Alexander J. Johnston

Increased Detection of Celiac Disease With Measurement of Deamidated Gliadin Peptide Antibody Before Endoscopy

BACKGROUND & AIMS Celiac disease is underdiagnosed. Many patients are examined by endoscopy, but celiac disease is missed or not detected. We evaluated the accuracy of finger prick-based point-of-care tests in the detection of celiac disease and developed an algorithm for diagnosis. METHODS We performed a prospective study of 2 groups of patients with celiac disease evaluated at the Royal Hallamshire Hospital in Sheffield (United Kingdom) from March 2013 through February 2014. In group 1, patients at high risk of celiac disease who tested positive for endomysial antibody (n = 55) were evaluated using the Biocard test (BHR Pharmaceuticals, Nuneaton, UK) and the Celiac Quick Test (Biohit Healthcare UK, Ellesmere Port, UK), which measure antibodies to tissue transglutaminase (anti-tTG), and the Simtomax test (Tillotts Pharma, Rheinfelden, Switzerland), which measures deamidated gliadin peptide antibodies (DGP). Patients in group 2 (508 consecutive patients who underwent an endoscopy examination for any indication) received the DGP test, and also were evaluated using a diagnostic algorithm that incorporated results from the DGP test and data on symptoms. In both groups, point-of-care tests were taken at the time of endoscopy and results were compared with results from histologic analyses of duodenal biopsy specimens from all patients. RESULTS In group 1, the DGP test identified patients with celiac disease with 94.4% sensitivity, the Celiac Quick Test identified patients with 77.8% sensitivity (P = .03 vs the DGP test), and the Biocard test identified patients with 72.2% sensitivity (P = .008 vs the DGP test). In group 2, the DGP test identified patients with celiac disease with 92.7% sensitivity (95% confidence interval, 83.0-97.3), 85.2% specificity (95% confidence interval, 81.5-88.3), a positive predictive value of 49.2% (95% confidence interval, 40.3-58.2), and a negative predictive value of 98.7% (95% confidence interval, 96.8-99.5). Measurement of serum anti-tTG identified patients with celiac disease with 91.2% sensitivity (95% confidence interval, 81.1-96.4), 87.5% specificity (95% confidence interval, 84.0-90.4), a positive predictive value of 53.0% (95% confidence interval, 43.6-62.2), and a negative predictive value of 98.5% (95% confidence interval, 96.5-99.4). The algorithm identified patients with celiac disease with 98.5% sensitivity; its use could reduce duodenal biopsies by 35%. CONCLUSIONS In a prospective study, a test for DGP identified patients with celiac disease with similar levels of sensitivity and specificity as standard serologic analysis of anti-tTG. Use of the DGP test before endoscopy could increase the accuracy of the diagnosis of celiac disease. Further studies, in lower-prevalence populations, are required to assess the impact of the test in clinical practice.

Point-of-care testing for celiac disease has a low sensitivity in endoscopy

BACKGROUND Celiac disease (CD) is a common but underdiagnosed condition. A rapid point-of-care test (POCT) could reduce lead times and missed diagnoses. OBJECTIVE To assess the utility of an immunoglobulin (Ig) A tissue transglutaminase (TTG) antibody POCT in an endoscopic setting. DESIGN Prospective observational study. SETTING A single UK university hospital. PATIENTS Patients presenting with suspected CD, known CD, and routine endoscopy for upper GI symptoms. INTERVENTIONS All patients were tested with POCT, serum TTG, endomysial antibody (EMA), and upper GI endoscopy with duodenal biopsies at the same visit. MAIN OUTCOME MEASUREMENTS Comparison was made with histology in all cases, with villous atrophy regarded as diagnostic of CD. RESULTS A total of 576 patients (63.5% female, mean [± standard deviation] age 49.7 years [± 17.6 years]) were recruited. A total of 523 patients had no prior diagnosis of CD, and 53 patients had known CD coming for reassessment. A total of 117 patients were newly diagnosed with CD, and 82 were positively identified by the POCT. Sensitivity, specificity, positive predictive value, and negative predictive value were 70.1%, 96.6%, 85.4%, and 91.8%, respectively. In comparison, TTG and EMA both performed significantly better than the POCT. Sensitivity and specificity of TTG were 91.0% and 83.5%, respectively, and EMA were 83.8% and 97.5%, respectively. Of patients with known CD coming for reassessment, 26 had villous atrophy, and POCT results were positive in 16 (61.5%). There was poor agreement between POCT and standard serology. LIMITATIONS High pre-test probability of CD. CONCLUSION The performance of this POCT was disappointing compared with standard serology and cannot at present be recommended within the context of an endoscopy unit.

High definition endoscopy with or without I-Scan increases the detection of celiac disease during routine endoscopy.

BACKGROUND AND AIMS Celiac disease remains underdiagnosed at endoscopy. We aimed to assess the utility of I-Scan (virtual chromo-endoscopy) to improve sensitivity of endoscopy to detect markers of villous atrophy in this condition. METHODS Patients from 2 UK hospitals were studied in 3 groups. Group 1: standard high definition, white light endoscopy (WLE); Group 2: WLE plus I-Scan; Group 3: non-high definition control group. The presence of endoscopic markers was recorded. At least 4 duodenal biopsies were taken from all patients. Serology was performed concurrently and observations were compared with histology. RESULTS 758 patients (62% female, mean age 52) were recruited (Group 1: 230; Group 2: 228; Group 3: 300). 135 (17.8%) new diagnoses of coeliac disease were made (21 Group 1; 24 Group 2; 89 Group 3). The sensitivity for detection of endoscopic markers of villous atrophy was significantly higher in both Group 1 (85.7%, p=0.0004) and Group 2 (75%, p=0.005) compared to non-high definition controls (41.6%). There was no significant difference between high definition only and I-Scan groups (p=0.47). In non-high definition endoscopy a missed diagnosis was associated with lesser degrees of villous atrophy (p=0.019) and low tTG titre (p=0.007). CONCLUSIONS High definition endoscopy with or without I-Scan increases the detection of celiac disease during routine endoscopy.

PTH-116 Point Of Care Testing For Adult Coeliac Disease: A Potential Role In Endoscopy

Introduction Endoscopic markers of coeliac disease (CD) lack sensitivity; therefore many centres take routine duodenal biopsies or have a low threshold for biopsy, ensuring high detection rates. Newly available, point of care tests (POCT) provide rapid findings unlike conventional serological markers, potentially reducing the need for duodenal biopsies. This study evaluates a new POCT (Simtomax) which detects IgA and IgG deamidated gliadin peptide (DGP) with comparisons made to conventional serological markers and histology. Methods Patients referred for a gastroscopy to a specialist CD list were prospectively recruited between March and November 2013. Patients were excluded if they were on a gluten free diet at the time of the test or if they had previously been diagnosed with seronegative villous atrophy. All patients had a duodenal biopsy as the gold standard for detecting CD. Concurrently serological testing for IgA tissue transglutaminase (TTG), endomysial antibody (EMA), total immunoglobulin A level and the DGP based rapid test was performed. Sensitivity, specificity, positive predictive (PPV) and negative predictive values (NPV) were calculated. Results 354 patients met the inclusion criteria (45.8% male mean age 53.3 +18.5). Of these, 52 (14.7% 11.2 – 18.9) had newly diagnosed CD and 302 were controls with a normal duodenal biopsy. The sensitivity, specificity, PPV and NPV for the POCT were 94, 83, 49 and 99% respectively. This compares with results for TTG of 92, 88, 57, 99 and EMA of 88, 97, 85, and 98% respectively. In a second cohort, 43 patients with known CD for re-assessment were recruited (20.9% male, mean age 49.4 +16.6). 16 (37% 23 -53) of these 16 patients (37%) had persistent villous atrophy despite a gluten free diet. POCT compared to histology showed sensitivity of 88% and specificity 41%. tTG showed sensitivity and specificity of 63 and 70% respectively and EMA 56 and 78% respectively. However agreement between histology and POCT was poor with concordance between results in only 60% (κ=0.274). tTG and EMA were marginally better with κ=0.321 and κ=0.345 respectively. Conclusion This is the first study to prospectively demonstrate the value of a novel POCT for adult CD in endoscopy compared to the gold standard of histology. The sensitivity and specificity of the POCT is comparable to conventional serology. Simtomax could be used to appropriately identify patients requiring a duodenal biopsy within the endoscopic setting. This strategy may be cost effective by reducing the number of routine duodenal biopsies taken. Further work is required to clarify the role of POCT for the assessment of histological remission in patients with known CD. Disclosure of Interest None Declared.

PTH-119 High Definition (hd) Endoscopy With I-scan For The Detection Of Markers Of Coeliac Disease: A Feasibility Study

Introduction Coeliac disease (CD) remains underdiagnosed. Previous studies have shown that up to 13% of patients with CD have undergone a previous gastroscopy where the opportunity to take duodenal biopsies and make a diagnosis had been missed. Clinicians may rely on the presence of endoscopic markers of CD to guide biopsy however these have been shown to lack the required sensitivity. A routine duodenal biopsy approach may solve this problem but this is time consuming and expensive. Methods to improve the macroscopic detection of CD at endoscopy to guide biopsy would seem advantageous. A single trial on I-Scan, a commercially available digital enhancement technique, has shown promising results in identifying markers of villous atrophy. However this was an uncontrolled, unblinded trial in high prevalence population (35% CD). We aimed to assess the utility of I-Scan in a lower prevalence population in a randomised controlled trial. Methods Patients on a single coeliac enriched endoscopy list were randomised into 2 groups. Group 1 standard HD white light endoscopy (WLE) and group 2 WLE plus I-Scan. The presence of endoscopic markers of CD, scalloping, mosaic pattern, nodularity, loss of duodenal folds or increased vascularity was noted throughout the duodenum. All patients received 4 biopsies from the second part of the duodenum and at least 1 biopsy from the bulb. Coeliac serology was taken at the time of endoscopy. Macroscopic markers of CD are compared to the presence of villous atrophy on histology as the gold standard. 3, 10-point likert scales for pain, discomfort and distress were used to assess tolerability. Results 116 patients (66 female, mean age 54.9 SD 17.5) have been recruited to date (55 into group 1 and 61 in group 2). In total 14 (12.1%) new diagnoses of CD have been made. I-Scan appears to enhance the appearance of markers for CD and in a single patient in group 2 CD markers that were not noted to be seen on WLE became apparent. Preliminary results show that endoscopic markers of CD across both groups currently have a sensitivity of 78.6% (48.8 – 94.3), specificity 82.4% (73.3 – 88.9), positive and negative predictive values of 37.9% (21.3 – 57.6) and 96.6 (89.5 – 99.1). Median tolerability scores were good in both groups but better in the I-Scan group than WLE alone (4/30 vs. 8/30 p 0.005). Conclusion The addition of I-Scan to standard endoscopy to aid the diagnosis of CD is well tolerated and is feasible. I-Scan appears to enhance the markings of coeliac disease, however a larger study is required to truly evaluate the effectiveness of I-Scan as an adjunct to standard endoscopy to increase CD diagnosis. Disclosure of Interest None Declared.

PTU-018 Can Chromoendoscopy help in Coeliac Disease as Part of a Duodenal Biopsy Strategy?

Introduction Chromoendoscopy is increasingly being used to detect, localise and characterise mucosal abnormalities, however its role in coeliac disease remains to be established. Endoscopic markers of coeliac disease (reduction of folds, scalloping, mosaic pattern, visible blood vessels and nodularity of the duodenal folds) are often difficult to recognise, therefore many centres take routine duodenal biopsies or have a low threshold for biopsy, ensuring high detection rates. This study evaluates if dye spray can improve identification of endoscopic markers of coeliac disease, potentially leading to a biopsy avoidance strategy. Methods Patients undergoing clinically indicated oesophogastroduodenoscopy (OGD) were prospectively recruited from a single endoscopy list between January 2011 and November 2012. Patients were divided into two groups: patients with no previous history of coeliac disease (Group 1, n = 201) and patients with established coeliac disease (Group 2, n = 24). Eight experienced endoscopists undertook all procedures, with endoscopic findings reported both before and after the use of indigo carmine dye spray. Endoscopic findings were compared using a McNemar test, with p values < 0.05 considered significant. In addition, endoscopic findings were compared to histological findings to determine sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) for differing endoscopic techniques. Results Of the 225 patients recruited, 97 (43%) had positive serology (either endomysial or tissue transglutaminase antibodies). In Group 1, 61(30%) were newly diagnosed coeliac patients with endoscopic markers identified in 44% (27/61). Dye spray use within the duodenum identified a further 5 patients (32/61, 52%), however this improvement in diagnostic yield was not statistically significant (P = 0.63). Sensitivity, specificity, positive and negative predictive values for standard endoscopy to detect coeliac disease were 44%, 99%, 93%, 80% respectively compared to 52%, 99%, 94%, 83% for chromoendoscopy. In Group 2, 12 patients had persisting Marsh 3 changes at biopsy, however endoscopic markers were identified in only 5 (21%) with dye only increasing yield by a further one patient (6/24, 25%). Conclusion Dye spray is easy to use and inexpensive (<£1/endoscopy), however in our study derived no additional benefit to conventional endoscopy for diagnosing patients with coeliac disease. Given the low sensitivity of endoscopic markers, we advocate duodenal biopsies in all patients where there is a high clinical suspicion of coeliac disease, irrespective of the endoscopic mucosal findings. Disclosure of Interest None Declared