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1
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Singh G, Rentsch C, Beattie W, Christensen B, Macrae F, Segal JP. Long-Term Follow Up of Patients Treated for Inflammatory Bowel Disease and Cytomegalovirus Colitis. Diagnostics (Basel) 2024; 14:2030. [PMID: 39335709 PMCID: PMC11431378 DOI: 10.3390/diagnostics14182030] [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: 07/22/2024] [Revised: 09/04/2024] [Accepted: 09/11/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND Pathological reactivation of latent Cytomegalovirus (CMV) is triggered by inflammation and immunosuppression; both present in the pathogenesis and treatment of Inflammatory Bowel Disease (IBD). Whether CMV reactivation is associated with escalating medical therapy, further hospital admissions, or worse clinical outcomes remains controversial. This study aimed to follow up IBD patients with an index episode of CMV colitis and analyse the clinical outcomes. METHODS A retrospective study of patients with IBD treated for CMV colitis was completed. The outcome results were collected at 6-month and 12-month time points after the first episode of CMV colitis. A total of 13 patients with Ulcerative Colitis and 1 with Crohn's Disease were included. RESULTS CMV colitis recurrence occurred in 29% of patients at 12 months. A total of 43% of patients had changed their biologic dose at 6 months and 29% had escalated their biologic dose at 12 months. At 12 months, 36% of patients had been re-hospitalised, including three colectomies. Disease remission was only achieved by 29% of patients at 12 months. CONCLUSIONS IBD patients with CMV colitis have substantial rates of re-hospitalisation, failed medical therapy, and colectomy. These risks may be greater at <6 months from an index episode of CMV colitis.
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Affiliation(s)
- Gurtej Singh
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville 3052, Australia
| | - Clarissa Rentsch
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville 3052, Australia
| | - William Beattie
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville 3052, Australia
- Department of Gastroenterology, University Hospital Geelong, Geelong 3220, Australia
| | - Britt Christensen
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville 3052, Australia
- Department of Medicine, The University of Melbourne, Parkville 3010, Australia
| | - Finlay Macrae
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville 3052, Australia
- Department of Medicine, The University of Melbourne, Parkville 3010, Australia
| | - Jonathan P. Segal
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville 3052, Australia
- Department of Medicine, The University of Melbourne, Parkville 3010, Australia
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2
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Chen Y, Zheng Q, Wang H, Tang P, Deng L, Li P, Li H, Hou J, Li J, Wang L, Peng J. Integrating transcriptomics and proteomics to analyze the immune microenvironment of cytomegalovirus associated ulcerative colitis and identify relevant biomarkers. BioData Min 2024; 17:26. [PMID: 39192288 DOI: 10.1186/s13040-024-00382-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 08/22/2024] [Indexed: 08/29/2024] Open
Abstract
BACKGROUND In recent years, significant morbidity and mortality in patients with severe inflammatory bowel disease (IBD) and cytomegalovirus (CMV) have drawn considerable attention to the status of CMV infection in the intestinal mucosa of IBD patients and its role in disease progression. However, there is currently no high-throughput sequencing data for ulcerative colitis patients with CMV infection (CMV + UC), and the immune microenvironment in CMV + UC patients have yet to be explored. METHOD The xCell algorithm was used for evaluate the immune microenvironment of CMV + UC patients. Then, WGCNA analysis was explored to obtain the co-expression modules between abnormal immune cells and gene level or protein level. Next, three machine learning approach include Random Forest, SVM-rfe, and Lasso were used to filter candidate biomarkers. Finally, Best Subset Selection algorithms was performed to construct the diagnostic model. RESULTS In this study, we performed transcriptomic and proteomic sequencing on CMV + UC patients to establish a comprehensive immune microenvironment profile and found 11 specific abnormal immune cells in CMV + UC group. After using multi-omics integration algorithms, we identified seven co-expression gene modules and five co-expression protein modules. Subsequently, we utilized various machine learning algorithms to identify key biomarkers with diagnostic efficacy and constructed an early diagnostic model. We identified a total of eight biomarkers (PPP1R12B, CIRBP, CSNK2A2, DNAJB11, PIK3R4, RRBP1, STX5, TMEM214) that play crucial roles in the immune microenvironment of CMV + UC and exhibit superior diagnostic performance for CMV + UC. CONCLUSION This 8 biomarkers model offers a new paradigm for the diagnosis and treatment of IBD patients post-CMV infection. Further research into this model will be significant for understanding the changes in the host immune microenvironment following CMV infection.
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Affiliation(s)
- Yang Chen
- Yunnan Provincial Laboratory of Clinical Virology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China
- Department of Pathology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, China
| | - Qingqing Zheng
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China
- Department of Pathology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, China
| | - Hui Wang
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China
- Department of Pathology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, China
| | - Peiren Tang
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China
- Department of Pathology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, China
| | - Li Deng
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China
- Department of Pathology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, China
| | - Pu Li
- Department of General Practice, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China
| | - Huan Li
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China
- Department of Pathology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, China
| | - Jianhong Hou
- Department of Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China.
| | - Jie Li
- Academy of Biomedical Engineering, Kunming Medical University, Kunming, Yunnan, 650500, China.
| | - Li Wang
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China.
- Department of Pathology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, China.
| | - Jun Peng
- Department of Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China.
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3
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Alhalabi M, Alziadan SM. A diagnostic dilemma: cytomegalovirus colitis as an uncommon comorbidity in inflammatory bowel disease: a case report. Virol J 2024; 21:188. [PMID: 39152468 PMCID: PMC11330031 DOI: 10.1186/s12985-024-02467-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Accepted: 08/13/2024] [Indexed: 08/19/2024] Open
Abstract
BACKGROUND The role of cytomegalovirus infection as an opportunistic pathogen in exacerbating ulcerative colitis and its response to treatment remain a topic of ongoing debate. Clinicians encounter numerous challenges, including the criteria for differentiating between an acute ulcerative colitis flare and true cytomegalovirus colitis, the diagnostic tests for identifying cytomegalovirus colitis, and determining the appropriate timing for initiating antiviral therapy. CASE PRESENTATION A 28-year-old Syrian female with a seven-year history of pancolitis presented with worsening bloody diarrhea, abdominal pain, and tenesmus despite ongoing treatment with azathioprine, mesalazine, and prednisolone. She experienced a new flare of acute severe ulcerative colitis despite recently completing two induction doses of infliximab (5 mg/kg) initiated four weeks prior for moderate-to-severe ulcerative colitis. She had no prior surgical history. Her symptoms included watery, bloody diarrhea occurring nine to ten times per day, abdominal pain, and tenesmus. Initial laboratory tests indicated anemia, leukocytosis, elevated C-reactive protein (CRP) and fecal calprotectin levels, and positive CMV IgG. Stool cultures, Clostridium difficile toxin, testing for Escherichia coli and Cryptosporidium, and microscopy for ova and parasites were all negative. Sigmoidoscopy revealed numerous prominent erythematous area with spontaneous bleeding. Biopsies demonstrated CMV inclusions confirmed by immunohistochemistry, although prior biopsies were negative. We tapered prednisolone and azathioprine and initiated ganciclovir at 5 mg/kg for ten days, followed by valganciclovir at 450 mg twice daily for three weeks. After one month, she showed marked improvement, with CRP and fecal calprotectin levels returning to normal. She scored one point on the partial Mayo score. The third induction dose of infliximab was administered on schedule, and azathioprine was resumed. CONCLUSION Concurrent cytomegalovirus infection in patients with inflammatory bowel disease presents a significant clinical challenge due to its associated morbidity and mortality. Diagnosing and managing this condition is particularly difficult, especially regarding the initiation or continuation of immunosuppressive therapies.
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Affiliation(s)
- Marouf Alhalabi
- Gastroenterology Department, Damascus Hospital, Almujtahed Street, Damascus, Syria.
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Onisor D, Brusnic O, Mocan S, Stoian M, Avram C, Boicean A, Dobru D. Cytomegalovirus in Ulcerative Colitis: An Unwanted "Guest". Pathogens 2024; 13:650. [PMID: 39204250 PMCID: PMC11356953 DOI: 10.3390/pathogens13080650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Revised: 07/23/2024] [Accepted: 07/30/2024] [Indexed: 09/03/2024] Open
Abstract
The role of cytomegalovirus (CMV) in the flare-up of ulcerative colitis (UC) is not clearly understood. CMV can cause similar symptoms in different clinical contexts, which may be attributed to the natural evolution of the viral infection, the patient's immune status, or its association with inflammatory bowel disease (IBD). This study aims to delineate the diverse manifestations of CMV-related lesions from clinical, endoscopic, and histopathological perspectives, alongside a brief narrative review of the literature. In managing IBD patients, it is crucial to be vigilant for signs of CMV reactivation, especially before the initiation of more intensive therapies.
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Affiliation(s)
- Danusia Onisor
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540139 Targu Mures, Romania; (D.O.); (D.D.)
- Gastroenterology Department, Mureș County Clinical Hospital, 540103 Targu Mures, Romania
| | - Olga Brusnic
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540139 Targu Mures, Romania; (D.O.); (D.D.)
- Gastroenterology Department, Mureș County Clinical Hospital, 540103 Targu Mures, Romania
| | - Simona Mocan
- Pathology Department, Emergency County Hospital, 540136 Targu Mures, Romania;
| | - Mircea Stoian
- Department of Anesthesiology and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania;
| | - Calin Avram
- Department of Medical Informatics and Biostatistics, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540139 Targu Mures, Romania
| | - Adrian Boicean
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania;
| | - Daniela Dobru
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540139 Targu Mures, Romania; (D.O.); (D.D.)
- Gastroenterology Department, Mureș County Clinical Hospital, 540103 Targu Mures, Romania
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5
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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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6
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Nguyen P, Shrestha A, Sane N, Abeywickrama D, Holt DQ, Bell S, Moore G, Goldberg R. Colonic cytomegalovirus DNA detection by polymerase chain reaction does not influence outcomes in inflammatory bowel disease and immunosuppressed cohorts. Intern Med J 2024; 54:283-289. [PMID: 37461367 DOI: 10.1111/imj.16176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 06/22/2023] [Indexed: 02/15/2024]
Abstract
BACKGROUND AND AIM Cytomegalovirus (CMV) colitis is associated with negative outcomes in inflammatory bowel disease (IBD) and immunosuppressed cohorts and therefore requires timely recognition for appropriate management. We aimed to evaluate the diagnostic tools for CMV colitis and their associations with clinical outcomes. METHODS A retrospective cohort study of patients in a metropolitan health service with colonic samples analysed for CMV between 2012 and 2022, stratified into IBD and non-IBD groups, was performed. The main outcome measures were the prevalence of positive and negative results for each CMV test, as well as need for colectomy, use of antiviral and hospital length of stay. RESULTS Five hundred eighty-two biopsies from 418 patients were included; the median age was 36 years (interquartile range, 24-52 years) and 223 (53.3%) were men. Four hundred sixty-one (79.2%) biopsies were from patients with IBD and 121 (20.8%) were from those without IBD. There were similar proportions of positive CMV histology (IBD 5.9% and non-IBD 7.4%) and tissue CMV polymerase chain reaction (PCR) in the two groups (IBD 5.6% and non-IBD 5.0%), but within each group, results were discordant. Positive CMV histology was significantly associated with need for colectomy in the IBD group, while positive tissue CMV PCR was not. Positive CMV histology, and tissue and serum CMV PCR were all significantly associated with antiviral use. Positive serum CMV PCR was significantly associated with colectomy. CONCLUSIONS Histopathology remains the most predictive tool in assessing CMV colitis, while qualitative tissue CMV PCR was found to have limited utility. Quantitative serum CMV PCR may be useful but requires further evaluation.
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Affiliation(s)
- Paul Nguyen
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Atul Shrestha
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia
| | - Nikhita Sane
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Dilini Abeywickrama
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Darcy Q Holt
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
- Department of Medicine, Monash University, Melbourne, Victoria, Australia
| | - Sally Bell
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
- Department of Medicine, Monash University, Melbourne, Victoria, Australia
| | - Gregory Moore
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
- Department of Medicine, Monash University, Melbourne, Victoria, Australia
| | - Rimma Goldberg
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia
- Department of Medicine, Monash University, Melbourne, Victoria, Australia
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7
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Salehi M, Shafiee N, Moradi M. Cytomegalovirus colitis in immunocompetent hosts: A case report and literature review. Clin Case Rep 2024; 12:e8435. [PMID: 38197061 PMCID: PMC10774537 DOI: 10.1002/ccr3.8435] [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: 11/15/2023] [Revised: 12/18/2023] [Accepted: 12/21/2023] [Indexed: 01/11/2024] Open
Abstract
Key Clinical Message Rectal bleeding can manifest cytomegalovirus (CMV) colitis even in immunocompetent patients, which can be cured with ganciclovir treatment. Abstract Cytomegalovirus (CMV) is an opportunistic virus widely affecting immunocompromised patients. Different manifestations varied from asymptomatic in immunocompetent individuals to end organ involvement, such as colitis in those with immunodeficiency. Despite the rarity of CMV colitis in immunocompetent hosts, we should consider it when the other conditions have been excluded. In this article, we have described a case of CMV colitis in an immunocompetent host and have performed a literature review on this entity. An immunocompetent 70-year-old female was admitted to the hospital with recurrent rectal bleeding. After various evaluations including laboratory analysis, stool examination, and colonoscopy, we have detected superficial lesions. Pathology and polymerase chain reaction reports favored CMV involvement. Her condition continues to improve after intravenous ganciclovir infusion. Rectal bleeding can manifest CMV colitis even in immunocompetent patients, which can be cured with ganciclovir treatment.
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Affiliation(s)
- Mohammadreza Salehi
- Department of Infectious DiseasesImam Khomeini Hospital, Tehran University of Medical SciencesTehranIran
| | - Nahid Shafiee
- Department of Infectious DiseasesImam Khomeini Hospital, Tehran University of Medical SciencesTehranIran
| | - Maryam Moradi
- Eye Research Center, The Five Senses Health InstituteRassoul Akram Hospital, Iran University of Medical SciencesTehranIran
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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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9
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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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10
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Alotaibi Y, AlLehibi A, Almtawa A, Alotaibi N, Alghamdi A, Alrajhi S, AlQutub A, AlEid A, Alamr A, Ibrahim BA, Alahmari M, Alhamidi H, Ahmad S, Alshammari F, Almotawa F, Altannir Y, Alghamdi A. Prevalence and Risk Factors of Cytomegalovirus Colitis in Inflammatory Bowel Disease Patients in Riyadh, Saudi Arabia: A Tertiary Center Experience. SAUDI JOURNAL OF MEDICINE & MEDICAL SCIENCES 2023; 11:305-313. [PMID: 37970458 PMCID: PMC10634466 DOI: 10.4103/sjmms.sjmms_175_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 08/14/2023] [Accepted: 08/27/2023] [Indexed: 11/17/2023]
Abstract
Background Patients with inflammatory bowel disease (IBD) are at a higher risk of cytomegalovirus (CMV) colitis because of their immunocompromised status. There are no studies from Saudi Arabia regarding the prevalence of CMV colitis in patients with IBD. Objective To determine the prevalence, characteristics, and risk factors of CMV colitis in patients with IBD in Riyadh, Saudi Arabia. Materials and Methods This retrospective study included patients with a confirmed diagnosis of IBD (aged 14-75 years) who were followed up at King Fahad Medical City, a referral care center in Riyadh, between January 2016 and December 2021; patients with indeterminate colitis or incomplete medical records were excluded. Results A total of 341 patients with IBD were included, of which 236 (72.2%) had Crohn's disease (CD) and 105 (27.8%) had ulcerative colitis (UC). Qualitative CMV PCR was done for 192 patients (60 UC and 132 CD patients), of which 14 patients were positive for CMV colitis (7.3%), and all positive CMV colitis cases were among UC patients (23.3%). However, the hematoxylin and eosin (H and E) stain and immunohistochemistry were negative for all patients. Most patients with CMV colitis were on steroids (71.4%), had at least one flare-up (64.3%), and were on biologic treatment (71.4%). Significant predictors of CMV colitis were hemoglobin (OR: 0.7; 95% CI: 0.51-0.96), albumin (OR: 0.88; 95% CI: 0.78-0.98), and C-reactive protein (OR: 1.03; 95% CI: 1.01-1.06) levels. Conclusion This study found that the prevalence of CMV colitis was 7.3% among patients with IBD, and no case was diagnosed in patients with CD. In addition, as all cases diagnosed using qualitative CMV PCR were negative on H and E stain and immunohistochemistry, there is need for large-scale studies to improve the diagnosis of CMV colitis.
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Affiliation(s)
- Yazeed Alotaibi
- Gastroenterology and Hepatology Department, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Abed AlLehibi
- Gastroenterology and Hepatology Department, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Abdullah Almtawa
- Gastroenterology and Hepatology Department, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Nawaf Alotaibi
- Gastroenterology and Hepatology Department, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Adel Alghamdi
- Gastroenterology and Hepatology Department, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Saad Alrajhi
- Gastroenterology and Hepatology Department, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Adel AlQutub
- Gastroenterology and Hepatology Department, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Ahmad AlEid
- Gastroenterology and Hepatology Department, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Abdulrhman Alamr
- Gastroenterology and Hepatology Department, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Bashaar Al Ibrahim
- Gastroenterology and Hepatology Department, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Mohammed Alahmari
- Gastroenterology and Hepatology Department, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Hussam Alhamidi
- Gastroenterology and Hepatology Department, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Shameem Ahmad
- Gastroenterology and Hepatology Department, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Fouad Alshammari
- Department of Internal Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Fahad Almotawa
- Department of Internal Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
- Department of Medicine, University of Bisha, Bisha, Saudi Arabia
| | | | - Ahmed Alghamdi
- Gastroenterology and Hepatology Department, King Fahad Medical City, Riyadh, Saudi Arabia
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11
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Sethi S, Nayak HK, Panigrahi C, Patra S, Panigrahi MK, Samal SC. Double infection in Crohn's disease. Indian J Gastroenterol 2023; 42:731-733. [PMID: 37145231 DOI: 10.1007/s12664-023-01355-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Affiliation(s)
- Shivam Sethi
- Department of Gastroenterology, All India Institute of Medical Sciences, Bhubaneswar, 751 019, India
| | - Hemanta Kumar Nayak
- Department of Gastroenterology, All India Institute of Medical Sciences, Bhubaneswar, 751 019, India.
| | - Chinmayee Panigrahi
- Department of Pathology, All India Institute of Medical Sciences, Bhubaneswar, 751 019, India
| | - Susama Patra
- Department of Pathology, All India Institute of Medical Sciences, Bhubaneswar, 751 019, India
| | - Manas Kumar Panigrahi
- Department of Gastroenterology, All India Institute of Medical Sciences, Bhubaneswar, 751 019, India
| | - Subash Chandra Samal
- Department of Gastroenterology, All India Institute of Medical Sciences, Bhubaneswar, 751 019, India
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12
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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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13
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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] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [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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14
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Cathomas M, Rosenberg R, Burri E, Javier-Gonzalez M, Weber A, Filipowicz Sinnreich M, Cathomas G, Galli R. Herpes simplex virus colitis mimicking acute severe ulcerative colitis: a case report and review of the literature. J Surg Case Rep 2023; 2023:rjad225. [PMID: 37124571 PMCID: PMC10139777 DOI: 10.1093/jscr/rjad225] [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: 03/13/2023] [Accepted: 04/04/2023] [Indexed: 05/02/2023] Open
Abstract
A 60-year-old female patient with longstanding left-sided ulcerative colitis presented with symptoms mimicking an acute flare and developed a colonic perforation shortly after starting steroid treatment. Following left hemicolectomy and Hartmann's procedure, rescue treatment with infliximab was started. Within a few days, the patient developed hepatic failure. Histology and immunohistochemistry of the specimen revealed extensive necrotizing herpes simplex virus colitis, and liver biopsy demonstrated herpes simplex virus hepatitis. Sixteen days after admission, the patient died from multiorgan failure. This compelling case of severe herpes simplex virus colitis raises awareness of a rare but potentially detrimental infection in patients with inflammatory bowel disease.
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Affiliation(s)
- Marionna Cathomas
- Correspondence address. Department of Surgery, Cantonal Hospital Baselland, 4410 Liestal, Switzerland. Tel: +41-925-32-00; E-mail:
| | - Robert Rosenberg
- Department of Surgery, Cantonal Hospital Baselland, Liestal, Switzerland
| | - Emanuel Burri
- Department of Gastroenterology and Hepatology, Medical University Clinic, Cantonal Hospital Baselland, Liestal, Switzerland
| | | | - Achim Weber
- Department of Pathology and Molecular Pathology, Institute of Molecular Cancer Research, University Hospital Zurich, Zurich, Switzerland
| | - Magdalena Filipowicz Sinnreich
- Department of Gastroenterology and Hepatology, Medical University Clinic, Cantonal Hospital Baselland, Liestal, Switzerland
| | - Gieri Cathomas
- Department of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland
- Institute of Tissue Medicine and Pathology, University Bern, Bern, Switzerland
| | - Raffaele Galli
- Department of Surgery, Cantonal Hospital Baselland, Liestal, Switzerland
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15
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Le-Trilling VTK, Ebel JF, Baier F, Wohlgemuth K, Pfeifer KR, Mookhoek A, Krebs P, Determann M, Katschinski B, Adamczyk A, Lange E, Klopfleisch R, Lange CM, Sokolova V, Trilling M, Westendorf AM. Acute cytomegalovirus infection modulates the intestinal microbiota and targets intestinal epithelial cells. Eur J Immunol 2023; 53:e2249940. [PMID: 36250419 DOI: 10.1002/eji.202249940] [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: 04/12/2022] [Revised: 08/29/2022] [Accepted: 10/14/2022] [Indexed: 02/04/2023]
Abstract
Primary and recurrent cytomegalovirus (CMV) infections frequently cause CMV colitis in immunocompromised as well as inflammatory bowel disease (IBD) patients. Additionally, colitis occasionally occurs upon primary CMV infection in patients who are apparently immunocompetent. In both cases, the underlying pathophysiologic mechanisms are largely elusive - in part due to the lack of adequate access to specimens. We employed the mouse cytomegalovirus (MCMV) model to assess the association between CMV and colitis. During acute primary MCMV infection of immunocompetent mice, the gut microbial composition was affected as manifested by an altered ratio of the Firmicutes to Bacteroidetes phyla. Interestingly, these microbial changes coincided with high-titer MCMV replication in the colon, crypt hyperplasia, increased colonic pro-inflammatory cytokine levels, and a transient increase in the expression of the antimicrobial protein Regenerating islet-derived protein 3 gamma (Reg3γ). Further analyses revealed that murine and human intestinal epithelial cell lines, as well as primary intestinal crypt cells and organoids represent direct targets of CMV infection causing increased cell death. Accordingly, in vivo MCMV infection disrupted the intestinal epithelial barrier and increased apoptosis of intestinal epithelial cells. In summary, our data show that CMV transiently induces colitis in immunocompetent hosts by altering the intestinal homeostasis.
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Affiliation(s)
| | - Jana-Fabienne Ebel
- Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Franziska Baier
- Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Kerstin Wohlgemuth
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Kai Robin Pfeifer
- Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Aart Mookhoek
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - Philippe Krebs
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - Madita Determann
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Benjamin Katschinski
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Alexandra Adamczyk
- Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Erik Lange
- Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Robert Klopfleisch
- Institute of Veterinary Pathology, Free University of Berlin, Berlin, Germany
| | - Christian M Lange
- Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Viktoriya Sokolova
- Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.,Inorganic Chemistry and Centre for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen, Essen, Germany
| | - Mirko Trilling
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Astrid M Westendorf
- Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
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16
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Monteleone G, Laudisi F, Stolfi C. Smad7 as a positive regulator of intestinal inflammatory diseases. CURRENT RESEARCH IN IMMUNOLOGY 2023; 4:100055. [PMID: 36714553 PMCID: PMC9881044 DOI: 10.1016/j.crimmu.2023.100055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/12/2023] [Accepted: 01/18/2023] [Indexed: 01/26/2023] Open
Abstract
In physiological conditions, the human gut contains more immune cells than the rest of the body, but no overt tissue damage occurs, because several regulatory mechanisms control the activity of such cells thus preventing excessive and detrimental responses. One such mechanism relies on the action of transforming growth factor (TGF)-β1, a cytokine that targets both epithelial cells and many immune cell types. Loss of TGF-β1 function leads to intestinal pathology in both mice and humans. For instance, disruption of TGF-β1 signaling characterizes the destructive immune-inflammatory response in patients with Crohn's disease and patients with ulcerative colitis, the major human inflammatory bowel disease (IBD) entities. In these pathologies, the defective TGF-β1-mediated anti-inflammatory response is associated with elevated intestinal levels of Smad7, an antagonist of TGF-β1 signaling. Consistently, knockdown of Smad7 restores TGF-β1 function thereby attenuating intestinal inflammation in patients with IBD as well as in mice with IBD-like colitis. Up-regulation of Smad7 and reduced TGF-β1 signaling occurs also in necrotizing enterocolitis, environmental enteropathy, refractory celiac disease, and cytomegalovirus-induced colitis. In this article, we review the available data supporting the pathogenic role of Smad7 in the gastrointestinal tract and discuss whether and how targeting Smad7 can help attenuate detrimental immuno-inflammatory responses in the gut.
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Affiliation(s)
- Giovanni Monteleone
- Corresponding author. Dipartimento di Medicina dei Sistemi, Università di Roma “Tor Vergata”, Via Montpellier 1, 00133, Rome, Italy.
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Ardura MI, Kim SC. Infectious Complications of Pediatric Inflammatory Bowel Disease. PEDIATRIC INFLAMMATORY BOWEL DISEASE 2023:687-697. [DOI: 10.1007/978-3-031-14744-9_49] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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18
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Le‐Trilling VTK, Ebel J, Baier F, Wohlgemuth K, Pfeifer KR, Mookhoek A, Krebs P, Determann M, Katschinski B, Adamczyk A, Lange E, Klopfleisch R, Lange CM, Sokolova V, Trilling M, Westendorf AM. Acute cytomegalovirus infection modulates the intestinal microbiota and targets intestinal epithelial cells. Eur J Immunol 2022. [DOI: 10.1002/eji.202249940 10.1002/eji.202249940] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Affiliation(s)
| | - Jana‐Fabienne Ebel
- Institute of Medical Microbiology University Hospital Essen University of Duisburg‐Essen Essen Germany
| | - Franziska Baier
- Institute of Medical Microbiology University Hospital Essen University of Duisburg‐Essen Essen Germany
| | - Kerstin Wohlgemuth
- Institute for Virology University Hospital Essen University of Duisburg‐Essen Essen Germany
| | - Kai Robin Pfeifer
- Institute of Medical Microbiology University Hospital Essen University of Duisburg‐Essen Essen Germany
| | - Aart Mookhoek
- Institute of Pathology University of Bern Bern Switzerland
| | - Philippe Krebs
- Institute of Pathology University of Bern Bern Switzerland
| | - Madita Determann
- Institute for Virology University Hospital Essen University of Duisburg‐Essen Essen Germany
| | - Benjamin Katschinski
- Institute for Virology University Hospital Essen University of Duisburg‐Essen Essen Germany
| | - Alexandra Adamczyk
- Institute of Medical Microbiology University Hospital Essen University of Duisburg‐Essen Essen Germany
| | - Erik Lange
- Institute of Medical Microbiology University Hospital Essen University of Duisburg‐Essen Essen Germany
| | - Robert Klopfleisch
- Institute of Veterinary Pathology Free University of Berlin Berlin Germany
| | - Christian M. Lange
- Department of Gastroenterology and Hepatology University Hospital Essen University of Duisburg‐Essen Essen Germany
| | - Viktoriya Sokolova
- Institute of Medical Microbiology University Hospital Essen University of Duisburg‐Essen Essen Germany
- Inorganic Chemistry and Centre for Nanointegration Duisburg‐Essen (CeNIDE) University of Duisburg‐Essen Essen Germany
| | - Mirko Trilling
- Institute for Virology University Hospital Essen University of Duisburg‐Essen Essen Germany
| | - Astrid M. Westendorf
- Institute of Medical Microbiology University Hospital Essen University of Duisburg‐Essen Essen Germany
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Goetgebuer RL, van der Woude CJ, Bakker L, van der Eijk AA, de Ridder L, de Vries AC. The diagnosis and management of CMV colitis in IBD patients shows high practice variation: a national survey among gastroenterologists. Scand J Gastroenterol 2022; 57:1321-1326. [PMID: 35771203 DOI: 10.1080/00365521.2022.2088244] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Clinical guidelines on cytomegalovirus (CMV) colitis in inflammatory bowel disease (IBD) are hampered by the low quality of evidence. In this study, we aim to explore the attitude and management of CMV colitis in IBD among gastroenterologists. METHODS A web-based survey was distributed to adult and pediatric gastroenterologists and trainees in academic and general hospitals in the Netherlands. The survey comprised data collection on respondents' demographics, attitudes towards the importance of CMV infection in IBD on a visual analogue scale (from 0 to 100), and diagnostic and therapeutic strategies. RESULTS A total of 73/131 invited respondents from 32 hospitals completed the survey (response rate of 56%). The importance of CMV infection was scored at a median 74/100. Respondents indicated CMV testing as appropriate in the clinical setting of steroid-refractory colitis (69% of respondents), hospitalized patients with active colitis (64%), immunomodulator or biological refractory colitis (55%) and active colitis irrespective of medication use (14%). CMV diagnostics include histology of colonic biopsies (88% of respondents), tissue CMV PCR (43%), serum CMV PCR (60%), CMV serology (25%) and fecal CMV PCR (4%). 82% of respondents start antiviral therapy after a positive CMV test on colonic biopsies (histology or PCR). CONCLUSIONS Most Dutch gastroenterologists acknowledge the importance of CMV colitis in IBD. Strategies vary greatly with regard to the indication for testing and diagnostic method, as well as indication for the start of antiviral therapy. These findings underline the need for pragmatic clinical studies on different management strategies, in order to reduce practice variation and improve the quality of care. Summary of the established knowledge on this subject:The clinical significance of CMV-associated colitis in IBD remains a matter of debateRecommendations regarding CMV colitis in current international guidelines are based on low to moderate evidence levels and different diagnostic strategies are proposed What are the significant and/or new findings of this study?We show that there is a high practice variation of diagnosis and management of CMV colitis in IBD amongst adult and pediatric gastroenterologistsThis study underlined the need for pragmatic studies and guidelines on different management strategies including cut-off values to start therapy.
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Affiliation(s)
- R L Goetgebuer
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - C J van der Woude
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - L Bakker
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - A A van der Eijk
- Department of Viroscience, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - L de Ridder
- Department of Pediatric Gastroenterology, Erasmus MC, Sophia Children's Hospital, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - A C de Vries
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
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20
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Lee J. [Cytomegalovirus Infection in Patients with Inflammatory Bowel Disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2022; 80:60-65. [PMID: 36004632 DOI: 10.4166/kjg.2022.094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 07/25/2022] [Accepted: 07/25/2022] [Indexed: 06/15/2023]
Abstract
A diagnostic evaluation for cytomegalovirus (CMV) infection is required in patients with inflammatory bowel disease (IBD) who do not respond to steroid or immunomodulatory treatment. However, there is no consensus on an accurate diagnostic method for CMV infection in patients with IBD, and it is difficult to clearly distinguish the exacerbation of ulcerative colitis from CMV colitis. According to several recent studies, the most accurate test method for CMV colitis is quantitative tissue DNA-quantitative PCR, which is recommended as the first-line diagnostic technique along with an immunohistochemistry stain. The benefit of antiviral therapy for CMV infection in patients with IBD is also controversial. Although the definition of viral load is unclear, antiviral therapy can lower the rate of colectomy in CMV infections with a high viral load in patients with IBD. This review presents the latest findings about CMV infections in IBD, based on recently reported studies.
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Affiliation(s)
- Jun Lee
- Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea
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21
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Wang W, Chen X, Pan J, Zhang X, Zhang L. Epstein-Barr Virus and Human Cytomegalovirus Infection in Intestinal Mucosa of Chinese Patients With Inflammatory Bowel Disease. Front Microbiol 2022; 13:915453. [PMID: 35711779 PMCID: PMC9195000 DOI: 10.3389/fmicb.2022.915453] [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] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 05/09/2022] [Indexed: 12/30/2022] Open
Abstract
Objective This study aimed to determine the frequency of Epstein–Barr virus (EBV), cytomegalovirus (CMV) in mucosa and blood of inflammatory bowel disease (IBD) patients in China and evaluate their correlation with the clinical disease activities. Methods Peripheral blood and endoscopic fresh colonic mucosal samples were collected from a cohort of 287 IBD patients and 50 controls. Viral DNA load was analyzed through quantitative real-time PCR. The clinical disease activity of ulcerative colitis (UC) and Crohn’s disease (CD) was assessed by the Mayo Clinic Score and Crohn’s disease activity index, respectively. Results Among 287 IBD patients, 228 (79.4%) were positive for EBV and 99 (34.5%) were positive for CMV. EBV and CMV infection rates are significantly higher than those in the control group (28.0%, p < 0.05; 4.0%, p < 0.05). In addition, EBV/CMV prevalence increases as clinical activities progress [For EBV infection, the prevalence was 53.93% (48/89) in the mild group, 87.00% (87/100) in the moderate group, and 94.90% (93/98) in the severe group; and for CMV infection, the prevalence was 3.37% (3/89) in the mild group, 27.00% (27/100) in the moderate group, and 70.41% (69/98) in the severe group]. EBV and CMV loads are related to clinical disease activities (p < 0.05). In addition, viral load in the intestinal mucosa of patients with acute exacerbation of IBD is higher than that of patients in remission. Conclusion High prevalence of EBV and CMV is found in patients with IBD, and their prevalence is related to clinical disease activities. In addition, the viral load in the intestinal mucosa is associated with the status of mucosa in the same patients (active phase versus remission phase). Detection of viral load on mucosal specimens with quantitative real-time PCR is a feasible method to monitor EBV and CMV infection in IBD patients.
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Affiliation(s)
- Wei Wang
- Department of Laboratory Medicine, Shanxi Provincial People's Hospital, Taiyuan, China
| | - Xin Chen
- Department of Laboratory Medicine, The 908th Hospital of Chinese PLA Joint Logistics Support Force, Nanchang, China
| | - Jie Pan
- Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, United States
| | - Xianhui Zhang
- Department of Rheumatology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Tongji Medical College, Huazhong University of Science and Technology, Taiyuan, China
| | - Liyun Zhang
- Department of Rheumatology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Tongji Medical College, Huazhong University of Science and Technology, Taiyuan, China
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22
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A case of localized colorectal wild-type ATTR amyloidosis complicated by early stage colorectal cancer and a CMV-associated ulcer during the long-term follow-up. Clin J Gastroenterol 2022; 15:603-610. [PMID: 35386058 DOI: 10.1007/s12328-022-01628-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Accepted: 03/18/2022] [Indexed: 10/18/2022]
Abstract
Gastrointestinal involvement is a rare manifestation of systemic amyloidosis, and few reports have been published on localized amyloidosis of the colon. Only one case report has been published on the long-term prognosis of localized colorectal amyloidosis, and there are no previous reports on localized colorectal ATTR amyloidosis. Here, we report an 80-year-old male with localized colorectal wild-type ATTR amyloidosis who presented with edematous mucosa with vascular changes throughout the colon. He did not exhibit any symptoms or endoscopic exacerbation for 8 years after diagnosis. However, after 8 years, he developed early stage colorectal cancer and cytomegalovirus-associated ulcer. He was treated with endoscopic submucosal dissection, which was relatively challenging due to his hemorrhagic condition and poor elevation of the submucosa caused by amyloid deposits. Since the tumor was completely resected, he will undergo regular follow-up. Our review of 20 previous cases of localized colorectal amyloidosis revealed its clinical features and long-term prognosis. Specifically, ours is the second case of a diffuse pan-colon type of colorectal localized amyloidosis, which may lead to various complications, such as colorectal cancer, over a long period of time, and thus, regular follow-up is necessary.
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23
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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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24
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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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25
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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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26
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Jena A, Mishra S, Singh AK, Sekar A, Sharma V. Cytomegalovirus in ulcerative colitis: an evidence-based approach to diagnosis and treatment. Expert Rev Gastroenterol Hepatol 2022; 16:109-120. [PMID: 35057693 DOI: 10.1080/17474124.2022.2032662] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
INTRODUCTION The detection of cytomegalovirus (CMV) in the setting of inflammatory bowel disease often creates confusion whether CMV is a 'bystander' or 'disease.' AREAS COVERED This review discusses the clinical conundrum of CMV in ulcerative colitis, approach to discriminate infection from disease, and therapeutic considerations (immunosuppressive and anti-CMV treatment). CMV disease should be considered in corticosteroid refractory- dependent and thiopurine refractory disease. Endoscopy may reveal deep punched out ulcers, irregular ulcers, or cobble-stoning. The diagnosis rests on the presence and abundance of viral inclusion bodies on hematoxylin and eosin stain, positive immunohistochemistry, and/or positive tissue polymerase chain reaction. CMV disease is associated with worse outcomes including increased colectomy rates. EXPERT OPINION The timing and duration of antiviral drugs in CMV disease is debatable but depends on the load of CMV in tissue. In high-grade infection, CMV needs to be treated while increasing immunosuppression may work in the setting of low-grade infection. Ganciclovir is the drug of choice for treatment of CMV disease. Tumor necrosis factor inhibitors may be useful for treating underlying disease activity in the setting of CMV. Other emerging therapies include fecal microbiota transplantation. Randomized studies are necessary to define the best timing and duration of anti-CMV therapy.
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Affiliation(s)
- Anuraag Jena
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Shubhra Mishra
- Department of Gastroenterology, AIG Hospitals, Hyderabad, India
| | - Anupam Kumar Singh
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Aravind Sekar
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vishal Sharma
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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27
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Sun L, Chen JM, Yang K, Zhang L, Ma ZY, Chen XM, Li M, Zhou X, Li P, Zhao HX, Xiao J, Qi LM, Wang P. Cytomegalovirus cell tropism and clinicopathological characteristics in gastrointestinal tract of patients with HIV/AIDS. Diagn Pathol 2022; 17:9. [PMID: 35027044 PMCID: PMC8759214 DOI: 10.1186/s13000-022-01193-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 01/02/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) has been recognized as one of the frequently occurring opportunistic infections (OIs) reported in the patients having human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). In addition, it has been identified as the factor leading to gastrointestinal (GI) tract disorder among HIV/AIDS population. CMV exhibits broad cell tropism in different organs. This study evaluated the CMV cell tropism and clinicopathological characteristics of CMV infection in the different GI regions in HIV/AIDS cases. METHODS Using nucleic acid in situ hybridization (ISH), CMV was detected in the gastrointestinal mucosal biopsy samples. The paraffin-embedded samples were stained with hematoxylin and eosin (HE) and immunohistochemistry (IHC), respectively. RESULTS A total of 32 HIV/AIDS patients were enrolled in this study. Fourteen of these patients underwent gastroscopy, while the remaining eighteen received colonoscopy. CMV-infected cells were observed at 46 GI sites. Among them, the colon was the region with the highest susceptibility to GI CMV infection (n = 12, 26.1%). The CMV giant cell inclusion bodies were detected in epithelial cells and mesenchymal cells, including histiocytes, smooth muscle cells, fibroblasts, and endothelial cells. In the duodenum, there were markedly more positive epithelial cells than mesenchymal cells (p = 0.033). In contrast, in the esophagus (p = 0.030), cardia (p = 0.003), rectum (p = 0.019), colon (p < 0.001), and cecum (p < 0.001), there were notably less positive epithelial cells than mesenchymal cells. The expression levels of PDGFRα and Nrp2 in the mesenchymal cells were higher than the epithelial cells in cardia, cecum, colon, sigmoid, and rectum, especially in the areas with ulcers. However, Nrp2 in the epithelial cells was higher than that in the duodenum. Moreover, the positive CMV DNA in peripheral blood was related to the CMV-positive cell count, as well as the ulceration in GI tract (p = 0.035 and 0.036, respectively). CONCLUSIONS The colon has been identified as the GI site with the highest susceptibility to CMV infection. There are different CMV-infected cells in the different sites of the GI that relate to the expression level of PDGFRα and Nrp2. CMV DNA positive in the blood is related to the positive CMV cell count, as well as ulceration in the GI tract.
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Affiliation(s)
- Lei Sun
- Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China.
| | - Jia-Min Chen
- Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China
| | - Kun Yang
- Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China
| | - Liang Zhang
- Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China
| | - Zhi-Yuan Ma
- Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China
| | - Xiang-Mei Chen
- Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China
| | - Man Li
- Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China
| | - Xingang Zhou
- Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China
| | - Ping Li
- Department of Gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Hong-Xin Zhao
- Center for Infectious Diseases, Beijing Ditan Hospital, Captial Medical University, Beijing, 100015, China
| | - Jiang Xiao
- Center for Infectious Diseases, Beijing Ditan Hospital, Captial Medical University, Beijing, 100015, China
| | - Li-Ming Qi
- Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China
| | - Peng Wang
- Department of Pathology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing, 100015, People's Republic of China.
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28
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Liang G, Cobián-Güemes AG, Albenberg L, Bushman F. The gut virome in inflammatory bowel diseases. Curr Opin Virol 2021; 51:190-198. [PMID: 34763180 DOI: 10.1016/j.coviro.2021.10.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 10/05/2021] [Accepted: 10/12/2021] [Indexed: 02/06/2023]
Abstract
Dysbiosis of the microbiome has been extensively studied in inflammatory bowel diseases (IBD). The roles of bacteria and fungi have been studied in detail, but viral communities, an important component of the microbiome, have been less thoroughly investigated. Metagenomics provided a way to fill this gap by using DNA sequencing to enumerate all viruses in a sample, termed the 'virome'. Such methods have now been employed in several studies to assess associations between viral communities and IBD, yielding several commonly seen properties, including an increase in tailed bacteriophage (Caudovirales) and a decrease in the spherical Microviridae. Numerous studies of single human viruses have been carried out, but no one virus has emerged as tightly associated, focusing attention on whole virome communities and further factors. This review provides an overview of research on the human virome in IBD, with emphasis on (1) dynamics of the gut virome, (2) candidate mechanisms of virome alterations with disease, (3) methods for studying the virome, and (4) potentially actionable implications of virome data.
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Affiliation(s)
- Guanxiang Liang
- Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104-6076, USA.
| | - Ana Georgina Cobián-Güemes
- Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104-6076, USA
| | - Lindsey Albenberg
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, 19104-4399, USA
| | - Frederic Bushman
- Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104-6076, USA.
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29
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Chinese consensus on diagnosis and treatment in inflammatory bowel disease (2018, Beijing). J Dig Dis 2021; 22:298-317. [PMID: 33905603 DOI: 10.1111/1751-2980.12994] [Citation(s) in RCA: 70] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 04/22/2021] [Indexed: 12/11/2022]
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30
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Involvement of Smad7 in Inflammatory Diseases of the Gut and Colon Cancer. Int J Mol Sci 2021; 22:ijms22083922. [PMID: 33920230 PMCID: PMC8069188 DOI: 10.3390/ijms22083922] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 03/30/2021] [Accepted: 04/07/2021] [Indexed: 02/07/2023] Open
Abstract
In physiological conditions, the human intestinal mucosa is massively infiltrated with various subsets of immune cells, the activity of which is tightly regulated by several counter-regulatory factors. One of these factors is transforming growth factor-β1 (TGF-β1), a cytokine produced by multiple cell types and targeting virtually all the intestinal mucosal cells. Binding of TGF-β1 to its receptors triggers Smad2/3 signaling, thus culminating in the attenuation/suppression of immune–inflammatory responses. In patients with Crohn’s disease and patients with ulcerative colitis, the major human inflammatory bowel diseases (IBD), and in mice with IBD-like colitis, there is defective TGF-β1/Smad signaling due to high levels of the intracellular inhibitor Smad7. Pharmacological inhibition of Smad7 restores TGF-β1 function, thereby reducing inflammatory pathways in patients with IBD and colitic mice. On the other hand, transgenic over-expression of Smad7 in T cells exacerbates colitis in various mouse models of IBD. Smad7 is also over-expressed in other inflammatory disorders of the gut, such as refractory celiac disease, necrotizing enterocolitis and cytomegalovirus-induced colitis, even though evidence is still scarce and mainly descriptive. Furthermore, Smad7 has been involved in colon carcinogenesis through complex and heterogeneous mechanisms, and Smad7 polymorphisms could influence cancer prognosis. In this article, we review the data about the expression and role of Smad7 in intestinal inflammation and cancer.
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31
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Song J, Bhuta R, Baig K, Parkman HP, Malik Z. COVID-19 infection manifesting as a severe gastroparesis flare: A case report. Medicine (Baltimore) 2021; 100:e25467. [PMID: 33832159 PMCID: PMC8036087 DOI: 10.1097/md.0000000000025467] [Citation(s) in RCA: 4] [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] [Received: 12/20/2020] [Revised: 03/12/2021] [Accepted: 03/18/2021] [Indexed: 12/23/2022] Open
Abstract
RATIONALE Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which commonly presents with symptoms including fever, cough, and dyspnea. More recently, however, some patients have tested positive for COVID-19 after developing gastrointestinal (GI) symptoms either solely or in conjunction with respiratory symptoms. This may be due to SARS-CoV-2 infection of the GI tract. In patients with chronic GI illnesses, COVID-19 may initially present as a flare of their underlying GI conditions as viruses have historically been implicated in exacerbations of GI disorders, including gastroparesis. PATIENT CONCERNS We report a case of a 37-year-old female with a history of diabetic gastroparesis who presented to the Emergency Department (ED) with nausea and vomiting similar to her gastroparesis flares. DIAGNOSES Her symptoms in the ED failed to improve with fluids and anti-emetic medications. After developing a fever, she was tested and found to be positive for COVID-19. INTERVENTIONS She was started on antibiotic, steroid, and antiviral medications. OUTCOMES Her symptoms improved, her fever defervesced on day 4 of hospitalization, and she was discharged on day 5 of hospitalization. The patient reported symptom improvement at a follow-up outpatient gastroenterology visit 2 months after hospitalization. LESSONS To the best of our knowledge, at the present time, this is the first report of a patient with COVID-19 presenting with signs and symptoms of a gastroparesis flare. This case illustrates that COVID-19 may present in an exacerbation of symptoms of an underlying disorder, such as a severe gastroparesis flare, in a patient with underlying gastroparesis. Initial presentation of these patients manifesting as a flare of their chronic GI disease, more severe than usual, should prompt an index of suspicion for COVID-19.
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Affiliation(s)
- Jun Song
- Temple University Hospital, Department of Medicine
| | - Rajiv Bhuta
- Section of Gastroenterology and Hepatology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA
| | - Kamal Baig
- Section of Gastroenterology and Hepatology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA
| | - Henry P. Parkman
- Section of Gastroenterology and Hepatology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA
| | - Zubair Malik
- Section of Gastroenterology and Hepatology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA
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32
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Axelrad JE, Cadwell KH, Colombel JF, Shah SC. The role of gastrointestinal pathogens in inflammatory bowel disease: a systematic review. Therap Adv Gastroenterol 2021; 14:17562848211004493. [PMID: 33868457 PMCID: PMC8020742 DOI: 10.1177/17562848211004493] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 03/04/2021] [Indexed: 02/04/2023] Open
Abstract
The inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), are chronic, progressive, inflammatory conditions of the gastrointestinal tract. Imbalance in the gut microbial community, or dysbiosis, and the subsequent immune response, represent the critical relationship between genetic susceptibility, microbes, and environment factors, that result in IBD. Gastrointestinal pathogens - a common cause of dysbiosis - have been implicated as an environmental trigger in new onset IBD, as well as flare of existing IBD. In this article, we systematically review clinical data regarding the association between specific gastrointestinal pathogens and IBD. Numerous bacteria, viruses, fungi, and parasites have been implicated in the pathogenesis of IBD, and exacerbations of existing disease. In this article, we will also specifically discuss the less recognized microbes that have an inverse association with IBD, including certain bacterial pathogens, such as Helicobacter pylori, and parasites, such as Trichuris species. Future prospective and experimental studies are required to establish causality and clarify potential mechanisms of enteric pathogens in modifying the risk and course of IBD.
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Affiliation(s)
| | - Ken H. Cadwell
- Division of Gastroenterology, Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA,Kimmel Center for Biology and Medicine at the Skirball Institute, NYU Grossman School of Medicine, New York, NY, USA,Department of Microbiology, NYU Grossman School of Medicine, New York, NY, USA
| | - Jean-Frederic Colombel
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Shailja C. Shah
- Section of Gastroenterology, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN,San Diego Health System, La Jolla, CA, USA,Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA
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33
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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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Ran Z, Wu K, Matsuoka K, Jeen YT, Wei SC, Ahuja V, Chen M, Hu PJ, Andoh A, Kim HJ, Yang SK, Watanabe M, Ng SC, Hibi T, Hilmi IN, Suzuki Y, Han DS, Leung WK, Sollano J, Ooi CJ, Qian J. Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology practice recommendations for medical management and monitoring of inflammatory bowel disease in Asia. J Gastroenterol Hepatol 2021; 36:637-645. [PMID: 32672839 DOI: 10.1111/jgh.15185] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 05/05/2020] [Accepted: 05/12/2020] [Indexed: 02/06/2023]
Abstract
Inflammatory bowel disease (IBD) has increased in incidence and prevalence in Asian countries since the end of the 20th century. Moreover, differences in the cause, phenotypes, and natural history of IBD between the East and West have been recognized. Therefore, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have established recommendations on medical management of IBD in Asia. Initially, the committee members drafted 40 recommendations, which were then assessed according to Grading of Recommendations Assessment, Development and Evaluation. Eight statements were rejected as this indicated that consensus had not been reached. The recommendations encompass pretreatment evaluation; medical management of active IBD; medical management of IBD in remission; management of IBD during the periconception period and pregnancy; surveillance strategies for colitis-associated cancer; monitoring side effects of thiopurines and methotrexate; and infections in IBD.
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Affiliation(s)
- Zhihua Ran
- Department of Gastroenterology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Kaichun Wu
- Department of Gastroenterology, Fourth Military Medical University, Xi'an, China
| | - Katsuyoshi Matsuoka
- Department of Gastroenterology, Toho University Sakura Medical Center, Chiba, Japan
| | - Yoon Tae Jeen
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Shu Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Pin-Jin Hu
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Akira Andoh
- Department of Gastroenterology, Shiga University, Otsu, Japan
| | - Hyo Jong Kim
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Siew Chien Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University, Tokyo, Japan
| | - Ida Normiha Hilmi
- Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Yasuo Suzuki
- Department of Internal Medicine, Toho University, Sakura, Japan
| | - Dong Soo Han
- Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
| | - Wai Keung Leung
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Hong Kong, Hong Kong
| | - Jose Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Choon Jin Ooi
- Gleneagles Medical Centre and Duke-NUS Medical School, Singapore
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College, Beijing, China
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Alacam S, Karabulut N, Bakir A, Onel M, Buyuk M, Gulluoglu M, Agacfidan A. Diagnostic significance of cytomegalovirus DNA quantitation in gastrointestinal biopsies: comparison with histopathological data and blood cytomegalovirus DNA. Eur J Gastroenterol Hepatol 2021; 33:40-45. [PMID: 32658013 DOI: 10.1097/meg.0000000000001840] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES This study aims to improve the diagnosis of gastrointestinal (GI) cytomegalovirus (CMV) disease. It presents the results of a novel study in which CMV blood viral load (BVL), tissue viral load (TVL) determined by PCR and hematoxylin-eosin (HE)/immunohistochemistry (IHC) results of GI biopsies are examined comparatively. METHODS CMV DNA was investigated by quantitative real-time PCR in blood and GI biopsy specimens of 76 patients suspected of CMV disease. Biopsies were also performed HE/IHC stainings in the pathology laboratory. RESULTS This study included 76 patients whose median age was 34.5 years and 58% (44) were male. Tissue CMV PCR positivity was detected in the highest colon (40/53;75.5%) samples. HE, IHC, blood and tissue CMV PCR positivity rates of all samples were 15.8, 25, 50 and 71.1%, respectively. When IHC was used as the gold standard test for ROC analysis, the optimal cutoff values for the maximum sensitivity and specificity for BVL and TVL were 1.91 log10 copies/ml and 3.82 log10 copies/mg, respectively. Sensitivity and specificity for the cutoff value of tissue CMV DNA were 78.9 and 74.3%, respectively (P < 0.001). CONCLUSION In this study, CMV DNA was detected in 71.1% of the tissue samples of the cases by PCR. Since the sensitivity of the histopathological examinations accepted as the gold standard is low, simultaneous with the histopathological examinations, determination of BVL, TVL and the identification of optimal cutoff values have been shown to support the diagnosis of GI CMV disease.
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Affiliation(s)
- Sema Alacam
- Division of Virology and Fundamental Immunology, Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University
| | - Nuran Karabulut
- Division of Virology and Fundamental Immunology, Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University
| | - Ayfer Bakir
- Division of Virology and Fundamental Immunology, Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University
| | - Mustafa Onel
- Division of Virology and Fundamental Immunology, Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University
| | - Melek Buyuk
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mine Gulluoglu
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ali Agacfidan
- Division of Virology and Fundamental Immunology, Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University
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Störkmann H, Rödel J, Stallmach A, Reuken PA. Are CMV-predictive scores in inflammatory bowel disease useful in clinical practice? ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 58:868-871. [PMID: 32947632 DOI: 10.1055/a-1221-5463] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
BACKGROUND Concurrent cytomegalovirus (CMV) in inflammatory bowel disease (IBD)-related colitis is an important scenario associated with high rates of colectomy and other morbidity. Due to the low incidence of CMV, testing of all patients is associated with an unacceptably high consumption of resources and delay in treatment. Therefore, several predictive scores have been developed to identify patients at risk for a CMV infection. METHODS We performed a retrospective single center study in a German University hospital including all IBD patients with available data on CMV-PCR analysis in whole blood between 2010 and 2018 and evaluated 2 prognostic scores for CMV infection for their diagnostic accuracy. RESULTS In the study, 907 patients with IBD and CMV-PCR were identified. Of them, 21 patients (2.3 %) had a positive CMV-PCR (≥ 1000 copies/mL), 14 of them in ulcerative colitis and 7 in Crohn's disease. The Berlin Score identified 667 patients (73.1 %) as potentially CMV-positive, resulting in a positive predictive value of 2.5 % and a negative predictive value of 98.3 %. In contrast, the Münster Score identified 60 patients as potentially CMV-positive, resulting in a PPV of 20 % and an NPV of 99.4 %. CONCLUSIONS Scoring systems can help to identify patients at risk for a CMV infection and minimize resource consumption and delay in treatment. Due to low incidence, a 2-step-algorithm, consisting of the Münster Score followed by a CMV-PCR if the score indicates a CMV infection, is preferable.
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Affiliation(s)
- Hedwig Störkmann
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - Jürgen Rödel
- Institute of Medical Microbiology, Jena University Hospital, Jena, Germany
| | - Andreas Stallmach
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - Philipp A Reuken
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
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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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Yang H, Wu K, Zhang H, Owyang Q, Miao Y, Gu F, Hu N, Zou K, Sheng J, Li J, Zheng P, Liu Y, Li J, Wang X, Wu Y, Yuan Y, Chen C, Pang Y, Cui M, Qian J. IgA, albumin, and eosinopenia as early indicators of cytomegalovirus infection in patients with acute ulcerative colitis. BMC Gastroenterol 2020; 20:294. [PMID: 32891125 PMCID: PMC7487863 DOI: 10.1186/s12876-020-01434-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Accepted: 08/21/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) infection can significantly complicate and worsen the condition of acute severe ulcerative colitis (UC) patients. We aimed to explore the predictive risk factors to prevent and identify CMV infection at an early stage in acute UC patients. METHODS A total of 115 moderate-to-severe active UC patients from 17 hospitals throughout China were enrolled. Active CMV infection was diagnosed by one of the following: CMV pp65 antigens, CMV IgM antibodies or CMV DNA. We identified the independent risk factors by multivariate analyses. RESULTS A total of 64 of 115 active UC patients had active CMV infection. Compared to the non-CMV-infected patients, the CMV-infected patients had a tendency to be male and to exhibit abdominal pain; fever; oral ulcers; eosinopenia; low albumin, immunoglobulin (Ig) A, IgM, and IgG levels; increased high-sensitivity C-reactive protein (hsCRP) levels; hyponatremia; pancolonic lesions; initial onset type; severe activity; and glucocorticoid (high-dose) and immunosuppressive agent use (P < 0.05). In further multivariate analyses, the use of high-dose glucocorticoids (OR 13.55, 95% CI 2.49-73.61, P < 0.01) and immunosuppressive agents (OR 11.23, 95% CI 1.05-119.99, P = 0.04) were independent risk factors for CMV infection. A decrease eosinophil and albumin levels were risk factors for CMV infection. With every 0.1*10^9/L decrease in the peripheral blood eosinophil level or 1 g/L decrease in the serum albumin level, the risk for CMV infection in UC patients increased by 5.21-fold (1/0.192) or 1.19-fold (1/0.839), respectively. CONCLUSIONS High-dose glucocorticoid and immunosuppressive agent treatment significantly increase the risk of CMV infection, and correcting eosinopenia and low albumin levels may help prevent CMV infection in UC patients.
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Affiliation(s)
- Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, P.R. China
| | - Kaichun Wu
- Department of Gastroenterology, Xijin Hospital, The Fourth Military Medical University, Xi'an, China
| | - Hongjie Zhang
- Department of Gastroenterology, Jiangsu Province Hospital, Nanjing, China
| | - Qin Owyang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Yinglei Miao
- Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Fang Gu
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Naizhong Hu
- Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Kaifang Zou
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Jianqiu Sheng
- Department of Gastroenterology, General Hospital of Beijing Military Region, Beijing, China
| | - Jin Li
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Ping Zheng
- Department of Gastroenterology, Shanghai General Hospital, Shanghai, China
| | - Yulan Liu
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China
| | - Junxia Li
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Xiaodi Wang
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Yongdong Wu
- Department of Gastroenterology, Beijing Friendship Hospital of Capital Medical University, Beijing, China
| | - Yaozong Yuan
- Department of Gastroenterology, Ruijin Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Chunxiao Chen
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang University, Beijing, China
| | - Yanhua Pang
- Department of Gastroenterology, Beijing Chao-Yang Hospital, Beijing, China
| | - Meihua Cui
- Department of Gastroenterology, Aerospace Central Hospital, Beijing, China
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, P.R. China.
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, P.R. China.
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van der Sloot KWJ, Voskuil MD, Visschedijk MC, Festen EAM, van Dullemen HM, Weersma RK, Alizadeh BZ, van Leer-Buter C, Dijkstra G. Latent cytomegalovirus infection does not influence long-term disease outcomes in inflammatory bowel disease, but is associated with later onset of disease. Scand J Gastroenterol 2020; 55:891-896. [PMID: 32633160 DOI: 10.1080/00365521.2020.1786853] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Cytomegalovirus (CMV) infection is common in the general population. CMV infection negatively affects disease course in transplant recipients and HIV patients. Whereas primary CMV infections may occur sporadically in seronegative patients, all seropositive patients with inflammatory bowel syndrome (IBD) are at risk for CMV reactivation due to the inflammatory mucosal and use of immunosuppressive medication. It is unclear whether latent CMV infection, and risk of reactivations, influences long-term disease outcomes. In this study, we aim to explore whether CMV infection affects disease outcomes in IBD patients. METHODS We performed a cross-sectional cohort study with 1404 patients with IBD from a single center. Clinical characteristics and disease outcomes were prospectively collected. We scrutinized CMV serology test results and performed additional CMV serology testing if serum was available. RESULTS Out of 699 IBD patients with CMV serology, 303 (43.3%) were seropositive, comparable to the general Dutch population. CMV seropositivity was associated with older age, longer IBD disease duration, non-Western origin, birth outside the Netherlands and a lower educational level (p-values ≤ .004). CMV seropositivity was not associated with more complicated long-term disease outcomes of IBD (p-values > .05). Seropositive patients presented with symptoms and were diagnosed at an older age compared to seronegative patients (p-values < .01). CONCLUSIONS CMV seropositivity does not influence disease outcomes of IBD patients and seems to be associated with a delay in IBD onset. Guidelines regarding CMV screening in patients with IBD are currently based on a low level of evidence. These data support the recommendation that routine CMV serology measurement is not necessary in the clinical care of IBD.
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Affiliation(s)
- Kimberley W J van der Sloot
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
- Department of Epidemiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Michiel D Voskuil
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
- Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Marijn C Visschedijk
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Eleonora A M Festen
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
- Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Hendrik M van Dullemen
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Rinse K Weersma
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Behrooz Z Alizadeh
- Department of Epidemiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Coretta van Leer-Buter
- Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
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Schofield JB, Haboubi N. Histopathological Mimics of Inflammatory Bowel Disease. Inflamm Bowel Dis 2020; 26:994-1009. [PMID: 31599934 DOI: 10.1093/ibd/izz232] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Indexed: 12/12/2022]
Abstract
This review article discusses the challenges of making a firm histopathological diagnosis of inflammatory bowel disease (IBD) on biopsy and resection material and the importance of its distinction from a range of other inflammatory and infective conditions that may closely mimic IBD. In many cases, the diagnosis of ulcerative colitis or Crohn's disease is straightforward, especially when patients have a typical presentation and characteristic histopathological features. Knowledge of the full clinical history is very important, particularly past and recent medical history, drug history, foreign travel, or known contact with individuals with specific infection. Discussion of all cases of suspected IBD within a multidisciplinary team meeting is required to ensure that clinical, radiological, and pathological features can be correlated. Mimics of IBD can be divided into 4 categories: 1) those due to specific infection, 2) those due to a specific localized inflammatory process, 3) those due to iatrogenic causes, and 4) other rarer causes. Accurate diagnosis of IBD and exclusion of these mimics are crucial for patient management. Once a diagnosis of IBD has been proffered by a pathologist, it is very difficult to "undiagnose" the condition when an alternative diagnosis or "mimic" has been subsequently identified. The histological diagnosis of each of these IBD mimics is discussed in detail, with guidance on how to avoid the pitfall of missing these sometimes very subtle and "difficult to diagnose" conditions.
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Yokoyama Y, Yamakawa T, Hirano T, Kazama T, Hirayama D, Wagatsuma K, Nakase H. Current Diagnostic and Therapeutic Approaches to Cytomegalovirus Infections in Ulcerative Colitis Patients Based on Clinical and Basic Research Data. Int J Mol Sci 2020; 21:ijms21072438. [PMID: 32244555 PMCID: PMC7177554 DOI: 10.3390/ijms21072438] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 03/28/2020] [Accepted: 03/30/2020] [Indexed: 12/12/2022] Open
Abstract
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus (the human herpesvirus 5) and an opportunistic pathogen that primarily infects HIV-positive and other immuno-compromised patients. Retrospective studies in the field of inflammatory bowel disease (IBD) have suggested a relationship between a concomitant colonic HCMV infection and poor outcomes in patients with an ulcerative colitis (UC) due to the presence of HCMV in surgical specimens of patients with a toxic megacolon or a steroid-resistant UC. Therefore, gastroenterologists have focused on the contribution of HCMV infections in the exacerbation of UC. Numerous studies have addressed the benefits of treating colonic HCMV reactivation in UC using an antiviral treatment. However, its clinical relevance remains uncertain as only a few prospective studies have assessed the direct relationship between clinical outcomes and the viral load of HCMV in colonic tissues. HCMV reactivation can be triggered by inflammation according to fundamental research studies. Thus, optimal control of intestinal inflammation is essential for preventing an HCMV reactivation in the intestinal mucosa. Indeed, several reports have indicated the effectiveness of an anti-tumor necrosis factor-alpha (TNFα) treatment in patients with an active UC and concomitant HCMV infections. In this review, we describe the mechanism of HCMV reactivation in UC cases and discuss the current issues regarding diagnosis and treatment of HCMV infections in UC patients.
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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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Qiu L, Volk E, Mais DD. Histopathologic Patterns of Colitis in Patients With Impaired Renal Function. Am J Clin Pathol 2020; 153:380-386. [PMID: 31679016 DOI: 10.1093/ajcp/aqz176] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
OBJECTIVES To characterize the histopathologic features of colitis in patients with impaired renal function. METHODS We retrospectively identified 413 patients who underwent colonoscopic evaluation for colitis between 2011 and 2015. Patients were divided into four groups based on estimated glomerular filtrate rates. Patients with impaired renal function were compared to overall and age-matched patients with normal renal function. RESULTS Compared to a preponderance of inflammatory bowel disease (33%) and lymphocytic colitis (9.6%) in patients with normal renal function, ischemic colitis (58%) was the predominant histopathologic pattern in the patients with impaired renal function. Infectious colitis was the second most common pattern (20.8%), with Clostridium difficile and cytomegalovirus infections being more frequent. Medication-induced injury was the third most common pattern, with crystal-associated injury being the exclusive pattern found in this study. CONCLUSIONS Colitis in patients with impaired renal function is etiologically distinct from that seen in patients with normal renal function.
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Affiliation(s)
- Lianqun Qiu
- Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at San Antonio
| | - Emily Volk
- Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at San Antonio
| | - Daniel D Mais
- Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at San Antonio
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Kosmidou M, Karavasili NT, Saridi M, Skamnelos A, Kavvadias A, Batistatou A, Gartzonika KG, Tsiara S, Katsanos KH, Christodoulou DK. Clostridium Difficile Infection in Patients Impact Suspected Cytomegalovirus Infection in Patients with Inflammatory Bowel Disease. Mater Sociomed 2020; 32:41-45. [PMID: 32410890 PMCID: PMC7219720 DOI: 10.5455/msm.2020.32.41-45] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Introduction Clostridium difficile infection (CDI) has been reported to be a cause of flare-ups in patients with inflammatory bowel disease (IBD). Cytomegalovirus (CMV) infection can cause severe disease and complications in immunocompromised patients in consequence of disease or therapy. Aim Our aim was to describe the prevalence and clinical outcomes of CDI with concomitant CMV infection in IBD patients hospitalized for flare-ups in association with the disease itself and medication used. Methods We prospectively identified consecutive patients referred for CDI management during 2015-2017. Stool samples were tested for Clostridium difficile toxin A and/or B and Glutamate Dehydrogenase in patients with clinical symptoms. CDI patients with IBD history were tested for anti-CMV IgG and IgM antibodies by chemiluminescent microparticle immunoassay and underwent histological analysis for CMV on colon biopsies. Data were collected for demographic characteristics, treatment and outcome. Results 125 patients with CDI were enrolled. Among these patients, 14 (11.2%) were diagnosed with IBD. The mean patient age of IBD patients was 52.5±15.4 years at diagnosis of CDI, 85.7% had UC, 14.3% CD, while the age of patients was shared. Eleven of the total of 14 patients (78.6%) tested positive for anti-CMV IgG. Of these, 3 patients (21.4%) exhibited high CMV IgG avidity, without detectable anti-CMV IgM and biopsy-proven CMV colitis. Of the 14 IBD patients with CDI, 8 patients (57.1%) were receiving anti-tumor necrosis factor (anti-TNF) therapy (21.4 % infliximab or golimumab, 7.1% vedolizumab or adalimumab) and 43.5% of patients were being treated with systemic corticosteroids. Four UC patients (28.6%) on steroids of the 14 CDI patients underwent a colectomy whereas none of the not on steroids patients underwent colectomy (p=0.25). Among them, 1 patient (7.1%) had recurrent CDI after 5 months from the first episode of CDI.These patients were treated with vancomycin, metronidazole and fidaxomicin. The mean age of patients that had a colectomy 65.5±9.32 (n=4) was higher than the mean age of those 47.30±14.49 (n=10) who improved (UMann-Whitney=6. p=0.04). Conclusions Immunosuppressive medications and older age are associated with increased risk of CDI and poor outcome. Although, CMV is a rare colonic pathogen in the immunocompetent patient, it should be included and screened when exacerbation of IBD occurs in patients receiving any type of immunosuppressive therapy.
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Affiliation(s)
- Maria Kosmidou
- 1st Division of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece
| | | | - Maria Saridi
- General Hospital of Corinth. Scientific Department of Social and Educational Policy, University of Peloponnese, Corinth. Hellenic Open University, Corinth, Greece
| | - Alexandros Skamnelos
- Division of Gastroenterology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece
| | - Athanasios Kavvadias
- Division of Gastroenterology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece
| | - Anna Batistatou
- Pathology Laboratory, Chair of Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece
| | - Konstantina G Gartzonika
- Microbiology Laboratory, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece
| | - Stavroula Tsiara
- 2nd Division of Internal Medicine, Chair of Infection Control Committee, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece
| | - Konstantinos H Katsanos
- Division of Gastroenterology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece
| | - Dimitrios K Christodoulou
- Division of Gastroenterology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece
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Jung KH, Kim J, Lee HS, Choi J, Jang SJ, Jung J, Kim MJ, Chong YP, Lee SO, Choi SH, Kim YS, Woo JH, Park SH, Yang DH, Ye BD, Yang SK, Kim SH. Clinical Implications of the CMV-Specific T-Cell Response and Local or Systemic CMV Viral Replication in Patients With Moderate to Severe Ulcerative Colitis. Open Forum Infect Dis 2019; 6:ofz526. [PMID: 31893211 PMCID: PMC6934884 DOI: 10.1093/ofid/ofz526] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 12/10/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The precise role of cytomegalovirus (CMV) in ulcerative colitis (UC) remains disputed. We evaluated the association of CMV-specific host immune responses and systemic or local viral replication with responses to systemic steroids in patients with moderate to severe UC. METHODS Patients who were hospitalized for moderate to severe UC between April 2015 and June 2016 were enrolled. At baseline, all enrolled patients underwent CMV-specific enzyme-linked immunospot assays, quantitative polymerase chain reaction (qPCR) analysis of blood and colonic tissue for CMV viral load, histopathological testing for CMV in colonic tissue by hematoxylin and eosin staining, and immunohistochemical (IHC) analysis. Clinical responses to steroid therapy based on the Oxford index were assessed on day 3. RESULTS Of the 80 patients evaluated, 28 (35.0%) had poor responses to steroid therapy on day 3 of intensive treatment. The presence of inclusion bodies (32.1%) and high-grade (≥3) positivity on IHC (50.0%), as well as colonic (mean 1440.4 copies/mg) and blood (mean, 3692.6 copies/mL) CMV viral load, were higher in steroid-refractory UC patients than the control group (13.5%, 1.9%, mean 429.2 copies/mg, and mean 231.2 copies/mL, respectively; P = .046, .009, .017, and .002, respectively). However, CMV-specific T-cell responses were not associated with steroid-refractory UC. Multivariate analysis revealed that a higher Mayo score (odds ratio [OR], 2.00; P = .002) and higher blood CMV viral load via qPCR analysis (OR, 3.58; P = .044) were independent risk factors for steroid-refractory UC. CONCLUSIONS In patients with moderate to severe UC, higher Mayo score and blood CMV expression determined by qPCR are independently associated with steroid refractoriness. CLINICALTRIALSGOV REGISTRATION NUMBER NCT02439372.
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Affiliation(s)
- Kyung Hwa Jung
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jihun Kim
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ho-Su Lee
- Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jene Choi
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Se Jin Jang
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jiwon Jung
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Min Jae Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yong Pil Chong
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang-Oh Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang-Ho Choi
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yang Soo Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jun Hee Woo
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang Hyoung Park
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Dong-Hoon Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Byong Duk Ye
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sung-Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Correspondence: S.-H. Kim, MD, PhD, Department of Infectious Diseases, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea ()
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Xuan L, Ren L, Han F, Gong L, Wan Z, Yang S, Liu H, Lv Y, Liu L. Cytomegalovirus Infection Exacerbates Experimental Colitis by Promoting IL-23 Production. Inflammation 2019; 43:326-335. [PMID: 31701354 DOI: 10.1007/s10753-019-01122-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Many studies have demonstrated an association between cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). Moreover, CMV infection is more common in patients with severe or steroid-refractory IBD. However, it is not clarified whether CMV worsens IBD or if it is merely a surrogate marker for IBD. Here, we used the dextran sodium sulfate (DSS)-induced colitis model to investigate if CMV infection exacerbates colitis. The mice were injected intraperitoneally with 10 MOI of murine CMV (MCMV) and thereafter, chronic colitis was induced by one cycle of DSS exposure. Anti-IL-23R mAb at 20 μg/mice and pyrrolidine dithiocarbamate (PDTC), an effective NF-κB inhibitor, at 50 mg/kg were administrated to the mice. The MCMV-infected mice had a shorter colon length and a higher histopathology score than the mock inoculum-treated mice, while anti-IL-23R mAb administration ameliorated the pathological changes. Expression of IL-23, phospho-NF-κB p65, and phospho-IκBα was upregulated in colon tissues of the MCMV-infected mice compared to mock inoculum-treated mice, while treatment with PDTC attenuated colonic IL-23 production. These data demonstrated that CMV infection could accelerate IBD development. This effect may be due to its activation on NF-κB signaling pathway and subsequently IL-23 production.
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Affiliation(s)
- Lingling Xuan
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Lulu Ren
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Feifei Han
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Lili Gong
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Zirui Wan
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Song Yang
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - He Liu
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Yali Lv
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China.
| | - Lihong Liu
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China.
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Abstract
Introduction: Despite the introduction of novel therapies and treatment strategies for ulcerative colitis (UC), many patients develop acute, severe episodes, warranting prompt care and aggressive management. There is a significant unmet need to improve outcomes in these patients. Clinicians must be able to identify those that will have worse prognosis and plan an aggressive therapy with an early/proactive adjustments in management if needed.Areas covered: The aim of this review is to evaluate the most recent evidence on the assessment and management of patients with acute severe ulcerative colitis. We searched the mainstream literature search engines for the most recent evidence on diagnosis and management of acute UC.Expert Opinion: The approach to patients with severe UC includes clinical and endoscopic assessment of disease severity and ruling out over-infections. While intravenous corticosteroids remain the first line therapy for acute severe colitis, many patients do not respond and require escalation to calcineurin inhibitors or infliximab, and may ultimately require colectomy. Even though several novel therapies are available or in development, their role in acute severe episodes of colitis is unknown.
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Affiliation(s)
- Rocío Sedano
- Division of Gastroenterology, Hospital Clínico de la Universidad de Chile, Santiago, Chile
| | - Rodrigo Quera
- Inflammatory Bowel Disease Program, Division of Gastroenterology, Clínica Las Condes, Santiago, Chile
| | - Daniela Simian
- Inflammatory Bowel Disease Program, Division of Gastroenterology, Clínica Las Condes, Santiago, Chile
| | - Andres J Yarur
- Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI, USA
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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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Ambelil M, Saulino DM, Ertan A, DuPont AW, Younes M. The Significance of So-Called Equivocal Immunohistochemical Staining for Cytomegalovirus in Colorectal Biopsies. Arch Pathol Lab Med 2019; 143:985-989. [PMID: 30702332 DOI: 10.5858/arpa.2018-0235-oa] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/14/2023]
Abstract
CONTEXT.— Recent studies examining immunohistochemical staining of colorectal biopsies for cytomegalovirus (CMV) reported that some cases showed only occasional small positive nuclei that were called equivocal for CMV. OBJECTIVES.— To determine the extent and clinical significance of equivocal CMV staining in colorectal biopsies. DESIGN.— Two-hundred twenty-one consecutive cases of colon and rectal biopsies that were stained for CMV by immunohistochemistry were retrieved from our files and reviewed. Staining results were recorded as negative, unequivocal, or equivocal. Results were correlated with clinicopathologic data, results of polymerase chain reaction studies for CMV, and treatment history. RESULTS.— Fifty-two cases (24% of all tested, 63% of positive cases) showed equivocal staining for CMV, and of these, 41 had follow-up information. Polymerase chain reaction for CMV was performed largely on blood samples and was not found to be sensitive for the detections of CMV proctocolitis. Of 25 patients who received antiviral treatment, 21 (84%) had complete resolution of symptoms, compared with 8 of 16 (50%) who did not receive antivirals (P = .02). There was no statistically significant difference in response to antiviral drugs in patients with equivocal and unequivocal CMV staining (P = .17). CONCLUSIONS.— Equivocal CMV staining likely represents true CMV proctocolitis. Prospective studies are needed to confirm these findings.
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Affiliation(s)
- Manju Ambelil
- From the Department of Pathology and Laboratory Medicine (Drs Ambelil, Saulino, and Younes) and the Department of Medicine, Section of Gastroenterology, Hepatology and Nutrition (Drs Ertan and DuPont), The University of Texas Health Science Center at Houston McGovern Medical School, and Memorial Hermann Hospital-TMC, Houston, Texas
| | - David M Saulino
- From the Department of Pathology and Laboratory Medicine (Drs Ambelil, Saulino, and Younes) and the Department of Medicine, Section of Gastroenterology, Hepatology and Nutrition (Drs Ertan and DuPont), The University of Texas Health Science Center at Houston McGovern Medical School, and Memorial Hermann Hospital-TMC, Houston, Texas
| | - Atilla Ertan
- From the Department of Pathology and Laboratory Medicine (Drs Ambelil, Saulino, and Younes) and the Department of Medicine, Section of Gastroenterology, Hepatology and Nutrition (Drs Ertan and DuPont), The University of Texas Health Science Center at Houston McGovern Medical School, and Memorial Hermann Hospital-TMC, Houston, Texas
| | - Andrew W DuPont
- From the Department of Pathology and Laboratory Medicine (Drs Ambelil, Saulino, and Younes) and the Department of Medicine, Section of Gastroenterology, Hepatology and Nutrition (Drs Ertan and DuPont), The University of Texas Health Science Center at Houston McGovern Medical School, and Memorial Hermann Hospital-TMC, Houston, Texas
| | - Mamoun Younes
- From the Department of Pathology and Laboratory Medicine (Drs Ambelil, Saulino, and Younes) and the Department of Medicine, Section of Gastroenterology, Hepatology and Nutrition (Drs Ertan and DuPont), The University of Texas Health Science Center at Houston McGovern Medical School, and Memorial Hermann Hospital-TMC, Houston, Texas
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Reply to Potential Pitfalls When Assessing the Impact of Cytomegalovirus in Inflammatory Bowel Disease. J Clin Gastroenterol 2019; 53:470. [PMID: 28697147 DOI: 10.1097/mcg.0000000000000848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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