|
1
|
Wang G, Zhao J, Jiang J, Huang A, Ye L, Jiang Z. The Positive Immunohistochemical Staining of Cytomegalovirus in Colon Biopsy Samples Suggests That the Viral DNA Load in qPCR Is High. Int J Surg Pathol 2025:10668969251339808. [PMID: 40375791 DOI: 10.1177/10668969251339808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/18/2025]
Abstract
Background and AimImmunohistochemistry (IHC) and/or polymerase chain reaction (PCR) are essential for confirming active cytomegalovirus (CMV) infection in patients with inflammatory bowel disease (IBD). A definitive cut-off has not yet been established; however, Roblin et al suggested a viral load threshold of > 250 viral copies/mg of tissue. In this study, we examined the concordance between IHC and quantitative real-time PCR (qPCR) in the detection of CMV in colonic biopsy specimens.MethodsA total of 170 samples that underwent IHC and qPCR were collected. The positive rate and concordance of IHC and qPCR were studied, and the impact of ulcer tissue on both detection methods was observed.ResultsIn a study of 170 hematoxylin-eosin (H&E) sections, 8 samples were found to be infected with cytomegalovirus. The positive rates of CMV detection using IHC and qPCR were 17% (29/170) and 25% (43/170), respectively. Among the IHC-positive samples, the qPCR positive rate was 100% (29/29), with all CMV-DNA loads > 250 copies/mg. The concordance between IHC and qPCR was 94% (kappa = 0.756, P < .001). IHC analysis revealed that positive cells in ulcerated mucosa were more frequent than those in nonulcerated mucosa (P < .001). Additionally, a total of 14 samples tested negative for CMV via IHC but positive through qPCR. Among these, 11 samples did not contain ulcerated tissue.ConclusionThe presence of one or more IHC-positive cells in colon biopsy samples indicates a high CMV-DNA load in qPCR (> 250 copies/mg). IHC-positive cells were more frequently observed in ulcerated mucosa compared to nonulcerated mucosa.
Collapse
Affiliation(s)
- Guanglan Wang
- Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China
| | - Jianmin Zhao
- Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China
| | - Junchang Jiang
- Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China
| | - Aihua Huang
- Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China
| | - Lingna Ye
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China
| | - Zhinong Jiang
- Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China
| |
Collapse
|
|
2
|
Szlak J, Magdziak A, Mróz A, Wieszczy-Szczepanik P, Reguła J, Zagórowicz E. Cytomegalovirus infection in patients with active ulcerative colitis: a prospective observational study. Eur J Gastroenterol Hepatol 2025:00042737-990000000-00534. [PMID: 40359279 DOI: 10.1097/meg.0000000000003001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
Abstract
OBJECTIVES The role of cytomegalovirus (CMV) infection in the course of inflammatory bowel disease is still controversial. We aimed to prospectively evaluate the course of ulcerative colitis in patients with exacerbation, in whom CMV status was examined using immunohistochemistry of bowel biopsies. METHODS In a single centre, we followed-up consecutive patients admitted for moderate or severe ulcerative colitis flare between 2016 and 2019. Colectomies, repeated hospitalisations, major treatment modifications, and quality of life (QoL) were recorded. The relationship between categorical variables was examined with the χ2 statistical test or Fisher's exact test. RESULTS Of 84 patients, 16 (19%) were CMV-positive. A Mayo endoscopic score of 3 was more frequent in CMV-positive than CMV-negative patients (81.2 vs. 51.5%; P = 0.048) as was corticosteroid treatment (81.2 vs. 54.4%; P = 0.015). Median follow-up was 2.1 years (range: 0.3-3.6 years). Colectomy was performed in 20 (23.8%) patients, with similar rates in CMV-positive (25%) and CMV-negative patients (23.5%; P = 1.0). Similarly, no differences were found in the frequency of hospitalisation and QoL. The percentage of patients who started biological treatment was higher in the CMV-negative than in the CMV-positive group (58.8 vs. 18.8%; P = 0.005). CONCLUSION CMV infection was present in 19% of consecutive patients hospitalised for ulcerative colitis flare. Corticosteroid treatment and severe endoscopic lesions were observed more often in patients with CMV-positive. In the following 2.1 years, the colectomy rate did not differ between patients with CMV-positive and CMV-negative. Routine screening for CMV in ulcerative colitis exacerbation is not advisable.
Collapse
Affiliation(s)
| | | | - Andrzej Mróz
- Department of Pathology and Laboratory Medicine, The Maria Sklodowska-Curie National Research Institute of Oncology
- Department of Pathomorphology, Medical Centre of Postgraduate Education
| | | | - Jaroslaw Reguła
- Department of Microbiology
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Centre of Postgraduate Education, Warsaw, Poland
| | - Edyta Zagórowicz
- Department of Microbiology
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Centre of Postgraduate Education, Warsaw, Poland
| |
Collapse
|
|
3
|
Gholami Shahrebabak M, Kouchaki H, Gholami Shahrebabak A, Ravankhah M, Abdollahi M, Akbari M, Lankarani KB. Systematic review and meta-analysis of cytomegalovirus-associated adverse outcomes and healthcare resource utilization in hospitalized patients with inflammatory bowel disease. Int J Colorectal Dis 2025; 40:101. [PMID: 40272527 PMCID: PMC12021708 DOI: 10.1007/s00384-025-04886-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/05/2025] [Indexed: 04/25/2025]
Abstract
PURPOSE Serious complications and unplanned healthcare utilization are reported among inflammatory bowel disease (IBD) hospitalizations with associated cytomegalovirus (CMV). The present systematic review and meta-analysis aimed to examine the in-hospital outcomes of CMV-related hospitalization in IBD patients. METHODS Electronic databases were systematically searched in PubMed, Web of Science (ISI), Scopus, Embase, and Google Scholar until February 2024. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Cochran's Q test and I2 statistics were applied to evaluate potential heterogeneity across eligible studies. The random-effects model obtained pooled odds ratio (OR) estimates and associated 95% confidence intervals (CI). RESULTS Sixteen articles were included in the meta-analysis, encompassing 5120 IBD patients diagnosed with comorbid CMV infection. Our findings indicated that compared to IBD patients without CMV, those with both CMV and IBD had a longer hospital length of stay (LOS) (8.65 days longer; 95% CI: 6.96, 10.34; P < 0.01), a greater colectomy risk (OR = 2.26; 95% CI: 1.53, 3.34; P < 0.01), and higher in-hospital mortality (OR = 2.83; 95% CI: 1.92, 4.16; P < 0.01). However, the difference in hospital charges between the two groups was not statistically significant (P = 0.78). Sensitivity analysis using the leave-one-out approach revealed significant changes in hospital costs after excluding certain studies. Additionally, subgroup analyses showed significant differences based on IBD subtypes for surgery risk and LOS. CONCLUSION Our findings suggest that CMV infection is associated with poorer outcomes in hospitalized IBD patients, highlighting the importance of early detection and appropriate management of CMV infection in this population to improve clinical outcomes and reduce healthcare resource utilization.
Collapse
Affiliation(s)
- Maryam Gholami Shahrebabak
- Department of Pediatrics, School of Medicine, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran
| | - Hosein Kouchaki
- Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- USERN Office, Fasa University of Medical Sciences, Fasa, Iran
| | - Azam Gholami Shahrebabak
- Department of Pediatrics, Afzalipour Hospital, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Mahdi Ravankhah
- Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mozhan Abdollahi
- Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maryam Akbari
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, 8th Floor, Building No. 2, Zand Avenue, Shiraz, Iran.
| | - Kamran B Lankarani
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, 8th Floor, Building No. 2, Zand Avenue, Shiraz, Iran.
| |
Collapse
|
|
4
|
Jentzer A, Cantais A, Roblin X, Barrau M, Garcin A, Bourlet T, Pozzetto B, Pillet S. Predictive Factors of Cytomegalovirus Colonic Reactivation in Patients with Active Ulcerative Colitis. Viruses 2025; 17:555. [PMID: 40284998 PMCID: PMC12031004 DOI: 10.3390/v17040555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Revised: 03/28/2025] [Accepted: 04/08/2025] [Indexed: 04/29/2025] Open
Abstract
Cytomegalovirus (CMV)-associated colitis reflects the adverse impact of CMV reactivation on ulcerative colitis (UC). Its diagnosis requires the detection of viral markers in intestinal biopsies sampled during endoscopy, which may constitute invasive and expensive analyses. Moreover, less than 30% of acute flare-ups in steroid refractory UC are associated with CMV colitis. This retrospective study aimed to identify non-invasive factors that are predictive of CMV reactivation, and was conducted from 2014 to 2019 in a cohort of UC patients consulting at the University Hospital of Saint-Etienne, France. Patient characteristics, disease activity, immunosuppressive treatment and tissue CMV DNA load were collected at the time of UC relapse. Factors potentially associated with CMV reactivation were analyzed through a multivariate analysis. A total of 173 UC patients providing 323 pairs of intestinal biopsies were analyzed. In the CMV seropositive subgroup, a Mayo endoscopic score ≥2 (OR 2.553, 95% CI 1.353-4.818, p = 0.004) was identified as a predictive factor of CMV colitis in the multivariate analysis; in contrast, biological parameters exhibited no predictive value. In addition, the use of anti-TNFα monoclonal antibodies was associated with a reduced risk of CMV reactivation (OR 0.384, 95% CI 0.158-0.935, p = 0.035). Intestinal biopsies appear to be unavoidable for assessing disease activity and CMV reactivation in UC patients.
Collapse
Affiliation(s)
- Alexandre Jentzer
- CIRI—Centre International de Recherche en Infectiologie (GIMAP Team, University of Lyon, Univerity of Saint-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1), Cedex 02, 42218 Saint-Etienne, France; (A.J.); (A.C.); (X.R.); (T.B.); (S.P.)
| | - Aymeric Cantais
- CIRI—Centre International de Recherche en Infectiologie (GIMAP Team, University of Lyon, Univerity of Saint-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1), Cedex 02, 42218 Saint-Etienne, France; (A.J.); (A.C.); (X.R.); (T.B.); (S.P.)
| | - Xavier Roblin
- CIRI—Centre International de Recherche en Infectiologie (GIMAP Team, University of Lyon, Univerity of Saint-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1), Cedex 02, 42218 Saint-Etienne, France; (A.J.); (A.C.); (X.R.); (T.B.); (S.P.)
- Department of Gastroenterology, University-Hospital of Saint-Etienne, Cedex 02, 42055 Saint-Etienne, France;
| | - Mathilde Barrau
- Department of Gastroenterology, University-Hospital of Saint-Etienne, Cedex 02, 42055 Saint-Etienne, France;
| | - Arnauld Garcin
- Clinical Research, Innovation and Pharmacology Unit (URCIP), SNA/EPIS, Faculty of Medicine Jacques Lisfranc, Saint-Etienne University Hospital, Cedex 02, 42023 Saint-Etienne, France;
| | - Thomas Bourlet
- CIRI—Centre International de Recherche en Infectiologie (GIMAP Team, University of Lyon, Univerity of Saint-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1), Cedex 02, 42218 Saint-Etienne, France; (A.J.); (A.C.); (X.R.); (T.B.); (S.P.)
- Laboratory of Infectious Agents and Hygiene, University-Hospital of Saint-Etienne, Cedex 02, 42055 Saint-Etienne, France
| | - Bruno Pozzetto
- CIRI—Centre International de Recherche en Infectiologie (GIMAP Team, University of Lyon, Univerity of Saint-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1), Cedex 02, 42218 Saint-Etienne, France; (A.J.); (A.C.); (X.R.); (T.B.); (S.P.)
- Laboratory of Infectious Agents and Hygiene, University-Hospital of Saint-Etienne, Cedex 02, 42055 Saint-Etienne, France
| | - Sylvie Pillet
- CIRI—Centre International de Recherche en Infectiologie (GIMAP Team, University of Lyon, Univerity of Saint-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1), Cedex 02, 42218 Saint-Etienne, France; (A.J.); (A.C.); (X.R.); (T.B.); (S.P.)
- Laboratory of Infectious Agents and Hygiene, University-Hospital of Saint-Etienne, Cedex 02, 42055 Saint-Etienne, France
| |
Collapse
|
|
5
|
George NA, Surendran S, Paulose RR, Pradeep M. Hyperacute reactivation of cytomegalovirus-induced gastroduodenitis during remission induction in a young male patient with granulomatosis with polyangiitis: a case report and review of literature. J Med Case Rep 2025; 19:68. [PMID: 39994816 PMCID: PMC11849236 DOI: 10.1186/s13256-025-05103-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Accepted: 01/31/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Cytomegalovirus is a pathogen known to aggravate the inflammatory response in autoimmune diseases via molecular mimicry. Although it is recognized that cytomegalovirus activation can happen during extended but variable periods of immunosuppression (14-90 days), it is rarely reported in conjunction with an acute flare-up of an autoimmune disease. Currently, there is no consensus on cytomegalovirus prophylaxis for patients initiating remission induction. CASE PRESENTATION Here, we present the case of a 31-year-old male patient of South Indian ethnicity, presenting with a 2-month history of fever, conductive hearing loss, and ear discharge. This was associated with symmetrical inflammatory polyarthritis for 1 month, unilateral painful conjunctivitis, and skin erythema for 5 days. Blood analyses showed elevated inflammatory markers; strongly positive anti-proteinase 3 and cytoplasmic antineutrophil cytoplasmic antibody levels; normal procalcitonin and complement levels; and negative anti-myeloperoxidase and perinuclear antineutrophil cytoplasmic antibody levels. A nasal endoscopy revealed a midline granuloma with vasculitis features on biopsy. Imaging revealed pulmonary nodules and otomastoiditis. Now diagnosed with granulomatosis with polyangiitis, the patient developed signs of gastroduodenitis within a day of initiation of immunosuppression with high-dose "pulse" intravenous methylprednisolone. We evaluated him for mesenteric ischemia/gastrointestinal vasculitis. However, the duodenal biopsies from the bleeding ulcers revealed a probable cytomegalovirus infection, confirmed with high serum viral loads. We treated him with a ganciclovir regimen and transitioned him to steroid-sparing immunosuppressant therapy with mycophenolate mofetil, which was selected over cyclophosphamide for its noninferior effectiveness and better safety profile in non-life-threatening granulomatosis with polyangiitis disease. The patient recovered uneventfully and is currently in remission. CONCLUSION Cytomegalovirus reactivation is possible during short-term steroid pulse therapy. Further research is needed to evaluate whether routine cytomegalovirus screening is warranted before starting immunosuppressive treatment with high-dose steroids in autoimmune conditions.
Collapse
Affiliation(s)
- Nisha Annie George
- Department of Infectious Diseases and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Sandeep Surendran
- Department of Rheumatology and Clinical Immunology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India.
| | - Roopa Rachel Paulose
- Department of Pathology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Manu Pradeep
- Department of Rheumatology and Clinical Immunology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| |
Collapse
|
|
6
|
Tian Y, Dai J, Yang Y, Guo X, Wang W, Li F, Wang J, Liu R. Relationship between the risk of intestinal mucosal Epstein-Barr virus and/or cytomegalovirus infection and peripheral blood NK cells numbers in patients with ulcerative colitis: a cross-sectional study in Chinese population. Front Microbiol 2024; 15:1498483. [PMID: 39697654 PMCID: PMC11652489 DOI: 10.3389/fmicb.2024.1498483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 11/21/2024] [Indexed: 12/20/2024] Open
Abstract
Objective This study aimed to analyze the relationship between the risk of common opportunistic pathogens Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection in intestinal mucosal tissues of Ulcerative Colitis (UC) patients and the number of peripheral blood NK cells. Methods UC patients admitted to a third-grade class-A hospital from January 2018 to December 2023 were selected as research population. Clinical data of the patients were collected from the electronic medical record system. Additionally, samples of intestinal mucosal tissues were obtained for real-time fluorescence quantitative PCR to detect and analyze the viral load of CMV and EBV. Blood samples were collected for lymphocyte subsets analysis. Multivariable logistic regression models analyses was used to determine the odds ratio (OR) and 95% confidence interval (95% CI) for the independent association between NK cells and EBV/CMV infections in UC. We further applied the restricted cubic spline analysis and smooth curve fitting to examine the non-linear relationship between them. Results 378 UC patients were enrolled. Of these patients, there were 194 patients (51.32%) with EBV /CMV infection. In multivariable logistic regression analyses NK cells was independently associated with EBV and/or CMV infection after adjusted potential confounders (OR 8.24, 95% CI 3.75-18.13, p < 0.001). A nonlinear relationship was found between NK cells and EBV/CMV infections, which had a threshold around 10.169. The effect sizes and CIs below and above the threshold were 0.535 (0.413-0.692), p < 0.001 and 1.034 (0.904-1.183), p > 0.05, respectively. Conclusion There was a non-linear relationship between NK cells and EBV/CMV infections. The risk for EBV/CMV infections was not increased with increasing NK cells in individuals with NK cells ≥ 10.169%, whereas the risk for EBV and/or CMV infection was increased with an decreasing NK cells in those with NK cells < 10.169%. The risk of EBV/CMV infections increases when NK cells were below a certain level.
Collapse
Affiliation(s)
- Ye Tian
- Department of Gastroenterology, Shanxi Provincial People’s Hospital, National Clinical Research Center for Digestive Diseases, Shanxi Inflammatory Bowel Disease Center, Taiyuan, China
| | - Jinghua Dai
- School of Nursing, Shanxi Medical University, Shanxi Provincial People’s Hospital, Taiyuan, China
| | - Yunfeng Yang
- Department of Gastroenterology, Shanxi Provincial People’s Hospital, National Clinical Research Center for Digestive Diseases, Shanxi Inflammatory Bowel Disease Center, Taiyuan, China
| | - Xiaofeng Guo
- Department of Gastroenterology, Shanxi Provincial People’s Hospital, National Clinical Research Center for Digestive Diseases, Shanxi Inflammatory Bowel Disease Center, Taiyuan, China
| | - Wei Wang
- Department of Laboratory Medicine, Shanxi Provincial People’s Hospital, Taiyuan, China
| | - Fengxia Li
- Department of Gastroenterology, Shanxi Provincial People’s Hospital, National Clinical Research Center for Digestive Diseases, Shanxi Inflammatory Bowel Disease Center, Taiyuan, China
| | - Juzi Wang
- Nursing Department, Shanxi Provincial People’s Hospital, Taiyuan, China
| | - Ruiyun Liu
- Shanxi Children’s Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| |
Collapse
|
|
7
|
Melotti L, Rinaldi M, Salice M, Dussias NK, Vanigli N, Calabrese C, Scaioli E, Gabrielli L, Lazzarotto T, Rosini F, Viale P, Gionchetti P, Giannella M, Rizzello F. Is CMV DNAemia an early marker of CMV colitis in patients with active ulcerative colitis? Microbiol Spectr 2024; 12:e0115924. [PMID: 39400159 PMCID: PMC11537068 DOI: 10.1128/spectrum.01159-24] [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: 05/09/2024] [Accepted: 07/11/2024] [Indexed: 10/15/2024] Open
Abstract
Cytomegalovirus (CMV) colitis is a serious concern worsening the prognosis of patients with ulcerative colitis (UC). We aimed to assess risk factors and prognostic impact of CMV colitis in patients with moderate-to-severe UC flare. We conducted a retrospective, observational, single-center study. Consecutive adult patients hospitalized for moderate-to-severe UC from January 2020 to June 2023 were included. The primary endpoint was a diagnosis of CMV-colitis according to immunohistochemistry on tissue biopsies. The secondary endpoint was the need for colectomy within 30 days. Overall, 135 patients were included. CMV colitis was diagnosed in n = 37 (27.4%): n = 19 (51.4%) endoscopically, the remaining on surgical specimens. Of them, n = 23 (62.2%) had positive CMV-DNAemia with a median value of 1,008 cp/mL (interquartile range 318-2,980). Differences between the two groups (CMV colitis vs non-CMV) included age (60 vs 41 years, P = 0.004), Charlson Comorbidity Index (1 vs 0, P = 0.003), steroid refractoriness (86.5% vs 62.2%, P = 0.007), and positive CMV-DNAemia (62.2% vs 10.1%, P < 0.001). At multivariable analysis, steroid-refractory disease, Charlson Comorbidity Index, and CMV-DNAemia were associated with CMV colitis. Overall, n = 54 (39.7%) patients underwent colectomy, and this was significantly more common in patients with CMV colitis vs non-CMV group (54.1% vs 34.4%, P = 0.049). Kaplan-Meier showed that antiviral therapy seems to have a relevant impact on colectomy (P < 0.001). CMV-DNA blood detection is independently associated with CMV-positive refractory UC. Since CMV colitis may increase the risk of colectomy and antiviral treatment seems to reduce such risk, prospective studies are needed to confirm the role of CMV-DNA blood detection to early diagnose CMV colitis. IMPORTANCE Cytomegalovirus (CMV) colonic reactivation worsens the prognosis of patients with active ulcerative colitis. Blood CMV-DNA reactivation is strongly associated with CMV colitis. Prompt diagnosis and treatment of CMV colitis can avoid surgery in most cases.
Collapse
Affiliation(s)
- Laura Melotti
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Dept of Medical and Surgical Sciences, IBD Unit- IRCCS Azienda Ospedaliero-Universitaria- Policlinico Sant'Orsola-Malpighi, Bologna, Italy
| | - Matteo Rinaldi
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Infectious Disease Unit, Department for Integrated Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Marco Salice
- Dept of Medical and Surgical Sciences, IBD Unit- IRCCS Azienda Ospedaliero-Universitaria- Policlinico Sant'Orsola-Malpighi, Bologna, Italy
| | - Nikolas K. Dussias
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Dept of Medical and Surgical Sciences, IBD Unit- IRCCS Azienda Ospedaliero-Universitaria- Policlinico Sant'Orsola-Malpighi, Bologna, Italy
| | - Nicholas Vanigli
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Dept of Medical and Surgical Sciences, IBD Unit- IRCCS Azienda Ospedaliero-Universitaria- Policlinico Sant'Orsola-Malpighi, Bologna, Italy
| | - Carlo Calabrese
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Dept of Medical and Surgical Sciences, IBD Unit- IRCCS Azienda Ospedaliero-Universitaria- Policlinico Sant'Orsola-Malpighi, Bologna, Italy
| | - Eleonora Scaioli
- Dept of Medical and Surgical Sciences, IBD Unit- IRCCS Azienda Ospedaliero-Universitaria- Policlinico Sant'Orsola-Malpighi, Bologna, Italy
| | - Liliana Gabrielli
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Microbiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Tiziana Lazzarotto
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Microbiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Francesca Rosini
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Pierluigi Viale
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Infectious Disease Unit, Department for Integrated Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Paolo Gionchetti
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Dept of Medical and Surgical Sciences, IBD Unit- IRCCS Azienda Ospedaliero-Universitaria- Policlinico Sant'Orsola-Malpighi, Bologna, Italy
| | - Maddalena Giannella
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Infectious Disease Unit, Department for Integrated Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Fernando Rizzello
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Dept of Medical and Surgical Sciences, IBD Unit- IRCCS Azienda Ospedaliero-Universitaria- Policlinico Sant'Orsola-Malpighi, Bologna, Italy
| |
Collapse
|
|
8
|
Yilmaz ZB, Memisoglu F, Akbulut S. Management of cytomegalovirus infection after liver transplantation. World J Transplant 2024; 14:93209. [PMID: 39295968 PMCID: PMC11317856 DOI: 10.5500/wjt.v14.i3.93209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 05/05/2024] [Accepted: 05/27/2024] [Indexed: 07/31/2024] Open
Abstract
Cytomegalovirus (CMV) infection is one of the primary causes of morbidity and mortality following liver transplantation (LT). Based on current worldwide guidelines, the most effective strategies for avoiding post-transplant CMV infection are antiviral prophylaxis and pre-emptive treatment. CMV- IgG serology is the established technique for pretransplant screening of both donors and recipients. The clinical presentation of CMV infection and disease exhibits variability, prompting clinicians to consistently consider this possibility, particularly within the first year post-transplantation or subsequent to heightened immunosuppression. At annual symposia to discuss CMV prevention and how treatment outcomes can be improved, evidence on the incorporation of immune functional tests into clinical practice is presented, and the results of studies with new antiviral treatments are evaluated. Although there are ongoing studies on the use of letermovir and maribavir in solid organ transplantation, a consensus reflected in the guidelines has not been formed. Determining the most appropriate strategy at the individual level appears to be the key to enhancing outcomes. Although prevention strategies reduce the risk of CMV disease, the disease can still occur in up to 50% of high-risk patients. A balance between the risk of infection and disease development and the use of immunosuppressants must be considered when talking about the proper management of CMV in solid organ transplant recipients. The objective of this study was to establish a comprehensive framework for the management of CMV in patients who have had LT.
Collapse
Affiliation(s)
- Zeynep Burcin Yilmaz
- Infectious Diseases and Clinical Microbiology, Inonu University Faculty of Medicine, Malatya 44280, Türkiye
| | - Funda Memisoglu
- Infectious Diseases and Clinical Microbiology, Inonu University Faculty of Medicine, Malatya 44280, Türkiye
| | - Sami Akbulut
- Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Türkiye
| |
Collapse
|
|
9
|
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.
Collapse
Affiliation(s)
- Marouf Alhalabi
- Gastroenterology Department, Damascus Hospital, Almujtahed Street, Damascus, Syria.
| | | |
Collapse
|
|
10
|
Onisor D, Brusnic O, Mocan S, Stoian M, Avram C, Boicean A, Dobru D. Cytomegalovirus in Ulcerative Colitis: An Unwanted "Guest". Pathogens 2024; 13:650. [PMID: 39204250 PMCID: PMC11356953 DOI: 10.3390/pathogens13080650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Revised: 07/23/2024] [Accepted: 07/30/2024] [Indexed: 09/03/2024] Open
Abstract
The role of cytomegalovirus (CMV) in the flare-up of ulcerative colitis (UC) is not clearly understood. CMV can cause similar symptoms in different clinical contexts, which may be attributed to the natural evolution of the viral infection, the patient's immune status, or its association with inflammatory bowel disease (IBD). This study aims to delineate the diverse manifestations of CMV-related lesions from clinical, endoscopic, and histopathological perspectives, alongside a brief narrative review of the literature. In managing IBD patients, it is crucial to be vigilant for signs of CMV reactivation, especially before the initiation of more intensive therapies.
Collapse
Affiliation(s)
- Danusia Onisor
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540139 Targu Mures, Romania; (D.O.); (D.D.)
- Gastroenterology Department, Mureș County Clinical Hospital, 540103 Targu Mures, Romania
| | - Olga Brusnic
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540139 Targu Mures, Romania; (D.O.); (D.D.)
- Gastroenterology Department, Mureș County Clinical Hospital, 540103 Targu Mures, Romania
| | - Simona Mocan
- Pathology Department, Emergency County Hospital, 540136 Targu Mures, Romania;
| | - Mircea Stoian
- Department of Anesthesiology and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania;
| | - Calin Avram
- Department of Medical Informatics and Biostatistics, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540139 Targu Mures, Romania
| | - Adrian Boicean
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania;
| | - Daniela Dobru
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540139 Targu Mures, Romania; (D.O.); (D.D.)
- Gastroenterology Department, Mureș County Clinical Hospital, 540103 Targu Mures, Romania
| |
Collapse
|
|
11
|
Van Eaton J, Hatch QM. Surgical Emergencies in Inflammatory Bowel Disease. Surg Clin North Am 2024; 104:685-699. [PMID: 38677830 DOI: 10.1016/j.suc.2023.11.012] [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] [Indexed: 04/29/2024]
Abstract
Inflammatory bowel disease (IBD) patients are at risk for undergoing emergency surgery for fulminant disease, toxic megacolon, bowel perforation, intestinal obstruction, or uncontrolled gastrointestinal hemorrhage. Unfortunately, medical advancements have failed to significantly decrease rates of emergency surgery for IBD. It is therefore important for all acute care and colorectal surgeons to understand the unique considerations owed to this often-challenging patient population.
Collapse
Affiliation(s)
- John Van Eaton
- Department of General Surgery, Madigan Army Medical Center, 9040A Jackson Avenue, JBLM, Tacoma, WA 98413, USA.
| | - Quinton M Hatch
- Department of General Surgery, Madigan Army Medical Center, 9040A Jackson Avenue, JBLM, Tacoma, WA 98413, USA
| |
Collapse
|
|
12
|
Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. Aktualisierte S3-Leitlinie Colitis ulcerosa (Version 6.2). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:769-858. [PMID: 38718808 DOI: 10.1055/a-2271-0994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
| |
Collapse
|
|
13
|
Huang D, Rennie M, Krasovec A, Nagubandi S, Liu S, Ge E, Khehra B, Au M, Sivagnanam S, Kwan V, Rogge C, Mitrev N, Kariyawasam V. Impact of cytomegalovirus on outcomes in acute severe ulcerative colitis: a retrospective observational study. Ther Adv Chronic Dis 2024; 15:20406223241233203. [PMID: 38560721 PMCID: PMC10981253 DOI: 10.1177/20406223241233203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Accepted: 01/25/2024] [Indexed: 04/04/2024] Open
Abstract
BACKGROUND Concomitant cytomegalovirus (CMV) is highly prevalent in acute severe ulcerative colitis (ASUC) but data for outcomes of CMV positivity in ASUC and the benefit of antiviral therapy remain unclear. OBJECTIVES We aim to determine the impact of CMV positivity, and antiviral therapy, on outcomes such as colectomy-free survival, length of hospital stay and readmission rate, among hospitalized patients with ASUC. DESIGN This is a retrospective, multicentre study of patients admitted with ASUC. METHODS CMV positivity was diagnosed from blood CMV DNA and inpatient colonic biopsies. Background demographics and disease characteristics, clinical characteristics and outcomes during admission and long-term outcomes were obtained from electronic medical records and compared according to the presence of CMV and the use of antiviral therapy. RESULTS CMV was detected in 40 (24%) of 167 ASUC admissions. Previous steroid exposure was the only clinical predictor of CMV positivity on multivariate analysis. Outcomes of greater requirement for rescue therapy (60% versus 33%), longer hospital stay (14.3 versus 9.9 days) and higher readmission rates at 3 and 12 months were associated with CMV positivity. No difference was found in the rate of colectomy or colectomy-free survival. Antiviral therapy was not associated with a lower risk of colectomy but did extend the time to colectomy (126 versus 36 days). CONCLUSION CMV positivity was associated with worse outcomes of need for rescue therapy, hospital stay and readmissions. Antiviral therapy was not found to reduce the risk of colectomy but did extend the time to colectomy. Further prospective studies will be required to more clearly determine its benefit in patients with concomitant CMV and ASUC.
Collapse
Affiliation(s)
- Dazhong Huang
- Department of Gastroenterology and Hepatology, Blacktown and Mt Druitt Hospital, Blacktown Road, Blacktown NSW 2148, Australia
- University of Western Sydney, Sydney, Australia
| | - Michael Rennie
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | | | - Shyam Nagubandi
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Sichang Liu
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Edward Ge
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Barinder Khehra
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Michael Au
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Shobini Sivagnanam
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- Australian Clinical Labs, Sydney, Australia
| | - Vu Kwan
- Westmead Hospital, Westmead, NSW, Australia
| | | | - Nikola Mitrev
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Viraj Kariyawasam
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
- IBD Sydney, Sydney, Australia
| |
Collapse
|
|
14
|
Bao MM, Kennedy JM, Dolinger MT, Dunkin D, Lai J, Dubinsky MC. Cytomegalovirus Colitis in a Patient with Severe Treatment Refractory Ulcerative Colitis. CROHN'S & COLITIS 360 2024; 6:otae014. [PMID: 38444641 PMCID: PMC10914341 DOI: 10.1093/crocol/otae014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Indexed: 03/07/2024] Open
Abstract
Background Cytomegalovirus (CMV) can be reactivated in ulcerative colitis (UC), but its role in progression of inflammation is unclear. Risk factors include severe colitis and treatment with immunosuppressive medications, particularly corticosteroids and immunomodulators. Methods We report a case of cytomegalovirus colitis in a pediatric patient with pancolitis who had been refractory to aminosalicylate, infliximab, and ustekinumab and was in clinical remission and with transmural response on upadacitinib. Results This is a case of a 13-year-old male with UC refractory to multiple therapies who were in clinical remission on upadacitinib 30 mg daily. He developed an acute increase in symptoms and did not respond to therapy escalation with increased upadacitinib 45 mg daily for 2 weeks and prednisone for 1 week. He was diagnosed with cytomegalovirus colitis on flexible sigmoidoscopy biopsy. He was treated with intravenous ganciclovir with tapering of immunosuppressive regimen. Despite initial response, he underwent subtotal colectomy and subsequent restorative proctocolectomy with ileal pouch anal-anastomosis. Conclusions Despite our patient having multiple risk factors for developing CMV colitis, upadacitinib may have played a role when considering its known impact on the herpes family of viruses. CMV colitis should be evaluated for in any patient who presents with worsening symptoms without evidence of other infection or response to increase in therapy.
Collapse
Affiliation(s)
- Michelle M Bao
- Division of Pediatric Gastroenterology, Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, NY, USA
| | - Juliana M Kennedy
- Division of Pediatric Gastroenterology, Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, NY, USA
| | - Michael T Dolinger
- Division of Pediatric Gastroenterology, Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, NY, USA
| | - David Dunkin
- Division of Pediatric Gastroenterology, Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, NY, USA
| | - Joanne Lai
- Division of Pediatric Gastroenterology, Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, NY, USA
| | - Marla C Dubinsky
- Division of Pediatric Gastroenterology, Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, NY, USA
| |
Collapse
|
|
15
|
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.
Collapse
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.)
| |
Collapse
|
|
16
|
Auyeung AB, Rayan MN, Tang X, Thomas S. Radiation proctitis with recurrent gastrointestinal bleeding complicated by cytomegalovirus. J R Coll Physicians Edinb 2023; 53:265-268. [PMID: 37905373 DOI: 10.1177/14782715231205916] [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] [Indexed: 11/02/2023] Open
Abstract
Cytomegalovirus (CMV) usually causes infections with mild symptoms in immunocompetent individuals. However, in immunocompromised patients, these infections can be serious or life-threatening. Following initial infection, CMV typically becomes dormant but remains lifelong in the host. Reactivation of the latent virus can occur in many organ systems, including the gastrointestinal (GI) tract. Radiation proctitis is a known risk factor associated with prostate radiation, with complicating ulceration and GI bleeding. We present the first case report of an immunocompetent 81-year-old male with multiple episodes of life-threatening GI bleeding, secondary to a non-healing CMV-positive rectal ulcer and CMV colitis following radiation for prostate cancer. Multiple insults including prostate radiation, repeated blood transfusions and CMV infection likely contributed to the recurrent bleeding episodes.
Collapse
Affiliation(s)
- Austin B Auyeung
- University of Central Florida College of Medicine, Graduate Medical Education/HCA Florida North Florida Hospital, Internal Medicine Residency Program, Gainesville, FL, USA
| | - Melanie N Rayan
- University of Central Florida College of Medicine, Graduate Medical Education/HCA Florida North Florida Hospital, Internal Medicine Residency Program, Gainesville, FL, USA
| | - Xiaolan Tang
- University of Central Florida College of Medicine, Graduate Medical Education/HCA Florida North Florida Hospital, Internal Medicine Residency Program, Gainesville, FL, USA
| | - Sanil Thomas
- Infectious Diseases Department, HCA Florida North Florida Hospital, Gainesville, FL, USA
| |
Collapse
|
|
17
|
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.
Collapse
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
| |
Collapse
|
|
18
|
Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1046-1134. [PMID: 37579791 DOI: 10.1055/a-2060-0935] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/16/2023]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
| |
Collapse
|
|
19
|
Ono Y, Gonzalez RS. Apoptosis, Crypt Dropout, and Equivocal Immunohistochemical Staining May Indicate Cytomegalovirus Infection in Inflammatory Bowel Disease Patients. Am J Surg Pathol 2023; Publish Ahead of Print:00000478-990000000-00182. [PMID: 37326315 DOI: 10.1097/pas.0000000000002071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Cytomegalovirus (CMV) colitis superimposed on inflammatory bowel disease (IBD) can be challenging to diagnose. This study aimed to determine what histologic clues and immunohistochemistry (IHC) utilization practices, if any, can help diagnose CMV superinfection in IBD. Colon biopsies were reviewed from all patients with CMV colitis with and without IBD between 2010 and 2021 at one institution, along with a separate cohort of IBD patients with negative CMV IHC. Biopsies were assessed for histologic features of activity and chronicity, phlebitis, fibrin thrombi, basal crypt apoptosis, CMV viral cytopathic effect (VCE), and CMV IHC positivity. Features between groups were compared, with statistical significance set at P-value <0.05. The study included 251 biopsies from 143 cases (21 CMV-only, 44 CMV+IBD, 78 IBD-only). Compared with the IBD-only group, the CMV+IBD group was more likely to show apoptotic bodies (83% vs. 64%, P=0.035) and crypt dropout (75% vs. 55%, P=0.045). CMV was detected by IHC in 18 CMV+IBD cases without VCE on hematoxylin and eosin (41%). In the 23 CMV+IBD cases where IHC was performed on all concurrent biopsies, IHC was positive in at least 1 biopsy in 22 cases. Six individual CMV+IBD biopsies with no VCE on hematoxylin and eosin demonstrated equivocal IHC staining. Of these, 5 had evidence of CMV infection. IBD patients with superimposed CMV infection are more likely to demonstrate apoptotic bodies and crypt dropout compared with their noninfected counterparts. Equivocal IHC staining for CMV may indicate true infection in IBD patients, and staining multiple biopsies from the same accession can improve CMV detection.
Collapse
Affiliation(s)
- Yuho Ono
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA
| | - Raul S Gonzalez
- Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA
| |
Collapse
|
|
20
|
Altunal LN, Ozel AS, C AK. Cytomegalovirus reactivation in ulcerative colitis patients: Early indicators. Niger J Clin Pract 2023; 26:765-770. [PMID: 37470651 DOI: 10.4103/njcp.njcp_616_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/21/2023]
Abstract
Background The association of. c ytomegalovirus (CMV) infection with ulcerative colitis (UC) still remains a controversial topic for the clinicians. Aim: In this study, we aimed to elucidate the CMV infection related parameters in the exacerbation of UC. Material and Methods In this study, 812 UC patients who have admitted to our institution between June 2008 and November 2020 were analyzed retrospectively. CMV infection was diagnosed by the detection of CMV DNA with polymerase chain reaction (PCR) in tissue biopsies with presence of clinical colitis symptoms. CMV negative UC patient group was defined as UC activation group with negative PCR results. Result A total of 153 patients met the inclusion criteria during the study period, with a median age of 41.8 years. CMV PCR positivity had been detected in tissue biopsy in 43 (28.1%) UC patients. CMV-positive patients had a statistically significant higher frequency of steroid resistance, treatment with azathioprine, longer disease duration, longer remission, and hospitalization day. The mean C-reactive protein (CRP) level, platelet to lymphocyte ratio (PLR) were higher, and mean albumin level was lower in CMV positive patients, with statistically significance. Also, colectomy and anti-tumor necrosis factor-α (TNF-α) therapy were more frequent in CMV-reactivated group in long-term follow-up. In a multivariable model, steroid resistance, treatment with azathioprine, long disease duration, low albumin value was independently associated with colonic CMV infection. Conclusion Steroid resistance, treatment with azathioprine, long disease duration, low albumin levels were significant risk factors for CMV colitis, among patients with UC activation.
Collapse
Affiliation(s)
- L N Altunal
- Department of Infectious Diseases, Health Sciences University Umraniye Training and Research Hospital, Istanbul, Turkey
| | - A S Ozel
- Health Sciences University Umraniye Training and Research Hospital, Istanbul, Turkey
| | - A K C
- Department of Gastroenterology, Health Sciences University Umraniye Training and Research Hospital, İstanbul, Turkey
| |
Collapse
|
|
21
|
Zarenezhad E, Abdulabbas HT, Kareem AS, Kouhpayeh SA, Barbaresi S, Najafipour S, Mazarzaei A, Sotoudeh M, Ghasemian A. Protective role of flavonoids quercetin and silymarin in the viral-associated inflammatory bowel disease: an updated review. Arch Microbiol 2023; 205:252. [PMID: 37249707 DOI: 10.1007/s00203-023-03590-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 05/14/2023] [Accepted: 05/18/2023] [Indexed: 05/31/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic recurrent inflammation of the gastrointestinal tract (GIT). IBD patients are susceptible to various infections such as viral infections due to the long-term consumption of immunosuppressive drugs and biologics. The antiviral and IBD protective traits of flavonoids have not been entirely investigated. This study objective included an overview of the protective role of flavonoids quercetin and silymarin in viral-associated IBD. Several viral agents such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV) and enteric viruses can be reactivated and thus develop or exacerbate the IBD conditions or eventually facilitate the disease remission. Flavonoids such as quercetin and silymarin are non-toxic and safe bioactive compounds with remarkable anti-oxidant, anti-inflammatory and anti-viral effects. Mechanisms of anti-inflammatory and antiviral effects of silymarin and quercetin mainly include immune modulation and inhibition of caspase enzymes, viral binding and replication, RNA synthesis, viral proteases and viral assembly. In the nutraceutical sector, natural flavonoids low bioavailability and solubility necessitate the application of delivery systems to enhance their efficacy. This review study provided an updated understanding of the protective role of quercetin and silymarin against viral-associated IBD.
Collapse
Affiliation(s)
- Elham Zarenezhad
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
| | - Hussein T Abdulabbas
- Department of Medical Microbiology, Medical College, Al Muthanna University, Al Muthanna, Iraq
| | - Ahmed Shayaa Kareem
- Department of Medical Laboratories Techniques, Imam Ja'afar Al-Sadiq University, Al-Muthanna, 66002, Iraq
| | - Seyed Amin Kouhpayeh
- Department of Pharmacology, Faculty of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Silvia Barbaresi
- Department of Movement and Sports Sciences, Ghent University, Ghent, Belgium
| | - Sohrab Najafipour
- Department of Microbiology, Faculty of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Abdulbaset Mazarzaei
- Department of Immunology, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr, Iran
| | - Mitra Sotoudeh
- Department of Nutrition, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr, Iran
| | - Abdolmajid Ghasemian
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.
| |
Collapse
|
|
22
|
Jentzer A, Fauteux-Daniel S, Verhoeven P, Cantais A, Novoa MY, Jospin F, Chanut B, Rochereau N, Bourlet T, Roblin X, Pozzetto B, Pillet S. Impact of Dextran-Sodium-Sulfate-Induced Enteritis on Murine Cytomegalovirus Reactivation. Viruses 2022; 14:2595. [PMID: 36560599 PMCID: PMC9781000 DOI: 10.3390/v14122595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/11/2022] [Accepted: 11/18/2022] [Indexed: 11/24/2022] Open
Abstract
(1) Background: Ulcerative colitis (UC) is an inflammatory bowel disease that causes inflammation of the intestines, which participates in human cytomegalovirus (HCMV) reactivation from its latent reservoir. CMV-associated colitis plays a pejorative role in the clinical course of UC. We took advantage of a model of chemically induced enteritis to study the viral reactivation of murine CMV (MCMV) in the context of gut inflammation. (2) Methods: Seven-week-old BALB/c mice were infected by 3 × 103 plaque-forming units (PFU) of MCMV; 2.5% (w/v) DSS was administered in the drinking water from day (D) 30 to D37 post-infection to induce enteritis. (3) Results: MCMV DNA levels in the circulation decreased from D21 after infection until resolution of the acute infection. DSS administration resulted in weight loss, high disease activity index, elevated Nancy index shortening of the colon length and increase in fecal lipocalin. However, chemically induced enteritis had no impact on MCMV reactivation as determined by qPCR and immunohistochemistry of intestinal tissues. (4) Conclusions: Despite the persistence of MCMV in the digestive tissues after the acute phase of infection, the gut inflammation induced by DSS did not induce MCMV reactivation in intestinal tissues, thus failing to recapitulate inflammation-driven HCMV reactivation in human UC.
Collapse
Affiliation(s)
- Alexandre Jentzer
- CIRI, Centre International de Recherche en Infectiologie, GIMAP Team, Univ Lyon, Univ St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 42023 Saint-Etienne, France
| | - Sébastien Fauteux-Daniel
- French Blood Establishment Auvergne-Rhône-Alpes, Scientific Department, 42270 Saint-Etienne, France
| | - Paul Verhoeven
- CIRI, Centre International de Recherche en Infectiologie, GIMAP Team, Univ Lyon, Univ St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 42023 Saint-Etienne, France
- Department of Infectious Agents and Hygiene, University-Hospital of Saint-Etienne, 42055 Saint-Etienne, France
| | - Aymeric Cantais
- CIRI, Centre International de Recherche en Infectiologie, GIMAP Team, Univ Lyon, Univ St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 42023 Saint-Etienne, France
| | - Melyssa Yaugel Novoa
- CIRI, Centre International de Recherche en Infectiologie, GIMAP Team, Univ Lyon, Univ St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 42023 Saint-Etienne, France
| | - Fabienne Jospin
- CIRI, Centre International de Recherche en Infectiologie, GIMAP Team, Univ Lyon, Univ St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 42023 Saint-Etienne, France
| | - Blandine Chanut
- CIRI, Centre International de Recherche en Infectiologie, GIMAP Team, Univ Lyon, Univ St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 42023 Saint-Etienne, France
| | - Nicolas Rochereau
- CIRI, Centre International de Recherche en Infectiologie, GIMAP Team, Univ Lyon, Univ St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 42023 Saint-Etienne, France
| | - Thomas Bourlet
- CIRI, Centre International de Recherche en Infectiologie, GIMAP Team, Univ Lyon, Univ St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 42023 Saint-Etienne, France
- Department of Infectious Agents and Hygiene, University-Hospital of Saint-Etienne, 42055 Saint-Etienne, France
| | - Xavier Roblin
- CIRI, Centre International de Recherche en Infectiologie, GIMAP Team, Univ Lyon, Univ St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 42023 Saint-Etienne, France
- Department of Gastroenterology, University-Hospital of Saint-Etienne, 42055 Saint-Etienne, France
| | - Bruno Pozzetto
- CIRI, Centre International de Recherche en Infectiologie, GIMAP Team, Univ Lyon, Univ St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 42023 Saint-Etienne, France
- Department of Infectious Agents and Hygiene, University-Hospital of Saint-Etienne, 42055 Saint-Etienne, France
| | - Sylvie Pillet
- CIRI, Centre International de Recherche en Infectiologie, GIMAP Team, Univ Lyon, Univ St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 42023 Saint-Etienne, France
- Department of Infectious Agents and Hygiene, University-Hospital of Saint-Etienne, 42055 Saint-Etienne, France
| |
Collapse
|
|
23
|
Muacevic A, Adler JR. Steroid Resistance/Dependence Might Be an Alarming Feature for Cytomegalovirus Infection Among Ulcerative Colitis Patients With Increased Disease Activity. Cureus 2022; 14:e30873. [PMID: 36337831 PMCID: PMC9618279 DOI: 10.7759/cureus.30873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/30/2022] [Indexed: 11/11/2022] Open
Abstract
Background/Aims This study aimed to determine the prevalence of cytomegalovirus (CMV) infection among patients with moderate to severe active ulcerative colitis (UC) and to determine the risk factors for CMV infection according to the demographic features of these patients. Patients/Methods A total of 183 patients with severe or moderate active UC were enrolled in the study after retrospective analysis. The disease severity of UC was determined according to the Mayo Score. CMV infection was investigated by real-time quantitative polymerase chain reaction (PCR) and the immunohistochemical (IHC) staining method in colonic mucosal biopsies. Results CMV infection was diagnosed in 33.9% of patients with UC. UC patients diagnosed with CMV infection had significantly higher Mayo Score levels (9.68 vs 8.56 and p=0.001). The long-term presence of UC disease, steroid, azathioprine (AZA), and anti-tumor necrosis factor-alpha (anti-TNF-alpha) usage increased the risk of CMV infection (p=0.001 and odds ratio=1.168; p=0.001 and odds ratio=2.967; p=0.004 and odds ratio=2.953; p=0.003 and odds ratio=3.861, respectively). CMV infection increases the risk of developing steroid resistance or dependency (p=0.002 and odds ratio=3.147; p=0.002 and odds ratio=5.085, respectively). Post-treatment clinical remission and mucosal healing rates were higher in CMV-negative patients than in CMV-positive patients (99.2% vs 91.9%, p=0.018 and 86.8% vs 70.9%, p=0.015). A higher rate of need for colectomy had been found in patients with CMV infection (5 patients vs 1 patient; p=0.034 and odds ratio=10.526). Conclusions The presence of CMV infection increases the severity of the disease and worsens clinical outcomes, leading to adverse treatment outcomes. CMV infection increases the requirement for colectomy. The presence of steroids, immunosuppressives such as AZA, and anti-TNF-alpha usage increases the occurrence of CMV infection. CMV infection should be suspected in patients with moderate to severe UC activity.
Collapse
|
|
24
|
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.
Collapse
Affiliation(s)
- Jun Lee
- Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea
| |
Collapse
|
|
25
|
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.
Collapse
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
| |
Collapse
|
|
26
|
Jena A, Mishra S, Singh AK, Sekar A, Sharma V. Cytomegalovirus in ulcerative colitis: an evidence-based approach to diagnosis and treatment. Expert Rev Gastroenterol Hepatol 2022; 16:109-120. [PMID: 35057693 DOI: 10.1080/17474124.2022.2032662] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 01/19/2022] [Indexed: 12/21/2022]
Abstract
INTRODUCTION The detection of cytomegalovirus (CMV) in the setting of inflammatory bowel disease often creates confusion whether CMV is a 'bystander' or 'disease.' AREAS COVERED This review discusses the clinical conundrum of CMV in ulcerative colitis, approach to discriminate infection from disease, and therapeutic considerations (immunosuppressive and anti-CMV treatment). CMV disease should be considered in corticosteroid refractory- dependent and thiopurine refractory disease. Endoscopy may reveal deep punched out ulcers, irregular ulcers, or cobble-stoning. The diagnosis rests on the presence and abundance of viral inclusion bodies on hematoxylin and eosin stain, positive immunohistochemistry, and/or positive tissue polymerase chain reaction. CMV disease is associated with worse outcomes including increased colectomy rates. EXPERT OPINION The timing and duration of antiviral drugs in CMV disease is debatable but depends on the load of CMV in tissue. In high-grade infection, CMV needs to be treated while increasing immunosuppression may work in the setting of low-grade infection. Ganciclovir is the drug of choice for treatment of CMV disease. Tumor necrosis factor inhibitors may be useful for treating underlying disease activity in the setting of CMV. Other emerging therapies include fecal microbiota transplantation. Randomized studies are necessary to define the best timing and duration of anti-CMV therapy.
Collapse
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
| |
Collapse
|
|
27
|
Kochan K, Keskin EB, Seven G, Bas S, Kiremitci S, Gecer M, Senturk H. Effects of tissue cytomegalovirus quantitative polymerase chain reaction in the management of ulcerative colitis flare-ups: Should we wave aside? Arab J Gastroenterol 2021; 22:297-304. [PMID: 34872846 DOI: 10.1016/j.ajg.2021.11.005] [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: 09/14/2021] [Revised: 11/13/2021] [Accepted: 11/16/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND STUDY AIMS The role of cytomegalovirus (CMV) infection for disease reactivation in ulcerative colitis (UC) patients remains controversial and diagnostic tests are yet to be standardized. We aimed to define the clinical relevance of CMV detection by mucosal polymerase chain reaction (PCR) in UC patients by comparing the clinical course of UC in CMV-treated and CMV-untreated groups in tissue CMV-PCR positive cases. PATIENTS AND METHODS In this retrospective study, 141 patients diagnosed with moderate-to-severe UC admitted to our clinic with disease flare, colonic tissue CMV PCR was assessed. RESULTS The median age of the study population was 39 years, and 99 (70.2%) patients were male. Eighty-eight (62.4%) patients were CMV-PCR (+) and 53 (37.6%) were CMV PCR (-). The CMV-PCR (+) and CMV PCR (-) groups showed no significant difference concerning age, sex, disease duration, site of involvement and disease activity and administered treatments. The median tissue CMV-PCR was 41,098 IU/mL (IQR:2,344.25-136,192). Thirty-four of 88 CMV-PCR (+) patients received antiviral therapy. The tissue CMV-PCR level of patients who received antiviral therapy was 124,381 IU/mL (IQR: 19,309-412,335), and it was 6,292 IU/mL (IQR: 997-71,154) in patients who did not receive antiviral therapy; (p < 0.001). Sixteen (47.1%) of 34 patients who received antiviral therapy achieved remission. Two of the non-responders underwent colectomy (one because of dysplasia and one who did not respond subsequent biologic agent either). Remaing 16 achieved remission by escalating the immunsuppresive/biologic agent therapy. CONCLUSION CMV infection is responsible for only a minority of cases of UC flares and all are steroid-resistant cases. Most of the patients non-responsive to antiviral treatment respond to increased anti-inflammatory treatment. Hesitancy in the decision of escalating immunsuppresive treatment rather than CMV disease may be responsible for worsening disease course and increased colectomy rate in a significant number of the patients who are tissue CMV-PCR (+).
Collapse
Affiliation(s)
- Koray Kochan
- Division of Gastroenterology, Bezmialem University School of Medicine, Istanbul, Turkey
| | - Elmas Biberci Keskin
- Division of Gastroenterology, Bezmialem University School of Medicine, Istanbul, Turkey
| | - Gulseren Seven
- Division of Gastroenterology, Bezmialem University School of Medicine, Istanbul, Turkey
| | - Suleyman Bas
- Division of Internal Medicine, Sancaktepe Sehit Prof. Dr. Ilhan Varank Training and Research Hospital, Istanbul, Turkey
| | - Sercan Kiremitci
- Division of Gastroenterology, Bezmialem University School of Medicine, Istanbul, Turkey
| | - Melin Gecer
- Division of Pathology, Bezmialem University School of Medicine, Istanbul, Turkey
| | - Hakan Senturk
- Division of Gastroenterology, Bezmialem University School of Medicine, Istanbul, Turkey.
| |
Collapse
|
|
28
|
Craviotto V, Furfaro F, Loy L, Zilli A, Peyrin-Biroulet L, Fiorino G, Danese S, Allocca M. Viral infections in inflammatory bowel disease: Tips and tricks for correct management. World J Gastroenterol 2021; 27:4276-4297. [PMID: 34366605 PMCID: PMC8316900 DOI: 10.3748/wjg.v27.i27.4276] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/01/2021] [Accepted: 05/15/2021] [Indexed: 02/06/2023] Open
Abstract
Over the past decades, the treatment of inflammatory bowel diseases (IBD) has become more targeted, anticipating the use of immune-modifying therapies at an earlier stage. This top-down approach has been correlated with favorable short and long-term outcomes, but it has also brought with it concerns regarding potential infectious complications. This large IBD population treated with immune-modifying therapies, especially if combined, has an increased risk of severe infections, including opportunistic infections that are sustained by viral, bacterial, parasitic, and fungal agents. Viral infections have emerged as a focal safety concern in patients with IBD, representing a challenge for the clinician: they are often difficult to diagnose and are associated with significant morbidity and mortality. The first step is to improve effective preventive strategies, such as applying vaccination protocols, adopt adequate prophylaxis and educate patients about potential risk factors. Since viral infections in immunosuppressed patients may present atypical signs and symptoms, the challenges for the gastroenterologist are to suspect, recognize and diagnose such complications. Appropriate treatment of common viral infections allows us to minimize their impact on disease outcomes and patients’ lives. This practical review supports this standard of care to improve knowledge in this subject area.
Collapse
Affiliation(s)
- Vincenzo Craviotto
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
| | - Federica Furfaro
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
| | - Laura Loy
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
| | - Alessandra Zilli
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
| | - Laurent Peyrin-Biroulet
- Department of Hepato-Gastroenterology and Inserm U954, University Hospital of Nancy, Lorraine University, Nancy 54511, France
| | - Gionata Fiorino
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milano, Italy
| | - Silvio Danese
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milano, Italy
| | - Mariangela Allocca
- Humanitas Clinical and Research Center, IRCCS, Rozzano 20089, Milano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milano, Italy
| |
Collapse
|
|
29
|
Leal T, Arroja B, Costa D, Ferreira C, Soares J, Gonçalves R. Colitis due to Cytomegalovirus and Herpes Simplex Type 2 as a Complication of a First Presentation of Inflammatory Bowel Disease. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2021; 29:56-60. [DOI: 10.1159/000514715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 01/06/2021] [Indexed: 11/19/2022]
Abstract
<b><i>Introduction:</i></b> The first presentation of ulcerative colitis may be an acute flare in about 15% of patients, requiring hospital admission. In acute severe steroid-refractory ulcerative colitis, cytomegalovirus (CMV) should be sought because it is a frequent cause of refractory disease. Herpes simplex colitis constitutes a rarer event in ulcerative colitis patients and it is usually associated with immunosuppression. <b><i>Case Presentation:</i></b> We report a case of a first presentation of ulcerative colitis complicated by CMV and herpes simplex type 2 coinfection. After a long period of systemic corticosteroids, the diagnosis of both CMV and herpes colitis was made. Despite antiviral treatment, colectomy was required due to a contained perforation. <b><i>Discussion/Conclusion:</i></b> This report highlights the importance of a high degree of suspicion for opportunistic infections in steroid/immunomodulator refractory ulcerative colitis, even in the first flare.
Collapse
|
|
30
|
Niv E, Ovadia B, Groisman G, Kopelman Y. CMV-Induced Severe Colonic Stricture in an Adult Crohn's Disease Patient. Dig Dis Sci 2021; 66:636-639. [PMID: 32219611 DOI: 10.1007/s10620-020-06206-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 03/10/2020] [Indexed: 12/09/2022]
Affiliation(s)
- Eva Niv
- Meuhedet Health Services, Hillel-Yaffe Medical Center, Hadera, Israel.
| | - Baruch Ovadia
- Department of Gastroenterology, Hillel-Yaffe Medical Center, Hadera, Israel
| | - Gabriel Groisman
- Department of Pathology, Hillel-Yaffe Medical Center, Hadera, Israel
| | - Yael Kopelman
- Department of Gastroenterology, Hillel-Yaffe Medical Center, Hadera, Israel
| |
Collapse
|
|
31
|
Kucharzik T, Dignass AU, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengießer K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 58:e241-e326. [PMID: 33260237 DOI: 10.1055/a-1296-3444] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Axel U Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Deutschland
| | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Deutschland
| | - Philip Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | - Klaus Kannengießer
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Andreas Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | | | - Andreas Stallmach
- Gastroenterologie, Hepatologie und Infektiologie, Friedrich Schiller Universität, Jena, Deutschland
| | - Jürgen Stein
- Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt/Main, Deutschland
| | - Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Niels Teich
- Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten, Leipzig, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
| |
Collapse
|
|
32
|
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.
Collapse
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
| |
Collapse
|
|
33
|
Jentzer A, Veyrard P, Roblin X, Saint-Sardos P, Rochereau N, Paul S, Bourlet T, Pozzetto B, Pillet S. Cytomegalovirus and Inflammatory Bowel Diseases (IBD) with a Special Focus on the Link with Ulcerative Colitis (UC). Microorganisms 2020; 8:1078. [PMID: 32698383 PMCID: PMC7409252 DOI: 10.3390/microorganisms8071078] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 07/10/2020] [Accepted: 07/12/2020] [Indexed: 12/16/2022] Open
Abstract
Cytomegalovirus (CMV) infects approximately 40% of adults in France and persists lifelong as a latent agent in different organs, including gut. A close relationship is observed between inflammation that favors viral expression and viral replication that exacerbates inflammation. In this context, CMV colitis may impact the prognosis of patients suffering from inflammatory bowel diseases (IBDs), and notably those with ulcerative colitis (UC). In UC, the mucosal inflammation and T helper cell (TH) 2 cytokines, together with immunomodulatory drugs used for controlling flare-ups, favor viral reactivation within the gut, which, in turn, increases mucosal inflammation, impairs corticoid and immunosuppressor efficacy (the probability of steroid resistance is multiplied by more than 20 in the case of CMV colitis), and enhances the risk for colectomy. This review emphasizes the virological tools that are recommended for exploring CMV colitis during inflammatory bowel diseases (IBD) and underlines the interest of using ganciclovir for treating flare-ups associated to CMV colitis in UC patients.
Collapse
Affiliation(s)
- Alexandre Jentzer
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Laboratory of infectious agents and hygiene, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
- Laboratory of Immunology, University Hospital Saint-Etienne, 42055 Saint-Etienne, 42055 Saint-Etienne, France
| | - Pauline Veyrard
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Department of Gastroenterology, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
| | - Xavier Roblin
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Department of Gastroenterology, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
| | - Pierre Saint-Sardos
- Laboratory of Bacteriology, University Hospital of Clermont-Ferrand, 63100 Clermont-Ferrand, France;
| | - Nicolas Rochereau
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
| | - Stéphane Paul
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Laboratory of Immunology, University Hospital Saint-Etienne, 42055 Saint-Etienne, 42055 Saint-Etienne, France
| | - Thomas Bourlet
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Laboratory of infectious agents and hygiene, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
| | - Bruno Pozzetto
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Laboratory of infectious agents and hygiene, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
| | - Sylvie Pillet
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Laboratory of infectious agents and hygiene, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
| |
Collapse
|
|
34
|
Magdziak A, Szlak J, Mróz A, Wieszczy P, Zagórowicz E. A stool test in patients with active ulcerative colitis helps exclude cytomegalovirus disease. Scand J Gastroenterol 2020; 55:664-670. [PMID: 32552149 DOI: 10.1080/00365521.2020.1771760] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objectives: In severe ulcerative colitis (UC) bowel biopsy is recommended to detect the cytomegalovirus (CMV) infection capable of complicating the course of the disease. Histopathology with immunohistochemistry (IHC) is time-consuming, and a blood polymerase chain reaction (PCR) for CMV DNA is used as an alternative, notwithstanding nothing more than a moderate correlation between the two. We aimed to detect CMV DNA in the stools of patients with active UC, and to compare the results with CMV IHC in bowel biopsies.Materials and methods: Measurement of CMV DNA in stools (copies/ml) entailed PCR, while biopsies assessed inflammation activity (Geboes scale), as well as counts of numbers of CMV IHC-positive cells/biopsy. The severity of UC was assessed using the Mayo score, stool calprotectin and concentrations of C-reactive protein in the blood.Results: 89 of the above pairs of tests for CMV were performed among 75 patients. CMV was detected in 36/89 stool specimens and 19/89 bowel biopsies. The sensitivity of the stool-CMV PCR was thus 84.7%, while specificity was of 71.4%. The negative predictive value was 94.3% and the positive predictive value 44.4%. No difference in the severity of UC was noted between the stool CMV DNA positive and negative groups. Similarly, there was no difference in the severity of UC between the CMV IHC positive and negative groups, except for the Geboes score, more often found to be higher in CMV IHC-positive patients (p = .002).Conclusions: CMV DNA was detected in the stools of 40.4% of patients with active UC. A negative test result may help to exclude bowel CMV disease.
Collapse
Affiliation(s)
- Agnieszka Magdziak
- The Maria Sklodowska-Curie National Research Institute of Oncology, Department of Microbiology, Warsaw, Poland
| | - Jakub Szlak
- The Maria Sklodowska-Curie National Research Institute of Oncology, Department of Gastroenterology, Warsaw, Poland
| | - Andrzej Mróz
- The Center of Postgraduate Medical Education, Department of Pathomorphology, Warsaw, Poland.,The Maria Sklodowska-Curie National Research Institute of Oncology, Department of Pathology and Laboratory Medicine, Warsaw, Poland
| | - Paulina Wieszczy
- The Maria Sklodowska-Curie National Research Institute of Oncology, Department of Cancer Prevention, Warsaw, Poland.,Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Edyta Zagórowicz
- The Maria Sklodowska-Curie National Research Institute of Oncology, Department of Gastroenterology, Warsaw, Poland.,The Center of Postgraduate Medical Education, Department of Gastroenterology and Hepatology and Clinical Oncology, Warsaw, Poland
| |
Collapse
|
|
35
|
Ghoshal UC, Rai S, Kulkarni A, Gupta A. Prediction of outcome of treatment of acute severe ulcerative colitis using principal component analysis and artificial intelligence. JGH OPEN 2020; 4:889-897. [PMID: 33102760 PMCID: PMC7578272 DOI: 10.1002/jgh3.12342] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 01/26/2020] [Accepted: 03/13/2020] [Indexed: 12/17/2022]
Abstract
Background and Aim About 15% patients with acute severe ulcerative colitis (UC) fail to respond to medical treatment and may require colectomy. An early prediction of response may help the treating team and the patients and their family to prepare for alternative treatment options. Methods Data of 263 patients (mean age 37.0 ± 14.0-years, 176, 77% male) with acute severe UC admitted during a 12-year period were used to study predictors of response using univariate analysis, multivariate linear principal component analysis (PCA), and nonlinear artificial neural network (ANN). Results Of 263 patients, 231 (87.8%) responded to the initial medical treatment that included oral prednisolone (n = 14, 5.3%), intravenous (IV) hydrocortisone (n = 238, 90.5%), IV cyclosporine (n = 9, 3.4%), and inflixmab (n = 2, 0.7%), and 28 (10.6%) did not respond and the remaining 4 (1.5%) died, all of whom did were also nonresponders. Nonresponding patients had to stay longer in the hospital and died more often. On univariate analysis, the presence of complications, the need for use of cyclosporin, lower Hb, platelets, albumin, serum potassium, and higher C-reactive protein were predictors of nonresponse. Hb and albumin were strong predictive factors on both PCA and ANN. Though the nonlinear modeling using ANN had a good predictive accuracy for the response, its accuracy for predicting nonresponse was lower. Conclusion It is possible to predict the response to medical treatment in patients with UC using linear and nonlinear modeling technique. Serum albumin and Hb are strong predictive factors.
Collapse
Affiliation(s)
- Uday C Ghoshal
- Department of GastroenterologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
| | - Sushmita Rai
- Department of GastroenterologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
| | - Akshay Kulkarni
- Department of GastroenterologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
| | - Ankur Gupta
- Department of GastroenterologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
| |
Collapse
|
|
36
|
Cho JH, Choi JH. Cytomegalovirus ileo-pancolitis presenting as toxic megacolon in an immunocompetent patient: A case report. World J Clin Cases 2020; 8:552-559. [PMID: 32110666 PMCID: PMC7031826 DOI: 10.12998/wjcc.v8.i3.552] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 10/13/2019] [Accepted: 10/29/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) enterocolitis presenting in the form of pancolitis or involving the small and large intestines in an immunocompetent patient is rarely encountered, and CMV enterocolitis presenting with a serious complication, such as toxic megacolon, in an immunocompetent adult has only been reported on a few occasions.
CASE SUMMARY We describe the case of a 70-year-old male with no history of inflammatory bowel disease or immunodeficiency who presented with toxic megacolon and subsequently developed massive hemorrhage as a complication of CMV ileo-pancolitis. The patient was referred to our institute for abdominal pain and distension. Abdominal X-ray showed marked dilatation of ileum and whole colon without air-fluid level, and sigmoidoscopy with biopsy failed to reveal any specific finding. After 7 d of conservative treatment, massive hematochezia developed, and he was diagnosed to have CMV enterocolitis by colonoscopy with biopsy. Although the diagnosis of CMV enterocolitis was delayed, the patient was treated successfully by repeat colonoscopic decompression and antiviral therapy with intravenous ganciclovir.
CONCLUSION This report cautions that CMV-induced colitis should be considered as a possible differential diagnosis in a patient with intractable symptoms of enterocolitis or megacolon of unknown cause, even when the patient is non-immunocompromised.
Collapse
Affiliation(s)
- Joon Hyun Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu 42415, South Korea
| | - Joon Hyuk Choi
- Department of Pathology, Yeungnam University College of Medicine, Daegu 42415, South Korea
| |
Collapse
|
|
37
|
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.
Collapse
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 ()
| |
Collapse
|
|
38
|
Monif GRG. Is ulcerative colitis a disease of a dysfunctional microbiota? Med Hypotheses 2019; 131:109300. [PMID: 31443761 DOI: 10.1016/j.mehy.2019.109300] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 06/17/2019] [Accepted: 07/03/2019] [Indexed: 01/07/2023]
Abstract
Using the gross pathology literature and the prior decoupling of Crohn's disease from inflammatory bowel disease, IDI's White Paper puts into question the current understanding of what ulcerative colitis is and how it can be therapeutically addressed. The pathology literature, when coupled with the ability of fecal enema therapy to achieve a remission rate significantly superior to those documented for biologics, puts focus on the dominant role of the gastrointestinal microbiota in both disease induction and its recovery. The concept of endogenous enterotoxogenesis is introduced.
Collapse
Affiliation(s)
- Gilles R G Monif
- Infectious Diseases Incorporated, 17121 Lakewood Drive, Bellevue, NE 68123-3954, United States.
| |
Collapse
|
|
39
|
Gong J, Meyerowitz EA, Isidro RA, Kaye KM. Primary cytomegalovirus infection with invasive disease in a patient with inflammatory bowel disease. BMJ Case Rep 2019; 12:12/9/e230056. [PMID: 31570344 PMCID: PMC6768388 DOI: 10.1136/bcr-2019-230056] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
A 37-year-old woman with a history of inflammatory bowel disease on mercaptopurine presented with a week of recurrent fever, headache, myalgias and mildly elevated serum transaminases and leucopenia. Her workup revealed primary cytomegalovirus (CMV) infection with atypical lymphocytosis, elevated viral load, positive IgM and negative IgG. Two weeks after her initial presentation, she developed odynophagia and diarrhoea prompting endoscopic evaluation with biopsies, which demonstrated CMV disease of the gastrointestinal tract. Her fever and systemic symptoms improved rapidly with initiation of intravenous ganciclovir. She was transitioned to and maintained on oral valganciclovir until two and half months after discharge when her symptoms and lab abnormalities had fully subsided.
Collapse
Affiliation(s)
- Jingyi Gong
- Internal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | | | - Raymond A Isidro
- Anatomic Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Kenneth M Kaye
- Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA
| |
Collapse
|
|
40
|
Maeda T, Sakai H, Ozawa N, Sugiyama T, Takada J, Kubota M, Ibuka T, Shirakami Y, Araki H, Shimizu M. Acute cytomegalovirus infection in an immunocompetent patient with ulcerative colitis: A case report. Exp Ther Med 2019; 18:2271-2277. [PMID: 31452714 DOI: 10.3892/etm.2019.7823] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 07/18/2019] [Indexed: 11/06/2022] Open
Abstract
Cytomegalovirus (CMV) is a ubiquitous member of the Herpesviridae family that can present with a variety of clinical manifestations, including encephalitis, retinitis, interstitial pneumonia and colitis. These serious symptoms are generally observed as opportunistic infections in immunocompromised hosts, including patients with acquired immunodeficiency syndrome and those receiving steroids and/or immunosuppressants. Symptomatic CMV infections in patients with ulcerative colitis are found in patients treated with steroids and/or immunosuppressants but rarely affect those who are not taking these agents. The present study reported the case of a young patient without concurrent use of immunosuppressive agents for the treatment of ulcerative colitis. The patient presented with acute mononucleosis and colitis caused by primary CMV infection. This was characterized by the presence of atypical lymphocytes and hepatosplenomegaly, elevation of transaminase levels, serology-positive anti-CMV IgM, and CMV antigenemia. Additionally, CMV-positive cells were histologically detected in colonic biopsy specimens. The patient's symptoms and clinical parameters improved following initiation of intravenous ganciclovir. It was concluded that even if patients with ulcerative colitis are not treated with steroids and/or immunosuppressants, significant attention should be paid to acute CMV infections in the context of severe or persistent colonic inflammation.
Collapse
Affiliation(s)
- Toshihide Maeda
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Hiroyasu Sakai
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Noritaka Ozawa
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Tomohiko Sugiyama
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Jun Takada
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Masaya Kubota
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Takashi Ibuka
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Yohei Shirakami
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Hiroshi Araki
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| | - Masahito Shimizu
- Department of Gastroenterology, Gifu University Hospital, Gifu 501-1194, Japan
| |
Collapse
|
|
41
|
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).
Collapse
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
| |
Collapse
|
|
42
|
A Practical Review of Cytomegalovirus in Gastroenterology and Hepatology. Gastroenterol Res Pract 2019; 2019:6156581. [PMID: 30984257 PMCID: PMC6431500 DOI: 10.1155/2019/6156581] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 02/05/2019] [Indexed: 02/06/2023] Open
Abstract
Human cytomegalovirus (CMV) is a ubiquitous Herpesviridae virus with a wide spectrum of pathology in humans. Host immunity is a major determinant of the clinical manifestation of CMV and can vary widely in the gastroenterology and hepatology practice setting. Immunocompetent patients generally develop a benign, self-limited mononucleosis-like syndrome whereas gastrointestinal tissue-invasive disease is more frequently seen in immunocompromised and inflammatory bowel disease patients. Additionally, liver allograft dysfunction is a significant consequence of CMV infection in liver transplant patients. While polymerase chain reaction and immunohistochemistry techniques allow for the reliable and accurate detection of CMV in the human host, the diagnostic value of different serologic, endoscopic, and histologic tests depends on a variety of factors. Similarly, latent CMV, CMV infection, and CMV disease carry different significance depending on the patient population, and the decision to initiate antiviral therapy can be complex and patient-specific. This review will focus on the pathophysiology, diagnosis, and management of CMV in patient populations relevant to the practice of gastroenterology and hepatology-liver transplant recipients, inflammatory bowel disease patients, and otherwise immunocompetent patients.
Collapse
|
|
43
|
Schenk W, Klugmann T, Borkenhagen A, Klecker C, Dietel P, Kirschner R, Schneider E, Bruns T, Stallmach A, Teich N. The detection of the cytomegalovirus DNA in the colonic mucosa of patients with ulcerative colitis is associated with increased long-term risk of proctocolectomy: results from an outpatient IBD clinic. Int J Colorectal Dis 2019; 34:393-400. [PMID: 30506156 DOI: 10.1007/s00384-018-3210-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/23/2018] [Indexed: 02/04/2023]
Abstract
PURPOSE Cytomegalovirus (CMV) infection has been found to be associated with a reactivation of ulcerative colitis (UC) and with an impaired response to medical therapy. In the past, only limited data were available on the long-term outcome for UC patients with positive tissue CMV-PCR in the colonic mucosa. METHODS Between January 2010 and April 2015, we performed a qualitative PCR screening for CMV DNA in one biopsy from most actively inflamed rectal mucosa (tCMV-PCR). All tCMV-PCR-positive patients received 900 mg of valganciclovir b.i.d. for at least 15 days. We analyzed the association of the tCMV-PCR status with the time to steroid-free remission (SFR) and with the risk of proctocolectomy during the further course. RESULTS One hundred eight consecutive patients (50 women, 58 men, median age 41 years, median UC duration 6 years) with active UC not responding to anti-inflammatory medication were analyzed. Eight of the 24 tCMV-PCR-positive patients (33.3%) compared to ten of the 84 tCMV-PCR-negative patients (11.9%) underwent proctocolectomy during a median follow-up of 52 months (p < 0.005). The median time from CMV diagnosis to colectomy was 501 days (median, interquartile range (IQR): 170, 902 days) in tCMV-PCR-positive and 958 days (IQR: 287, 1328 days) in tCMV-PCR-negative patients (p < 0.01). The median time to SFR was 126 days in tCMV-PCR-positive patients vs. 63 days in tCMV-PCR-negative patients (p < 0.01). CONCLUSIONS The detection of the CMV DNA in the colonic mucosa of patients with active UC is associated with a longer time to steroid-free UC remission and with an increased rate and earlier need of proctocolectomy.
Collapse
Affiliation(s)
- Wiebke Schenk
- Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten, Leipzig und Schkeuditz, Leipzig, Germany
- Klinik für Innere Medizin IV, Universitätsklinikum Jena, Jena, Germany
| | - Tobias Klugmann
- Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten, Leipzig und Schkeuditz, Leipzig, Germany
| | - Annett Borkenhagen
- Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten, Leipzig und Schkeuditz, Leipzig, Germany
| | - Chris Klecker
- Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten, Leipzig und Schkeuditz, Leipzig, Germany
| | - Peter Dietel
- Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten, Leipzig und Schkeuditz, Leipzig, Germany
| | - Ralf Kirschner
- MVZ Labor Dr. Reising-Ackermann und Kollegen, Leipzig, Germany
| | | | - Tony Bruns
- Klinik für Innere Medizin IV, Universitätsklinikum Jena, Jena, Germany
| | - Andreas Stallmach
- Klinik für Innere Medizin IV, Universitätsklinikum Jena, Jena, Germany
| | - Niels Teich
- Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten, Leipzig und Schkeuditz, Leipzig, Germany.
- Medizinische Fakultät der Friedrich-Schiller-Universität Jena, Jena, Germany.
| |
Collapse
|
|
44
|
Mavropoulou E, Ternes K, Mechie NC, Bremer SCB, Kunsch S, Ellenrieder V, Neesse A, Amanzada A. Cytomegalovirus colitis in inflammatory bowel disease and after haematopoietic stem cell transplantation: diagnostic accuracy, predictors, risk factors and disease outcome. BMJ Open Gastroenterol 2019; 6:e000258. [PMID: 30899538 PMCID: PMC6398871 DOI: 10.1136/bmjgast-2018-000258] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Revised: 12/27/2018] [Accepted: 12/28/2018] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Concurrent cytomegalovirus (CMV) colitis in inflammatory bowel disease (IBD) and after haematopoietic stem cell transplantation (HSCT) is an important clinical entity associated with high rates of morbidity and mortality. METHODS A retrospective study of 47 patients with IBD and 61 HSCT patients was performed regarding the evaluation of diagnostic accuracy of applied methods, predictors, risk factors for CMV disease manifestation, the proportion of patients with antiviral treatment and disease outcome. RESULTS The sensitivity of quantitative PCR (qPCR) with a cut-off value of >250 copies/mg for CMV colitis in patients with IBD and HSCT patients was 79% and 92%, respectively. Predictors for CMV colitis in the IBD cohort were anaemia and the presence of endoscopic ulcers. Glucocorticoids, calcineurin inhibitors and >2 concurrent lines of treatment with immunosuppressive drugs could be identified as risk factors for CMV colitis in the IBD cohort with an OR of 7.1 (95% CI 1.7 to 29.9), 21.3 (95% CI 2.4 to 188.7) and 13.4 (95% CI 3.2 to 56.1), respectively. Predictors and risk factors for CMV gastroenteritis in the HSCT cohort was the presence of endoscopic ulcers (OR 18.6, 95% CI 3.3 to 103.7) and >2 concurrent lines of treatment with immunosuppressive drugs. Antiviral therapy was administered in 70% of patients with IBD and 77% of HSCT patients with CMV disease. 71% of antiviral-treated patients with IBD showed an improvement of their disease activity and 14% underwent colectomy. The mortality rate of HSCT patients was 21% irrespective of their CMV status. CONCLUSIONS In addition to the implementation of histological methods, qPCR may be performed in patients with suspected high-risk IBD and HSCT patients for CMV colitis. Independent validations of these results in further prospective studies are needed.
Collapse
Affiliation(s)
- Eirini Mavropoulou
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | - Kristin Ternes
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | - Nicolae-Catalin Mechie
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | | | - Steffen Kunsch
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | - Volker Ellenrieder
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | - Albrecht Neesse
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| | - Ahmad Amanzada
- Department of Gastroenterology and Gastrointestinal Oncology, Universitatsklinikum Gottingen, Gottingen, Germany
| |
Collapse
|
|
45
|
Tun GSZ, Raza M, Hale MF, Lobo AJ. Polymerase chain reaction for detection of mucosal cytomegalovirus infection in patients with acute ulcerative colitis. Ann Gastroenterol 2018; 32:81-87. [PMID: 30598596 PMCID: PMC6302192 DOI: 10.20524/aog.2018.0318] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Accepted: 09/10/2018] [Indexed: 12/21/2022] Open
Abstract
Background Cytomegalovirus (CMV) infection is associated with acute exacerbations of ulcerative colitis (UC) but its clinical relevance remains uncertain. The primary aim of this study was to assess the prevalence of CMV infection in UC patients using viral polymerase chain reaction (PCR) analysis of mucosal biopsy samples. Secondary aims were to establish whether the disease was due to a primary infection or reactivation and to note associated risk factors and clinical outcomes. Methods Since 2011, a policy of biopsy for CMV infection was adopted for severe UC patients in a large tertiary center. A retrospective review was undertaken to identify patients with mucosal biopsies for exacerbations of UC from October 2011 through January 2014. Results Sixty biopsies for CMV PCR were obtained from 52 patients, 15 of whom were positive. In these patients, 9/9 tested were seropositive for anti-CMV IgG, while none were seropositive for anti-CMV IgM. Steroid refractory disease was a significant predictor of CMV positivity; however, there was no difference between the CMV-positive and -negative groups in rates of immunosuppression, or clinical and endoscopic severity. Six patients in the CMV-positive group received infliximab; all received concurrent antiviral therapy and did not require surgery. Conclusions PCR of mucosal biopsies detected CMV infection due to viral reactivation in almost a third of patients with deteriorating or acute severe UC. Steroid refractory disease was significantly associated with CMV positivity, but no significant relationship was demonstrated with either disease severity or immunosuppression in our cohort. Treatment with anti-tumor necrosis factor agents was administered safely in combination with antiviral drugs.
Collapse
Affiliation(s)
- Gloria S Z Tun
- Gastroenterology Department, Sheffield Teaching Hospital NHS Foundation Trust, United Kingdom
| | - Mohammad Raza
- Gastroenterology Department, Sheffield Teaching Hospital NHS Foundation Trust, United Kingdom
| | - Melissa F Hale
- Gastroenterology Department, Sheffield Teaching Hospital NHS Foundation Trust, United Kingdom
| | - Alan J Lobo
- Gastroenterology Department, Sheffield Teaching Hospital NHS Foundation Trust, United Kingdom
| |
Collapse
|
|
46
|
Bhut B, Kulkarni A, Rai V, Agrawal V, Verma A, Jain M, Marak RSK, Dixit AK, Ghoshal UC. A rare case of disseminated histoplasmosis in a patient with Crohn's disease on immunosuppressive treatment. Indian J Gastroenterol 2018; 37:472-474. [PMID: 30168074 DOI: 10.1007/s12664-018-0886-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Bhavesh Bhut
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Akshay Kulkarni
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Varnika Rai
- Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Vinita Agrawal
- Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Abhai Verma
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Manoj Jain
- Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Rungmei S K Marak
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Ajai Kumar Dixit
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Uday C Ghoshal
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India.
| |
Collapse
|
|
47
|
Siegmund B. Cytomegalovirus infection associated with inflammatory bowel disease. Lancet Gastroenterol Hepatol 2018; 2:369-376. [PMID: 28397701 DOI: 10.1016/s2468-1253(16)30159-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Revised: 10/11/2016] [Accepted: 10/13/2016] [Indexed: 12/18/2022]
Abstract
Refractory colitis in patients with inflammatory bowel disease is a complicated clinical disorder that might, in some patients, even necessitate surgery. Hence the diagnosis of additional complications is of utmost importance. Colitis mediated by cytomegalovirus is one such complication. The high seroprevalence and latent nature of cytomegalovirus, with the possibility of viral replication without mediating disease, poses a real challenge for the diagnosis of cytomegalovirus-mediated colitis. The challenge in daily clinical practice is to distinguish cytomegalovirus replication from cytomegalovirus-mediated colitis in patients with inflammatory bowel disease who have refractory colitis. This Review discusses the scientific literature and provides a diagnostic and therapeutic algorithm for clinical practice.
Collapse
Affiliation(s)
- Britta Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie, Rheumatologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
| |
Collapse
|
|
48
|
Detection of Cytomegalovirus in Colonic Mucosa of Children With Inflammatory Bowel Disease: Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr 2018; 67:221-224. [PMID: 29601437 DOI: 10.1097/mpg.0000000000001976] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Although it has been recommended to perform sigmoidoscopy to screen for cytomegalovirus (CMV) reactivation in acute severe colitis, the frequency of CMV reactivation in children with inflammatory bowel disease (IBD) is unknown. The aim of this study was to determine the frequency and management of CMV detection in colonic mucosa of children with IBD. METHODS In a retrospective study, consecutive IBD patients, <17 years old, with moderate to severe colitis who had sigmoid biopsy specimens evaluated for CMV by hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and polymerase chain reaction (PCR) were included. RESULTS A total of 90 sigmoid biopsies were collected from 67 patient encounters from 58 patients with colitis: 61 patient encounters (91%) with UC/IBD-U including biopsy samples from colectomy specimens of eight patients who had colectomy during the study period. Medication exposure included corticosteroids for 40 (69%) patients, and immunosuppressive agents for 31 (53.4%) patients. Four of 61 patient encounters (6.6%) with UC/IBD-U, two with corticosteroid refractory disease, had positive biopsies for CMV by PCR but negative H&E and IHC. They responded to escalated medical therapy, without needing anti-viral therapy, and none required colectomy over a median duration of follow up of 1.1 year (IQR 1-1.6). CONCLUSIONS CMV presence is uncommon in colonic mucosa of children with IBD. Studies examining the underlying sero-prevalence of CMV and its role of reactivation of colitis are required to determine if the current recommendation for routine sigmoidoscopy to exclude CMV infection in corticosteroid-refractory acute severe colitis is justified.
Collapse
|
|
49
|
Nowacki TM, Bettenworth D, Meister T, Heidemann J, Lenze F, Schmidt HH, Heinzow HS. Novel score predicts risk for cytomegalovirus infection in ulcerative colitis. J Clin Virol 2018; 105:103-108. [PMID: 29940421 DOI: 10.1016/j.jcv.2018.06.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Revised: 06/04/2018] [Accepted: 06/05/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Cytomegalovirus (CMV) infection is associated with relapse and exacerbation of ulcerative colitis (UC), especially in immunosuppressed patients. OBJECTIVES The aim of this study was to identify risk factors for CMV colitis and to develop a predictive risk score to estimate the probability of CMV colitis in UC patients supporting clinical decision making. STUDY DESIGN A cohort of 239 UC-patients was retrospectively analyzed. Univariate and multivariate regression analysis identified several independent risk factors for CMV colitis and a predictive risk score was established using ROC analysis. RESULTS CMV colitis is common in patients with severe ulcerative colitis. Clinical UC activity, disease duration and extent as well as the use of steroids and anti-TNF-α agents were identified as risk factors (p < 0.05 each). Based on five predictive parameters, a web-based risk score was developed. A strong correlation between the predicted and actual rates of CMV colitis was found (AUC: 0.855; 95% CI 0.79-0.92; p < 0.0001). CONCLUSIONS Our study supports the pathogenic relevance of CMV in UC. The predictive risk score estimates the risk of CMV colitis and might aid in clinical decision making, especially when timely modifications of therapeutic regimens are needed and reliable diagnostic tools are not readily available.
Collapse
Affiliation(s)
- Tobias M Nowacki
- Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany.
| | - Dominik Bettenworth
- Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
| | - Tobias Meister
- Department of Gastroenterology, HELIOS Albert-Schweitzer Hospital, Northeim, Germany
| | - Jan Heidemann
- Department of Gastroenterology, Klinikum Bielefeld, Bielefeld, Germany
| | - Frank Lenze
- Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
| | - Hartmut H Schmidt
- Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
| | - Hauke S Heinzow
- Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
| |
Collapse
|
|
50
|
Johnson J, Affolter K, Boynton K, Chen X, Valentine J, Peterson K. CMV Disease in IBD: Comparison of Diagnostic Tests and Correlation with Disease Outcome. Inflamm Bowel Dis 2018; 24:1539-1546. [PMID: 29718356 DOI: 10.1093/ibd/izy045] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND Significance of cytomegalovirus (CMV) in inflammatory bowel disease (IBD) is unclear due to pathobiology, numerous CMV tests, and disparate treatment outcomes. METHODS Retrospective chart review was done on patients with positive qualitative CMV tissue polymerase chain reaction (PCR) from 2005-2013 at a tertiary referral hospital. Frequency of PCR+, hematoxylin and eosin staining(HE)+, histopathology and immunohistochemistry (IHC)+ was assessed. IHC was assessed on a sample of PCR- tissues. Surgery rates were correlated with CMV testing and treatment. RESULTS PCR was done on 310 samples from 180 patients. Thirty-seven samples were PCR+ (51.4% PCR+ only, 35.1% IHC/PCR+, 13.5% HE/IHC/PCR+). The H&E frequently failed to detect CMV identified on extensive IHC. Of 13 PCR- samples tested with IHC, 100% were negative. Twenty-five patients were CMV+ (40% PCR+, 40% IHC/PCR+, 20% HE/IHC/PCR+). Surgery rates increased with number of positive tests: 60% in IHC/PCR+ and 80% in HE/IHC/PCR+, compared to 26.8% in PCR- or PCR+ (P = 0.03, P = 0.02, respectively). There were 20/25 PCR+ patients who received CMV treatment. Surgery occurred in 80% of HE+ patients despite treatment and 100% of IHC+ patients without treatment. CONCLUSIONS Rates of CMV+ testing and surgical risk varied by test modality. PCR+ results were most frequent but alone did not detect clinically significant CMV. HE+ testing was least frequent and associated with highest surgical rate, despite treatment. CMV treatment may benefit IHC+ patients most, supporting immunostaining as optimal diagnostic test for clinically significant CMV in IBD. In PCR+ samples, HE frequently did not detect CMV identified on extensive IHC. In PCR- samples, data suggest IHC is likely negative. Consider using qualitative PCR to guide extensive immunostaining.
Collapse
Affiliation(s)
- Jessica Johnson
- Division of Gastroenterology and Hepatology, University of Utah, Salt Lake City, UT, USA
| | | | | | | | - John Valentine
- Division of Gastroenterology and Hepatology, University of Utah
| | | |
Collapse
|