Celiac Disease The Great Masquerader Anca M. Safta MD
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1 Celiac Disease The Great Masquerader Anca M. Safta MD
2 Disclosures Dr. Anca Safta - none Angie Almond, M.Ed., RD, LDN invited attendee of The Gluten Free Summit sponsored by General Mills Wake Forest Baptist Medical Center
3 Outline Definition Clinical Manifestations Symptomatic Asymptomatic Refractory Diagnosis Serology HLA Biopsy Treatment
4 Definition Enteropathy Caused by permanent sensitivity to gluten Occurs in genetically susceptible individuals DQ2 and/or DQ8 positive HLA haplotype is necessary but not sufficient Celiac disease is an autoimmune condition A unique autoimmune disorder because: both the environmental trigger (gluten) and the autoantigen (tissue Transglutaminase) are known elimination of the environmental trigger leads to a complete resolution of the disease
5 What is gluten? Broad term for various proteins, called prolamin(e)s Each grain has its own specific prolamin Wheat: gliadin Rye: secalin Barley: hordein Oat: avenin Wake Forest Baptist Medical Center
6 Dietary Factors 33 amino acid peptide in gliadin contains critical epitopes high in glutamine and proline Resistant to digestion in lumen Penetrates epithelial barrier Modified by the enzyme tissue transglutaminase deamidates glutamine residues to glutamic acid Resulting higher affinity binding to HLA DQ2 molecule on the surface of antigen-presenting cells Wake Forest Baptist Medical Center
7 What is not celiac disease? Wheat allergy IgE-mediated food allergy Diagnosed by RAST, skin prick or patch testing, dietary elimination/challenge Fructan sensitivity Bothersome gastrointestinal symptoms related to ingestion of fructans Frequently associated with Irritable Bowel Syndrome (IBS) Gluten sensitivity GI or systemic symptoms that improve on gluten-free diet in an individual who does not meet objective criteria for the diagnosis Diagnosis of exclusion Wake Forest Baptist Medical Center
8 Dietary Factors The Grass Family - (GRAMINEAE) Subfamily Festucoideae Tribe Zizaneae Oryzeae Hordeae Aveneae Festuceaea Chlorideae wild rice rice wheat oat finger millet teff rye (ragi) barley Wake Forest Baptist Medical Center
9 Pathogenesis Genetic predisposition Environmental triggers Dietary Non dietary?
10 Genetics Strong HLA association 90-95% of patients HLA-DQ2 also found in 20-30% of controls Most of the remainder are HLA - DQ8 10% of patients have an affected first degree relative
11 Pathogenesis Genetics Gluten Necessary Causes Pathogenesis? Gender Infant feeding Infections Others Risk Factors Celiac disease Wake Forest Baptist Medical Center 11
12 Pathophysiology Sequelae Malabsorption of micronutrients Iron Folate Calcium Vitamin D Increased intestinal permeability may permit entry of other toxins which might induce autoimmune diseases
13 The Celiac Iceberg Symptomatic Celiac Disease Manifest mucosal lesion Silent Celiac Disease Latent Celiac Disease Normal Mucosa Genetic susceptibility: DQ2, DQ8 Positive serology
14 Prevalence of Celiac Disease is Higher in Other Autoimmune Conditions Type 1 Diabetes Mellitus: % Thyroiditis: 4-8% Arthritis: % Autoimmune liver diseases: 6-8% Idiopathic dilated cardiomyopathy: 5.7% IgA nephropathy: 3.6% IgA deficiency: 7% Can complicate serologic screening
15 Prevalence of Celiac Disease is Higher in some Genetic Disorders Down Syndrome: 4-19% Turner Syndrome: 4-8% Williams Syndrome: % Sjögren s Syndrome: 2-15%
16 Prevalence of Celiac Disease is Higher in Relatives Healthy population: 1:133 Population with symptoms: 1:40 1st degree relatives: 1:18 to 1:22 2nd degree relatives: 1:24 to 1:39 Fasano, et al, Arch of Intern Med, Volume 163: , 2003 Wake Forest Baptist Medical Center
17 Gastrointestinal Manifestations ( Classic ) Most common age of presentation: 6-24 months in West, diagnosis by 2 yrs Chronic or recurrent diarrhea Abdominal distension Anorexia Failure to thrive or weight loss Abdominal pain Vomiting Constipation Irritability Rarely: Celiac crisis
18 Classic Celiac Disease
19 Non Gastrointestinal Manifestations Clinical Masquerader Most common age of presentation: older child to adult Dermatitis Herpetiformis Dental enamel hypoplasia of permanent teeth Osteopenia/Osteoporosis Short Stature Iron-deficient anemia/resistant to oral Fe Hepatitis Arthritis Epilepsy with occipital calcifications Delayed Puberty Listed in descending order of strength of evidence
20 Dermatitis Herpetiformis Erythematous macule > urticarial papule > tense vesicles Severe pruritus Symmetric distribution 90% no GI symptoms Skin biopsy = IgA deposits GFD may take 6-12 months Garioch JJ, et al. Br J Dermatol. 1994;131: Fry L. Baillieres Clin Gastroenterol. 1995;9: Reunala T, et al. Br J Dermatol. 1997;
21 Recurrent Apthous Stomatitis By permission of C. Mulder, Amsterdam (Netherlands)
22 Dental Enamel Defects Involve the secondary dentition May be the only presenting sign of Celiac Disease
23 Osteoporosis Low bone mineral density improves in children on a gluten-free diet.
24 Celiac Disease Complicated by Enteropathy-Associated T-cell Lymphoma (EATL) By permission of G. Holmes, Derby (UK)
25 Short Stature/Delayed Puberty Short stature in children / teens: ~10% of short children and teens have evidence of celiac disease Delayed menarche: Higher prevalence in teens with untreated Celiac Disease
26 Iron Deficient Anemia - Resistant to Oral Iron Supplementation Most common non-gi manifestation in some adult studies 5-8% of adults with unexplained iron deficiency anemia have Celiac Disease In children with newly diagnosed Celiac Disease: Anemia is common Little evidence that Celiac Disease is common in children presenting with anemia
27 Diagnosis Confirm diagnosis before treating diagnosis of Celiac Disease mandates a strict gluten-free diet for life following the diet is not easy QOL implications Failure to treat has potential long term adverse health consequences increased morbidity and mortality
28 Serological Tests Antigliadin antibodies (AGA) New: Deaminated Gliadin Peptide antibodies (DGP) Antiendomysial antibodies (EMA) Anti tissue transglutaminase antibodies (ttg) first generation (guinea pig protein) second generation (human recombinant) HLA typing
29 Endoscopic Findings Scalloping Normal Appearing Scalloping Nodularity
30 Histological Features Normal 0 Infiltrative 1 Hyperplastic 2 Partial atrophy 3a Subtotal atrophy 3b Total atrophy 3c Horvath K. Recent Advances in Pediatrics, 2002.
31 Predicted Response to GFD 70% report significant symptomatic improvement in 2 weeks Symptoms resolve before histology Histologic healing may take up to 1 year, but improvement typically seen within 6 months Damage: proximal distal Healing: distal proximal Wake Forest Baptist Medical Center
32 Non-Responsive Celiac Disease (NRCD) Definition Persistence of signs, symptoms and/or typical CD lab abnormalities despite adherence to GFD for 6 months Primary NRCD: Initial lack of response to GFD Secondary NRCD Recrudescence of signs / symptoms / lab abnormalities after initial response to GFD Wake Forest Baptist Medical Center
33 Etiology of Non-Responsive Celiac Disease Dietary non-adherence Incorrect diagnosis Pancreatic insufficiency IBD IBS Bacterial overgrowth Protein-losing enteropathy Lymphocytic colitis Collagenous colitis Ulcerative jejunitis T-cell lymphoma Fructose intolerance Tropical sprue Refractory Celiac Disease
34 Refractory Celiac Disease: Definition Presence of villous atrophy despite at least 12 months of strict GFD with exclusion of other causes Rare complication of CD: < 1% Wake Forest Baptist Medical Center
35 Refractory Celiac Disease Genetics Histology Genetics Histology Trigger Auto-Ab and Response to GFD Auto-Ab Celiac Disease Wake Forest Baptist Medical Center RCD
36 Refractory CD Characteristics Weight loss Persistent positive serology Classification Type I RCD: +CD3, CD4, CD8 T cell markers Polyclonal T cell population Type II RCD: + CD3, -CD4, -CD8 T cell markers Oligoclonal T cell population Associated more commonly with malnutrition, ulcerative jejunitis, lymphocytic gastritis Risk of enteropathy associated T cell lymphoma Wake Forest Baptist Medical Center
37 Refractory Celiac Disease RCD is the least common cause of NRCD Confirm diagnosis Rule out presence of other pathological states Classification is important for management and prognosis RCD I: polyclonal, better prognosis RCD II: monoclonal, poor prognosis, EATL associated Early, aggressive therapy warranted Wake Forest Baptist Medical Center
38 Gluten-Free Diet Angie Almond, M.Ed., RD, LDN Wake Forest Baptist Medical Center
39 Gluten Free Diet The ONLY Treatment for Celiac Disease is a Gluten-free diet (GFD) Strict, lifelong diet Avoid: Wheat Rye Barley
40 Gluten-Containing Grains to Avoid Wheat Bulgar Filler Wheat Bran Couscous Graham flour Wheat Starch Durum Kamut Wheat Germ Einkorn Matzo Flour/Meal Barley Emmer Semolina Barley Malt/ Extract Faro Spelt Rye Triticale Wake Forest Baptist Medical Center
41 Sources of Gluten OBVIOUS SOURCES Bread Bagels Cakes Cereal Cookies Pasta / noodles Pastries / pies Rolls Wake Forest Baptist Medical Center
42 Sources of Gluten POTENTIAL SOURCES Candy Communion wafers Cured Pork Products Drink mixes Gravy Imitation meat / seafood Sauce Self-basting turkeys Deli meats Soy sauce Wake Forest Baptist Medical Center
43 Ingredients to Question (may contain gluten) Seasonings and spice blends or mixes Modified food starch Flavorings Dextrin Maltodextrin Glucose syrup Caramel color Wake Forest Baptist Medical Center
44 Gluten Free Labeling Voluntary for manufacturers As of August 5, 2014, if a product that is labeled gluten-free, it must meet the FDA requirements Does NOT contain an ingredient that is a whole, gluten-containing grain Does NOT contain an ingredient derived from a gluten-containing grain and has NOT been processed to remove gluten Product must contain <20 ppm of gluten Wake Forest Baptist Medical Center
45 Allergen Advisory Statements Processed in a facility that also processes Voluntary and not defined by any federal regulations Some manufacturers use them and some don t Products labeled gluten-free and have an advisory statement for wheat, the food is NOT mislabeled and must contain <20 ppm of gluten, even when the source is from crosscontact 20 ppm = less than 1 drop in a gallon of liquid Wake Forest Baptist Medical Center
46 Gluten-Free Grains and Starches Amaranth Arrowroot Buckwheat Corn Flax Millet Montina Oats* Potato Quinoa Rice Sorghum Tapioca Teff Flours made from nuts, beans and seeds *for possible cross-contamination with gluten containing grains Wake Forest Baptist Medical Center
47 What About Oats? Naturally gluten-free Oats are often grown in fields near wheat, barley or rye Harvesting and transporting oats often results in crosscontact with gluten-containing grains Difficult to separate grains at mills due to their similar size and shape Recommend avoiding all oats, including GF oats for the first year after diagnosis Small percentage of people with CD do not tolerate pure, uncontaminated oats
48 Other Items to Consider Lipstick/Gloss/Balms Mouthwash/Toothpaste Play-Doh Vitamin, Herbal, and Mineral preparations Prescription or OTC Medications Wake Forest Baptist Medical Center
49 The Key to Dietary Compliance is Follow Up Care NASPGHAN Guidelines apply to adults and children The health effects are motivation When one believes they are real Testing measures the health effects of eating gluten Follow up testing provides important feedback Test results are a powerful motivator especially for those who do not have symptoms when they eat gluten Wake Forest Baptist Medical Center
50 The Key to Dietary Compliance is Follow-Up Care Patients/parents look to the physician to tell them when follow-up testing is needed Patients with CD are not followed consistently and follow-up exams are often inadequate Pediatric patients that are lost to follow-up are more likely to have a poorly controlled disease Proactive follow-up measures can reinforce adherence Best patient outcomes require ongoing evaluation, monitoring, and support by experienced providers Wake Forest Baptist Medical Center Barnea L., et al.digestion. 2014;90: M.L. Hermon, et al. Clin Gastroenterol Hepatol August ; 10(8):
51 Take Home Points Think Celiac Disease Clinical Masquerader Accurate diagnosis is vital Gluten-free diet is only treatment and is challenging Celiac Disease is a life-long disease that requires on-going, skilled multidisciplinary follow-up to achieve the best outcomes.
52 Questions Wake Forest Baptist Medical Center
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