Defining and Assessing the Reproducibility of Crohn's Disease Endoscopic Lesions: A Delphi-like Method from the GETAID.

BACKGROUND AND AIMS: Defining and assessing the reproducibility of Crohn's disease [CD] endoscopic lesions is essential in assessing endoscopic healing. METHODS: Twelve endoscopic CD experts from the GETAID defined aphthoid erosions [AE], superficial ulcerations [SU], deep ulcerations [DU], stenosis, and fistulas according to a Delphi-like method. Thirty different GETAID physicians declared if they found acceptable each definition. Intra- and inter-observer agreements were investigated using 100 videos with one tagged specific lesion [AE, SU, DU, or sham lesion] read by 15 independent endoscopists at baseline and 1 month later in a randomised order. Video quality was determined by an external reader. According to kappa estimate [κ ±standard error], intra or inter-observer agreement was qualified as 'moderate' [0.4-0.6], 'substantial' [0.6-0.8], or 'almost perfect' [0.8-1.0]. RESULTS: Among 30 different experts, 83% to 97% found acceptable the definitions retrieved from the Delphi-like method. Intra-observer κ was 0.717 [±0.019] for SU, 0.681 [±0.027] for AE, 0.856 [±0.014] for DU, showing 'substantial' agreement. It was 0.801 [±0.016] for any ulceration [DU or SU]. There was a high variability across readers from 'moderate' to 'almost perfect' agreement. Inter-observer κ was 0.548 [±0.042] for SU, 0.554 [±0.028] for AE 0.694 [±0.041] for DU, and 0.705 [±0.042] for any ulceration. Inter-observer agreement increased when reading the 53 high-quality videos: 0.787 [±0.064] [p = 0.001], 0.607 [±0.043] [p = 0.001], and 0.782 [±0.064][p = 0.001] for DU, AE, and any ulceration, respectively. CONCLUSIONS: Despite variable intra-agreement level across readers, the GETAID definitions for CD endoscopic lesions provided 'substantial' inter-observer agreements, especially in case of high-quality videos.

Serum calprotectin as a biomarker for Crohn's disease.

BACKGROUND AND AIMS: In Crohn's disease, correlation between clinical assessment and disease activity at tissue level is weak. Our aim was to evaluate the value of serum calprotectin as a biomarker for Crohn's disease. METHODS: The STORI trial patients (n=115) were studied at baseline, in clinical remission before infliximab withdrawal, or at the time of relapse after infliximab withdrawal. Forty healthy controls were also studied. Serum calprotectin level was measured by ELISA. Data were analyzed through correlation analyses, Kaplan Meier curves and Cox model, using available Crohn's Disease Activity Index (CDAI), Crohn's Disease Endoscopic Index of Severity (CDEIS), fecal calprotectin and C-reactive protein levels (hsCRP). RESULTS: Median serum calprotectin was 8892 ng/mL (range: 410-125,000 ng/mL) in Crohn disease patients as compared with 1318 ng/mL (range: 215.8-3770 ng/mL) in controls (P<0.0001). Serum calprotectin was significantly higher for active disease (median=19,584 ng/mL) than for inactive disease (median=8353 ng/mL) (P<0.0001). Serum calprotectin correlated with hsCRP (r=0.4092, P<0.0001) and CDAI (r=0.4442, P<0.0001), but not with CDEIS, on the contrary to fecal calprotectin (r=0.6458, 0.5515, 0.2577 with P<0.0001, P<0.0001, P=0.019 respectively). In multivariate analysis, serum calprotectin used as a discrete variable (threshold: 5675 ng/ml), appeared complementary to hsCRP (>5 mg/l) and fecal calprotectin (>250 µg/g) to predict relapse after infliximab withdrawal (P=0.0173, 0.0024 and 0.0002; HR: 3.191, 3.561 and 4.120). CONCLUSIONS: As a CD biomarker, serum calprotectin has a similar profile as hsCRP. It is also complementary to fecal calprotectin and hsCRP for prediction of relapse after infliximab withdrawal.

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).

BACKGROUND: Crohn's disease incidence rates have stabilised in industrialised countries since the 1980s. Conversely, a continuing increase in childhood-onset Crohn's disease incidence has been reported. AIM: To confirm trends in inflammatory bowel disease (IBD) incidence in northern France over an extended time period (1988-2007) with a focus on childhood-onset Crohn's disease. METHODS: The IBD patients recorded in the EPIMAD registry between 1988 and 2007 were included. Standardised incidence rates were calculated for Crohn's disease and ulcerative colitis in the entire population, and separately according to age. Evolution of phenotypes at diagnosis was also studied. RESULTS: A total of 12 084 incident IBD cases (7428 Crohn's disease and 4656 ulcerative colitis) were recorded. Crohn's disease incidence rates increased from 5.2 cases/100 000 persons in 1988-1990 to 6.7 in 2006-2007 (+29%), stabilising after a peak at 7.1 in 1997-1999. Crohn's disease incidence rates in the 10-19-year age category increased by 71%, from 6.5 (1988-1990) to 11.1 (2006-2007). The frequency of initial ileo-colonic localisation increased from 52.9% in 1988-1990 to 68.6% in 2006-2007 (P<0.0001). Ulcerative colitis incidence rates decreased during the same period. CONCLUSIONS: From 1988 to 2007, Crohn's disease incidence increased by 29% in northern France and by 71% in the 10-19-year-old age group. Consequently, studies on Crohn's disease risk factors should focus on the population under 20 years of age.

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

BACKGROUND: Ileocaecal resection for penetrating Crohn's disease is still challenging with a high rate of post-operative morbidity and faecal diversion. AIM: To report retrospectively the results of pre-operative management for penetrating Crohn's disease focusing on the rate of post-operative major morbidities and need for faecal diversion. METHODS: Between 1997 and 2007, 78 patients with penetrating Crohn's disease underwent a first ileocaecal resection after a pre-operative management consisting in bowel rest, nutritional therapy, intravenous antibiotics, weaning off steroids and immunosuppressors, and drainage of abscesses when appropriate. RESULTS: Resection was performed for terminal ileitis associated with (n = 41), abscesses (n = 37) or both (n = 5). A pre-operative nutritional therapy was performed in 50 patients (68%) for 23 days (range, 7-69 days) along with a weaning off steroids and immunosuppressors. A diverting stoma was performed for six patients (7.7%). There was no post-operative death. Post-operative complications were classified as minor in 10 patients (12.8%), and major in four patients (5%). Overall, the post-operative course was uneventful in 58 patients (74%). CONCLUSION: Pre-operative management for penetrating Crohn's disease allowed ileocaecal resection with low rates of post-operative morbidity and faecal diversion.

[Inflammatory bowel disease: genetic or environmental diseases?]. / Maladies inflammatoires chroniques de l'intestin: maladies génétiques ou de l'environnement?

Pathophysiology of inflammatory bowel diseases depends on the interaction between genetic susceptibility and environmental factors leading to a deregulated immune intestinal response resulting in bowel lesions. Epidemiologic variations of inflammatory bowel diseases with time (incidence, prevalence) and space suggest a role for risk environmental factors, but so far only smoking habits and appendectomy have been identified as influencing the risk of occurrence and the course of the diseases. Studies of monozygotic and dizygotic twins and the existence of familial aggregation are strong evidence for an important, but not exclusive, role for genetic susceptibility. Since the discovery of NOD2/CARD15 mutations, numerous genes have been associated with inflammatory bowel diseases, some of them involved in the regulation of innate immunity and cellular clearance of infectious agents (autophagy). Thus, new hypothesis include a key role of mucosal human microbiota which could be partly influenced by environmental factors generated by modern life. The improvement of life hygiene, the change of food composition and habits, the industrial pollution in developed countries, may influence, directly or by the way of modifying intestinal human microbiota, inflammatory bowel diseases risk occurrence.

Opportunistic infections in patients with inflammatory bowel disease: prevention and diagnosis.

Because of the increasing use of immunosuppressive and biological drugs, the occurrence of opportunistic infections has become a key safety issue for patients with inflammatory bowel disease (IBD). Consequently, improvement of healthcare workers' knowledge of this domain is urgent. In this review, the preventive measures that would help to reduce the rate of opportunistic infections in patients with IBD are listed, and the management of situations frequently confronting doctors is considered. In the absence of national and international recommendations, the information given here should help doctors to optimise patient outcomes.

Nodular regenerative hyperplasia in patients with inflammatory bowel disease treated with azathioprine.

AIM: To assess the characteristics and clinical course of nodular regenerative hyperplasia (NRH) in patients with inflammatory bowel disease treated with azathioprine, so as to estimate the frequency of this complication and search for risk factors. METHODS: Cases were identified through a systematic survey of patients followed at 11 centres. At one centre, the cumulative risk of NRH was estimated and a case-control study was undertaken to identify risk factors. RESULTS: 37 cases of NRH (30 male, 7 female) were identified between 1994 and 2005. The median dose of azathioprine was 2 mg/kg/d (range 1.5 to 3.0). The median time between the start of azathioprine and the diagnosis of NRH was 48 months (range 6 to 187). After a median follow up period of 16 months (range 1 to 138), 14 patients developed complications of portal hypertension. Using multivariate analysis, male sex and stricturing behaviour were the two risk factors associated with NRH in patients treated with azathioprine. The cumulative risk calculated from the database (one centre) was 0.5% at 5 years (95% confidence interval, 0.11 to 0.89) and 1.25% at 10 years (0.29 to 2.21). CONCLUSIONS: NRH is a rare but potentially severe complication of azathioprine in patients with inflammatory bowel disease. Clinicians should be aware of this complication, and should monitor liver function tests and platelet counts closely in their patients.