N R Lewis

Meta-analysis: deamidated gliadin peptide antibody and tissue transglutaminase antibody compared as screening tests for coeliac disease.

Background  Following the appreciation of the importance of gliadin deamidation in the immunopathogenesis of coeliac disease, diagnostic tests based on antibodies to deamidated gliadin peptides have been developed and shown to have high sensitivity and specificity.

A UK study assessing the population prevalence of self-reported gluten sensitivity and referral characteristics to secondary care.

Background Reports suggest that gluten sensitivity (GS) exists in the absence of coeliac disease (CD). This clinical entity has been termed noncoeliac gluten sensitivity (NCGS). Objectives To determine the population prevalence of self-reported GS and referral characteristics to secondary care. Patients and methods A UK population-based questionnaire screened for GS and related symptoms. Diagnostic outcomes were also analyzed in patients referred to secondary care with GS. CD diagnosis entailed a positive coeliac serology (endomysial and/or tissue transglutaminase antibodies) plus Marsh 1–3 on duodenal biopsies. NCGS diagnosis was based on exclusion of CD. Clinical comparisons were made between NCGS and CD. Results A total of 1002 adults in the population (female 55%, mean age 39 years). The self-reported prevalence for GS was 13% (female 79%, mean age 39.5 years, P<0.0001), with 3.7% consuming a gluten-free diet and 0.8% known to have a doctor diagnosis of CD. Individuals with GS had an increased prevalence of fulfilling the Rome III criteria for irritable bowel syndrome, in comparison with those without GS (20 vs. 3.89%, odds ratio 6.23, P<0.0001). In secondary care 200 GS patients (female 84%, mean age 39.6 years) were investigated, in whom 7% were found to have CD and 93% to have NCGS. All CD patients were human leucocyte antigen DQ2 or DQ8 positive compared with 53% of NCGS cases (P=0.0003). Nutritional deficiencies (P⩽0.003), autoimmune disorders (23.1 vs. 9.7%, P=0.0001) and a lower mean BMI (23.7 vs. 25.8, P=0.001) were significantly associated with CD compared with NCGS. Conclusion GS is commonly self-reported with symptoms suggesting an association with irritable bowel syndrome. The majority of patients have NCGS, an entity which demonstrates clinical and immunologic difference to CD.

No increase in risk of fracture, malignancy or mortality in dermatitis herpetiformis: a cohort study

Background  Dermatitis herpetiformis forms part of the same spectrum of gluten‐sensitive disorders as coeliac disease yet may have different risks of morbidity and mortality.

Cholesterol profile in people with newly diagnosed coeliac disease: a comparison with the general population and changes following treatment.

Recent studies have suggested that untreated coeliac disease is associated with lower total cholesterol than in the general population while the effect of treatment with a gluten-free diet on the cholesterol profile of clinically apparent coeliac disease is not known. We measured the cholesterol profile at diagnosis, and compared this with Health Survey for England figures, and again following 12 months treatment with a gluten-free diet in 100 consecutive adults with coeliac disease attending the Royal Hallamshire Hospital, Sheffield, UK. The mean total cholesterol was 4.84 (SD 1.2) mmol/l in adults (mean age 51 (SD 16) years) newly diagnosed with coeliac disease. At diagnosis of coeliac disease, men had 21% lower and women had 9% lower mean total cholesterol in comparison to the general population (difference in age-adjusted mean total cholesterol -1.09 mmol/l (95% CI -0.97, - 1.21); -0.46 mmol/l (95% CI -0.24, -0.68), respectively). There was no change in mean total cholesterol following treatment. However, there was a small but statistically significant increase of 0.12 mmol/l (95% CI 0.05, 0.18) in the mean HDL-cholesterol. Total cholesterol was lower at diagnosis in coeliac patients than in the general population and did not increase with 1 year of a gluten-free diet while HDL-cholesterol increased following treatment. Any increase in risk of IHD or stroke in people with coeliac disease is unlikely due to an adverse cholesterol profile either before diagnosis or after treatment with a gluten-free diet.

Risk of morbidity in contemporary celiac disease

Celiac disease is one of the most common chronic diseases encountered in the Western world with a serological prevalence of approximately 1%. Since it is so common, much comorbidity will occur either as associations or simply by chance, or as complications of the disorder. Many of the published studies purporting to establish the frequency of these occurrences have been limited by factors such as the source and number of patients considered, choice of control groups and ascertainment bias. Recent epidemiological studies have attempted to minimize these sources of error and provide more reliable information. Autoimmune diseases constitute clinically important associations, of which Type 1 diabetes mellitus and thyroid disorders are the most important. Several liver disorders, including primary biliary cirrhosis and primary sclerosing cholangitis, are also associated. The frequency of malignant complications of celiac disease is much lower than earlier studies have indicated, with lymphoma increased by approximately fivefold and the absolute number of tumors is small. The increase in fracture risk in celiac disease is only modest. Although neurological and psychiatric conditions affect celiac patients, no disorder specifically associated with celiac disease has been identified. Reproductive problems have been overexaggerated. It is important that these co-morbidities are recognized because if not, symptoms will be falsely attributed to deliberate or inadvertent ingestion of gluten, rather than prompt a search for a second diagnosis. Furthermore, in a patient with an established diagnosis that is considered falsely to account for the whole clinical picture, celiac disease is likely to remain undetected.

Morbidity and Mortality Associated with Celiac Disease

Since celiac disease (CD) is common, with a serological prevalence of about 1 % in the Western world, comorbidity will occur by chance, as associations or as complications. Recent epidemiological studies designed to address the frequency of these occurrences have tried to minimize problems with earlier investigations which have been limited by factors such as the source and number of patients considered, choice of control groups, and ascertainment bias. Autoimmune diseases constitute clinically important associations, of which type 1 diabetes mellitus and thyroid disorders are the best studied. The frequency of malignant complications is lower than earlier studies have indicated, with lymphoma increased about fivefold. The absolute number of tumors is small. The increase in fracture risk is modest. Neurological and psychiatric conditions occur, but no disorder specifically associated with CD has been identified. Infertility associated with CD has been overexaggerated. It is important that comorbidities are identified; otherwise, symptoms may be falsely attributed to CD in relapse rather than prompt a search for another diagnosis. Furthermore, in a patient with an established diagnosis that appears to account for the whole clinical picture, CD may be overlooked.

PTU-047 High prevalence of clostridium difficile ribotype 078 in IBD outpatients

Background and Objectives Point prevalence studies have reported higher carriage rates of C. difficile in IBD patients compared with the general population, but longitudinal prospective data are lacking. The objectives of this observational study were to investigate and molecularly characterise isolates of C. difficile, collected prospectively on a monthly basis over a one-year period among IBD outpatients and healthy controls (HC). Methods At enrolment, recruited participants had established diagnoses of UC (n=16) and Crohn’s disease (n=6) and reported no recent hospitalisation or exposure to antibiotics. PCR ribotype and toxin status (cytotoxigenic culture) were determined for all +ive stool cultures. All participants underwent a monthly telephone interview to identify potential risk factors for C. difficile acquisition (changes in medications, exposure to antibiotics, clinic attendances, hospitalisation) and to assess for disease activity (Harvey-Bradshaw Index and Simple Clinical Activity Colitis Index). Results Two patients underwent physician-initiated laboratory testing of C. difficile during the sample collection phase, although no participants developed or were treated for C. difficile infection. C. difficile was cultured from 29/223 samples (13%) representing 16/22 patients and 1 of 5 HC with concurrent antibiotic exposure in 6/29 visits (20%). Of the toxin +ive isolates (n=25; 078, 005, 302 and 015), 72% (n=21) were PCR ribotype 078. Toxigenic negative ribotypes included 023, 026 and 656. Of those toxin +ive isolates, 9 samples (36%) were associated with relapsing IBD of which 7/9 were ribotype 078. Multiple stool specimens also tested +ive for different ribotypes in 3 patients with UC, all of whom were taking regular immunosuppressants. WGS studies of the 078 isolates revealed marked genetic similarity, with only 3 of the 21 isolates varying by 1 or more nucleotides when compared to the 078 reference genome, suggesting there may have been a common source for cross-transmission. Conclusions The high prevalence of PCR ribotype 078 in this IBD outpatient cohort is consistent with the recent emergence of this strain in the community. These results reinforce the importance of testing all in-and outpatients with an apparent flare or relapsing IBD for carriage of toxigenic C. difficile to inform optimal management strategies. Future research is needed to understand the predominance of 078 isolates in IBD, particularly in the context of clinical relapse.

PWE-116 Association Of Faecal Calprotectin With Extent And Distribution Of Inflammation In Ibd

Introduction Calprotectin is a protein released by neutrophils in response to the presence of inflammation in the bowel.1 Faecal calprotectin (FC) has been shown to be useful in the diagnosis of inflammatory bowel disease (IBD) as it correlates with mucosal disease activity and can help to predict response to treatment or relapse.1–3 Data from small, selected case series have observed FC correlates better with colonic rather than ileal Crohn’s disease (CD)4 and median FC concentrations are higher in extensive or left-sided ulcerative colitis (UC) disease than in proctitis.5 We report the association of FC concentration with extent and distribution of inflammation in consecutively performed tests at our centre. Methods All FC tests performed between 01/07/12 and 31/12/12 were systematically collected and associations with activity and distribution using endoscopic, histological and radiological data explored. Proximal disease was defined as inflammation affecting the terminal ileum and ascending colon; left-sided disease as inflammation limited to the colorectum distal to the splenic flexure and pan-colitis with inflammation extending proximal to the splenic flexure. Results 203 (n = 160 CD; n = 43 UC) patients with IBD had FC tests performed of whom 96 (47.3%) had endoscopic, histological or radiological evidence of active disease. The mean age of IBD patients was 44.7 (SD 17.0) years and 58% were female. The mean FC concentration was significantly higher in patients with active pan-colitis (1038.1 iu (SD 1104.1)) than in active left-sided disease (mean 820.2 iu (SD 1535.1)); p = 0.01. The mean FC concentration was significantly higher in active pan-colitis than in active proximal disease (mean difference -669.3 iu (95% CI-1046.3, -292.4)); p = <0.001. There was no significant difference in the mean FC concentration between active proximal or left-sided disease (mean difference –451.5 (95% CI -965.9, 62.9) or between CD and UC (mean difference 148.5 (95% CI-369.1–666.1). Conclusion Mean FC concentrations are significantly higher in active pan-colitis than in active left-sided or proximal disease, perhaps reflective of the greater extent of inflammation. Further work is required to explore why FC concentrations are lower in proximal disease despite presence of active inflammation. References World J Gastroenterol 2012;18(46):6782–6789 Gut 2005:54:364–368 Inflammatory Bowel Diseases 2013;19(2):332–341 Am J Gastroenterol 2010:105:162–169 Scandinavian Journal of Gastroenterology 2011:46:1081–1091 Disclosure of Interest None Declared.

PTH-126 A Functional Model of of a ‘Seven Day Acute Gastroenterology Service’: Looking Beyond Out-Of-Hours Endoscopy

Introduction Early involvement and management by specialists has been shown to have a favourable impact on outcomes in a number of acute medical conditions. Increased patient mortality at weekends has also been attributed to limited access to specialist services. While an increasing number of hospitals provide an out-of-hours service for upper gastrointestinal bleeding, examples of a comprehensive acute Gastroenterology services are infrequent. Methods In January 2007, we established an acute gastroenterology service to provide consultant-lead assessment and management for all patients identified through acute servieces with symptoms related to gastrointestinal and hepato-pancreatico-biliary conditions. The consultant of the week lead and delivered the service supported by a registrar and a dedicated inpatient endoscopy team, free from any commitment to elective services. Inpatient care was supported by daily consultant led ward rounds. We achieved the ‘critical mass’ to deliver this service by consolidating all inpatient work on on site. Results Mean LOS of all patients discharged with a gastroenterology HRG, from the specialist gastroenterology ward was 7.6 days, and from non-specialist medical beds was 9.6 days. Overall the specialist gastroenterology ward provided care for 1.8 times more patients compared with other Medical wards of the same size at NUH. Actual mean LOS (for the period of 2011–2012) was significantly shorter than the ‘expected’ LOS, and than mean peer LOS for 4 main diagnostic categories (table) with no significant increase in readmission rates. Discharge rates were maintained at the same level during the weekend (mean 4 discharges per weekday and on Saturday, with a peak of 6 discharges on Fridays and a dip to a mean of 3 discharges on Sunday. Abstract PTH-126 Table 1 Diagnosis NUH actual LOS (days) NUH expected LOS (days) Peer mean LOS (days) % difference GI Bleed 4.2 5.8 5.8 -27% Acute colitis 6.3 7.2 7.6 -15% ALD 6.6 11.7 11.5 -43% Other liver disease 5.8 8.7 6.9 -15% Abstract PTH-126 Figure 1 Conclusion Specialist led care can be provided to all patients with acute gastrointestinal and hepato-pancreatico-biliary conditions. A functional 7-day ‘acute gastroenterology’ can be sustained to provide high quality and intensity of care with favourable outcomes. Disclosure of Interest None Declared.

PTH-091 Is the diagnosis of coeliac disease associated with socio-economic status? A population-based study: Abstract PTH-091

Introduction The rate of diagnosis of coeliac disease in developed countries has increased dramatically since the introduction of serological tests without an obvious environmental precipitant. Little is known about the socio-economic distribution of coeliac disease; there is some evidence that it is less common in more deprived social groups.1 We quantified the incidence of new diagnoses of coeliac disease by socio-economic status in a large, contemporary and population-based cohort. Methods The postcode of residence at diagnosis in consecutive incident adult cases of coeliac disease (n = 837) between January 2000 and December 2006 at Nottingham University Hospital and Royal Hallamshire Hospital was used to determine the Index of Multiple Deprivation 2007 (IMD07) score.2 Incidence rates were calculated using the total adult population for Sheffield and Nottingham derived from UK 2001 National Census categorised into corresponding IMD07 quintiles and Poisson models were fitted. Results There was a strong, independent graded association between the incidence rate of new diagnoses of coeliac disease and socio-economic status. The incidence rate of coeliac disease was twice as high for the least deprived quintile (age- and sex-adjusted IRR* 1.93, 95% CI 1.61 to 2.44) compared with the most deprived quintile. Socio-economic status in incident coeliac disease was not associated with more severe coeliac disease (OR for quintile V to quintile I for presence of malabsorption 1.04, 95% CI 0.47 to 2.28; and for Marsh 3b, 3c histological change OR 0.87, 95% CI 0.56 to 1.34) (Abstract 091). Abstract PTH-091 Incidence of coeliac disease by socio-economic status Quintiles of rank of IMD07 score N Rate/1000 population Crude IRR (95% CI) Adjusted* IRR (95% CI) I Most deprived 160 0.07 1.00 1.00 II Below average 125 0.09 1.23 (0.99 to 1.58) 1.22 (0.96 to 1.53) III Average 170 0.13 1.69 (1.36 to 2.09) 1.61 (1.30 to 2.00) IV Above average 168 0.15 1.97 (1.59 to 2.44) 1.82 (1.50 to 2.30) V Least deprived 189 0.17 2.20 (1.79 to 2.71) 1.93 (1.61 to 2.44) Conclusion The rate of new diagnoses of coeliac disease was twice as high in people from affluent areas compared with that in people living in poorer areas. This striking difference could be due to variation in environmental exposures such as breastfeeding practices3 or could be accounted for by differences in uptake and utilisation of health services.