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Intestinal fibrosis is a major complication of the inflammatory bowel diseases (IBD) and although inflammation is necessary for its development, it would appear that it plays a minor role in its progression as anti-inflammatory treatments in IBD do not prevent fibrosis once it has started. The processes that regulate fibrosis would thus appear to be distinct from those regulating inflammation and, therefore, a detailed understanding of these pathways is vital to the development of anti-fibrogenic strategies. There have been several recent reviews exploring what is known, and what remains unknown, about the development of intestinal fibrosis. This review is designed to add to this literature but with a focus on the cellular components that are involved in the development of fibrogenesis and the major molecular mediators that impact on these cells. The aim is to heighten the understanding of the factors involved in intestinal fibrogenesis so that detailed research can be encouraged in order to advance the processes that could lead to effective treatments., (© 2015 Published on behalf of European Crohn’s and Colitis Organisation.)

The fourth scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on the relevance of intestinal fibrosis in the disease course of inflammatory bowel disease (IBD). The objective was to better understand the pathophysiological mechanisms of intestinal fibrosis, to identify useful markers and imaging modalities of fibrosis in order to assess its presence and progression, and, finally, to point out possible approaches for the prevention and the treatment of fibrosis. The results of this workshop are presented in three separate manuscripts. This first section describes the most important mechanisms that contribute to the initiation and progression of intestinal fibrosis in IBD including the cellular and molecular mediators, the extracellular matrix molecules and matrix metalloproteinases/tissue inhibitors of metalloproteinases-system, the microbiota products, the role of fat, genetic and epigenetic factors, as well as the currently available experimental models. Furthermore, it identifies unanswered questions in the field of intestinal fibrosis and provides a framework for future research., (Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: There are concerns about the effect of inflammatory bowel diseases (IBD) on fertility, pregnancy and pregnancy outcomes, but no long-term data on the health of offspring born to IBD mothers. The aims were to assess the short- and long-term effects of maternal IBD on the morbidity and development of their offspring., Methods: Female IBD patients and controls completed questionnaires on their pregnancy outcome, and their offspring's short- and long-term health and development., Results: IBD and control mothers (159 and 175, respectively) were recruited. Medical data of 412 IBD and 417 control offspring were recorded. IBD mothers had significantly more singleton pregnancies, their offspring's birth weight was significantly lower, and they breastfed significantly less compared to controls (P=0.028, 0.007, and <0.0001, respectively). There were significantly more congenital anomalies (mainly limb deformities) among the IBD offspring (P<0.035). Offspring born post-maternal IBD diagnosis, compared to pre-diagnosis, tended to have more neurodevelopmental problems (e.g., gross motor delay, P=0.03). IBD was significantly more prevalent in the offspring of IBD mothers, while allergies and atopic dermatitis were more frequent in offspring of control mothers. More offspring of IBD mothers taking medications during pregnancy were born preterm and had lower birth weights compared to offspring of IBD mothers not taking medications during pregnancy. Children of mothers taking steroids had the lowest birth weights, compared to those of IBD mothers taking 5ASAs or immunomodulators., Conclusions: Maternal IBD affects pregnancy and the offspring's immediate and long-term morbidity, specifically, congenital anomalies and neurodevelopmental problems., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: It has long been believed that breastfeeding provides protection against ulcerative colitis and Crohn disease. Studies designated to test this hypothesis were conducted without reaching conclusive results., Objective: The aim of this meta-analysis was to examine the role of breastfeeding in preventing inflammatory bowel disease and to summarize the evidence gathered about this subject., Design: A meta-analysis was performed on 17 relevant articles that were found by using MEDLINE, EMBASE, the Internet, and articles' references. The publications were fully reviewed and divided, on the basis of their quality, into 3 groups., Results: Studies showed heterogeneous results. The pooled odds ratios of all the 17 reviewed studies, calculated according to the random-effects model, were 0.67 (95% CI: 0.52, 0.86) for Crohn disease and 0.77 (0.61, 0.96) for ulcerative colitis. However, only 4 studies for Crohn disease and 4 for ulcerative colitis were eventually included in the highest quality group. In this group, the pooled odds ratio was 0.45 (0.26, 0.79) for Crohn disease and 0.56 (0.38, 0.81) for ulcerative colitis., Conclusions: The results of this meta-analysis support the hypothesis that breastfeeding is associated with lower risks of Crohn disease and ulcerative colitis. However, because only a few studies were graded to be of high quality, we suggest that further research, conducted with good methodology and large sample sizes, should be carried out to strengthen the validity of these observations.

Described is a 15-year-old boy who presented with an ulcerative destructive soft palate lesion, skin lesions, and prolonged history of weakness and abdominal pain associated with abnormal liver functions. A midline destructive lesion was considered. However biopsies revealed chronic inflammation. After thorough investigation including colon, liver, skin and uvular biopsies a diagnosis of Inflammatory Bowel Disease in association of Autoimmune Sclerosing Cholangitis was made. Treatment with steroids improved his symptoms, normalized liver functions and enhanced healing of the skin and palatal lesions. This case demonstrates the involvement of the palate in a rare systemic disease and to our knowledge is the first description of Sclerosing Cholangitis presenting as an ulcerative lesion of the soft palate.

Background: The association between smoking and inflammatory bowel disease (IBD) is well established. There are, however, no large scale studies of passive smoking in inflammatory bowel disease and this has never been surveyed in the Jewish population of Israel., Aim: To study the passive smoking exposure of Jewish IBD patients in Israel in a large scale multicentre study., Methods: Patients with established IBD, aged 18-70 years, were interviewed regarding smoking and other habits. Two controls, one clinic and one neighbourhood, matched by age, sex, community group, and education, were sought for each subject., Results: Five hundred and thirty-four patients (273 ulcerative colitis (UC) and 261 Crohn's disease (CD)), 478 clinic controls and 430 community controls were interviewed. There were no significant differences in the passive smoking habits between IBD patients and their controls. Fifty-one percent of UC patients, 50% of the clinic controls and 58% of the community controls were exposed to passive smoking at home (NS); similar results were found among CD patients (50%, 55% and 56%, respectively). When a quantitative exposure index was used UC patients were significantly less exposed to passive smoking than were their community controls (7.46 +/- 8.40 vs 9.36 +/- 9.46, n = 229, P< 0.031). There was no difference in the exposure to passive smoking among CD patients and their controls. No differences in exposure to passive smoking were found when UC patients who had never smoked were compared with their controls. When the quantitative index was used 'never-smoked' CD patients tended to be less exposed to passive smoking at home than their community controls (5.40 +/- 7.60 vs 8.04 +/- 8.72, P < 0.05)., Conclusion: There is a lack of association between passive smoking and IBD in Jewish patients in Israel. When a quantitative exposure index was used UC patients were found to be less exposed to passive smoking than their community controls.

Aim: Environmental as well as genetic factors play a role in the pathogenesis of inflammatory bowel diseases. The effects of smoking and diet have been demonstrated. Other factors have not been extensively investigated., Patients: Preillness non dietary habits and factors were studied in 88 patients with recent onset of inflammatory bowel diseases (55 with ulcerative colitis and 33 with Crohn's disease) and in matched 76 population and 68 clinic controls., Results: No significant differences were found in relation to education, housing, birth weight, breast feeding in infancy and current weight. The current body mass index was significantly lower in patients as compared to clinic controls (p < 0.05). More patients had low levels of physical activity during the preillness period as compared to controls (p < 0.001 vs clinic controls), while more controls engaged in moderate (p < 0.05) or high levels of physical activity in the corresponding periods. Patients spent fewer hours in strenuous physical activity as compared to controls (NS). Patients slept fewer hours per day (p < 0.05 vs clinic controls). More patients than controls experienced stressful life events during the year prior to onset of symptoms (p < 0.05 for patients with Crohn's disease against both controls and all patients vs population controls)., Conclusions: Other environmental factors besides smoking and diet may affect the pathogenesis of inflammatory bowel disease.

Background: The effect of environmental factors has been demonstrated in the pathogenesis of inflammatory bowel disease (IBD). Nutrition may be one of them., Aim: To investigate the pre-illness diet in patients with recent IBD in comparison with matched population and clinic controls., Methods: Quantified dietary histories were obtained from 87 patients with recent IBD (54 ulcerative colitis (UC) and 33 Crohn's disease (CD)) and 144 controls. Odds ratios (OR) for IBD were derived for intake levels of various foods., Results: A high sucrose consumption was associated with an increased risk for IBD (OR 2.85 (p = 0.03) against population controls and 5.3 (p = 0.00) against clinic controls). Lactose consumption showed no effect while fructose intake was negatively associated with risk for IBD (NS). Similar trends were noted in UC and CD. A high fat intake was associated with an increased risk for UC; this was particularly marked for animal fat (OR 4.09, p = 0.02) and cholesterol (OR 4.57, p = 0.02). A high intake of fluids (p = 0.04), magnesium (p = 0.04), vitamin C, and fruits (NS) was negatively associated with the risk for IBD, while a positive association was found for retinol (p = 0.01). Most of the findings were similar in UC and CD except for potassium and vegetable consumption which showed a negative association only with risk for CD., Conclusions: An association was found between pre-illness diet and subsequent development of UC and CD. The effect of dietary components may be primary or modulatory.

We determined the relative utility of inflammatory markers in evaluating disease activity in adolescent patients with inflammatory bowel disease (IBD). Sixty-one adolescent patients and 50 age and sex matched volunteers who served as controls were evaluated prospectively. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cell count (WBCC), and the leukocyte adhesiveness/aggregation (LAA) test were determined in each patient. There were 28 subjects in remission and 33 in relapse. Their percentage of aggregated white blood cells in the peripheral blood was 7 +/- 5 and 16 +/- 8, respectively, when compared with the control group (5 +/- 3) (p < 0.0001). Moreover, the LAA test was the only one which could effectively classify patients with IBD into their correct diagnostic categories of remission, mild-moderate, or moderate-severe disease activity. The LAA test is superior to other acute phase reactants used in daily practice to detect the presence of inflammation as well as for the assessment of its severity in adolescent patients with IBD. In addition, our findings may have biological relevance to the disease process and its potential manipulation by anti-adhesive agents.

Background/aims: An excess of smokers in patients with Crohn's disease (CD) and a paucity of smokers in patients with ulcerative colitis (UC) were reported in many studies. The aim of this study was to examine the association between smoking and inflammatory bowel disease (IBD) in Israel., Methods: Two independent studies were performed. Patients with recent IBD in comparison with matched population and outpatient controls and patients with chronic UC and CD were studied. Altogether, 475 subjects were investigated., Results: In both studies, the presence of current smokers was lower in CD (9% and 18%) than in UC (24% and 26%). The proportions of nonsmokers in both studies were similar (UC, 61% and 65%; CD, 67% and 70%) and comparable to those found in their two control groups (57% and 61%; 63% and 68%, respectively) and to the general population of Israel. All differences in smoking habits between patient groups and their controls were not statistically significant, except for the paucity of current smokers in the small group of patients with newly diagnosed CD (P < 0.05). A matched analysis produced similar results., Conclusions: The expected associations between smoking and IBD could not be confirmed. Two hypotheses are considered: (1) the association between smoking and IBD may not be universal, and (2) our findings may be related to the higher genetic predisposition to IBD in Jewish people.