Disclosures CELIAC DISEASE UPDATE OR GLUTEN RELATED DISORDERS 2015 Scientific Advisory Board: Alvine Pharmaceuticals, Alba Therapeutics, ImmunsanT Peter HR Green MD Columbia University New York, NY GLUTEN RELATED DISORDERS CELIAC DISEASE GLUTEN ATAXIA, DERMATITIS HERPETIFORMIS WHEAT ALLERGY GLUTEN RELATED DISORDERS General public and food industry have developed great interest in gluten >>>> medical community GLUTEN SENSITIVITY (NON-CELIAC) 1
Increasing Prevalence of Celiac Disease Analysis of NHANES data CD overall 0.71% (95% CI 0.58 0.86%) Among whites 1.01% (95% CI 0.78 1.31% Only 17% with CD were diagnosed Percentage Positive: +TTG, +EMA Rubio-Tapia et al. Gastroenterology 2009; 137: 88-93 PATHOGENESIS OF CELIAC DISEASE GENETIC FACTORS Autoantibodies (ttg, EMA) GLUTEN EPITHELIUM Innate response LAMINA PROPRIA Adaptive response Intraepithelial lymphocytosis + Villous atrophy ENVIRONMENTAL FACTORS GASTROINTESTINAL AND SYSTEMIC MANIFESTATIONS 2
ENVIRONMENTAL FACTORS THE SWEDISH EPIDEMIC ENVIRONMENTAL FACTORS Celiac disease in childhood and adulthood breast feeding (?) NO timing of gluten introduction NO cesarean section GI infections (rotavirus, campylobacter) season of birth antibiotic use iron supplements in pregnancy PPI use H pylori (protective) NOT CLEAR WHY CD CAN OCCUR AT ANY AGE Pediatrics 2008;122:528-34. CELIAC ANTIBODY TESTS PATHOLOGY-THE GOLD STANDARD ANTIGLIADIN: not sensitive nor specific DEAMIDATED GLIADIN PEPTIDE: sensitive and specific DGP IgG>IgA TISSUE TRANSGLUTAMINASE IgA ENDOMYSIAL: sensitive and very specific, but costly and observer dependent Adding more blood tests increases sensitivity?? DGP IgG and IgA + ttg IgA Marsh I, II total subtotal Villous atrophy (Marsh IIIa, b, c) partial 3
PEDIATRIC CELIAC DISEASE (CHONY-CUMC) Modes of Presentation N=224 (2000-2008) PRESENTATION OF CELIAC DISEASE (ADULTS) DIAGNOSIS OF CELIAC DISEASE why the underdiagnosis? Anemia (13%) Diarrhea (36%) N = 1499 Patient Endoscopist Case Finder Pathologist Bone disease (5%) Screening (8%) Incidental at EGD (4%) 4
ROLE OF THE ENDOSCOPIST Guidelines: need 4 6 biopsies Rostom A et al. Gastroenterology. 2006 Pais et al GIE 2008 Guidelines: need 4 6 biopsies Determined degree of adherence to guidelines and the result of adherence Analyzed the results of biopsy specimens of 132,352 patients (Caris, Dallas, TX) 2006-2009 Only 35% of patients had 4 specimens submitted Gastrointest Endosc. 2011;74:103-9. NUMBER OF SPECIMENS OF SMALL BOWEL BIOPSIES Gastrointest Endosc. 2011;74:103-9. ADHERENCE ACCORDING TO INDICATION Indication % with 4 specimens OR for diagnosis of CD when 4 specimens Anemia 37.8 2.65 (2.13-3.30) Diarrhea 43.9 1.86 (1.46-2.37) Dyspepsia 33.0 2.94 (1.94-4.43) Heartburn 30.0 1.84 (1.33-2.55) Weight loss 38.8 1.83 (1.08-3.11) Suspected celiac disease/malabsorption 38.5 7.37 (4.70-11.57) Gastrointest Endosc. 2011;74:103-9. 5
DIAGNOSIS COMPARED TO NUMBER OF BIOPSY SPECIMENS Number of Specimens and Probability of CD CONCLUSIONS CORI DATA BASE Among those with iron deficiency, anemia, weight loss or diarrhea undergoing EGD during the years 2004-2009 (n= 13,091) Only 5,576 (43%) underwent small intestinal biopsy: Biopsy rates are increasing but even in 2009 only 51% of individuals undergoing EGD with signs/symptoms of CD have a small bowel biopsy. Groups that are less likely to have a biopsy: Non-white Male Indication: weight loss 6
Biopsies of the bulb can be assessed for villous atrophy and intraepithelial lymphocytosis Bulb biopsies increased the yield of diagnosis by 13% 7
BIOPSY 4 to 6 in descending duodenum 2 from bulb (increases diagnosis by 13%) Gonzales, GIE 2010 WHAT ABOUT ULTRA SHORT CELIAC DISEASE, CELIAC DISEASE CONFINED TO THE BULB? 8
Other food avoidances 52% Dairy 59% Soy 25% Alternative Diagnoses 38% Small Intestinal Bacterial Overgrowth 50% Fructose Intolerance 16% Lactose Intolerance 9% other food intolerances 9% Microscopic Colitis 9% Gastroparesis 3% Pelvic Floor Dysfunction 3% NON CELIAC GLUTEN SENSITIVITY = NCGS PEOPLE WHO AVOID GLUTEN = PWAGs CONCLUSIONS In a specialist center PWAG are similar to those with CD Alternative diagnoses especially SIBO and other food intolerances (fructose) are common Many of the patients have persistent symptoms despite GFD Not all PWAG are NCGS Gluten sensitive IBS patients, n= 34 Celiac disease while eating gluten was excluded 9
NON-CELIAC GLUTEN SENSITIVITY Exists (self diagnosis + non traditional practitioners) Mechanism unclear gluten, permeability Some other component of gluten containing foods or wheat (ATIs) FODMAPs Fermentable, Oligo-, Di-, Mono-saccharides And Polyolse Exclude lactose and fructose intolerance, SIBO, microscopic colitis 10