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Szlak J, Magdziak A, Mróz A, Wieszczy-Szczepanik P, Reguła J, Zagórowicz E. Cytomegalovirus infection in patients with active ulcerative colitis: a prospective observational study. Eur J Gastroenterol Hepatol 2025:00042737-990000000-00534. [PMID: 40359279 DOI: 10.1097/meg.0000000000003001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
Abstract
OBJECTIVES The role of cytomegalovirus (CMV) infection in the course of inflammatory bowel disease is still controversial. We aimed to prospectively evaluate the course of ulcerative colitis in patients with exacerbation, in whom CMV status was examined using immunohistochemistry of bowel biopsies. METHODS In a single centre, we followed-up consecutive patients admitted for moderate or severe ulcerative colitis flare between 2016 and 2019. Colectomies, repeated hospitalisations, major treatment modifications, and quality of life (QoL) were recorded. The relationship between categorical variables was examined with the χ2 statistical test or Fisher's exact test. RESULTS Of 84 patients, 16 (19%) were CMV-positive. A Mayo endoscopic score of 3 was more frequent in CMV-positive than CMV-negative patients (81.2 vs. 51.5%; P = 0.048) as was corticosteroid treatment (81.2 vs. 54.4%; P = 0.015). Median follow-up was 2.1 years (range: 0.3-3.6 years). Colectomy was performed in 20 (23.8%) patients, with similar rates in CMV-positive (25%) and CMV-negative patients (23.5%; P = 1.0). Similarly, no differences were found in the frequency of hospitalisation and QoL. The percentage of patients who started biological treatment was higher in the CMV-negative than in the CMV-positive group (58.8 vs. 18.8%; P = 0.005). CONCLUSION CMV infection was present in 19% of consecutive patients hospitalised for ulcerative colitis flare. Corticosteroid treatment and severe endoscopic lesions were observed more often in patients with CMV-positive. In the following 2.1 years, the colectomy rate did not differ between patients with CMV-positive and CMV-negative. Routine screening for CMV in ulcerative colitis exacerbation is not advisable.
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Affiliation(s)
| | | | - Andrzej Mróz
- Department of Pathology and Laboratory Medicine, The Maria Sklodowska-Curie National Research Institute of Oncology
- Department of Pathomorphology, Medical Centre of Postgraduate Education
| | | | - Jaroslaw Reguła
- Department of Microbiology
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Centre of Postgraduate Education, Warsaw, Poland
| | - Edyta Zagórowicz
- Department of Microbiology
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Centre of Postgraduate Education, Warsaw, Poland
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Zhang H, Gu X, He W, Zhao SL, Cao ZJ. Epstein-Barr virus infection is an independent risk factor for surgery in patients with moderate-to-severe ulcerative colitis. World J Gastroenterol 2025; 31:104758. [PMID: 40308799 PMCID: PMC12038525 DOI: 10.3748/wjg.v31.i16.104758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 03/18/2025] [Accepted: 04/14/2025] [Indexed: 04/27/2025] Open
Abstract
BACKGROUND Epstein-Barr virus (EBV) infection of the intestinal mucosa is associated with surgical risk in ulcerative colitis (UC); however, the exact effect remains unclear. AIM To determine whether EBV infection can predict the need for colectomy and to develop a surgical risk predictive model. METHODS This was a single-center retrospective study of 153 patients with moderate-to-severe UC between September 2012 and May 2023. EBV-encoded small RNA (EBER) in situ hybridization and immunohistochemistry (IHC) were used for EBV testing and assessment. Cytomegalovirus (CMV) was detected by IHC. Logistic regression analysis was conducted to identify risk factors for colectomy and develop a predictive risk model. RESULTS EBER-positivity in the intestinal mucosa was present in 40.4% (19/47) and 4.7% (5/106) of patients in the surgery and non-surgery groups, respectively, with significant differences between the groups (P < 0.01, odds ratio = 13.707). The result of multivariate logistic regression revealed that age, EBV infection in the colonic mucosa, CMV infection in the colonic mucosa, and treatment with three or more immunosuppressive agents before admission were significant independent predictors of colectomy. A nomogram incorporating these variables demonstrated good discriminative ability, and exhibited good calibration and clinical utility. IHC showed that EBV-infected cells mainly included B and T lymphocytes in patients with high EBER concentrations. CONCLUSION EBV infection of the intestinal mucosa is a significant independent risk factor for colectomy in patients with moderate-to-severe UC. The nomogram model, which includes EBV infection, effectively predicts colectomy risk.
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Affiliation(s)
- Hui Zhang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
| | - Xi Gu
- Division of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
| | - Wei He
- Division of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
| | - Shu-Liang Zhao
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
| | - Zhi-Jun Cao
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
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3
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Ebrahimi R, Masouri MM, Salehi Amniyeh Khozani AA, Ramadhan Hussein D, Nejadghaderi SA. Safety and efficacy of fecal microbiota transplantation for viral diseases: A systematic review of clinical trials. PLoS One 2024; 19:e0311731. [PMID: 39432486 PMCID: PMC11493255 DOI: 10.1371/journal.pone.0311731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Accepted: 09/21/2024] [Indexed: 10/23/2024] Open
Abstract
BACKGROUND Gut microbiota play important roles in several diseases like viral infections. In this systematic review, our objective was to assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating various viral diseases. METHODS We conducted searches on databases including PubMed, Web of Science, Scopus, and Google Scholar until November 2023. Clinical trials reported outcomes related to safety of FMT or its efficacy in patients with viral diseases were included. We excluded other types of studies that enrolled healthy individuals or patients with other disorders and did not use FMT. The assessment of bias risk was conducted using the National Institutes of Health (NIH) study quality evaluation tool. RESULTS Eight studies with total 196 participants were included. Viral diseases were human immunodeficiency virus (HIV), hepatitis B, COVID-19 and Clostridioides difficile coinfection, and cytomegalovirus colitis. In hepatitis B cases, HBeAg clearance was significant in those received FMT (p<0.01), while it was not significant in another one (p = 0.19). A clinical response was noted in 37.5% of patients with cytomegalovirus colitis, with an equal percentage achieving clinical remission post-FMT. There was a significant reduction in Clostridioides difficile relapse rate in FMT group than controls in coinfection of Clostridioides difficile and COVID-19 (2.17% vs. 42.5%, p<0.05). In patients with HIV, partial engraftment of the donor microbiome and increases in alpha diversity were observed after FMT. No severe adverse events were reported. Most studies had fair or good qualities. CONCLUSIONS Our findings revealed FMT as a promising, safe treatment for some viral diseases. It improved viral clearance, clinical outcomes, and inflammation. However, the varying responses and small sample sizes call for more trials on FMT in viral diseases.
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Affiliation(s)
- Rasoul Ebrahimi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | | | | | - Seyed Aria Nejadghaderi
- HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
- Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
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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.
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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
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Misaki M, Sagami S, Yamana Y, Maeda M, Hojo A, Miyatani Y, Maeda I, Nakano M, Hibi T, Kobayashi T. A case of cytomegalovirus esophagitis difficult to distinguish from Crohn's disease exacerbation. Clin J Gastroenterol 2024; 17:593-597. [PMID: 38782847 DOI: 10.1007/s12328-024-01978-z] [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: 12/26/2023] [Accepted: 04/27/2024] [Indexed: 05/25/2024]
Abstract
Patients with Crohn's disease are at higher risk of opportunistic infection, especially if treated with immunosuppressive therapy. Cytomegalovirus has been reported to cause ulcerated lesions mainly in the lower gastrointestinal tract of inflammatory bowel disease patients. We herein report a rare case of Crohn's disease complicated with cytomegalovirus esophagitis, which was difficult to distinguish from exacerbation of Crohn's disease. Diagnostic values of clinical course, blood tests, endoscopic and histological examinations are limited but the present case was therapeutically diagnosed by antiviral therapy in combination with histological evidence of cytomegalovirus.
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Affiliation(s)
- Mika Misaki
- Department of Gastroenterology and Hepatology, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Shintaro Sagami
- Department of Gastroenterology and Hepatology, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-Ku, Tokyo, 108-8642, Japan
| | - Yoko Yamana
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-Ku, Tokyo, 108-8642, Japan
| | - Masa Maeda
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-Ku, Tokyo, 108-8642, Japan
| | - Aya Hojo
- Department of Gastroenterology and Hepatology, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-Ku, Tokyo, 108-8642, Japan
| | - Yusuke Miyatani
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-Ku, Tokyo, 108-8642, Japan
| | - Ichiro Maeda
- Department of Pathology, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Masaru Nakano
- Department of Gastroenterology and Hepatology, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-Ku, Tokyo, 108-8642, Japan
| | - Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-Ku, Tokyo, 108-8642, Japan
| | - Taku Kobayashi
- Department of Gastroenterology and Hepatology, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-Ku, Tokyo, 108-8642, Japan.
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Huang D, Rennie M, Krasovec A, Nagubandi S, Liu S, Ge E, Khehra B, Au M, Sivagnanam S, Kwan V, Rogge C, Mitrev N, Kariyawasam V. Impact of cytomegalovirus on outcomes in acute severe ulcerative colitis: a retrospective observational study. Ther Adv Chronic Dis 2024; 15:20406223241233203. [PMID: 38560721 PMCID: PMC10981253 DOI: 10.1177/20406223241233203] [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: 07/02/2023] [Accepted: 01/25/2024] [Indexed: 04/04/2024] Open
Abstract
BACKGROUND Concomitant cytomegalovirus (CMV) is highly prevalent in acute severe ulcerative colitis (ASUC) but data for outcomes of CMV positivity in ASUC and the benefit of antiviral therapy remain unclear. OBJECTIVES We aim to determine the impact of CMV positivity, and antiviral therapy, on outcomes such as colectomy-free survival, length of hospital stay and readmission rate, among hospitalized patients with ASUC. DESIGN This is a retrospective, multicentre study of patients admitted with ASUC. METHODS CMV positivity was diagnosed from blood CMV DNA and inpatient colonic biopsies. Background demographics and disease characteristics, clinical characteristics and outcomes during admission and long-term outcomes were obtained from electronic medical records and compared according to the presence of CMV and the use of antiviral therapy. RESULTS CMV was detected in 40 (24%) of 167 ASUC admissions. Previous steroid exposure was the only clinical predictor of CMV positivity on multivariate analysis. Outcomes of greater requirement for rescue therapy (60% versus 33%), longer hospital stay (14.3 versus 9.9 days) and higher readmission rates at 3 and 12 months were associated with CMV positivity. No difference was found in the rate of colectomy or colectomy-free survival. Antiviral therapy was not associated with a lower risk of colectomy but did extend the time to colectomy (126 versus 36 days). CONCLUSION CMV positivity was associated with worse outcomes of need for rescue therapy, hospital stay and readmissions. Antiviral therapy was not found to reduce the risk of colectomy but did extend the time to colectomy. Further prospective studies will be required to more clearly determine its benefit in patients with concomitant CMV and ASUC.
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Affiliation(s)
- Dazhong Huang
- Department of Gastroenterology and Hepatology, Blacktown and Mt Druitt Hospital, Blacktown Road, Blacktown NSW 2148, Australia
- University of Western Sydney, Sydney, Australia
| | - Michael Rennie
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | | | - Shyam Nagubandi
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Sichang Liu
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Edward Ge
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Barinder Khehra
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Michael Au
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Shobini Sivagnanam
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- Australian Clinical Labs, Sydney, Australia
| | - Vu Kwan
- Westmead Hospital, Westmead, NSW, Australia
| | | | - Nikola Mitrev
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Viraj Kariyawasam
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
- IBD Sydney, Sydney, Australia
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Rivière P, Li Wai Suen C, Chaparro M, De Cruz P, Spinelli A, Laharie D. Acute severe ulcerative colitis management: unanswered questions and latest insights. Lancet Gastroenterol Hepatol 2024; 9:251-262. [PMID: 38340753 DOI: 10.1016/s2468-1253(23)00313-8] [Citation(s) in RCA: 24] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 08/30/2023] [Accepted: 09/05/2023] [Indexed: 02/12/2024]
Abstract
Acute severe ulcerative colitis (ASUC) is a distinctive ulcerative colitis flare presentation characterised by the presence of systemic inflammation as well as bloody diarrhoea, and occurs at least once in 25% of patients with ulcerative colitis during their disease course. Each episode carries a risk of complications, need for colectomy, and mortality. Little is known about ASUC pathogenesis, although impaired host-microbiota crosstalk involving pathobionts is suspected. In this Review, we discuss unanswered questions and results from the latest research on the medical-first-line, second-line, and potential third-line therapies-and surgical management of ASUC. We detail promising options for management, such as the use of enteral nutrition in combination with intravenous steroids, the ability to predict early failure of first-line or second-line therapies, and the emerging role of JAK inhibitors. An optimal framework to personalise therapy on the basis of multiomics tools is yet to be developed.
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Affiliation(s)
- Pauline Rivière
- CHU de Bordeaux, Centre Medico-Chirurgical Magellan, Hôpital Haut-Lévêque, Gastroenterology Department, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
| | - Christopher Li Wai Suen
- Department of Gastroenterology, Austin Health and Department of Medicine, Austin Academic Centre, The University of Melbourne, Melbourne, VIC, Australia
| | - María Chaparro
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Madrid, Spain; Universidad Autonoma de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
| | - Peter De Cruz
- Department of Gastroenterology, Austin Health and Department of Medicine, Austin Academic Centre, The University of Melbourne, Melbourne, VIC, Australia
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, Milan Italy; Colon and Rectal Surgery Division, IRCCS Humanitas Research Hospital, Milan, Italy
| | - David Laharie
- CHU de Bordeaux, Centre Medico-Chirurgical Magellan, Hôpital Haut-Lévêque, Gastroenterology Department, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France.
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Bao MM, Kennedy JM, Dolinger MT, Dunkin D, Lai J, Dubinsky MC. Cytomegalovirus Colitis in a Patient with Severe Treatment Refractory Ulcerative Colitis. CROHN'S & COLITIS 360 2024; 6:otae014. [PMID: 38444641 PMCID: PMC10914341 DOI: 10.1093/crocol/otae014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Indexed: 03/07/2024] Open
Abstract
Background Cytomegalovirus (CMV) can be reactivated in ulcerative colitis (UC), but its role in progression of inflammation is unclear. Risk factors include severe colitis and treatment with immunosuppressive medications, particularly corticosteroids and immunomodulators. Methods We report a case of cytomegalovirus colitis in a pediatric patient with pancolitis who had been refractory to aminosalicylate, infliximab, and ustekinumab and was in clinical remission and with transmural response on upadacitinib. Results This is a case of a 13-year-old male with UC refractory to multiple therapies who were in clinical remission on upadacitinib 30 mg daily. He developed an acute increase in symptoms and did not respond to therapy escalation with increased upadacitinib 45 mg daily for 2 weeks and prednisone for 1 week. He was diagnosed with cytomegalovirus colitis on flexible sigmoidoscopy biopsy. He was treated with intravenous ganciclovir with tapering of immunosuppressive regimen. Despite initial response, he underwent subtotal colectomy and subsequent restorative proctocolectomy with ileal pouch anal-anastomosis. Conclusions Despite our patient having multiple risk factors for developing CMV colitis, upadacitinib may have played a role when considering its known impact on the herpes family of viruses. CMV colitis should be evaluated for in any patient who presents with worsening symptoms without evidence of other infection or response to increase in therapy.
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Affiliation(s)
- Michelle M Bao
- Division of Pediatric Gastroenterology, Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, NY, USA
| | - Juliana M Kennedy
- Division of Pediatric Gastroenterology, Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, NY, USA
| | - Michael T Dolinger
- Division of Pediatric Gastroenterology, Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, NY, USA
| | - David Dunkin
- Division of Pediatric Gastroenterology, Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, NY, USA
| | - Joanne Lai
- Division of Pediatric Gastroenterology, Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, NY, USA
| | - Marla C Dubinsky
- Division of Pediatric Gastroenterology, Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, NY, USA
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Maresca R, Varca S, Di Vincenzo F, Ainora ME, Mignini I, Papa A, Scaldaferri F, Gasbarrini A, Giustiniani MC, Zocco MA, Laterza L. Cytomegalovirus Infection: An Underrated Target in Inflammatory Bowel Disease Treatment. J Clin Med 2023; 13:130. [PMID: 38202138 PMCID: PMC10779749 DOI: 10.3390/jcm13010130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 12/20/2023] [Accepted: 12/22/2023] [Indexed: 01/12/2024] Open
Abstract
CMV infection is still a matter of concern in IBD patients, especially regarding the disease's relapse management. Why IBD patients, particularly those affected by ulcerative colitis, are more susceptible to CMV reactivation is not totally explained, although a weakened immune system could be the reason. Various techniques, ranging from serology to histology, can be employed to detect intestinal CMV infection; however, there is currently disagreement in the literature regarding the most effective diagnostic test. Furthermore, CMV involvement in steroid resistance has been broadly discussed, but whether CMV infection is a cause or consequence of the disease severity and, consequently, steroid refractoriness is still debated. Its potential contribution to the lack of response to advanced therapy and small molecules must be more valued and wholly explored. In this review, we look at the actual literature on CMV in IBD patients, and we suggest a pragmatic algorithm for clinical practice management of CMV infection.
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Affiliation(s)
- Rossella Maresca
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Simone Varca
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Federica Di Vincenzo
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Maria Elena Ainora
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
| | - Irene Mignini
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
| | - Alfredo Papa
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Franco Scaldaferri
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Antonio Gasbarrini
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Maria Cristina Giustiniani
- Department of Pathology, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy;
| | - Maria Assunta Zocco
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Lucrezia Laterza
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
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Post CS, Cheng J, Pantanowitz L, Westerhoff M. Utility of Machine Learning to Detect Cytomegalovirus in Digital Hematoxylin and Eosin-Stained Slides. J Transl Med 2023; 103:100225. [PMID: 37527779 DOI: 10.1016/j.labinv.2023.100225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Revised: 07/01/2023] [Accepted: 07/25/2023] [Indexed: 08/03/2023] Open
Abstract
Rapid and accurate cytomegalovirus (CMV) identification in immunosuppressed or immunocompromised patients presenting with diarrhea is essential for therapeutic management. Due to viral latency, however, the gold standard for CMV diagnosis remains to identify viral cytopathic inclusions on routine hematoxylin and eosin (H&E)-stained tissue sections. Therefore, biopsies may be taken and "rushed" for pathology evaluation. Here, we propose the use of artificial intelligence to detect CMV inclusions on routine H&E-stained whole-slide images to aid pathologists in evaluating these cases. Fifty-eight representative H&E slides from 30 cases with CMV inclusions were identified and scanned. The resulting whole-slide images were manually annotated for CMV inclusions and tiled into 300 × 300 pixel patches. Patches containing annotations were labeled "positive," and these tiles were oversampled with image augmentation to account for class imbalance. The remaining patches were labeled "negative." Data were then divided into training, validation, and holdout sets. Multiple deep learning models were provided with training data, and their performance was analyzed. All tested models showed excellent performance. The highest performance was seen using the EfficientNetV2BO model, which had a test (holdout) accuracy of 99.93%, precision of 100.0%, recall (sensitivity) of 99.85%, and area under the curve of 0.9998. Of 518,941 images in the holdout set, there were only 346 false negatives and 2 false positives. This shows proof of concept for the use of digital tools to assist pathologists in screening "rush" biopsies for CMV infection. Given the high precision, cases screened as "positive" can be quickly confirmed by a pathologist, reducing missed CMV inclusions and improving the confidence of preliminary results. Additionally, this may reduce the need for immunohistochemistry in limited tissue samples, reducing associated costs and turnaround time.
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Affiliation(s)
- Corey S Post
- Department of Pathology, Michigan Medicine, Ann Arbor, Michigan.
| | - Jerome Cheng
- Department of Pathology, Michigan Medicine, Ann Arbor, Michigan
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11
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Zhong B, Amundsen T, Farmer C. Invasive Gastrointestinal Mucormycosis. ACG Case Rep J 2023; 10:e01161. [PMID: 37753101 PMCID: PMC10519550 DOI: 10.14309/crj.0000000000001161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 08/29/2023] [Indexed: 09/28/2023] Open
Abstract
Invasive mucormycosis is an opportunistic fungal infection that can be devastating in immunosuppressed patients. Gastrointestinal infection is rare, but carries among the highest mortality rates of its major clinical presentations. We present a case of invasive gastrointestinal mucormycosis in a patient who underwent recent chemotherapy and autologous stem cell transplant. Initial histopathology revealed cytomegalovirus infection, which was treated before subsequent diagnosis of mucormycosis on repeat bowel biopsy. Our case highlights a myriad of risk factors that increase the potential for serious infection by this pervasive fungus.
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Affiliation(s)
- Boris Zhong
- Department of Internal Medicine, Baylor Scott & White Medical Center, Temple, TX
| | - Tyson Amundsen
- Department of Gastroenterology, University of Tennessee, Memphis, TN
| | - Christopher Farmer
- Department of Internal Medicine, Baylor Scott & White Health, Round Rock, TX
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12
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Zhu F, Hu Z, Yu W, Dai F, Jing D, Zhou G. Ulcerative Colitis Concomitant with Cytomegalovirus Infection, Bullous Sweet's Syndrome, and Acute Myeloid Leukemia: A Case Report and Literature Review. J Inflamm Res 2023; 16:3715-3723. [PMID: 37663756 PMCID: PMC10473406 DOI: 10.2147/jir.s422057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 08/11/2023] [Indexed: 09/05/2023] Open
Abstract
Background Ulcerative colitis (UC) is a chronic, relapsing progressive inflammatory immune disease. There is still no cure for it. Even worse, UC may predispose patients to opportunistic infections, and several extra-intestinal manifestations (EIMs) and comorbidities may antedate, occur with, or postdate the onset of UC, which may increase the mortality risk. But case reports of UC patients simultaneously concomitant with opportunistic infection, EIM, and comorbidity are extremely rare. Case Presentation We report a case of 51-year-old male patient with incipient UC accompanied by cytomegalovirus (CMV) infection and bullous Sweet's syndrome (bSS, a cutaneous EIM of UC) after treatment with oral mesalazine and prednisolone for 3 weeks. After clearance of the CMV infection by using ganciclovir, the patient was administered two cycles of infliximab to cure UC and bSS; however, he developed acute myeloid leukemia (AML) a month later and died after two cycles of chemotherapy. Conclusion Based on this rare case of UC concomitant with CMV infection, bSS and AML, we recommend that it is important to distinguish between an acute UC flare and opportunistic infections, especially in patients receiving immunosuppressive therapy, and monitor EIMs and comorbidities timely. Particular attention should be paid to cancer surveillance. Clinicians should be mindful of these facts to adopt optimal therapeutic options to address all aspects of UC. Early initiation of biological therapy may be of benefit to patients with newly diagnosed severe UC.
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Affiliation(s)
- Fengqin Zhu
- Department of Gastroenterology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272000, People’s Republic of China
- Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, People’s Republic of China
| | - Zongjing Hu
- Department of Gastroenterology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272000, People’s Republic of China
| | - Wei Yu
- Department of Gastroenterology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272000, People’s Republic of China
| | - Fengxian Dai
- Department of Gastroenterology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272000, People’s Republic of China
| | - Dehuai Jing
- Department of Gastroenterology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272000, People’s Republic of China
| | - Guangxi Zhou
- Department of Gastroenterology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272000, People’s Republic of China
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13
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Cohen NA, Zafer M, Setia N, Anderson MJ, Sakuraba A, Dalal S, Pekow J, Cohen RD, Rubin DT, Micic D. Serum Cytomegalovirus Polymerase Chain Reaction Test Is a Valuable Negative Predictor of Infection in Acute Severe Ulcerative Colitis. Dig Dis Sci 2023; 68:897-901. [PMID: 35781654 DOI: 10.1007/s10620-022-07607-4] [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: 03/10/2022] [Accepted: 06/20/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Diagnosis of cytomegalovirus (CMV) colitis in the setting of severe ulcerative colitis (UC) remains a clinical challenge. This study aimed to determine the utility of serum CMV polymerase chain reaction (PCR) as a non-invasive test for the diagnosis of CMV superinfection in patients hospitalized with UC. METHODS This retrospective study included consecutive admitted patients with UC who had serum testing for CMV completed as part of standard hospital procedure and CMV colitis diagnosed by expert pathologists. RESULTS Two hundred and six patients with UC were included; 13 patients (6%) had histologically confirmed CMV colitis. Eleven of 13 patients with CMV colitis (84%) and 3 of 193 (1.5%) patients without CMV colitis had a positive serum PCR test (p < 0.0001). ROC analysis showed that a CMV PCR level of 259 IU/mL had a sensitivity and specificity of 77% and 99%, respectively, for diagnosis of CMV colitis with an AUC of 0.9 (p < 0.0001). Serum CMV PCR level significantly correlated to the number of inclusion bodies on biopsy specimens with data available (n = 8) (r = 0.8, p = 0.02). CMV positivity did not predict the need for salvage therapy, admission or 1-year colectomy rates. CONCLUSION Serum CMV PCR has an excellent negative predictive value and demonstrates a strong correlation with CMV positivity on histology. This work supports a rationale for serum CMV PCR testing on admission to assess the risk of CMV colitis in patients with severe UC.
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Affiliation(s)
- Nathaniel A Cohen
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC4076, Chicago, IL, 60637, USA
| | - Maryam Zafer
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC4076, Chicago, IL, 60637, USA
| | - Namrata Setia
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC4076, Chicago, IL, 60637, USA
| | - Michael J Anderson
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC4076, Chicago, IL, 60637, USA
| | - Atsushi Sakuraba
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC4076, Chicago, IL, 60637, USA
| | - Sushila Dalal
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC4076, Chicago, IL, 60637, USA
| | - Joel Pekow
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC4076, Chicago, IL, 60637, USA
| | - Russell D Cohen
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC4076, Chicago, IL, 60637, USA
| | - David T Rubin
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC4076, Chicago, IL, 60637, USA
| | - Dejan Micic
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC4076, Chicago, IL, 60637, USA.
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Thavamani A, Umapathi KK, Sferra TJ, Sankararaman S. Cytomegalovirus Infection Is Associated With Adverse Outcomes Among Hospitalized Pediatric Patients With Inflammatory Bowel Disease. Gastroenterology Res 2023; 16:1-8. [PMID: 36895701 PMCID: PMC9990534 DOI: 10.14740/gr1588] [Citation(s) in RCA: 4] [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: 11/21/2022] [Accepted: 12/27/2022] [Indexed: 03/11/2023] Open
Abstract
BACKGROUND Adults with inflammatory bowel disease (IBD) are at increased risk of developing cytomegalovirus (CMV) colitis, which is associated with adverse outcomes. Similar studies in pediatric IBD patients are lacking. METHODS We analyzed non-overlapping years of National Inpatient Sample (NIS) and Kids Inpatient Database (KID) between 2003 and 2016. We included all patients < 21 years with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC). Patients with coexisting CMV infection during that admission were compared with patients without CMV infection for outcome measures such as in-hospital mortality, disease severity, and healthcare resource utilization. RESULTS We analyzed a total of 254,839 IBD-related hospitalizations. The overall prevalence rate of CMV infection was 0.3% with an overall increasing prevalence trend, P < 0.001. Approximately two-thirds of patients with CMV infection had UC, which was associated with almost 3.6 times increased risk of CMV infection (confidence interval (CI): 3.11 to 4.31, P < 0.001). IBD patients with CMV had more comorbid conditions. CMV infection was significantly associated with increased odds of in-hospital mortality (odds ratio (OR): 3.58; CI: 1.85 to 6.93, P < 0.001) and severe IBD (OR: 3.31; CI: 2.54 to 4.32, P < 0.001). CMV-related IBD hospitalizations had increased length of stay by 9 days while incurring almost $65,000 higher hospitalization charges, P < 0.001. CONCLUSIONS The prevalence of CMV infection is increasing in pediatric IBD patients. CMV infections significantly corelated with increased risk of mortality and severity of IBD leading to prolonged hospital stay and higher hospitalization charges. Further prospective studies are needed to better understand the factors leading to this increasing CMV infection.
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Affiliation(s)
- Aravind Thavamani
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, UH Rainbow Babies and Children’s Hospital/Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | | | - Thomas J. Sferra
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, UH Rainbow Babies and Children’s Hospital/Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Senthilkumar Sankararaman
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, UH Rainbow Babies and Children’s Hospital/Case Western Reserve University School of Medicine, Cleveland, OH, USA
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15
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Goetgebuer RL, van der Woude CJ, Bakker L, van der Eijk AA, de Ridder L, de Vries AC. The diagnosis and management of CMV colitis in IBD patients shows high practice variation: a national survey among gastroenterologists. Scand J Gastroenterol 2022; 57:1321-1326. [PMID: 35771203 DOI: 10.1080/00365521.2022.2088244] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Clinical guidelines on cytomegalovirus (CMV) colitis in inflammatory bowel disease (IBD) are hampered by the low quality of evidence. In this study, we aim to explore the attitude and management of CMV colitis in IBD among gastroenterologists. METHODS A web-based survey was distributed to adult and pediatric gastroenterologists and trainees in academic and general hospitals in the Netherlands. The survey comprised data collection on respondents' demographics, attitudes towards the importance of CMV infection in IBD on a visual analogue scale (from 0 to 100), and diagnostic and therapeutic strategies. RESULTS A total of 73/131 invited respondents from 32 hospitals completed the survey (response rate of 56%). The importance of CMV infection was scored at a median 74/100. Respondents indicated CMV testing as appropriate in the clinical setting of steroid-refractory colitis (69% of respondents), hospitalized patients with active colitis (64%), immunomodulator or biological refractory colitis (55%) and active colitis irrespective of medication use (14%). CMV diagnostics include histology of colonic biopsies (88% of respondents), tissue CMV PCR (43%), serum CMV PCR (60%), CMV serology (25%) and fecal CMV PCR (4%). 82% of respondents start antiviral therapy after a positive CMV test on colonic biopsies (histology or PCR). CONCLUSIONS Most Dutch gastroenterologists acknowledge the importance of CMV colitis in IBD. Strategies vary greatly with regard to the indication for testing and diagnostic method, as well as indication for the start of antiviral therapy. These findings underline the need for pragmatic clinical studies on different management strategies, in order to reduce practice variation and improve the quality of care. Summary of the established knowledge on this subject:The clinical significance of CMV-associated colitis in IBD remains a matter of debateRecommendations regarding CMV colitis in current international guidelines are based on low to moderate evidence levels and different diagnostic strategies are proposed What are the significant and/or new findings of this study?We show that there is a high practice variation of diagnosis and management of CMV colitis in IBD amongst adult and pediatric gastroenterologistsThis study underlined the need for pragmatic studies and guidelines on different management strategies including cut-off values to start therapy.
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Affiliation(s)
- R L Goetgebuer
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - C J van der Woude
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - L Bakker
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - A A van der Eijk
- Department of Viroscience, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - L de Ridder
- Department of Pediatric Gastroenterology, Erasmus MC, Sophia Children's Hospital, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - A C de Vries
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
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Lee J. [Cytomegalovirus Infection in Patients with Inflammatory Bowel Disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2022; 80:60-65. [PMID: 36004632 DOI: 10.4166/kjg.2022.094] [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: 07/11/2022] [Revised: 07/25/2022] [Accepted: 07/25/2022] [Indexed: 06/15/2023]
Abstract
A diagnostic evaluation for cytomegalovirus (CMV) infection is required in patients with inflammatory bowel disease (IBD) who do not respond to steroid or immunomodulatory treatment. However, there is no consensus on an accurate diagnostic method for CMV infection in patients with IBD, and it is difficult to clearly distinguish the exacerbation of ulcerative colitis from CMV colitis. According to several recent studies, the most accurate test method for CMV colitis is quantitative tissue DNA-quantitative PCR, which is recommended as the first-line diagnostic technique along with an immunohistochemistry stain. The benefit of antiviral therapy for CMV infection in patients with IBD is also controversial. Although the definition of viral load is unclear, antiviral therapy can lower the rate of colectomy in CMV infections with a high viral load in patients with IBD. This review presents the latest findings about CMV infections in IBD, based on recently reported studies.
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Affiliation(s)
- Jun Lee
- Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea
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17
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Jena A, Mishra S, Singh AK, Sekar A, Sharma V. Cytomegalovirus in ulcerative colitis: an evidence-based approach to diagnosis and treatment. Expert Rev Gastroenterol Hepatol 2022; 16:109-120. [PMID: 35057693 DOI: 10.1080/17474124.2022.2032662] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 01/19/2022] [Indexed: 12/21/2022]
Abstract
INTRODUCTION The detection of cytomegalovirus (CMV) in the setting of inflammatory bowel disease often creates confusion whether CMV is a 'bystander' or 'disease.' AREAS COVERED This review discusses the clinical conundrum of CMV in ulcerative colitis, approach to discriminate infection from disease, and therapeutic considerations (immunosuppressive and anti-CMV treatment). CMV disease should be considered in corticosteroid refractory- dependent and thiopurine refractory disease. Endoscopy may reveal deep punched out ulcers, irregular ulcers, or cobble-stoning. The diagnosis rests on the presence and abundance of viral inclusion bodies on hematoxylin and eosin stain, positive immunohistochemistry, and/or positive tissue polymerase chain reaction. CMV disease is associated with worse outcomes including increased colectomy rates. EXPERT OPINION The timing and duration of antiviral drugs in CMV disease is debatable but depends on the load of CMV in tissue. In high-grade infection, CMV needs to be treated while increasing immunosuppression may work in the setting of low-grade infection. Ganciclovir is the drug of choice for treatment of CMV disease. Tumor necrosis factor inhibitors may be useful for treating underlying disease activity in the setting of CMV. Other emerging therapies include fecal microbiota transplantation. Randomized studies are necessary to define the best timing and duration of anti-CMV therapy.
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Affiliation(s)
- Anuraag Jena
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Shubhra Mishra
- Department of Gastroenterology, AIG Hospitals, Hyderabad, India
| | - Anupam Kumar Singh
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Aravind Sekar
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vishal Sharma
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Ghazi HF, Alubaidi GT, Fahad HM. SERO-PREVALENCE OF EPSTEIN-BARR VIRUS IN IRAQI INFLAMMATORY BOWEL DISEASE. WIADOMOSCI LEKARSKIE (WARSAW, POLAND : 1960) 2022; 75:1979-1984. [PMID: 36129082 DOI: 10.36740/wlek202208207] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
OBJECTIVE The aim: Determine the frequency of anti-viral capsid antigen IgM, IgG and IgA in inflammatory bowel disease. PATIENTS AND METHODS Materials and methods: Case controlled study conducted during involved 60 Crohn's disease, 60 ulcerative colitis and 60 subjects as a control group with negative gastroin¬testinal symptoms. Diagnosis and disease classification were established according to Montreal disease classification of inflammatory bowel diseases. Measurement of serum anti-VCA IgM, IgG and IgA was done, using ELISA method. RESULTS Results: The current results showed a higher frequency of EBV seropositivity among both Crohn's disease and ulcerative colitis 96.67% in comparison with controls 78.33. None statistical significance observed according to sex of patients. IgM were significantly associated with younger than 16 years 33.33%. IgA anti-VCA were significantly frequent within 17-40 years old comprising 100%. Patients with colonic and ileocolonic site of lesions were significantly have frequent anti-VCA IgA 96.43% and 96%. In ulcerative colitis IgM subtype of anti-VCA 35.71% frequent in extensive colitis. Anti-VCA IgG were statistically significant with moderate and severe ulcerative colitis cases 100%. Also, anti-VCA IgA associated with severity of ulcerative colitis 100% of mild cases, 96.43% of moderate cases and 100% of severe cases. CONCLUSION Conclusion: EBV seropositivity were detected among IBD cases, however viral infection might be associated with distinct and severe cases that requires anti-viral therapy.
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Affiliation(s)
- Haider F Ghazi
- DEPARTMENT OF MICROBIOLOGY, COLLEGE OF MEDICINE, AL-NAHRAIN UNIVERSITY, BAGHDAD, IRAQ
| | - Ghassaq T Alubaidi
- MEDICAL RESEARCH UNIT, COLLEGE OF MEDICINE, AL-NAHRAIN UNIVERSITY, BAGHDAD, IRAQ
| | - Hayfaa M Fahad
- DEPARTMENT OF MICROBIOLOGY, COLLEGE OF MEDICINE, AL-IRAQI UNIVERSITY, BAGHDAD, IRAQ
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Histologic features of colonic infections. DER PATHOLOGE 2021; 43:16-30. [PMID: 34767063 PMCID: PMC8588779 DOI: 10.1007/s00292-021-01015-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 09/23/2021] [Indexed: 11/29/2022]
Abstract
Background The histopathologic diagnosis of infectious colitis remains relevant despite recent advances in microbiologic techniques. Objective This article aims to describe the histologic features of selected infectious diseases of the colon. Materials and methods Existing reports on histopathologic and clinical aspects of colonic infectious agents were reviewed. Results While histology alone may not be as sensitive as current microbiologic methods, tissue identification of infectious agents still plays an important role in patient care. Infectious colitis can have a variety of clinical manifestations, ranging from strongyloidiasis, which can cause a smoldering, subclinical infection for decades, to syphilis, which can clinically mimic cancer or inflammatory bowel disease. Therefore, the histopathologic identification of infection as the cause of a patient’s colitis has a considerable impact on treatment decisions. Morphologic overlap can occur between infection and other diseases, however. Moreover, some infections can elicit various tissue responses beyond acute colitis. Immunosuppressed patients may not mount an inflammatory response to pathogens such as cytomegalovirus or adenovirus. Sexually transmitted proctocolitis can cause plasma-cell-rich inflammation. Gastrointestinal histoplasmosis is more likely to cause diffuse histiocyte infiltration rather than the expected granuloma formation. In some cases, ancillary tests are useful, but equivocal results can cause diagnostic dilemmas. Conclusion Given the range with which colonic infectious disorders can manifest, pathologists should be aware of the typical features of infectious colitis, as well as findings beyond the classic morphologies.
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Temtem T, Whitworth J, Zhang J, Bagga B. Cytomegalovirus in pediatric inflammatory bowel disease patients with acute severe colitis. Clin Res Hepatol Gastroenterol 2021; 45:101625. [PMID: 33662784 DOI: 10.1016/j.clinre.2021.101625] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Revised: 12/28/2020] [Accepted: 01/03/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND The prevalence and significance of cytomegalovirus (CMV) colitis in pediatric acute severe colitis is unknown. The aim of this study was to determine the prevalence of CMV in colonic mucosa of children with acute severe refractory colitis and compare the clinical characteristics and outcomes of CMV positive and negative patients. METHODS In a case-control study, colonic biopsy specimens from children with severe refractory colitis were tested for CMV, and matched with non-refractory IBD controls. We characterized CMV positive patients by assessing laboratory values, concurrent medications, and need for surgery as compared with CMV negative refractory colitis patients. RESULTS Colonic biopsies from 96 patients were evaluated for CMV; 48 with severe refractory colitis, and 48 non-refractory controls. There was an increased prevalence of CMV in severe refractory colitis [7/48 (14.6%), P < 0.0001]; all were previously CMV negative. Viral DNA burden on immunohistochemistry was not predictive of response to antiviral therapy or need for surgery at 12 months. Lymphopenia was seen in all CMV positive patients, but this did not demonstrate statistical significance (P = 0.09). We did not see an association between azathioprine or infliximab use and the need for surgery at 12 months. CONCLUSIONS There is an increased prevalence of CMV in colonic biopsies of pediatric patients with severe refractory colitis. Viral burden does not predict clinical outcomes or subsequent need for colectomy.
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Affiliation(s)
- Tsega Temtem
- Le Bonheur Children's Hospital, USA; Department of Pediatrics, Division of Gastroenterology, University of Tennessee Health Sciences Center, USA; University of Louisville, School of Medicine, USA.
| | - John Whitworth
- Le Bonheur Children's Hospital, USA; Department of Pediatrics, Division of Gastroenterology, University of Tennessee Health Sciences Center, USA.
| | - Jie Zhang
- Le Bonheur Children's Hospital, USA; Department of Pathology, University of Tennessee Health Sciences Center. Memphis, TN, USA.
| | - Bindiya Bagga
- Le Bonheur Children's Hospital, USA; Department of Pediatrics, Division of Infectious Diseases, USA.
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21
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Coccolini F, Improta M, Sartelli M, Rasa K, Sawyer R, Coimbra R, Chiarugi M, Litvin A, Hardcastle T, Forfori F, Vincent JL, Hecker A, Ten Broek R, Bonavina L, Chirica M, Boggi U, Pikoulis E, Di Saverio S, Montravers P, Augustin G, Tartaglia D, Cicuttin E, Cremonini C, Viaggi B, De Simone B, Malbrain M, Shelat VG, Fugazzola P, Ansaloni L, Isik A, Rubio I, Kamal I, Corradi F, Tarasconi A, Gitto S, Podda M, Pikoulis A, Leppaniemi A, Ceresoli M, Romeo O, Moore EE, Demetrashvili Z, Biffl WL, Wani I, Tolonen M, Duane T, Dhingra S, DeAngelis N, Tan E, Abu-Zidan F, Ordonez C, Cui Y, Labricciosa F, Perrone G, Di Marzo F, Peitzman A, Sakakushev B, Sugrue M, Boermeester M, Nunez RM, Gomes CA, Bala M, Kluger Y, Catena F. Acute abdomen in the immunocompromised patient: WSES, SIS-E, WSIS, AAST, and GAIS guidelines. World J Emerg Surg 2021; 16:40. [PMID: 34372902 PMCID: PMC8352154 DOI: 10.1186/s13017-021-00380-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Accepted: 06/18/2021] [Indexed: 02/08/2023] Open
Abstract
Immunocompromised patients are a heterogeneous and diffuse category frequently presenting to the emergency department with acute surgical diseases. Diagnosis and treatment in immunocompromised patients are often complex and must be multidisciplinary. Misdiagnosis of an acute surgical disease may be followed by increased morbidity and mortality. Delayed diagnosis and treatment of surgical disease occur; these patients may seek medical assistance late because their symptoms are often ambiguous. Also, they develop unique surgical problems that do not affect the general population. Management of this population must be multidisciplinary.This paper presents the World Society of Emergency Surgery (WSES), Surgical Infection Society Europe (SIS-E), World Surgical Infection Society (WSIS), American Association for the Surgery of Trauma (AAST), and Global Alliance for Infection in Surgery (GAIS) joined guidelines about the management of acute abdomen in immunocompromised patients.
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Affiliation(s)
- Federico Coccolini
- grid.144189.10000 0004 1756 8209General, Emergency and Trauma Surgery Department, Pisa University Hospital, Via Paradisa, 2, 56124 Pisa, Italy
| | - Mario Improta
- grid.8982.b0000 0004 1762 5736Emergency Department, Pavia University Hospital, Pavia, Italy
| | | | - Kemal Rasa
- Department of Surgery, Anadolu Medical Center, Kocaali, Turkey
| | - Robert Sawyer
- grid.268187.20000 0001 0672 1122General Surgery Department, Western Michigan University, Kalamazoo, MI USA
| | - Raul Coimbra
- grid.488519.90000 0004 5946 0028Department of General Surgery, Riverside University Health System Medical Center, Moreno Valley, CA USA
| | - Massimo Chiarugi
- grid.144189.10000 0004 1756 8209General, Emergency and Trauma Surgery Department, Pisa University Hospital, Via Paradisa, 2, 56124 Pisa, Italy
| | - Andrey Litvin
- grid.410686.d0000 0001 1018 9204Department of Surgical Disciplines, Immanuel Kant Baltic Federal University, Kaliningrad, Russia
| | - Timothy Hardcastle
- Emergency and Trauma Surgery, Inkosi Albert Luthuli Central Hospital, Mayville, South Africa
| | - Francesco Forfori
- grid.144189.10000 0004 1756 8209Intensive Care Unit, Pisa University Hospital, Pisa, Italy
| | - Jean-Louis Vincent
- grid.4989.c0000 0001 2348 0746Departement of Intensive Care, Erasme Univ Hospital, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Andreas Hecker
- grid.411067.50000 0000 8584 9230Departementof General and Thoracic Surgery, University Hospital of Giessen, Giessen, Germany
| | - Richard Ten Broek
- grid.10417.330000 0004 0444 9382General Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Luigi Bonavina
- grid.416351.40000 0004 1789 6237General Surgery, San Donato Hospital, Milano, Italy
| | - Mircea Chirica
- grid.450307.5General Surgery, CHUGA-CHU Grenoble Alpes UGA-Université Grenoble Alpes, Grenoble, France
| | - Ugo Boggi
- grid.144189.10000 0004 1756 8209General Surgery, Pisa University Hospital, Pisa, Italy
| | - Emmanuil Pikoulis
- grid.5216.00000 0001 2155 08003rd Department of Surgery, Attiko Hospital, National & Kapodistrian University of Athens, Athens, Greece
| | - Salomone Di Saverio
- grid.18887.3e0000000417581884General Surgery, Varese University Hospital, Varese, Italy
| | - Philippe Montravers
- grid.411119.d0000 0000 8588 831XDépartement d’Anesthésie-Réanimation, CHU Bichat Claude Bernard, Paris, France
| | - Goran Augustin
- grid.4808.40000 0001 0657 4636Department of Surgery, Zagreb University Hospital Centre and School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Dario Tartaglia
- grid.144189.10000 0004 1756 8209General, Emergency and Trauma Surgery Department, Pisa University Hospital, Via Paradisa, 2, 56124 Pisa, Italy
| | - Enrico Cicuttin
- grid.144189.10000 0004 1756 8209General, Emergency and Trauma Surgery Department, Pisa University Hospital, Via Paradisa, 2, 56124 Pisa, Italy
| | - Camilla Cremonini
- grid.144189.10000 0004 1756 8209General, Emergency and Trauma Surgery Department, Pisa University Hospital, Via Paradisa, 2, 56124 Pisa, Italy
| | - Bruno Viaggi
- grid.24704.350000 0004 1759 9494ICU Department, Careggi University Hospital, Firenze, Italy
| | - Belinda De Simone
- grid.418056.e0000 0004 1765 2558Department of Digestive, Metabolic and Emergency Minimally Invasive Surgery, Centre Hospitalier Intercommunal de Poissy/Saint Germain en Laye, Saint Germain en Laye, France
| | - Manu Malbrain
- grid.8767.e0000 0001 2290 8069Faculty of Engineering, Department of Electronics and Informatics, Vrije Universiteit Brussel, Brussels, Belgium
| | - Vishal G. Shelat
- General and Emergency Surgery, Tan Tock Seng Hospital, Kuala Lumpur, Malaysia
| | - Paola Fugazzola
- grid.8982.b0000 0004 1762 5736General and Emergency Surgery, Pavia University Hospital, Pavia, Italy
| | - Luca Ansaloni
- grid.8982.b0000 0004 1762 5736General and Emergency Surgery, Pavia University Hospital, Pavia, Italy
| | - Arda Isik
- grid.411776.20000 0004 0454 921XGeneral Surgery, School of Medicine, Istanbul Medeniyet University, Istanbul, Turkey
| | - Ines Rubio
- grid.81821.320000 0000 8970 9163Department of General Surgery, La Paz University Hospital, Madrid, Spain
| | - Itani Kamal
- grid.38142.3c000000041936754XGeneral Surgery, VA Boston Health Care System, Boston University, Harvard Medical School, Boston, MA USA
| | - Francesco Corradi
- grid.144189.10000 0004 1756 8209Intensive Care Unit, Pisa University Hospital, Pisa, Italy
| | - Antonio Tarasconi
- grid.411482.aGeneral Surgery, Parma University Hospital, Parma, Italy
| | - Stefano Gitto
- grid.8404.80000 0004 1757 2304Gastroenterology and Transplant Unit, Firenze University Hospital, Firenze, Italy
| | - Mauro Podda
- grid.7763.50000 0004 1755 3242General and Emergency Surgery, Cagliari University Hospital, Cagliari, Italy
| | - Anastasia Pikoulis
- grid.5216.00000 0001 2155 0800Medical Department, National & Kapodistrian University of Athens, Athens, Greece
| | - Ari Leppaniemi
- grid.15485.3d0000 0000 9950 5666Abdominal Center, Helsinki University and Helsinki University Hospital, Helsinki, Finland
| | - Marco Ceresoli
- grid.18887.3e0000000417581884General Surgery, Monza University Hospital, Monza, Italy
| | - Oreste Romeo
- grid.268187.20000 0001 0672 1122Department of Surgery, Western Michigan University School of Medicine, Kalamazoo, MI USA
| | - Ernest E. Moore
- grid.239638.50000 0001 0369 638XTrauma Surgery, Denver Health, Denver, CL USA
| | - Zaza Demetrashvili
- grid.412274.60000 0004 0428 8304General Surgery, Tbilisi State Medical University, Tbilisi, Georgia
| | - Walter L. Biffl
- grid.415402.60000 0004 0449 3295Emergency and Trauma Surgery, Scripps Memorial Hospital La Jolla, La Jolla, CA USA
| | - Imitiaz Wani
- General Surgery, Government Gousia Hospital, Srinagar, Kashmir India
| | - Matti Tolonen
- grid.15485.3d0000 0000 9950 5666Abdominal Center, Helsinki University and Helsinki University Hospital, Helsinki, Finland
| | | | - Sameer Dhingra
- National Institute of Pharmaceutical Education and Research, Hajipur (NIPER-H), Vaishali, Bihar India
| | - Nicola DeAngelis
- grid.50550.350000 0001 2175 4109General Surgery Department, Henry Mondor University Hospital, Paris, France
| | - Edward Tan
- grid.10417.330000 0004 0444 9382Emergency Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Fikri Abu-Zidan
- General Surgery, UAE University Hospital, Sharjah, United Arab Emirates
| | - Carlos Ordonez
- grid.8271.c0000 0001 2295 7397Division of Trauma and Acute Care Surgery, Department of Surgery, Fundación Valle del Lili, Universidad del Valle, Cali, Colombia
| | - Yunfeng Cui
- grid.265021.20000 0000 9792 1228Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, Tianjin, China
| | | | - Gennaro Perrone
- grid.411482.aGeneral Surgery, Parma University Hospital, Parma, Italy
| | | | - Andrew Peitzman
- grid.21925.3d0000 0004 1936 9000General Surgery, University of Pittsburgh School of Medicine, Pittsburgh, USA
| | - Boris Sakakushev
- First Clinic of General Surgery, University Hospital St George Plovdiv, Plovdiv, Bulgaria
| | - Michael Sugrue
- General Surgery, Letterkenny Hospital, Letterkenny, Ireland
| | - Marja Boermeester
- grid.5650.60000000404654431Department of Surgery, Academic Medical Center, Amsterdam, Netherlands
| | | | - Carlos Augusto Gomes
- Department of Surgery, Faculdade de Ciências Médicas e da Saúde de Juiz de Fora, Hospital Universitário Terezinha de Jesus, Juiz de Fora, Brazil
| | - Miklosh Bala
- grid.17788.310000 0001 2221 2926General Surgery, Hadassah Hospital, Jerusalem, Israel
| | - Yoram Kluger
- General Sugery, Ramabam Medical Centre, Tel Aviv, Israel
| | - Fausto Catena
- grid.411482.aGeneral Surgery, Parma University Hospital, Parma, Italy
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22
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Tanaka M, Nakanishi M, Miyazaki H, Morita R, Eguchi H, Takeda Y, Katayama M, Tanaka M, Bamba M, Shigematsu T. Granulocyte and Monocyte Adsorptive Apheresis for Ulcerative Colitis in a Patient with Low Bone Mineral Density Due to Fanconi-Bickel Syndrome. Intern Med 2021; 60:2413-2417. [PMID: 33612684 PMCID: PMC8381163 DOI: 10.2169/internalmedicine.6707-20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Systemic steroid is required for the exacerbation of ulcerative colitis (UC), although its administration should be avoided in patients with a low bone mineral density (BMD) exacerbated by side effects of steroids. We herein report the successful induction of remission in an UC case with a low BMD due to Fanconi-Bickel syndrome-or glycogen storage disease type XI-using granulocyte and monocyte adsorptive apheresis (GMA). For a 43-year-old woman with a BMD of 50% the young adult mean, GMA was performed 2 times a week for a total of 10 times. GMA might be a steroid-free treatment option for UC patients with a low BMD.
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Affiliation(s)
- Makoto Tanaka
- Department of Gastroenterology and Hepatology, Saiseikai Shigaken Hospital, Imperial Gift Foundation Inc., Japan
| | - Mayuko Nakanishi
- Department of Gastroenterology and Hepatology, Saiseikai Shigaken Hospital, Imperial Gift Foundation Inc., Japan
| | - Hajime Miyazaki
- Department of Gastroenterology and Hepatology, Saiseikai Shigaken Hospital, Imperial Gift Foundation Inc., Japan
| | - Ryuichi Morita
- Department of Gastroenterology and Hepatology, Saiseikai Shigaken Hospital, Imperial Gift Foundation Inc., Japan
| | - Hiroki Eguchi
- Department of Gastroenterology and Hepatology, Saiseikai Shigaken Hospital, Imperial Gift Foundation Inc., Japan
| | - Yoshiya Takeda
- Department of Gastroenterology and Hepatology, Saiseikai Shigaken Hospital, Imperial Gift Foundation Inc., Japan
| | - Masanobu Katayama
- Department of Gastroenterology and Hepatology, Saiseikai Shigaken Hospital, Imperial Gift Foundation Inc., Japan
| | - Motoo Tanaka
- Department of Gastroenterology and Hepatology, Saiseikai Shigaken Hospital, Imperial Gift Foundation Inc., Japan
| | - Masamichi Bamba
- Department of Diagnostic Pathology, Saiseikai Shigaken Hospital, Imperial Gift Foundation Inc., Japan
| | - Tadashi Shigematsu
- Department of Gastroenterology and Hepatology, Saiseikai Shigaken Hospital, Imperial Gift Foundation Inc., Japan
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23
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Kucharzik T, Ellul P, Greuter T, Rahier JF, Verstockt B, Abreu C, Albuquerque A, Allocca M, Esteve M, Farraye FA, Gordon H, Karmiris K, Kopylov U, Kirchgesner J, MacMahon E, Magro F, Maaser C, de Ridder L, Taxonera C, Toruner M, Tremblay L, Scharl M, Viget N, Zabana Y, Vavricka S. ECCO Guidelines on the Prevention, Diagnosis, and Management of Infections in Inflammatory Bowel Disease. J Crohns Colitis 2021; 15:879-913. [PMID: 33730753 DOI: 10.1093/ecco-jcc/jjab052] [Citation(s) in RCA: 248] [Impact Index Per Article: 62.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- T Kucharzik
- Department of Gastroenterology, Klinikum Lüneburg, University of Hamburg, Lüneburg, Germany
| | - P Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
| | - T Greuter
- University Hospital Zürich, Department of Gastroenterology and Hepatology, Zürich, Switzerland, and Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois CHUV, University Hospital Lausanne, Lausanne, Switzerland
| | - J F Rahier
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Yvoir, Belgium
| | - B Verstockt
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium, and Department of Chronic Diseases, Metabolism and Ageing, TARGID-IBD, KU Leuven, Leuven, Belgium
| | - C Abreu
- Infectious Diseases Service, Centro Hospitalar Universitário São João, Porto, Portugal
- Instituto de Inovação e Investigação em Saúde [I3s], Faculty of Medicine, Department of Medicine, University of Porto, Portugal
| | - A Albuquerque
- Gastroenterology Department, St James University Hospital, Leeds, UK
| | - M Allocca
- Humanitas Clinical and Research Center - IRCCS -, Rozzano [Mi], Italy
- Humanitas University, Department of Biomedical Sciences, Milan, Italy
| | - M Esteve
- Hospital Universitari Mútua Terrassa, Digestive Diseases Department, Terrassa, Catalonia, and Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas CIBERehd, Madrid, Spain
| | - F A Farraye
- Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - H Gordon
- Department of Gastroenterology, Barts Health NHS Trust, Royal London Hospital, London, UK
| | - K Karmiris
- Department of Gastroenterology, Venizeleio General Hospital, Heraklion, Greece
| | - U Kopylov
- Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel, and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - J Kirchgesner
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Saint-Antoine, Department of Gastroenterology, Paris, France
| | - E MacMahon
- Department of Infectious Diseases, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - F Magro
- Gastroenterology Department, Centro Hospitalar São João, Porto, Portugal
- Institute of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Portugal
| | - C Maaser
- Outpatient Department of Gastroenterology, Department of Geriatrics, Klinikum Lüneburg, University of Hamburg, Lüneburg, Germany
| | - L de Ridder
- Department of Paediatric Gastroenterology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - C Taxonera
- IBD Unit, Department of Gastroenterology, Hospital Clínico San Carlos and Instituto de Investigación del Hospital Clínico San Carlos [IdISSC], Madrid, Spain
| | - M Toruner
- Ankara University School of Medicine, Department of Gastroenterology, Ankara, Turkey
| | - L Tremblay
- Centre Hospitalier de l'Université de Montréal [CHUM] Pharmacy Department and Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada
| | - M Scharl
- University Hospital Zürich, Department of Gastroenterology and Hepatology, Zürich, Switzerland
| | - N Viget
- Department of Infectious Diseases, Tourcoing Hospital, Tourcoing, France
| | - Y Zabana
- Hospital Universitari Mútua Terrassa, Digestive Diseases Department, Terrassa, Catalonia, and Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas CIBERehd, Madrid, Spain
| | - S Vavricka
- University Hospital Zürich, Department of Gastroenterology and Hepatology, Zürich, Switzerland
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24
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Gugliesi F, Pasquero S, Griffante G, Scutera S, Albano C, Pacheco SFC, Riva G, Dell’Oste V, Biolatti M. Human Cytomegalovirus and Autoimmune Diseases: Where Are We? Viruses 2021; 13:260. [PMID: 33567734 PMCID: PMC7914970 DOI: 10.3390/v13020260] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 02/03/2021] [Accepted: 02/05/2021] [Indexed: 12/14/2022] Open
Abstract
Human cytomegalovirus (HCMV) is a ubiquitous double-stranded DNA virus belonging to the β-subgroup of the herpesvirus family. After the initial infection, the virus establishes latency in poorly differentiated myeloid precursors from where it can reactivate at later times to cause recurrences. In immunocompetent subjects, primary HCMV infection is usually asymptomatic, while in immunocompromised patients, HCMV infection can lead to severe, life-threatening diseases, whose clinical severity parallels the degree of immunosuppression. The existence of a strict interplay between HCMV and the immune system has led many to hypothesize that HCMV could also be involved in autoimmune diseases (ADs). Indeed, signs of active viral infection were later found in a variety of different ADs, such as rheumatological, neurological, enteric disorders, and metabolic diseases. In addition, HCMV infection has been frequently linked to increased production of autoantibodies, which play a driving role in AD progression, as observed in systemic lupus erythematosus (SLE) patients. Documented mechanisms of HCMV-associated autoimmunity include molecular mimicry, inflammation, and nonspecific B-cell activation. In this review, we summarize the available literature on the various ADs arising from or exacerbating upon HCMV infection, focusing on the potential role of HCMV-mediated immune activation at disease onset.
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Affiliation(s)
- Francesca Gugliesi
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Selina Pasquero
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Gloria Griffante
- Department of Translational Medicine, Molecular Virology Unit, University of Piemonte Orientale Medical School, 28100 Novara, Italy;
| | - Sara Scutera
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Camilla Albano
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Sergio Fernando Castillo Pacheco
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Giuseppe Riva
- Otorhinolaryngology Division, Department of Surgical Sciences, University of Turin, 10126 Turin, Italy;
| | - Valentina Dell’Oste
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Matteo Biolatti
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
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25
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Onpoaree N, Veeravigrom M, Sanpavat A, Suratannon N, Sintusek P. Unremitting diarrhoea in a girl diagnosed anti-N-methyl-D-aspartate-receptor encephalitis: A case report. World J Clin Cases 2020; 8:4866-4875. [PMID: 33195655 PMCID: PMC7642535 DOI: 10.12998/wjcc.v8.i20.4866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 07/27/2020] [Accepted: 09/25/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Asymptomatic cytomegalovirus (CMV) infection is common in children; in contrast, in children with a weakened immune system, invasive CMV can occur. This is the first case report of a severe manifestation of CMV esophago-enterocolitis in a girl diagnosed with anti-N-methyl-D-aspartate-receptor (anti-NMDAR) encephalitis who received only a moderate dose of corticosteroid therapy. CASE SUMMARY A 12-year-old-Thai girl presented with acute behavioural change and headache for 6 d. Electroencephalogram and positivity for NMDAR autoantibodies were compatible with anti-NMDAR encephalitis. Hence, she received pulse methylprednisolone 10 mg/kg per day for 4 d and continued with prednisolone 1.2 mg/kg per day. On day 42 of corticosteroid therapy, she developed unremitting vomiting and diarrhoea. Endoscopy showed multiple ulcers and erythaematous mucosa along the gastrointestinal tract. Tissue CMV viral load and viral-infected cells confirmed CMV esophago-enterocolitis. Therefore, the patient received ganciclovir 5 mg/kg per dose every 12 h for 3 wk and then 5 mg/kg per dose once daily for 3 wk. Unremitting diarrhoea slowly improved from stool output 1-4 L per day to 1-2 L per day after 3 wk of treatment. Pulse methylprednisolone 20 mg/kg for 5 d was initiated and continued with prednisolone 1 mg/kg per day. After this repeated pulse methylprednisolone treatment, surprisingly, diarrhoea subsided. Immunologic work-up was performed to rule out underlying immune deficiency with unremarkable results. CONCLUSION Unremitting diarrhoea from CMV esophago-enterocolitis subsided with antiviral and methylprednisolone therapy, implying the immune and NMDAR dysregulation in anti-NMDAR encephalitis.
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Affiliation(s)
- Norrapat Onpoaree
- Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Montida Veeravigrom
- Division of Neurology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Anapat Sanpavat
- Division of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Narissara Suratannon
- Division of Allergy, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Palittiya Sintusek
- Division of Gastroenterology and Pediatric Gastroenterology and Hepatology Research Unit, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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26
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Abstract
Despite multiple studies, the role of cytomegalovirus [CMV] infection in exacerbating the severity of inflammation in ulcerative colitis [UC], and its response to treatment, remain debatable. Additionally, the optimal diagnostic tests for CMV infection in the setting of UC relapse, and timing of antiviral treatment initiation, remain unclear. The challenge faced by gastroenterologists is to differentiate between an acute UC flare and true CMV colitis. It seems that the presence of CMV colitis, as defined by the presence of intranuclear or intracellular inclusion bodies on haematoxylin and eosin [H&E] staining and/or positive immunohistochemistry [IHC] assay on histology, is associated with more severe colitis. Patients with CMV infection and acute severe colitis are more resistant to treatment with corticosteroids than non-infected patients. This refractoriness to steroids is related to colonic tissue CMV viral load and number of inclusion bodies [high-grade CMV infection] which may have a pronounced effect on clinical outcomes and colectomy rates. Whereas many studies showed no effect for antiviral treatment on colectomy rates in CMV-infected UC patients, there was a significant difference in colectomy rates of patients with high-grade infection who received anti-viral therapy compared with those who did not receive treatment. It was therefore proposed that high-grade CMV disease indicates that the virus is acting as a pathogen, whereas in those with low-grade CMV disease, the severity of IBD itself is more likely to influence outcome. The different algorithms that have been put forward for the management of patients with UC and concomitant CMV infection are discussed.
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Affiliation(s)
- Fadi H Mourad
- Department of Internal Medicine, American University of Beirut Medical Centre, Beirut, Lebanon
- Gastroenterology and Liver Services, Concord Hospital, Sydney, NSW, Australia
| | - Jana G Hashash
- Department of Internal Medicine, American University of Beirut Medical Centre, Beirut, Lebanon
| | - Viraj C Kariyawasam
- Gastroenterology and Liver Services, Concord Hospital, Sydney, NSW, Australia
| | - Rupert W Leong
- Gastroenterology and Liver Services, Concord Hospital, Sydney, NSW, Australia
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27
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Jentzer A, Veyrard P, Roblin X, Saint-Sardos P, Rochereau N, Paul S, Bourlet T, Pozzetto B, Pillet S. Cytomegalovirus and Inflammatory Bowel Diseases (IBD) with a Special Focus on the Link with Ulcerative Colitis (UC). Microorganisms 2020; 8:1078. [PMID: 32698383 PMCID: PMC7409252 DOI: 10.3390/microorganisms8071078] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 07/10/2020] [Accepted: 07/12/2020] [Indexed: 12/16/2022] Open
Abstract
Cytomegalovirus (CMV) infects approximately 40% of adults in France and persists lifelong as a latent agent in different organs, including gut. A close relationship is observed between inflammation that favors viral expression and viral replication that exacerbates inflammation. In this context, CMV colitis may impact the prognosis of patients suffering from inflammatory bowel diseases (IBDs), and notably those with ulcerative colitis (UC). In UC, the mucosal inflammation and T helper cell (TH) 2 cytokines, together with immunomodulatory drugs used for controlling flare-ups, favor viral reactivation within the gut, which, in turn, increases mucosal inflammation, impairs corticoid and immunosuppressor efficacy (the probability of steroid resistance is multiplied by more than 20 in the case of CMV colitis), and enhances the risk for colectomy. This review emphasizes the virological tools that are recommended for exploring CMV colitis during inflammatory bowel diseases (IBD) and underlines the interest of using ganciclovir for treating flare-ups associated to CMV colitis in UC patients.
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Affiliation(s)
- Alexandre Jentzer
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Laboratory of infectious agents and hygiene, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
- Laboratory of Immunology, University Hospital Saint-Etienne, 42055 Saint-Etienne, 42055 Saint-Etienne, France
| | - Pauline Veyrard
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Department of Gastroenterology, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
| | - Xavier Roblin
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Department of Gastroenterology, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
| | - Pierre Saint-Sardos
- Laboratory of Bacteriology, University Hospital of Clermont-Ferrand, 63100 Clermont-Ferrand, France;
| | - Nicolas Rochereau
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
| | - Stéphane Paul
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Laboratory of Immunology, University Hospital Saint-Etienne, 42055 Saint-Etienne, 42055 Saint-Etienne, France
| | - Thomas Bourlet
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Laboratory of infectious agents and hygiene, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
| | - Bruno Pozzetto
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Laboratory of infectious agents and hygiene, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
| | - Sylvie Pillet
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Laboratory of infectious agents and hygiene, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
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Araki M, Shinzaki S, Yamada T, Arimitsu S, Komori M, Shibukawa N, Mukai A, Nakajima S, Kinoshita K, Kitamura S, Murayama Y, Ogawa H, Yasunaga Y, Oshita M, Fukui H, Masuda E, Tsujii M, Kawai S, Hiyama S, Inoue T, Tanimukai H, Iijima H, Takehara T. Psychologic stress and disease activity in patients with inflammatory bowel disease: A multicenter cross-sectional study. PLoS One 2020; 15:e0233365. [PMID: 32453762 PMCID: PMC7250441 DOI: 10.1371/journal.pone.0233365] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 05/04/2020] [Indexed: 12/13/2022] Open
Abstract
Background and aims Psychologic stress can affect the pathogenesis of inflammatory bowel disease (IBD), but the precise contribution of psychologic stress to IBD remains unclear. We investigated the association of psychologic stress with disease activity in patients with IBD, especially in terms of mental state and sleep condition. Methods This was a multi-center observational study comprising 20 institutions. Data were collected using survey forms for doctors and questionnaires for patients, and the association of psychologic stress with clinical parameters was investigated. Mental state was evaluated using the Center for Epidemiologic Studies Depression (CES-D) scale, and sleep condition was evaluated by querying patients about the severity of insomnia symptoms. Results A total of 1078 IBD patients were enrolled, including 303 patients with Crohn’s disease and 775 patients with ulcerative colitis. Seventy-five percent of IBD patients believed that psychologic stress triggered an exacerbation of their disease (PSTE group) and 25% did not (non-PSTE group). The CES-D scores were significantly higher for patients with clinically active disease than for those in remission in the PSTE group (median (interquartile range) = 7 (4–9.5) vs. 5 (3–7), p < .0001), but not in the non-PSTE group (5 (2–8) vs. 4 (3–7), p = 0.78). Female sex and disease exacerbation by factors other than psychologic stress were independent factors of psychologic stress-triggered disease exacerbation. Also, patients with insomnia had higher disease activity than those without insomnia, especially in the PSTE group. Conclusions A worsened mental state correlates with disease activity in IBD patients, especially those who believe that their disease is exacerbated by psychologic stress.
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Affiliation(s)
- Manabu Araki
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Shinichiro Shinzaki
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Takuya Yamada
- Department of Gastroenterology, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | | | - Masato Komori
- Department of Gastroenterology, Osaka Rosai Hospital, Sakai, Osaka, Japan
| | | | - Akira Mukai
- Department of Gastroenterology, Sumitomo Hospital, Osaka, Japan
| | - Sachiko Nakajima
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan
| | - Kazuo Kinoshita
- Department of Gastroenterology, Otemae Hospital, Osaka, Japan
| | - Shinji Kitamura
- Department of Gastroenterology, Sakai City Medical Center, Sakai, Osaka, Japan
| | - Yoko Murayama
- Department of Gastroenterology and Hepatology, Itami City Hospital, Itami, Hyogo, Japan
| | - Hiroyuki Ogawa
- Department of Gastroenterology, Nishinomiya Municipal Central Hospital, Nishinomiya, Hyogo, Japan
| | - Yuichi Yasunaga
- Department of Gastroenterology, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
| | - Masahide Oshita
- Department of Internal Medicine, Osaka Police Hospital, Osaka, Japan
| | - Hiroyuki Fukui
- Department of Gastroenterology, Yao Municipal Hospital, Yao, Osaka, Japan
| | - Eiji Masuda
- Department of Gastroenterology, National Hospital Organization Osaka-minami National Hospital, Kawachinagano, Osaka, Japan
| | - Masahiko Tsujii
- Department of Gastroenterology, Higashiosaka City Medical Center, Higashiosaka, Osaka, Japan
| | - Shoichiro Kawai
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Satoshi Hiyama
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Takahiro Inoue
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Hitoshi Tanimukai
- Faculty of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hideki Iijima
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- * E-mail:
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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Yokoyama Y, Yamakawa T, Hirano T, Kazama T, Hirayama D, Wagatsuma K, Nakase H. Current Diagnostic and Therapeutic Approaches to Cytomegalovirus Infections in Ulcerative Colitis Patients Based on Clinical and Basic Research Data. Int J Mol Sci 2020; 21:ijms21072438. [PMID: 32244555 PMCID: PMC7177554 DOI: 10.3390/ijms21072438] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 03/28/2020] [Accepted: 03/30/2020] [Indexed: 12/12/2022] Open
Abstract
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus (the human herpesvirus 5) and an opportunistic pathogen that primarily infects HIV-positive and other immuno-compromised patients. Retrospective studies in the field of inflammatory bowel disease (IBD) have suggested a relationship between a concomitant colonic HCMV infection and poor outcomes in patients with an ulcerative colitis (UC) due to the presence of HCMV in surgical specimens of patients with a toxic megacolon or a steroid-resistant UC. Therefore, gastroenterologists have focused on the contribution of HCMV infections in the exacerbation of UC. Numerous studies have addressed the benefits of treating colonic HCMV reactivation in UC using an antiviral treatment. However, its clinical relevance remains uncertain as only a few prospective studies have assessed the direct relationship between clinical outcomes and the viral load of HCMV in colonic tissues. HCMV reactivation can be triggered by inflammation according to fundamental research studies. Thus, optimal control of intestinal inflammation is essential for preventing an HCMV reactivation in the intestinal mucosa. Indeed, several reports have indicated the effectiveness of an anti-tumor necrosis factor-alpha (TNFα) treatment in patients with an active UC and concomitant HCMV infections. In this review, we describe the mechanism of HCMV reactivation in UC cases and discuss the current issues regarding diagnosis and treatment of HCMV infections in UC patients.
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Jung KH, Kim J, Lee HS, Choi J, Jang SJ, Jung J, Kim MJ, Chong YP, Lee SO, Choi SH, Kim YS, Woo JH, Park SH, Yang DH, Ye BD, Yang SK, Kim SH. Clinical Implications of the CMV-Specific T-Cell Response and Local or Systemic CMV Viral Replication in Patients With Moderate to Severe Ulcerative Colitis. Open Forum Infect Dis 2019; 6:ofz526. [PMID: 31893211 PMCID: PMC6934884 DOI: 10.1093/ofid/ofz526] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 12/10/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The precise role of cytomegalovirus (CMV) in ulcerative colitis (UC) remains disputed. We evaluated the association of CMV-specific host immune responses and systemic or local viral replication with responses to systemic steroids in patients with moderate to severe UC. METHODS Patients who were hospitalized for moderate to severe UC between April 2015 and June 2016 were enrolled. At baseline, all enrolled patients underwent CMV-specific enzyme-linked immunospot assays, quantitative polymerase chain reaction (qPCR) analysis of blood and colonic tissue for CMV viral load, histopathological testing for CMV in colonic tissue by hematoxylin and eosin staining, and immunohistochemical (IHC) analysis. Clinical responses to steroid therapy based on the Oxford index were assessed on day 3. RESULTS Of the 80 patients evaluated, 28 (35.0%) had poor responses to steroid therapy on day 3 of intensive treatment. The presence of inclusion bodies (32.1%) and high-grade (≥3) positivity on IHC (50.0%), as well as colonic (mean 1440.4 copies/mg) and blood (mean, 3692.6 copies/mL) CMV viral load, were higher in steroid-refractory UC patients than the control group (13.5%, 1.9%, mean 429.2 copies/mg, and mean 231.2 copies/mL, respectively; P = .046, .009, .017, and .002, respectively). However, CMV-specific T-cell responses were not associated with steroid-refractory UC. Multivariate analysis revealed that a higher Mayo score (odds ratio [OR], 2.00; P = .002) and higher blood CMV viral load via qPCR analysis (OR, 3.58; P = .044) were independent risk factors for steroid-refractory UC. CONCLUSIONS In patients with moderate to severe UC, higher Mayo score and blood CMV expression determined by qPCR are independently associated with steroid refractoriness. CLINICALTRIALSGOV REGISTRATION NUMBER NCT02439372.
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Affiliation(s)
- Kyung Hwa Jung
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jihun Kim
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ho-Su Lee
- Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jene Choi
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Se Jin Jang
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jiwon Jung
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Min Jae Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yong Pil Chong
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang-Oh Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang-Ho Choi
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yang Soo Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jun Hee Woo
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang Hyoung Park
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Dong-Hoon Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Byong Duk Ye
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sung-Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Correspondence: S.-H. Kim, MD, PhD, Department of Infectious Diseases, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea ()
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31
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Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK, Hayee B, Lomer MCE, Parkes GC, Selinger C, Barrett KJ, Davies RJ, Bennett C, Gittens S, Dunlop MG, Faiz O, Fraser A, Garrick V, Johnston PD, Parkes M, Sanderson J, Terry H, Gaya DR, Iqbal TH, Taylor SA, Smith M, Brookes M, Hansen R, Hawthorne AB. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut 2019; 68:s1-s106. [PMID: 31562236 PMCID: PMC6872448 DOI: 10.1136/gutjnl-2019-318484] [Citation(s) in RCA: 1517] [Impact Index Per Article: 252.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 06/10/2019] [Accepted: 06/10/2019] [Indexed: 02/06/2023]
Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
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Affiliation(s)
- Christopher Andrew Lamb
- Newcastle University, Newcastle upon Tyne, UK
- Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Nicholas A Kennedy
- Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
- University of Exeter, Exeter, UK
| | - Tim Raine
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Philip Anthony Hendy
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
- Imperial College London, London, UK
| | - Philip J Smith
- Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
| | - Jimmy K Limdi
- The Pennine Acute Hospitals NHS Trust, Manchester, UK
- University of Manchester, Manchester, UK
| | - Bu'Hussain Hayee
- King's College Hospital NHS Foundation Trust, London, UK
- King's College London, London, UK
| | - Miranda C E Lomer
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Gareth C Parkes
- Barts Health NHS Trust, London, UK
- Barts and the London School of Medicine and Dentistry, London, UK
| | - Christian Selinger
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
- University of Leeds, Leeds, UK
| | | | - R Justin Davies
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
- University of Cambridge, Cambridge, UK
| | - Cathy Bennett
- Systematic Research Ltd, Quorn, UK
- Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
| | | | - Malcolm G Dunlop
- University of Edinburgh, Edinburgh, UK
- Western General Hospital, Edinburgh, UK
| | - Omar Faiz
- Imperial College London, London, UK
- St Mark's Hospital, Harrow, UK
| | - Aileen Fraser
- University Hospitals Bristol NHS Foundation Trust, Bristol, UK
| | | | | | - Miles Parkes
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Jeremy Sanderson
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | | | - Daniel R Gaya
- Glasgow Royal Infirmary, Glasgow, UK
- University of Glasgow, Glasgow, UK
| | - Tariq H Iqbal
- Queen Elizabeth Hospital Birmingham NHSFoundation Trust, Birmingham, UK
- University of Birmingham, Birmingham, UK
| | - Stuart A Taylor
- University College London, London, UK
- University College London Hospitals NHS Foundation Trust, London, UK
| | - Melissa Smith
- Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
- Brighton and Sussex Medical School, Brighton, UK
| | - Matthew Brookes
- Royal Wolverhampton NHS Trust, Wolverhampton, UK
- University of Wolverhampton, Wolverhampton, UK
| | - Richard Hansen
- Royal Hospital for Children Glasgow, Glasgow, UK
- University of Glasgow, Glasgow, UK
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Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
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33
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Xuan L, Ren L, Han F, Gong L, Wan Z, Yang S, Liu H, Lv Y, Liu L. Cytomegalovirus Infection Exacerbates Experimental Colitis by Promoting IL-23 Production. Inflammation 2019; 43:326-335. [PMID: 31701354 DOI: 10.1007/s10753-019-01122-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Many studies have demonstrated an association between cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). Moreover, CMV infection is more common in patients with severe or steroid-refractory IBD. However, it is not clarified whether CMV worsens IBD or if it is merely a surrogate marker for IBD. Here, we used the dextran sodium sulfate (DSS)-induced colitis model to investigate if CMV infection exacerbates colitis. The mice were injected intraperitoneally with 10 MOI of murine CMV (MCMV) and thereafter, chronic colitis was induced by one cycle of DSS exposure. Anti-IL-23R mAb at 20 μg/mice and pyrrolidine dithiocarbamate (PDTC), an effective NF-κB inhibitor, at 50 mg/kg were administrated to the mice. The MCMV-infected mice had a shorter colon length and a higher histopathology score than the mock inoculum-treated mice, while anti-IL-23R mAb administration ameliorated the pathological changes. Expression of IL-23, phospho-NF-κB p65, and phospho-IκBα was upregulated in colon tissues of the MCMV-infected mice compared to mock inoculum-treated mice, while treatment with PDTC attenuated colonic IL-23 production. These data demonstrated that CMV infection could accelerate IBD development. This effect may be due to its activation on NF-κB signaling pathway and subsequently IL-23 production.
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Affiliation(s)
- Lingling Xuan
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Lulu Ren
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Feifei Han
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Lili Gong
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Zirui Wan
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Song Yang
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - He Liu
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Yali Lv
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China.
| | - Lihong Liu
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China.
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Yilmaz Karadag F, Arslan F, Caskurlu H, Cag Y, Vahaboglu H. Efficacy of antiviral treatment in cytomegalovirus detected ulcerative colitis: meta-analysis of available data. Scand J Gastroenterol 2019; 54:1346-1352. [PMID: 31718340 DOI: 10.1080/00365521.2019.1688860] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Aim: This meta-analysis aimed to pool available data regarding the efficacy of ganciclovir treatment among cytomegalovirus-detected ulcerative colitis patients.Methods: We screened PubMed, Ovid, Web of Science and Cochrane databases for relevant studies, and four investigators independently evaluated the studies for eligibility. The primary outcome was surgical resection or death from ulcerative colitis. The data were then pooled via DerSimonian-Laird estimator and Mantel-Haenszel (MH) method, two points added for continuity correction and random-effects model fitted in the Bayesian framework. We first constructed a Bugs model with Student t-distribution as prior for between-study heterogeneity. The model was fitted by Gibbs sampler (JAGS) to produce a marginal posterior distribution.Results: Our screening identified 15 eligible studies for final data synthesis and combined data from 191 ganciclovir-treated and 166 non-treated patients. Effect estimates from the fixed-effects meta-analysis model did not encourage ganciclovir treatment (OR, 1.43; 95% CIs [0-95, 2.16]), with a negligible unaccounted heterogeneity (I2 = 0%). The Bayesian random-effects model generated high-density credible intervals, suggesting a high probability, that future studies will also not encourage ganciclovir treatment (mu, 1.028; 95% credible intervals [0.054, 2.238]; 80% credible intervals [0.401, 1.703]) which indicates that future studies will favor non-treatment of ulcerative colitis with ganciclovir.Conclusions: Data produced in this study do not encourage ganciclovir treatment for UC patients. However, studies included in this analysis were observational, and thus, inherited severe selection bias. We suggest randomized controlled studies be conducted to make firm recommendations in this context.
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Affiliation(s)
- Fatma Yilmaz Karadag
- Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji, Istanbul Medeniyet Universitesi, Istanbul, Turkey
| | - Ferhat Arslan
- Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji, Istanbul Medeniyet Universitesi, Istanbul, Turkey
| | - Hulya Caskurlu
- Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji, Istanbul Medeniyet Universitesi, Istanbul, Turkey
| | - Yasemin Cag
- Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji, Istanbul Medeniyet Universitesi, Istanbul, Turkey
| | - Haluk Vahaboglu
- Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji, Istanbul Medeniyet Universitesi, Istanbul, Turkey
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Oh SJ, Lee CK, Kim YW, Jeong SJ, Park YM, Oh CH, Kim JW, Kim HJ. True cytomegalovirus colitis is a poor prognostic indicator in patients with ulcerative colitis flares: the 10-year experience of an academic referral inflammatory bowel disease center. Scand J Gastroenterol 2019; 54:976-983. [PMID: 31356759 DOI: 10.1080/00365521.2019.1646798] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Background and aims: The impact of cytomegalovirus (CMV) colitis on long-term outcomes of ulcerative colitis (UC) flares remains controversial. Methods: A total of 257 UC patients with moderate-to-severe flares were observed for a mean follow-up of 41.2 months. CMV colitis was defined as histopathologic confirmation of CMV inclusions obtained from macroscopic endoscopic lesions in patients with UC flares. An independent gastrointestinal pathologist prospectively reviewed all specimens. A poor outcome was defined as any of hospitalization, colectomy or death during the follow-up period. Results: The prevalence of CMV colitis was 14% (36/257) over the 10-year study period (2007-2016). When compared to the controls, patients with CMV colitis were characterized by older age, higher disease activity, endoscopic deep ulcerations and more frequent use of immunosuppressive drugs (all p < .05). In total, 57 outcome events (50 hospitalizations, seven colectomies) were observed among the study population (44.7% in patients with CMV colitis vs. 18.9% in controls). The cumulative probability of a poor outcome was significantly greater in the patients with CMV colitis than in the controls (log-rank test p < .001). In a multivariable analysis, CMV colitis remained as an independent predictor of a poor outcome (hazard ratio; 2.27; 95% confidence interval: 1.12-4.60). Despite a generally favorable response to antiviral therapy (79%), the risk of recurrent CMV colitis remained quite high (57%). Most of the recurrences developed within 8 months (75%). Conclusions: True CMV colitis is a poor prognostic indicator among patients with UC flares. An effective strategy for managing recurrent CMV colitis is urgently needed (KCT0003296).
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Affiliation(s)
- Shin Ju Oh
- Center for Crohn's and Colitis, Department of Gastroenterology, Kyung Hee University College of Medicine , Seoul , South Korea
| | - Chang Kyun Lee
- Center for Crohn's and Colitis, Department of Gastroenterology, Kyung Hee University College of Medicine , Seoul , South Korea
| | - Youn-Wha Kim
- Department of Pathology, Kyung Hee University College of Medicine , Seoul , South Korea
| | - Su Jin Jeong
- Department of Statistics Support, Medical Science Research Institute, Kyung Hee University Medical Center , Seoul , South Korea
| | - Yoo Min Park
- Center for Crohn's and Colitis, Department of Gastroenterology, Kyung Hee University College of Medicine , Seoul , South Korea
| | - Chi Hyuk Oh
- Center for Crohn's and Colitis, Department of Gastroenterology, Kyung Hee University College of Medicine , Seoul , South Korea
| | - Jung-Wook Kim
- Center for Crohn's and Colitis, Department of Gastroenterology, Kyung Hee University College of Medicine , Seoul , South Korea
| | - Hyo Jong Kim
- Center for Crohn's and Colitis, Department of Gastroenterology, Kyung Hee University College of Medicine , Seoul , South Korea
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Reply to Potential Pitfalls When Assessing the Impact of Cytomegalovirus in Inflammatory Bowel Disease. J Clin Gastroenterol 2019; 53:470. [PMID: 28697147 DOI: 10.1097/mcg.0000000000000848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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Potential Pitfalls When Assessing the Impact of Cytomegalovirus in Inflammatory Bowel Disease. J Clin Gastroenterol 2019; 53:394-395. [PMID: 28277375 DOI: 10.1097/mcg.0000000000000812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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Clos-Parals A, Rodríguez-Martínez P, Cañete F, Mañosa M, Ruiz-Cerulla A, José Paúles M, Llaó J, Gordillo J, Fumagalli C, Garcia-Planella E, Ojanguren I, Cabré E, Guardiola J, Domènech E. Prognostic Value of the Burden of Cytomegalovirus Colonic Reactivation Evaluated by Immunohistochemical Staining in Patients with Active Ulcerative Colitis. J Crohns Colitis 2019; 13:385-388. [PMID: 30346606 DOI: 10.1093/ecco-jcc/jjy173] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Colonic cytomegalovirus [CMV] reactivation has been involved in steroid refractoriness in patients with active ulcerative colitis [UC]. The benefits of antiviral therapy in this clinical setting are still under debate, but the burden of viral reactivation has been associated with a poorer outcome in some studies. Our aim was to assess whether the burden of CMV reactivation measured by the number of viral inclusions by immunohistochemistry [IHC-CMV] is associated with a risk of colectomy. METHODS Biopsy sets of UC patients with positive IHC-CMV were identified from the Pathology departments of three university hospitals. All biopsies were reviewed by expert pathologists, and the maximum number of IHC-CMV-positive cells in each biopsy set was re-assessed. Epidemiological and clinical features and clinical outcomes were recorded. RESULTS Forty-six positive IHC-CMV cases with UC were included. At the time of CMV reactivation, 70% were receiving corticosteroids, 33% azathioprine, and 24% anti-tumour necrosis factor [TNF] agents. Thirty-two patients [70%] were treated with antiviral therapy. The median number of IHC-CMV-positive cells was 2 cells/biopsy [IQR 1-4]. Fourteen patients [30%] underwent colectomy, and 4 of them [29%] showed persistence of CMV in the surgical specimen. In the multivariate analysis, colectomy was only associated with >2 positive cells/biopsy [p = 0.048] and younger age [p = 0.023]. CONCLUSIONS The burden of CMV colonic reactivation in patients with active UC, as measured by IHC, seems to be related to the risk of colectomy, and more data is needed to understand whether antiviral therapy guided by CMV burden will alter the clinical outcome.
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Affiliation(s)
- Ariadna Clos-Parals
- Department of Gastroenterology, Hospital Germans Trias i Pujol, Badalona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | | | - Fiorella Cañete
- Department of Gastroenterology, Hospital Germans Trias i Pujol, Badalona, Spain
| | - Míriam Mañosa
- Department of Gastroenterology, Hospital Germans Trias i Pujol, Badalona, Spain
- Centro de Investigaciones Biomédicas em Red de Enfermedades hepáticas y digestivas [CIBEREHD], Madrid, Spain
| | | | - Mª José Paúles
- Department of Pathology, Hospital Bellvitge [L'Hospitalet], Spain
| | - Jordina Llaó
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain
| | - Jordi Gordillo
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain
| | - Caterina Fumagalli
- Department of Pathology, Hospital Santa Creu i Sant Pau, Barcelona, Spain
| | | | - Isabel Ojanguren
- Department of Pathology, Hospital Germans Trias i Pujol, Badalona, Spain
| | - Eduard Cabré
- Department of Gastroenterology, Hospital Germans Trias i Pujol, Badalona, Spain
- Centro de Investigaciones Biomédicas em Red de Enfermedades hepáticas y digestivas [CIBEREHD], Madrid, Spain
| | - Jordi Guardiola
- Department of Gastroenterology, Hospital Bellvitge [L'Hospitalet], Spain
| | - Eugeni Domènech
- Department of Gastroenterology, Hospital Germans Trias i Pujol, Badalona, Spain
- Centro de Investigaciones Biomédicas em Red de Enfermedades hepáticas y digestivas [CIBEREHD], Madrid, Spain
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A Practical Review of Cytomegalovirus in Gastroenterology and Hepatology. Gastroenterol Res Pract 2019; 2019:6156581. [PMID: 30984257 PMCID: PMC6431500 DOI: 10.1155/2019/6156581] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 02/05/2019] [Indexed: 02/06/2023] Open
Abstract
Human cytomegalovirus (CMV) is a ubiquitous Herpesviridae virus with a wide spectrum of pathology in humans. Host immunity is a major determinant of the clinical manifestation of CMV and can vary widely in the gastroenterology and hepatology practice setting. Immunocompetent patients generally develop a benign, self-limited mononucleosis-like syndrome whereas gastrointestinal tissue-invasive disease is more frequently seen in immunocompromised and inflammatory bowel disease patients. Additionally, liver allograft dysfunction is a significant consequence of CMV infection in liver transplant patients. While polymerase chain reaction and immunohistochemistry techniques allow for the reliable and accurate detection of CMV in the human host, the diagnostic value of different serologic, endoscopic, and histologic tests depends on a variety of factors. Similarly, latent CMV, CMV infection, and CMV disease carry different significance depending on the patient population, and the decision to initiate antiviral therapy can be complex and patient-specific. This review will focus on the pathophysiology, diagnosis, and management of CMV in patient populations relevant to the practice of gastroenterology and hepatology-liver transplant recipients, inflammatory bowel disease patients, and otherwise immunocompetent patients.
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Abstract
PURPOSE OF REVIEW Cytomegalovirus (CMV) colitis is a relatively common end-organ infectious complication in immunocompromised hosts which negatively affects clinical outcomes. This paper presents the contemporary approaches to the diagnosis and management of CMV colitis and discusses some of the controversies of this condition, focusing on methods of diagnosis. RECENT FINDINGS While certain risk factors for CMV colitis are well recognized, the clinical as well as endoscopic features of this condition are nonspecific. Rapid diagnosis and management are usually needed, especially in critically ill patients, which necessitate invasive diagnostic procedures. Hematoxylin and eosin staining of colonic mucosal tissue may show the typical viral inclusions associated with CMV colitis that are highly specific for this condition. However, the staining has low sensitivity compared to immunohistochemistry, which is considered the gold standard for diagnosis of CMV colitis. Tissue polymerase chain reaction (PCR) is highly sensitive for diagnosis, but is controversial for many reasons, detailed in this paper. A high index of suspicion is needed, and once diagnosis is made, treatment should be highly considered to improve the outcome of these severely ill patients. Noninvasive diagnostic tests will be available in the future and will hopefully improve the diagnosis and care of patients with CMV colitis.
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Affiliation(s)
- Anat Yerushalmy-Feler
- Pediatric Gastroenterology Unit, Pediatrics Department, "Dana-Dwek" Children's Hospital, Tel Aviv Sourasky Medical Center, 6 Weizman Street, 6423906, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | | | - Shlomi Cohen
- Pediatric Gastroenterology Unit, Pediatrics Department, "Dana-Dwek" Children's Hospital, Tel Aviv Sourasky Medical Center, 6 Weizman Street, 6423906, Tel Aviv, Israel. .,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Kredel LI, Mundt P, van Riesen L, Jöhrens K, Hofmann J, Loddenkemper C, Siegmund B, Preiß JC. Accuracy of diagnostic tests and a new algorithm for diagnosing cytomegalovirus colitis in inflammatory bowel diseases: a diagnostic study. Int J Colorectal Dis 2019; 34:229-237. [PMID: 30276706 DOI: 10.1007/s00384-018-3170-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/25/2018] [Indexed: 02/04/2023]
Abstract
PURPOSE The optimal method for detecting CMV colitis in patients with inflammatory bowel disease (IBD) has not been established. We wanted to investigate which diagnostic test would be most accurate when defining CMV colitis rather by the further clinical course than by using another diagnostic modality. METHODS All consecutive patients with moderately or severely active IBD who had been tested for CMV by PCR, histology, or antigenemia assay at the two campuses CBF and CCM of the Charité - Universitätsmedizin Berlin between September 2006 and September 2009 were included in this retrospective study. During that time, in patients with a positive CMV test, immunosuppressive treatment of any kind was immediately reduced and antiviral treatment was started. This allowed identifying patients who responded to antiviral treatment and those who only responded to later escalation of immunosuppressive therapy. RESULTS One hundred and nine patients were identified, out of whom nine were considered to have clinically relevant CMV colitis. Sensitivity and specificity were 1 and 0.94 for CMV PCR and 0.5 and 1 for pp65 antigen immunofluorescence assay from peripheral blood, 0.67 and 0.98 for immunohistochemistry, and 0.17 and 0.98 for hematoxylin-eosin staining. When using absence of leukocytosis, splenomegaly, and steroid refractory disease as clinical parameters to test for CMV colitis, blood CMV PCR and immunohistochemistry were able to exclude CMV colitis in negative patients with a 75% likelihood of positive patients to have clinically relevant CMV colitis. CONCLUSIONS Blood-based CMV PCR together with simple clinical parameters can exclude clinically relevant CMV colitis at a high specificity.
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Affiliation(s)
- Lea I Kredel
- Medizinische Klinik mit Schwerpunkt Gastroenterologie, Infektiologie und Rheumatologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Pamela Mundt
- Medizinische Klinik mit Schwerpunkt Gastroenterologie, Infektiologie und Rheumatologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, 12203, Berlin, Germany
- Praxis Jessen + Kollegen, Akademische Lehrpraxis der Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Linda van Riesen
- Medizinische Klinik mit Schwerpunkt Gastroenterologie, Infektiologie und Rheumatologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, 12203, Berlin, Germany
- Klinik für Innere Medizin - Schwerpunkt Gastroenterologie, DRK Kliniken Westend, Berlin, Germany
| | - Korinna Jöhrens
- Institut für Pathologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Jörg Hofmann
- Institut für Virologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | | | - Britta Siegmund
- Medizinische Klinik mit Schwerpunkt Gastroenterologie, Infektiologie und Rheumatologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Jan C Preiß
- Medizinische Klinik mit Schwerpunkt Gastroenterologie, Infektiologie und Rheumatologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, 12203, Berlin, Germany.
- Klinik für Innere Medizin - Gastroenterologie, Diabetologie und Hepatologie, Vivantes Klinikum Neukölln, Berlin, Germany.
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Zhang L, Wu TT. Inflammatory Bowel Disease. SURGICAL PATHOLOGY OF NON-NEOPLASTIC GASTROINTESTINAL DISEASES 2019:373-424. [DOI: 10.1007/978-3-030-15573-5_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Mavropoulou E, Ternes K, Mechie NC, Bremer SCB, Kunsch S, Ellenrieder V, Neesse A, Amanzada A. Cytomegalovirus colitis in inflammatory bowel disease and after haematopoietic stem cell transplantation: diagnostic accuracy, predictors, risk factors and disease outcome. BMJ Open Gastroenterol 2019; 6:e000258. [PMID: 30899538 PMCID: PMC6398871 DOI: 10.1136/bmjgast-2018-000258] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Revised: 12/27/2018] [Accepted: 12/28/2018] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Concurrent cytomegalovirus (CMV) colitis in inflammatory bowel disease (IBD) and after haematopoietic stem cell transplantation (HSCT) is an important clinical entity associated with high rates of morbidity and mortality. METHODS A retrospective study of 47 patients with IBD and 61 HSCT patients was performed regarding the evaluation of diagnostic accuracy of applied methods, predictors, risk factors for CMV disease manifestation, the proportion of patients with antiviral treatment and disease outcome. RESULTS The sensitivity of quantitative PCR (qPCR) with a cut-off value of >250 copies/mg for CMV colitis in patients with IBD and HSCT patients was 79% and 92%, respectively. Predictors for CMV colitis in the IBD cohort were anaemia and the presence of endoscopic ulcers. Glucocorticoids, calcineurin inhibitors and >2 concurrent lines of treatment with immunosuppressive drugs could be identified as risk factors for CMV colitis in the IBD cohort with an OR of 7.1 (95% CI 1.7 to 29.9), 21.3 (95% CI 2.4 to 188.7) and 13.4 (95% CI 3.2 to 56.1), respectively. Predictors and risk factors for CMV gastroenteritis in the HSCT cohort was the presence of endoscopic ulcers (OR 18.6, 95% CI 3.3 to 103.7) and >2 concurrent lines of treatment with immunosuppressive drugs. Antiviral therapy was administered in 70% of patients with IBD and 77% of HSCT patients with CMV disease. 71% of antiviral-treated patients with IBD showed an improvement of their disease activity and 14% underwent colectomy. The mortality rate of HSCT patients was 21% irrespective of their CMV status. CONCLUSIONS In addition to the implementation of histological methods, qPCR may be performed in patients with suspected high-risk IBD and HSCT patients for CMV colitis. Independent validations of these results in further prospective studies are needed.
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Affiliation(s)
- Eirini Mavropoulou
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | - Kristin Ternes
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | - Nicolae-Catalin Mechie
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | | | - Steffen Kunsch
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | - Volker Ellenrieder
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | - Albrecht Neesse
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | - Ahmad Amanzada
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
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Philipose J, El Douaihy Y, Liliane DK. An Unusual Case of Bloody Diarrhea in a Young Man. Gastroenterology 2018; 155:1695-1696. [PMID: 30145360 DOI: 10.1053/j.gastro.2018.06.089] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 05/29/2018] [Accepted: 06/25/2018] [Indexed: 12/02/2022]
Affiliation(s)
- Jobin Philipose
- Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, New York
| | - Youssef El Douaihy
- Department of Gastroenterology, Staten Island University Hospital, Northwell Health, Staten Island, New York
| | - Deeb Khouri Liliane
- Department of Gastroenterology, Staten Island University Hospital, Northwell Health, Staten Island, New York
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Chao G, Li X, Ji Y, Zhu Y, Li N, Zhang N, Feng Z, Niu M. CTLA-4 regulates T follicular regulatory cell differentiation and participates in intestinal damage caused by spontaneous autoimmunity. Biochem Biophys Res Commun 2018; 505:865-871. [PMID: 30301533 DOI: 10.1016/j.bbrc.2018.09.182] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Accepted: 09/28/2018] [Indexed: 12/16/2022]
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Siegmund B. Cytomegalovirus infection associated with inflammatory bowel disease. Lancet Gastroenterol Hepatol 2018; 2:369-376. [PMID: 28397701 DOI: 10.1016/s2468-1253(16)30159-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Revised: 10/11/2016] [Accepted: 10/13/2016] [Indexed: 12/18/2022]
Abstract
Refractory colitis in patients with inflammatory bowel disease is a complicated clinical disorder that might, in some patients, even necessitate surgery. Hence the diagnosis of additional complications is of utmost importance. Colitis mediated by cytomegalovirus is one such complication. The high seroprevalence and latent nature of cytomegalovirus, with the possibility of viral replication without mediating disease, poses a real challenge for the diagnosis of cytomegalovirus-mediated colitis. The challenge in daily clinical practice is to distinguish cytomegalovirus replication from cytomegalovirus-mediated colitis in patients with inflammatory bowel disease who have refractory colitis. This Review discusses the scientific literature and provides a diagnostic and therapeutic algorithm for clinical practice.
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Affiliation(s)
- Britta Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie, Rheumatologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
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Johnson J, Affolter K, Boynton K, Chen X, Valentine J, Peterson K. CMV Disease in IBD: Comparison of Diagnostic Tests and Correlation with Disease Outcome. Inflamm Bowel Dis 2018; 24:1539-1546. [PMID: 29718356 DOI: 10.1093/ibd/izy045] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND Significance of cytomegalovirus (CMV) in inflammatory bowel disease (IBD) is unclear due to pathobiology, numerous CMV tests, and disparate treatment outcomes. METHODS Retrospective chart review was done on patients with positive qualitative CMV tissue polymerase chain reaction (PCR) from 2005-2013 at a tertiary referral hospital. Frequency of PCR+, hematoxylin and eosin staining(HE)+, histopathology and immunohistochemistry (IHC)+ was assessed. IHC was assessed on a sample of PCR- tissues. Surgery rates were correlated with CMV testing and treatment. RESULTS PCR was done on 310 samples from 180 patients. Thirty-seven samples were PCR+ (51.4% PCR+ only, 35.1% IHC/PCR+, 13.5% HE/IHC/PCR+). The H&E frequently failed to detect CMV identified on extensive IHC. Of 13 PCR- samples tested with IHC, 100% were negative. Twenty-five patients were CMV+ (40% PCR+, 40% IHC/PCR+, 20% HE/IHC/PCR+). Surgery rates increased with number of positive tests: 60% in IHC/PCR+ and 80% in HE/IHC/PCR+, compared to 26.8% in PCR- or PCR+ (P = 0.03, P = 0.02, respectively). There were 20/25 PCR+ patients who received CMV treatment. Surgery occurred in 80% of HE+ patients despite treatment and 100% of IHC+ patients without treatment. CONCLUSIONS Rates of CMV+ testing and surgical risk varied by test modality. PCR+ results were most frequent but alone did not detect clinically significant CMV. HE+ testing was least frequent and associated with highest surgical rate, despite treatment. CMV treatment may benefit IHC+ patients most, supporting immunostaining as optimal diagnostic test for clinically significant CMV in IBD. In PCR+ samples, HE frequently did not detect CMV identified on extensive IHC. In PCR- samples, data suggest IHC is likely negative. Consider using qualitative PCR to guide extensive immunostaining.
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Affiliation(s)
- Jessica Johnson
- Division of Gastroenterology and Hepatology, University of Utah, Salt Lake City, UT, USA
| | | | | | | | - John Valentine
- Division of Gastroenterology and Hepatology, University of Utah
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Zagórowicz E, Przybysz A, Szlak J, Magdziak A, Wieszczy P, Mróz A. Detection of cytomegalovirus by immunohistochemistry of colonic biopsies and quantitative blood polymerase chain reaction: evaluation of agreement in ulcerative colitis. Scand J Gastroenterol 2018. [PMID: 29513050 DOI: 10.1080/00365521.2018.1447596] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Cytomegalovirus (CMV) often reactivates in ulcerative colitis (UC). In diagnostics, along with immunohistochemistry (IHC) of colonic biopsies, blood CMV polymerase chain reaction (PCR) is gaining increasing application. We aimed to assess agreement between the density of infected colonic cells by IHC and the viral load in the blood by PCR. MATERIAL AND METHODS We retrospectively identified patients with active UC or indeterminate colitis in whom blood CMV PCR had been performed while biopsies had been taken simultaneously. The latter were re-evaluated and the numbers of IHC-positive cells per square millimetre counted. RESULTS The analyses extended to 234 sample pairs, among which there were 184 cases (78.6% of the total) in which IHC was equal to 0. The median among the remaining 50 non-zero values for IHC was 1.7 cells/mm2. PCR was equal to 0 in 192 cases (82.1%), while the median among the remaining 42 non-zero values was 4995.3 IU/ml. The Spearman correlation coefficient was 0.43 (p < .001). The area under the curve (AUC) values did not differ significantly between different IHC cut-offs. The highest AUC of 0.753 was obtained while predicting if IHC would be above the 3rd quartile (>5.6 cells/mm2), where PCR > 0 had a sensitivity of 0.615 and a specificity of 0.846. CONCLUSIONS In active CMV colitis, the specificity and negative predictive value of blood PCR are high, while the sensitivity grows with the intensity of colon infection. A highly positive result could justify the administration of antiviral treatment being brought forward in selected patients.
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Affiliation(s)
- Edyta Zagórowicz
- a Department of Oncological Gastroenterology , The Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology , Warsaw , Poland
- b Department of Gastroenterology, Hepatology and Clinical Oncology , Poland and Medical Centre for Postgraduate Education , Warsaw , Poland
| | - Agnieszka Przybysz
- a Department of Oncological Gastroenterology , The Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology , Warsaw , Poland
| | - Jakub Szlak
- a Department of Oncological Gastroenterology , The Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology , Warsaw , Poland
| | - Agnieszka Magdziak
- c Department of Microbiology , The Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology , Warsaw , Poland
| | - Paulina Wieszczy
- b Department of Gastroenterology, Hepatology and Clinical Oncology , Poland and Medical Centre for Postgraduate Education , Warsaw , Poland
- d Department of Cancer Prevention , The Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology , Warsaw , Poland
| | - Andrzej Mróz
- e Department of Pathology and Laboratory Medicine , The Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology , Warsaw , Poland
- f Department of Pathomorphology , Medical Centre for Postgraduate Education , Warsaw , Poland
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Antiviral Treatment for Colonic Cytomegalovirus Infection in Ulcerative Colitis Patients Significantly Improved Their Surgery Free Survival. J Clin Gastroenterol 2018; 52:e27-e31. [PMID: 27875354 DOI: 10.1097/mcg.0000000000000759] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND The frequency of cytomegalovirus (CMV) colitis in steroid-refractory inflammatory bowel disease has been reported to range from 15.8% to 34.0%. Infected patients are more likely to become hospitalized, have longer lengths of stay, and higher mortality rates. Current data are limited to small scale studies and showed conflicting result regarding the role of antiviral therapy. AIMS (1) To investigate the role of antiviral treatment in ulcerative colitis (UC) patients with CMV infection. (2) To investigate the role of viremia in the outcomes of these patients. MATERIALS AND METHODS The Cleveland Clinic pathology database identified 1478 patients who had colon biopsy and were tested for CMV during 1990 to 2013. After inclusion and exclusion, 41 UC patients were selected. Among them, 24 (58.5%) received treatment, 17 (41.5%) did not. A total of 14 demographic data and 4 clinical outcomes (surgery free survival, hospitalization, rehospitalization, and mortality) were compared between treated and nontreated patients. The same outcomes were also compared in patients who received treatment based on their viremia status. RESULTS All demographic variables are similar between those treated and nontreated groups. Antiviral therapy significantly improved the surgery free survival within 30 days, and lasted 70 months (P<0.01). In contrast, hospitalization, rehospitalization, and mortality were comparable (P>0.05). No significant difference was observed in any of the clinical outcomes based on viremia status. CONCLUSIONS Our small scale study demonstrates that antiviral treatment for colonic CMV infection significantly improves the surgery free survival short-term and long-term in patients with UC.
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Abstract
PURPOSE OF REVIEW Patients with inflammatory bowel disease (IBD) are predisposed to infections. Cytomegalovirus (CMV) colitis in adult IBD patients, particularly ulcerative colitis (UC), is related to severe or steroid-refractory disease. The aim of this review is to summarize the data on the prevalence and role of CMV colitis in children with IBD. RECENT FINDINGS Data on CMV colitis in children continue to be very limited due to its rarity. As in adults, children with coexisting UC and CMV tend to have more severe colitis, are resistant to corticosteroids, and are at high risk for colectomies on short- and long-term follow-up. In children, as in adults, the significance of CMV colitis, in terms of whether CMV is a pathogen that aggravates acute severe colitis or simply reflects disease severity, is still unknown.
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Affiliation(s)
- Anat Yerushalmy-Feler
- Pediatric Gastroenterology Unit, "Dana-Dwek" Children's Hospital, Tel Aviv Sourasky Medical Center, 6 Weizman Street, 6423906, Tel Aviv, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | | | - Shlomi Cohen
- Pediatric Gastroenterology Unit, "Dana-Dwek" Children's Hospital, Tel Aviv Sourasky Medical Center, 6 Weizman Street, 6423906, Tel Aviv, Israel.
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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