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1
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Ben-Tov A, Achler T, Patalon T, Gazit S, Yanai H, Shulman S, Assa A. The Prevalence and Characteristics of Inflammatory Bowel Disease-related Ocular Involvement in Children. Inflamm Bowel Dis 2025; 31:1256-1262. [PMID: 39046811 DOI: 10.1093/ibd/izae160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Indexed: 07/27/2024]
Abstract
BACKGROUND Ocular manifestations (OMs) in patients with inflammatory bowel disease (IBD) are uncommon, particularly in children. We aimed to explore the prevalence and characteristics of IBD-associated OM in a large cohort study. METHODS A cross-sectional study was performed using the Maccabi Healthcare Services (MHS) database. The eligible population included all patients diagnosed with IBD as children (<18 years) between January 2005 and July 2023. RESULTS Out of 2567 children with IBD (males 55%, Crohn's disease 64%), 78 (3%) were diagnosed with OM at any time during the disease course. In 54 patients (69%), the ocular disease occurred after IBD diagnosis with a median time of 2.6 (0.47-7) years between the 2 events, whereas in 24 patients (31%), ocular involvement preceded IBD diagnosis with a median time of 2.1 (0.6-5.7) years. The presence of ocular involvement was associated with increased usage of systemic corticosteroids (P < .001) and biologic agents (P = .04). There were 55 patients with ocular involvement during childhood who were ever diagnosed with IBD. In this population, ocular involvement was also associated with increased usage of systemic corticosteroids (P < .001). The prevalence of OM among patients with IBD did not change significantly over time (P = .75), with a prevalence of 2.3% at the end of the study period. CONCLUSIONS The prevalence of ocular involvement in children with IBD is rare and steady; it is also associated with a greater usage of systemic corticosteroids and biologic agents, potentially representing a more severe disease course.
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Affiliation(s)
- Amir Ben-Tov
- Kahn Sagol Maccabi (KSM) Research & Innovation Center, Maccabi Healthcare Services, Tel Aviv, Israel
- Pediatric Gastroenterology Institute, Dana-Dwek Children's Hospital, Tel Aviv, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Tomer Achler
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Tal Patalon
- Kahn Sagol Maccabi (KSM) Research & Innovation Center, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Sivan Gazit
- Kahn Sagol Maccabi (KSM) Research & Innovation Center, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Henit Yanai
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Shiri Shulman
- Ophthalmology Institute, Assuta Medical Center, Tel Aviv, Israel
- Faculty of health sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Amit Assa
- The Juliet Keidan IInstitute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University, Jerusalem, Israel
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2
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Songel-Sanchis B, Cosín-Roger J. Analysis of the Incidence of Ocular Extraintestinal Manifestations in Inflammatory Bowel Disease Patients: A Systematic Review. Diagnostics (Basel) 2024; 14:2815. [PMID: 39767176 PMCID: PMC11675585 DOI: 10.3390/diagnostics14242815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 12/10/2024] [Accepted: 12/13/2024] [Indexed: 01/11/2025] Open
Abstract
Background: Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, primarily affects the gastrointestinal tract. Additionally, extraintestinal manifestations may occur in the liver, musculoskeletal system and eyes. Its etiology remains unknown, and further research is required in order to develop pharmacological drugs which achieve complete remission of the pathology. Objective: The aim of this study was to analyze the incidence of ocular extraintestinal manifestations in IBD patients. Methods: A total of six searches were carried out on the medical publication server "PubMed" in June and July 2024, using different keywords; a total of 323 results were obtained, of which 34 were finally selected for study. Results: Ocular extraintestinal manifestations in IBD patients are more common in the anterior pole of the eye, with uveitis, scleritis and episcleritis being the most usual ones. In the case of the posterior pole, the most common manifestations are posterior uveitis and optic neuritis. Conclusions: The incidence of ocular complications whose origin is inflammatory, such as uveitis, scleritis, episcleritis and neuritis, is higher than that of complications of non-inflammatory origin.
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Affiliation(s)
| | - Jesús Cosín-Roger
- Departamento de Farmacología and CIBERehd, Facultad de Medicina, Universidad de Valencia, Av. Blasco Ibáñez, 15, 46010 Valencia, Spain;
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Alsoudi AF, Wai KM, Koo E, McConnell RA, Pham NH, Do BK, Ludwig CA, Kossler AL, Mruthyunjaya P, Rahimy E. Risk of Intestinal Complications, Extraintestinal Morbidity, and Mortality in Patients with Crohn's Disease and Ocular Involvement. Ocul Immunol Inflamm 2024; 32:2486-2493. [PMID: 39401331 DOI: 10.1080/09273948.2024.2413895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 09/29/2024] [Accepted: 10/01/2024] [Indexed: 10/23/2024]
Abstract
PURPOSE Patients with Crohn's disease (CD) and subsequent ocular manifestations may have worse outcomes when compared to matched patients with CD without ocular disease. METHODS In this retrospective cohort study, an aggregated electronic health records research network, TriNetX (Cambridge, MA, USA), was used to identify patients diagnosed with CD stratified by the presence or absence of ocular involvement with at least 1 year of follow-up. Propensity score matching (PSM) was performed to control for baseline demographics and medical comorbidities. RESULTS Patients with CD with ocular disease showed a greater risk of undergoing bowel resections (RR: 2.06, 95% CI: 1.48-2.85, p < 0.001), developing other CD-related gastrointestinal complications (RR: 1.31, CI: 1.15-1.49, p < 0.001), or acquiring Clostridioides difficile infections (RR: 2.19, CI: 1.89-2.54, p < 0.001). Further, patients with CD with ocular sequelae had a greater risk of developing NASH (RR: 1.43, CI: 1.31-1.56, p < 0.001), CD-related nutrient deficiencies (RR: 1.38, CI: 1.29-1.49, p < 0.001), iron deficiency anemia (RR: 1.41, CI: 1.33-1.50, p < 0.001), CD-related dermatological disease (RR: 1.84, CI: 1.65-2.05, p < 0.001), osteoporosis (RR: 1.49, CI: 1.37-1.64, p < 0.001) and primary sclerosing cholangitis (RR: 1.63, CI: 1.11-2.38, p = 0.011). Among patients with CD with ocular involvement, there was an elevated risk of MI (RR: 1.36, CI: 1.14-1.63, p < 0.001), stroke (RR: 1.42, CI: 1.18-1.70, p < 0.001), VTE (RR: 1.37, CI: 1.22-1.54, p < 0.001), and sepsis (RR: 1.53, CI: 1.37-1.71, p < 0.001). CONCLUSIONS Patients who have CD and subsequent ocular involvement have an increased risk of local intestinal complications, extraintestinal morbidity, and cardiovascular complications when compared to patients with CD without ocular involvement.
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Affiliation(s)
- Amer F Alsoudi
- Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA
| | - Karen M Wai
- Byers Eye Institute, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA
| | - Euna Koo
- Byers Eye Institute, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA
| | - Ryan A McConnell
- Department of Gastroenterology, Palo Alto Medical Foundation, Palo Alto, California, USA
| | - Nathan H Pham
- Department of Gastroenterology, University of Washington Seattle, Seattle, Washington, USA
| | - Brian K Do
- Department of Ophthalmology, MedStar Georgetown University Hospital, Washington, District of Columbia, USA
- The Retina Group of Washington, Chevy Chase, Maryland, USA
| | - Cassie A Ludwig
- Byers Eye Institute, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA
| | - Andrea L Kossler
- Byers Eye Institute, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA
| | - Prithvi Mruthyunjaya
- Byers Eye Institute, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA
| | - Ehsan Rahimy
- Byers Eye Institute, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA
- Department of Ophthalmology, Palo Alto Medical Foundation, Palo Alto, California, USA
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4
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Yao Y, Wang Q, Wei W. Association between iridocyclitis and immune-related disease: A 2-sample Mendelian randomization study. Medicine (Baltimore) 2024; 103:e40663. [PMID: 39612419 PMCID: PMC11608751 DOI: 10.1097/md.0000000000040663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 11/06/2024] [Indexed: 12/01/2024] Open
Abstract
The genetic basis of iridocyclitis, an inflammatory eye disease, remains poorly understood, particularly in relation to autoimmune diseases. This study aimed to explore the causal associations between 6 immune-related diseases and iridocyclitis using Mendelian randomization (MR). A total of 230 single nucleotide polymorphisms (SNPs) significantly associated with systemic lupus erythematosus, ankylosing spondylitis (AS), rheumatoid arthritis (RA), Graves disease (GD), Crohn disease (CD), and allergic contact dermatitis were identified based on stringent MR assumptions. These SNPs served as instrumental variables to estimate the causal effect of each autoimmune disease on iridocyclitis risk. The analysis utilized the inverse variance weighted method, complemented by sensitivity analyses including MR-Egger regression and leave-one-out testing to assess pleiotropy and robustness. The MR analysis revealed significant associations between genetically predicted AS (odds ratio [OR]: 1.544, 95% confidence interval [CI]: 1.494-1.595, P = 1.99 × 10-226), RA (OR: 1.207, 95% CI: 1.052-1.385, P = .003), and CD (OR: 1.654, 95% CI: 1.263-2.166, P = 2.54 × 10⁻⁶) with an increased risk of iridocyclitis. Conversely, higher genetically predicted GD was associated with a decreased risk of iridocyclitis (OR: 0.763, 95% CI: 0.674-0.865, P = .0002). Although systemic lupus erythematosus and allergic contact dermatitis appeared to have a protective effect, these results were not statistically significant, and no causal relationship could be established. Heterogeneity was observed among the SNPs, but no significant horizontal pleiotropy was detected. This study identifies potential genetic links between AS, RA, CD, GD, and the risk of iridocyclitis, providing new insights into the genetic underpinnings of this eye disease. The results support the need for further investigation into the genetic and molecular mechanisms underlying these associations.
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Affiliation(s)
- Yao Yao
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Capital Medical University, Beijing, China
| | - Qian Wang
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Capital Medical University, Beijing, China
| | - Wenbin Wei
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Capital Medical University, Beijing, China
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5
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Alizadeh M, Motwani K, Siaton BC, Abutaleb A, Ravel J, Cross RK. Factors Associated With Extraintestinal Manifestations of Inflammatory Bowel Disease in SPARC-IBD. Inflamm Bowel Dis 2024; 30:2027-2036. [PMID: 38102817 PMCID: PMC11532592 DOI: 10.1093/ibd/izad280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Indexed: 12/17/2023]
Abstract
BACKGROUND Extraintestinal manifestations (EIMs) of inflammatory bowel diseases (IBDs) are a common and debilitating feature of disease, occurring in up to 40% of patients with IBD, yet predicting who may develop them is difficult. The goal of our study was to better characterize which patients may be at highest risk of developing not only 1 EIM, but also multiple EIMs, across both diseases. METHODS A retrospective study of participants enrolled in the SPARC IBD (Study of Prospective Adult Research Cohort with IBD) registry was performed, and demographic and clinical data were analyzed. A total of 1211 patients with data available on EIMs were included, and differences among variables with vs without EIMs were assessed. RESULTS A total of 329 participants with at least 1 EIM were identified, compared with 882 participants without any EIMs. Crohn's disease patients and women were more likely to have 2 or more EIMs (P = .005 and P ≤ .001, respectively). Participants with ocular manifestations were likeliest to have at least 2 EIMs (P ≤ .001). Even when diagnosis was controlled for, involvement of the right colon (P = .021) was predictive of IBD-associated arthritis across both diseases in a multivariate generalized linear model. CONCLUSIONS This is the first comprehensive large-cohort assessment of how EIMs relate to one another at the individual vs systems levels. Further, our analysis is the first to recognize specific locations of colon involvement associated with EIMs of IBD, regardless of IBD type. These results are important in identifying patients at risk of developing future EIMs and may help with risk stratification when choosing treatments.
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Affiliation(s)
- Madeline Alizadeh
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Kiran Motwani
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Bernadette C Siaton
- Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Ameer Abutaleb
- Department of Surgery, George Washington University School of Medicine and Health Sciences, Washington, DC, USA
| | - Jacques Ravel
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Raymond K Cross
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
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Khrom M, Long M, Dube S, Robbins L, Botwin GJ, Yang S, Mengesha E, Li D, Naito T, Bonthala NN, Ha C, Melmed G, Rabizadeh S, Syal G, Vasiliauskas E, Ziring D, Brant SR, Cho J, Duerr RH, Rioux J, Schumm P, Silverberg M, Ananthakrishnan AN, Faubion WA, Jabri B, Lira SA, Newberry RD, Sandler RS, Xavier RJ, Kugathasan S, Hercules D, Targan SR, Sartor RB, Haritunians T, McGovern DPB. Comprehensive Association Analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease. Gastroenterology 2024; 167:315-332. [PMID: 38490347 PMCID: PMC11193636 DOI: 10.1053/j.gastro.2024.02.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 02/11/2024] [Accepted: 02/13/2024] [Indexed: 03/17/2024]
Abstract
BACKGROUND & AIMS Patients with inflammatory bowel disease (IBD) frequently develop extraintestinal manifestations (EIMs) that contribute substantially to morbidity. We assembled the largest multicohort data set to date to investigate the clinical, serologic, and genetic factors associated with EIM complications in IBD. METHODS Data were available in 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs (eg, ankylosing spondylitis [ankylosing spondylitis and sacroiliitis], primary sclerosing cholangitis [PSC], peripheral arthritis, and skin and ocular manifestations) across 4 cohorts (Cedars-Sinai Medical Center, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort). Clinical and serologic parameters were analyzed by means of univariable and multivariable regression analyses using a mixed-effects model. Within-case logistic regression was performed to assess genetic associations. RESULTS Most EIMs occurred more commonly in female subjects (overall EIM: P = 9.0E-05, odds ratio [OR], 1.2; 95% CI, 1.1-1.4), with CD (especially colonic disease location; P = 9.8E-09, OR, 1.7; 95% CI, 1.4-2.0), and in subjects who required surgery (both CD and UC; P = 3.6E-19, OR, 1.7; 95% CI, 1.5-1.9). Smoking increased risk of EIMs except for PSC, where there was a "protective" effect. Multiple serologic associations were observed, including with PSC (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-flagellin) and any EIM (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-Pseudomonas fluorescens-associated sequence). We identified genome-wide significant associations within major histocompatibility complex (ankylosing spondylitis and sacroiliitis, P = 1.4E-15; OR, 2.5; 95% CI, 2.0-3.1; PSC, P = 2.7E-10; OR, 2.8; 95% CI, 2.0-3.8; ocular, P = 2E-08, OR, 3.6; 95% CI, 2.3-5.6; and overall EIM, P = 8.4E-09; OR, 2.2; 95% CI, 1.7-2.9) and CPEB4 (skin, P = 2.7E-08; OR, 1.5; 95% CI, 1.3-1.8). Genetic associations implicated tumor necrosis factor, JAK-STAT, and IL6 as potential targets for EIMs. Contrary to previous reports, only 2% of our subjects had multiple EIMs and most co-occurrences were negatively correlated. CONCLUSIONS We have identified demographic, clinical, and genetic associations with EIMs that revealed underlying mechanisms and implicated novel and existing drug targets-important steps toward a more personalized approach to IBD management.
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MESH Headings
- Humans
- Female
- Male
- Adult
- Cholangitis, Sclerosing/immunology
- Cholangitis, Sclerosing/genetics
- Cholangitis, Sclerosing/diagnosis
- Cholangitis, Sclerosing/complications
- Middle Aged
- Colitis, Ulcerative/immunology
- Colitis, Ulcerative/genetics
- Colitis, Ulcerative/diagnosis
- Crohn Disease/immunology
- Crohn Disease/genetics
- Crohn Disease/diagnosis
- Adolescent
- Risk Factors
- Child
- Spondylitis, Ankylosing/genetics
- Spondylitis, Ankylosing/immunology
- Spondylitis, Ankylosing/diagnosis
- Spondylitis, Ankylosing/complications
- Genetic Predisposition to Disease
- Young Adult
- Sex Factors
- Skin Diseases/etiology
- Skin Diseases/immunology
- Skin Diseases/genetics
- Eye Diseases/etiology
- Eye Diseases/immunology
- Eye Diseases/diagnosis
- Eye Diseases/genetics
- Eye Diseases/epidemiology
- Phenotype
- Inflammatory Bowel Diseases/genetics
- Inflammatory Bowel Diseases/immunology
- Inflammatory Bowel Diseases/diagnosis
- Logistic Models
- Aged
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Affiliation(s)
- Michelle Khrom
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Millie Long
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina
| | - Shishir Dube
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Lori Robbins
- Palmetto Digestive Health Specialists, Charleston, South Carolina
| | - Gregory J Botwin
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Shaohong Yang
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Emebet Mengesha
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Dalin Li
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Takeo Naito
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Nirupama N Bonthala
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Christina Ha
- Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Gil Melmed
- Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Shervin Rabizadeh
- Department of Pediatrics, Pediatric Inflammatory Bowel Disease Program, Cedars-Sinai Medical Center, Los Angeles, California
| | - Gaurav Syal
- Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Eric Vasiliauskas
- Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - David Ziring
- Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Steven R Brant
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
| | - Judy Cho
- Icahn School of Medicine at Mount Sinai, Dr Henry D. Janowitz Division of Gastroenterology, New York, New York
| | - Richard H Duerr
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - John Rioux
- Department of Medicine, Université de Montréal and Research Center, Montreal Heart Institute, Montréal, Québec, Canada
| | - Phil Schumm
- Department of Public Health Sciences, University of Chicago, Chicago, Illinois
| | - Mark Silverberg
- University of Toronto, Samuel Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
| | | | | | - Bana Jabri
- University of Chicago, Pritzker School of Medicine, Chicago, Illinois
| | - Sergio A Lira
- Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Rodney D Newberry
- Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri
| | - Robert S Sandler
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina
| | - Ramnik J Xavier
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts
| | - Subra Kugathasan
- Children's Healthcare of Atlanta Combined Center for Pediatric Inflammatory Bowel Disease, Atlanta, Georgia; Emory School of Medicine, Atlanta, Georgia
| | | | - Stephan R Targan
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - R Balfour Sartor
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina
| | - Talin Haritunians
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Dermot P B McGovern
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California.
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AWARE-IBD Diagnostic Delay Working Group. Sources of diagnostic delay for people with Crohn's disease and ulcerative colitis: Qualitative research study. PLoS One 2024; 19:e0301672. [PMID: 38857292 PMCID: PMC11164383 DOI: 10.1371/journal.pone.0301672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 03/20/2024] [Indexed: 06/12/2024] Open
Abstract
OBJECTIVE An improved understanding of the causes and experience of diagnostic delay in Inflammatory Bowel Disease (IBD). METHODS Framework analysis of semi-structured interviews with 20 adults with IBD. RESULTS Participants' prior knowledge of normal bowel function/IBD was limited. Symptoms were sometimes misattributed to mild/transient conditions or normalised until intolerable. Family pressures, work, education, mistrust of doctors, fear and embarrassment could exacerbate delays. Poor availability of face-to-face appointments deterred people from seeing a GP. Patients feared that by the time they got to see their GP, their symptoms would have resolved. Patients instead self-managed symptoms, but often regretted not seeking help earlier. Limited time in consultations, language barriers, embarrassment, and delays in test results subsequently delayed specialist referrals. GPs misattributed symptoms to other conditions due to atypical or non-specific presentations, leading to reduced trust in health systems. Patients complained of poor communication, delays in accessing test results, appointments, and onward referrals-all associated with clinical deterioration. GPs were sometimes unable to 'fast-track' patients into specialist care. Consultations and endoscopies were often difficult experiences for patients, especially for non-English speakers who are also less likely to receive information on mental health support and the practicalities of living with IBD. CONCLUSIONS The framework analysis demonstrates delay in the diagnosis of IBD at each stage of the patient journey. RECOMMENDATIONS Greater awareness of IBD amongst the general population would facilitate presentation to healthcare services through symptom recognition by individuals and community advice. Greater awareness in primary care would help ensure IBD is included in differential diagnosis. In secondary care, greater attention to the wider needs of patients is needed-beyond diagnosis and treatment. All clinicians should consider atypical presentations and the fluctuating nature of IBD. Diagnostic overshadowing is a significant risk-where other diagnoses are already in play the risk of delay is considerable.
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Affiliation(s)
- AWARE-IBD Diagnostic Delay Working Group
- Sheffield CTRU, University of Sheffield, Regent Court, Sheffield, United Kingdom
- The Medical School, The University of Sheffield, Sheffield, United Kingdom
- Academic Unit of Medical Education, The Medical School, The University of Sheffield, Sheffield, United Kingdom
- Sheffield Inflammatory Bowel Disease Centre, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
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8
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Momayez Sanat Z, Vahedi H, Malekzadeh R, Fanni Z. A systematic review and meta-analysis of extra-intestinal manifestation of inflammatory bowel disease in the Eastern Mediterranean Region (EMRO) countries. Ann Med Surg (Lond) 2024; 86:2892-2899. [PMID: 38694357 PMCID: PMC11060319 DOI: 10.1097/ms9.0000000000001543] [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: 08/25/2023] [Accepted: 11/17/2023] [Indexed: 05/04/2024] Open
Abstract
Background Inflammatory bowel disease which is subgrouped mainly to ulcerative colitis and Crohn's disease is thought to be a multi-organ disease. Most organs can be involved in the disease course in addition to gastrointestinal tract involvement. In this systematic review we aimed to assess the prevalence of these manifestations in Eastern Mediterranean Regional Office (EMRO) countries. Method The present systematic review and meta-analysis study was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guideline. Joanna Briggs Institute (JBI) Critical Appraisal Checklist was admired for the quality evaluation of the included studies. For determining the heterogeneity, we used Cochran test and I2 statistics. Result Finally, 12 studies were included in our study. Based on the results of our study the prevalence of arthritis in ulcerative colitis and Crohn's disease patients was 7.1% (95% CI: 2.6-18.2%) and 13.5% (95% CI: 2.6-47.3%), respectively. Prevalence of arthralgia in ulcerative colitis patients was 18.4% (95% CI: 14.3-23.3%). skin involvement prevalence was 9.9% (95% CI 4.7-19.6%) in inflammatory bowel disease (IBD) patients. ocular involvement prevalence was 7.2% (95% CI 17-25.8%) in IBD patients. PSC prevalence in ulcerative colitis and Crohn's disease patients was 3.5% (95% CI: 1.7-7.3%) and 2.7% (95% CI: 1.3-5.5%), respectively. Conclusion Based on the results of this study arthralgia and arthritis were the most common extra-intestinal manifestation of IBD followed by dermatologic and ocular involvements. This extra-intestinal manifestation can challenge the patients' management and identifying their pattern is important during the disease course.
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Affiliation(s)
- Zahra Momayez Sanat
- Tehran University of Medical Sciences
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Homayoon Vahedi
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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9
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Dong X, Gong LL, Hong MZ, Pan JS. Investigating the shared genetic architecture between primary sclerosing cholangitis and inflammatory bowel diseases: a Mendelian randomization study. BMC Gastroenterol 2024; 24:77. [PMID: 38373892 PMCID: PMC10875759 DOI: 10.1186/s12876-024-03162-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 02/07/2024] [Indexed: 02/21/2024] Open
Abstract
BACKGROUND Several studies have found that primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) are closely associated. However, the direction and causality of their interactions remain unclear. Thus, this study employs Mendelian Randomization to explore whether there are causal associations of genetically predicted PSC with IBD. METHODS Genetic variants associated with the genome-wide association study (GWAS) of PSC were used as instrumental variables. The statistics for IBD, including ulcerative colitis (UC), and Crohn's disease (CD) were derived from GWAS. Then, five methods were used to estimate the effects of genetically predicted PSC on IBD, including MR Egger, Weighted median (WM), Inverse variance weighted (IVW), Simple mode, and Weighted mode. Last, we also evaluated the pleiotropic effects, heterogeneity, and a leave-one-out sensitivity analysis that drives causal associations to confirm the validity of the analysis. RESULTS Genetically predicted PSC was significantly associated with an increased risk of UC, according to the study (odds ratio [OR] IVW= 1.0014, P<0.05). However, none of the MR methods found significant causal evidence of genetically predicted PSC in CD (All P>0.05). The sensitivity analysis results showed that the causal effect estimations of genetically predicted PSC on IBD were robust, and there was no horizontal pleiotropy or statistical heterogeneity. CONCLUSIONS Our study corroborated a causal association between genetically predicted PSC and UC but did not between genetically predicted PSC and CD. Then, we identification of shared SNPs for PSC and UC, including rs3184504, rs9858213, rs725613, rs10909839, and rs4147359. More animal experiments and clinical observational studies are required to further clarify the underlying mechanisms of PSC and IBD.
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Affiliation(s)
- Xuan Dong
- Department of Hepatology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
- Hepatology Research Institute, Fujian Medical University, Fuzhou, Fujian, China
- Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hosptial, Fujian Medical University, Fuzhou, Fujian, China
- Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou, Fujian, China
| | - Li-Li Gong
- Department of General Practice, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, China
| | - Mei-Zhu Hong
- Department of Traditional Chinese Medicine, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China.
| | - Jin-Shui Pan
- Department of Hepatology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
- Hepatology Research Institute, Fujian Medical University, Fuzhou, Fujian, China.
- Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hosptial, Fujian Medical University, Fuzhou, Fujian, China.
- Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou, Fujian, China.
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10
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Gordon H, Burisch J, Ellul P, Karmiris K, Katsanos K, Allocca M, Bamias G, Barreiro-de Acosta M, Braithwaite T, Greuter T, Harwood C, Juillerat P, Lobaton T, Müller-Ladner U, Noor N, Pellino G, Savarino E, Schramm C, Soriano A, Michael Stein J, Uzzan M, van Rheenen PF, Vavricka SR, Vecchi M, Zuily S, Kucharzik T. ECCO Guidelines on Extraintestinal Manifestations in Inflammatory Bowel Disease. J Crohns Colitis 2024; 18:1-37. [PMID: 37351850 DOI: 10.1093/ecco-jcc/jjad108] [Citation(s) in RCA: 74] [Impact Index Per Article: 74.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Indexed: 06/24/2023]
Affiliation(s)
- Hannah Gordon
- Department of Gastroenterology, Barts Health NHS Trust, London, Centre for Immunobiology, Blizard Institute, Faculty of Medicine, Barts & The London Medical School, Queen Mary University of London, UK
| | - Johan Burisch
- Gastrounit, medical division, Hvidovre Hospital, University of Copenhagen, Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Denmark
| | - Pierre Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
| | | | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, Division of Internal Medicine, University and Medical School of Ioannina, Ioannina, Greece
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Giorgos Bamias
- GI Unit, 3rd Academic Department of Internal Medicine, National and Kapodistrian University of Athens, Sotiria Hospital, Athens, Greece
| | - Manuel Barreiro-de Acosta
- University Hospital Santiago De Compostela CHUS, Department of Gastroenterology - IBD Unit, Santiago De Compostela, Spain
| | - Tasanee Braithwaite
- School of Immunology and Microbiology, King's College London, The Medical Eye Unit, Guy's and St Thomas' Hospital NHS Foundation Trust, London, UK
| | - Thomas Greuter
- Division of Gastroenterology and Hepatology, GZO - Zurich Regional Health Center, Wetzikon, Division of Gastroenterology and Hepatology, University Hospital Lausanne - CHUV, Lausanne, Switzerland; Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Catherine Harwood
- Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London; Department of Dermatology, Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Pascal Juillerat
- Gastroenterology, Clinic for Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland; Crohn and Colitis Center, Gastro-entérologie Beaulieu SA, Lausanne, Switzerland
| | - Triana Lobaton
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent; Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Ulf Müller-Ladner
- Department of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus Liebig University Giessen, Bad Nauheim, Germany
| | - Nurulamin Noor
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Gianluca Pellino
- Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona UAB, Barcelona, Spain; Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Christoph Schramm
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Alessandra Soriano
- Gastroenterology Division and IBD Center, Internal Medicine Department, Azienda Unità Sanitaria Locale - IRCCS, 42122 Reggio Emilia, Italy
| | - Jürgen Michael Stein
- Interdisciplinary Crohn Colitis Centre Rhein-Main, Frankfurt/Main, Department of Gastroenterology and Clinical Nutrition, DGD Clinics Sachsenhausen, Frankfurt/Main, Germany
| | - Mathieu Uzzan
- Department of Gastroenterology, Hôpital Henri Mondor, APHP, Créteil, France
| | - Patrick F van Rheenen
- Department of Paediatric Gastroenterology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Stephan R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital, Zurich, Switzerland
| | - Maurizio Vecchi
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Stephane Zuily
- Vascular Medicine Division and French Referral Center for Rare Auto-Immune Diseases, Université de Lorraine, INSERM, DCAC and CHRU-Nancy, Nancy, France
| | - Torsten Kucharzik
- Department of Gastroenterology, Lüneburg Hospital, University of Münster, Lüneburg, Germany
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11
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Rodriguez Duran M, O'Keefe GAD. Ocular extraintestinal manifestations and treatments in patients with inflammatory bowel disease. FRONTIERS IN OPHTHALMOLOGY 2024; 3:1257068. [PMID: 38983096 PMCID: PMC11182217 DOI: 10.3389/fopht.2023.1257068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 12/06/2023] [Indexed: 07/11/2024]
Abstract
Between 3-47% of patients with inflammatory bowel disease (IBD) have extraintestinal manifestations (EIMs), and between 1.3-86.9% of patients with IBD suffer from ocular EIMs (O-EIMs) making the eye the third most common organ affected. These O-EIMs exist among a spectrum, with a variety of types and amounts of inflammation which can lead to decreased vision, and in some cases, vision loss, without treatment. We performed a literature review concerning O-EIMs in patients who had or were later found to have a diagnosis of IBD in order to identify ocular EIMs that commonly occur with IBD and to assess which patients with IBD may be at higher risk of developing O-EIMs. We were also interested in ascertaining whether O-EIMs were more common in specific populations of people or in specific subtypes of IBD. Lastly, we explored the common treatments of O-EIMs in patients with IBD. Upon review of the literature, we found that the most common O-EIMs are episcleritis and uveitis. Anterior uveitis is more commonly seen, although, inflammation may occur in the posterior segment of the eye as well and may also manifest as retinal vasculitis. While these diagnoses are sometimes known retrospectively, most patients present with nonspecific eye complaints of which decreased vision with or without pain is the most common. Visual symptoms associated with ocular EIMs may be non-specific so physicians should have a low threshold to refer to ophthalmology for visual complaints. It is important to keep in mind that ocular EIMs can cluster with skin and joint EIMs. Screening should be prioritized for female patients with Crohn's disease and concurrent arthritis. Treatments for O-EIMs are outlined and compared in this paper as well.
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Affiliation(s)
- Mariana Rodriguez Duran
- Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, United States
| | - Ghazala A Datoo O'Keefe
- Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, United States
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12
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Zhou KZ, Wu PF, Ling XZ, Zhang J, Wang QF, Zhang XC, Xue Q, Zhang T, Han W, Zhang GX. miR-460b-5p promotes proliferation and differentiation of chicken myoblasts and targets RBM19 gene. Poult Sci 2024; 103:103231. [PMID: 37980764 PMCID: PMC10685028 DOI: 10.1016/j.psj.2023.103231] [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: 08/09/2023] [Revised: 09/30/2023] [Accepted: 10/20/2023] [Indexed: 11/21/2023] Open
Abstract
The meat production of broilers is crucial to economic benefits of broiler industries, while the slaughter performance of broilers is directly determined by skeletal muscle development. Hence, the broiler breeding for growth traits shows a great importance. As a kind of small noncoding RNA, microRNA (miRNA) can regulate the expression of multiple genes and perform a wide range of regulation in organisms. Currently, more and more studies have confirmed that miRNAs are closely associated with skeletal muscle development of chickens. Based on our previous miR-seq analysis (accession number: PRJNA668199), miR-460b-5p was screened as one of the key miRNAs probably involved in the growth regulation of chickens. However, the regulatory effect of miR-460b-5p on the development of chicken skeletal muscles is still unclear. Therefore, miR-460b-5p was further used for functional validation at the cellular level in this study. The expression pattern of miR-460b-5p was investigated in proliferation and differentiation stages of chicken primary myoblasts. It was showed that the expression level of miR-460b-5p gradually decreased from the proliferation stage (GM 50%) to the lowest at 24 h of differentiation. As differentiation proceeded, miR-460b-5p expression increased significantly, reaching the highest and stabilizing at 72 h and 96 h of differentiation. Through mRNA quantitative analysis of proliferation marker genes, CCK-8 and Edu assays, miR-460b-5p was found to significantly facilitate the transition of myoblasts from G1 to S phase and promote chicken myoblast proliferation. mRNA and protein quantitative analysis of differentiation marker genes, as well as the indirect immunofluorescence results of myotubes, revealed that miR-460b-5p significantly stimulated myotube development and promote chicken myoblast differentiation. In addition, the target relationship was validated for miR-460b-5p according to the dual-luciferase reporter assay and mRNA quantitative analysis, which indicates that miR-460b-5p was able to regulate RBM19 expression by specifically binding to the 3' UTR of RBM19. In summary, miR-460b-5p has positive regulatory effects on the proliferation and differentiation of chicken myoblasts, and RBM19 is a target gene of miR-460b-5p.
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Affiliation(s)
- Kai-Zhi Zhou
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
| | - Peng-Fei Wu
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
| | - Xuan-Ze Ling
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
| | - Jin Zhang
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
| | - Qi-Fan Wang
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
| | - Xin-Chao Zhang
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
| | - Qian Xue
- Poultry Institute, Chinese Academy of Agricultural Sciences, Yangzhou 225125, China
| | - Tao Zhang
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China
| | - Wei Han
- Poultry Institute, Chinese Academy of Agricultural Sciences, Yangzhou 225125, China
| | - Gen-Xi Zhang
- College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, China.
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13
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Marsool MDM, Vora N, Marsool ADM, Pati S, Narreddy M, Patel P, Gadam S, Prajjwal P. Ulcerative colitis: Addressing the manifestations, the role of fecal microbiota transplantation as a novel treatment option and other therapeutic updates. Dis Mon 2023; 69:101606. [PMID: 37357103 DOI: 10.1016/j.disamonth.2023.101606] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/27/2023]
Abstract
The prevalence and incidence of Ulcerative Colitis (UC), a recurrent and remitting inflammatory condition, are rising. Any part of the colon may be affected, beginning with inflammation of the mucosa in the rectum and continuing proximally continuously. Bloody diarrhea, tenesmus, fecal urgency, and stomach pain are typical presenting symptoms. Many patients present with extraintestinal manifestations (EIMs) including musculoskeletal, ocular, renal, hepatobiliary, and dermatological presentation, among others. Most cases are treated with pharmacological therapy including mesalazine and glucocorticoids. Fecal microbiota transplantation (FMT) is a novel procedure that is increasingly being used to treat UC, however, its use yet remains controversial because of uncertain efficacy. FMT can lower gut permeability and consequently disease severity by boosting short-chain fatty acids production, helping in epithelial barrier integrity preservation. Upadacitinib (JAK Kinase inhibitor) is another newer treatment option, which is an FDA-approved drug that is being used to treat UC. This review article provides a comprehensive review of the EIMs of UC, the role of FMT along with various recent clinical trials pertaining to FMT as well as other diagnostic and therapeutic updates.
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Affiliation(s)
| | - Neel Vora
- B. J. Medical College, Ahmedabad, India
| | | | - Shefali Pati
- St George's University, School of Medicine, Grenada
| | | | - Parth Patel
- Pramukhswami Medical College, Karamsad, India
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14
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Bao W, Wang L, Liu X, Li M. Predicting diagnostic biomarkers associated with immune infiltration in Crohn's disease based on machine learning and bioinformatics. Eur J Med Res 2023; 28:255. [PMID: 37496049 PMCID: PMC10369716 DOI: 10.1186/s40001-023-01200-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 06/26/2023] [Indexed: 07/28/2023] Open
Abstract
OBJECTIVE The objective of this study is to investigate potential biomarkers of Crohn's disease (CD) and the pathological importance of infiltration of associated immune cells in disease development using machine learning. METHODS Three publicly accessible CD gene expression profiles were obtained from the GEO database. Inflammatory tissue samples were selected and differentiated between colonic and ileal tissues. To determine the differentially expressed genes (DEGs) between CD and healthy controls, the larger sample size was merged as a training unit. The function of DEGs was comprehended through disease enrichment (DO) and gene set enrichment analysis (GSEA) on DEGs. Promising biomarkers were identified using the support vector machine-recursive feature elimination and lasso regression models. To further clarify the efficacy of potential biomarkers as diagnostic genes, the area under the ROC curve was observed in the validation group. Additionally, using the CIBERSORT approach, immune cell fractions from CD patients were examined and linked with potential biomarkers. RESULTS Thirty-four DEGs were identified in colon tissue, of which 26 were up-regulated and 8 were down-regulated. In ileal tissues, 50 up-regulated and 50 down-regulated DEGs were observed. Disease enrichment of colon and ileal DEGs primarily focused on immunity, inflammatory bowel disease, and related pathways. CXCL1, S100A8, REG3A, and DEFA6 in colon tissue and LCN2 and NAT8 in ileum tissue demonstrated excellent diagnostic value and could be employed as CD gene biomarkers using machine learning methods in conjunction with external dataset validation. In comparison to controls, antigen processing and presentation, chemokine signaling pathway, cytokine-cytokine receptor interactions, and natural killer cell-mediated cytotoxicity were activated in colonic tissues. Cytokine-cytokine receptor interactions, NOD-like receptor signaling pathways, and toll-like receptor signaling pathways were activated in ileal tissues. NAT8 was found to be associated with CD8 T cells, while CXCL1, S100A8, REG3A, LCN2, and DEFA6 were associated with neutrophils, indicating that immune cell infiltration in CD is closely connected. CONCLUSION CXCL1, S100A8, REG3A, and DEFA6 in colonic tissue and LCN2 and NAT8 in ileal tissue can be employed as CD biomarkers. Additionally, immune cell infiltration is crucial for CD development.
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Affiliation(s)
- Wenhui Bao
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Spleen and Gastroenterology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, No.354 Beima Road, Hongqiao District, Tianjin, China
| | - Lin Wang
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Nephrology Department, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiaoxiao Liu
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Department of Comprehensive Rehabilitation, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Ming Li
- Spleen and Gastroenterology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, No.354 Beima Road, Hongqiao District, Tianjin, China.
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15
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Granstam E, Rönnblom A. Occurrence of uveitis in a population-based cohort of inflammatory bowel diseases followed for 10 years: an observational study. BMJ Open Ophthalmol 2023; 8:e001318. [PMID: 37493645 PMCID: PMC10351296 DOI: 10.1136/bmjophth-2023-001318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 06/27/2023] [Indexed: 07/27/2023] Open
Abstract
OBJECTIVE The coexistence of inflammatory bowel diseases (IBDs) and uveitis has been known for 100 years. The reported frequency by which these conditions appear in the same patient has varied considerably. The aim of this study was to investigate the occurrence of uveitis in a well-defined population-based cohort of patients with IBD including all age groups and followed for at least 10 years. METHOD AND ANALYSIS All newly diagnosed patients with ulcerative colitis and Crohn's disease in the county of Uppsala between 2005 and 2009 were prospectively followed. At the end of 2022, the medical notes were checked and all contacts with the healthcare system regarding ocular symptoms were scrutinised. RESULTS A total of 330 patients with ulcerative colitis and 153 patients with Crohn's disease were included in the cohort. Four hundred and forty-two of these (91.5%) could be followed for 10 years or until death. Thirteen patients with ulcerative colitis were affected by uveitis (3.9%), and one of the patients with Crohn's disease (0.7%). Most often the uveitis was diagnosed after the bowel disease (median 8.9 years, 7.7 years SD). CONCLUSION Low occurrence of uveitis was identified in the IBD population. All affected individuals except one were diagnosed with ulcerative colitis. Most of the patients had their eye disease around 10 years later than their IBD diagnosis. It is suggested that systemic anti-inflammatory treatment for the IBD protects against intraocular inflammation in this cohort.
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Affiliation(s)
- Elisabet Granstam
- Center for Clinical Research Region Västmanland, Uppsala Universitet, Västerås, Sweden
- Ophthalmology, Region Västmanland, Västerås, Sweden
| | - Anders Rönnblom
- Medical Sciences, Uppsala University Faculty of Medicine, Uppsala, Sweden
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16
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Wang CR, Tsai HW. Seronegative spondyloarthropathy-associated inflammatory bowel disease. World J Gastroenterol 2023; 29:450-468. [PMID: 36688014 PMCID: PMC9850936 DOI: 10.3748/wjg.v29.i3.450] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 11/18/2022] [Accepted: 12/21/2022] [Indexed: 01/12/2023] Open
Abstract
Seronegative spondyloarthropathy (SpA) usually starts in the third decade of life with negative rheumatoid factor, human leukocyte antigen-B27 genetic marker and clinical features of spinal and peripheral arthritis, dactylitis, enthesitis and extra-articular manifestations (EAMs). Cases can be classified as ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis, or juvenile-onset spondyloarthritis. Joint and gut inflammation is intricately linked in SpA and inflammatory bowel disease (IBD), with shared genetic and immunopathogenic mechanisms. IBD is a common EAM in SpA patients, while extraintestinal manifestations in IBD patients mostly affect the joints. Although individual protocols are available for the management of each disease, the standard therapeutic guidelines of SpA-associated IBD patients remain to be established. Nonsteroidal anti-inflammatory drugs are recommended as initial therapy of peripheral and axial SpA, whereas their use is controversial in IBD due to associated disease flares. Conventional disease-modifying anti-rheumatic drugs are beneficial for peripheral arthritis but ineffective for axial SpA or IBD therapy. Anti-tumor necrosis factor monoclonal antibodies are effective medications with indicated use in SpA and IBD, and a drug of choice for treating SpA-associated IBD. Janus kinase inhibitors, approved for treating SpA and ulcerative colitis, are promising therapeutics in SpA coexistent with ulcerative colitis. A tight collaboration between gastroenterologists and rheumatologists with mutual referral from early accurate diagnosis to appropriately prompt therapy is required in this complex clinical scenario.
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Affiliation(s)
- Chrong-Reen Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan
| | - Hung-Wen Tsai
- Department of Pathology, National Cheng Kung University Hospital, Tainan 70403, Taiwan
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17
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Zhou T, Xu W, Wang Q, Jiang C, Li H, Chao Y, Sun Y, A L. The effect of the "Oral-Gut" axis on periodontitis in inflammatory bowel disease: A review of microbe and immune mechanism associations. Front Cell Infect Microbiol 2023; 13:1132420. [PMID: 36923589 PMCID: PMC10008960 DOI: 10.3389/fcimb.2023.1132420] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 01/31/2023] [Indexed: 03/02/2023] Open
Abstract
Periodontitis and inflammatory bowel diseases (IBD) are inflammatory diseases of the gastrointestinal tract that share common features of microbial-induced ecological dysregulation and host immune inflammatory response. The close relationship between periodontitis and IBD is characterized by a higher prevalence of IBD in patients with periodontitis and a higher prevalence and severity of periodontitis in patients with IBD, indicating that periodontitis and IBD are different from the traditional independent diseases and form an "Oral-Gut" axis between the two, which affect each other and thus form a vicious circle. However, the specific mechanisms leading to the association between the two are not fully understood. In this article, we describe the interconnection between periodontitis and IBD in terms of microbial pathogenesis and immune dysregulation, including the ectopic colonization of the gut by pathogenic bacteria associated with periodontitis that promotes inflammation in the gut by activating the host immune response, and the alteration of the oral microbiota due to IBD that affects the periodontal inflammatory response. Among the microbial factors, pathogenic bacteria such as Klebsiella, Porphyromonas gingivalis and Fusobacterium nucleatum may act as the microbial bridge between periodontitis and IBD, while among the immune mechanisms, Th17 cell responses and the secreted pro-inflammatory factors IL-1β, IL-6 and TNF-α play a key role in the development of both diseases. This suggests that in future studies, we can look for targets in the "Oral-Gut" axis to control and intervene in periodontal inflammation by regulating periodontal or intestinal flora through immunological methods.
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Affiliation(s)
- Tianyu Zhou
- Department of Oral Implantology, School and Hospital of Stomatology, Jilin University, Changchun, China
| | - Wenzhou Xu
- Department of Periodontology, School and Hospital of Stomatology, Jilin University, Changchun, China
- Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, Changchun, China
| | - Qiqi Wang
- Department of Periodontology, School and Hospital of Stomatology, Jilin University, Changchun, China
| | - Cong Jiang
- Department of Oral Implantology, School and Hospital of Stomatology, Jilin University, Changchun, China
| | - Hongyan Li
- Department of Periodontology, School and Hospital of Stomatology, Jilin University, Changchun, China
| | - Yang Chao
- Department of Gastroendoscopy, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Yue Sun
- Department of Oral Implantology, School and Hospital of Stomatology, Jilin University, Changchun, China
- Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, Changchun, China
- *Correspondence: Yue Sun, ; Lan A,
| | - Lan A
- Department of Oral Implantology, School and Hospital of Stomatology, Jilin University, Changchun, China
- Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, Changchun, China
- *Correspondence: Yue Sun, ; Lan A,
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18
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Pytrus W, Akutko K, Pytrus T, Turno-Kręcicka A. A Review of Ophthalmic Complications in Inflammatory Bowel Diseases. J Clin Med 2022; 11:7457. [PMID: 36556071 PMCID: PMC9781961 DOI: 10.3390/jcm11247457] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 11/27/2022] [Accepted: 12/11/2022] [Indexed: 12/23/2022] Open
Abstract
Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic immune-mediated conditions caused by various polygenic and environmental factors. Clinical manifestations of IBD primarily occur in the gastrointestinal tract, but many patients are affected by extraintestinal complications, including eye diseases. Ocular disorders are the third most common extraintestinal manifestation (EIM), following musculoskeletal and mucocutaneous involvement. Episcleritis, frequently occurring in IBD patients, may be associated with exacerbation of the intestinal disease. Uveitis does not correlate with IBD activity but may be related to the presence of other EIMs, particularly erythema nodosum and peripheral arthritis. Early detection and specific therapy of ocular manifestations of IBD are fundamental to avoiding sight-threatening complications. Therefore, ophthalmic evaluation should be performed in all IBD patients. Systemic corticosteroids or immunosuppressants may be inevitable in severe cases to control ocular inflammation. Persistent and relapsing conditions usually respond well to TNF-α-inhibitors. Interdisciplinary cooperation between gastroenterologists and ophthalmologists is fundamental in initiating the appropriate treatment for patients.
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Affiliation(s)
- Wiktoria Pytrus
- Ophthalmonology Clinical Centre SPEKTRUM, 53-334 Wroclaw, Poland
| | - Katarzyna Akutko
- 2nd Department and Clinic of Paediatrics, Gastroenterology and Nutrition, Wroclaw Medical University, 50-369 Wroclaw, Poland
| | - Tomasz Pytrus
- 2nd Department and Clinic of Paediatrics, Gastroenterology and Nutrition, Wroclaw Medical University, 50-369 Wroclaw, Poland
| | - Anna Turno-Kręcicka
- Clinical Department of Ophthalmology, Wroclaw Medical University, 50-556 Wroclaw, Poland
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19
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Li JX, Chiang CC, Chen SN, Lin JM, Tsai YY. The Prevalence of Ocular Extra-Intestinal Manifestations in Adults Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:15683. [PMID: 36497759 PMCID: PMC9737331 DOI: 10.3390/ijerph192315683] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 11/21/2022] [Accepted: 11/22/2022] [Indexed: 06/17/2023]
Abstract
Patients with inflammatory bowel disease (IBD) have a greater frequency of ocular extra-intestinal manifestations (O-EIMs) than the general population, while Crohn's disease (CD) and ulcerative colitis (UC) have inconsistent prevalence, according to previous studies. This study aimed to examine the prevalence of O-EIMs in CD and UC, respectively. We systemically reviewed O-EIMs and IBD across several online databases. Inclusion criteria are as follows: (1) observational studies examining the association between O-EIMs and IBD, such as cross-sectional, case-control, or cohort studies; (2) human and adult individuals; and (3) with case and control groups consisting of patients with and without O-EIMs, respectively. Patients under the age of 18 or any study on pediatric IBD will be excluded. The prevalence of uveitis in adults was determined by 21 studies comprising 190,941 individuals with IBD, including 62,874 CD and 128,067 UC. The pooled analysis revealed significantly increased odds of uveitis in patients with CD than with UC (pooled odd ratio (OR) 1.603, 95% confidence interval 1.254-2.049). The subgroup analysis revealed that European populations had significantly higher odds of developing uveitis and episcleritis in patients with CD than UC (pooled OR 1.683 and 2.401, respectively). Although O-EIMs may be the prodrome of IBD, no consistent finding was obtained as a result of the high heterogeneity from the two included studies. This meta-analysis indicates the significantly increased odds of uveitis in adults with CD than those with UC. In subgroup analysis, European with CD seemed to have higher odds of uveitis and episcleritis than those with UC. Nonetheless, the link between O-EIMs and IBD remained unclear.
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Affiliation(s)
- Jing-Xing Li
- Department of General Medicine, China Medical University Hospital, Taichung 404327, Taiwan
- School of Medicine, China Medical University, Taichung 404328, Taiwan
- Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei 116216, Taiwan
| | - Chun-Chi Chiang
- School of Medicine, China Medical University, Taichung 404328, Taiwan
- Department of Ophthalmology, China Medical University Hospital, Taichung 404327, Taiwan
- Department of Optometry, Asia University, Taichung 413305, Taiwan
| | - San-Ni Chen
- Department of Ophthalmology, China Medical University Hospital, Taichung 404327, Taiwan
- School of Medicine, National Taiwan University, Taipei 116216, Taiwan
| | - Jane-Ming Lin
- Department of Ophthalmology, China Medical University Hospital, Taichung 404327, Taiwan
- School of Chinese Medicine, China Medical University, Taichung 404328, Taiwan
| | - Yi-Yu Tsai
- School of Medicine, China Medical University, Taichung 404328, Taiwan
- Department of Ophthalmology, China Medical University Hospital, Taichung 404327, Taiwan
- Department of Optometry, Asia University, Taichung 413305, Taiwan
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20
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Murphy ME, Bhattacharya S, Axelrad JE. Diagnosis and Monitoring of Ulcerative Colitis. Clin Colon Rectal Surg 2022; 35:421-427. [PMID: 36591402 PMCID: PMC9797286 DOI: 10.1055/s-0042-1758047] [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: 01/04/2023]
Abstract
Ulcerative colitis is one of the two main subtypes of inflammatory bowel disease, along with Crohn's disease. Understanding the clinical and endoscopic features of ulcerative colitis is critical in achieving a timely diagnosis. An initial evaluation includes assessing clinical symptoms, inflammatory markers, endoscopic findings, and determination of the presence or absence of extraintestinal manifestations. Initial disease management should consider disease severity at the time of diagnosis as well as prognostication, or the determination of risk factors present with a high likelihood of severe disease in the future. Once appropriate therapy has been initiated, ongoing monitoring is crucial, which may include repeated clinical assessments over time, measuring noninvasive markers of inflammation, and endoscopic and histologic reevaluation. An important aspect of disease monitoring in ulcerative colitis is dysplasia surveillance; there are many patient-specific risk factors which influence surveillance strategies. Utilizing appropriate surveillance techniques is necessary for early detection of dysplasia and colorectal neoplasia.
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Affiliation(s)
- Megan E. Murphy
- Division of Gastroenterology, Department of Medicine, Inflammatory Bowel Disease Center at NYU Langone Health, NYU Grossman School of Medicine, New York, New York
| | - Sumona Bhattacharya
- Division of Gastroenterology, Department of Medicine, Inflammatory Bowel Disease Center at NYU Langone Health, NYU Grossman School of Medicine, New York, New York
| | - Jordan E. Axelrad
- Division of Gastroenterology, Department of Medicine, Inflammatory Bowel Disease Center at NYU Langone Health, NYU Grossman School of Medicine, New York, New York
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21
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Ocular Manifestations in Patients with Inflammatory Bowel Disease in the Biologics Era. J Clin Med 2022; 11:jcm11154538. [PMID: 35956153 PMCID: PMC9369806 DOI: 10.3390/jcm11154538] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/29/2022] [Accepted: 08/01/2022] [Indexed: 01/27/2023] Open
Abstract
Background: Extra-intestinal manifestations are frequent in inflammatory bowel disease (IBD). Ocular disorders are generally under diagnosed as they are challenging diagnosis. Aims: We assessed the prevalence of ophthalmological manifestations in patients with IBD, and investigated characteristics associated with ocular manifestations. Methods: We performed a retrospective study including patients followed for IBD and had an ophthalmologic visit from January 2013 to July 2020, among 1432 patients followed during this period. Two groups were considered: the first group included patients whose an ocular diagnosis was considered as “related to IBD”, and the second group including patients whose an ocular diagnosis was considered “not related to IBD”. Results: Among 1432 patients with IBD, eighty-seven (6.1%) patients had an ophthalmologic visit. Fifty-three patients (3.7%) were considered to have an ocular extra-intestinal manifestation or an iatrogenic effect of IBD treatment, and 34 diagnoses (2.4%) were considered not related to IBD. Inflammatory surface pathologies were the most frequent (33.2%), including 15 patients with dry eye (17.2%), 9 with blepharitis (10.3%), and 5 with chalazions (meibomian cyst) (5.7%). Uveitis was diagnosed in 13 patients (14.9%), episcleritis in 5 patients (5.7%), and scleritis in 2 patients (2.3%). Characteristics of patients with an ophthalmological diagnosis “related to IBD” versus “not related to IBD” were not statistically different. Conclusion: In our cohort, less than 5% of patients had ophthalmological extra-intestinal manifestation. The most frequent ocular diagnosis were dry eye and uveitis. No disease characteristics of IBD were found to be associated with ocular manifestations.
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22
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Shah J, Shah A, Hassman L, Gutierrez A. Ocular Manifestations of Inflammatory Bowel Disease. Inflamm Bowel Dis 2021; 27:1832-1838. [PMID: 33501989 DOI: 10.1093/ibd/izaa359] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Indexed: 12/13/2022]
Abstract
Inflammatory bowel disease (IBD) is characterized by intestinal inflammation; however, it is also known to have extraintestinal manifestations. Ocular manifestations of IBD include keratopathy, episcleritis, scleritis, and uveitis and are among the most common extraintestinal manifestations. These diseases can lead to significant ocular morbidity if unrecognized and left untreated. A review of the literature was performed on PubMed and is summarized and critically appraised in this article with the aim being to describe the varying ocular manifestations of IBD and outlining their treatments. Ultimately, a framework is provided to investigate ocular symptoms in patients with IBD. An ocular review of systems is also provided as a tool to equip gastroenterologists and internal medicine physicians to be able to recognize and triage ocular complaints appropriately.
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Affiliation(s)
- Janaki Shah
- Department of Internal Medicine, Washington University in St. Louis, St. Louis, Missouri, USA
| | - Aaditya Shah
- Department of Ophthalmology, Washington University in St. Louis, St. Louis, MO, USA
| | - Lynn Hassman
- Department of Ophthalmology, Washington University in St. Louis, St. Louis, MO, USA
| | - Alexandra Gutierrez
- Department of Internal Medicine, Washington University in St. Louis, St. Louis, Missouri, USA
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23
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Rogler G, Singh A, Kavanaugh A, Rubin DT. Extraintestinal Manifestations of Inflammatory Bowel Disease: Current Concepts, Treatment, and Implications for Disease Management. Gastroenterology 2021; 161:1118-1132. [PMID: 34358489 PMCID: PMC8564770 DOI: 10.1053/j.gastro.2021.07.042] [Citation(s) in RCA: 426] [Impact Index Per Article: 106.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 07/28/2021] [Accepted: 07/28/2021] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel diseases (IBDs) are systemic diseases that manifest not only in the gut and gastrointestinal tract, but also in the extraintestinal organs in many patients. The quality of life for patients with IBD can be substantially affected by these extraintestinal manifestations (EIMs). It is important to have knowledge of the prevalence, pathophysiology, and clinical presentation of EIMs in order to adapt therapeutic options to cover all aspects of IBD. EIMs can occur in up to 24% of patients with IBD before the onset of intestinal symptoms, and need to be recognized to initiate appropriate diagnostic procedures. EIMs most frequently affect joints, skin, or eyes, but can also affect other organs, such as the liver, lung, and pancreas. It is a frequent misconception that a successful therapy of the intestinal inflammation will be sufficient to treat EIMs satisfactorily in most patients with IBD. In general, peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum can be associated with active intestinal inflammation and can improve on standard treatment of the intestinal inflammation. However, anterior uveitis, ankylosing spondylitis, and primary sclerosing cholangitis usually occur independent of disease flares. This review provides a comprehensive overview of epidemiology, pathophysiology, clinical presentation, and treatment of EIMs in IBD.
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Affiliation(s)
- Gerhard Rogler
- Department of Gastroenterology & Hepatology, Department of Medicine, Zurich University Hospital, Zurich, Switzerland
| | - Abha Singh
- University of California, San Diego, La Jolla, CA, USA
| | | | - David T. Rubin
- University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA
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24
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Takeuchi M, Mizuki N, Ohno S. Pathogenesis of Non-Infectious Uveitis Elucidated by Recent Genetic Findings. Front Immunol 2021; 12:640473. [PMID: 33912164 PMCID: PMC8072111 DOI: 10.3389/fimmu.2021.640473] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 03/22/2021] [Indexed: 01/01/2023] Open
Abstract
Uveitis is a generic term for inflammation of the uvea, which includes the iris, ciliary body, and choroid. Prevalence of underlying non-infectious uveitis varies by race and region and is a major cause of legal blindness in developed countries. Although the etiology remains unclear, the involvement of both genetic and environmental factors is considered important for the onset of many forms of non-infectious uveitis. Major histocompatibility complex (MHC) genes, which play a major role in human immune response, have been reported to be strongly associated as genetic risk factors in several forms of non-infectious uveitis. Behçet’s disease, acute anterior uveitis (AAU), and chorioretinopathy are strongly correlated with MHC class I-specific alleles. Moreover, sarcoidosis and Vogt-Koyanagi-Harada (VKH) disease are associated with MHC class II-specific alleles. These correlations can help immunogenetically classify the immune pathway involved in each form of non-infectious uveitis. Genetic studies, including recent genome-wide association studies, have identified several susceptibility genes apart from those in the MHC region. These genetic findings help define the common or specific pathogenesis of ocular inflammatory diseases by comparing the susceptibility genes of each form of non-infectious uveitis. Interestingly, genome-wide association of the interleukin (IL)23R region has been identified in many of the major forms of non-infectious uveitis, such as Behçet’s disease, ocular sarcoidosis, VKH disease, and AAU. The interleukin-23 (IL-23) receptor, encoded by IL23R, is expressed on the cell surface of Th17 cells. IL-23 is involved in the homeostasis of Th17 cells and the production of IL-17, which is an inflammatory cytokine, indicating that a Th17 immune response is a common key in the pathogenesis of non-infectious uveitis. Based on the findings from the immunogenetics of non-infectious uveitis, a personalized treatment approach based on the patient’s genetic make-up is expected.
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Affiliation(s)
- Masaki Takeuchi
- Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Nobuhisa Mizuki
- Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Shigeaki Ohno
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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25
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Hanzel J, Ma C, Casteele NV, Khanna R, Jairath V, Feagan BG. Vedolizumab and Extraintestinal Manifestations in Inflammatory Bowel Disease. Drugs 2021; 81:333-347. [PMID: 33400241 DOI: 10.1007/s40265-020-01460-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
In Crohn's disease and ulcerative colitis, inflammation is not limited to the digestive tract. Extraintestinal manifestations (EIMs), which affect up to 50% of patients, can substantially impair quality of life. EIMs may parallel luminal disease activity or have an independent course. They most commonly involve the musculoskeletal system (e.g., peripheral or axial arthritis) and skin (e.g., erythema nodosum and pyoderma gangrenosum). Less commonly, the hepatobiliary tract (e.g., primary sclerosing cholangitis [PSC]) and the eye (e.g., episcleritis, scleritis, and uveitis) are involved. Although the pathophysiology of EIMs is poorly understood, they are likely either manifestations of a primary systemic immune disease with variable expression amongst organs, or secondary phenomena to bowel inflammation. Additional pathophysiologic mechanisms may include aberrant lymphocyte homing mediated by ectopic expression of gut-specific chemokines and adhesion molecules, cross-reactivity between microbial and self-antigens, autoantibodies against epitopes shared by the intestine and extraintestinal tissues, elevated serum concentrations of cytokines, and alterations in innate immunity. Many EIMs independent of intestinal disease activity can be successfully treated with tumor necrosis factor (TNF) antagonists. The efficacy of vedolizumab-a monoclonal antibody targeting the α4β7 integrin-for the treatment of EIMs is uncertain, but data are emerging from post hoc analyses of randomized controlled trials, prospective and retrospective cohort studies, and case series. Vedolizumab may be effective in treating EIMs related to luminal disease activity (e.g., type 1 peripheral arthritis and erythema nodosum) but has not shown biochemical improvement in PSC. Its postulated role in the development of de novo EIMs is heavily confounded by the high proportion of patients previously exposed to TNF antagonists; new EIMs could result from TNF antagonist treatment cessation rather than being caused by vedolizumab. A common limitation of clinical studies is the lack of multidisciplinary involvement in the diagnosis and monitoring of EIMs, which may lead to misdiagnosis and overreporting. Future studies should rigorously measure EIMs in parallel with objective measures of luminal disease activity to provide more robust data on the relative efficacy of new drugs, especially as increasing numbers of gut-selective compounds enter clinical development.
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Affiliation(s)
- Jurij Hanzel
- Department of Gastroenterology, University Medical Center Ljubljana, Ljubljana, Slovenia.,Alimentiv, #200, 100 Dundas Street, London, N6A 5B6, ON, Canada.,, Hullenbergweg 278-308, 1101 BV, Amsterdam, The Netherlands
| | - Christopher Ma
- Alimentiv, #200, 100 Dundas Street, London, N6A 5B6, ON, Canada.,Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, 6D61 Teaching Research Wellness Building, 3280 Hospital Drive NW, Calgary, Alberta, T2N 4Z6, Canada
| | - Niels Vande Casteele
- Alimentiv, #200, 100 Dundas Street, London, N6A 5B6, ON, Canada.,Department of Medicine, University of California San Diego, 9500 Gilman Drive #0956, La Jolla, CA, 92093, USA
| | - Reena Khanna
- Division of Gastroenterology, University of Western Ontario, 1151 Richmond Street, London, N6A 2K7, ON, Canada
| | - Vipul Jairath
- Alimentiv, #200, 100 Dundas Street, London, N6A 5B6, ON, Canada.,Division of Gastroenterology, University of Western Ontario, 1151 Richmond Street, London, N6A 2K7, ON, Canada.,Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada
| | - Brian G Feagan
- Alimentiv, #200, 100 Dundas Street, London, N6A 5B6, ON, Canada. .,Division of Gastroenterology, University of Western Ontario, 1151 Richmond Street, London, N6A 2K7, ON, Canada. .,Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada. .,Department of Medicine, University of Western Ontario, London, ON, Canada.
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26
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Jansen FM, Vavricka SR, den Broeder AA, de Jong EM, Hoentjen F, van Dop WA. Clinical management of the most common extra-intestinal manifestations in patients with inflammatory bowel disease focused on the joints, skin and eyes. United European Gastroenterol J 2020; 8:1031-1044. [PMID: 32921269 PMCID: PMC7724540 DOI: 10.1177/2050640620958902] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Extra-intestinal manifestations (EIMs) of inflammatory bowel disease (IBD) occur
frequently and contribute to morbidity and reduced quality of life. The
musculoskeletal, ocular and cutaneous organ systems are frequently involved in
IBD-related EIMs. By focusing on manifestations involving the joints, skin and
eyes, this review will discuss the most common clinically relevant and
burdensome EIMs that affect IBD patients, and strives for early recognition,
adequate treatment and timely referral. For this purpose, we aimed to create a
comprehensive overview on this topic, with the main focus on the treatment of
reactive and associated EIMs, including spondyloarthropathies, pyoderma
gangrenosum, erythema nodosum, psoriasis and anterior uveitis. The recently
developed biologicals enable simultaneous treatment of inflammatory disorders.
This review can be used as a helpful guide in daily clinical practice for
physicians who are involved in the treatment of IBD patients.
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Affiliation(s)
- Fenna M Jansen
- Department of Medicine, Division of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Stephan R Vavricka
- Department of Medicine, Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Alfons A den Broeder
- ³Department of Medicine, Division of Rheumatology, Sint Maartenskliniek, Nijmegen, The Netherlands
| | - Elke Mgj de Jong
- Department of Medicine, Division of Dermatology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Frank Hoentjen
- Department of Medicine, Division of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Willemijn A van Dop
- Department of Medicine, Division of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
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27
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Guillo L, D'Amico F, Serrero M, Angioi K, Loeuille D, Costanzo A, Danese S, Peyrin-Biroulet L. Assessment of extraintestinal manifestations in inflammatory bowel diseases: A systematic review and a proposed guide for clinical trials. United European Gastroenterol J 2020; 8:1013-1030. [PMID: 32778004 DOI: 10.1177/2050640620950093] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND AND AIMS Extraintestinal manifestations are common in inflammatory bowel disease patients, although there are few data available on their diagnosis, management and follow-up. We systematically reviewed the literature evidence to evaluate tools and investigations used for the diagnosis and for the assessment of the treatment response in inflammatory bowel disease patients with extraintestinal manifestations. METHODS We searched in PubMed, Embase and Web of Science from January 1999-December 2019 for all interventional and non-interventional studies published in English assessing diagnostic tools and investigations used in inflammatory bowel disease patients with extraintestinal manifestations. RESULTS Forty-five studies (16 interventional and 29 non-interventional) were included in our systematic review, enrolling 7994 inflammatory bowel disease patients. The diagnostic assessment of extraintestinal manifestations was performed by dedicated specialists in a percentage of cases ranging from 60-100% depending on the specific condition. The clinical examination was the most frequent diagnostic strategy, accounting for 35 studies (77.8%). In patients with primary sclerosing cholangitis or rheumatological symptoms, biochemical and imaging tests were also performed. Anti-TNF agents were the most used biological drugs for the treatment of extraintestinal manifestations (20 studies, 44.4%), and the treatment response varied from 59.1% in axial spondyloarthritis to 88.9% in ocular manifestations. No benefit was detected in primary sclerosing cholangitis patients after treatment with biologics. CONCLUSIONS In the clinical management of inflammatory bowel disease patients with extraintestinal manifestations the collaboration of dedicated specialists for diagnostic investigations and follow-up is key to ensure the best of care approach. However, international guidelines are needed to homogenise and standardise the assessment of extraintestinal manifestations.
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Affiliation(s)
- Lucas Guillo
- Department of Gastroenterology, University Hospital of Marseille Nord, University of Aix-Marseille, Marseille, France
| | - Ferdinando D'Amico
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Mélanie Serrero
- Department of Gastroenterology, University Hospital of Marseille Nord, University of Aix-Marseille, Marseille, France
| | - Karine Angioi
- Department of Ophthalmology, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France
| | - Damien Loeuille
- Ingénierie Moléculaire et Ingénierie Articulaire (IMoPA), UMR-7365 CNRS, University of Lorraine and University Hospital of Nancy, Nancy, France
| | - Antonio Costanzo
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Dermatology, Humanitas Clinical and Research Center - IRCCS, Milan, Italy
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Department of Gastroenterology, Humanitas Clinical and Research Center - IRCCS, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
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28
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Kayar Y, Dertli R, Konur S, Agin M, Baran B, Ormeci AC, Akyuz F, Demir K, Besisik F, Kaymakoglu S. The development of extraintestinal manifestation and related risk factors in Crohn's patients. Ir J Med Sci 2020; 190:597-604. [PMID: 32748219 DOI: 10.1007/s11845-020-02326-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Accepted: 07/23/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND Crohn's disease (CD) primarily involves gastrointestinal tract; however, it can present with extraintestinal manifestations (EIMs), which leads to significant morbidity. Frequency of EIMs and associated risk factors vary due to genetic and environmental differences in studies. AIM To examine the frequency and risk factors associated with EIMs in CD. METHOD Patients with CD under follow-up from March 1986 to October 2011 were included in this study. Demographics, type of EIMs, autoimmune diseases, and clinical features of CD were recorded. Frequency of EIMs and associated risk factors were analyzed. RESULTS Three hundred thirty-six patients with CD were included in the study (mean follow-up duration 7.54 years). 55.4% (n: 186) were male and the mean age at diagnosis of CD was 30.6 years (range, 10.3-68.2 years). At least one EIM was detected in 47.3% and multiple EIMs in 22.9% of the cohort. Oral, joint, and skin involvements (32.4%, 24.7%, 9.2%, respectively) were the most common EIMs. Female gender (OR: 2.19, 95% CI: 1.34-3.58, p = 0.001), corticosteroid usage (OR: 2.32, 95% CI: 1.28-4.22, p = 0.007), and positive family history (OR: 5.61, 95% CI: 1.95-3.58, p = 0.001) were independent risk factors for EIM development. Colonic involvement (OR: 3.93, 95% CI: 1.59-9.68, p = 0.003), no surgical operation (OR: 2.31, 95% CI: 1.14-4.68, p = 0.020), and corticosteroid usage (OR: 2.85, 95% CI: 1.07-7.61, p = 0.037) were independent risk factors for multiple EIM development. CONCLUSION Although the immunological and clinical associations between EIMs and CD cannot be fully elucidated, identifying specific relationships of immune-mediated diseases will help to better understand CD pathogenesis.
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Affiliation(s)
- Yusuf Kayar
- Department of Internal Medicine, Division of Gastroenterology, Van Education and Research Hospital, Saglik Bilimleri University, 65100, Van, Turkey.
| | - Ramazan Dertli
- Department of Internal Medicine, Division of Gastroenterology, Van Education and Research Hospital, Saglik Bilimleri University, 65100, Van, Turkey
| | - Sevki Konur
- Department of Internal Medicine, Van Education and Research Hospital, Saglik Bilimleri University, Van, Turkey
| | - Mehmet Agin
- Department of Pediatry, Division of Gastroenterology, Van Education and Research Hospital, Saglik Bilimleri University, Van, Turkey
| | - Bulent Baran
- Department of Internal Medicine, Division of Gastroenterology, Koç University, Istanbul, Turkey
| | - Asli Ciftcibasi Ormeci
- Department of Internal Medicine, Division of Gastroenterology, Istanbul University, Istanbul, Turkey
| | - Filiz Akyuz
- Department of Internal Medicine, Division of Gastroenterology, Istanbul University, Istanbul, Turkey
| | - Kadir Demir
- Department of Internal Medicine, Division of Gastroenterology, Istanbul University, Istanbul, Turkey
| | - Fatih Besisik
- Department of Internal Medicine, Division of Gastroenterology, Istanbul University, Istanbul, Turkey
| | - Sabahattin Kaymakoglu
- Department of Internal Medicine, Division of Gastroenterology, Istanbul University, Istanbul, Turkey
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29
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Parfenov AI, Kagramanova AV, Knyazev OV. [Systemic manifestations of inflammatory bowel diseases]. TERAPEVT ARKH 2020; 92:4-11. [PMID: 32598711 DOI: 10.26442/00403660.2020.02.000535] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Indexed: 01/06/2023]
Abstract
The article is devoted to the current data regarding the pathogenesis, classification and frequency of extraintestinal manifestations (EIMs) in inflammatory bowel diseases. We discuss two distinct theories of EIMs pathogenesis. First, EIMs arise from an extension of antigen-specific immune responses from the intestine to non-intestinal sites. Second, EIMs are independent inflammatory events initiated or perpetuated by the presence of IBD or by shared genetic or environmental risk factors in the host. These mechanisms are not mutually exclusive and may contribute to varying degrees in different EIMs. Early diagnosis of EIMs contributes to prevention disability and enhancement of quality of life of IBD patients. It is concluded that treatment of extraintestinal manifestations should be carried out taking into account the course of the IBD and the multidisciplinary approach, which requires close cooperation of doctors of various specialties. Assessment of prognostic markers and predictors for EIM in IBD will be part of a future investigation.
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Affiliation(s)
- A I Parfenov
- Loginov Moscow Clinical Scientific Practical Center
| | | | - O V Knyazev
- Loginov Moscow Clinical Scientific Practical Center
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30
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Jumani L, Kataria D, Ahmed MU, Shah MAA, Raja K, Shaukat F. The Spectrum of Extra-intestinal Manifestation of Crohn's Disease. Cureus 2020; 12:e6928. [PMID: 32190481 PMCID: PMC7067350 DOI: 10.7759/cureus.6928] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 02/10/2020] [Indexed: 12/24/2022] Open
Abstract
Introduction Extra-intestinal manifestations (EIM) play an important role in the mortality, morbidity, and quality of life in patients with Crohn's disease (CD). Understanding the prevalence and clinical course of these manifestations is important to understand and manage CD. Materials and methods The hospital records of 103 patients diagnosed with CD between July 2016 and December 2019 at a tertiary care hospital in Pakistan were reviewed retrospectively. Baseline demographic and clinical characteristics including sex, age, follow-up duration, CD phenotype at diagnosis, clinical features, and course of EIMs were noted. The diagnosis of CD was based on clinical features in combination with endoscopic and radiologic findings. CD phenotype at diagnosis was assessed using the Montreal Classification by the World Congress of Gastroenterology (WCOG). Results The mean age at diagnosis of CD was 31 ±8 years. The most common age group as per the Montreal classification at diagnosis was 17-40 years (68.93%). The most common localization of disease was ileocolonic (70.87%), and the most common disease behavior was non-stricturing and non-penetrating (82.52%). In this study, 41 (39.8%) patients had a minimum of one EIM. The most common EIM was anal skin tags (29.12%), while 24 (23.30%) patients had elevated liver function tests (LFTs), three (2.91%) had peripheral arthritis, and 12 (11.65%) had cutaneous manifestations, the most common being erythema nodosum (7.76%). The most common ophthalmological manifestation was anterior uveitis (3.88%). Conclusions EIMs are prevalent in CD patients in Pakistan, yet very little is known about them. Further large-scale studies are needed to assess the frequency and impact of EIMs on patients with CD.
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Affiliation(s)
- Laraib Jumani
- Internal Medicine, Pakistan Institute of Medical Sciences, Islamabad, PAK
| | - Deepak Kataria
- Internal Medicine, Shaheed Mohtarma Benazir Bhutto Medical University, Larkana, PAK
| | | | | | - Kunal Raja
- Internal Medicine, Shaheed Mohtarma Benazir Bhutto Medical University, Larkana, PAK
| | - Faizan Shaukat
- Internal Medicine, Jinnah Post Graduate Medical Center, Karachi, PAK
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Ribaldone DG, Pellicano R, Actis GC. The gut and the inflammatory bowel diseases inside-out: extra-intestinal manifestations. MINERVA GASTROENTERO 2019; 65:309-318. [PMID: 30994321 DOI: 10.23736/s1121-421x.19.02577-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
An increasing deal of attention is being conveyed on the extra-intestinal manifestations (EIM) of inflammatory bowel diseases (IBD). We compiled the present review in an attempt to upgrade the accuracy of the classification of such polymorphic entities. We focused on three patterns. First, the conventional EIM localized to bone and joints, to the eye, to the biliary tree and to the skin. Second, the so-called IBD-like syndromes accompanied by bone marrow-derived anomalies of innate or acquired immunity. Third, specific disorders of the skin and of the lungs. EIM are thought to derive from an altered gut permeability, the release of cross-reacting antigens, and subsequent peripheral inflammation; T helper 17 cells boosted by a polymorphic interleukin 23 circuitry would be the main effectors of this chain. Inflammatory bowel disease-like pictures would derive from inborn errors of the immune response causing undue inflammation home to the gut. Monogenic IBD belong to this subset, and are of specific pediatric interest. Psoriasis, chronic obstructive pulmonary disease, and IBD are all inflammatory disorders of the barrier organs: skin, lungs, and gut. The demonstration that specific antigen hyper- or hyporesponsiveness raised at any of the three districts can modulate the response of the other two sites, has led to the innovative concept of a system-wide mucosal immunological organ. An improved knowledge of these entities has not only a speculative importance, but can also bear a clinical impact, insofar as EIM prove often more disabling than the underlying IBD itself.
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Affiliation(s)
| | - Rinaldo Pellicano
- Unit of Gastroenterology, Molinette-S. Giovanni Antica Sede Hospital, Turin, Italy
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Biedermann L, Renz L, Fournier N, Rossel JB, Butter M, Bluemel S, Vavricka SR, Rogler G, Scharl M. Uveitis manifestations in patients of the Swiss Inflammatory Bowel Disease Cohort Study. Therap Adv Gastroenterol 2019; 12:1756284819865142. [PMID: 31447932 PMCID: PMC6693019 DOI: 10.1177/1756284819865142] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 06/14/2019] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND The knowledge about risk factors for the onset of uveitis manifestations in patients with inflammatory bowel disease (IBD) is still limited. Here, we aimed to provide an overview of the clinical factors associated with the onset of uveitis in the Swiss IBD Cohort Study (SIBDCS). METHODS We included epidemiological and clinical data from 1840 patients with Crohn's disease (CD) and 1426 patients with ulcerative colitis (UC) followed up in the SIBDCS between 2006 and 2018. Associations between disease characteristics and uveitis were assessed in univariate and multivariate analyses. RESULTS Overall, we identified 285 patients with uveitis. Uveitis was more frequent in patients with CD (11.1%; 205 of 1635) than UC (5.6%; 80 of 1346; odds ratio 2.11, p < 0.001). The occurrence of uveitis manifestations in patients with UC and CD was significantly associated with the onset of other extraintestinal manifestations, also in multivariate analyses. The onset of uveitis was associated with the hallmark features of severe disease in both CD and UC, including a higher clinical disease activity index and the use of immunomodulators or calcineurin inhibitors. In CD, uveitis was more frequent in females and showed a positive correlation with a positive family history of IBD. CONCLUSIONS Our data demonstrate that uveitis in IBD occurs more often in CD as well as in women and is associated with a more severe disease course. This might guide physicians' awareness in at-risk patients to the presence of uveitis extraintestinal manifestations and help to improve patient care.
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Affiliation(s)
- Luc Biedermann
- Department of Gastroenterology and Hepatology,
University Hospital Zürich, University of Zürich, Zürich, Switzerland
| | - Laura Renz
- Department of Gastroenterology and Hepatology,
University Hospital Zürich, University of Zürich, Zürich, Switzerland
| | - Nicolas Fournier
- Institute of Social and Preventive Medicine
(IUMSP), Lausanne University Hospital, Lausanne, Switzerland
| | - Jean-Benoît Rossel
- Institute of Social and Preventive Medicine
(IUMSP), Lausanne University Hospital, Lausanne, Switzerland
| | - Matthias Butter
- Department of Gastroenterology and Hepatology,
University Hospital Zürich, University of Zürich, Zürich, Switzerland
| | - Sena Bluemel
- Department of Gastroenterology and Hepatology,
University Hospital Zürich, University of Zürich, Zürich, Switzerland
| | - Stephan R. Vavricka
- Department of Gastroenterology and Hepatology,
University Hospital Zürich, University of Zürich, Zürich, Switzerland
| | - Gerhard Rogler
- Department of Gastroenterology and Hepatology,
University Hospital Zürich, University of Zürich, Zürich, Switzerland
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Hedin CRH, Vavricka SR, Stagg AJ, Schoepfer A, Raine T, Puig L, Pleyer U, Navarini A, van der Meulen-de Jong AE, Maul J, Katsanos K, Kagramanova A, Greuter T, González-Lama Y, van Gaalen F, Ellul P, Burisch J, Bettenworth D, Becker MD, Bamias G, Rieder F. The Pathogenesis of Extraintestinal Manifestations: Implications for IBD Research, Diagnosis, and Therapy. J Crohns Colitis 2019; 13:541-554. [PMID: 30445584 DOI: 10.1093/ecco-jcc/jjy191] [Citation(s) in RCA: 131] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
This article reports on the sixth scientific workshop of the European Crohn's and Colitis Organisation [ECCO] on the pathogenesis of extraintestinal manifestations [EIMs] in inflammatory bowel disease [IBD]. This paper has been drafted by 15 ECCO members and 6 external experts [in rheumatology, dermatology, ophthalmology, and immunology] from 10 European countries and the USA. Within the workshop, contributors formed subgroups to address specific areas. Following a comprehensive literature search, the supporting text was finalized under the leadership of the heads of the working groups before being integrated by the group consensus leaders.
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Affiliation(s)
- C R H Hedin
- Gastroenterology unit, Patient Area Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - S R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - A J Stagg
- Centre for Immunobiology, Bart's and The London Medical School, Queen Mary University of London, London, UK
| | - A Schoepfer
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
| | - T Raine
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Teaching Hospitals NHS Foundation Trust, Cambridge, UK
| | - L Puig
- Department of Dermatology, Hospital de la Santa Creu i Sant Pau. Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain
| | - U Pleyer
- University Eye Clinic, Uveitis Center, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - A Navarini
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
| | | | - J Maul
- Gastroenterologie am Bayerischen Platz, Berlin, Germany
- Department of Medicine (Gastroenterology, Infectious Diseases, Rheumatology), Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - K Katsanos
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Ioannina School of Medical Sciences, Ioannina, Greece
| | - A Kagramanova
- IBD Department, The Loginov Moscow Clinical Scientific Centre, Moscow, Russia
| | - T Greuter
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
- Gastroenterology Research Unit, Mayo Clinic, Rochester, MN, USA
| | - Y González-Lama
- IBD Unit, Gastroenterology and Hepatology Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain
| | - F van Gaalen
- Department of Rheumatology, Leiden University Medical Center [LUMC], Leiden, Netherlands
| | - P Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
| | - J Burisch
- Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
- Abdominal Center K, Medical Section, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - D Bettenworth
- Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
| | - M D Becker
- Department of Ophthalmology, Triemli Hospital, Zurich, Switzerland & Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany
| | - G Bamias
- National and Kapodistrian University of Athens, GI Unit, 3rd Academic Department of Internal Medicine, Sotiria Hospital, Athens, Greece
| | - F Rieder
- Department of Gastroenterology, Hepatology and Nutrition; Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
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Greuter T, Vavricka SR. Extraintestinal manifestations in inflammatory bowel disease - epidemiology, genetics, and pathogenesis. Expert Rev Gastroenterol Hepatol 2019; 13:307-317. [PMID: 30791773 DOI: 10.1080/17474124.2019.1574569] [Citation(s) in RCA: 120] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, primarily of, but not restricted to the gut. Extraintestinal manifestations (EIMs) are frequently observed and involve the joints, eyes, hepatobiliary tract, and skin. Areas covered: In this review, we discuss classical EIM focusing on epidemiology, genetics, and pathogenesis, highlighting recent advances in the understanding of EIM. We further discuss treatment-induced immunological phenomena, which are increasingly recognized and might challenge IBD-treating physicians in the era of biological treatment. Expert opinion: EIM considerably contributes to morbidity and mortality. Genetic studies have revealed a common genetic background between EIM and IBD and among specific EIM. Identified protein interactions have been shown to cluster in shared biological pathways. However - despite these recent advances - pathogenesis of EIM is at best partially understood. Several pathogenic mechanisms have been proposed such as upregulation of tumor necrosis factor, aberrant lymphocyte homing, and cross-reactive antigen presentation. It still remains unclear whether EIM is a direct result of the inflammatory process in the gut or rather a consequence of a shared genetic background leading to dysfunctional immune responses to environmental stimuli. Exploration and understanding of EIM genetics and pathophysiology will pave the road for better and more efficacious treatment options in the future.
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Affiliation(s)
- Thomas Greuter
- a Department of Gastroenterology and Hepatology , University Hospital Zurich , Zurich , Switzerland
| | - Stephan R Vavricka
- a Department of Gastroenterology and Hepatology , University Hospital Zurich , Zurich , Switzerland.,b Center for Gastroenterology and Hepatology , Zurich , Switzerland
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Abstract
Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disorder of the colon that causes continuous mucosal inflammation extending from the rectum to the more proximal colon, with variable extents. UC is characterized by a relapsing and remitting course. UC was first described by Samuel Wilks in 1859 and it is more common than Crohn's disease worldwide. The overall incidence and prevalence of UC is reported to be 1.2-20.3 and 7.6-245 cases per 100,000 persons/year respectively. UC has a bimodal age distribution with an incidence peak in the 2nd or 3rd decades and followed by second peak between 50 and 80 years of age. The key risk factors for UC include genetics, environmental factors, autoimmunity and gut microbiota. The classic presentation of UC include bloody diarrhea with or without mucus, rectal urgency, tenesmus, and variable degrees of abdominal pain that is often relieved by defecation. UC is diagnosed based on the combination of clinical presentation, endoscopic findings, histology, and the absence of alternative diagnoses. In addition to confirming the diagnosis of UC, it is also important to define the extent and severity of inflammation, which aids in the selection of appropriate treatment and for predicting the patient's prognosis. Ileocolonoscopy with biopsy is the only way to make a definitive diagnosis of UC. A pathognomonic finding of UC is the presence of continuous colonic inflammation characterized by erythema, loss of normal vascular pattern, granularity, erosions, friability, bleeding, and ulcerations, with distinct demarcation between inflamed and non-inflamed bowel. Histopathology is the definitive tool in diagnosing UC, assessing the disease severity and identifying intraepithelial neoplasia (dysplasia) or cancer. The classical histological changes in UC include decreased crypt density, crypt architectural distortion, irregular mucosal surface and heavy diffuse transmucosal inflammation, in the absence of genuine granulomas. Abdominal computed tomographic (CT) scanning is the preferred initial radiographic imaging study in UC patients with acute abdominal symptoms. The hallmark CT finding of UC is mural thickening with a mean wall thickness of 8 mm, as opposed to a 2-3 mm mean wall thickness of the normal colon. The Mayo scoring system is a commonly used index to assess disease severity and monitor patients during therapy. The goals of treatment in UC are three fold-improve quality of life, achieve steroid free remission and minimize the risk of cancer. The choice of treatment depends on disease extent, severity and the course of the disease. For proctitis, topical 5-aminosalicylic acid (5-ASA) drugs are used as the first line agents. UC patients with more extensive or severe disease should be treated with a combination of oral and topical 5-ASA drugs +/- corticosteroids to induce remission. Patients with severe UC need to be hospitalized for treatment. The options in these patients include intravenous steroids and if refractory, calcineurin inhibitors (cyclosporine, tacrolimus) or tumor necrosis factor-α antibodies (infliximab) are utilized. Once remission is induced, patients are then continued on appropriate medications to maintain remission. Indications for emergency surgery include refractory toxic megacolon, colonic perforation, or severe colorectal bleeding.
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Biancardi AL, Zaltman C, Troncoso LL, Luiz RR, Moraes HVD. The Role of Clinical-Demographic Characteristics in Ophthalmic Manifestations of Inflammatory Bowel Disease. Inflamm Bowel Dis 2019; 25:e15-e16. [PMID: 29757370 DOI: 10.1093/ibd/izy159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Affiliation(s)
- Ana Luiza Biancardi
- Department of Ophthalmology, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Cyrla Zaltman
- Gastroenterology Division, Department of Internal Medicine, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Leandro Lopes Troncoso
- Department of Ophthalmology, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Ronir Raggio Luiz
- Institute for Studies in Public Health, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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Ocular features of the HLA-B27-positive seronegative spondyloarthropathies. Curr Opin Ophthalmol 2018; 29:552-557. [DOI: 10.1097/icu.0000000000000525] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Ottaviano G, Salvatore S, Salvatoni A, Martelossi S, Ventura A, Naviglio S. Ocular Manifestations of Paediatric Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. J Crohns Colitis 2018. [PMID: 29518184 DOI: 10.1093/ecco-jcc/jjy029] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Ocular extraintestinal manifestations [O-EIMs] are known complications of Crohn's disease [CD], ulcerative colitis [UC], and inflammatory bowel disease unclassified [IBD-U]. However, data on their prevalence in children are scarce and there are no clear recommendations on what follow-up should be offered. We aimed to review available data on O-EIMs in children. METHODS In January 2018, we performed a systematic review of published English literature using PubMed and EMBASE databases and disease-specific queries. RESULTS Fifteen studies [7467 patients] reported data on O-EIMs prevalence in children. Overall prevalence of O-EIMs was 0.62-1.82%. Uveitis was the most common O-EIM. Meta-analysis showed that children with CD are at increased risk of O-EIMs as compared with children with UC and IBD-U (odds ratio [OR] 2.70, 95% confidence interval [CI] 1.51-4.83). Five studies [357 patients] reported data on ophthalmological screening in asymptomatic children: mild asymptomatic uveitis was identified in a variable proportion of patients [1.06-23.1%], more frequently in male patients with CD and colonic involvement. No evidence of ocular complications from untreated uveitis was detected. A total of 23 case reports [24 patients] were identified. CONCLUSIONS Data on O-EIMs in children are scarce. Prevalence of O-EIMs is lower than in adults but may be underestimated because of the possibility of asymptomatic uveitis; however, the long-term significance of this condition is unknown. Children with CD may be at increased risk of O-EIMs. No recommendations on routine ophthalmological examination can be made, but a low threshold for ophthalmological referral should be maintained. Larger studies in paediatric IBD populations are needed.
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Affiliation(s)
- Giorgio Ottaviano
- Pediatric Department, Ospedale 'F. Del Ponte', Università dell'Insubria, Varese, Italy
| | - Silvia Salvatore
- Pediatric Department, Ospedale 'F. Del Ponte', Università dell'Insubria, Varese, Italy
| | - Alessandro Salvatoni
- Pediatric Department, Ospedale 'F. Del Ponte', Università dell'Insubria, Varese, Italy
| | - Stefano Martelossi
- Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy
| | - Alessandro Ventura
- Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy.,Department of Medicine, Surgery, and Health Sciences, University of Trieste, Trieste, Italy
| | - Samuele Naviglio
- Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy.,Department of Medicine, Surgery, and Health Sciences, University of Trieste, Trieste, Italy
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Troncoso LL, Biancardi AL, de Moraes Jr HV, Zaltman C. Ophthalmic manifestations in patients with inflammatory bowel disease: A review. World J Gastroenterol 2017; 23:5836-5848. [PMID: 28932076 PMCID: PMC5583569 DOI: 10.3748/wjg.v23.i32.5836] [Citation(s) in RCA: 78] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Revised: 06/29/2017] [Accepted: 07/12/2017] [Indexed: 02/06/2023] Open
Abstract
Clinical manifestations of inflammatory bowel disease (IBD) are not locally restricted to the gastrointestinal tract, and a significant portion of patients have involvement of other organs and systems. The visual system is one of the most frequently affected, mainly by inflammatory disorders such as episcleritis, uveitis and scleritis. A critical review of available literature concerning ocular involvement in IBD, as it appears in PubMed, was performed. Episcleritis, the most common ocular extraintestinal manifestation (EIM), seems to be more associated with IBD activity when compared with other ocular EIMs. In IBD patients, anterior uveitis has an insidious onset, it is longstanding and bilateral, and not related to the intestinal disease activity. Systemic steroids or immunosuppressants may be necessary in severe ocular inflammation cases, and control of the underlying bowel disease is important to prevent recurrence. Our review revealed that ocular involvement is more prevalent in Crohn's disease than ulcerative colitis, in active IBD, mainly in the presence of other EIMs. The ophthalmic symptoms in IBD are mainly non-specific and their relevance may not be recognized by the clinician; most ophthalmic manifestations are treatable, and resolve without sequel upon prompt treatment. A collaborative clinical care team for management of IBD that includes ophthalmologists is central for improvement of quality care for these patients, and it is also cost-effective.
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Affiliation(s)
- Leandro Lopes Troncoso
- Department of Ophthalmology, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-913, Brazil
| | - Ana Luiza Biancardi
- Department of Ophthalmology, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-913, Brazil
| | | | - Cyrla Zaltman
- Department of Internal Medicine, Gastroenterology Division, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-913, Brazil
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40
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Abstract
BACKGROUND Data on ocular manifestations of inflammatory bowel disease (IBD) in children are limited. Some authors have reported a high prevalence of asymptomatic uveitis, yet the significance of these observations is unknown and there are no recommendations on which ophthalmologic follow-up should be offered. METHODS Children with IBD seen at a single referral center for pediatric gastroenterology were offered ophthalmologic evaluation as part of routine care for their disease. Ophthalmologic evaluation included review of ocular history as well as slit-lamp and fundoscopic examination. Medical records were also reviewed for previous ophthalmologic diagnoses or complaints. RESULTS Data from 94 children were included (52 boys; median age 13.4 yr). Forty-six patients had a diagnosis of Crohn's disease, 46 ulcerative colitis, and 2 IBD unclassified. Intestinal disease was in clinical remission in 70% of the patients; fecal calprotectin was elevated in 64%. One patient with Crohn's disease had a previous diagnosis of clinically manifest uveitis (overall uveitis prevalence: 1.06%; incidence rate: 0.3 per 100 patient-years). This patient was also the only one who was found to have asymptomatic uveitis at slit-lamp examination. A second patient had posterior subcapsular cataract associated with corticosteroid treatment. No signs of intraocular complications from previous unrecognized uveitis were observed in any patient. CONCLUSIONS Children with IBD may have asymptomatic uveitis, yet its prevalence seems lower than previously reported, and it was not found in children without a previous diagnosis of clinically manifest uveitis. No ocular complications from prior unrecognized uveitis were observed.
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Fiorino G, Manetti N, Armuzzi A, Orlando A, Variola A, Bonovas S, Bossa F, Maconi G, DʼIncà R, Lionetti P, Cantoro L, Fries W, Annunziata ML, Costa F, Terpin MM, Biancone L, Cortelezzi CC, Amato A, Ardizzone S, Danese S, Guidi L, Rizzuto G, Massella A, Andriulli A, Massari A, Lorenzon G, Ghione S, Kohn A, Ventra A, Annese V. The PROSIT-BIO Cohort: A Prospective Observational Study of Patients with Inflammatory Bowel Disease Treated with Infliximab Biosimilar. Inflamm Bowel Dis 2017; 23:233-243. [PMID: 28092307 DOI: 10.1097/mib.0000000000000995] [Citation(s) in RCA: 114] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Few data are available on the safety and efficacy of infliximab biosimilar CT-P13 in patients with ulcerative colitis and Crohn's disease. METHODS A prospective, multicenter, cohort study using a structured database. RESULTS Consecutive patients (313 Crohn's disease and 234 ulcerative colitis) were enrolled from 31 referral centers; 311 patients were naive to anti-tumor necrosis factor alpha, 139 had a previous exposure to biologics, and the remaining 97 were switched to CT-P13 after a mean of 18 ± 14 infusions of infliximab. The mean follow-up was 4.3 ± 2.8 months, and the total follow-up time was 195 patient-years. After 2061 infusions, 66 serious adverse events were reported (12.1%), 38 (6.9%) of them were infusion-related reactions. The biosimilar had to be stopped in 29 (5.3%) cases for severe infusion reactions (8 naive, 19 previous exposed, and 2 switch), and in further 16 patients (2.9%) for other serious adverse events. Infusion reactions were significantly more frequent in patients pre-exposed to infliximab than to other anti-tumor necrosis factor alpha (incidence rate ratio = 2.82, 95% CI: 1.05-7.9). The efficacy of the biosimilar was evaluated in 434 patients who received treatment for at least 8 weeks, using time-to-event methods for censored observations: 35 patients were primary failures (8.1%). After further 8, 16, and 24 weeks, the efficacy estimations were 95.7%, 86.4%, and 73.7% for naive, 97.2%, 85.2%, and 62.2% for pre-exposed, and 94.5%, 90.8%, and 78.9% for switch, respectively (log-rank P = 0.64). CONCLUSIONS Although no direct comparison was performed, preliminary data on efficacy and safety of CT-P13 were in line with those of infliximab.
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Affiliation(s)
- Gionata Fiorino
- 1IBD Center, Department of Gastroenterology, Humanitas Research Hospital, Humanitas University, Rozzano, Italy; 2Department of Gastroenterology, AOU Careggi, Florence, Italy; 3IBD Unit, Complesso Integrato Columbus-Gemelli Hospital Catholic University Foundation, Rome, Italy; 4Department of Internal Medicine 2, IBD Unit, Riuniti Villa Sofia-Cervello Hospital, Palermo, Italy; 5Unit of Gastroenterology, Centro Malattie Retto-Intestinali, Sacro Cuore Don Calabria Hospital, Negrar, Italy; 6Gastroenterology Unit, IRCCS-CSS Hospital, San Giovanni Rotondo, Italy; 7Gastroenterology and IBD Unit, Luigi Sacco University Hospital, Milan, Italy; 8Unit of Gastroenterology, University of Padova, Padova, Italy; 9Department of Gastroenterology and Nutrition, Meyer Children's Hospital, Florence, Italy; 10Unit of Gastroenterology, S. Camillo-Forlanini Hospital, Rome, Italy; 11Clinical Unit for Chronic Bowel Disorders, University of Messina, Messina, Italy; 12Department of Gastroenterology, IRCCS Policlinico, San Donato Milanese-Milano, Italy; 13Unit of Gastroenterology, AOUP, Pisa, Italy; 14Department of Gastroenterology and Endoscopy, AO Hospital, Legnano, Italy; 15Department of Systems Medicine, Gastroenterology, University of Rome Tor Vergata, Roma, Italy; 16Unit of Gastroenterology, AOU di Circolo Fondazione Macchi, Varese, Italy; 17Department of Gastroenterology, Ospedale Valduce, Como, Italy; and 18Department of Gastroenterology, Fatebenefratelli-Oftalmico Hospital, Milano, Italy
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Abstract
PURPOSE OF REVIEW Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) are numerous and can often involve the eye. This review highlights the ocular complications associated with IBD including the critical role the ophthalmologist can play in the diagnosis of IBD, the pathogenesis of IBD, its ocular complications, and the treatment of ocular inflammation associated with IBD. RECENT FINDINGS Polygenic and environmental influences, as well as gut microbial dysbiosis, have been implicated in the pathogenesis of IBD. IBD and its EIMs appear to respond well to TNFα-targeted biologics. SUMMARY IBD is thought to be caused by polygenic and environmental influences, including a dysbiotic gut microbiota. It is a systemic immune-mediated disease with varying types of ocular manifestations that can precede, occur simultaneously, or follow intestinal involvement. The diagnosis of IBD can be confused with other seronegative spondyloarthropathies as well as Behçet's disease. Treatment of IBD-associated ocular inflammation can range from corticosteroids to steroid-sparing immunosuppression such as azathioprine or methotrexate. Refractory disease can respond well to TNFα inhibitors.
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Affiliation(s)
- Akshay S Thomas
- Casey Eye Institute, Oregon Health and Sciences University, Portland, Oregon, USA
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43
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Li YC, Li WZ, Wu CR, Feng Y, Ren L, Mi C, Li Y. Prevalence and characteristics of ophthalmological extra-intestinal manifestations in Chinese patients with inflammatory bowel disease. Int J Ophthalmol 2016; 9:1476-1479. [PMID: 27803867 DOI: 10.18240/ijo.2016.10.18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2016] [Accepted: 08/09/2016] [Indexed: 01/13/2023] Open
Abstract
AIM To investigate the prevalence of ophthalmological extra-intestinal manifestations (O-EIMs) in Chinese patients with inflammatory bowel disease (IBD) and to identify risk factors for the development of O-EIMs. METHODS The study population consisted of Chinese patients with a definite diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) in a large teaching hospital between January 1995 and December 2014. Demographic and clinical characteristics of patients were extracted retrospectively. RESULTS In this twenty-year cohort, 645 IBD patients (517 with UC, 128 with CD) were registered. Among them 122 (18.9%) exhibited at least one EIM. Of 13 patients (2.0%) developed O-EIMs, 7 of CD (5.5%) and 6 of UC (1.2%). Clinical ophthalmological manifestations included redness (76.9%), burning (61.5%), pain (38.5%), itching (15.4%) of eyes and vision change (7.7%). O-EIMs included episcleritis (7), uveitis (5) and dry eye (1). O-EIMs were more prevalent in female (odds ratio for male 0.61, 95% confidence interval 0.52-0.73, P<0.0001), and patients who had IBD diagnosis at young age (odds ratio for patients aged >30 years 0.76, 95% confidence interval 0.65-0.88, P<0.0001). CONCLUSION The frequency of O-EIMs in Chinese patients with IBD is lower than the rates reported in the studies of European and American countries. Episcleritis and uveitis are the most common O-EIMs. O-EIMs are more frequent in patients with CD and more prevalent in female and patients who have IBD diagnosis at young age.
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Affiliation(s)
- Ying-Chao Li
- Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Wei-Zhi Li
- Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Chang-Rui Wu
- Department of Ophthalmology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Yun Feng
- Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Li Ren
- Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Chen Mi
- Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Yang Li
- Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
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Pouillon L, Bossuyt P, Peyrin-Biroulet L. Considerations, challenges and future of anti-TNF therapy in treating inflammatory bowel disease. Expert Opin Biol Ther 2016; 16:1277-90. [PMID: 27329436 DOI: 10.1080/14712598.2016.1203897] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Crohn's disease (CD) and ulcerative colitis (UC) are chronic disabling conditions. Monoclonal antibody therapy directed against tumor necrosis factor-alpha (anti-TNF) has revolutionized the care of patients with inflammatory bowel disease (IBD). AREAS COVERED Considerations before starting anti-TNF therapy are highlighted: the best time to start with anti-TNF therapy, either alone or in combination with an immunomodulator, the choice of an anti-TNF agent and the contra-indications to anti-TNF therapy. Primary nonresponse and secondary loss of response are discussed. De-escalating therapy, the role of therapeutic drug monitoring and the use of biosimilars, are handled. Finally, the future directions of anti-TNF therapy are emphasized. EXPERT OPINION Anti-TNF therapy remains the cornerstone in the treatment of IBD. When initiating long-term therapy, safety and cost issues are of great importance. The therapeutic armamentarium in the treatment of IBD is rapidly growing. Therefore, the challenge is to optimize the use and refine the exact position of anti-TNF therapy in the near future, with personalized medicine as the ultimate goal.
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Affiliation(s)
- Lieven Pouillon
- a Department of Hepato-Gastroenterology , University Hospitals Leuven, Uz Gasthuisberg , Leuven , Belgium
| | - Peter Bossuyt
- b Imelda GI Clinical Research Centre , Imeldaziekenhuis Bonheiden , Bonheiden , Belgium
| | - Laurent Peyrin-Biroulet
- c Inserm U954 and Department of Gastroenterology , Nancy University Hospital, Université de Lorraine , Vandœuvre-lès-Nancy , France
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