Celiac Disease Ce. Celiac Disease. Barry Z. Hirsch, M.D. Baystate Pediatric Gastroenterology and Nutrition. baystatehealth.org/bch
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1 Celiac Disease Ce Celiac Disease Barry Z. Hirsch, M.D. Baystate Pediatric Gastroenterology and Nutrition baystatehealth.org/bch Autoimmune Disease Inappropriate inflammation 1
2 1/21/15 Celiac Disease Classic Autoimmune disease Chronic= Lifelong Organ specific= Small intestines Damage done by White Blood Cells= Lymphocytes Unique features Known trigger: Gluten Gene : HLA-DQ2 HLA-DQ8 Treatment: Diet alone Case Report PF was a 3 y/o girl born 10,000 years ago who presents with diarrhea bloating and weight loss Her diet typically consisted mostly of berries, root vegetables and occassionally meat Recently the child s father had learned how to grow some of his own food 2
3 Grew grains -wife would grind into powder and mix with water Within months of consuming the new food: mother and daughter got thinner dad grew larger. History 10,000 years ago transitioned from huntergatherers to farmers and grain consumption increased 1887 British physician Samuel Gee described the condition - errors in diet may perhaps be the cause Recommended Bread lightly toasted 3
4 History 1940s Dutch physician Willem Karel Dicke deaths declined from 35% to 0 during the bread shortages of the WWII climbed afterwards Rx Wheat free diet 1952 Dicke -identified gluten as the trigger s Serologic testing -> identification of asymptomatic cases 2000s Gene testing Epidemiology Western Europe and US highest incidence- 1:133 people Infrequent in African Americans and Hispanics Women 2:1 Monozygotic twins % concordance 4
5 Increased Incidence Gastroenterology July;137(1): ,133 young adults (sera were collected between 1948 and 1954) 12,768 sex-matched controls 7210 young males drawn X increase mortality in undiagnosed celiac 4X increase in prevalence Associated Condtions Lymphocytic colitis (15-27%) Down Syndrome ( 12%) Type 1 Diabetes ( 5-6%) Autoimmune thyroiditis (5%) Chronic Fatigue Syndrome ( 2%) 5
6 Prolamins= toxic proteins (Plant storage glycoproteins with a high proline and gutamine content soluble in alcohols) Wheat=gliadin (anti-gliadin antibody) Barley=secalin Rye=hordein Oat =avenin safe in most patients with Celiac Rice =orzenin Corn =zein What s missing? Where s the GLUTEN? What s Gluten? Botany : combination of 2 proteins: gliadin (wheat prolamin) and glutelin (non-prolamin wheat protein) Baking: Any flour washed to remove the starch yielding a tough, viscid substance Celiac disease used to describe collectively prolamins from wheat rye and barley Gluten Free Diet no wheat, rye, barley New FDA Regulation Aug
7 Vital Wheat Gluten Washed wheat dissolving the starch leaving a pure powdered gluten Main ingredient in Seitan- Vegetarian Wheat Meat What s Gluten? Botany : combination of 2 proteins: gliadin (wheat prolamin) and glutelin (non-prolamin wheat protein) Baking: Any flour washed to remove the starch yielding a tough, viscid substance Celiac disease used to describe collectively prolamins from wheat rye and barley Gluten Free Diet no wheat, rye, barley New FDA Regulation Aug
8 Wheat Highest protein content of any grain Second only to rice in consumption of vegetable protein 1. Improves constipation 2. Treatment for Irritable Bowel Syndrome 3. Prevents Colon Cancer 4. Weight loss 5. Prevents Heart Disease 8
9 1/21/15 Wheat Germ Germ embryo for the next generation -Vitamin E -Folate -Thiamine -Zinc -Magnesium -Polyunsaturated fats (essential fatty acids) Endosperm Bulk of the Grain Carbohydrate and gluten 9
10 1/21/15 Milling Grain Non-Gluten Food Proteins 10
11 Gluten-> Release of Zonulin Zonulin -> Opens tight junctions Celiac Patients have more Zonulin and their tight junctions stay open longer Leaky Gut Intact Gluten -> Enterocyte -> IL-15 IL-15-> Recruits Lymphocyte to attack the enterocyte 11
12 Damaged Enterocytes -> TTGA (Tissue transglutaminase) TTGA-> Modifies the Gluten Modified Gluten -> Antigen Presenting Cell Expressing HLA-DQ2 or HLA-DQ8 receptors APC-Gluten Combination recruits: Helper T- cells Killer T- Cells Mature B-cell -> TTGA Antibodies Antigliadin Antibodies Inflammatory Cascade From: Scientific American 12
13 From: Scientific American July 2009 Biopsy X 3 Gold standard Diagnosis GFD Challenge 13
14 IgG IgM Serologic testing IgA IgA Antibodies to gliadin (deamidated) IgA Antibodies to endomysium (lines connective tissue smooth muscle) IgA antibody to tissue transglutaminase enzyme - TTGA Total IgA IgA deficiency ( 1:300 people) Genetic testing HLA DQ2 ( DQA1*05; DQB1*02) HLA DQ8 (DQA1*03; DQB1*0302) Homozygosity DQ2 highest risk of celiac and complications 30-40% of normals will have genes 95-99% of celiac patients have at least one of these genes 14
15 Clinical Presentation Clinical Manifestations None Failure to thrive Diarrhea Constipation Irritability Weakness Abdominal pain Vomiting Rashes Short stature Anemia Fatigue Numbness Vitamin deficiency 15
16 Dermatitis herpetiformis Celiac Sequelae Osteoperosis Anemia Tooth enamel destruction Neurological problems Intestinal lymphoma Short stature 16
17 Treatment Gluten Free Diet?Avoid lactose initially until intestinal lining heals Multivitamin at least initially Who is this? 17
18 Therapy beyond diet. Degrade gluten fragments so they can t elicit an immune response- (ALVOO3- marginal success in trials) 18
19 Future Treatments??? Block Zonulin (Larazotide clinical trials ongoing) Future Treatments??? Block tissue transglutaminase (in vitro) Block HLA-DQ2 from attaching (in vitro) 19
20 Future Treatments??? Vaccinate with gluten fragments to induce tolerance (Nexvax2 human trials) Block migration of Killer T-cells (CCX282-B human trials) Hookworms to dampen T-cell response Is Celiac Disease the same as wheat allergy? Celiac Disease vs Wheat Allergy T- cell Response No other food allergies Dermatitis herpetiformis Response to food may be subtle Associated with short stature, failure to thrive Biospy villous atrophy with lymphocytes B-Cells -> IgE Abs food Multiple food allergies Eczema, hives Response to food often immediate and dramatic Rarely affects growth Biopsy = Eosinophils 20
21 Controversies If blood tests negative and bx negative but respond to GFD Is it Celiac? Can I be allergic to gluten without having celiac? Can I be intolerant to gluten without being allergic or having celiac? Controversies Are Oats safe to eat? Should everyone with Irritable Bowel Syndrome be checked for Celiac? 21
22 Controversies Should asymptomatic Celiac patients be on GFD? Is it OK to cheat on the diet if I do not have symptoms? Should asymptomatic family members be screened? Controversies If serology positive do I still need Bx? If blood tests positive and bx negative is it still Celiac? If blood tests negative but bx positive is it still Celiac? 22
23 The End 23
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