Perianal Fistula After Ileoanal Pouch in Patients With Ulcerative Colitis: A Review of 475 Patients Operated on at a Major IBD Center.

BACKGROUND: Ileoanal pouch anastomosis is the surgical treatment of choice for patients with intractable ulcerative colitis. Perianal disease is a feature that is often present in Crohn's disease and infrequently in ulcerative colitis. OBJECTIVE: The aim of this study is to identify the incidence and factors associated with the development of postoperative perianal fistula in patients undergoing ileoanal pouch anastomosis for ulcerative colitis. DESIGN: A prospectively collected database at the time of surgery with subsequent follow-up was utilized. SETTING: The study was conducted at a high-volume single institution. PATIENTS: We studied a series of 475 consecutive patients with preoperative diagnosis of ulcerative colitis who underwent ileoanal pouch anastomosis. MAIN OUTCOME MEASURES: The incidence of postoperative perianal fistula and the factors correlating with its development were primary outcome measures of the study. RESULTS: The overall number of patients developing perianal fistulas was 44 of 475 (9%). Eleven patients with perianal fistula (25%) required return to ileostomy, of which 7 had pouch excision. Patients who developed a postoperative perianal fistula had a younger age at the onset of disease, had a lower age at index surgery, and were more likely to be subsequently classified as indeterminate colitis or Crohn's disease. Patients developing perianal fistulas were also more likely to develop partial dehiscence or stricture of the ileoanal anastomosis. LIMITATIONS: This study spans nearly 40 years during which the surgical procedure evolved. CONCLUSIONS: Young age at the onset of disease, lower age at surgery, and postoperative diagnosis of Crohn's disease and indeterminate colitis were the factors correlating with perianal fistulas. Delayed healing of the ileoanal anastomosis with partial separation and/or stricture also correlated with the onset of perianal fistulas. The severity of rectal inflammation at the time of surgery or the presence of stapled versus handsewn anastomosis did not correlate with the development of perianal fistulas. See Video Abstract at http://links.lww.com/DCR/B705. FSTULA PERIANAL POSTERIOR A RESERVORIO ILEOANAL EN PACIENTES CON COLITIS ULCERATIVA UNA REVISIN DE PACIENTES OPERADOS EN UN CENTRO PRINCIPAL DE EII: ANTECEDENTES:El reservorio ileoanal es el tratamiento quirúrgico de elección para los pacientes con colitis ulcerativa intratable. La enfermedad perianal es una característica que a menudo está presente en la enfermedad de Crohn y con poca frecuencia en la colitis ulcerativa.OBJETIVO:El objetivo del estudio es identificar la incidencia y los factores asociados con el desarrollo de fístula perianal posoperatoria en pacientes sometidos a reservorio ileoanal por colitis ulcerativa.DISEÑO:Base de datos recopilada prospectivamente en el momento de la cirugía con seguimiento subsecuente.ENTORNO CLÍNICO:El estudio se llevó a cabo en una única institución de gran volumen.PACIENTES:Estudiamos una serie de 475 pacientes consecutivos con diagnóstico preoperatorio de colitis ulcerativa a los que se les realizó reservorio ileoanal.PRINCIPALES MEDIDAS DE VALORACIÓN:La incidencia de fístula perianal posoperatoria y los factores que se correlacionan con su desarrollo fueron las principales medidas de resultado del estudio.RESULTADOS:El número total de pacientes que desarrollaron fístulas perianales fue 44 de 475 (9%). Once pacientes con fístula perianal (25%) requirieron volver a la ileostomía, de los cuales 7 tuvieron resección del reservorio. Los pacientes que desarrollaron fístula perianal posoperatoria tenían edad más temprana al inicio de la enfermedad, menor edad en el momento de la cirugía inicial y tenían más probabilidades de ser clasificados posteriormente como colitis indeterminada o enfermedad de Crohn. Los pacientes que desarrollaron fístulas perianales también fueron más propensos a desarrollar dehiscencia parcial o estenosis de la anastomosis ileoanal.LIMITACIONES:Este estudio abarca casi 40 años durante los cuales ha evolucionado el procedimiento quirúrgico.CONCLUSIONES:Edad temprana al inicio de la enfermedad, menor edad al momento de la cirugía, diagnóstico postoperatorio de enfermedad de Crohn y colitis indeterminada fueron los factores que se correlacionaron con las fístulas perianales. El retraso en la cicatrización de la anastomosis ileoanal con separación parcial y/o estenosis también se correlacionó con la aparición de fístulas perianales. La gravedad de la inflamación rectal en el momento de la cirugía o la presencia de anastomosis con grapas versus anastomosis manual no se correlacionó con el desarrollo de fístulas perianales. Consulte Video Resumen en http://links.lww.com/DCR/B705.

Systematic review with meta-analysis: The prevalence, risk factors and outcomes of upper gastrointestinal tract Crohn's disease.

AIMS: Upper gastrointestinal Crohn's disease (UGI-CD) is an important subclassification of Crohn's Disease (CD). We performed a systematic review and meta-analysis to evaluate the prevalence, risk factors, and clinical outcomes associated with UGI-CD. METHODS: We searched Embase and Medline for articles reporting the clinical information of UGI-CD in CD patients, through 27 October 2020. Disease location and phenotype were coded according to the Montreal classification, and results were pooled with random effects by DerSimonian and Laird model. RESULTS: 26 articles were included. The prevalence of UGI-CD was 13%. UGI-CD was most commonly found in the stomach (56%) and was associated with concurrent ileocolonic involvement (54%). Non-stricturing, non-penetrating UGI-CD was the most common behavioral phenotype (61%). L4-jejunal disease was associated with the highest rates of surgery. Region of origin did not significantly influence the location and phenotype of UGI-CD. Young, male patients presenting with erythema nodosum, aphthous ulcers and stricturing-phenotype are more likely to have UGI-CD, which in turn is linked to increased risk of hospitalization and surgery. CONCLUSION: UGI-CD is present in 13% of patients with CD, and patients with L4-jejunal disease are more likely to require surgery. Further studies examining the effect of ethnicity and region on UGI-CD are needed.

Gene Polymorphisms of NOD2, IL23R, PTPN2 and ATG16L1 in Patients with Crohn's Disease: On the Way to Personalized Medicine?

Genetic and environmental factors are involved in the pathogenesis of inflammatory bowel diseases (IBD). The study aimed at investigating the potential influence of single nucleotide polymorphisms (SNPs) NOD2 rs2066844, NOD2 rs2066845, NOD2 rs2066847, IL23R rs11209026, PTPN2 rs2542151, PTPN2 rs7234029, and ATG16L1 rs2241880 on the response to immunomodulatory therapies and disease course in Crohn's disease (CD). This is an uncontrolled retrospective monocentric study including patients from the IBD outpatient clinic of Heidelberg University Hospital. Therapy responses and disease courses were related to genetic findings. 379 patients with CD were included. The presence of at least one PTPN2 rs7234029 risk allele was associated with nonresponse to anti-interleukin-12/23 treatment (89.9% vs. 67.6%, p = 0.005). The NOD2 rs2066844 risk allele was associated with a first-degree family history of colon cancer (12.7% vs. 4.7%, p = 0.02), the ATG16L1 rs2241880 risk allele with ileal CD manifestation (p = 0.027), and the IL23R rs11209026 risk allele with a higher rate of CD-related surgeries per disease year (0.08 vs. 0.02, p = 0.025). The results of this study underline the relevance of genetic influences in CD. The association of the PTPN2 rs7234029 risk allele with nonresponse to anti-interleukin-12/23 treatment in CD patients is a novel finding and requires further investigation.

Location is important: differentiation between ileal and colonic Crohn's disease.

Crohn's disease can affect any part of the gastrointestinal tract; however, current European and national guidelines worldwide do not differentiate between small-intestinal and colonic Crohn's disease for medical treatment. Data from the past decade provide evidence that ileal Crohn's disease is distinct from colonic Crohn's disease in several intestinal layers. Remarkably, colonic Crohn's disease shows an overlap with regard to disease behaviour with ulcerative colitis, underlining the fact that there is more to inflammatory bowel disease than just Crohn's disease and ulcerative colitis, and that subtypes, possibly defined by location and shared pathophysiology, are also important. This Review provides a structured overview of the differentiation between ileal and colonic Crohn's disease using data in the context of epidemiology, genetics, macroscopic differences such as creeping fat and histological findings, as well as differences in regard to the intestinal barrier including gut microbiota, mucus layer, epithelial cells and infiltrating immune cell populations. We also discuss the translation of these basic findings to the clinic, emphasizing the important role of treatment decisions. Thus, this Review provides a conceptual outlook on a new mechanism-driven classification of Crohn's disease.

Modern Management of Perianal Crohn's Disease: A Review.

Perianal Crohn's disease (CD) is a complex manifestation of CD that affects approximately 10% of patients. The spectrum of disease is quite variable, ranging from relatively mild disease to severe, aggressive manifestations that result in frequent hospitalizations, multiple surgeries, and poor quality of life. Despite significant recent advances in surgical and medical management, treatment remains challenging and frequently requires a multidisciplinary medical-surgical approach. The goal of this article is to review the current literature regarding the work-up, treatment, and future directions of therapy. Crucial features of effective management include the precise identification of manifestations, control of sepsis, limiting rectal inflammation, frequently with use of antitumor necrosis factor agents, and avoidance of extensive surgery.

Classification of Inflammatory Bowel Disease from Formalin-Fixed, Paraffin-Embedded Tissue Biopsies via Imaging Mass Spectrometry.

PURPOSE: Discrimination between ulcerative colitis (UC) and Crohn's disease (CD) by histologic features alone can be challenging and often leads to inaccurate initial diagnoses in inflammatory bowel disease (IBD) patients. This is mostly due to an overlap of clinical and histologic features. However, exact diagnosis is not only important for patient treatment but it also has a socioeconomic impact. It is therefore important to develop and improve diagnostic tools complementing traditional histomorphological approaches. EXPERIMENTAL DESIGN: In this retrospective proof-of-concept study, the utilization of MALDI imaging is explored in combination with multi-variate data analysis methods to classify formalin-fixed, paraffin-embedded (FFPE) colon biopsies from UC (87 biopsies, 14 patients), CD (71 biopsies, 14 patients), and normal colonic (21 biopsies, 14 patients) tissues. RESULTS: The proposed method results in an overall balanced accuracy of 85.7% on patient and of 80.4% on sample level, thus demonstrating that the assessment of IBD from FFPE tissue specimens via MALDI imaging is feasible. CONCLUSIONS AND CLINICAL RELEVANCE: The results emphasize the high potential of this method to distinguish IBD subtypes in FFPE tissue sections, which is a prerequisite for further investigations in retrospective multicenter studies, as well as for a future implementation into clinical routine.

From Paris to Montreal: disease regression is common during long term follow-up of paediatric Crohn's disease.

Introduction: Paediatric Crohn's disease (PCD) often presents with extensive and a frequent pan-enteric phenotype at onset. However, its long term evolution into adulthood, especially since the widespread use of biological agents, is not well characterised. We conducted a single centre cohort study of all PCD patients transitioned to adult care to assess the long term disease evolution in the era of biologic therapy.Methods: We conducted a retrospective observational, study of all PCD patients who were subsequently transferred to the care of an adult gastroenterology unit and had a minimum follow up of 2 years. We examined the case notes for evolution of disease location and behaviour. Disease location and behaviour was characterised using Paris classification at diagnosis and Montreal classification at last follow-up. In addition, we examined variables associated with complicated disease behaviour and the need for CD related intestinal resection.Results: In total, 132 patients were included with a median age at diagnosis of 13 (IQR 11-14) and a median follow up of 11 years (range 4-14). At diagnosis, 23 (17.4%), 39 (29.6%) and 70 (53%) patients had ileal, colonic and ileocolonic disease respectively. In addition, 31 (23.5%) patients had L4a or L4b disease at diagnosis (proximal or distal to the ligament of treitz respectively) and 13 patients (9.8%) had both whilst 27 (20.4%) patients had perianal disease. At diagnosis, 27 (20.4%) patients had complicated disease behaviour but 83 (62.9)% of patients had an extensive 'pan-enteric' phenotype. Of these patients only 55 (66.3%) retained the pan-enteric phenotype at last follow-up (p = .0002). Disease extension was noted in 25 (18.9%) of patients and regression was noted in 47 (35.6%) of patients, whereas upper GI disease was noted in significantly fewer patients at last follow-up (21, 15.9%) (p = .0001). More patients had complicated disease behaviour (46 patients, 34.9%, p = .0018) at last follow-up. There was a high exposure to both thiopurines 121 (91.7%) and biologics 84 (63.6%). The cumulative probability (95% CI) of surgery was 0.05 (0.02, 0.11) at 1 year, 0.17 (0.11, 0.24) at 3 years and 0.22 (0.15, 0.30) at 5 years. Neither disease location nor behaviour were associated with the need for intestinal resectional surgery.Conclusions: Over the course of an extended follow-up period, there appeared to be changes in both disease location and behaviour in PCD. Interestingly, a significant proportion of patients had disease involution which may be related to a high rate of exposure to thiopurines and biologics. We were unable to identify any variables associated with complicated disease course or the need for intestinal surgery.

Lower Risk of B1-to-pB3-Stage Migration in Crohn's Disease Upon Immunosuppressive and Anti-TNF Treatment in the Swiss IBD Cohort Study.

BACKGROUND: While the long-term evolution of disease behavior in Crohn's disease has been well described in the pre-anti-TNF era, our knowledge thereon remains scarce after the introduction of anti-TNF. AIMS: Our investigation examined the long-term evolution of disease concerning Montreal classification's B-stages over time in patients enrolled into the Swiss IBD Cohort Study between 2006 and 2017. METHODS: We analyzed prospectively collected SIBDCS data using a Markov model and multivariate testing for effects of treatment and other confounders on B-stage migration over time. The primary outcome was a transition in disease behavior from B1 to either B2 or pB3, or from B2 to pB3, respectively. RESULTS: The 10- and 15-year probability of remaining in B1 was 0.61 and 0.48, as opposed to a probability to migrate to B2 or B3 of 0.25 or 0.14, and 0.32 or 0.2, after 10 and 15 years, respectively. In multivariate testing, the hazard ratio for migrating from B1 to pB3 (HR 0.27) and from B2 to pB3 (HR 0.12) was lower in patients > 40 years compared to patients < 17 years. We found that immunosuppression (HR 0.38) and treatment with anti-TNF for > 1 year (HR 0.30) were associated with a decreased likelihood of transitioning from stage B1 to pB3. CONCLUSIONS: While in the anti-TNF era most patients with Crohn's disease will eventually develop stricturing and/or penetrating complications, our data indicate that immunosuppressive and anti-TNF treatment for more than 1 year reduce the risk of transitioning from stage B1 to pB3 in the long-term run.

Identifying Patients With Inflammatory Bowel Diseases in an Administrative Health Claims Database: Do Algorithms Generate Similar Findings?

Application of selective algorithms to administrative health claims databases allows detection of specific patients and disease or treatment outcomes. This study identified and applied different algorithms to a single data set to compare the numbers of patients with different inflammatory bowel disease classifications identified by each algorithm. A literature review was performed to identify algorithms developed to define inflammatory bowel disease patients, including ulcerative colitis, Crohn's disease, and inflammatory bowel disease unspecified in routinely collected administrative claims databases. Based on the study population, validation methods, and results, selected algorithms were applied to the Optum Clinformatics® Data Mart database from June 2000 to March 2017. The patient cohorts identified by each algorithm were compared. Three different algorithms were identified from literature review and selected for comparison (A, B, and C). Each identified different numbers of patients with any form of inflammatory bowel disease (323 833; 246 953, and 171 537 patients, respectively). The proportions of patients with ulcerative colitis, Crohn's disease, and inflammatory bowel disease unspecified were 32.0% to 47.5%, 38.6% to 43.8%, and 8.7% to 26.6% of the total population with inflammatory bowel disease, respectively, depending on the algorithm applied. Only 5.1% of patients with inflammatory bowel disease unspecified were identified by all 3 algorithms. Algorithm C identified the smallest cohort for each disease category except inflammatory bowel disease unspecified. This study is the first to compare numbers of inflammatory bowel disease patients identified by different algorithms from a single database. The differences between results highlight the need for validation of algorithms to accurately identify inflammatory bowel disease patients.

Should We Divide Crohn's Disease Into Ileum-Dominant and Isolated Colonic Diseases?

Crohn's disease (CD) is an inflammatory bowel disease that can involve any region of the gastrointestinal tract. First described in 1932 as terminal ileitis or regional enteritis, it predominately involves the ileum with or without colonic involvement. Isolated colonic CD was first described in 1960 and since then the phenotypic classification of CD has evolved to stratify patients into isolated ileal, ileocolonic, or isolated colonic involvement. In the current review we evaluate the published literature regarding differences in epidemiology, natural history, pathogenesis, response to therapy, and disease monitoring, when stratified by disease location. Based on the available evidence consideration could be given to a new classification for CD, which splits it into ileum dominant (isolated ileal and ileocolonic) and isolated colonic disease. This may allow for a more optimized approach to clinical care and scientific research for CD.

Redefining the IBDs using genome-scale molecular phenotyping.

The IBDs, Crohn's disease and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract resulting from an aberrant immune response to enteric microbiota in genetically susceptible individuals. Disease presentation and progression within and across IBDs, especially Crohn's disease, are highly heterogeneous in location, severity of inflammation and other phenotypes. Current clinical classifications fail to accurately predict disease course and response to therapies. Genome-wide association studies have identified >240 loci that confer risk of IBD, but the clinical utility of these findings remains unclear, and mechanisms by which the genetic variants contribute to disease are largely unknown. In the past 5 years, the profiling of genome-wide gene expression, epigenomic features and gut microbiota composition in intestinal tissue and faecal samples has uncovered distinct molecular signatures that define IBD subtypes, including within Crohn's disease and ulcerative colitis. In this Review, we summarize studies in both adult and paediatric patients that have identified different IBD subtypes, which in some cases have been associated with distinct clinical phenotypes. We posit that genome-scale molecular phenotyping in large cohorts holds great promise not only to further our understanding of the diverse molecular causes of IBD but also for improving clinical trial design to develop more personalized disease management and treatment.

Capsule endoscopy findings for the diagnosis of Crohn's disease: a nationwide case-control study.

BACKGROUND: Capsule endoscopy can be used to identify the early stage of small bowel Crohn's disease (CD). We evaluated significant small bowel capsule endoscopy (SBCE) findings that can lead to early diagnosis of CD. METHODS: We retrospectively accumulated clinical and SBCE data of 108 patients (63 with and 45 without CD). Types of small bowel mucosal injuries, including erosion, ulceration, and cobblestone appearance, and the alignment of diminutive lesions were compared between patients with and without CD. Inter- and intra-observer agreement in the determination of lesions was assessed in 25 pairs of SBCE from the two groups. RESULTS: Under SBCE, cobblestone appearance (33% vs. 2%, p < 0.0001), longitudinal ulcers (78% vs. 20%, p < 0.0001), and irregular ulcers (84% vs. 60%, p < 0.01) were more frequently found in patients with CD. Linear erosion (90% vs. 38%, p < 0.0001) and irregular erosion (89% vs. 64%, p < 0.005) were also more frequent in patients with CD. Furthermore, circumferential (75% vs. 9%, p < 0.0001) and longitudinal (56% vs. 7%, p < 0.0001) alignment of diminutive lesions, mainly observed in the 1st tertile of the small bowel, was more frequent in patients with CD. Good intra-observer agreement was found for ulcers, cobblestone appearance, and lesion alignment. However, inter-observer agreement of SBCE findings differed among observers. CONCLUSIONS: Circumferential or longitudinal alignment of diminutive lesions, especially in the upper small bowel, may be a diagnostic clue for CD under SBCE, while inter-observer variations should be cautiously considered when using SBCE.

Association Between Plasma Level of Collagen Type III Alpha 1 Chain and Development of Strictures in Pediatric Patients With Crohn's Disease.

BACKGROUND & AIMS: There are few serum biomarkers to identify patients with Crohn's disease (CD) who are at risk for stricture development. The extracellular matrix components, collagen type III alpha 1 chain (COL3A1) and cartilage oligomeric matrix protein (COMP), could contribute to intestinal fibrosis. We investigated whether children with inflammatory CD (B1) who later develop strictures (B2) have increased plasma levels of COL3A1 or COMP at diagnosis, compared with children who remain B1. We compared results with previously studied biomarkers, including autoantibodies against colony-stimulating factor 2 (CSF2). METHODS: We selected 161 subjects (mean age, 12.2 y; 62% male) from the Risk Stratification and Identification of Immunogenic and Microbial Markers of Rapid Disease Progression in Children with Crohn's cohort, completed at 28 sites in the United States and Canada from 2008 through 2012. The children underwent colonoscopy and upper endoscopy at diagnosis and were followed up every 6 months for 36 months; plasma samples were collected at baseline. Based on CD phenotype, children were separated to group 1 (B1 phenotype at diagnosis and follow-up evaluation), group 2 (B2 phenotype at diagnosis), or group 3 (B1 phenotype at diagnosis who developed strictures during follow-up evaluation). Plasma samples were collected from patients and 40 children without inflammatory bowel disease (controls) at baseline and analyzed by enzyme-linked immunosorbent assay to measure COL3A1 and COMP. These results were compared with those from a previous biomarker study. The Kruskal-Wallis test and the pairwise Dunn test with Bonferroni correction were used to compare differences among groups. RESULTS: The median baseline concentration of COL3A1 was significantly higher in plasma from group 3 vs group 1 (P < .01) and controls (P = .01). Median baseline plasma concentrations of COMP did not differ significantly among groups. A model comprising baseline concentrations of COL3A1 and anti-CSF2 identified patients with B2 vs B1 CD with an area under the curve of 0.80 (95% CI, 0.71-0.89); the combined concentration identified patients with strictures with a sensitivity value of 0.70 (95% CI, 0.55-0.83) and a specificity value of 0.83 (95% CI, 0.67-0.93). CONCLUSIONS: We found median plasma concentrations of COL3A1, measured by enzyme-linked immunosorbent assay at diagnosis, to be significantly higher in patients with CD who later developed strictures than in patients without strictures. The combination of concentrations of COL3A1 and anti-CSF2 might be used to identify pediatric patients at CD diagnosis who are at risk for future strictures. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00790543.

Crohn Disease: A 5-Point MR Enterocolonography Classification Using Enteroscopic Findings.

OBJECTIVE: The objectives of our study were to establish the efficacy of a 5-point MR enterocolonography classification for assessing Crohn disease (CD) activity, compare this classification with a validated MRI score (i.e., the MR index of activity [MaRIA]), and compare both with endoscopic findings, which were assessed using the Crohn disease endoscopic index of severity (CDEIS). MATERIALS AND METHODS: Seventy (derivation cohort) and 50 (validation cohort) patients with CD were retrospectively enrolled in this study. We developed a 5-point MR enterocolonography classification that consists of visual assessments alone. MR enterocolonography results were evaluated for each bowel segment (rectum; sigmoid, descending, transverse, and ascending colon; terminal and proximal ileum; and jejunum) by one observer in the derivation phase and independently by three observers in the validation phase using the 5-point MR enterocolonography classification lexicon and MaRIA. Areas under the ROC curves (AUCs) in discriminating endoscopic deep ulcers were compared between the MR enterocolonography classification and MaRIA. Interobserver reproducibility was assessed using weighted kappa coefficients. RESULTS: The AUCs of the MR enterocolonography classification were 89.0% in the derivation phase and 88.5%, 81.0%, and 77.3% for the three observers in the validation phase. The AUCs of the MR enterocolonography classification were statistically noninferior to those of MaRIA (p < 0.001). The cross-validation accuracy was 81.9% in the derivation phase and 81.5% in the validation phase. The MR enterocolonography classification showed good reproducibility. CONCLUSION: The 5-point MR enterocolonography classification was shown to be effective for evaluating CD activity in the large and small bowel.

Study of disease phenotype and its association with prognosis of paediatric inflammatory bowel disease in China.

BACKGROUND: To investigate the unique features of inflammatory bowel disease (IBD) in children, we wanted to identify whether there might be a strong correlation between the disease phenotype and its prognosis at various ages in paediatric patients. METHODS: We collected data from patients diagnosed with IBD (ulcerative colitis (UC) or Crohn's disease (CD)) from 2002 to 2016. The diagnosis was made according to the Porto criteria and Paris Classification. Patient characteristics, clinical manifestations and treatments were collected. Risk factors for surgery, mortality and relapse were analysed by Cox proportional hazard models. RESULTS: Of the 143 patients, 113 had CD, and 30 had UC; there were 89 males and 54 females with a median age of 9 years (y). Thirteen patients in the 0-2 y group were identified as having mutations in IL-10 receptor A, and this mutation was significantly more common in this age group than in 3-9 and 10-16 y patients. The risk factor for surgery was the B3 phenotype; risk factors for death were age 0-2 y and B3 phenotype; 0-2 y, B3 phenotype and steroid dependency were risk factors for early relapse. CONCLUSIONS: Clinical manifestations of the onset of IBD in infants and toddlers were extensive and aggressive and were closely associated with early relapse and death. It is of particular interest that some of these patients developed IBD due to monogenic disorders; thus, introduction of genetic testing is essential for these patients.

Late-Onset Crohn's Disease Is A Subgroup Distinct in Genetic and Behavioral Risk Factors With UC-Like Characteristics.

Background: Age of onset is linked to variations in clinical phenotypes and natural history in Crohn's disease (CD). We aim to define etiologically more homogenous subgroups in CD based on ages of onset. Methods: We examined the distribution of CD polygenetic risk score (PRS) across ages of diagnosis in a Caucasian cohort of 2344 independent CD patients. We identified subgroups with a distinct distribution of PRS and compared those groups in genetics, demographic characteristics, clinical subphenotypes, and serological markers. The results were replicated in an independent cohort of 13,065 CD patients from the International Inflammatory Bowel Diseases Genetic Consortium (IIBDGC). Results: We identified a late-onset (LO) subgroup in CD (age at diagnosis ≥ 55 years) with significantly lower PRS compared with the intermediate group (age at diagnosis between 5 and 55 years) in both cohorts. Smoking cessation, a risk factor for ulcerative colitis (UC) and protective factor for CD, had a higher rate in this LO subgroup in comparison with the intermediate group. We also compared the LO group with the intermediate group, and, consistent with previous reports, the LO group more often had colonic CD, had less penetrating disease behavior, and had less need for surgery. Serological analysis showed that LO CD patients were more antineutrophil cytoplasmic antibody positive and less antisaccharomyces cerevisiae antibody positive compared with the intermediate group. Variance component analysis indicated that overall genetic contribution to LO CD was lower relative to the middle group, and genetic heterogeneity testing indicated that LO CD was different from the middle group in underlying genetic architecture. Conclusions: Late-onset CD is subgroup distinct in genetic and behavioral risk factors with UC-like characteristics. 10.1093/ibd/izy148_video1izy148.video15791413461001.

Validation of the "German Inflammatory Bowel Disease Activity Index (GIBDI)": An Instrument for Patient-Based Disease Activity Assessment in Crohn's Disease and Ulcerative Colitis.

INTRODUCTION: Assessment of disease activity in Crohn's disease (CD) and ulcerative colitis (UC) is usually based on the physician's evaluation of clinical symptoms, endoscopic findings, and biomarker analysis. The German Inflammatory Bowel Disease Activity Index for CD (GIBDICD) and UC (GIBDIUC) uses data from patient-reported questionnaires. It is unclear to what extent the GIBDI agrees with the physicians' documented activity indices. METHODS: Data from 2 studies were reanalyzed. In both, gastroenterologists had documented disease activity in UC with the partial Mayo Score (pMS) and in CD with the Harvey Bradshaw Index (HBI). Patient-completed GIBDI questionnaires had also been assessed. The analysis sample consisted of 151 UC and 150 CD patients. Kappa coefficients were determined as agreement measurements. RESULTS: Rank correlations were 0.56 (pMS, GIBDIUC) and 0.57 (HBI, GIBDICD), with p < 0.001. The absolute agreement for 2 categories of disease activity (remission yes/no) was 74.2 % (UC) and 76.6 % (CD), and for 4 categories (none/mild/moderate/severe) 60.3 % (UC) and 61.9 % (CD). The kappa values ranged between 0.47 for UC (2 categories) and 0.58 for CD (4 categories). DISCUSSION: There is satisfactory agreement of GIBDI with the physician-documented disease activity indices. GIBDI can be used in health care research without access to assessments of medical practitioners. In clinical practice, the index offers a supplementary source of information.

Characteristics and Incidence Trends for Pediatric Inflammatory Bowel Disease in Daegu-Kyungpook Province in Korea: a Multi-Center Study.

BACKGROUND: Inflammatory bowel disease (IBD) is a heterogeneous chronic disease of unknown etiology. Although it is an important disease that shows a rapid increase in pediatric population, there are no pediatric studies that represent a specific region in Korea. Therefore, we studied the epidemiological and phenotypic characteristics of pediatric IBD in Daegu-Kyungpook province, Korea. METHODS: We included 122 children with pediatric IBD initially diagnosed at one of four university hospitals in Daegu-Kyungpook province between July 2010 and June 2016. We investigated the incidence trends, and the clinical characteristics at diagnosis were compared by Paris classification. RESULTS: We included 122 children: 98 with Crohn's disease (CD) and 24 with ulcerative colitis (UC). The average age at diagnosis was 13.6 years for IBD. The incidence shows an increasing trend. CD showed a significant increase, whereas UC appears to be increasing slowly. In CD, there was a significant male predominance. For disease activity sites, the most common location was L3 (77.6%), indicating ileocolonic involvement as the major type. B1 (88.8%) was the most common disease behaviors type. Perianal disease was noted in 43 patients (43.9%) and weight loss in 60 (61.2%). In UC, E4 (58.4%) was the most common disease activity site, indicating pancolonic involvement as the major type. CONCLUSION: We found that the number of pediatric patients with IBD is increasing rapidly in Daegu-Kyungpook province in Korea. Our study also revealed that the characteristics of pediatric IBD in our province differ somewhat from those of pediatric IBD in Western countries.

Crohn's Disease Candidate Gene Alleles Predict Time to Progression from Inflammatory B1 to Stricturing B2, or Penetrating B3 Phenotype.

AIM: Crohn's disease (CD) patients are mostly diagnosed with the uncomplicated inflammatory form of disease; however, the majority will progress to complicated stricturing or penetrating disease over time. It is important to identify patients at risk for disease progression at an early stage. The aim of our study was to examine the role of 33 candidate CD genes as possible predictors of disease progression and their influence on time to progression from an inflammatory to a stricturing or penetrating phenotype. METHODS: Patients with an inflammatory phenotype at diagnosis were followed for 10 years and 33 CD-associated polymorphisms were genotyped. To test for association with CD, 449 healthy individuals were analyzed as the control group. RESULTS: Ten years after diagnosis, 39.1% of patients had not progressed beyond an inflammatory phenotype, but 60.9% had progressed to complicated disease, with average time to progression being 5.91 years. Association analyses of selected single nucleotide polymorphisms (SNPs) confirmed associations with CD for 12 SNPs. Furthermore, seven loci were associated with disease progression, out of which SNP rs4263839 in the gene TNFSF15 showed the strongest association with disease progression and the frameshift mutation rs2066847 in the gene NOD2 showed the strongest association with time to progression. CONCLUSIONS: The results of our study identified specific genetic biomarkers as useful predictors of both disease progression and speed of disease progression in patients with CD.