathologic features of CMV infection in UC using surgical specimens. The aim of this study was to investigate the clinicopathologic features of CMV infection in UC patients who had undergone colectomy. MATERIAL AND METHODS Surgical specimens taken from UC patients were examined for CMV infection. The patients were divided into three groups: severe, refractory, and UC-associated dysplasia or cancer according to the operative indications. CMV infection rates were evaluated and a comparison of clinical parameters was made between CMV-positive and CMV-negative patients, and the risk factors for CMV infection were analyzed using multivariate analyses. RESULTS It was found that 25% of 32 patients were positive for CMV in the severe UC group; 8.3% of 72 patients were positive for CMV in the refractory UC group. None of the 22 patients was positive for CMV in the UC-associated dysplasia or cancer group. The CMV-positive rate in the severe UC group was significantly higher than that in the other groups (p<0.05). Patients' age at the time of operation was higher in the CMV-positive group than in the CMV-negative group among the patients with severe UC (p<0.01), and age at operation was an independent risk factor for CMV infection. CONCLUSIONS CMV is found more frequently in severe UC than refractory UC and UC-associated cancer or dysplasia. Higher age can be a risk factor for CMV infection in patients with severe UC. However, a high steroid dose may not always be a risk factor for CMV infection.
Collapse
Affiliation(s)
- Tetsu Kojima
- Department of Surgical Oncology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
| | | | | | | | | | | |
Collapse
|
|
50
|
Lichtenstein GR, Abreu MT, Cohen R, Tremaine W. American Gastroenterological Association Institute technical review on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology 2006; 130:940-87. [PMID: 16530532 DOI: 10.1053/j.gastro.2006.01.048] [Citation(s) in RCA: 334] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Gary R Lichtenstein
- Hospital of the University of Pennsylvania University of Pennsylvania School of Medicine Philadelphia, Pennsylvania, USA
| | | | | | | |
Collapse
|