Crohn's Disease after Proctocolectomy and IPAA for Ulcerative Colitis.

BACKGROUND: Proctocolectomy with IPAA is considered curative for ulcerative colitis. However, signs of Crohn's disease can develop postoperatively in some cases. OBJECTIVE: Our aim was to document the postoperative diagnosis of Crohn's disease, to identify potential preoperative predictive factors, and to review the evolution of patients on treatment. DESIGN: This is a retrospective cohort study. SETTINGS: This study was conducted at a tertiary care center in Montreal, Canada. PATIENTS: A total of 301 patients underwent an IPAA for ulcerative colitis between 1985 and 2014. MAIN OUTCOME MEASURES: The primary outcome was the cumulative incidence of the postoperative diagnosis of Crohn's disease. RESULTS: During a median follow-up of 68 months, Crohn's disease was diagnosed at a median time of 77 months (8-270) in 38 patients (12.6%). The cumulative incidence of Crohn's disease was 7.5% at 5 years postoperatively and gradually increased to 17.7% and 33.0% at 10 and 20 years. The following predictive factors for Crohn's disease were observed on univariate analysis: current tobacco smoking at surgery (HR 3.56 (95% CI, 1.54-8.22)), suspicion of indeterminate colitis (HR 3.50 (95% CI, 1.69-7.24)), presence of mouth ulcers before surgery (HR 2.16 (95% CI, 1.03-4.53)), and age at diagnosis of ulcerative colitis (HR 0.94 (95% CI, 0.90-0.97)). Suspicion of indeterminate colitis (HR 3.18 (95% CI 1.46-6.93); p = 0.004) and age at diagnosis (HR 0.95 (95% CI, 0.91-0.99); p = 0.018) remained statistically significant on multivariate analysis. Postoperative inflammatory disease was controlled by medical therapy in most patients. Removal of the pouch was necessary in 16% of patients with Crohn's disease. LIMITATIONS: This was a retrospective single-center study. CONCLUSIONS: Diagnosis of Crohn's disease can occur at a distance from surgery with an increasing cumulative incidence over time. Preoperative predictive factors are few and should not determine candidacy for surgery. Therapeutic options are identical to those available for treatment of typical Crohn's disease and allow a favorable evolution in most patients. See Video Abstract at http://links.lww.com/DCR/B372. BROTE DE CROHN DESPUS DE UNA PROCTOCOLECTOMA CON ANASTOMOSIS DE RESERVORIO LEOANAL EN CASOS DE COLITIS ULCEROSA: ANTECEDENTES:La proctocolectomía con reservorio ileo-anal se considera curativa para la colitis ulcerosa. Sin embargo, signos de enfermedad de Crohn pueden desarrollarse después de la operación en algunos casos.OBJETIVO:Nuestro objetivo fue documentar el diagnóstico postoperatorio de la enfermedad de Crohn, identificar posibles factores predictivos preoperatorios y revisar la evolución de los pacientes con tratamiento.DISEÑO:Estudio retrospectivo de cohortes.AJUSTES:Centro de atención terciaria en Montreal, Canadá.PACIENTES:301 pacientes portadores de un reservorio íleo-anal realizados por colitis ulcerosa entre 1985 y 2014.PRINCIPALES MEDIDAS DE RESULTADO:Acumulación de la incidencia en el diagnóstico postoperatorio de enfermedad de Crohn.RESULTADOS:Durante una media de 68 meses de seguimiento, la enfermedad de Crohn fué diagnosticada en un tiempo medio de 77 meses (8-270) en 38 pacientes (12,6%). La acumulación de incidencia de la enfermedad de Crohn fue del 7,5% a los 5 años después de la operación y aumentó gradualmente a 17,7 y 33,0% a los 10 y 20 años. Los siguientes factores predictivos para la enfermedad de Crohn se observaron en el análisis univariado: tabaquismo activo al momento de la cirugía (cociente de riesgo (HR) 3.56 (intervalo de confianza del 95% (IC) 1.54-8.22)), sospecha de colitis indeterminada (HR 3.50 (IC del 95% 1.69-7.24)), presencia de úlceras en la boca antes de la cirugía (HR 2.16 (IC 95% 1.03-4.53)) y edad al diagnóstico de colitis ulcerosa (HR 0.94 (IC 95% 0.90-0.97)). La sospecha de colitis indeterminada (HR 3.18 (IC 95% 1.46-6.93), p = 0.004) y la edad al momento del diagnóstico (HR 0.95 (IC 95% 0.91-0.99), p = 0.018) permanecieron estadísticamente significativos en el análisis multivariado. La reacción inflamatoria intestinal postoperatoria fue controlada con tratamiento médico en la mayoría de los pacientes. El retiro del reservorio íleo-anal fue necesario en 16% de los pacientes con enfermedad de Crohn.LIMITACIONES:Estudio retrospectivo de centro único.CONCLUSIONES:El diagnóstico de la enfermedad de Crohn puede ocurrir a distancia de la cirugía con la acumulación de incidencia creciente con el tiempo. Los factores predictivos preo-peratorios son pocos y no pueden determinar la candidatura para la cirugía. Las opciones terapéuticas son idénticas a las disponibles para el tratamiento de la enfermedad de Crohn típica y permiten una evolución favorable en la mayoría de los pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B372. (Traducción-Dr. Xavier Delgadillo).

Patients With Inflammatory Bowel Disease Are Unaware of the Impact of Smoking on Their Disease.

BACKGOUND: Tobacco is one of the most significant risk factors for inflammatory bowel disease (IBD). GOALS: The main objective was to assess the knowledge of patients with IBD regarding the effects of tobacco on their disease. Secondary objectives were to determine the source of their knowledge, the influence of their knowledge on their intent to quit smoking, and the association between patients' characteristics and their knowledge. STUDY: Patients with IBD completed a self-administered questionnaire on demographic data, severity of disease, and effects of tobacco on their disease. RESULTS: In total 259 patients [182 with Crohn's disease, 77 with ulcerative colitis (UC)] participated. The prevalence of current smokers, exsmokers, and nonsmokers was 19.6%, 40.2%, and 40.2%, respectively. Patients with Crohn's disease were more aware of the effects of tobacco on their disease compared with those with UC (57.7% vs. 13.0%, P<0.0001). In informed patients, the main source of information was the gastroenterologist (56.9%). The intent to quit smoking was superior in informed patients compared with those uninformed (78.6% vs. 47.8%, P=0.046). Older patients (odds ratio=0.97, P=0.01) and patients with UC (odds ratio=0.11, P<0.0001) were less likely to be informed. CONCLUSIONS: Only half of patients with IBD are aware of the risks of smoking associated with their disease, whereas their intent to quit smoking is directly related to their awareness. In the scope of IBD's treatment, management of smoking cessation should be undertaken in all smokers.

Biologics in inflammatory bowel disease: what are the data?

BACKGROUND: Over the last decade, biologics have gained an important place for the treatment of moderate to severe inflammatory bowel disease (IBD), and many randomized control trials have evaluated their efficacy. AIM: The goal of this review is to analyze the results of these trials and to highlight the evidence and indications emerging from these studies for their implementation in the management of IBD patients. METHODS: A PubMed search was realized to screen high-quality clinical trials studying biologic agents currently available in clinics for the treatment of IBD. Words used were: "infliximab," "adalimumab," "certolizumab," "golimumab," "natalizumab," "vedolizumab," "ustekinumab," "azathioprine," "methotrexate," "Crohn's disease," and "ulcerative colitis." RESULTS: In Crohn's disease, studies supporting induction and maintenance therapies were documented for infliximab, adalimumab, certolizumab, natalizumab, vedolizumab, and ustekinumab. Infliximab, adalimumab, and certolizumab have evidences for fistulizing Crohn's disease and only infliximab and adalimumab have evidences for mucosal healing. In ulcerative colitis, studies supporting induction, maintenance, and mucosal healing were found with infliximab, adalimumab, golimumab, and vedolizumab. Only infliximab was associated with evidences for combination therapy with thiopurine and acute severe colitis in ulcerative colitis. CONCLUSION: Management with biologics in IBD patients is well validated by high-quality clinical trials.

CD47 fusion protein targets CD172a+ cells in Crohn's disease and dampens the production of IL-1ß and TNF.

In mice, the transfer of CD172a(+) (SIRP-α) dendritic cells (DCs) elicits T cell-driven colitis, whereas treatment with CD47-Fc protein, a CD172a-binding agent, confers protection. The aim of this study was to elucidate the nature and functional properties of human CD172a(+) DCs in chronic intestinal inflammation. Here, we show that CD172a(+)CD11c(+) cells accumulate in the mesenteric lymph nodes (mLNs) and inflamed intestinal mucosa in patients with Crohn's disease (CD). These cells are distinct from resident DCs and may coexpress markers typically associated with monocyte-derived inflammatory DCs such as CD14 and/or DC-SIGN, E-Cadherin, and/or CX3CR1. Spontaneous IL-1ß and TNF production by HLA-DR(+) cells in CD tissues is restricted to those expressing CD172a. An avidity-improved CD47 fusion protein (CD47-Var1) suppresses the release of a wide array of inflammatory cytokines by CD172a(+) cells, which may include HLA-DR(-)CD172a(+) neutrophils, in inflamed colonic explant cultures and impairs the ability of HLA-DR(+)CD172a(+) cells to activate memory Th17 but not Th1 responses in mLNs. In conclusion, targeting CD172a(+) cells may represent novel therapeutic perspectives for patients with CD.

Human basophils interact with memory T cells to augment Th17 responses.

Basophils are a rare population of granulocytes that have long been associated with IgE-mediated and Th2-associated allergic diseases. However, the role of basophils in Th17 and/or Th1 diseases has not been reported. In the present study, we report that basophils can be detected in the mucosa of Th17-associated lung and inflammatory bowel disease and accumulate in inflamed colons containing large quantities of IL-33. We also demonstrate that circulating basophils increased memory Th17 responses. Accordingly, IL-3- or IL-33-activated basophils amplified IL-17 release in effector memory T cells (T(EM)), central memory T cells (T(CM)), and CCR6(+) CD4 T cells. More specifically, basophils promoted the emergence of IL-17(+)IFN-γ(-) and IL-17(+)IFN-γ(+), but not IL-17(-)IFN-γ(+) CD4 T cells in T(EM) and T(CM). Mechanistic analysis revealed that the enhancing effect of IL-17 production by basophils in T(EM) involved the ERK1/2 signaling pathway, occurred in a contact-independent manner, and was partially mediated by histamine via H(2) and H(4) histamine receptors. The results of the present study reveal a previously unknown function for basophils in augmenting Th17 and Th17/Th1 cytokine expression in memory CD4 T cells. Because basophils accumulated in inflamed inflammatory bowel disease tissues, we propose that these cells are key players in chronic inflammatory disorders beyond Th2.

Phenotypic and genotypic characteristics of inflammatory bowel disease in French Canadians: comparison with a large North American repository.

OBJECTIVES: Phenotype characteristics of inflammatory bowel disease (IBD) may differ significantly among ethnic subpopulations. The aim of this study was to characterize the IBD phenotype in French Canadians, the most prominent founder population in North America. METHODS: Using well-characterized phenotype data in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)-IBD Genetics Consortium repository on patients with IBD, we compared phenotypic characteristics of 202 French Canadians with those of 1,287 other Caucasian patients. These included diagnosis, anatomical location, disease behavior, extraintestinal manifestations, surgical history, and family history of IBD. RESULTS: French-Canadian patients with Crohn's disease (CD) were less likely to have stricturing disease (11 vs. 21%, P=0.005; odds ratio (OR): 0.45, 95% confidence interval (95% CI): 0.24-0.85). Using a stringent definition of ethnicity (three out of four grandparents being French Canadians, as opposed to self-report, n=148), French Canadians had a tendency toward developing fistulizing CD (37 vs. 28%, P=0.07), and there was an increased prevalence of sacroiliitis among those with IBD (4 vs. 2%, P=0.045). Among French Canadians, the numbers of current smokers in CD (40 vs. 25%, P=0.006) and former smokers in ulcerative colitis (UC) (35 vs. 20%, P=0.03) were significantly higher. The prevalence of one of the three main variants of nucleotide-binding oligomerization domain containing 2 (NOD2) single-nucleotide polymorphisms (SNPs) among French-Canadian CD patients was 43.2%. The 3020insC SNP correlated with small bowel disease in French Canadians (25 [corrected] vs. 0%, P=0.006). CONCLUSIONS: French Canadians show an IBD phenotype profile distinct from other Caucasian IBD populations, with an accentuated association between smoking status and IBD. This unique profile may have implications regarding the need for a different approach to the management of IBD in this population.

Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.

Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1 x 10(-13), combined odds ratio OR = 0.73) and 12q15 (rs1558744, combined P = 2.5 x 10(-12), combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0 x 10(-16), combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3 x 10(-8), combined OR = 0.56; rs10889677, combined P = 1.3 x 10(-8), combined OR = 1.29).

Inflammatory bowel disease characteristics among African Americans, Hispanics, and non-Hispanic Whites: characterization of a large North American cohort.

OBJECTIVES: Inflammatory bowel disease (IBD), comprising primarily of Crohn's disease (CD) and ulcerative colitis (UC), is increasingly prevalent in racial and ethnic minorities. This study was undertaken to characterize racial differences in disease phenotype in a predominantly adult population. METHODS: Phenotype data on 830 non-Hispanic white, 127 non-Hispanic African American, and 169 Hispanic IBD patients, recruited from six academic centers, were abstracted from medical records and compiled in the NIDDK-IBD Genetics Consortium repository. We characterized racial differences in family history, disease location and behavior, surgical history, and extraintestinal manifestations (EIMs) using standardized definitions. RESULTS: African American CD patients were more likely than whites to develop esophagogastroduodenal CD (OR = 2.8; 95% CI: 1.4-5.5), colorectal disease (OR = 1.9; 95% CI: 1.1-3.4), perianal disease (OR = 1.7; 95% CI: 1.03-2.8), but less likely to have ileal involvement (OR = 0.55; 95% CI: 0.32-0.96). They were also at higher risk for uveitis (OR = 5.5; 95% CI: 2.3-13.0) and sacroiliitis (OR = 4.0; 95% CI: 1.55-10.1). Hispanics had higher prevalence of perianal CD (OR = 2.9; 95% CI: 1.8-4.6) and erythema nodosum (3.3; 95% CI: 1.7-6.4). Among UC patients, Hispanics had more proximal disease extent. Both African American and Hispanic CD patients, but not UC patients, had lower prevalences of family history of IBD than their white counterparts. CONCLUSIONS: There are racial differences in IBD family history, disease location, and EIMs that may reflect underlying genetic variations and have important implications for diagnosis and management of disease. These findings underscore the need for further studies in minority populations.