Antoine Cortot

Epidemiology and Natural History of Inflammatory Bowel Diseases

In the West, the incidence and prevalence of inflammatory bowel diseases has increased in the past 50 years, up to 8-14/100,000 and 120-200/100,000 persons, respectively, for ulcerative colitis (UC) and 6-15/100,000 and 50-200/100,000 persons, respectively, for Crohns disease (CD). Studies of migrant populations and populations of developing countries demonstrated a recent, slow increase in the incidence of UC, whereas that of CD remained low, but CD incidence eventually increased to the level of UC. CD and UC are incurable; they begin in young adulthood and continue throughout life. The anatomic evolution of CD has been determined from studies of postoperative recurrence; CD begins with aphthous ulcers that develop into strictures or fistulas. Lesions usually arise in a single digestive segment; this site tends to be stable over time. Strictures and fistulas are more frequent in patients with ileal disease, whereas Crohns colitis remains uncomplicated for many years. Among patients with CD, intestinal surgery is required for as many as 80% and a permanent stoma required in more than 10%. In patients with UC, the lesions usually remain superficial and extend proximally; colectomy is required for 10%-30% of patients. Prognosis is difficult to determine. The mortality of patients with UC is not greater than that of the population, but patients with CD have greater mortality than the population. It has been proposed that only aggressive therapeutic approaches, based on treatment of early recurrent lesions in asymptomatic individuals, have a significant impact on progression of these chronic diseases.

Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study

Data on the natural history of elderly-onset inflammatory bowel disease (IBD) are scarce. Methods In a French population-based cohort we identified 841 IBD patients >60u2005years of age at diagnosis from 1988 to 2006, including 367 Crohns disease (CD) and 472 ulcerative colitis (UC). Results Median age at diagnosis was similar for CD (70 years (IQR: 65–76)) and UC (69u2005years (64–74)). Median follow-up was 6u2005years (2–11) for both diseases. At diagnosis, in CD, pure colonic disease (65%) and inflammatory behaviour (78%) were the most frequent phenotype. At maximal follow-up digestive extension and complicated behaviour occurred in 8% and 9%, respectively. In UC, 29% of patients had proctitis, 45% left-sided and 26% extensive colitis without extension during follow-up in 84%. In CD cumulative probabilities of receiving corticosteroids (CSs), immunosuppressants (ISs) and anti tumor necrosis factor therapy were respectively 47%, 27% and 9% at 10u2005years. In UC cumulative probabilities of receiving CS and IS were 40% and 15%, respectively at 10u2005years. Cumulative probabilities of surgery at 1 year and 10u2005years were 18% and 32%, respectively in CD and 4% and 8%, respectively in UC. In CD complicated behaviour at diagnosis (HR: 2.6; 95% CI 1.5 to 4.6) was associated with an increased risk for surgery while CS was associated with a decreased risk (HR: 0.5; 0.3 to 0.8). In UC CS was associated with an increased risk (HR: 2.2; 1.1 to 4.6) for colectomy. Conclusions Clinical course is mild in elderly-onset IBD patients. This information would need to be taken into account by physicians when therapeutic strategies are established.

The changing pattern of Crohn’s disease incidence in northern France: a continuing increase in the 10‐ to 19‐year‐old age bracket (1988–2007)

Aliment Pharmacol Ther 2011; 33: 1133–1142

Epidemiology of inflammatory bowel diseases: New insights from a French population-based registry (EPIMAD)

Most data regarding the natural history of inflammatory bowel diseases and their therapeutic management are from tertiary referral-centres. However, the patients followed in these centres represent a selected sample and extrapolation of these data to the general population is disputable. The EPIMAD Registry covers a large area of Northern France with almost 6 million inhabitants representing 9.3% of the entire French population. From 1988 to 2008, 18,170 incident patients were recorded in the registry including 8071 incident Crohns disease, 5113 incident ulcerative colitis and 591 unclassified inflammatory bowel disease cases. The aim of this study was to review some of the most recent information obtained from this large population-based registry since its launch in 1988.

Pre-operative management is associated with low rate of post-operative morbidity in penetrating Crohn?s disease

Aliment Pharmacol Ther 2010; 32: 459–465

Action ofin situ nitroglycerin on upper anal canal pressure of patients with terminal constipation

Nitroglycerin (NTG)in situreduces the pressure of the upper anal sphincter (UAS). We have tested the effects of NTG on the UAS of patients with terminal constipation. We studied two groups of constipated patients. Group 1 consisted of 11 patients (nine females and two males) with hypertonicity of the UAS (>70 mm Hg); age was 49.5±15.6 years. Group 2 consisted of 10 patients (nine females and one male) without hypertonicity; age was 40.1±14.1 years. Group 3 consisted of eight asymptomatic controls (four females and four males); age was 51.7±6.9 years. After a 10-minute resting pressure recording of the UAS with a water-filled balloon, the probe was pulled through the outside and the UAS was assessed after spreading 5 mg of placebo and then 5 mg of NTG on the balloon. Resting pressure (RP), delay of the pressure decrease (DP), pressure after five minutes either during the NTG (PN5) or placebo (PP5) period, and mean duration of the pressure decrease (MD) were measured. None of the subjects experienced a decrease of PP5vs.RP. All patients in Group 1 (106.2vs.38.4 mm Hg), Group 2 (57.9vs.31.4 mm Hg), and controls (62.2vs.33.7 mm Hg) experienced a significant decrease of pressure of the UAS (P<0.005). Delay of the pressure decrease was less than two minutes, with wide interindividual variability of duration of the pressure decrease. Mild side effects—anal pain and transient headache—were reported in five patients.In situNTG significantly reduced UAS Pressure in all groups. NTG has to be evaluated in anal pathology, especially in patients with hypertonic sphincter terminal constipation or acute hypertonicity of the sphincter due to a fissure.

Long-term outcome after first intestinal resection in pediatric-onset Crohn's disease: a population-based study.

Background:To describe long-term postoperative evolution of pediatric-onset Crohns disease (CD) and identify predictors of outcome we studied a population-based cohort (1988–2004) of 404 patients (0–17 years), of which 130 underwent surgery. Methods:Risks for a second resection and first need for immunosuppressors (IS) and/or biologics were estimated by survival analysis and Cox models used to determine predictors of outcome. Impact of time of first surgery on nutritional catch-up was studied using regression. Results:In all, 130 patients (70 females) with a median age at diagnosis of 14.2 years (interquartile range: 12–16) were followed for 13 years (9.4–16.6). Probability of a second resection was 8%, 17%, and 29% at 2, 5, and 10 years, respectively. In multivariate analysis, age <14, stenosing (B2) and penetrating (B3) behaviors and upper gastrointestinal location (L4) at diagnosis were associated with an increased risk of second resection. Probability of receiving IS or biologics was 18%, 34%, and 47% at 2, 5, and 10 years, respectively. In multivariate analysis, L4 was a risk factor for requiring IS or biologics, while surgery within 3 years after CD diagnosis was protective. Catch-up in height and weight was better in patients who underwent surgery within 3 years after CD diagnosis than those operated on later. Conclusions:In this pediatric-onset CD study, mostly performed in a prebiologic era, a first surgery performed within 3 years after CD diagnosis was associated with a reduced need for IS and biologics and a better catch-up in height and weight compared to later surgery.

Aluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice

The increasing incidence of inflammatory bowel diseases (IBDs) in developing countries has highlighted the critical role of environmental pollutants as causative factors in their pathophysiology. Despite its ubiquity and immune toxicity, the impact of aluminum in the gut is not known. This study aimed to evaluate the effects of environmentally relevant intoxication with aluminum in murine models of colitis and to explore the underlying mechanisms. Oral administration of aluminum worsened intestinal inflammation in mice with 2,4,6-trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis and chronic colitis in interleukin 10-negative (IL10−/−) mice. Aluminum increased the intensity and duration of macroscopic and histologic inflammation, colonic myeloperoxidase activity, inflammatory cytokines expression, and decreased the epithelial cell renewal compared with control animals. Under basal conditions, aluminum impaired intestinal barrier function. In vitro, aluminum induced granuloma formation and synergized with lipopolysaccharide to stimulate inflammatory cytokines expression by epithelial cells. Deleterious effects of aluminum on intestinal inflammation and mucosal repair strongly suggest that aluminum might be an environmental IBD risk factor.

Effects of Infliximab Therapy on Abdominal Fat and Metabolic Profile in Patients with Crohn's Disease

Background: Tumor necrosis factor is an adipocytokine possessing a well‐established lipolytic effect. In Crohns disease (CD) patients, infliximab therapy may thus result in visceral fat accumulation, which is associated with an increased risk of metabolic syndrome. Methods: A total of 132 CD patients were investigated. In a first prospective study, magnetic resonance imaging (MRI) quantification of subcutaneous and visceral abdominal fat was performed before and 8 weeks after initiation of infliximab induction therapy (5 mg/kg at weeks 0, 2, and 6) in 21 responding patients treated for perianal disease. In a second prospective study, fasting glycemia, glycated hemoglobin (HbA1c), HDL, LDL, and total cholesterol and triglyceride levels were assessed in 111 responding patients receiving infliximab infusions every 8 weeks, with a mean follow‐up of 41 weeks. Results: A significant homogeneous 18% increase in total abdominal fat was observed in the 21 CD patients after infliximab induction therapy (P = 0.027), independently of body mass index evolution. Infliximab maintenance therapy was associated with a decrease in glycemia (P < 0.0001) and HbA1c (P = 0.0005) concentrations, together with an increase in both total cholesterol (P = 0.02) and HDL cholesterol (P = 0.008) concentrations. All glycemic and lipid parameters remained within the normal range throughout the study. Conclusions: Infliximab induction therapy is associated with a significant increase in abdominal fat tissue in CD patients. Infliximab maintenance therapy has no deleterious effects on lipid profile and is accompanied by a decrease in glycemia and HbA1c concentrations, probably by reversing the impairment of tumor necrosis factor‐induced insulin‐mediated glucose uptake. (Inflamm Bowel Dis 2009;)

Vaccination and Risk for Developing Inflammatory Bowel Disease: A Meta-Analysis of Case–Control and Cohort Studies

BACKGROUND & AIMSnEnvironmental factors may play a key role in the pathogenesis of inflammatory bowel disease (IBD). Whether vaccination is associated causally with IBD is controversial. We performed a meta-analysis of case-control and cohort studies on the association between vaccination and the risk for IBD.nnnMETHODSnStudies and abstracts investigating the relationship between vaccination and subsequent risk for developing IBD were reviewed. Childhood or adult immunizations with any vaccine type, at any dose, and with any vaccine schedule were used as inclusion criteria.nnnRESULTSnEleven studies were included in the systematic review and meta-analysis: 8 case-control studies and 3 cohort studies. Studied vaccines were bacille Calmette-Guérin), vaccines against diphtheria, tetanus, smallpox, poliomyelitis, pertussis, H1N1, measles, rubella, mumps, and the combined measles, mumps, and rubella vaccine. Only a few details about vaccine type or route of administration were found in studies. Overall, there was no association between childhood immunization and risk for developing IBD: bacille Calmette-Guérin, relative risk (RR) of 1.04 (95% confidence interval [CI], 0.78-1.38), diphtheria, RR of 1.24 (95% CI, 0.80-1.94), tetanus, RR of 1.27 (95% CI, 0.77-2.08), smallpox, RR of 1.08 (95% CI, 0.70-1.67), poliomyelitis, RR of 1.79 (95% CI, 0.88-3.66), an measles containing vaccines, RR of 1.33 (95% CI, 0.31-5.80) in cohort studies, and RR of 0.85 (95% CI, 0.60-1.20) in case-control studies. Subgroup analysis for Crohns disease (CD) and ulcerative colitis (UC) found an association between the poliomyelitis vaccine and risk for developing CD (RR, 2.28; 95% CI, 1.12-4.63) or UC (RR, 3.48; 95% CI, 1.2-9.71). The RR of developing IBD after H1N1 vaccination was 1.13 (95% CI, 0.97-1.32).nnnCONCLUSIONSnResults of this meta-analysis show no evidence supporting an association between childhood immunization or H1N1 vaccination in adults and risk of developing IBD. The association between the poliomyelitis vaccine and the risk for CD or UC should be analyzed with caution because of study heterogeneity.