Dietary intake of children with inflammatory bowel disease and of healthy controls

Introduction: The assessment of dietary intake by examination is a tool that allows knowing the habits and detecting certain nutritional deficiencies. Thus, it is essential in chronic disease and especially in children, where deficiencies can have a negative impact on growth and pubertal development. Objectives: Compare the dietary intake between children with inflammatory bowel disease (IBD) and healthy controls. Methods: Twenty-nine healthy controls (12 girls; mean age: 12.7 ± 1.9 years) and 21 IBD patients (11 girls; 14.3 ± 1.3 years) recruited from August 2011 to October 2012. Dietary intake was assessed by 24h recall. Results: No differences were found between IBD patients and healthy controls regarding dietary intake (table). Both IBD patients and healthy controls had excessive protein consumption. Furthermore, there are deficiencies for some nutriments (fibers, calcium and magnesium). Qualitative analysis revealed that both, IBD patients and healthy controls showed increased snacking and bad lipids distribution, especially for saturated lipids. Conclusion: Both children with IBD and health controls have a food imbalance and a low intake of minerals and vitamins. No differences between children with IBD and healthy controls were found.

Targeting inflammasomes in rheumatic diseases.

Inflammasomes are key inducers of inflammation in response to exogenous and endogenous stimuli, because they regulate the processing and secretion of the proinflammatory cytokines IL-1β and IL-18. Thus, inflammasomes have a crucial role in host defence against infection, but they can also be involved in inflammatory diseases. Indeed, the NLRP3 (NOD-, LRR- and pyrin domain-containing 3) inflammasome has been shown to play a part in several inflammatory rheumatic disorders, although the mechanisms involved are better elucidated in some of these diseases than in others. In particular, the pathogenesis of cryopyrin-associated periodic syndromes and microcrystal-induced arthritides is thought to be dependent on activation of the NLRP3 inflammasome, and IL-1 inhibition has shown efficacy as a therapeutic strategy in both groups of conditions. In this Review, we describe the current understanding of the mechanisms that trigger the inflammasome, and consider the relevance of the inflammasome to a variety of rheumatic diseases. In addition, we discuss the current therapies targeting this molecular complex, as well as future therapeutic prospects.

First-line therapies in inflammatory bowel disease.

Background and Aims: Medical therapy of inflammatory bowel disease (IBD) is becoming more complex, given the increasing choice of drugs to treat Crohn's disease (CD) and ulcerative colitis (UC). We aimed to summarize the current guidelines for first-line treatments in IBD. Methods: An extensive literature search with focus on the guidelines of the European Crohn's and Colitis Organisation for the diagnosis and treatment of CD and UC was performed. First-line treatments were defined as the following drug categories: 5-aminosalicylates, budesonide, systemic steroids, azathioprine, 6-mercaptopurine, methotrexate, infliximab, adalimumab and certolizumab pegol. The following drug categories were not included: cyclosporine and tacrolimus (not yet approved by Swissmedic for IBD treatment). Results: Treatment recommendations for the following clinically frequent situations are presented according to disease severity: ileocecal CD, colonic CD, proximal small bowel CD and perianal CD. For UC the following situations are presented: ulcerative proctitis, left-sided colitis and pancolitis. Conclusions: We provide a summary on the use of first-line therapies for clinically frequent situations in patients with CD and UC.

Low prevalence of behavioural and emotional problems among Swiss paediatric patients with inflammatory bowel disease.

OBJECTIVES: Whether behavioural and emotional maladjustment is more prevalent in children with inflammatory bowel disease (IBD) than in healthy controls remains controversial. The aim of this study was to assess paediatric IBD patients for problems with emotional and behavioural adjustment and to examine associations with clinical and demographic variables. METHODS: Data from paediatric patients with IBD enrolled in the Swiss IBD Cohort Study and the results of both the parent-rated Strengths and Difficulties Questionnaire (SDQ) and the self-reported Child Depression Inventory (CDI) were analysed. Of the 148 registered patients, 126 had at least one questionnaire completed and were included. RESULTS: The mean age of 71 patients with Crohn's disease (44 males, 27 females) was 13.4 years, and 12.8 years for the 55 patients with ulcerative or indeterminate colitis. The mean duration of disease was 1.2 and 2.7 years, respectively. The total score of the SDQ was abnormal in 11.4% of cases compared to 10% in the normal population. Abnormal sub-scores were found in 20.2% of subjects for the domain of emotional problems and in 17.1% for problems with peers. The total CDI T score indicated a significantly lower prevalence of clinical depression in IBD patients than in normal youth. No correlation between the total SDQ scores or the CDI T scores and gender, type or duration of IBD, inflammatory markers or disease scores was found. CONCLUSIONS: The prevalence of problems with behavioural and emotional adjustment among Swiss paediatric IBD patients is low and comparable to that of the normal population.

Acute inflammatory reaction associated with endoluminal bypass grafts.

PURPOSE: Nonspecific inflammatory reactions characterized by local tenderness, fever, and flu-like discomfort have been seen in patients undergoing endoluminal graft placement in the abdominal aorta or the femoral arteries. We undertook a study to assess the clinical and laboratory parameters of this inflammation. METHODS: Ten patients with femoropopliteal artery (n = 9) or aortic (n = 1) lesions were treated with EndoPro System 1 stent-grafts made of nitinol alloy and covered with a polyester (Dacron) fabric. Eleven patients implanted with a bare nitinol stent served as the control group. RESULTS: In the stent-graft group, four patients showed clinical signs of acute inflammation manifested by fever and local tenderness. Three of these patients suffered thrombosis of the stent-grafts during the first month of follow-up. Plasma levels of interleukin-1 beta and interleukin-6 in all stent-graft patients were markedly increased 1 day after intervention (7.3 +/- 2.8 versus 90.2 +/- 34.1 pg/mL and 15.6 +/- 5.8 versus 175.5 +/- 66.3 pg/mL, respectively; p < 0.01). This was followed by an increase in fibrinogen (3.0 +/- 0.2 versus 5.0 +/- 0.2 g/L; p < 0.05) and C-reactive protein (14.6 +/- 3.3 versus 77.5 +/- 15.0 mg/L; p < 0.01) at 1 week. No direct correlation between the inflammatory markers and symptoms could be found. In vitro analysis showed that individual components of the stent-graft did not activate human neutrophils, whereas the intact stent-graft itself induced a marked neutrophil activation. CONCLUSIONS: The component of the self-expanding stent-graft responsible for the nonspecific inflammatory reaction was not identified in this study. It is likely that the stent-graft itself or some as yet unrecognized element of the device other than the Dacron fabric or metal alloy may be a potent in vivo inducer of cytokine reaction by neutrophils.

Peroxisomal and microsomal lipid pathways associated with resistance to hepatic steatosis and reduced pro-inflammatory state.

Accumulation of fat in the liver increases the risk to develop fibrosis and cirrhosis and is associated with development of the metabolic syndrome. Here, to identify genes or gene pathways that may underlie the genetic susceptibility to fat accumulation in liver, we studied A/J and C57Bl/6 mice that are resistant and sensitive to diet-induced hepatosteatosis and obesity, respectively. We performed comparative transcriptomic and lipidomic analysis of the livers of both strains of mice fed a high fat diet for 2, 10, and 30 days. We found that resistance to steatosis in A/J mice was associated with the following: (i) a coordinated up-regulation of 10 genes controlling peroxisome biogenesis and β-oxidation; (ii) an increased expression of the elongase Elovl5 and desaturases Fads1 and Fads2. In agreement with these observations, peroxisomal β-oxidation was increased in livers of A/J mice, and lipidomic analysis showed increased concentrations of long chain fatty acid-containing triglycerides, arachidonic acid-containing lysophosphatidylcholine, and 2-arachidonylglycerol, a cannabinoid receptor agonist. We found that the anti-inflammatory CB2 receptor was the main hepatic cannabinoid receptor, which was highly expressed in Kupffer cells. We further found that A/J mice had a lower pro-inflammatory state as determined by lower plasma levels and IL-1β and granulocyte-CSF and reduced hepatic expression of their mRNAs, which were found only in Kupffer cells. This suggests that increased 2-arachidonylglycerol production may limit Kupffer cell activity. Collectively, our data suggest that genetic variations in the expression of peroxisomal β-oxidation genes and of genes controlling the production of an anti-inflammatory lipid may underlie the differential susceptibility to diet-induced hepatic steatosis and pro-inflammatory state.

Epidemiology of inflammatory bowel disease: Is there a shift towards onset at a younger age?

OBJECTIVES: Increasing numbers of paediatric and adolescent patients with Crohn disease (CD) and ulcerative colitis (UC) are reported. To determine whether this observation is a consequence of a shift towards onset at a younger age, we analysed retrospective data from patients enrolled in the Swiss IBD Cohort Study (SIBDCS). PATIENTS AND METHODS: The SIBDCS is a disease-based cohort in Switzerland, which collects retrospective and prospective data on a large sample of patients with inflammatory bowel disease (IBD). Patients, diagnosed from 1980, were stratified according to diagnosis of CD and UC. Age at disease onset (age at first symptoms and age at diagnosis) was analysed in relation to calendar year of disease onset. Data were extracted from physician and patient questionnaires. Linear regressions of age at disease onset by calendar year of disease onset adjusted by sex, country of birth, and education were performed. RESULTS: Adjusted regression coefficients for CD and UC were significantly positive, that is, age at disease onset has increased with time. Male sex was associated with an increase in age at disease onset, and birth in Switzerland with a decrease. These associations were statistically significant. CONCLUSIONS: The results from the SIBDCS do not support the hypothesis that disease onset of both CD and UC occur today at a younger age. On the contrary, our results show that there is a significant trend for age at disease onset occurring at an older age today as compared with recent decades. We conclude that the observation of increasing numbers of paediatric and adolescent patients with IBD is not caused by a trend towards disease onset at a younger age, but that this may rather be a consequence of the overall increasing incidence of these conditions.

Gender differences in paediatric patients of the swiss inflammatory bowel disease cohort study.

PURPOSE: Gender differences in paediatric patients with inflammatory bowel disease (IBD) are frequently reported as a secondary outcome and the results are divergent. To assess gender differences by analysing data collected within the Swiss IBD cohort study database since 2008, related to children with IBD, using the Montreal classification for a systematic approach. METHODS: Data on gender, age, anthropometrics, disease location at diagnosis, disease behaviour, and therapy of 196 patients, 105 with Crohn's disease (CD) and 91 with ulcerative or indeterminate colitis (UC/IC) were retrieved and analysed. RESULTS: THE CRUDE GENDER RATIO (MALE : female) of patients with CD diagnosed at <10 years of age was 2.57, the adjusted ratio was 2.42, and in patients with UC/IC it was 0.68 and 0.64 respectively. The non-adjusted gender ratio of patients diagnosed at ≥10 years was 1.58 for CD and 0.88 for UC/IC. Boys with UC/IC diagnosed <10 years of age had a longer diagnostic delay, and in girls diagnosed with UC/IC >10 years a more important use of azathioprine was observed. No other gender difference was found after analysis of age, disease location and behaviour at diagnosis, duration of disease, familial occurrence of IBD, prevalence of extra-intestinal manifestations, complications, and requirement for surgery. CONCLUSION: CD in children <10 years affects predominantly boys with a sex ratio of 2.57; the impact of sex-hormones on the development of CD in pre-pubertal male patients should be investigated.

Pseudotumeur inflammatoire de la caroncule [Inflammatory pseudotumor of the caruncle].

A 6-year-old girl exhibited a recent caruncular tumor which was increasing in size. It was removed after a CT scan had showed a both medial and superficial mass. Fortunately, histological tests only found inflammatory cells attesting that the mass was due to an inflammation of this area. Inflammation is one of the different processes that may increase the size of the caruncle, but sometimes, only histopathology can provide conclusive evidence.

Prevalence of inflammatory bowel disease in the canton of Vaud (Switzerland) : a population-based cohort study

Abstract : Background and aims: Because of the changing epidemiology of Inflammatory Bowel Diseases (IBD), we set out to characterize the population-based prevalence of Crohn's Disease (CD) and Ulcerative Colitis (UC) in a defined population of Switzerland. Methods: Adult IBD patients were identified by across-matched review of histological, hospital and gastroenterologist files throughout a geographical defined population (Canton of Vaud). Demographic factors statistically significantly associated with prevalence were evaluated using a stepwise Poisson regression analysis. Results were compared to IBD prevalence rates in other population-based studies and time trends were performed, based on a systematic literature review. Results: Age and sex-adjusted prevalence rates were 205.7 IBD (100.7 CD and 105.0 UC) cases per 10,5 inhabitants. Among 1016 IBD patients (519 CD and 497 UC), females outnumbered males in CD (p<0.001), but males were more represented in elderly UC patients (p=0.008). Thus, being a mate was statistically associated with UC (Relative Risk (RR) 1.25; p=0.013), whereas being a female was associated with CD (RR 1.27; p=0.007). Living in an urban zone was associated with both CD and UC (RR 1.49; p<0.001, 1.63; p<0.001, respectively). From 1960 to 2005, increases in UC and CD prevalences of 2.4% (95%CI, 2.1%-2.8%; p<0.001) and 3.6% (95%CI, 3.1%-4.1%; p<0.001) per annum were found in industrialised countries. Résumé de synthèse : 1. Introduction : Étant donné l'évolution constante des donnés épidémiologiques sur les maladies inflammatoires chroniques de l'intestin (MICI), nous avons recherché à caractériser la prévalence de la maladie de Crohn (MC) et de la colite ulcéreuse (CU) dans une population définie de la Suisse. 2. Méthodes : Nous avons identifiés, dans une population délimitée au Canton de Vaud, les patients adultes atteints de maladies inflammatoires de l'intestin en regroupant les données histologiques et médicales disponibles à l'hôpital et au cabinet du gastroentérologue. Pour nos analyses, nous avons utilisé la méthode de la régression de Poisson afin d'identifier les facteurs démographiques significativement liés avec la prévalence. Ensuite, nos résultats ont été comparés aux valeurs de prévalence des MICI issues d'autres études de population (revue systématique de la littérature) afin de dégager les tendances de leur évolution au cours du temps. 3. Résultats : La prévalence des MICI pondérée selon l'âge et le sexe était de 205.7 cas (100.7 MC et 105.0 CU) pour 10,5 habitants. Parmi les 1016 patients identifiés (519 MC et 497 CU), les femmes étaient plus représentées que les hommes dans la MC (P<0.0001), alors que la proportion d'hommes dépassait celle des femmes chez les patients âgés atteints de CU (p=0.008). Par conséquent, le fait d'être un homme était statistiquement associé à la CU (Risque relatif (RR) 1.25, p=0.013), et celui d'être une femme était associé à la MC (RR 1.27 ; p=0.007). L'étude a également montré qu'habiter en zone urbaine était significativement associé avec les deux types de MICI (RR (MC) 1.49; p<0.001, (CU) 1.63; p<0.001). Enfin, il a été mis en évidence dans les pays industrialisés, entre 1960 et 2005, une augmentation annuelle des taux de prévalences de 2.4% (95% IC, 2.1 %-2.8% ; p<0.001) pour la MC et de 3.6% (95% IC, 3.1 %-4.1 % ; p<0.001) pour la CU. 4. Conclusion : L'extrapolation de nos données au niveau Suisse fournit une estimation de 12 000 cas de MICI pour le pays soit 1 cas pour 500 habitants. Notre étude contribue également à démontrer une augmentation de la prévalence des MICI en Europe.

The course of inflammatory bowel disease during pregnancy and postpartum: a prospective European ECCO-EpiCom Study of 209 pregnant women.

BACKGROUND: The impact of pregnancy on the course of IBD is still controversial. AIM: To investigate the impact of pregnancy on IBD and to search for factors with potential impact on remission. METHODS: Pregnant IBD women from 12 European countries were enrolled between January 2003 and December 2006 and compared at conception (1:1) with nonpregnant IBD women. Data on disease course were prospectively collected at each trimester during pregnancy and in the postpartum (6 months) using a standardised questionnaire. RESULTS: A total of 209 pregnant IBD women were included: 92 with Crohn's disease (CD; median age 31 years, range 17-40) and 117 with ulcerative colitis (UC; median age 32 years, range 19-42). No statistically significant difference in disease course during pregnancy and postpartum was observed between pregnant and nonpregnant CD women. Longer disease duration in CD and immunosuppressive therapy were found to be risk factors for activity during pregnancy. Pregnant UC women were more likely than nonpregnant UC women to relapse both during pregnancy (RR 2.19; 95% CI: 1.25-3.97, 0.004) and postpartum (RR 6.22; 95% CI: 2.05-79.3, P = 0.0004). During pregnancy, relapse was mainly observed in the first (RR 8.80; 95% CI 2.05-79.3, P < 0.0004) and the second trimester (RR 2.84, 95% CI 1.2-7.45, P = 0.0098). CONCLUSIONS: Pregnant women with Crohn's disease had a similar disease course both during pregnancy and after delivery as the nonpregnant women. In contrast, pregnant women with ulcerative colitis were at higher risk of relapse during pregnancy and in the postpartum than nonpregnant ulcerative colitis women.

Immunoscintigraphic localization of inflammatory lesions: concept, radiolabelling and in vitro testing of a granulocyte specific antibody.

Current nuclear medicine techniques for the localization of inflammatory processes are based on injection of 111In labelled autologous granulocytes which need to be isolated and radiolabelled in vitro before reinjection. A new technique is presented here that obviates the need for cell isolation by the direct intravenous injection of a granulocyte specific 123I labelled monoclonal antibody. In this publication the basic parameters of the antibody granulocyte interaction are described. Antibody binding does not inhibit vital functions of the granulocytes, such as chemotaxis and superoxide generation. Scatchard analysis of binding data reveals an apparent affinity of the antibody for granulocytes of 6.8 X 10(9) l/mol and approximately 7.1 X 10(4) binding sites per cell. Due to the high specificity of the antibody, the only expected interference is from CEA producing tumors.