Prevalence of Inflammatory Bowel Disease Unclassified, as Estimated Using the Revised Porto Criteria, among Korean Pediatric Patients with Inflammatory Bowel Disease.

Purpose: Few studies have reported the prevalence of inflammatory bowel disease unclassified (IBDU) among Korean pediatric IBD (PIBD) population. To address this gap, we used two tertiary centers and nationwide population-based healthcare administrative data to estimate the prevalence of Korean pediatric IBDU at the time of diagnosis. Methods: We identified 136 patients aged 2-17 years with newly diagnosed IBD (94 Crohn's disease [CD] and 42 ulcerative colitis [UC]) from two tertiary centers in Korea between 2005 and 2017. We reclassified these 136 patients using the revised Porto criteria. To estimate the population-based prevalence, we analyzed Korean administrative healthcare data between 2005 and 2016, which revealed 3,650 IBD patients, including 2,538 CD and 1,112 UC. By extrapolating the reclassified results to a population-based dataset, we estimated the prevalence of PIBD subtypes. Results: Among the 94 CD, the original diagnosis remained unchanged in 93 (98.9%), while the diagnosis of one (1.1%) patient was changed to IBDU. Among the 42 UC, the original diagnosis remained unchanged in 13 (31.0%), while the diagnoses in 11 (26.2%), 17 (40.5%), and one (2.4%) patient changed to atypical UC, IBDU, and CD, respectively. The estimated prevalences of CD, UC, atypical UC, and IBDU in the Korean population were 69.5%, 9.4%, 8.0%, and 13.1%, respectively. Conclusion: This study is the first in Korea to estimate the prevalence of pediatric IBDU. This prevalence (13.1%) aligns with findings from Western studies. Large-scale prospective multicenter studies on PIBDU are required to examine the clinical features and outcomes of this condition.

Clinical features of inflammatory bowel disease unclassified: a case-control study.

BACKGROUND: Approximately 10-15% of inflammatory bowel disease (IBD) patients with overlapping features of ulcerative colitis (UC) and Crohn's disease (CD) are termed as inflammatory bowel disease unclassified (IBDU). This study aimed to describe the clinical features of IBDU and evaluate the potential associated factors of reclassification. METHODS: The clinical data of 37 IBDU patients were retrospectively analyzed from November 2012 to November 2020. 74 UC and 74 CD patients were randomly selected and age- and sex-matched with the 37 IBDU patients. Clinical characteristics were compared between the three patient groups. Potential factors associated with the IBDU reclassification were evaluated. RESULTS: 60% of IBDU patients displayed rectal-sparing disease, and 70% of them displayed segmental disease. In comparison to UC and CD, the IBDU group demonstrated higher rates of gastrointestinal bleeding (32.4%), intestinal perforation (13.5%), spontaneous blood on endoscopy (51.4%), and progression (56.8%). The inflammation proceeded relatively slowly, manifesting as chronic alterations like pseudopolyps (78.4%) and haustra blunt or disappearance (56.8%). 60% of IBDU patients exhibited crypt abscess, and 16.7% of them exhibited fissuring ulcers or transmural lymphoid inflammation. The proportions of IBDU patients receiving immunosuppressants, surgery, and infliximab were basically the same as those of CD patients. During the 79 (66, 91) months of follow-up, 24.3% of IBDU patients were reclassified as UC, while 21.6% were reclassified as CD. The presence of intestinal hemorrhaging was associated with CD reclassification, while hypoalbuminemia was associated with UC reclassification. CONCLUSIONS: IBDU may evolve into UC or CD during follow-up, and hemorrhage was associated with CD reclassification. Different from the other two groups, IBDU exhibited a more acute onset and a gradual progression. When an IBD patient presents with transmural inflammation or crypt abscess but lacks transmural lymphoid aggregates or fissuring ulcers, the diagnosis of IBDU should be considered.

Some Drugs Have Two Faces: Paradoxical Colitis in a Patient with Psoriatic Arthritis Previously Treated with Etanercept and IL-17 Inhibitors.

Tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17) inhibitors are among the most potent treatments for inflammatory arthropathies including rheumatoid arthritis, psoriasis, and spondyloarthropathies. The availability of these biologic agents have revolutionized the management of these conditions and improved patient outcomes. Though generally safe, these biologics may contribute to the induction or exacerbation of colitis. This paradoxical colitis has been observed in patients on TNF-α inhibitor etanercept and IL-17 inhibitors (secukinumab and ixekizumab). We report a case of a 46-year-old female with psoriasis and psoriatic arthritis who presented with gastrointestinal symptoms after treatment with etanercept and IL-17 inhibitors. She was later diagnosed with paradoxical indeterminate colitis that was masked and treated by subsequent biologics given for her RA and psoriatic arthritis. In this report, we will discuss the importance of considering paradoxical colitis in the differential diagnosis for patients even several years after TNF-α/IL-17 inhibitor initiation and explain why careful consideration must be made when initiating these colitis-inducing agents to treat patients with inflammatory disorders.

Prevalence of Extraintestinal Manifestations in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Inflammatory bowel disease (IBD) is a multisystem disease impacting various body systems including musculoskeletal, ocular, skin, hepatobiliary, pulmonary, cardiac, and haematological systems. The extraintestinal manifestations of IBD are frequent, common in both ulcerative colitis (UC) and Crohn's disease (CD), and impact the morbidity and mortality of patients. METHODS: The Embase, Embase classic, and PubMed databases were searched between January 1979 and December 2021. A random effects model was performed to find the pooled prevalence of joint, ocular, and skin extraintestinal manifestations of UC and CD. RESULTS: Fifty-two studies were included that reported on 352 454 patients. The prevalence of at least 1 joint, ocular, or skin extraintestinal manifestation in all IBD, UC, and CD was 24%, 27%, and 35% respectively. The prevalence between UC and CD were similar for pyoderma gangrenosum and axial joint manifestations. Ocular manifestations were found to be more common in CD than in UC. Peripheral joint manifestations and erythema nodosum were found to be more common in CD than UC. DISCUSSION: To our knowledge, this is the first meta-analysis that reports on the prevalence of at least 1 joint, ocular, or skin extraintestinal manifestation in IBD. Our results are largely consistent with figures and statements quoted in the literature. However, our findings are based on significantly larger cohort sizes. Thus, our results have the potential to better power studies and more accurately counsel patients.

The prevalence of joint, ocular, or skin extraintestinal manifestations in IBD, UC, and CD was 24%, 27%, and 35% respectively. Ocular manifestations were more common in CD. Peripheral joint manifestations and erythema nodosum were more common in CD.

Ubiquitous Colonic Ileal Metaplasia Consistent with the Diagnosis of Crohn's Colitis among Indeterminate Colitis Cohorts.

Background: Inadequate differentiated diagnostic features of predominantly colonic inflammatory bowel diseases i.e., ulcerative colitis and Crohn's colitis, may lead to inexact diagnosis of "indeterminate colitis". About 15% of indeterminate colitis patients are diagnosed at colonoscopy, in colonic biopsies, and/or at colectomy. Managing outcomes of indeterminate colitis, given its unpredictable clinical presentation, depends on future diagnosis of colitis, Crohn's colitis or ulcerative colitis. Objective: Overview the diagnostic efficacy of ectopic colonic ileal metaplasia and human α-defens 5 (DEFA5 alias HD5) for accurate delineation of indeterminate colitis into authentic Crohn's colitis and/ or ulcerative colitis. Design: We describe a targeted protein for potentially differentiating indeterminate colitis into an accurate clinical subtype diagnosis of inflammatory bowel diseases i.e., ulcerative colitis and Crohn's colitis. Patients: Twenty-one patients with the clinically inexact diagnosis of indeterminate colitis were followed, reassessed and data analyzed. Main outcome measures: We observed that (i) some patients had their original diagnosis changed from indeterminate colitis to either ulcerative colitis or Crohn's colitis; and (ii) human α-defensin 5 is aberrantly overexpressed in Crohn's colitis. Results: Fifteen of the twenty-one (71.4%) patients with indeterminate colitis had their inconclusive diagnosis changed; nine patients changed to ulcerative colitis and six to Crohn's colitis. In human colon surgical samples, Human α-defensin-5 was significantly upregulated in Crohn's colitis. In addition, Human α-defensin 5 processing enzyme, matrix metalloptotease-7 was inversely expressed compared to Human α- Defensin 5. Limitation: Due to the sequence homology of the α-defensin class of proteins, preceding efforts to raise antibodies (Abs) against DEFA5 have limitations to produce adequate specificity. The Abs used in previous assays recognizes the α-defensins, active α-defensins 5 and inactive pro- α-defensins 5. Monoclonal antibodies (mAbs) to determine specificity and sensitivity of α-defensins 5, which is diagnostic of CC disease, and NOT other α-defensins is the limitation to overcome. Conclusion: It is feasible to differentiate ulcerative colitis from Crohn's colitis among patients with inexact diagnosis of indeterminate colitis using Human α-defensin 5 as a molecular biosignature delineator.

Focal Active Colitis: What Are Its Clinical Implications? A Narrative Review.

Focal active colitis (FAC) is described as a histolopathological term indicating the isolated finding of focal neutrophil infiltration in the colonic crypts. Currently, there exist numerous debates regarding the clinical significance of diagnosing FAC, which may or may not have clinical relevance as it is frequently detected in colorectal biopsies without any other microscopic abnormalities. The objective of this narrative review is to provide an overview of the available evidence concerning the clinical implications of FAC, both in the adult population (among five studies available in the scientific literature) and in the pediatric context (based on two available studies).

A nationwide study of patients hospitalized with indeterminate colitis: a comparison with Crohn's disease and ulcerative colitis.

PURPOSE: Indeterminate colitis (IC) is subtype of colonic inflammatory bowel disease (IBD) that has features of both Crohn's disease (CD) and ulcerative colitis (UC). There have also been no studies to date examining patients hospitalized with IC in the United States (US). METHODS: We examined the demographic and clinical characteristics of patients admitted with IC and compared them with patients admitted with CD and UC. We also analyzed trends in cost and length of stay (LOS). RESULTS: Patients admitted with IC tended to be female (58%), Caucasian (72%), and younger [39 (SD: 23) years]. Patients with IC underwent lower endoscopy at higher rates (26%; CD: p < 0.001, UC: p = 0.08) but bowel surgery at lower rates compared to those with CD (11% vs. 16%; p = 0.04). Patients with IC were found to have a higher rate of bowel obstruction (4% vs. 0.7%, p = 0.004) than those with UC, but lower rates of abscess and obstruction compared to patients with CD (p < 0.001). When the analysis was confined to patients who underwent bowel surgery, IC patients still demonstrated higher rates of lower endoscopy (p = 0.03) but lower rates of abscess compared to CD patients (p = 0.049). Costs increased significantly over time for CD- and UC-related hospitalizations, but not for admissions related to IC. CONCLUSION: This is the first nationwide US study illustrating the demographics and clinical characteristics of patients hospitalized with IC. We conclude that IC has notable differences in hospitalization characteristics compared to the main two IBD subtypes.

Inflammatory Bowel Disease: Clinical Diagnosis and Pharmaceutical Management.

Inflammatory bowel disease has an enormous impact on public health, medical systems, economies, and social conditions. Biologic therapy has ameliorated the treatment and clinical course of patients with inflammatory bowel disease. The efficacy and safety profiles of currently available therapies are still less that optimal in numerous ways, highlighting the requirement for new therapeutic targets. A bunch of new drug studies are underway in inflammatory bowel disease with promising results. This is an outlined guideline of clinical diagnosis and pharmaceutical therapy of inflammatory bowel disease. Outline delineates the overall recommendations on the modern principles of desirable practice to bolster the adoption of best implementations and exploration as well as inflammatory bowel disease patient, gastroenterologist, and other healthcare provider education. Inflammatory bowel disease encompasses Crohn's disease and ulcerative colitis, the two unsolved medical inflammatory bowel disease-subtypes condition with no drug for cure. The signs and symptoms on first presentation relate to the anatomical localization and severity of the disease and less with the resulting diagnosis that can clinically and histologically be non-definitive to interpret and establish criteria, specifically in colonic inflammatory bowel disease when the establishment is inconclusive is classified as indeterminate colitis. Conservative pharmaceuticals and accessible avenues do not depend on the disease phenotype. The first line management is to manage symptoms and stabilize active disease; at the same time maintenance therapy is indicated. Nutrition and diet do not play a primary therapeutic role but is warranted as supportive care. There is need of special guideline that explore solution of groundwork gap in terms of access limitations to inflammatory bowel disease care, particularly in developing countries and the irregular representation of socioeconomic stratification with a strategic plan, for the unanswered questions and perspective for the future, especially during the surfaced global COVID-19 pandemic caused by coronavirus SARS-CoV2 impacting on both the patient's psychological functioning and endoscopy services. Establishment of a global registry system and accumulated experiences have led to consensus for inflammatory bowel disease management under the COVID-19 pandemic. Painstakingly, the pandemic has influenced medical care systems for these patients. I briefly herein viewpoint summarize among other updates the telemedicine roles during the pandemic and how operationally inflammatory bowel disease centers managed patients and ensured quality of care. In conclusion: inflammatory bowel disease has become a global emergent disease. Serious medical errors are public health problem observed in developing nations i.e., to distinguish inflammatory bowel disease and infectious and parasitic diseases. Refractory inflammatory bowel disease is a still significant challenge in the management of patients with Crohn's disease and ulcerative colitis. There are gaps in knowledge and future research directions on the recent newly registered pharmaceuticals. The main clinical outcomes for inflammatory bowel disease were maintained during the COVID-19 pandemic period.

Inflammatory Bowel Disease: Clinical Diagnosis and Surgical Treatment-Overview.

This article is an overview of guidelines for the clinical diagnosis and surgical treatment of predominantly colonic inflammatory bowel diseases (IBD). This overview describes the systematically and comprehensively multidisciplinary recommendations based on the updated principles of evidence-based literature to promote the adoption of best surgical practices and research as well as patient and specialized healthcare provider education. Colonic IBD represents idiopathic, chronic, inflammatory disorders encompassing Crohn's colitis (CC) and ulcerative colitis (UC), the two unsolved medical subtypes of this condition, which present similarity in their clinical and histopathological characteristics. The standard state-of-the-art classification diagnostic steps are disease evaluation and assessment according to the Montreal classification to enable explicit communication with professionals. The signs and symptoms on first presentation are mainly connected with the anatomical localization and severity of the disease and less with the resulting diagnosis "CC" or "UC". This can clinically and histologically be non-definitive to interpret to establish criteria and is classified as indeterminate colitis (IC). Conservative surgical intervention varies depending on the disease phenotype and accessible avenues. The World Gastroenterology Organizations has, for this reason, recommended guidelines for clinical diagnosis and management. Surgical intervention is indicated when conservative treatment is ineffective (refractory), during intractable gastrointestinal hemorrhage, in obstructive gastrointestinal luminal stenosis (due to fibrotic scar tissue), or in the case of abscesses, peritonitis, or complicated fistula formation. The risk of colitis-associated colorectal cancer is realizable in IBD patients before and after restorative proctocolectomy with ileal pouch-anal anastomosis. Therefore, endoscopic surveillance strategies, aimed at the early detection of dysplasia, are recommended. During the COVID-19 pandemic, IBD patients continued to be admitted for IBD-related surgical interventions. Virtual and phone call follow-ups reinforcing the continuity of care are recommended. There is a need for special guidelines that explore solutions to the groundwork gap in terms of access limitations to IBD care in developing countries, and the irregular representation of socioeconomic stratification needs a strategic plan for how to address this serious emerging challenge in the global pandemic.

The association between pre-colectomy thiopurine use and risk of neoplasia after ileal pouch anal anastomosis in patients with ulcerative colitis or indeterminate colitis: a propensity score analysis.

BACKGROUND: The risk of neoplasia of the pouch or residual rectum in patients with ulcerative colitis (UC) who undergo total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is incompletely investigated. Thiopurine use is associated with a reduced risk of colorectal neoplasia in patients with UC. We tested the hypothesis that thiopurine use prior to TPC may be associated with a reduced risk of primary neoplasia after IPAA. METHODS: We conducted a retrospective cohort analysis of patients from a tertiary referral center from January 2008 to December 2017. Eligible patients with UC or IC underwent TPC with IPAA and had at least two pouchoscopies with biopsies ≥ 6 months after surgery. Propensity score analysis was conducted to match thiopurine exposed vs unexposed groups based on clinical covariates. Multivariable Cox regression analysis estimated the risk of neoplasia. RESULTS: A total of 284 patients with UC or IC (57.4% male, median age 35.6 years) were analyzed. Ninety-seven patients (34.2%) were confirmed to have thiopurine exposure ≥ 12 weeks immediately prior to TPC ("exposed") and 187 (65.8%) were confirmed to have no thiopurine exposure for at least 365 days prior to TPC ("non-exposed"). Compared to non-exposed patients, patients with thiopurine exposure less often had dysplasia (7.2% vs 23.0%, p = 0.001) and had lower grades of dysplasia before colectomy. After IPAA, patients with neoplasia were older (44.0 vs 34.8 years, p = 0.03), more likely to have had dysplasia as colectomy indication (44.4% vs 15.4%, p = 0.007), and more likely to require pouch excision (55.6% vs 10.2%, p < 0.0001), compared to patients without neoplasia. On propensity-matched cohort analysis, no factors were significantly associated with risk of primary neoplasia. CONCLUSION: Thiopurine exposure for at least the 12 weeks prior to TPC in patients with UC or IC does not appear to be independently associated with risk of primary neoplasia following IPAA.

Indeterminate Colitis - Update on Treatment Options.

Indeterminate colitis (IC) is described in approximately 5-15% of patients with inflammatory bowel disease (IBD). It usually reflects a difficulty or lack of clarity in distinguishing between ulcerative colitis (UC) and Crohn's disease (CD) on biopsy or colectomy specimens. The diagnostic difficulty may explain the variability in the reported prevalence and incidence of IC. Clinically, most IC patients tend to evolve over time to a definite diagnosis of either UC or CD. IC has also been interchangeably described as inflammatory bowel disease unclassified (IBDU). This review offers an overview of the available limited literature on the conventional medical and surgical treatments for IC. In contrast to the numerous studies on the medical management of UC and CD, there are very few data from dedicated controlled trials on the treatment of IC. The natural evolution of IC more closely mimics UC. Regarding medical options for treatment, most patients diagnosed with IC are treated similarly to UC, and treatment choices are based on disease severity. Others are managed similarly to CD if there are features suggestive of CD, including fissures, skin tags, or rectal sparing. In medically refractory IC, surgical treatment options are limited and include total proctocolectomy (TPC) and ileal pouch-anal anastomosis (IPAA), with its associated risk factors and complications. Post-surgical complications and pouch failure rates were historically thought to be more common in IC patients, but recent meta-analyses reveal similar rates between UC and IC patients. Future therapies in IBD are focused on known mechanisms in the disease pathways of UC and CD. Owing to the lack of IC-specific studies, clinicians have traditionally and historically extrapolated the data to IC patients based on their symptomatology, clinical course, and endoscopic findings.

Does perioperative biological therapy increase 30-day post-operative complication rates in inflammatory bowel disease patients undergoing intra-abdominal surgery? A systematic review.

BACKGROUND: Biopharmaceuticals revolutionised inflammatory bowel disease (IBD) treatment. However, it is postulated they compromise immunity, collagen production and angiogenesis resulting in infective post-operative complications and altered wound/anastomotic healing. Research has failed to agree on risks associated with perioperative biologics therefore it was anticipated that a systematic review may provide a consensus and contribute recommendations for clinical practice. METHODS: A systematic review conducted as per PRISMA guidelines included a methodical search of PubMed, Google Scholar, EMBASE/Ovid and Cochrane Library using MeSH and/or keywords for papers published between 01/01/1998 and 04/02/2019.The population analysed included adult ulcerative colitis, Crohn's disease, Indeterminate Colitis or IBD unclassified patients. The intervention was intra-abdominal surgery in patients treated with biological therapy in the preceding 12 weeks compared to patients who had intra-abdominal surgery without biological therapy within the defined timeframe. The primary outcome was surgical site infection (SSI) with secondary outcomes including wound dehiscence, intra-abdominal sepsis/abscess, systemic infection and anastomotic breakdown within 30 days post-procedure. Papers were evaluated by two independent reviewers and those included were assessed for quality/bias using the Newcastle-Ottowa scale. RESULTS: 2064 UC, Crohn's and IC patients were analysed across 8 included studies. Several studies' multivariate analyses demonstrated corticosteroids to be independent predictors of morbidity. There are no increased complications associated with anti-TNFα exposure while vedolizumab increased SSI and small bowel obstruction. CONCLUSION: Prospective studies and randomised control trials are required to clarify study outcomes and recommendations published to date. Presently, biologics should continue to be used and considered beneficial in this population.

Inflammatory bowel disease in Tuzla Canton, Bosnia-Herzegovina: A prospective 10-year follow-up.

BACKGROUND: The incidence and prevalence of inflammatory bowel disease (IBD) vary between regions but have risen globally in recent decades. A lack of data from developing nations limits the understanding of IBD epidemiology. AIM: To perform a follow-up review of IBD epidemiology in the Tuzla Canton of Bosnia-Herzegovina during a 10-year period (2009-2019). METHODS: We prospectively evaluated the hospital records of both IBD inpatients and outpatients residing in Tuzla Canton for the specified period of time between January 1, 2009 and December 31, 2019. Since all our patients had undergone proximal and distal endoscopic evaluations at the hospital endoscopy unit, we used the hospital's database as a primary data source, alongside an additional cross-relational search of the database. Both adult and pediatric patients were included in the study. Patients were grouped by IBD type, phenotype, age, and gender. Incidence rates were calculated with age standardization using the European standard population. Trends in incidence and prevalence were evaluated as a 3-year moving average and average annual percentage change rates. RESULTS: During the 10-year follow-up period, 651 patients diagnosed with IBD were monitored (of whom 334, or 51.3%, were males, and 317, or 48.7%, were females). Of all the patients, 346 (53.1%) had been diagnosed with ulcerative colitis (UC), 292 (44.9%) with Crohn's disease (CD), and 13 (2%) with indeterminate colitis (IC). We observed 440 newly diagnosed patients with IBD: 240 (54.5%) with UC, 190 (43.2%) with CD, and 10 (2.3%) with IC. The mean annual crude incidence rates were found to be 9.01/100000 population for IBD [95% confidence interval (CI): 8.17-9.85], with 4.91/100000 (95%CI: 4.29-5.54) for UC and 3.89/100000 (95%CI: 3.34-4.44) for CD. Calculated IBD prevalence in 2019 was 146.64/100000 (95%CI: 128.09-165.19), with 77.94/100000 (95%CI: 68.08-87.70) for UC and 65.77/100000 (95%CI: 54.45-74.1) for CD. The average annual IBD percentage change was 0.79% (95%CI: 0.60-0.88), with -2.82% (95%CI: -2.67 to -2.97) for UC and 6.92% (95%CI: 6.64-7.20) for CD. During the study period, 24,509 distal endoscopic procedures were performed. The incidence of IBD was 3.16/100 examinations (95%CI: 2.86-3.45) or 1.72/100 examinations (95%CI: 1.5-1.94) for UC and 1.36/100 examinations (95%CI: 1.17-1.56) for CD. CONCLUSION: Trends in the incidence and prevalence of IBD in Tuzla Canton are similar to Eastern European averages, although there are significant epidemiological differences within geographically close and demographically similar areas.

The Clinical Characteristics and Treatment Outcomes of Concomitant Eosinophilic Esophagitis and Inflammatory Bowel Disease.

Background: The clinical characteristics and treatment outcomes in patients with eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) have not been extensively investigated. Methods: We determined treatment outcomes and frequencies of disease-related complications in patients with EoE and IBD. Results: Among 69 patients who met inclusion criteria, 39 (56.5%) had a diagnosis of Crohn disease. Clinical and histologic response rates to proton pump inhibitors and topical steroids were 25.9% and 24.4%, respectively. Conclusions: Lower than expected clinical and histologic response rates for EoE suggest the combination of EoE and IBD is a medically refractory phenotype with more difficult to treat EoE.

Molecular Genetic Architecture of Monogenic Pediatric IBD Differs from Complex Pediatric and Adult IBD.

Inflammatory bowel disease (IBD) manifests as a complex disease resulting from gene-environment interactions or as a monogenic disease resulting from deleterious mutations. While monogenic IBD is predominantly pediatric, only one-quarter of complex IBD is pediatric. In this study, we were the first to systematically compare genetic architecture between monogenic and complex pediatric and adult IBD on genetic and molecular pathway levels. Genes reported as causal for monogenic pediatric IBD and related syndromes and as risk factors for pediatric and adult complex IBD were analyzed using CytoScape and ClueGO software tools to elucidate significantly enriched Gene Ontology (GO) terms. Despite the small overlap (seven genes) between monogenic IBD genes (85) and complex IBD loci (240), GO analysis revealed several enriched GO terms shared between subgroups (13.9%). Terms Th17 cell differentiation and Jak/STAT signaling were enriched in both monogenic and complex IBD subgroups. However, primary immunodeficiency and B-cell receptor signaling pathway were specifically enriched only for pediatric subgroups, confirming existing clinical observations and experimental evidence of primary immunodeficiency in pediatric IBD patients. In addition, comparative analysis identified patients below 6 years of age to significantly differ from complex pediatric and adult IBD and could be considered a separate entity.

Epidemiological profile of inflammatory bowel disease in Caxias do Sul, Brazil: a cross-sectional study

ABSTRACT BACKGROUND: Inflammatory bowel diseases affect mostly young patients and have a huge impact on their quality of life and growing treatment costs. Currently, there are few Brazilian studies concerning their epidemiological profile. OBJECTIVE: The aim of this study was to describe the regional clinical and epidemiological profile of these pathological conditions in Caxias do Sul, Brazil. DESIGN AND SETTING: Cross-sectional study in Caxias do Sul (RS), Brazil. METHODS: A search for patients was conducted in the municipality's special medications pharmacy using the International Classification of Diseases, and medical records were manually reviewed for data collection. Sixty-seven patients were included. RESULTS: The patients' mean age was 46.5 years and females predominated (71.6%). Ulcerative colitis was the most prevalent disease (70%) and Montreal E3 was the most prevalent presentation. The mean age at diagnosis was 39 years. Most patients had recently undergone colonoscopy (67%). Only five patients (7.4%) had records of hospital admission due to the disease, while 12 (18%) underwent a surgical procedure during follow-up. Sixty patients (89.5%) were using aminosalicylates, while less than one fifth were using immunosuppressants or immunobiological drugs: 19.4% and 14.9%, respectively. CONCLUSION: The profile of inflammatory bowel disease patients in this region of Brazil is similar in some characteristics to other published Brazilian data, although it differs in others such as higher frequency of pancolitis. A prospective study on these patients is planned in this region, in order to improve the data quality.

Outcome of Ileal Pouch-anal Anastomosis in Patients With Indeterminate Colitis: A Systematic Review and Meta-analysis.

BACKGROUND: Indeterminate colitis [IC] is type of inflammatory bowel disease that exhibits features of both ulcerative colitis [UC] and Crohn's disease [CD]. The present meta-analysis aimed to assess the outcomes of ileal pouch-anal anastomosis [IPAA] in patients with IC in comparison with patients with UC. METHODS: A PRISMA-compliant systematic review of the outcome of IPAA in patients with IC was conducted. Electronic databases were searched, and full-text articles were reviewed to extract essential data. Main outcome measures were pouch failure and pouch-related complications. RESULTS: A total of 17 studies were included in this meta-analysis. There were 1057 patients with IC and 6511 patients with UC. The weighted mean pouch failure rate in patients with IC was 7.5 (95% confidence interval [CI]: 4.8-10.2) and the weighted mean complication rate was 67 [95% CI: 53.5-80.5]. As compared with patients with UC, patients with IC had significantly higher odds of developing complications after IPAA (odds ratio [OR]: 2.6, p <0.001): pouch fistula [OR:4.98, p <0.001], pelvic sepsis [OR:3.98, p =0.002], pelvic or cuff abscess [OR: 4.5, p <0.001], perineal complications [OR: 5.13, p <0.001], and ultimate diagnosis of CD [OR: 2.57, p <0.001]. Patients with IC and UC had similar odds of pouch failure, pouchitis, anastomotic leak, stricture, and small bowel obstruction. CONCLUSIONS: Patients with IC had similar pouch failure rates, yet higher overall complication rates than patients with UC. Complications that tend to be higher after IPAA for patients with IC include pouch fistula, pelvic sepsis, abscess, perineal complications, and ultimate diagnosis of Crohn's disease.

Is ulcerative colitis a disease of a dysfunctional microbiota?

Using the gross pathology literature and the prior decoupling of Crohn's disease from inflammatory bowel disease, IDI's White Paper puts into question the current understanding of what ulcerative colitis is and how it can be therapeutically addressed. The pathology literature, when coupled with the ability of fecal enema therapy to achieve a remission rate significantly superior to those documented for biologics, puts focus on the dominant role of the gastrointestinal microbiota in both disease induction and its recovery. The concept of endogenous enterotoxogenesis is introduced.

Comparison of the use of wireless capsule endoscopy with magnetic resonance enterography in children with inflammatory bowel disease.

BACKGROUND: Magnetic resonance enterography (MRE) and wireless capsule endoscopy (WCE) are equally accepted modalities for noninvasive screening of small bowel involvement (SBI) in children with Crohn's disease (CD) and indeterminate colitis (IC) albeit there is a paucity of data comparing the two and thereby guiding the clinician in selecting the ideal diagnostic approach. Therefore, the goal of this study is to provide additional evidence for capsule endoscopy role in the evaluation of established Crohn's disease exacerbation compared to MRE in relation to Pediatric Crohn's Disease Activity Index (PCDAI), and histological indices. AIM: To prospectively compare the findings of MRE and WCE and their agreement with PCDAI or histology in children with CD or IC. METHODS: Consecutive patients diagnosed with CD and IC were screened for inclusion. After informed consent, patient's demographic and clinical data was abstracted. The current pediatric disease activity index (PCDAI) and endoscopic findings were included. Patients underwent MRE and WCE including preprocedural patency capsule within a maximum of 7 d of each other. Pathological presence of active small bowel disease in ileal and duodenal biopsies were collected if the endoscopy was performed within 2 mo of the WCE study. Patients who failed to pass the PC were excluded from the study. WCE was read by two different experienced gastroenterologists (Attard TM and Colombo JM) blinded to each other's findings and to the findings on MRE (Mardis NJ). Agreement between WCE reviewers, WCE and MRE findings and concordance between positive PCDAI and SBI based on MRE compared with WCE was computed. RESULTS: Forty-five patients were included in the study, 18 withdrew and 27 (20 males and 20 CD), mean age (standard deviation) 13.46 (2.4) years, completed the study protocol. There were no instances of capsule retention. Concordance between gastroenterologist reviewers was excellent for the diagnosis of small intestinal CD with good correlation between the two Lewis scores (r = 0.875, P < 0.001). Concordance between WCE and MRE was poor (69%). In CD patients, when both MRE and WCE were compared using PCDAI > 10 as the standard reference reflecting active small intestinal CD, the sensitivity of MRE and WCE were 100% and 83% respectively and the specificity of MRE and WCE were 57.14% and 78.6%, respectively. If the histology in ileum or/and duodenum was used as the reference for active small bowel involvement, WCE had a higher specificity as compared to MRE (83.3% vs 50%). In patients with Crohn's disease, those with a positive PCDAI (> 10) were more likely to have a positive WCE as compared to those with a negative PCDAI (83% vs 21%; P = 0.018). CONCLUSION: We suggest that MRE and WCE have a complementary role in the assessment of SBI in CD. WCE detected SBI with a much higher specificity while MRE had a higher sensitivity.