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Gholami Shahrebabak M, Kouchaki H, Gholami Shahrebabak A, Ravankhah M, Abdollahi M, Akbari M, Lankarani KB. Systematic review and meta-analysis of cytomegalovirus-associated adverse outcomes and healthcare resource utilization in hospitalized patients with inflammatory bowel disease. Int J Colorectal Dis 2025; 40:101. [PMID: 40272527 PMCID: PMC12021708 DOI: 10.1007/s00384-025-04886-x] [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] [Accepted: 04/05/2025] [Indexed: 04/25/2025]
Abstract
PURPOSE Serious complications and unplanned healthcare utilization are reported among inflammatory bowel disease (IBD) hospitalizations with associated cytomegalovirus (CMV). The present systematic review and meta-analysis aimed to examine the in-hospital outcomes of CMV-related hospitalization in IBD patients. METHODS Electronic databases were systematically searched in PubMed, Web of Science (ISI), Scopus, Embase, and Google Scholar until February 2024. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Cochran's Q test and I2 statistics were applied to evaluate potential heterogeneity across eligible studies. The random-effects model obtained pooled odds ratio (OR) estimates and associated 95% confidence intervals (CI). RESULTS Sixteen articles were included in the meta-analysis, encompassing 5120 IBD patients diagnosed with comorbid CMV infection. Our findings indicated that compared to IBD patients without CMV, those with both CMV and IBD had a longer hospital length of stay (LOS) (8.65 days longer; 95% CI: 6.96, 10.34; P < 0.01), a greater colectomy risk (OR = 2.26; 95% CI: 1.53, 3.34; P < 0.01), and higher in-hospital mortality (OR = 2.83; 95% CI: 1.92, 4.16; P < 0.01). However, the difference in hospital charges between the two groups was not statistically significant (P = 0.78). Sensitivity analysis using the leave-one-out approach revealed significant changes in hospital costs after excluding certain studies. Additionally, subgroup analyses showed significant differences based on IBD subtypes for surgery risk and LOS. CONCLUSION Our findings suggest that CMV infection is associated with poorer outcomes in hospitalized IBD patients, highlighting the importance of early detection and appropriate management of CMV infection in this population to improve clinical outcomes and reduce healthcare resource utilization.
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Affiliation(s)
- Maryam Gholami Shahrebabak
- Department of Pediatrics, School of Medicine, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran
| | - Hosein Kouchaki
- Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- USERN Office, Fasa University of Medical Sciences, Fasa, Iran
| | - Azam Gholami Shahrebabak
- Department of Pediatrics, Afzalipour Hospital, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Mahdi Ravankhah
- Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mozhan Abdollahi
- Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maryam Akbari
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, 8th Floor, Building No. 2, Zand Avenue, Shiraz, Iran.
| | - Kamran B Lankarani
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, 8th Floor, Building No. 2, Zand Avenue, Shiraz, Iran.
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Tian Y, Dai J, Yang Y, Guo X, Wang W, Li F, Wang J, Liu R. Relationship between the risk of intestinal mucosal Epstein-Barr virus and/or cytomegalovirus infection and peripheral blood NK cells numbers in patients with ulcerative colitis: a cross-sectional study in Chinese population. Front Microbiol 2024; 15:1498483. [PMID: 39697654 PMCID: PMC11652489 DOI: 10.3389/fmicb.2024.1498483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 11/21/2024] [Indexed: 12/20/2024] Open
Abstract
Objective This study aimed to analyze the relationship between the risk of common opportunistic pathogens Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection in intestinal mucosal tissues of Ulcerative Colitis (UC) patients and the number of peripheral blood NK cells. Methods UC patients admitted to a third-grade class-A hospital from January 2018 to December 2023 were selected as research population. Clinical data of the patients were collected from the electronic medical record system. Additionally, samples of intestinal mucosal tissues were obtained for real-time fluorescence quantitative PCR to detect and analyze the viral load of CMV and EBV. Blood samples were collected for lymphocyte subsets analysis. Multivariable logistic regression models analyses was used to determine the odds ratio (OR) and 95% confidence interval (95% CI) for the independent association between NK cells and EBV/CMV infections in UC. We further applied the restricted cubic spline analysis and smooth curve fitting to examine the non-linear relationship between them. Results 378 UC patients were enrolled. Of these patients, there were 194 patients (51.32%) with EBV /CMV infection. In multivariable logistic regression analyses NK cells was independently associated with EBV and/or CMV infection after adjusted potential confounders (OR 8.24, 95% CI 3.75-18.13, p < 0.001). A nonlinear relationship was found between NK cells and EBV/CMV infections, which had a threshold around 10.169. The effect sizes and CIs below and above the threshold were 0.535 (0.413-0.692), p < 0.001 and 1.034 (0.904-1.183), p > 0.05, respectively. Conclusion There was a non-linear relationship between NK cells and EBV/CMV infections. The risk for EBV/CMV infections was not increased with increasing NK cells in individuals with NK cells ≥ 10.169%, whereas the risk for EBV and/or CMV infection was increased with an decreasing NK cells in those with NK cells < 10.169%. The risk of EBV/CMV infections increases when NK cells were below a certain level.
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Affiliation(s)
- Ye Tian
- Department of Gastroenterology, Shanxi Provincial People’s Hospital, National Clinical Research Center for Digestive Diseases, Shanxi Inflammatory Bowel Disease Center, Taiyuan, China
| | - Jinghua Dai
- School of Nursing, Shanxi Medical University, Shanxi Provincial People’s Hospital, Taiyuan, China
| | - Yunfeng Yang
- Department of Gastroenterology, Shanxi Provincial People’s Hospital, National Clinical Research Center for Digestive Diseases, Shanxi Inflammatory Bowel Disease Center, Taiyuan, China
| | - Xiaofeng Guo
- Department of Gastroenterology, Shanxi Provincial People’s Hospital, National Clinical Research Center for Digestive Diseases, Shanxi Inflammatory Bowel Disease Center, Taiyuan, China
| | - Wei Wang
- Department of Laboratory Medicine, Shanxi Provincial People’s Hospital, Taiyuan, China
| | - Fengxia Li
- Department of Gastroenterology, Shanxi Provincial People’s Hospital, National Clinical Research Center for Digestive Diseases, Shanxi Inflammatory Bowel Disease Center, Taiyuan, China
| | - Juzi Wang
- Nursing Department, Shanxi Provincial People’s Hospital, Taiyuan, China
| | - Ruiyun Liu
- Shanxi Children’s Hospital Affiliated to Shanxi Medical University, Taiyuan, China
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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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Fredrick TW, DeFoster RE. 66-Year-Old Woman With Fatigue and Hypotension. Mayo Clin Proc 2024; 99:986-991. [PMID: 38520447 DOI: 10.1016/j.mayocp.2023.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 08/30/2023] [Accepted: 09/06/2023] [Indexed: 03/25/2024]
Affiliation(s)
- Thomas W Fredrick
- Resident in Internal Medicine, Mayo Clinic School of Graduate Medical Education, Rochester, MN
| | - Ruth E DeFoster
- Advisor to resident and Consultant in Hospital Internal Medicine, Mayo Clinic, Rochester, MN.
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Farrier DL, Chiang D, Arora AS. 19-Year-Old Man With Abdominal Pain, Vomiting, Bloody Diarrhea, and Rash. Mayo Clin Proc 2024; 99:980-985. [PMID: 38520446 DOI: 10.1016/j.mayocp.2023.08.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 08/17/2023] [Accepted: 08/21/2023] [Indexed: 03/25/2024]
Affiliation(s)
- David L Farrier
- Resident in Internal Medicine, Mayo Clinic School of Graduate Medical Education, Rochester, MN, USA
| | - David Chiang
- Resident in Internal Medicine, Mayo Clinic School of Graduate Medical Education, Rochester, MN, USA
| | - Amindra S Arora
- Advisor to residents and Consultant in Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
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Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. Aktualisierte S3-Leitlinie Colitis ulcerosa (Version 6.2). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:769-858. [PMID: 38718808 DOI: 10.1055/a-2271-0994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
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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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Selvan B, Pendse AA, Zhang C, Cauthen J, Kappus MR, Messina JA. Refractory Cytomegalovirus Colitis Followed by De Novo Inflammatory Bowel Disease Post-Orthotopic Liver Transplantation. ACG Case Rep J 2023; 10:e01232. [PMID: 38111784 PMCID: PMC10727682 DOI: 10.14309/crj.0000000000001232] [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: 08/30/2023] [Accepted: 11/14/2023] [Indexed: 12/20/2023] Open
Abstract
Cytomegalovirus (CMV) and inflammatory bowel disease (IBD) are both immune-mediated complications that affect orthotopic liver transplantation patients. In this report, we present a 60-year-old man who underwent orthotopic liver transplantation for cryptogenic cirrhosis with serologies notable for CMV-seropositive donor and seronegative recipient. His post-transplant course was initially complicated by probable refractory CMV colitis. However, his gastrointestinal symptoms persisted, eventually leading to a diagnosis of post-transplant de novo IBD. The discussion highlights theories regarding the association between CMV and IBD, a topic that has been widely debated for decades.
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Affiliation(s)
| | - Avani A. Pendse
- Department of Pathology, Duke University School of Medicine, Durham, NC
| | - Cecelia Zhang
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, NC
| | - Jeffriann Cauthen
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, NC
| | - Matthew R. Kappus
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, NC
| | - Julia A. Messina
- Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC
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Ren K, Yong C, Wang Y, Wei H, Zhao K, He B, Cui M, Chen Y, Wang J. Cytomegalovirus Pneumonia in Inflammatory Bowel Disease: Literature Review and Clinical Recommendations. Infect Drug Resist 2023; 16:6195-6208. [PMID: 37724090 PMCID: PMC10505384 DOI: 10.2147/idr.s420244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Accepted: 08/22/2023] [Indexed: 09/20/2023] Open
Abstract
Aim The objective was to elucidate the correlation between CMVP and immunosuppressive therapy in IBD patients, we hope this review could expand on the significance of CMV as an opportunistic pathogen and the potential impact on morbidity and mortality in IBD patients. Methods Records and clinical trajectories linked to CMVP in IBD patients were extracted from the PubMed database, irrespective of language barriers. The reference lists incorporated in these studies were manually inspected. Conclusions were generated using straightforward descriptive analysis. Results In total, 18 IBD patients, including Crohn's disease (CD, 67%) and Ulcerative Colitis (UC, 33%), affected by CMVP were identified from 17 published articles. A minority of these patients (17%) exhibited active disease, whereas the majority (83%) presented with quiescent disease. Fever (100%) and dyspnea (44%) emerged as the most prevalent clinical symptoms. All the patients had undergone immunosuppressive therapy. A significant proportion, up to 89%, had received thiopurine treatment prior to the CMVP diagnosis. Interestingly, none of the patients were subjected to biological therapy. Half of the patients manifested with Hemophagocytic Lymphohistiocytosis (HLH). Almost all patients (94%) were administered antiviral treatment and a substantial 83% experienced full recovery. Immunosuppressive agents were either tapered or discontinued altogether. A subset of patients, 17%, suffered fatal outcomes. Conclusion Our findings underscore the need for heightened suspicion of CMVP in IBD patients who exhibit symptoms such as fever and dyspnea. During the COVID-19 pandemic, CMVP should be considered a potential differential diagnosis. It was observed that CMVP primarily transpires during CD remission. Azathioprine emerged as the predominant immunosuppressant linked to CMV reactivation. The prompt application of effective antiviral therapy can substantially enhance patient outcomes. CMV vaccine might serve as a viable prevention strategy.
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Affiliation(s)
- Keyu Ren
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Chunming Yong
- Department of Emergency, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Yanting Wang
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Hongyun Wei
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Kun Zhao
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Baoguo He
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Mingjuan Cui
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Yunqing Chen
- Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Jin Wang
- Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
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Hamada N, Maeda R, Suyama A, Yuzurio S, Oda W, Suwaki T. Acute Hemorrhagic Rectal Ulcer Complicated by Cytomegalovirus Enteritis following Steroid Pulse Therapy for Acute Exacerbation of Interstitial Pneumonia. Intern Med 2023; 62:2335-2339. [PMID: 36543211 PMCID: PMC10484779 DOI: 10.2169/internalmedicine.0823-22] [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: 08/16/2022] [Accepted: 11/10/2022] [Indexed: 12/24/2022] Open
Abstract
We herein report a rare case of acute hemorrhagic rectal ulcer (AHRU) complicated by cytomegalovirus enteritis following steroid pulse therapy for interstitial pneumonia. An 86-year-old woman underwent steroid pulse therapy for interstitial pneumonia. She was bedridden with dyspnea and suddenly developed melena. Colonoscopy revealed AHRU, which did not improve with conservative treatment, but did improve with ganciclovir administration for cytomegalovirus enteritis. This gastrointestinal complication has not received much attention by pulmonologists who perform steroid pulse therapy for interstitial pneumonia. Delayed treatment of this complications can be fatal. Caution should be taken when administering steroid pulse therapy to bedridden patients with interstitial pneumonia.
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Affiliation(s)
- Noboru Hamada
- Department of Respiratory Medicine, Okayama City Hospital, Japan
| | - Ruri Maeda
- Department of Respiratory Medicine, Okayama City Hospital, Japan
| | - Atsuhito Suyama
- Department of Respiratory Medicine, Okayama City Hospital, Japan
| | - Shouta Yuzurio
- Department of Respiratory Medicine, Okayama City Hospital, Japan
| | - Wakako Oda
- Department of Pathology, Okayama City Hospital, Japan
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Ozdemir B, Atay A, Kayhan MA, Ozin YO, Gokce DT, Altunsoy A, Guner R. Tissue quantitative RT-PCR test for diagnostic significance of cytomegalovirus infection in patients with inflammatory bowel disease and treatment response: Cytomegalovirus infection in patients with inflammatory bowel disease. Medicine (Baltimore) 2023; 102:e34463. [PMID: 37543790 PMCID: PMC10402982 DOI: 10.1097/md.0000000000034463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/28/2023] [Accepted: 07/03/2023] [Indexed: 08/07/2023] Open
Abstract
Cytomegalovirus (CMV) is an opportunistic pathogen that exacerbates inflammatory bowel disease (IBD). There are no clear diagnostic criteria for CMV infection in IBD patients. The aim of this study was to evaluate the importance of the diagnosis of CMV infection with CMV-DNA polymerase chain reaction (PCR) in the colonic mucosa and the response to antiviral treatment. We retrospectively analyzed the clinical data of 30 patients with IBD (24 men, 6 women; median age: 42 years) who were hospitalized because of IBD exacerbation and whose samples were assessed by tissue CMV-DNA PCR positivity. Most of the IBD patients had ulcerative colitis (90%). The CMV-DNA PCR median value was 8848 copies/mL of tissue (range 90-242,936 copies/mL). Blood CMV-DNA PCR was found to be positive in a small group (33.3%, 10/30) of tissue CMV-DNA PCR-positive cases. immunohistochemistry tests were positive in only 5 of the 23 patients positive for CMV-DNA PCR in the colonic mucosa, and high remission (25/30, 83.3%) was detected with antiviral therapy. Recurrence of CMV colitis infection was observed in 9 of 25 patients who had remission with antiviral therapy. The tissue CMV-DNA PCR test was found to be more useful than blood CMV-DNA PCR and immunohistochemistry tests for diagnosing CMV colitis, and the tissue CMV-DNA PCR test enabled rapid and appropriate treatment.
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Affiliation(s)
- Burcu Ozdemir
- Department of Infectious Diseases and Clinical Microbiology Clinic, Ankara City Hospital, Ankara, Turkey
| | - Ali Atay
- Department of Gastroenterology, Ankara City Hospital, Ankara, Turkey
| | | | | | | | - Adalet Altunsoy
- Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences Ankara City Hospital, Ankara, Turkey
| | - Rahmet Guner
- Department of Infectious Diseases and Clinical Microbiology Clinic, Ankara Yildirim Beyazit University, Ankara City Hospital, Ankara, Turkey
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12
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Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1046-1134. [PMID: 37579791 DOI: 10.1055/a-2060-0935] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/16/2023]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
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13
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Meeralam Y, Al Qurashi B, Al Masoudi A, Alhejaili TL, Khayat M, Aljoaid AM, Al Harthi W, Hafiz WA, Shariff MK. Cytomegalovirus Colitis in a Patient With Ulcerative Colitis on Vedolizumab Monotherapy. Cureus 2023; 15:e35473. [PMID: 36999101 PMCID: PMC10043637 DOI: 10.7759/cureus.35473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/15/2023] [Indexed: 02/28/2023] Open
Abstract
Cytomegalovirus (CMV) is a human herpes-type virus with variable clinical manifestations. Infections in immunocompetent patients are usually asymptomatic or mild, and severe infections are generally seen in immunosuppressed individuals. CMV colitis is not uncommon in patients with ulcerative colitis (UC) and is mostly associated with the use of steroids, immunomodulators like azathioprine, and biologics like infliximab, which have systemic immunosuppressive effects. Vedolizumab is an anti-integrin antibody that is gut-selective without any systemic effects. We report an unusual presentation of a female patient with UC who had concomitant CMV colitis and erythema nodosum, who was on vedolizumab, and not on any steroids or other immunosuppressants. She responded well to anti-viral treatment and steroids.
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Affiliation(s)
- Yaser Meeralam
- Digestive and Liver Health Center, King Abdullah Medical City, Makkah, SAU
| | - Bushra Al Qurashi
- Internal Medicine Department, King Abdullah Medical City, Makkah, SAU
| | - Assel Al Masoudi
- Internal Medicine Department, King Abdullah Medical City, Makkah, SAU
| | - Talal L Alhejaili
- Digestive and Liver Health Center, King Abdullah Medical City, Makkah, SAU
| | - Mohammed Khayat
- Digestive and Liver Health Center, King Abdullah Medical City, Makkah, SAU
| | - Anas M Aljoaid
- Digestive and Liver Health Center, King Abdullah Medical City, Makkah, SAU
| | - Wallaa Al Harthi
- Digestive and Liver Health Center, King Abdullah Medical City, Makkah, SAU
| | - Waleed A Hafiz
- Department of Medicine, College of Medicine, Umm Al-Qura University, Makkah, SAU
| | - Mohammed K Shariff
- Digestive and Liver Health Center, King Abdullah Medical City, Makkah, SAU
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14
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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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Yang H, Ran Z, Jin M, Qian JM. Current Status of Opportunistic Infection in Inflammatory Bowel Disease Patients in Asia: A Questionnaire-Based Multicenter Study. Gut Liver 2022; 16:726-735. [PMID: 35611664 PMCID: PMC9474486 DOI: 10.5009/gnl210217] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 08/05/2021] [Accepted: 10/01/2021] [Indexed: 02/04/2023] Open
Abstract
Background/Aims Opportunistic infection in inflammatory bowel disease (IBD) has become a serious problem. However, its status of doctors' opinions and test equipment in hospitals are unclear. The aim of the study was to investigate these issues to improve the prognosis of IBD patients. Methods This retrospective, multicenter study was conducted by 83 investigators who were members of the Asian Organization for Crohn's and Colitis. Data on opportunistic infection were collected from hospital databases between January 2017 and December 2017. The survey consisted of 11 items. Results Most physicians appreciated the diagnostic value of tissue cytomegalovirus (CMV) DNA, accounting for 86.1% of members in China, 37.5% in Japan, 52.9% in South Korea, and 66.7% in Southeast Asia. Only 83.1% of hospitals had the ability to test for CMV immunohistochemistry in Asia. Hepatitis B surface antigen (HBsAg) screening was recommended by all members. However, only 66.7% in China, 70.6% in South Korea, and 66.7% in Southeast Asia agreed to routinely vaccinate IBD patients when HBsAg tested negative. Most members preferred metronidazole (74.7%) as the first choice for patients with Clostridium difficile infection. However, the proportion of stool C. difficile toxin test was lower in China than in other areas (75.0% in China vs 95.8% in Japan and 100% in South Korea and Southeast Asia, p<0.05). Conclusions Opportunistic infection from CMV, hepatitis B virus, and C. difficile should be of high concern for IBD patients. More efforts are needed, such as understanding consensus in clinical practice and improving testing facilities in hospitals.
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Affiliation(s)
- Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Zhihua Ran
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Meng Jin
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Jia-Ming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
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16
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Chen Y, Shen J. Core indicators of an evaluation and guidance system for quality of care in inflammatory bowel disease centers: A critical review. EClinicalMedicine 2022; 46:101382. [PMID: 35434585 PMCID: PMC9011022 DOI: 10.1016/j.eclinm.2022.101382] [Citation(s) in RCA: 6] [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: 11/16/2021] [Revised: 02/18/2022] [Accepted: 03/22/2022] [Indexed: 02/07/2023] Open
Abstract
The mission of the IBD Quality Care Evaluation Center (IBDQCC) is to establish indicators of quality of care (QoC), certify IBD units to generate a network of IBD quality care, and eventually improve the national level of IBD healthcare. The final list of 28 core and 13 secondary IBD QoC indicators suitable for the healthcare system in China were selected using a Delphi consensus methodology. Units that met all core indicators were qualified as "regional"; units that met all core indicators together with more than 50% of the secondary indicators received a rating of "excellence." Using the selected QoC core indicators for certifying IBD units, a network of IBD quality care units covering the majority of IBD patients in China was established. Funding This work was financially supported by Cultivation Funding for Clinical Scientific Research Innovation, Renji Hospital, School of Medicine, Shanghai Jiaotong University (RJPY-LX-004), National Natural Science Foundation of China (No. 81,770,545), Shanghai Science and Technology Innovation Initiative (21SQBS02302), and Cultivated Funding for Clinical Research Innovation, Renji Hospital, School of Medicine, Shanghai Jiaotong University (RJPY-LX-004).
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Affiliation(s)
- Yueying Chen
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 160# Pu Jian Ave, Shanghai 200127, China
| | - Jun Shen
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 160# Pu Jian Ave, Shanghai 200127, China
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17
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Kwon J, Fluxá D, Farraye FA, Kröner PT. Cytomegalovirus-related colitis in patients with inflammatory bowel disease. Int J Colorectal Dis 2022; 37:685-691. [PMID: 35132443 DOI: 10.1007/s00384-022-04099-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/23/2022] [Indexed: 02/04/2023]
Abstract
PURPOSE We aimed to examine the role of cytomegalovirus (CMV) infection in patients with inflammatory bowel disease (IBD), which remains highly debated. METHODS Retrospective, observational study using the Nationwide Inpatient Sample (NIS) 2015-2017. Patients with ICD9/10CM codes for Crohn's disease (CD), ulcerative colitis (UC), and CMV colitis were included in the study. The primary outcome was the odds of CMV colitis in patients with IBD compared to patients without IBD. Secondary outcomes were differences in inpatient morbidity, mortality, resource utilization, colectomy rates, hospital length of stay (LOS), and inflation-adjusted total hospitalization costs. RESULTS A total of 992,445 patients with IBD were identified, out of which 520 (0.05%) had associated CMV colitis. Patients with IBD had significantly higher odds of CMV colitis compared to patients without IBD (aOR: 19.76, p < 0.01), having an even greater association with UC (aOR: 31.13, p < 0.01). CMV colitis in patients with CD was associated with a significant increase in odds of mortality, shock, and ICU stay, while patients with UC had higher odds of colectomy. The patients with IBD and CMV colitis had higher odds of acute kidney injury, multiorgan failure, markedly increased additional hospital costs, and LOS compared to patients with IBD and no CMV colitis. CONCLUSION IBD has a significant association with CMV colitis, and the presence of CMV colitis in patients with IBD was associated with higher mortality, morbidity, and hospital costs. Prospectively designed studies may better elucidate the risk factors and impact of CMV colitis on patients with IBD.
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Affiliation(s)
- Joshua Kwon
- Department of Internal Medicine, Mayo Clinic, Jacksonville, FL, USA.
| | - Daniela Fluxá
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Francis A Farraye
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Paul T Kröner
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
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18
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Watanabe Y, Hayashi K, Terai S. A Rare Case of Ulcerative Colitis with Severe Pneumocystis jirovecii Pneumonia and Cytomegalovirus Colitis: A Case Report and Literature Review. Intern Med 2022; 61:339-344. [PMID: 34373380 PMCID: PMC8866792 DOI: 10.2169/internalmedicine.7953-21] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Pneumocystis jirovecii pneumonia (PJP) and cytomegalovirus (CMV) colitis are opportunistic infections that occur during immunosuppressive treatments for ulcerative colitis (UC). The prognosis of PJP and CMV colitis is very poor. We herein report a rare case of a 74-year-old UC patient with PJP and CMV colitis that was successfully treated with intensive therapy. PJP progresses rapidly, so the timing and choice of treatment are critical. Furthermore, a literature review of similar cases suggested that prophylactic therapy for opportunistic infections might be important, especially in the elderly. This case will serve as a reference for successful treatment in future cases.
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Affiliation(s)
- Yusuke Watanabe
- Division of Preemptive Medicine for Digestive Disease and Healthy Active Life, School of Medicine, Niigata University, Japan
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan
| | - Kazunao Hayashi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan
- Department of Preventive and Minimally Invasive Medicine for Digestive Desease, Niigata University, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan
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19
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Ihara K, Isono H, Isono M, Akaiwa Y, Kobayashi K, Oogi M, Oogi T. Cytomegalovirus colitis with a new diagnosis of ulcerative colitis in an elderly woman. J Rural Med 2022; 17:85-88. [PMID: 35432635 PMCID: PMC8984622 DOI: 10.2185/jrm.2021-053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 11/12/2021] [Indexed: 12/03/2022] Open
Abstract
Objectives: Cytomegalovirus (CMV) colitis is generally diagnosed in
immunocompromised patients. It is rare for patients who are not immunocompromised to
develop CMV colitis. Cases of CMV colitis in patients with inflammatory bowel disease have
also been reported. We encountered a case of CMV colitis with a new diagnosis of severe
ulcerative colitis and demonstrated the importance of suspecting ulcerative colitis in
immunocompetent patients with CMV colitis. Patient: A 78-year-old woman was hospitalized with fever and diarrhea that
had lasted for a month. Colonoscopy revealed continuous diffuse edema, mucosal redness,
and multiple punched-out ulcers with bleeding, suggesting cytomegalovirus (CMV) colitis,
although she was not immunocompromised. Immunohistochemical staining revealed CMV-positive
cells, and CMV colitis was diagnosed. One month later, a colonoscopy was conducted owing
to persistent symptoms despite initiating the prescribed antiviral drug. A complete loss
of vascular pattern, easy bleeding of the crude mucosa, and exacerbation of multiple
punched-out ulcers were observed. She was diagnosed with severe ulcerative colitis. The
symptoms of ulcerative colitis disappeared with prednisolone and 5-amino salicylic acid
treatment. Conclusion: Ulcerative colitis should be suspected in immunocompetent
patients with CMV colitis.
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Affiliation(s)
- Kousuke Ihara
- Department of General Medicine, HITO Medical Center, Ehime, Japan
| | - Hiroki Isono
- Department of General Medicine, HITO Medical Center, Ehime, Japan
| | - Momoko Isono
- Department of General Medicine, HITO Medical Center, Ehime, Japan
| | - Yuzuru Akaiwa
- Department of Internal Medicine, HITO Medical Center, Ehime, Japan
| | | | - Maki Oogi
- Department of Internal Medicine, HITO Medical Center, Ehime, Japan
| | - Tomohiro Oogi
- Department of Internal Medicine, HITO Medical Center, Ehime, Japan
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20
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Jain S, Namdeo D, Sahu P, Kedia S, Sahni P, Das P, Sharma R, Gupta V, Makharia G, Dar L, Travis SPL, Ahuja V. High mucosal cytomegalovirus DNA helps predict adverse short-term outcome in acute severe ulcerative colitis. Intest Res 2021; 19:438-447. [PMID: 33147897 PMCID: PMC8566826 DOI: 10.5217/ir.2020.00055] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Revised: 07/08/2020] [Accepted: 07/08/2020] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND/AIMS Predictors of short-term outcome of intravenous (IV) steroid therapy in acute severe ulcerative colitis (ASUC) have been well described, but the impact of cytomegalovirus (CMV) infection as a predictor of outcome remains debatable. We investigated the role of quantitative CMV polymerase chain reaction (PCR) as a predictor of short-term outcome in patients with ASUC. METHODS Consecutive patients with ASUC satisfying Truelove and Witts criteria hospitalized at All India Institute of Medical Sciences (AIIMS) from May 2016 to July 2019 were included; all received IV steroid. The primary outcome measure was steroid-failure defined as the need for rescue therapy (with ciclosporin or infliximab) or colectomy during admission. AIIMS' index (ulcerative colitis index of severity > 6 at day 1+fecal calprotectin > 1,000 μg/g at day 3), with quantitative CMV PCR on biopsy samples obtained at initial sigmoidoscopy were correlated with the primary outcome. RESULTS Thirty of 76 patients (39%) failed IV corticosteroids and 12 (16%) underwent surgery. Patients with steroid failure had a significantly higher mucosal CMV DNA than responders (3,454 copies/mg [0-2,700,000] vs. 116 copies/mg [0-27,220]; P< 0.01). On multivariable analysis, mucosal CMV DNA load > 2,000 copies/mg (odds ratio [OR], 10.2; 95% confidence interval [CI], 2.6-39.7; P< 0.01) and AIIMS' index (OR, 39.8; 95% CI, 4.4-364.4; P< 0.01) were independent predictors of steroid-failure and need for colectomy. The combination correctly predicted outcomes in 84% of patients with ASUC. CONCLUSIONS High mucosal CMV DNA ( > 2,000 copies/mg) independently predicts failure of IV corticosteroids and short-term risk of colectomy and it has an additional value to the established markers of disease severity in patients with ASUC.
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Affiliation(s)
- Saransh Jain
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi,
India
| | - Divya Namdeo
- Microbiology, All India Institute of Medical Sciences, New Delhi,
India
| | - Pabitra Sahu
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi,
India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi,
India
| | - Peush Sahni
- Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi,
India
| | - Prasenjit Das
- Pathology, All India Institute of Medical Sciences, New Delhi,
India
| | - Raju Sharma
- Radiodiagnosis, All India Institute of Medical Sciences, New Delhi,
India
| | - Vipin Gupta
- Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford,
UK
| | - Govind Makharia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi,
India
| | - Lalit Dar
- Microbiology, All India Institute of Medical Sciences, New Delhi,
India
| | - Simon PL Travis
- Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford,
UK
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi,
India
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21
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The Impact of Human Herpesviruses in Clinical Practice of Inflammatory Bowel Disease in the Era of COVID-19. Microorganisms 2021; 9:microorganisms9091870. [PMID: 34576764 PMCID: PMC8468540 DOI: 10.3390/microorganisms9091870] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 08/27/2021] [Accepted: 08/31/2021] [Indexed: 02/06/2023] Open
Abstract
Human herpesviruses (HHVs): herpes simplex virus (HSV) types 1 (HSV-1) and 2 (HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), HHV-6, HHV-7, and HHV-8, are known to be part of a family of DNA viruses that cause several diseases in humans. In clinical practice of inflammatory bowel disease (IBD), the complication of CMV enterocolitis, which is caused by CMV reactivation under disruption of intestinal barrier function, inflammation, or strong immunosuppressive therapy, is well known to affect the prognosis of disease. However, the relationship between other HHVs and IBD remains unclear. In the transplantation field, reactivation of other viruses, such as HHV-6, could cause colitis under immunosuppressed condition. Recent research revealed that combined infection of some HHVs could be a risk factor for colectomy in patients with ulcerative colitis. This suggests that it would be important to clarify HHV behavior in the treatment for patients with IBD, especially in those under immunosuppressive therapies. Looking at the relationship with recently emerged novel coronaviruses (SARS-CoV-2), there are reports describe that SARS-CoV-2 might induce reactivation of HSV-1, EBV, VZV (herpes zoster), and HHV-6/7. If SARS-CoV-2 infection becomes common, vigilance against HHV reactivation may become more crucial. In this review, we discuss the impact of HHVs in clinical practice of inflammatory bowel diseases, especially during the SARS-CoV-2 pandemic.
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22
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Voet M, Calon T, Hendriks M, Schreuder RM. Severe Complication of Thiopurine Treatment in a Young Woman with Crohn's Disease. Eur J Case Rep Intern Med 2021; 8:002350. [PMID: 33869095 DOI: 10.12890/2021_002350] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 02/25/2021] [Indexed: 02/07/2023] Open
Abstract
Case description A 28-year old woman receiving thiopurine treatment for Crohn's disease presented with a systemic primo cytomegalovirus (CMV) infection affecting the gut (colitis), liver (hepatitis), lungs (pneumonitis) and eyes (retinitis). Secondary to this systemic infection, she developed splenomegaly, pancytopenia and lymphadenopathy. Anti-viral treatment resulted in complete resolution of clinical, biochemical and radiological abnormalities within 6 weeks. Conclusion Early recognition is crucial since CMV infection in a patient receiving thiopurine treatment may result in serious complications. LEARNING POINTS Cytomegalovirus (CMV) infection in patients receiving thiopurine treatment may result in serious complications.This case report describes extensive primo CMV infection causing colitis, hepatitis, pneumonitis and retinitis in a patient receiving thiopurine treatment.Early recognition and treatment of the infection is crucial.
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Affiliation(s)
- Mpj Voet
- Department of Internal Medicine, Catharina Ziekenhuis, Eindhoven, The Netherlands
| | - Tga Calon
- Department of Internal Medicine, Catharina Ziekenhuis, Eindhoven, The Netherlands
| | - Mmc Hendriks
- Department of Internal Medicine, Catharina Ziekenhuis, Eindhoven, The Netherlands
| | - R M Schreuder
- Department of Gastroenterology and Hepatology, Catharina Ziekenhuis, Eindhoven, The Netherlands
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Leal T, Arroja B, Costa D, Ferreira C, Soares J, Gonçalves R. Colitis due to Cytomegalovirus and Herpes Simplex Type 2 as a Complication of a First Presentation of Inflammatory Bowel Disease. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2021; 29:56-60. [DOI: 10.1159/000514715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 01/06/2021] [Indexed: 11/19/2022]
Abstract
<b><i>Introduction:</i></b> The first presentation of ulcerative colitis may be an acute flare in about 15% of patients, requiring hospital admission. In acute severe steroid-refractory ulcerative colitis, cytomegalovirus (CMV) should be sought because it is a frequent cause of refractory disease. Herpes simplex colitis constitutes a rarer event in ulcerative colitis patients and it is usually associated with immunosuppression. <b><i>Case Presentation:</i></b> We report a case of a first presentation of ulcerative colitis complicated by CMV and herpes simplex type 2 coinfection. After a long period of systemic corticosteroids, the diagnosis of both CMV and herpes colitis was made. Despite antiviral treatment, colectomy was required due to a contained perforation. <b><i>Discussion/Conclusion:</i></b> This report highlights the importance of a high degree of suspicion for opportunistic infections in steroid/immunomodulator refractory ulcerative colitis, even in the first flare.
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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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Okuno H, Ogino H, Ihara E, Nishioka K, Iboshi Y, Chinen T, Ochiai T, Akiho H, Nakamura K, Gotoda T, Ogawa Y. Interleukin-1β as a Predictor of Glucocorticoid Response in Ulcerative Colitis. Digestion 2021; 102:357-367. [PMID: 32434191 DOI: 10.1159/000507435] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Accepted: 03/22/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND/AIM Currently, there are no established biomarkers to differentiate between glucocorticoid (GC)-resistant and GC-sensitive ulcerative colitis (UC); however, interleukin (IL)-1β could be one such candidate biomarker. The aim of this study was to investigate whether mucosally expressed IL-1β could predict the response to GC in patients with UC. METHODS A total of 27 mucosal tissue samples from 10 patients with GC-resistant UC (GC-resistant group), 9 patients with GC-sensitive UC (GC-sensitive group), and 8 control patients (control group) were analyzed by qRT-PCR for the expression of IL-1β, GC receptor α (GRα), GRβ, and other inflammatory mediators. Rachmilewitz endoscopic index (REI) between the GC-resistant and GC-sensitive groups was matched to avoid any potential influence of inflammation. RESULTS The REI did not significantly differ between the GC-resistant and GC-sensitive groups. Mucosally expressed IL-1β levels in the GC-resistant group were significantly higher than those in the GC-sensitive group. However, there were no significant differences in the expression levels of GRα, GRβ, and other inflammatory mediators between the 2 groups. We could distinguish between the GC-resistant and GC-sensitive groups with a sensitivity of 90.0% and specificity of 77.8% based on mucosally expressed IL-1β. CONCLUSIONS Mucosally expressed IL-1β can be used as a predictor of GC response in patients with UC.
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Affiliation(s)
- Hiroaki Okuno
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Haruei Ogino
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan,
| | - Eikichi Ihara
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kei Nishioka
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoichiro Iboshi
- Department of Gastroenterology, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan
| | - Takatoshi Chinen
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toshiaki Ochiai
- Department of Internal Medicine, Saiseikai Fukuoka General Hospital, Fukuoka, Japan
| | - Hirotada Akiho
- Department of Gastroenterology, Kitakyushu Municipal Medical Center, Fukuoka, Japan
| | - Kazuhiko Nakamura
- Department of Gastroenterology, Harasanshin Hospital, Fukuoka, Japan
| | - Takuji Gotoda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Kucharzik T, Dignass AU, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengießer K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 58:e241-e326. [PMID: 33260237 DOI: 10.1055/a-1296-3444] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Axel U Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Deutschland
| | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Deutschland
| | - Philip Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | - Klaus Kannengießer
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Andreas Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | | | - Andreas Stallmach
- Gastroenterologie, Hepatologie und Infektiologie, Friedrich Schiller Universität, Jena, Deutschland
| | - Jürgen Stein
- Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt/Main, Deutschland
| | - Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Niels Teich
- Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten, Leipzig, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
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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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28
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Bohossian HB, Lopes EW, Roller LA, Ananthakrishnan AN, Zukerberg LR. Case 8-2020: An 89-Year-Old Man with Recurrent Abdominal Pain and Bloody Stools. N Engl J Med 2020; 382:1042-1052. [PMID: 32160667 DOI: 10.1056/nejmcpc1913476] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Hacho B Bohossian
- From the Department of Medicine, Newton-Wellesley Hospital, Newton (H.B.B.), and the Department of Medicine, Tufts University School of Medicine (H.B.B.), the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Massachusetts General Hospital, and the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Harvard Medical School, Boston - all in Massachusetts
| | - Emily W Lopes
- From the Department of Medicine, Newton-Wellesley Hospital, Newton (H.B.B.), and the Department of Medicine, Tufts University School of Medicine (H.B.B.), the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Massachusetts General Hospital, and the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Harvard Medical School, Boston - all in Massachusetts
| | - Lauren A Roller
- From the Department of Medicine, Newton-Wellesley Hospital, Newton (H.B.B.), and the Department of Medicine, Tufts University School of Medicine (H.B.B.), the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Massachusetts General Hospital, and the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Harvard Medical School, Boston - all in Massachusetts
| | - Ashwin N Ananthakrishnan
- From the Department of Medicine, Newton-Wellesley Hospital, Newton (H.B.B.), and the Department of Medicine, Tufts University School of Medicine (H.B.B.), the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Massachusetts General Hospital, and the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Harvard Medical School, Boston - all in Massachusetts
| | - Lawrence R Zukerberg
- From the Department of Medicine, Newton-Wellesley Hospital, Newton (H.B.B.), and the Department of Medicine, Tufts University School of Medicine (H.B.B.), the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Massachusetts General Hospital, and the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Harvard Medical School, Boston - all in Massachusetts
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29
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Wisniewski A, Kirchgesner J, Seksik P, Landman C, Bourrier A, Nion-Larmurier I, Marteau P, Cosnes J, Sokol H, Beaugerie L. Increased incidence of systemic serious viral infections in patients with inflammatory bowel disease associates with active disease and use of thiopurines. United European Gastroenterol J 2019; 8:303-313. [PMID: 32529821 DOI: 10.1177/2050640619889763] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background The magnitude and drivers of the risk of serious viral infections in Inflammatory Bowel diseases (IBD) are unclear. Objective The objective of this study was to assess the incidence and risk factors for systemic serious viral infections in IBD patients. Methods Using MICISTA, a database detailing prospective characteristics and complications of IBD, we identified patients that were followed for IBD in 2005-2014 outside the context of organ transplantation, HIV infection or chronic viral hepatitis. We estimated incidences of systemic serious viral infections, defined by the need for hospitalization or permanent organ damage. Standardized incidence ratios (SIRs) were calculated using the French hospital database. We performed a case-control study nested in MICISTA for assessing the role of exposure to IBD drugs and IBD clinical activity in the risk of developing infection. Results We identified 31 patients with serious viral infections among 2645 patients followed for 15,383 person-years. We observed 13 cases of cytomegalovirus, 10 Epstein-Barr virus, 5 varicella zoster virus and 3 herpes simplex virus infections. No deaths occurred. The incidence rate of infections in patients with IBD was 2.02/1000 person-years, and the SIR was 3.09 (95% confidence interval (CI), 1.98-4.20; p = 0.0002) in the study population. By multivariate analysis, increased risk of infection was associated with exposure to thiopurines (odds ratio (OR), 3.48; 95% CI, 1.36-8.90; p = 0.009), and clinically active IBD at onset of infection (OR, 3.35; 95% CI, 1.23-9.23; p = 0.02). Conclusions The incidence of systemic serious viral infections in patients with IBD is tripled compared to general population. Clinically active IBD and exposure to thiopurines are the main drivers of the risk.
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Affiliation(s)
- Andrew Wisniewski
- Gastroenterology Department of Charles-Lemoyne hospital, Université de Sherbrooke, Montréal, Canada
| | - Julien Kirchgesner
- Department of Gastroenterology, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Université, AP-HP Hôpital Saint-Antoine, Paris, France
| | - Philippe Seksik
- Department of Gastroenterology, INSERM, Centre de recherche Saint-Antoine, Sorbonne Université, AP-HP Hôpital Saint-Antoine, Paris, France
| | - Cécilia Landman
- Department of Gastroenterology, AP-HP Hôpital Saint-Antoine, Paris, France
| | - Anne Bourrier
- Department of Gastroenterology, INSERM, Centre de recherche Saint-Antoine, Sorbonne Université, AP-HP Hôpital Saint-Antoine, Paris, France
| | | | - Philippe Marteau
- Department of Liver Diseases, INSERM, Centre de recherche Saint-Antoine, Sorbonne Université, AP-HP Hôpital Saint-Antoine, Paris, France
| | - Jacques Cosnes
- Department of Gastroenterology, AP-HP Hôpital Saint-Antoine, Paris, France
| | - Harry Sokol
- Department of Liver Diseases, INSERM, Centre de recherche Saint-Antoine, Sorbonne Université, AP-HP Hôpital Saint-Antoine, Paris, France
| | - Laurent Beaugerie
- Department of Gastroenterology, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Université, AP-HP Hôpital Saint-Antoine, Paris, France
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Maeda T, Sakai H, Ozawa N, Sugiyama T, Takada J, Kubota M, Ibuka T, Shirakami Y, Araki H, Shimizu M. Acute cytomegalovirus infection in an immunocompetent patient with ulcerative colitis: A case report. Exp Ther Med 2019; 18:2271-2277. [PMID: 31452714 DOI: 10.3892/etm.2019.7823] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 07/18/2019] [Indexed: 11/06/2022] Open
Abstract
Cytomegalovirus (CMV) is a ubiquitous member of the Herpesviridae family that can present with a variety of clinical manifestations, including encephalitis, retinitis, interstitial pneumonia and colitis. These serious symptoms are generally observed as opportunistic infections in immunocompromised hosts, including patients with acquired immunodeficiency syndrome and those receiving steroids and/or immunosuppressants. Symptomatic CMV infections in patients with ulcerative colitis are found in patients treated with steroids and/or immunosuppressants but rarely affect those who are not taking these agents. The present study reported the case of a young patient without concurrent use of immunosuppressive agents for the treatment of ulcerative colitis. The patient presented with acute mononucleosis and colitis caused by primary CMV infection. This was characterized by the presence of atypical lymphocytes and hepatosplenomegaly, elevation of transaminase levels, serology-positive anti-CMV IgM, and CMV antigenemia. Additionally, CMV-positive cells were histologically detected in colonic biopsy specimens. The patient's symptoms and clinical parameters improved following initiation of intravenous ganciclovir. It was concluded that even if patients with ulcerative colitis are not treated with steroids and/or immunosuppressants, significant attention should be paid to acute CMV infections in the context of severe or persistent colonic inflammation.
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Affiliation(s)
- Toshihide Maeda
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Hiroyasu Sakai
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Noritaka Ozawa
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Tomohiko Sugiyama
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Jun Takada
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Masaya Kubota
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Takashi Ibuka
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Yohei Shirakami
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Hiroshi Araki
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Masahito Shimizu
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
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31
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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: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
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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32
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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: 53] [Impact Index Per Article: 8.8] [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
Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disorder of the colon that causes continuous mucosal inflammation extending from the rectum to the more proximal colon, with variable extents. UC is characterized by a relapsing and remitting course. UC was first described by Samuel Wilks in 1859 and it is more common than Crohn's disease worldwide. The overall incidence and prevalence of UC is reported to be 1.2-20.3 and 7.6-245 cases per 100,000 persons/year respectively. UC has a bimodal age distribution with an incidence peak in the 2nd or 3rd decades and followed by second peak between 50 and 80 years of age. The key risk factors for UC include genetics, environmental factors, autoimmunity and gut microbiota. The classic presentation of UC include bloody diarrhea with or without mucus, rectal urgency, tenesmus, and variable degrees of abdominal pain that is often relieved by defecation. UC is diagnosed based on the combination of clinical presentation, endoscopic findings, histology, and the absence of alternative diagnoses. In addition to confirming the diagnosis of UC, it is also important to define the extent and severity of inflammation, which aids in the selection of appropriate treatment and for predicting the patient's prognosis. Ileocolonoscopy with biopsy is the only way to make a definitive diagnosis of UC. A pathognomonic finding of UC is the presence of continuous colonic inflammation characterized by erythema, loss of normal vascular pattern, granularity, erosions, friability, bleeding, and ulcerations, with distinct demarcation between inflamed and non-inflamed bowel. Histopathology is the definitive tool in diagnosing UC, assessing the disease severity and identifying intraepithelial neoplasia (dysplasia) or cancer. The classical histological changes in UC include decreased crypt density, crypt architectural distortion, irregular mucosal surface and heavy diffuse transmucosal inflammation, in the absence of genuine granulomas. Abdominal computed tomographic (CT) scanning is the preferred initial radiographic imaging study in UC patients with acute abdominal symptoms. The hallmark CT finding of UC is mural thickening with a mean wall thickness of 8 mm, as opposed to a 2-3 mm mean wall thickness of the normal colon. The Mayo scoring system is a commonly used index to assess disease severity and monitor patients during therapy. The goals of treatment in UC are three fold-improve quality of life, achieve steroid free remission and minimize the risk of cancer. The choice of treatment depends on disease extent, severity and the course of the disease. For proctitis, topical 5-aminosalicylic acid (5-ASA) drugs are used as the first line agents. UC patients with more extensive or severe disease should be treated with a combination of oral and topical 5-ASA drugs +/- corticosteroids to induce remission. Patients with severe UC need to be hospitalized for treatment. The options in these patients include intravenous steroids and if refractory, calcineurin inhibitors (cyclosporine, tacrolimus) or tumor necrosis factor-α antibodies (infliximab) are utilized. Once remission is induced, patients are then continued on appropriate medications to maintain remission. Indications for emergency surgery include refractory toxic megacolon, colonic perforation, or severe colorectal bleeding.
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Dawood M, Tauseef A, Patel J. Cytomegalovirus infection in the setting of occult ulcerative colitis: case report and review of the literature. J Community Hosp Intern Med Perspect 2018; 8:382-385. [PMID: 30559952 PMCID: PMC6292355 DOI: 10.1080/20009666.2018.1554100] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Accepted: 11/19/2018] [Indexed: 02/08/2023] Open
Abstract
CMV can infect a variety of organs including gastrointestinal tract, meninges, eyes and other organs depending upon the nature of immune system but it can also manifest as a flare-up in ulcerative colitis patients. It usually presents as loose stools, bright red blood in the stool and weight loss in the patient. In the setting of an Immunocompetent patient, CMV colitis has been diagnosed in patients with occult inflammatory bowel disease. It is usually diagnosed on histology secondary to endoscopic biopsy. We herein report a case of a 73 years old female with CMV colitis found to have underlying ulcerative colitis.
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Affiliation(s)
- Mustafa Dawood
- Internal Medicine, Greater Baltimore Medical Centre, Towson, USA
| | - Abubakar Tauseef
- Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Janki Patel
- Internal Medicine, Greater Baltimore Medical Centre, Towson, USA
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Henmi Y, Kakimoto K, Inoue T, Nakazawa K, Kubota M, Hara A, Mikami T, Naka Y, Hirata Y, Hirata Y, Sakanaka T, Nouda S, Okada T, Kawakami K, Takeuchi T, Tominaga K, Higuchi K. Cytomegalovirus infection in ulcerative colitis assessed by quantitative polymerase chain reaction: risk factors and effects of immunosuppressants. J Clin Biochem Nutr 2018; 63:246-251. [PMID: 30487677 PMCID: PMC6252306 DOI: 10.3164/jcbn.18-14] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Accepted: 02/21/2018] [Indexed: 01/11/2023] Open
Abstract
We investigated the risk factors of and appropriate treatment for cytomegalovirus colitis in patients with ulcerative colitis, using quantitative polymerase chain reaction analysis to detect cytomegalovirus in the colonic mucosa. Between February 2013 and January 2017, patients with exacerbated ulcerative colitis who were admitted to our hospital were consecutively enrolled in this retrospective, single-center study. Patients were evaluated for cytomegalovirus using serology (antigenemia) and quantitative polymerase chain reaction analyses of the colonic mucosa, which were sampled during colonoscopy. Of 86 patients, 26 (30.2%) had positive quantitative polymerase chain reaction results for cytomegalovirus; only 4 were also positive for antigenemia. The ages of the cytomegalovirus DNA-positive patients were significantly higher than those of negative patients (p = 0.002). The mean endoscopic score of cytomegalovirus DNA-positive patients was significantly higher than that of cytomegalovirus DNA-negative patients. Treatment with combined immunosuppressants was associated with an increased risk of cytomegalovirus. Fourteen of 15 (93.3%) cytomegalovirus DNA-positive patients who were negative for antigenemia showed a clinical response to treatment with additional oral tacrolimus, without ganciclovir. cytomegalovirus reactivation in active ulcerative colitis is associated with age and combined immunosuppressant therapy. Because additional treatment with tacrolimus was effective, patients who are negative for antigenemia and cytomegalovirus DNA-positive colonic mucosa may recover without antiviral therapy.
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Affiliation(s)
- Yujiro Henmi
- 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
- *To whom correspondence should be addressed. E-mail:
| | - Kazuki Kakimoto
- 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
| | - Takuya Inoue
- 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
| | - Kei Nakazawa
- 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
| | - Minori Kubota
- 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
| | - Azusa Hara
- 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
| | - Takashi Mikami
- 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
| | - Yutaka Naka
- 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
| | - Yuki Hirata
- 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
| | - Yoshimasa Hirata
- 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
| | - Taisuke Sakanaka
- 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
| | - Sadaharu Nouda
- 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
| | - Toshihiko Okada
- 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
| | - Ken Kawakami
- 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
| | - Toshihisa Takeuchi
- 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
| | - Kazunari Tominaga
- 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
| | - Kazuhide Higuchi
- 2nd Department of Internal Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
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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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Ahmed I, Kassem W, Salam Y, Furnari M, Mehta T. Outcome of Cytomegalovirus Colitis in Inflammatory Bowel Disease with Different Regimes of Ganciclovir. Middle East J Dig Dis 2018; 10:220-229. [PMID: 31049169 PMCID: PMC6488501 DOI: 10.15171/mejdd.2018.114] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Accepted: 09/02/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) infection is common in individuals with inflammatory bowel disease (IBD) and is responsible for relapse, increased severity, and poor outcome if left untreated. Ganciclovir is the mainstay of treatment but data regarding its use, mode of administration, and duration of treatment is poorly described. We reviewed the practice of treating CMV colitis with different regimes of ganciclovir at a district NHS hospital to compare the clinical outcome. METHODS 35 patients with IBD and concurrent diagnosis of CMV infection were evaluated. The parameters studied were clinical outcome in term of clinical response, length of hospital stay, readmission, or colectomy with three different regimes of ganciclovir, in addition to treatment for IBD. RESULTS 35 patients with IBD (ulcerative colitis = 23, Crohn's disease = 5, Indeterminate colitis = 7) and positive diagnosis of CMV infection were studied. Clinical outcome with two weeks of intravenous (IV) ganciclovir regime was superior than one week of IV ganciclovir and two weeks of oral Valganciclovir in term of clinical response on day 15 (95.8% vs 74%, 24.3%, respectively p = 0.45) and colectomy rate within 3 months (6.25% vs 27.3%, vs 25%, respectively). CONCLUSION CMV colitis is associated with poor outcome in patient with IBD if left untreated. 2 weeks IV ganciclovir was associated with a better outcome than 1 week of IV treatment or oral treatment.
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Affiliation(s)
- Iftikhar Ahmed
- School of Medicine, University of Southampton, UK
- Department of Medicine, Aldara Hospital and Medical Centre, Riyadh, KSA
| | - Wael Kassem
- Department of Medicine, Aldara Hospital and Medical Centre, Riyadh, KSA
| | - Yazen Salam
- School of Medicine, Alfaisal University, Riyadh, KSA
| | | | - Tina Mehta
- Department of Gastroenterology, Royal United Hospital Bath, UK
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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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Levin A, Yaari S, Stoff R, Caplan O, Wolf DG, Israeli E. Diagnosis of Cytomegalovirus Infection during Exacerbation of Ulcerative Colitis. Digestion 2018; 96:142-148. [PMID: 28848127 DOI: 10.1159/000479865] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 07/27/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND/AIMS The role of cytomegalovirus (CMV) reactivation during exacerbations of ulcerative colitis (UC) is yet a matter of debate, and assessment of CMV infection in UC patients remains an ongoing challenge. We aimed to identify associated parameters and compare detection methods for CMV infection during UC exacerbation. METHODS Clinical, pathological and virological parameters were retrospectively analyzed in all patients hospitalized in our institution for UC exacerbation between January 2009 and April 2015, who underwent full evaluation for CMV infection in colonic tissue by histopathology, immunohistochemistry (IHC) and CMV-PCR. RESULTS Of 28 patients who underwent full examination for tissue CMV-infection, 13 (46.4%) were found to be positive for CMV. Tissue CMV-PCR was more sensitive for the detection of CMV infection than histopathology and IHC. CMV-positive patients had a statistically higher frequency of recent steroid treatment and fever, with higher mean partial Mayo scores and lower mean albumin levels. There were no significant differences between CMV-positive and CMV-negative patients in terms of age, severity of colitis and disease duration. In a multivariable model, only recent steroid treatment and fever were independently associated with colonic CMV infection. CONCLUSIONS This study provides a clinical model to detect the presence of CMV infection in patients hospitalized with UC exacerbation, which could direct proper investigation and facilitate timely empirical therapy.
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Affiliation(s)
- Avi Levin
- Strang Laboratory of Apoptosis and Cancer Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA
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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: 12] [Impact Index Per Article: 1.7] [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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Hosomi S, Watanabe K, Nishida Y, Yamagami H, Yukawa T, Otani K, Nagami Y, Tanaka F, Taira K, Kamata N, Tanigawa T, Shiba M, Watanabe T, Nagahara H, Maeda K, Fujiwara Y. Combined Infection of Human Herpes Viruses: A Risk Factor for Subsequent Colectomy in Ulcerative Colitis. Inflamm Bowel Dis 2018; 24:1307-1315. [PMID: 29668948 DOI: 10.1093/ibd/izy005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Little is known about the prevalence and pathogenicity of human herpes viruses except for cytomegalovirus (CMV) in patients with inflammatory bowel disease (IBD). The aim of this study was to determine the prevalence of human herpes viruses on colonic mucosa in patients with IBD and assess the long-term outcomes in these patients. METHODS We examined the colonic mucosal specimens from 66 patients with ulcerative colitis (UC), 54 patients with Crohn's disease (CD), and 29 healthy patients to identify the 6 most common types of human herpes virus, using multiplex polymerase chain reaction (PCR) technique. RESULTS Herpes simplex virus (HSV)-1/2 and varicella-zoster virus (VZV) were not detected in any of the groups. There was a higher prevalence of Epstein-Barr virus (EBV) (21.2%) and CMV (15.1%) in patients with UC than in patients with CD (EBV 9.3%, CMV 0%) and patents in the healthy control group (EBV 0%, CMV 3.4%). The prevalence of human herpes virus (HHV)-6A/B and HHV-7 was not statistically different among the groups. Five UC patients with inflammation had coexisting CMV and EBV or HHV-6. The combined infection of CMV with EBV or HHV-6 was a significant and independent prognostic factor for subsequent colectomy in patients with UC. CONCLUSIONS The increased prevalence of CMV coexisting with EBV/HHV-6 infection was associated with the clinical course in patients with UC. 10.1093/ibd/izy005_video1izy005_Video_15786489376001.
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Affiliation(s)
- Shuhei Hosomi
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kenji Watanabe
- Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Hyogo, Japan
| | - Yu Nishida
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hirokazu Yamagami
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Tomomi Yukawa
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Koji Otani
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yasuaki Nagami
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Fumio Tanaka
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Koichi Taira
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Noriko Kamata
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Tetsuya Tanigawa
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Masatsugu Shiba
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Toshio Watanabe
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hisashi Nagahara
- Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kiyoshi Maeda
- Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yasuhiro Fujiwara
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
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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: 9] [Impact Index Per Article: 1.3] [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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Grossberg LB, Ezaz G, Grunwald D, Cohen J, Falchuk KR, Feuerstein JD. A National Survey of the Prevalence and Impact of Cytomegalovirus Infection Among Hospitalized Patients With Ulcerative Colitis. J Clin Gastroenterol 2018; 52:241-245. [PMID: 27811628 DOI: 10.1097/mcg.0000000000000736] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
GOALS To estimate the effect of cytomegalovirus (CMV) in patients with ulcerative colitis (UC), and compare these outcomes to patients with CMV without UC. BACKGROUND The impact of CMV infection in UC is not well understood. STUDY We analyzed records from the Nationwide Inpatient Sample (NIS) of patients with UC and CMV between 2006 and 2012. Differences in outcomes were determined between patients with UC and CMV and those with UC without CMV. Secondary analysis compared outcomes of patients with UC and CMV to patients with CMV alone. RESULTS Patients with UC and CMV (n=145) had longer length of stay (16.31 vs. 5.52 d, P<0.0001), higher total charges ($111,835.50 vs. $39.895, P=0.001), and were less likely to be discharged home without services (50.0% vs. 81.83%, P<0.0001) compared with patients with UC without CMV (n=32,290). On regression analysis, CMV was significantly associated with higher total charges (P<0.01) and longer length of stay (P<0.01), but not for increased need for colorectal surgery. When comparing patients with UC and CMV to patients with CMV alone (n=14,960), patients with CMV alone had a higher Charlson Comorbidity Index and a trend toward higher in-hospital mortality. CONCLUSIONS CMV infection in hospitalized patients with UC is associated with a longer length of stay, increased total charges, and fewer routine discharges, but not increased surgery or mortality. Patients with CMV alone had the worst outcomes of all groups suggesting that CMV in UC patients may not have the same negative impact as in other diseases.
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Affiliation(s)
- Laurie B Grossberg
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA
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Cohen S, Martinez-Vinson C, Aloi M, Turner D, Assa A, de Ridder L, Wolters VM, de Meij T, Alvisi P, Bronsky J, Kopylov U. Cytomegalovirus Infection in Pediatric Severe Ulcerative Colitis-A Multicenter Study from the Pediatric Inflammatory Bowel Disease Porto Group of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. Pediatr Infect Dis J 2018; 37:197-201. [PMID: 29424814 DOI: 10.1097/inf.0000000000001724] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Data on the clinical course and outcomes of pediatric patients with cytomegalovirus (CMV) infection complicating acute severe ulcerative colitis (ASC) are very limited. The aim of our study was to compare outcomes of children with ASC who were CMV positive or CMV negative. METHODS This was a multicenter retrospective case-controlled study, from centers affiliated with the Pediatric Inflammatory Bowel Disease Porto Group of European Society of Pediatric Gastroenterology, Hepatology, and Nutrition. We included CMV-positive children hospitalized for ASC and compared their colectomy rate during hospitalization and up to 1 year thereafter, matched with CMV-negative controls. RESULTS A total of 56 children were included; 15 CMV positive and 41 CMV negative. More CMV-positive patients were resistant to intravenous corticosteroids as compared with CMV negative (93% and 56% respectively, P = 0.009). Fourteen of the CMV-positive children (93%) were treated with ganciclovir [5/14 (36%) with 5 mg/kg and 9/14 (64%) with 10 mg/kg]. During hospitalization, 3 (20%) CMV-positive and 3 (7.8%) CMV-negative patients required colectomy (P = 0.17). By 12 months, 5 (33%) and 5 (13%) CMV-positive and CMV-negative patients required colectomy, respectively (P = 0.049); the significance was not retained on multivariate analysis. CONCLUSIONS A higher prevalence of CMVpositivity was found in pediatric ulcerative colitis patients who required colectomy within 12 months of hospitalization for ASC. Further studies are needed to clarify the impact of CMV infection on the outcome of acute severe colitis in pediatric patients.
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Lv YL, Han FF, Jia YJ, Wan ZR, Gong LL, Liu H, Liu LH. Is cytomegalovirus infection related to inflammatory bowel disease, especially steroid-resistant inflammatory bowel disease? A meta-analysis. Infect Drug Resist 2017; 10:511-519. [PMID: 29276397 PMCID: PMC5733908 DOI: 10.2147/idr.s149784] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Human cytomegalovirus (HCMV) infection has been associated with inflammatory bowel disease (IBD). Numerous studies have been conducted to analyze the association between HCMV infection and risk of IBD and steroid-resistant IBD, but no clear consensus had been reached. OBJECTIVES The aim of this study was to confirm this relationship precisely by doing a systematic review and meta-analysis. STUDY DESIGN We identified relevant studies through a search of PubMed and Embase. Studies were eligible for inclusion if they 1) evaluated the association between HCMV infection and IBD disease; 2) evaluated the association between HCMV infection and steroid-resistant IBD disease; 3) were case-control studies or nested case-control studies; 4) provided the numbers (or percentage) of positivity for HCMV infection in cases and controls, respectively. Data were extracted and analyzed independently by two investigators. RESULTS AND CONCLUSION A total of 18 studies including 1,168 patients and 951 health groups was identified, and HCMV infection was distinctly confirmed as a risk factor for the occurrence and development of IBD. When involving 17 studies including 1,306 IBD patients, a total of 52.9% of patients in the cytomegalovirus (CMV)-positive groups were observed to have steroid resistance, compared with 30.2% of patients in the CMV-negative groups. There was a significant difference in the risk of steroid resistance between people exposed to HCMV infection and those not exposed HCMV infection in IBD patients. This meta-analysis suggested that HCMV infection is associated with an increased risk for IBD and steroid-resistant IBD.
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Affiliation(s)
- Ya-li Lv
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Fei-fei Han
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Yang-jie Jia
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Zi-rui Wan
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Li-li Gong
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - He Liu
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Li-hong Liu
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
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Kopylov U, Papamichael K, Katsanos K, Waterman M, Bar-Gil Shitrit A, Boysen T, Portela F, Peixoto A, Szilagyi A, Silva M, Maconi G, Har-Noy O, Bossuyt P, Mantzaris G, Barreiro de Acosta M, Chaparro M, Christodoulou DK, Eliakim R, Rahier JF, Magro F, Drobne D, Ferrante M, Sonnenberg E, Siegmund B, Muls V, Thurm T, Yanai H, Dotan I, Raine T, Levin A, Israeli E, Ghalim F, Carbonnel F, Vermeire S, Ben-Horin S, Roblin X. Impact of Infliximab and Cyclosporine on the Risk of Colectomy in Hospitalized Patients with Ulcerative Colitis Complicated by Cytomegalovirus-A Multicenter Retrospective Study. Inflamm Bowel Dis 2017; 23:1605-1613. [PMID: 28590343 DOI: 10.1097/mib.0000000000001160] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) is frequently detected in patients with ulcerative colitis (UC). The impact of CMV infection on the outcome of UC exacerbation remains unclear. The benefit of combining antiviral with anti-inflammatory treatment has not been evaluated yet. The aim of this study was to compare the outcome of CMV-positive hospitalized patients with UC treated with antiviral therapy either alone or combined with salvage anti-inflammatory therapy (infliximab [IFX] or cyclosporine A [CsA]). METHODS This was a multicenter retrospective study of hospitalized CMV-positive patients with UC. The patients were classified into 2 groups: antiviral-if treated with antivirals alone; combined-if treated with both antiviral and anti-inflammatory therapy. The outcomes included the rate of colectomy in both arms during the course of hospitalization and after 3/12 months. RESULTS A total of 110 patients were included; 47 (42.7%) patients did not receive IFX nor CsA; 36 (32.7%) received IFX during hospitalization or within 1 month before hospitalization; 20 (18.1%) patients received CsA during hospitalization; 7 (6.4%) were exposed to both IFX and CsA. The rate of colectomy was 14.5% at 30 days, 20.0% at 3 months, and 34.8% at 12 months. Colectomy rates were similar across treatment groups. No clinical and demographic variables were independently associated with the risk of colectomy. CONCLUSIONS IFX or cyclosporine therapy is not associated with additional risk for colectomy over antiviral therapy alone in hospitalized CMV-positive patients with UC.
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Affiliation(s)
- Uri Kopylov
- 1Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; 2Department of Gastroenterology, Evaggelismos Hospital, Athens, Greece; 3Department of Clinical and Experimental Medicine, KU Leuven, Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven, Belgium; 4Department of Gastroenterology, University Hospital of Ioannina, Ioannina, Greece; 5Department of Gastroenterology, Rambam Health Care Campus, B. Rappaport Faculty of Medicine, the Technion, Haifa, Israel; 6Shaare Zedek Medical Center, Digestive Diseases Institute, Jerusalem, Israel; 7Department of Gastroenterology, Herlev University Hospital, Herlev, Denmark; 8Department of Gastroenterology, Hospital Universidade Coimbra, Coimbra, Portugal; 9Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal; 10Department of Gastroenterology, Jewish General Hospital, Montreal, Québec, Canada; 11Department of Gastroenterology, Luigi Sacco' University Hospital, Milan, Italy; 12Department of Gastroenterology, Imelda GI Clinical Research Center, Bonheiden, Belgium; 13IBD Unit, Gastroenterology Department, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain; 14Department of Gastroenterology, Hospital Universitario de La Princesa, Madrid, Spain; 15Department of Gastroenterology, CHU Dinant Godinne, UCL Namur, Yvoir, Belgium; 16Department of Gastroenterology, University Medical Centre Ljubljana, Slovenia; 17Department of Medicine (Gastroenterology, Infectious Diseases, Rheumatology), Charité-Universitätsmedizin Berlin, Berlin, Germany; 18Department of Gastroenterology and Hepatology, CHU Saint-Pierre, Université Libre de Bruxelles, Brussels, Belgium; 19Department of Gastroenterology and Liver Diseases, IBD Center, Tel Aviv Sourasky Medical Center, Affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel; 20Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; 21Department of Gastroenterology, Hadassah Medical Center, Jerusalem, Israel; 22Service de Gastroentérologie, Hôpital Universitaire de Bicêtre, Université Paris Sud, Assistance Publique-Hôpitaux de Paris, le Kremlin Bicêtre, Paris, France; and 23Department of Gastroenterology, CHU de Saint-Etienne, Saint Etiennne, France
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Harbord M, Eliakim R, Bettenworth D, Karmiris K, Katsanos K, Kopylov U, Kucharzik T, Molnár T, Raine T, Sebastian S, de Sousa HT, Dignass A, Carbonnel F. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 2: Current Management. J Crohns Colitis 2017; 11:769-784. [PMID: 28513805 DOI: 10.1093/ecco-jcc/jjx009] [Citation(s) in RCA: 850] [Impact Index Per Article: 106.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Marcus Harbord
- Imperial College London, and Chelsea and Westminster Hospital, London, UK
| | - Rami Eliakim
- Department of Gastroenterology and Hepatology, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | | | - Konstantinos Karmiris
- Department of Gastroenterology, Venizeleio General Hospital, Heraklion, Crete, Greece
| | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Ioannina, Greece
| | - Uri Kopylov
- Department of Gastroenterology, Tel-Hashomer Sheba Medical Center, and Sackler School of Medicine, Tel Aviv University, Israel
| | - Torsten Kucharzik
- Department of Internal Medicine and Gastroenterology, Hospital Lüneburg, Lüneburg, Germany
| | - Tamás Molnár
- First Department of Medicine, University of Szeged, Szeged, Hungary
| | - Tim Raine
- Department of Medicine, University of Cambridge, Cambridge, UK
| | | | - Helena Tavares de Sousa
- Gastroenterology Department, Algarve Hospital Center; Biomedical Sciences & Medicine Department, University of Algarve, Faro, Portugal
| | - Axel Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Frankfurt/Main, Germany
| | - Franck Carbonnel
- Department of Gastroenterology, CHU Bicêtre, Université Paris Sud, Paris, France
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Kang SH, Lee KM, Shin SJ, Lim SK, Hwang JC, Kim JH. Cytomegalovirus Gastric Ulcer Complicated with Pyloric Obstruction in a Patient with Ulcerative Colitis. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2017. [PMID: 28637105 DOI: 10.4166/kjg.2017.69.6.359] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
In patients with inflammatory bowel disease (IBD), cytomegalovirus (CMV) infections could aggravate the course of IBD but it is difficult to distinguish CMV infection from IBD exacerbation endoscopically. Usually, CMV tends to localize to the colon and other organic involvements were reported very rare in the IBD patients. Herein, we report a case that CMV gastric ulcer complicated with pyloric obstruction in a patient with ulcerative colitis during ganciclovir therapy, which was resolved by surgical gastrojejunostomy with review of literature.
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Affiliation(s)
- Sung Hwan Kang
- Division of Gastroenterology, Department of Internal Medicine, Sungae Hospital, Seoul, Korea
| | - Kee Myung Lee
- Division of Gastroenterology, Department of Internal Medicine, Ajou University School of Medicine, Suwon, Korea
| | - Sung Jae Shin
- Division of Gastroenterology, Department of Internal Medicine, Ajou University School of Medicine, Suwon, Korea
| | - Sun Kyo Lim
- Division of Gastroenterology, Department of Internal Medicine, Ajou University School of Medicine, Suwon, Korea
| | - Jae Chul Hwang
- Division of Gastroenterology, Department of Internal Medicine, Ajou University School of Medicine, Suwon, Korea
| | - Jin Hong Kim
- Division of Gastroenterology, Department of Internal Medicine, Ajou University School of Medicine, Suwon, Korea
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Umar S, Clarke K, Bilimoria F, Bilal M, Singh S, Silverman J. Diagnostic yield from colon biopsies in patients with inflammatory bowel disease and suspected cytomegalovirus infection: is it worth it? Ann Gastroenterol 2017; 30:429-432. [PMID: 28655979 PMCID: PMC5479995 DOI: 10.20524/aog.2017.0153] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2017] [Accepted: 04/21/2017] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Patients with inflammatory bowel disease (IBD) are often immunosuppressed and are at risk for reactivation of latent cytomegalovirus (CMV) infection. We examined the diagnostic yield from colon biopsies in IBD patients with suspected CMV infection. METHODS Patients above 18 years of age who underwent testing for CMV on colon biopsies between January 1st, 2012, and December 31st, 2015, were identified from a pathology data base. A positive CMV result was included only if testing included both hematoxylin/eosin staining and immunohistochemistry from two or more biopsy samples. RESULTS One hundred twenty-five patients met the inclusion criteria. Of these, 99 had a diagnosis of IBD: 30 with Crohn's disease, 63 with ulcerative colitis, and 6 with indeterminate colitis. As regards treatment, 21.2% of the patients had biologic therapy alone, 13.1% received immunomodulators, and 11.1% were treated with combined biologic and immunomodulator therapy within 3 months of the colon biopsy. In addition, 32.3% of the patients were on steroids. Of the 99 IBD patients, only 1 had biopsy-proven CMV colitis. CONCLUSION The yield from colon biopsies with hematoxylin/eosin staining and immunohistochemistry to test for CMV in IBD flare is very low. Further multicenter studies with large numbers of patients are needed to compare all testing modalities in the same cohort of patients. This may help identify which subgroup of IBD patients are likely to benefit from specific modalities of CMV testing, with potential cost-saving implications.
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Affiliation(s)
- Shifa Umar
- Department of Internal Medicine (Shifa Umar)
| | - Kofi Clarke
- Division of Gastroenterology, Hepatology and Nutrition (Kofi Clarke, Shailendra Singh)
| | - Farshaad Bilimoria
- Department of Pathology (Farshaad Bilimoria, Jan Silverman), Allegheny Health Network, Pittsburgh, PA
| | - Mohammad Bilal
- Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX (Mohammad Bilal), USA
| | - Shailendra Singh
- Division of Gastroenterology, Hepatology and Nutrition (Kofi Clarke, Shailendra Singh)
| | - Jan Silverman
- Department of Pathology (Farshaad Bilimoria, Jan Silverman), Allegheny Health Network, Pittsburgh, PA
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Park SC, Jeen YM, Jeen YT. Approach to cytomegalovirus infections in patients with ulcerative colitis. Korean J Intern Med 2017; 32:383-392. [PMID: 28490715 PMCID: PMC5432807 DOI: 10.3904/kjim.2017.087] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 03/06/2017] [Indexed: 12/16/2022] Open
Abstract
Cytomegalovirus (CMV) reactivation is common in patients with severe ulcerative colitis (UC), and may ref lect exacerbation of mucosal inf lammation and/or administration of immunosuppressants. The question of whether CMV is an active pathogen or 'an innocent bystander' in the exacerbation of UC remains controversial. Patients with UC exacerbated by reactivated CMV experience worse prognoses than those without CMV reactivation and antiviral therapy significantly reduces the need for colectomy in patients with severe UC and high-grade CMV infection, indicating that CMV plays a role in UC prognosis. Therefore, the CMV status of patients on immunosuppressants, particularly those with steroid-refractory or -dependent UC, should be tested. When CMV is detected, be performed based on should adequate treatment the extent of the viral load and the presence of certain clinical features including a large ulcer. Anti-tumor necrosis factor agents may be useful for treating CMV colitis complicating UC.
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Affiliation(s)
- Sung Chul Park
- Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Korea
| | - Yoon Mi Jeen
- Department of Pathology, Soon Chun Hyang University Seoul Hospital, Seoul, Korea
- Correspondence to Yoon Mi Jeen, M.D. Department of Pathology, Soon Chun Hyang University Seoul Hospital, 59 Daesagwan-ro, Yongsan-gu, Seoul 04401, Korea Tel: +82-2-709-9435 Fax: +82-2-709-9441 E-mail:
| | - Yoon Tae Jeen
- Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea
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