Serological markers predict inflammatory bowel disease years before the diagnosis
Fiona D M van Schaik,1 Bas Oldenburg,1 Andrew R Hart,2 Peter D Siersema,1
Stefan Lindgren,3 Olof Grip,3 Birgit Teucher,4 Rudolf Kaaks,4
Manuela M Bergmann,5 Heiner Boeing,5 Franck Carbonnel,6 Prevost Jantchou,6Marie-Christine Boutron-Ruault,6 Anne Tjønneland,7 Anja Olsen,7
Francesca L Crowe,8 Petra H M Peeters,9 Martijn G H van Oijen,1
H Bas Bueno-de-Mesquita1
Objective Anti-neutrophil cytoplasmic antibodies and
anti-Saccharomyces cerevisiae mannan antibodies
(ASCAs) have been detected in the serum of patients
with ulcerative colitis (UC) and Crohn’s disease (CD) andtheir unaffected family members.
The aim of this study was to establish the value of serological markers as
predictors of UC and CD.
Design Individuals who developed CD or UC were
identified from the European Prospective Investigation
into Cancer and Nutrition (EPIC) study. At recruitment,
none of the participants had a diagnosis of CD or UC.
For each incident case, two controls were randomly selectedmatched for centre, date of birth, sex, date of recruitment and time of follow-up.
Serum of cases and controls obtained at recruitment were analysed for ASCAIgG, ASCA IgA, perinuclear anti-neutrophil cytoplasmic
antibody (pANCA), antibodies against Escherichia coli
outer membrane porin C (OmpC) and flagellin CBir1.
Conditional logistic regression was used to determine
risk of CD and UC. Receiver operating characteristic
curves were constructed to test accuracy.
Results A total of 77 individuals were diagnosed with
CD and 167 with UC after a mean follow-up of 4.5
(SD 3.2) and 4.4 (SD 3.1) years following blood
collection, respectively. Combinations of pANCA, ASCA,anti-CBir1 and anti-OmpC were most accurate in
predicting incident CD and UC (area under curve 0.679
and 0.657, respectively). The predictive value of the
combination of markers increased when time to
diagnosis of CD or UC decreased.
Conclusion A panel of serological markers is able to
predict development of CD and UC in individuals from
a low-risk population.
Pôle pharmaceutique, University Hospital, Besançon, France. firstname.lastname@example.org
Low sunshine exposure might contribute to the pathogenesis of inflammatory bowel disease (IBD).
To assess the geographic distribution of IBD incidence in relation to sunshine exposure in France to test the hypothesis that higher sun exposure is associated with lower IBD risk.
Using the national health insurance database, incidence rates of Crohn’s disease (CD) and ulcerative colitis (UC) were estimated for each of the 94 French administrative areas (‘départements’), between 2000 and 2002. The surface UV radiation intensity was obtained by combining modelling and satellite data from Meteosat, the European meteorological satellite. Relationships between incidence rates and sun exposure were tested for significance by using a Poisson regression. We mapped smoothed relative risks (sRR) for CD and UC, using a Bayesian approach and adjusting for sun exposure, to search for geographical variations.
Areas with a smoothed RR of CD incidence significantly above 1 corresponded to areas with low sunshine exposure, whereas those with high or medium sunlight exposure had smoothed RRs either lower than 1 or not significantly different from 1. There was no association between sun exposure and UC incidence.
This geographic study suggests that low sunlight exposure is associated with an increased incidence of Crohn’s disease. Further studies are needed to determine if this association is causal.
© 2011 Blackwell Publishing Ltd.
INSERM, UMRS, Centre for Research in Epidemiology and Population Health, Institut Gustave Roussy, Université Paris Sud, Villejuif, France.
Diet composition has long been suspected to contribute to inflammatory bowel disease (IBD), but has not been thoroughly assessed, and has been assessed only in retrospective studies that are prone to recall bias. The aim of the present study was to evaluate the role of dietary macronutrients in the etiology of IBD in a large prospective cohort.
The Etude Épidémiologique des femmes de la Mutuelle Générale de l’Education Nationale cohort consists of women living in France, aged 40-65 years, and free of major diseases at inclusion. A self-administered questionnaire was used to record dietary habits at baseline. Questionnaires on disease occurrence and lifestyle factors were completed every 24 months. IBDs were assessed in each questionnaire until June 2005, and subsequently validated using clinical and pathological criteria. We estimated the association between nutrients or foods and IBD using Cox proportional hazards models adjusted for energy intake.
Among 67,581 participants (705,445 person-years, mean follow-up since completion of the baseline dietary questionnaire 10.4 years), we validated 77 incident IBD cases. High total protein intake, specifically animal protein, was associated with a significantly increased risk of IBD, (hazards ratio for the third vs. first tertile and 95% confidence interval being 3.31 and 1.41-7.77 (P trend=0.007), and 3.03 and 1.45-6.34 (P trend=0.005) for total and animal protein, respectively). Among sources of animal protein, high consumption of meat or fish but not of eggs or dairy products was associated with IBD risk.
High protein intake is associated with an increased risk of incident IBD in French middle-aged women.
Service de Gastroentérologie et Nutrition, CHU Jean Minjoz, 25000 Besançon, France. email@example.com
Rapid increase in Crohn’s disease (CD) and ulcerative colitis (UC) incidence in developed countries, occurrence of CD in spouses and lack of complete concordance in monozygotic twins are strong arguments for the role of environmental factors in inflammatory bowel disease (IBD). Only two environmental factors have an established role in IBD. Smoking is a risk factor for CD and a protective factor for UC; appendectomy is a protective factor for UC. Many other environmental factors for IBD have been investigated. These are infectious agents, diet, drugs, stress and socio-economic factors. They are detailed in this paper. Among them, adherent invasive E. coli, infectious gastroenteritis, oral contraceptives and antibiotics could play a role in CD. To date, three theories integrate environmental factors to pathogenesis of IBD: hygiene, infection and cold chain. Much work remains to be done to identify risk factors for IBD. As exemplified by smoking, research of environmental risk factors of IBD is useful since it may lead to an improved disease course among patients and perhaps, to appropriate prevention among predisposed subjects. Further studies in this field are eagerly awaited.
Copyright 2009 Elsevier Masson SAS. All rights reserved.
[Oral corticosteroids are efficient in recurrent intussusception associated with intestinal lymphoid hyperplasia].
Service de pédiatrie, CHU Saint-Jacques, 2, place Saint-Jacques, 25000 Besançon, France. firstname.lastname@example.org
We report a case of recurrent intussusception in a 6-year-old boy associated with Intestinal Lymphoid Hyperplasia (ILH). A single course of steroids resulted in resolution of both symptoms and hyperplasia. We conclude that steroids treatment must be considered in recurrent intussusception associated with ILH and no other lead point identified (lymphoma or intestinal malformation) instead of a more radical surgical approach by a ileum resection.
Pediatrics Department, Besançon Teaching Hospital, Besançon, France.
Upper gastrointestinal endoscopy (UGIE) is appropriate in many situations in adults and children. Recommendations for UGIE use in children were published recently by the French-language Paediatric Hepatology, Gastroenterology, and Nutrition Group (GFHGNP).
PATIENTS AND METHODS:
We retrospectively reviewed the 293 UGIE procedures undertaken in 251 children between January 1, 2001 and June 30, 2003 by 2 senior endoscopists. The UGIE procedures were categorized as appropriate or inappropriate based on GFHGNP recommendations, and diagnostic efficiency was compared in the 2 groups with the chi2 test followed by multivariate logistic regression analysis.
Of the 293 UGIE procedures, 52 (17.7%) were considered inappropriate. Diagnostic efficiency was 51% in the appropriate group versus 17.3% in the inappropriate group (odds ratio, 4.2; 95% CI, 2-8.7; P < 10(-3)). The proportion of appropriate UGIE procedures was higher among inpatients than outpatients (odds ratio, 2.51; 95% CI, 1.24-5.08; P = 0.01). Inappropriate reasons for performing UGIE included isolated failure to thrive and follow-up after neonatal esophagogastroduodenitis. Nine inappropriate UGIE procedures contributed useful information: ulcerative esophagitis in 1 patient, hemorrhagic esophagitis in 4 patients, duodenitis in 1 patient, and malabsorption in 3 patients caused in 1 case by cow’s milk allergy and in 2 cases to fully documented celiac disease.
UGIE was usually performed appropriately in our pediatric hospital. Inappropriate UGIE procedures were more common in outpatients than in admitted patients. Awareness of the recommendations for appropriate UGIE use needs to be improved among office-based and hospital-based physicians.
[Environmental risk factors in Crohn’s disease and ulcerative colitis (excluding tobacco and appendicectomy)].
Service de Pédiatrie, CHU Saint Jacques, Besançon.
A rapid increase in the incidence of Crohn’s disease and ulcerative colitis in developed countries, the occurrence of Crohn’s disease in spouses, and a lack of complete concordance in monozygotic twins are strong arguments for the role of environmental factors in inflammatory bowel disease (IBD). Research in the field of environmental factors in IBD is based upon epidemiological (geographical and case-control), clinical and experimental studies. The role of two environmental factors has clearly been established in IBD. Smoking is a risk factor for Crohn’s disease and a protective factor for ulcerative colitis; appendectomy is a protective factor for ulcerative colitis. Many other environmental factors for IBD have been investigated, including infectious agents, diet, drugs, stress and social status. They are detailed in the present review. Among them, atypical Mycobacteria, oral contraceptives and antibiotics could play a role in Crohn’s disease. To date, three hypotheses associate environmental factors with the pathophysiology of IBD (loss of tolerance of intestinal immune system towards commensal bacterial flora): the hygiene, infection and cold chain hypotheses. Much work remains to be done to identify risk factors for IBD. Research identifying environmental factors that might cause a predisposition to IBD is useful. It may lead to disease prevention in subjects who are genetically predisposed and disease improvement in patients.