Ulcerative Colitis: Gower-Rousseau C

Colombel JF, Vernier-Massouille G, Cortot A, Gower-Rousseau C, Salomez JL. · Registre des Maladies Inflammatoires Chroniques de l'Intestin (EPIMAD), service d'épidemiologie et de santé publique, Hôpital Calmette et service d'hépato-gastroentérologie, Hôpital Huriez, CH et U Lille, France. · Bull Acad Natl Med. · Pubmed #18402167 No free full text.

Abstract: Inflammatory bowel diseases (IBD) are a public health problem in industrialized countries, where 1 in 1000 people are affected Most patients are young adults. The incidence of IBD has increased considerably in western countries since the second world war but is beginning to level off. On the other hand, the incidence is still rising in low-incidence areas such as Eastern Europe, Asia and developing countries. Differences in incidence rates across age, time, and geographic areas suggest that environmental factors are involved in IBD, but only cigarette smoking and appendectomy have consistently been identified as risk factors. An important role of genetic factors in IBD was first suggested by epidemiological studies showing familial aggregation of IBD and by twin studies. In 2001, the first CD susceptibility gene, NOD2/CARD15 on chromosome 16, was characterized. Other susceptibility genes have since been located. Their identification should help to understand the complex interaction between the environment and the intestinal immune system.

Lerebours E, Gower-Rousseau C, Merle V, Brazier F, Debeugny S, Marti R, Salomez JL, Hellot MF, Dupas JL, Colombel JF, Cortot A, Benichou J. · Registre des Maladies Inflammatoires Chroniques de l'Intestin (EPIMAD), Service d'Epidémiologie et de Santé Publique, Hôpital Calmette, CHU de Lille, 59037 Lille Cedex, France. · Am J Gastroenterol. · Pubmed #17100973 No free full text.

Abstract: BACKGROUND AND AIMS: Stress is often perceived by patients with inflammatory bowel disease (IBD) as the leading cause of their disease. The aim of this study was to assess whether stress, evaluated through life event (LE) occurrence, is associated with IBD onset. METHODS: Incident cases of IBD, including 167 patients with Crohn's disease (CD) and 74 with ulcerative colitis (UC), were compared with two control groups, one of 69 patients with acute self-limited colitis (ASLC) and another of 255 blood donors (BDs). Stress was assessed using Paykel's self-questionnaire of LEs. Only LEs occurring within 6 months before the onset of symptoms in IBD cases and ASLC controls and before blood donation in BD controls were registered. Anxiety and depression were assessed using Bate's and Beck's questionnaires, respectively. RESULTS: In univariate analysis, occurrence of LEs was more frequent in the 6-month period prior to diagnosis in CD cases than in UC cases or either control group. After adjustment for depression and anxiety scores as well as other characteristics such as smoking status and sociodemographic features, this association appeared no longer significant. No associations were noted between occurrence of LEs and onset of UC relative to controls. CONCLUSIONS: Despite its separate association with CD, LE occurrence does not appear to be an independent risk factor for IBD onset.

Auvin S, Molinié F, Gower-Rousseau C, Brazier F, Merle V, Grandbastien B, Marti R, Lerebours E, Dupas JL, Colombel JF, Salomez JL, Cortot A, Turck D. · Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Hospital, Lille, France. · J Pediatr Gastroenterol Nutr. · Pubmed #15990630 No free full text.

Abstract: OBJECTIVE: To assess the incidence and location at diagnosis of inflammatory bowel disease in children and adolescents in northern France between 1988 and 1999. METHODS: A 12-year prospective population-based study was conducted by gastroenterologists and pediatric gastroenterologists of northern France (1,312,141 children <17 years of age). RESULTS: From 1988 to 1999, 509 cases of childhood inflammatory bowel disease were recorded (7.2% of all inflammatory bowel disease cases in Northern France): 367 Crohn disease, 122 ulcerative colitis and 20 indeterminate colitis. The mean standardized incidence was 3.1/10(5) for inflammatory bowel disease as a whole (2.3 for Crohn disease, 0.8 for ulcerative colitis and 0.12 for indeterminate colitis). Crohn disease location at diagnosis was: small bowel and colon (71%), colon only (10%) and small bowel only (19%). Location of initial ulcerative colitis was: proctitis (11%), left colitis (57%) and pancolitis (32%). Although ulcerative colitis incidence remained stable (0.8), Crohn disease incidence increased from 2.1 in 1988 to 1990 to 2.6 in 1997 to 1999 (P = 0.2). CONCLUSIONS: The incidence of Crohn disease in the children of northern France showed an increasing trend (20%; not significant) during the 12-year period while the incidence of ulcerative colitis remained stable. In the entire population(children and adults)the incidence of Crohn disease increased significantly (+23%; P < 0.001), while the incidence of ulcerative colitis decreased (-17%; P < 0.0001).

Baron S, Turck D, Leplat C, Merle V, Gower-Rousseau C, Marti R, Yzet T, Lerebours E, Dupas JL, Debeugny S, Salomez JL, Cortot A, Colombel JF. · Registre des Maladies Inflammatoires Chroniques de l'Intestin (EPIMAD), Service d'Epidémiologie et de Santé Publique, Hôpital Calmette, Lille, France. · Gut. · Pubmed #15710983 links to  free full text

Abstract: BACKGROUND: Environmental exposures in early life have been implicated in the aetiology of inflammatory bowel disease. OBJECTIVE: To examine environmental risk factors prior to the development of inflammatory bowel disease in a paediatric population based case control study. METHODS: A total of 222 incident cases of Crohn's disease and 60 incident cases of ulcerative colitis occurring before 17 years of age between January 1988 and December 1997 were matched with one control subject by sex, age, and geographical location. We recorded 140 study variables in a questionnaire that covered familial history of inflammatory bowel disease, events during the perinatal period, infant and child diet, vaccinations and childhood diseases, household amenities, and the family's socioeconomic status. RESULTS: In a multivariate model, familial history of inflammatory bowel disease (odds ratio (OR) 4.3 (95% confidence interval 2.3-8)), breast feeding (OR 2.1 (1.3-3.4)), bacille Calmette-Guerin vaccination (OR 3.6 (1.1-11.9)), and history of eczema (OR 2.1 (1-4.5)) were significant risk factors for Crohn's disease whereas regular drinking of tap water was a protective factor (OR 0.56 (0.3-1)). Familial history of inflammatory bowel disease (OR 12.5 (2.2-71.4)), disease during pregnancy (OR 8.9 (1.5-52)), and bedroom sharing (OR 7.1 (1.9-27.4)) were risk factors for ulcerative colitis whereas appendicectomy was a protective factor (OR 0.06 (0.01-0.36)). CONCLUSIONS: While family history and appendicectomy are known risk factors, changes in risk based on domestic promiscuity, certain vaccinations, and dietary factors may provide new aetiological clues.

Molinié F, Gower-Rousseau C, Yzet T, Merle V, Grandbastien B, Marti R, Lerebours E, Dupas JL, Colombel JF, Salomez JL, Cortot A. · Registre des Maladies Inflammatoires Chroniques de l'Intestin (EPIMAD), Service d'Epidémiologie et de Santé Publique, Hôpital Calmette, CHR&U de Lille, 59037 Lille Cedex, France. · Gut. · Pubmed #15138211 links to  free full text

Abstract: BACKGROUND: Northern France was characterised by a high incidence of Crohn's disease (CD) and a low incidence of ulcerative colitis (UC) according to the first inquiry undertaken in the late 1980s. AIMS: To assess the trends in the incidence of inflammatory bowel disease (IBD) over a 12 year period (1988-1999) in the same area of Northern France. PATIENTS: Patients living in Northern France (Nord, Pas-de-Calais, Somme, and Seine Maritime--total of 5,790,526 inhabitants) between 1988 and 1999 were included in the study. Case ascertainment was established according to methodology previously described. METHODS: Trends in incidence were studied using a Poisson regression model in four three year periods (1988-90, 1991-93, 1994-96, and 1997-99) adjusted for age at diagnosis and sex. Incidence rates were standardised for age with the European standard population. RESULTS: During 1988-99, 7066 cases of IBD were recorded (56.8% CD, 37.7% UC, and 5.5% indeterminate colitis). Mean annual incidence rate of CD increased from 5.2/100,000 inhabitants in 1988-90 to 6.4 in 1997-99 (adjusted p for trend <0.001). In contrast, the incidence of UC decreased from 4.2 to 3.5 (adjusted p for trend <0.001). The ileocolonic subtype of CD increased by 25% even though median age at diagnosis and frequency of digestive investigations were not different. CONCLUSIONS: Contrary to what has been reported in other countries in Northern Europe, the incidence of CD increased by 23% in 12 years in Northern France while that of UC decreased by 17% during the same period. This indicates that some factors which influence IBD frequency (in both directions) are still at work in this area of Europe, and that further studies aimed at identifying these should be performed. The rising incidence of CD could enhance the burden of this disease on the public health system in France.

Zouali H, Lesage S, Merlin F, Cézard JP, Colombel JF, Belaiche J, Almer S, Tysk C, O'Morain C, Gassull M, Christensen S, Finkel Y, Modigliani R, Gower-Rousseau C, Macry J, Chamaillard M, Thomas G, Hugot JP, Anonymous00017, Anonymous00018. · Fondation Jean Dausset-CEPH, Paris, France. · Gut. · Pubmed #12477763 links to  free full text

Abstract: BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex genetic disorders. CARD15/NOD2, a member of the Ced4 superfamily which includes Apaf-1 and CARD4/NOD1, has recently been associated with genetic predisposition to CD but additional genetic factors remain to be identified. Because CARD4/NOD1 shares many structural and functional similarities with CARD15, we tested its putative role in IBD. PATIENTS AND METHODS: The 11 exons of CARD4 were screened for the presence of variants in 63 unrelated IBD patients. The only non-private genetic variation encoding for a substitution in the peptidic chain was genotyped in 381 IBD families (235 CD, 58 UC, 81 mixed, and seven indeterminate colitis families) using a polymerase chain reaction-restriction fragment length polymorphism procedure. Genotyping data were analysed by the transmission disequilibrium test. RESULTS: Five of nine sequence variations identified in the coding sequence of the gene encoded for non-conservative changes (E266K, D372N, R705Q, T787M, and T787K). Four were present in only one family. The remaining variant (E266K), which exhibited an allele frequency of 0.28, was not associated with CD, UC, or IBD. Furthermore, IBD patients carrying sequence variations in their CARD4 gene had a similar phenotype to those with a normal sequence. CONCLUSION: Our results suggest that CARD4 does not play a major role in genetic susceptibility to IBD.

Lesage S, Zouali H, Cézard JP, Colombel JF, Belaiche J, Almer S, Tysk C, O'Morain C, Gassull M, Binder V, Finkel Y, Modigliani R, Gower-Rousseau C, Macry J, Merlin F, Chamaillard M, Jannot AS, Thomas G, Hugot JP, Anonymous00210, Anonymous00211, Anonymous00212. · Fondation Jean Dausset-CEPH, 27 rue Juliette Dodu, 75010 Paris, France. · Am J Hum Genet. · Pubmed #11875755 links to  free full text

Abstract: CARD15/NOD2 encodes a protein involved in bacterial recognition by monocytes. Mutations in CARD15 have recently been found in patients with Crohn disease (CD), a chronic inflammatory condition of the digestive tract. Here, we report the mutational analyses of CARD15 in 453 patients with CD, including 166 sporadic and 287 familial cases, 159 patients with ulcerative colitis (UC), and 103 healthy control subjects. Of 67 sequence variations identified, 9 had an allele frequency >5% in patients with CD. Six of them were considered to be polymorphisms, and three (R702W, G908R, and 1007fs) were confirmed to be independently associated with susceptibility to CD. Also considered as potential disease-causing mutations (DCMs) were 27 rare additional mutations. The three main variants (R702W, G908R, and 1007fs) represented 32%, 18%, and 31%, respectively, of the total CD mutations, whereas the total of the 27 rare mutations represented 19% of DCMs. Altogether, 93% of the mutations were located in the distal third of the gene. No mutations were found to be associated with UC. In contrast, 50% of patients with CD carried at least one DCM, including 17% who had a double mutation. This observation confirmed the gene-dosage effect in CD. The patients with double-dose mutations were characterized by a younger age at onset (16.9 years vs. 19.8 years; P=.01), a more frequent stricturing phenotype (53% vs. 28%; P=.00003; odds ratio 2.92), and a less frequent colonic involvement (43% vs. 62%; P=.003; odds ratio 0.44) than were seen in those patients who had no mutation. The severity of the disease and extraintestinal manifestations were not different for any of the CARD15 genotypes. The proportion of familial and sporadic cases and the proportion of patients with smoking habits were similar in the groups of patients with CD with or without mutation. These findings provide tools for a DNA-based test of susceptibility and for genetic counseling in inflammatory bowel disease.

Hugot JP, Chamaillard M, Zouali H, Lesage S, Cézard JP, Belaiche J, Almer S, Tysk C, O'Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G. · Fondation Jean Dausset CEPH, 27 rue J. Dodu 75010 Paris, France. · Nature. · Pubmed #11385576 No free full text.

Abstract: Crohn's disease and ulcerative colitis, the two main types of chronic inflammatory bowel disease, are multifactorial conditions of unknown aetiology. A susceptibility locus for Crohn's disease has been mapped to chromosome 16. Here we have used a positional-cloning strategy, based on linkage analysis followed by linkage disequilibrium mapping, to identify three independent associations for Crohn's disease: a frameshift variant and two missense variants of NOD2, encoding a member of the Apaf-1/Ced-4 superfamily of apoptosis regulators that is expressed in monocytes. These NOD2 variants alter the structure of either the leucine-rich repeat domain of the protein or the adjacent region. NOD2 activates nuclear factor NF-kB; this activating function is regulated by the carboxy-terminal leucine-rich repeat domain, which has an inhibitory role and also acts as an intracellular receptor for components of microbial pathogens. These observations suggest that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn's disease that can now be further investigated.

Laharie D, Debeugny S, Peeters M, Van Gossum A, Gower-Rousseau C, Bélaïche J, Fiasse R, Dupas JL, Lerebours E, Piotte S, Cortot A, Vermeire S, Grandbastien B, Colombel JF. · Registre des MICI du Nord-Ouest de la France (EPIMAD), France. · Gastroenterology. · Pubmed #11231934 No free full text.

Abstract: BACKGROUND & AIMS: The rarity of inflammatory bowel disease (IBD) in both husband and wife is often given as an argument against an infectious origin. We registered conjugal instances of IBD in Northern France and in Belgium between 1989 and 2000. METHODS: Couples were assigned to group A if both partners had symptoms of IBD before cohabitation, to group B if one spouse had IBD before cohabitation and the other experienced first symptoms afterwards, and to group C if both partners got the disease after cohabitation. Risk of IBD was assessed in their offspring. RESULTS: Thirty conjugal instances were registered. Seventeen were concordant for Crohn's disease and 3 for ulcerative colitis; 10 were mixed. Two belonged to group A, 6 to group B, and 22 to group C. In group C, IBD occurred in the first affected spouse an average of 9 years after cohabitation and in the second spouse an average of 8.5 years later. Group C conjugal forms were more frequent than expected by chance (P < 0.02). Fifty-four children were born to 25 couples; among them 9, of whom 4 were siblings, developed Crohn's disease at a median age of 15 years. CONCLUSIONS: The frequency of conjugal forms of IBD suggests an etiologic role for environmental factors. Offspring of 2 affected parents have a high risk of developing IBD.

Rolland N, Grandbastien B, Merle V, Gower-Rousseau C, Yzet T, Marti R, Lerebours E, Dupas JL, Czernichow P, Salomez JL, Lebrun T, Cortot A. · CRESGE-Centre de Recherches Economiques Sociologiques et de Gestion, Lille, France. · Gastroenterol Clin Biol. · Pubmed #10416112 No free full text.

Abstract: OBJECTIVES: The aim of this study was to assess the cost of the first management of inflammatory bowel disease (IBD) from the onset of first symptoms until 6 weeks after the diagnosis. This cost was calculated in French francs (FF) for all IBD and namely for Crohn's disease (CD), ulcerative colitis (UC), and ulcerative proctitis (UP). MATERIAL AND METHODS: Data concerning 258 patients were collected by the mean of a standardized questionnaire from 3 different sources: the patient, his general practitioner, and his gastroenterologist. RESULTS: Two hundred and fifty eight patients were included: 144 CD (55.8%), 76 UC (29.5%), 30 UP (11.6%), and 8 chronic unclassifiable colitis (CUC) (3.1%). The mean direct costs of the diagnosis (m +/- SD) were 23,116 +/- 40,820 FF for CD, 10,628 +/- 17,316 FF for UC and 3,451 +/- 2,743 FF for UP. Although unplanned hospitalizations occurred in only 38% of the patients (98/258), they represented the 3/4 of the mean costs: 78.2% for CD and 64% for UC. Indirect costs generated by days off work were 4,719 +/- 6,610 FF for CD, 2,996 +/- 6,897 FF for UC and 1,230 +/- 3,622 FF for UP. CONCLUSION: The first management of a patient with CD was twice more expensive than the one with UC and 6.5 times than the one with UP.

Grandbastien B, Gower-Rousseau C, Merle V, Dupas JL, Yzet T, Lerebours E, Marti R, Laine I, Cortot A, Salomez JL. · Registre des Maladies Inflammatoires Chroniques de l'Intestin du Nord-Ouest de la France (EPIMAD), Service d'Epidémiologie, Hôpital Calmette, Lille. · Rev Epidemiol Sante Publique. · Pubmed #10214676 No free full text.

Abstract: BACKGROUND: The period of time required for the diagnosis of a chronic illness depends on initial clinical symptoms and their perception by the patient and the physicians. The aim of this study was to describe the procedures of diagnosis of incident cases of Inflammatory Bowel Disease (IBD). METHODS: Patients reported by the Registry of inflammatory bowel disease of northern France (EPIMAD) in 1994 were included. Standardized questionnaires describing clinical history, patient behavior, medical consultations and examinations were collected by an interviewer practitioner from three sources: patients, general practitioners (GP) and gastroenterologists (GE). Patients were divided in 2 groups according to the time between symptom onset and diagnosis: more than 9 months or less than 9 months (D > 9 and D < or = 9). RESULTS: 258 patients were included: 144 Crohn's disease (CD) (56%), 106 ulcerative colitis (UC) (41%) and 8 chronic unclassifiable colitis (CUC). Median time between symptom onset and diagnosis was 3 months, 196 (76%) patients belonged to the group D < or = 9 and 62 (24%) to the group D > 9. There was no difference between the 2 groups for initial clinical symptoms. The delay between symptom onset and the consultation to the GP and the GE was longer in the group D > 9: respectively 1 month vs 0 and 7.6 vs 2. Thirty-five percent of patients in the group D > 9 had consulted more than one GP vs 14% (p < 0.05). Diagnosis management by the GE was the same in both groups. Patients of group D < or = 9 had more often perceived their symptoms as serious (p < 0.05). CONCLUSIONS: Delay to diagnosis in a quarter of patients with IBD was more than 9 months. This later diagnosis was not due to patient management by the GE but rather to a longer delay to consulting the GP and between GP and GE referral. Patient interpretation of the symptoms could also explain the variability of this delay.