AGA Abstracts
villous atrophy were either missed or appeared later. Targeted investigations with attention to history, laboratory results, and response to specific therapy are vital in differentiating between CD and NCE. Etiologies of Non Celiac Enteropathy
Survival by Kaplan-Meier method according to the presence of the total number of the following VCE features: proximal focal erythema, non-progression of the capsule to the distal small intestine. + = censored
Symptoms in NCE vs. Celiac Disease
149 A 10-Year Retrospective Study of Non-Responsive and Refractory Celiac Disease at a Tertiary Care Center Jeffrey M. Basile, Christopher Hammerle, Sheila E. Crowe Introduction: Non-responsive celiac disease (NRCD) is a failure to respond to being on a gluten-free diet (GFD) for greater than 6 months. Refractory celiac disease (RCD) is a subtype of NRCD with severe malabsorption and persistent intestinal damage. Patients with RCD are categorized by the absence (RCD type I) or presence (RCD type II) of an aberrant monoclonal intraepithelial T lymphocyte proliferation. We retrospectively reviewed the patients with celiac disease (CD) at the University of Virginia Health System (UVAHS) over the past ten years to assess the frequency, associated causes, and co-morbidities of NRCD including RCD. Methods: We conducted a chart review of all patients diagnosed with celiac disease followed over the past ten years at UVAHS. To be included, patients had to either have biopsy-proven celiac disease (a MARSH score of ≥ III or I to II with serological evidence of CD) or biopsy-proven dermatitis herpetiformis. NRCD was defined as a lack of clinical response or persistent laboratory abnormalities (anemia, transaminitis, or TTG IGA>30 [normal up to 20]) despite adherence to a GFD for 6 months or recurrence of symptoms (weight loss, diarrhea, or abdominal pain) after 6 months on a GFD. Results: 272 patients with CD were identified (69% female, 96% Caucasian). 97 of these CD patients (36%) were non-responders to a GFD (78% female, 94% Caucasian). Associated conditions in NRCD included diabetes mellitus (18%), thyroid disease (22%), osteopenia (8%), osteoporosis (23%), anemia (58%), elevated liver enzymes (32%), hypoalbuminemia (26%), vitamin D deficiency, (56%), folate deficiency (5%), and vitamin B12 deficiency (16%). Causes of nonresponsiveness included dietary noncompliance (32%), irritable bowel syndrome (21%), microscopic colitis (10%), gastroparesis (5%), bacterial overgrowth (4%), pancreatic insufficiency (3%), and RCD (13%). 19 of the 97 NRCD patients (20%) met criteria for RCD (3 type I, 14 type II, and 2 untyped). All of the RCD patients had evidence of malabsorption. 17 RCD patients were treated with steroids (89%) and 14 with thiopurines (74%). 11 RCD patients required temporary supplemental nutrition (enteral or parenteral). 2 RCD patients died of a celiac-related disease process (enteropathy-associated T-cell lymphoma and neurological inflammatory disorder). Conclusion: Over one-third of CD patients in our study had NRCD and one-fifth of NRCD patients had RCD. The cause of GFD failure in patients with CD was multifactorial in our population and inadvertent gluten exposure was the most common reason for non-responsiveness. Multiple co-morbidities were also found in patients with NRCD. Further evaluation of our NRCD and RCD patients in ongoing prospective studies could help determine criteria for prognosis and strategies to optimize medical management.
148 Video Capsule Endoscopy in Patients With Suspected Refractory Celiac Disease Stijn J. Van Weyenberg, Fokko Smits, Maarten A. Jacobs, Sietze T. Van Turenhout, Gerd Bouma, Chris J. Mulder Introduction - Video capsule endoscopy (VCE) allows inspection of the small intestine of patients with celiac disease (CD) not responding to a gluten free diet. Especially identification of patients with refractory celiac disease (RCD) type II or enteropathy associated T-cell lymphoma (EATL) can be of great prognostic importance. It is not clear whether specific VCE-parameters are associated with these conditions. We aimed to evaluate pre-defined VCE-features in patients with CD and symptoms despite a gluten free diet and aimed to identify parameters discriminating between RCD type I and type II, and to identify features associated with RCD type II or EATL. Methods - We performed a retrospective, blinded evaluation of 52 VCE-studies performed in patients with suspected RCD. Patients were classified as either uncomplicated, but symptomatic CD (n=22), RCD type I (n=12) or type II (n=11), and EATL (n=7) according to small bowel histology and flowcytometry. VCEstudies were evaluated for the presence of villous atrophy, mosaic pattern, scalloping of folds, mucosal fissures, focal erythema, erosions or ulcers, strictures and masses in both the proximal as the distal small intestine. Results - In multivariate analysis, none of the studied features reliably discriminated between RCD type I and type II. In multivariate analysis, the presence of proximal focal erythema (OR 6.5; 95% CI 1.2 - 34.3; p=0.028) and absence of progression of the capsule to the distal intestine (OR 15.7; 95% CI 1.2 - 207.4; p=0.037) were independently associated with the presence of RCD type II or EATL. Of the 29 patients with none of these two features, one (3.4%) died during follow-up. Of the 16 patients with one of both features was present, three (18.8%) died during follow-up. Of the seven patients with both features present, six (85.7%) died during follow-up (figure 4). These associations were statistically significant (p<0.0001). Conclusions - VCE is able to demonstrate a wide range of abnormalities in the small intestine of patients with suspected RCD. None of the studied VCE-features was able to reliably discriminate between RCD type I and type II. However, proximal focal erythema and absence of progression of the capsule to the distal intestine were strongly associated with RCD II and EATL. Additionally, the presence of these features was associated with mortality.
150 The Origin of Aberrant IEL in RCD II Patients Roy L. van Wanrooij, Greetje J. Tack, Anton Langerak, Boudewina M. von Blomberg, Danielle Heideman, Gerd Bouma, Chris J. Mulder, Marco W. Schreurs Background & Aims: Aberrant intra-epithelial lymphocytes (IEL) are the hallmark of refractory celiac disease type II (RCD II) and considered a premalignant cell population from which aggressive enteropathy-associated T cell lymphoma (EATL) can evolve. Elucidating the origin and phenotype of aberrant IEL enables a better understanding of this cell population, which possibly leads to new therapeutic options. The aim of this study was to gain further insight in the origin of aberrant IEL by analyzing T-cell receptor (TCR) rearrangements, and by immunophenotypic characterization of aberrant IEL in comparison with their normal counterparts. Material & Methods: Biopsies obtained from RCD II patients that visited the out-patient gastroenterology department at the VU University Medical Centre in the Netherlands between 2003-2010 were analyzed for the presence of T-cell receptor (TCR) gamma, delta and beta chain rearrangements. Furthermore, IEL were isolated from biopsies and analyzed for expression of Ki-67, PCNA, HLA-DR, NKG2D, IL-15Ralpha and granzyme B using four color FACS analyses. Results: TCR rearrangement analyses were performed on biopsies obtained from 14 RCD II patients at time of diagnosis and from 4 patients previously treated with Cladribine and/or autologous stemcell transplantation. Four groups could be
AGA Abstracts
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