Celiac and Gluten Related Disorders: A Refresher Course

1. Did you know? A Refresher Course on Celiac and Gluten Related Disorders April10, 2018

2. Objectives: Identify patients who would benefit from the Gluten Free Diet (GFD) 2. Describe the difference between celiac disease and non-celiac gluten sensitivity 3. Identify nutritional difficulties with the GFD

3. U.S. gluten-free products market revenue by product, 2014 - 2025 (USD Million) http://www.grandviewresearch.com/industry-analysis/gluten-free-products-market

4. Gluten Related Disorders

5. REACTIONS TO GLUTEN CELIAC DISEASE WHEAT ALLERGY GLUTEN SENSITIVITY

6. Celiac Disease (CD) Chronic inflammatory disorder in genetically predisposed individuals caused by the ingestion of: Wheat Rye Barley Inappropriate immune response  Small Intestinal Patchy Inflammation Gastrointestinal complaints Nutrient malabsorption Extra-intestinal symptoms: Fatigue, arthralgias etc Fasano, 2003

7. Clinical Manifestations: Celiac Disease is a unique autoimmune condition Gastrointestinal (“classical”) Non-gastrointestinal (“atypical”) Asymptomatic

8. Gastrointestinal Manifestations (“Classic”) Diarrhea or constipation Abdominal distension, pain Anorexia Failure to thrive or weight loss Vomiting

9. Non-Gastrointestinal Manifestations Presentation: older child to adult Iron deficiency anemia Dermatitis Herpetiformis Dental enamel hypoplasia of permanent teeth Hepatitis Osteopenia/Osteoporosis, Arthritis Short Stature Delayed Puberty

10. Asymptomatic - Silent: No or minimal symptoms, “damaged” mucosa and positive serology - Identified by screening asymptomatic individuals from groups at risk: • First degree relatives • Down syndrome patients • Type 1 diabetes patients

11. Pathophysiology Sequelae Malabsorption of nutrients: iron, folate, calcium, and vitamin D Increased intestinal permeability may permit entry of other toxins which might induce autoimmune diseases

12. Diagnosing Celiac Disease:Accurate Serological Tests Allowed for Screening Type 1 DM, Down

13. Diagnosing Celiac Disease:Genetic (HLA) Testing DQ2 found in 95% of celiac patients DQ8 found in remaining patients DQ2 found in ~30% of general population High negative predictive value - Negativity for DQ2/DQ8 excludes diagnosis of Celiac Disease with 99% confidence!

14. Diagnosing Celiac Disease:Endoscopy still the Gold Standard

15. Celiac Disease Follow Up Our Center’s Time Table for follow up: At time of diagnosis • Discussion of pathology results • Comprehensive nutrition counseling 3 months after diagnosis • Discussion of diet progress • Address issues with diet 6 months after diagnosis • Labs: celiac serologies, vitamin levels 1 year after initial diagnosis • Labs: celiac serologies, vitamin levels • Rescope to assess for histologic healing

16. Celiac Disease Follow Up Nutrition Labs - To be done on a yearly basis - Hemoglobin, Iron, Ferritin - Folate, Thiamine, B12, Zinc - Vitamin D, Calcium Adjunct studies - Bone density scan - Repeat endoscopy 1 year after diagnosis to document healing

17. Major Complications of Celiac Disease Short stature Dental Enamel Hypoplasia Recurrent stomatitis Infertility Osteoporosis Neurological Disturbances, Ataxia Intestinal Lymphoma

18. NON CELIAC GLUTEN SENSITIVITY (NCGS) Unable to tolerate gluten and develop an adverse reaction when eating gluten Symptoms may resemble celiac disease Negative celiac serology Wheat allergy is ruled out NO small intestinal damage-normal histology Currently the diagnosis is made by exclusion, and an elimination diet and 'open challenge’ • Symptoms disappear after gluten is withdrawn from diet • Symptoms reoccur after gluten challenge

19. NCGS FACTS: The lack of clear diagnostic marker/criteria may have led to NCGS underdiagnosed by physicians for many years The prevalence of NCGS is estimated to be between 3% to 6% The research estimates that 18 million Americans have NCGS. The genetic component of NCGS is not yet completely understood Only 50% of NCGS patients express HLA-DQ2 or HLA-DQ8, indicating that these genes are not necessary to develop NCGS. Sapone A et al. BMC Med 2012;10:13

20. PATHOGENESIS The pathophysiology of NCGS is unclear. Possible speculations: Increased permeability of the small intestine Gluten induced low grade inflammation Opioid-like activity of gluten Innate immune reaction to non-gluten components of wheat Placebo effect of gluten withdrawal/challenge Di Sabatino et al J ClinGastroenterol 2013 Green P et al BMJ 2015

21. Symptoms: Abdominal Pain, bloating, flatulence Eczema and/or rash Headache Foggy mind Fatigue Diarrhea Depression/anxiety Joint Pain Numbness in the legs, arms or fingers

22. IBS and NCGS There is a complex relationship between IBS and diet Gluten ingestion may elicit GI symptoms in patients with IBS-diarrhea (IBS-D) Gluten alters bowel barrier functions in patients with IBS-D, particularly in HLA DQ2/8-positive patients In this subgroup that gluten elimination may improve patient symptoms in IBS Besides gluten, other wheat derivatives could play a role in causing symptoms in IBS • Amylase-trypsin inhibitors • Fructans

23. Get the Right Diagnosis • Never start the GFD before proper testing is completed! • After 4-6 months of a GFD, serology levels may return to normal. • 1monthon the GFD can change the result of the biopsy • .

24. Why the Right Diagnosis? Mother rushed to hospital with severe stomach cramps … and gave birth to baby boy she had no idea she was expecting • Teresa Howard, 43, thought she was suffering from a wheat intolerance • She was rushed to hospital and gave birth to her third son two hours later 

25. Gluten Free Diet Overview

26. Gluten-Containing Ingredients to Avoid • Wheat • Barley • Barley Malt /Extract • Brewer’s yeast • Rye • Other Types of Wheat: Spelt Kamut Emmer Einkorn Semolina Faro Bulgur Couscous Durum Triticale Filler

27. For foods regulated by the FDA, the consumer should look for the terms in products not labeled gluten free: Wheat Barley Malt Rye Oats Brewer’s yeast FALCPA…shopping made easier!(Food Allergy Labeling Consumer Protection Act)

28. What about Manufactured in a plant… “Before we come in, was any part of your house produced In a facility that also handles wheat, milk, eggs or soy?”

29. Allergen advisory statements for wheat: do they help US consumers with celiac disease make safe food choices? T Thompson, TB Lyons and A Jones, European Journal of Clinical Nutrition (2016) 70, 1341–1347; doi:10.1038/ejcn.2016.155; published online 14 September 2016 Precautionary labeling for wheat or gluten on products not labeled gluten-free but appearing to be free of gluten-containing ingredients was NOT a useful predictor of gluten content.

30. Gluten Exposure Gluten Detective

31. Nutritional Consequences of the GFD The GFD can be missing important nutrients needed for optimal health and wellness Lacks fiber Lacks iron Lacks B vitamins- folate, niacin, B12 Lacks calcium Phosphorous Zinc

32. Nutrition Deficiencies Lead to: Iron deficiency anemia • Supplementation is frequently required • Iron rich foods should be included Reduced bone mineral density Weight gain on GFD due to high fat, sugar and calorie content Constipation • Change in diet, low fiber from high fiber can cause constipation: abdominal pain, cramping, bloating

33. Gluten-free products Traditionally used starches not whole grain flours Typically use white rice, potato, tapioca and corn Additional ingredients • Added oils and fat (commonly palm oil for texture) • Added sugar • Added protein (soy, eggs, whey protein) • Added gums for stability and moisture (guar, xanthum, cellulose)

34. Gluten-Free and Still Not Feeling Better? FEEL FULL FAST AFTER FOOD NAUSEA CONSTIPATION VOMITING DIARRHEA OR LOOSE STOOL GAS BLOATING

35. Common Nutritional Problems on GFD Lactose intolerance • 30-60% in newly diagnosed • Caused by intestinal injury in untreated CD • May resolve on GF diet Constipation • Change in diet, low fiber from high fiber can cause constipation: abdominal pain, cramping, bloating

36. “Non-Responsive” Celiac Disease • Persistent or recurrent signs/symptoms occur in ~30% of patients • Others included: • Peptic ulcer disease (2) • Crohn’s disease (1) • Duodenal adenoCA (1), • Food allergy (1) • Gastroparesis (1)

38. How Much gluten? “Adult CD patients evidently consume, on average, potentially unsafe levels of gluten while on a GFD. Mean daily consumptions for adults were determined to be 244 mg (stool analysis), 363 mg (urine analysis) and >228 mg (ALV003- 1221 trial analysis), with the latter value likely to be greater than the former values.” People with celiac disease should not consume more than 10 mg of gluten per day This is approximately 1/8th of a tsp of or the equivalent of 17 one ounce servings of labeled gluten-free food containing just under 20 parts per million of gluten.

39. Gluten Exposure Recheck labels of favorite everyday foods as ingredients can change. • Check label of foods not labeled gluten free for ingredients Look for sources of contamination at home and away from home: Use separate toaster, condiment containers, colanders Meal preparation: • Clean counter space before preparing GF meal, clean pots, pans, bowls, utensils should be cleaned and free of food residue Eating at restaurants, school, daycare or social events Social and religious occasion

40. Gluten Contamination Elimination Diet(GCED) • Modified gluten free diet of whole unprocessed foods. • Typically 3-6 month duration. • Aims to eliminate any source of gluten contamination in an already strict diet.

41. GCED When to use of the GCED The diagnosis of CD is correct The patient has been on a strict GFD for more than 12 months The patients has been seen by a knowledgeable dietitian to review the diet for possible gluten exposure An EGD has shown continue damage of a Marsh 3, regardless of celiac antibody test and symptoms Proper education, support and follow up can be provided over the next 3 months When not to start the GCED Diagnosis of CD is not clear Not helpful for Non celiac gluten sensitivity (NCGS) Pt has not been on the GFD for more than 12 months No damage or a Marsh 1-2 is seen on the biopsy, not for pts with elevated celiac antibodies with normal biopsy

42. GCED

43. Barriers to Compliance: Require Help from a Skilled Dietitian Diet too restrictive Cross contamination No allowance for occasional “cheating” Uncomfortable in social setting Dining away from home Religious considerations Too expensive Gluten free foods can be 3 -5 X more expensive than their wheat counterpart Tasteless Too difficult Elderly Illiterate Mental/psychological impairment Survey on reason for non-compliance to the GFD

44. Medical Nutrition Practice Group Dietitians in Gluten Intolerance Diseases (DIGID) www.mnpgdpg.org Evidence Analysis Library (EAL) on CD www.adaevidencelibrary.com Celiac Disease Toolkit Companion to AND’s Evidence-Based Nutrition Practice Guideline Academy of Nutrition and Dietetics Resources

45. Dr. Alessio Fasano’s Gluten Freedom Shelley Case, Dietitian Gluten Free: The Definitive Resource Guide America’s Test Kitchen The How Can It Be Gluten Free Resources

46. umm For more information or to make an appointment: 410-328-6749 pedsgi@som.umaryland.edu www.umm.edu/celiac Pam Cureton RDN, LDN pcureton@som.umaryland.edu

47. QUESTIONS?