4/6/18. A clinical and practical presentation of Celiac Disease. Objectives. History of Celiac disease. Lacey Yzeik, MS, RDN, LDN Clinical Dietitian

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1 A clinical and practical presentation of Celiac Disease Lacey Yzeik, MS, RDN, LDN Clinical Dietitian Objectives Define Celiac disease and the modern clinical practices (Type, pathophysiology, symptoms, screening, testing, diagnosis). Define Gluten and the Gluten Free Diet (sources, risks, products, lifestyle). Differentiate between gluten intolerance, gluten allergy and celiac disease. Relationship between celiac disease, Type 1 Diabetes and other autoimmune disorders. Discuss current research. History of Celiac disease First identified in 2 nd Century AD Aretaeus of Cappadocia, a Greek Physician, describes a malabsorptive diarrhea affecting children Referred to it as The Coeliac Affection AKA: Koiliakos (from the Greek word Koelia for abdomen) If the stomach be irretentive of the food and if it pass through undigested and crude and nothing ascends into the body, we call such person coeliacs Guandalini S. (2007). A Brief History of Celiac Disease. Impact: A Publication of the University of Chicago Celiac Disease Center. Volume 7 Issue 3. 1

2 History of Celiac disease Relationship of diet 19 th century Dr. Mathew Baillie published observations on a chronic diarrheal disorder of adults causing malnutrition and characterized by gas-distended abdomen Suggested advantage to living on rice 1888 Samuel Gee, leading pediatrician Documented improvement following the reduction/removal of certain foods from diet and the relapse after reintroduction Sidney Haas, an American pediatrician - Carbohydrates are the culprit in celiac disease and treats 10 children with a banana diet (eliminated bread, crackers, potatoes, all cereals) 1930 s William Dicke, a Dutch pediatrician - shows wheat and rye protein, not starch was the only culprit During WWII children with celiac disease improve when they lack access to wheat, further strengthening the relationship between wheat ingestion and celiac disease Guandalini S. (2007). A Brief History of Celiac Disease. Impact: A Publication of the University of Chicago Celiac Disease Center. Volume 7 Issue 3. History of Celiac disease 1950 s Margot Shiner, a pediatric gastroenterologist, develops biopsy technique to examine the small intestines to observe the pathologic changes in celiac disease 1964 The anti-gliadin antibody is discovered 1980 s Celiac disease associated with other autoimmune disease: Thyroid, diabetes, down s syndrome 1990 s The genetic markers HLA-DQ2 and HLA-DQ8 are identified and the antitransglutaminase antibodies are identified Guandalini S. (2007). A Brief History of Celiac Disease. Impact: A Publication of the University of Chicago Celiac Disease Center. Volume 7 Issue 3. Prevalence Estimated to affect 1 in 100 people worldwide 2.5 million Americans are undiagnosed Celiac Disease (2018, January) Retrieve from 2

3 Epidemiology Diagnosed vs. undiagnosed varies from country to country: One to two in Finland One to 10 in the US, Argentina and Germany Wide regional differences: Germany 0.3% compared to Finland 2.4% 1.5 to 2 times as high among women as men Affects all races and ethnic groups 0.2% in African Americans and 0.3% in Hispanics 1% in whites Affects all age groups 70% of new patients are diagnosed above the age of 20 years Fasano A, Catassi C. Clinical Practice: Celiac Disease. The New England Journal of Medicine. 2012;367: What is Celiac disease (CD)? AKA: Celiac sprue, non-tropical sprue, gluten sensitive enteropathy Inappropriate T cell-mediated autoimmune response to the ingestion of gluten that affects the small intestine When T cells present the gluten peptide molecules, they produce cytokines that start the inflammatory and autoimmune reaction and stimulate plasma cells to produce antibodies to gliadin, transglutaminase and endomysium Characterized by a broad range of symptoms, a specific serum autoantibody response and variable damage to the small intestinal mucosa Simply: Ingestion of gluten damages the villi of the small intestines causing paralysis Nutrients cannot be absorbed properly leading to malnutrition Mahan K, Escott-Stump S. (2008). Krause s Food and Nutrition Therapy. St. Louis, MO: Saunders Elsevier. Rubio-Tapia A, Hill I, Kelly C, Calderwood A, Murray J. American College of Gastroenterology Clinical Guideline: Diagnosis and management of celiac disease. Am J Gastroenterol. 2013; 108(5): Fasano A, Catassi C. Clinical Practice: Celiac Disease. The New England Journal of Medicine. 2012;367: VISUAL DISPLAY OF CELIAC DAMAGE Figure 1: Celiac Disease. (Keough Institute, 2015) 3

4 Screening and Diagnosis Must be consuming gluten prior to testing Gluten Challenge (approximately 8 weeks) Screening tests: Widely used and most accurate: Tissue Transglutaminase Antibodies (ttg-iga) Elevated levels Other tests included: IgA Endomysial Antibody (EMA) under 2 years old Total Serum IgA Deaminated gliadin peptide (DGP IgA and IgG) Genetic Testing Rubio-Tapia A, Hill I, Kelly C, Calderwood A, Murray J. American College of Gastroenterology Clinical Guideline: Diagnosis and management of celiac disease. Am J Gastroenterol. 2013; 108(5): Genetic Testing CD is highly genetic HLA DQ2 and DQ8 genes Carried by people with CD but also 25-30% of general population Not diagnostic, not indicative development of CD Increases risk of development: 3% with gene, 1% of general population First-degree family members with the same genotype as the family member with CD, have up to a 40% risk of developing CD. The overall risk of developing CD when the genotype is unknown is 7% to 20%. Rubio-Tapia A, Hill I, Kelly C, Calderwood A, Murray J. American College of Gastroenterology Clinical Guideline: Diagnosis and management of celiac disease. Am J Gastroenterol. 2013; 108(5): Who should be screened: 1. Patients with symptoms, signs or labs suggestive or malabsorption (chronic diarrhea with weight loss, steatorrhea, post prandial abdominal pain and bloating). 2. Patients with symptoms, signs or laboratory evidence for which CD is treatable cause. 3. Patients with first degree family member with confirmed diagnosis of CD who show signs or symptoms or are asymptomatic. 4. Patients who have elevated serum aminotransferase levels when no other etiology is found. 5. Patients with Type 1 Diabetes with digestive symptoms, signs or laboratory evidence suggestive of CD. Rubio-Tapia A, Hill I, Kelly C, Calderwood A, Murray J. American College of Gastroenterology Clinical Guideline: Diagnosis and management of celiac disease. Am J Gastroenterol. 2013; 108(5):

5 Diagnosis Tissue Transglutaminase Antibodies (ttg-iga) Intestinal biopsy via Upper GI Confirms CD diagnosis An intestinal (duodenal) biopsy is considered the gold standard for diagnosis because it will tell you (1) if you have CD (2) if your symptoms improve on a gluten-free diet due to a placebo effect (you feel better because you think you should) (3) if you have a different gastrointestinal disorder or sensitivity which responds to change in your diet Rubio-Tapia A, Hill I, Kelly C, Calderwood A, Murray J. American College of Gastroenterology Clinical Guideline: Diagnosis and management of celiac disease. Am J Gastroenterol. 2013; 108(5): Intestinal Biopsy Characteristic histological findings in patients with CD: Increased density of intra-epithelial lymphocytes IELS (white blood cells found in the immune system) <25/100 epithelial cells is significant Crypt hyperplasia with a decreased villi/crypt ratio Blunted or atrophic villi shrinking or flattening due to gluten exposure Mononuclear cell infiltration in the lamina propria Epithelial changes, including structural abnormalities in epithelial cells May show scalloping and/or flattening of duodenal folds, fissuring over the folds, and a mosaic pattern of mucosa of folds A modified Marsh classification for villous abnormalities Use to assess the severity of villous atrophy Rubio-Tapia A, Hill I, Kelly C, Calderwood A, Murray J. American College of Gastroenterology Clinical Guideline: Diagnosis and management of celiac disease. Am J Gastroenterol. 2013; 108(5): Modified Marsh Classification of Gluten-induced smallintestinal damage Figure 2: Marsh Staging. (Celiac.org 2018) 5

6 Healthy vs Disease Endoscopy Normal Celiac Disease Figure 3: Endoscopic and biopsy findings in patients with and without celiac disease. (American Family Physicians. 2007) Algorithm for Diagnosing Celiac Disease Figure 4: Algorithm for Diagnosis Celiac Disease. (Bai J, Ciacci C, Corazza G, Fried M, Olano C. et al. 2016) Why is it difficult to diagnose? Wide spectrum of clinical characteristics, which can vary during a lifetime Symptoms may overlap with those of irritable bowel syndrome Patients may have mainly extra-intestinal manifestations, or even no symptoms There is a lack of awareness about CD among clinicians (and patients) There is a lack of diagnostic capabilities in some geographic areas Fasano A, Catassi C. Clinical Practice: Celiac Disease. The New England Journal of Medicine. 2012;367:

7 Types of Celiac Disease 1. Classical 2. Non-classical 3. Asymptomatic 4. Refractory Classical Celiac Disease Classic signs and symptoms of malabsorption Abdominal bloating and pain Chronic diarrhea Pale, foil smelling or fatty stool (steatorrhea) Weight loss Fatigue Irritability and behavioral issues Dental enamel defects of the permanent teeth Delayed growth and puberty (kids) Failure to thrive Fasano A, Catassi C. Clinical Practice: Celiac Disease. The New England Journal of Medicine. 2012;367: Rubio-Tapia A, Hill I, Kelly C, Calderwood A, Murray J. American College of Gastroenterology Clinical Guideline: Diagnosis and management of celiac disease. Am J Gastroenterol. 2013; 108(5): Non-Classical Celiac Disease Mild gastrointestinal symptoms without clear signs of malabsorption or seemingly unrelated symptoms Unexplained iron deficiency anemia Vitamin deficiency (B12 and folate) Fatigue Bone or joint pain Osteoporosis or osteopenia (bone loss) Depression or anxiety Peripheral neuropathy Seizures or migraines Missed menstrual period Infertility or recurrent miscarriages Canker sores inside the mouth Dermatitis herpetiformis (itchy skin rash) Fasano A, Catassi C. Clinical Practice: Celiac Disease. The New England Journal of Medicine. 2012;367: Rubio-Tapia A, Hill I, Kelly C, Calderwood A, Murray J. American College of Gastroenterology Clinical Guideline: Diagnosis and management of celiac disease. Am J Gastroenterol. 2013; 108(5):

8 Asymptomatic Celiac Disease Patients do not complain of any symptoms Still experience villous atrophy damage to their small intestine Tested due to high likelihood of CD: familial CD, autoimmune disease and associated conditions Positive results and better overall feeling/health after implementing gluten free diet Fasano A, Catassi C. Clinical Practice: Celiac Disease. The New England Journal of Medicine. 2012;367: Rubio-Tapia A, Hill I, Kelly C, Calderwood A, Murray J. American College of Gastroenterology Clinical Guideline: Diagnosis and management of celiac disease. Am J Gastroenterol. 2013; 108(5): Refractory Celiac Disease AKA: Refractory Sprue Definition: Persistent or recurrent symptoms of malabsorption and villous atrophy despite strict adherence to a gluten-free diet (GFD) for at least 6-12 months in the absence of other causes of non-responsive treated CD. Seen in adults (middle aged or elderly), never encountered in pediatric population Symptoms are severe and require additional therapeutic intervention besides GFD Classified as Type 1 or Type 2 Type 1: nutrition, adherence, pharmacologic Type 2: clinical response less certain and prognosis poor Rubio-Tapia A, Murray J. Classification and Management of Refractory Celiac Disease. Gut. 2010; 59: [PubMed: } Possible CD Symptoms Over 200 identified symptoms Abdominal bloating and pain Chronic diarrhea Vomiting Constipation Pale, foil smelling or fatty stool (steatorrhea) Weight loss Fatigue Irritability and behavioral issues Dental enamel defects of the permanent teeth Delayed growth and puberty Short stature Failure to thrive ADHD Unexplained iron deficiency anemia Fatigue Bone or joint pain Arthritis Osteoporosis or osteopenia (bone loss) Liver and biliary tract disorders (transaminitis, fatty liver, etc.) Depression or anxiety Peripheral neuropathy Seizures or migraines Missed menstrual period Infertility or recurrent miscarriages Canker sores inside the mouth **Digestive symptoms are more common in infants and children Dermatitis herpetiformis (itchy skin rash) 8

9 Autoimmune and other conditions associated with CD Autoimmune Thyroid Disease 26% Dermatitis Herpetiformis 25% Down s Syndrome 12% Liver disease 10% Peripheral neuropathy 10-12% Lymphocytic colitis 15-27% Type 1 Diabetes 6-10% Unexplained infertility 12% Fasano A, Catassi C. Clinical Practice: Celiac Disease. The New England Journal of Medicine. 2012;367: Rubio-Tapia A, Hill I, Kelly C, Calderwood A, Murray J. American College of Gastroenterology Clinical Guideline: Diagnosis and management of celiac disease. Am J Gastroenterol. 2013; 108(5): Celiac Disease and Type 1 Diabetes Link first established in the 1960 s Prevalence is about 6% in Type 1 Diabetes compared to 1% in general population Autoimmune mediated diseases with common susceptibility factors Genetics (HLA) Environmental Factors: introduction's of solids, breast-feeding, viral infections Gut microbiome More research is needed Recommendation: Type 1 Diabetes: get screened for CD CD: get screened for Type 1 Diabetes Crohn A, Sofia AM, Kupfer SS. Type 1 Diabetes and celiac disease: clinical overlap and new insights into disease pathogenesis. Current diabetes reports. 2014;14:517 Long term health effects of Undiagnosed or untreated CD Iron deficiency anemia Early onset osteoporosis or osteopenia Infertility and miscarriage Lactose intolerance Vitamin and mineral deficiencies Central and peripheral nervous system disorders Pancreatic insufficiency Intestinal lymphomas and other GI cancers (malignancies) Gall bladder malfunction Neurological manifestations including ataxia, epileptic seizures, dementia, migraine, neuropathy, myopathy, and multifocal leucoencephalopathy 9

10 Recommendations after diagnosis Follow-up with physician Monitor symptoms Laboratory test Full blood count, iron status, Vitamin B12, calcium, Vitamin D CD serology tests abnormal IgA anti-tissue transglutaminase antibodies indicate poor dietary adherence Duodenal biopsies controversial if labs are OK Healing takes anywhere between 6-24 months Every 2-3 years or if symptoms re-occur after strict adherence Counseling by a Registered Dietitian: Assessment of nutritional status and adherence to gluten-free diet Support groups (shown to aid in level of adherence) Psychological consult (if needed) Treatment There is only one: Lifelong adherence to a Gluten free diet (GFD) Implementation of Gluten free diet Removal of gluten will result in symptomatic, serologic, and histological remission in most Approx. 70% report improvement in symptoms within 2 weeks of starting the gluten free diet Growth and development in children return to normal with adherence to a gluten free diet. Strict adherence results in normalization of celiac disease-specific antibodies Villous changes can happen within months after starting gluten free diet. Complete resolution may take years and may not be achieved in some. 10

11 What is Gluten? Definition: rubbery protein mass that remains when wheat dough is washed to remove starch Storage protein of wheat, rye and barley Wheat peptides: gliadin and glutenin Rye peptides: secalinus Barley peptides: hordeins Used widely in food processing to give dough desired baking properties, add flavors and improve texture Limited nutritional value that can be replaced by other dietary proteins Wide range of gluten free substitutes are available Mahan K, Escott-Stump S. (2008). Krause s Food and Nutrition Therapy. St. Louis, MO: Saunders Elsevier. Rubio-Tapia A, Hill I, Kelly C, Calderwood A, Murray J. American College of Gastroenterology Clinical Guideline: Diagnosis and management of celiac disease. Am J Gastroenterol. 2013; 108(5): Gluten Containing Grains and their Derivatives Various forms of wheat and wheat derivatives such as : Rye Wheat, Wheat berries, Durum, Emmer, Semolina, Spelt, Farina, farro, graham, KAMUT Khorasan wheat, einkorn wheat Barley Triticale Malt Various forms: malted barley flour, malted milk or milkshakes, malt extract, malt syrup, malt flavoring, malt vinegar Brewer s Yeast Wheat starch can be processed to remove presence of gluten to below 20ppm to adhere to labeling law What is Gluten? (2018, March). Retrieved from Gluten Free Diet and Food Label Reading Guide. (2018, February). Retrieved from Combined-Gluten-Free-Diet-and-Food-Label-Reading-Guide.pdf Oats Oat protein has a different chemical structure Shown to be tolerated by most 70g (~2.5oz) per day for adults and 25g (0.88oz) per day for children If symptoms occur it is usually because: Intolerance to increase fiber, contamination with gluten, development of immune response to oat protein (like gluten) MUST be Gluten-free oats With Inclusion: Monitoring Anti-tTG antibody levels Biopsy 2-3 years Follow-up and monitoring by physician and dietitian What is Gluten? (2018, March). Retrieved from Gluten Free Diet and Food Label Reading Guide. (2018, February). Retrieved from Combined-Gluten-Free-Diet-and-Food-Label-Reading-Guide.pdf 11

12 Gluten Containing Foods Pastas, noodles Crackers, pancakes, waffle, breads, pastries, and baked goods Cereal and granola Corn flakes and rice cereals often contain Malt extract/flavoring Granola is often made with regular oats, not gluten free oats Breading and coating mixes Sauces, gravies and soups Anything made with traditional wheat flours Beer and malt beverages What is Gluten? (2018, March). Retrieved from Gluten Free Diet and Food Label Reading Guide. (2018, February). Retrieved from Combined-Gluten-Free-Diet-and-Food-Label-Reading-Guide.pdf Hidden Sources of Gluten Postage stamps/envelope glue Makeup Herbal or nutritional supplements Communion wafers Drugs and over the counter medications Vitamins and supplements Play-dough Ingredients of another name: Modified food starch, caramel color, dextrin, soy sauce, brewer s yeast, etc. Cross contamination toaster, eating out of the house, shared condiments, etc. What is Gluten? (2018, March). Retrieved from Gluten Free Diet and Food Label Reading Guide. (2018, February). Retrieved from Combined-Gluten-Free-Diet-and-Food-Label-Reading-Guide.pdf Gluten-Free Foods Fruit and vegetables Meat and poultry Fish and seafood Dairy Beans, legumes and nuts Grains/starch rice, corn, soy, potato, tapioca, quinoa, millet, sorghum, etc. May still contain gluten if processed, seasoned, boxed, canned, frozen, sauced, marinated, breaded, cooked in a shared facility, and so on. 12

13 Eating Gluten Free Read the ingredients label avoid all products with wheat, rye, barley, malt or triticale Wheat free doesn t mean gluten free Confirm the GF status with the product manufacturer or use an app (GF scanner) Look for the words or symbol: Gluten-Free Contains shared facility warning Educate yourself about cross-contamination Eating out of the house Toasters, cutting boards, flour sifters, shared containers, cooking surfaces, pizzerias, non-certified baked goods, fried foods (French fries and wings in the same fryer) Be cautious of hidden sources of gluten Find favorite products both GF specific and standard Pay attention to symptoms If not improving may need to re-evaluate and alter diet/habits Plan and pack food When it doubt, go without Gluten Free Diet and Food Label Reading Guide. (2018, February). Retrieved from Combined-Gluten-Free-Diet-and-Food-Label-Reading-Guide.pdf Complications with Gluten-Free Diet Nutritional deficiencies: lack of fortified foods (bread, cereals) Iron, calcium, and folate Lack of fiber Time consuming (plan everything, pack food, etc.) Inconvenient Expensive Restrictive What is Gluten? (2018, March). Retrieved from Gluten Free Diet and Food Label Reading Guide. (2018, February). Retrieved from Combined-Gluten-Free-Diet-and-Food-Label-Reading-Guide.pdf Gluten-Free Diet and T1D MAY improve glycemic control not always the case Untreated CD (intestinal damage) can increase risk of hypoglycemia due to malabsorption of sugars and nutrients Processed GF foods can be higher in sugar, lower fiber, higher fat Quick or delayed absorption leading to irregular or unexplained BG levels Crohn A, Sofia AM, Kupfer SS. Type 1 Diabetes and celiac disease: clinical overlap and new insights into disease pathogenesis. Current diabetes reports. 2014;14:517 13

14 Gluten Free Labeling Law enacted : August 5 th, 2013 Can only be labeled GF if a product has been processed to remove any gluten AND tests below 20ppm of gluten Under the Food Allergen Labeling and Consumer Protection Act of 2004, if a food or an ingredient contains wheat or protein from wheat, the word wheat must be clearly stated on the food label If another term for wheat is used in an ingredient list, the word wheat must be included on the food label either in the ingredient list or in a separate Contains statement All packaged food products regulated by the U.S. Food and Drug Administration that are labeled on or after January 1, 2006, must be in compliance For foods regulated by the U.S. Department of Agriculture (meat products, poultry products, egg products), only the common or usual name of ingredients is currently required Gluten-Free Food Labeling Final Rule. (2018, March). Retrieved from RegulatoryInformation/Allergens/ucm htm Food Allergen Labeling and Consumer Protection Act of (2018, March). Retrieved from GuidanceDocumentsRegulatoryInformation/Allergens/ucm htm GLUTEN FREE PRODUCT SYMBOLS Figure 4: Gluten Free Product Symbols (Google Images, 2018) Gluten-Free Products Gluten properties are not present so they must be replaced. Highly processed: Usually higher fat Higher carbs and sugar, Low fiber Higher sodium Not fortified with vitamins and minerals Products are getting better 14

15 Gluten-free fads No real research to support except for celiac disease Common Fads: Weight loss Anti-inflammatory/joint health Aids in resolution of other disease symptoms (autism, MS) One bit of advice: Get tested while still eating gluten to first rule out CD, go to an allergist to see if you have an allergy, do an elimination diet Other Gluten Related disorders 1. Non-Celiac gluten sensitivity 2. Wheat allergy Non-Celiac Gluten Sensitivity AKA: Gluten Sensitivity, Gluten Intolerance, Non-Celiac Gluten Intolerance. Non-Celiac wheat sensitivity Some signs and symptoms of CD No atrophy or damage Negative for celiac disease Lack of tests and biomarkers Relies on patient description/reporting Improvement after removal of gluten per pt. reporting Questionable intolerance is it really gluten? Leanard M, Sapone A, Catassi C and Fasano, A. Celiac Disease and Nonceliac Gluten-sensitivity: A Review. JAMA. 2017:318(7): Fasano A. A clinical guide to Gluten-Related Disorders. Lippincott Williams and Wilkins. Philadelphia, PA

16 Wheat Allergy Defined as adverse Type-2 helper T cell-immunologic reaction to wheat proteins Presents soon after wheat ingestion Signs of anaphylaxis swelling or itching of mouth, throat or skin; nasal congestion; water eyes and difficulty breathing More common in children 2% and 9% in children 0.5% and 3% in adults Fasano A. A clinical guide to Gluten-Related Disorders. Lippincott Williams and Wilkins. Philadelphia, PA Differences among CD, Allergy, Sensitivity Figure 5: Fasano A, Catassi C (Celiac Disease 2012) Future Therapies Various companies looking at testing and treatment options Various options being tested Pre-Clinical, Phase I and Phase II studies Future Therapies for Celiac Disease. (2018, January) Retrieve from 16

17 In-Office Testing for CD in pediatric patients Study done in Spain using a Point-of-care test (POCT) 100 children 18 years of younger, all experiencing GI symptoms, none following gluten free diet 48 were diagnosed with CD prior to POCT POCT found to be 100% accurate in children under 10 POCT found to be about 90% accurate in children over 10 Accuracy of In-Office Testing For Celiac Disease in Pediatric Patients. (2018, February). Retrieved from blog/2018/02/accuracy-office-testing-celiac-disease-pediatric-patients/ New testing option Use of HLA-DQ-gluten tetrameter test 143 individuals with genotype HLA-DQ2 4 groups: confirmed CD following GF diet confirmed CD who were NOT following a GF diet CD ruled out but were following GF diet control group of 52 without CD and who were consuming gluten Able to predict presence of CD in 2/3 cases 100% accurate in predicting the ABSENCE of the disease Simply: quickly and easily eliminate possibility of CD for majority of patients, leaving only a small percentage to follow standard CD diagnosis path New Testing Option for Possible Celiac Disease Sufferers. (2018, February). Retrieved from new-testing-option-possible-celiac-disease-sufferers/ A few possible treatment options Immunogenx: IMGX003 A mixture of two gluten-specific enzymes that break down gluten proteins into small, harmless fragments. Administered as a supplement to a gluten-free diet for the potential treatment of celiac disease The only CD treatment that has been shown to lessen gluten-induced intestinal mucosal injury, as well as improve symptoms in clinical trials. Innovate Biopharmaceuticals: INN-202 (Larozetide Acetate) A tight junction regulator, which helps restore leaky or open junctions to a normal state (caused by ingestion of gluten in CD The reaction that causes intestinal villi damage Ingested prior to meal, Larazotide may help keep the tight junctions closed, thus reducing the intestinal-inflammatory process in response to gluten. Plus many more 17

18 Key Clinical Points Once considered a GI disorder mainly effecting children and Caucasians, CD is now known to affect different ages, races and ethnic groups and it may manifest without GI symptoms Measurements of the IgA-anti-tissue transglutaminase antibodies is the preferred initial screening test for CD because of high sensitivity and specificity Diagnosis confirmed by upper endoscopy with duodenal biopsy May not be necessary in children with strong clinical and serological evidence Gluten causes celiac disease enteropathy, cornerstone treatment is a strict gluten free diet for life. Gluten sensitivity may occur in the absence of CD and a definitive diagnosis should be made before implementing lifelong gluten-free diet Several new testing and treatment options are being researched to improve treatment and the process of diagnosing and screening for CD. Helpful websites/resources Academy of Nutrition and Dietetics Celiac Disease Nutrition Guide Websites: American Celiac Society Celiac Disease Foundation Celiac Sprue Association/USA Inc. Gluten Intolerance Group of North America Gluten-Free Apps Find me Gluten-Free Gluten-Free scanner References 1. Accuracy of In-Office Testing For Celiac Disease in Pediatric Patients. (2018, February). Retrieved from celiac.org/blog/2018/02/accuracy-office-testing-celiac-disease-pediatric-patients/ 2. Bai J, Ciacci C, Corazza G, Fried M, Olano C. et al. World Gastroenterology Organization Global Guidelines: Celiac Disease Coeliac Disease. (2018, March). (Image) Retrieved from 4. Celiac Disease. (2018, March) (image) Retrieved from 5. Celiac Disease? (2018, January) Retrieve from 6. Crohn A, Sofia AM, Kupfer SS. Type 1 Diabetes and celiac disease: clinical overlap and new insights into disease pathogenesis. Current diabetes reports. 2014;14: Fasano A. A clinical guide to Gluten-Related Disorders. Lippincott Williams and Wilkins. Philadelphia, PA Fasano A, Catassi C. Clinical Practice: Celiac Disease. The New England Journal of Medicine. 2012;367: Food Allergen Labeling and Consumer Protection Act of (2018, March). Retrieved from ucm htm 10. Future Therapies for Celiac Disease. (2018, January) Retrieve from future-therapies-celiac-disease/ 18

19 References 11. Gluten Free Diet and Food Label Reading Guide. (2018, February). Retrieved from wp/wp-content/uploads/2017/07/combined-gluten-free-diet-and-food-label-reading-guide.pdf 12. Gluten-Free Food Labeling Final Rule. (2018, March). Retrieved from GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/Allergens/ucm htm 13. Guandalini S. (2007). A Brief History of Celiac Disease. Impact: A Publication of the University of Chicago Celiac Disease Center. Volume 7 Issue Leanard M, Sapone A, Catassi C and Fasano, A. Celiac Disease and Nonceliac Gluten-sensitivity: A Review. JAMA. 2017:318(7): Mahan K, Escott-Stump S. (2008). Krause s Food and Nutrition Therapy. St. Louis, MO: Saunders Elsevier. 16. New Testing Option for Possible Celiac Disease Sufferers. (2018, February). Retrieved from celiac.org/blog/2018/01/new-testing-option-possible-celiac-disease-sufferers/ 17. Rubio-Tapia A, Hill I, Kelly C, Calderwood A, Murray J. American College of Gastroenterology Clinical Guideline: Diagnosis and management of celiac disease. Am J Gastroenterol. 2013; 108(5): What is Gluten? (2018, March). Retrieved from 19