1. CELIAC DISEASE A Lifetime Without Beer Kyle Mulligan Northwestern Ontario Medical Program

2. Outline Epidemiology Pathogenesis Clinical Features Associated Conditions Diagnosis Treatment

3. Epidemiology True prevalence unknown Variable symptoms Slight female preponderance Highest prevalence in Western Europe and emigrants (North America, Australia) Also India, South America, North Africa Low African-Caribbean, Chinese, Japanese

4. Prevalence Studies One case in every 300 newborns 1 in 266 prevalence for asymptomatic cases in blood donors In the USA, elevated antiendomysial antibodies in 1:250 healthy blood donors Relatively common and Underdiagnosed.

5. Pathogenesis Immune system abnormally activated by gluten Gliadin portion of wheat protein Prolamines (insoluble proteins) in rye, barley and oats

6. Pathogenesis Genetic, immunologically-mediated, small intestine enteropathy in which intestinal villi are destroyed by cellular and humoral- mediated immunologic reaction to gliadin protein Results in malabsorption

7. Pathogenesis Inappropriate T-cell mediated immune response in genetically predisposed people 10% prevalence among 1 st degree relatives 95% express HLA-DQ which presents gluten-derived gliadin peptides to stimulate T-cells Delaying exposure to gluten may alter disease

8. Pathogenesis Viral exposures may trigger an immunologic response Adenovirus type 12 implicated Enzyme tissue transglutaminase is one of the targets of the autoimmune response in celiac disease

9. CLINICAL: Classical children Present btwn 4-24m with impaired growth, FTT, diarrhea, and abdominal distension Vomiting common, pallor, edema Gradual onset Wt gain velocity slows then wt loss Severe: growth delays, iron and folate deficiency anemia, rickets, pubertal delay

10. CLINICAL: Atypical children Older child and adolescents Recurrent abdominal pain,  transaminases, recurrent aphthous stomatitis, defects in dental enamel, angular cheilitis Arthralgia Depression, irritability, poor school performance Atopic dermatitis

12. CLINICAL: adults 20% of cases occur in people >60 yo May present in pregnancy and post-partum as anemia Episodic or nocturnal diarrhea, flatulence, and weight loss Symptomatic lactose intolerance because of the enteropathy

13. CLINICAL: adults Steatorrhea often absent especially if disease proximal small intestine Abdominal discomfort and bloating common and may be Dx as IBS Malaise and “tired all the time” very common Consider with stomatitis, angular cheilitis

15. CLINICAL: adults Only 50% with diarrhea Most common presentation is Fe deficiency

16. Extra-Intestinal Manifestations Nutritional deficiencies: Iron deficiency anemia Folate/B 12 (anemia, glossitis, peripheral neuropathy, Vitamin K (coagulopathy, purpura) Vitamin D which can lead to hypocalcemia/tetany, elevated ALP, and osteoporosis Protein (edema, ascites) Vitamin A (night blindness)

17. Associated Conditions Dermatitis Herpetiformis Intensely pruritic papulovesicular lesions occurring symmetrically over extensor surfaces, buttocks, trunk, neck, and scalp Responds to gluten free diet Diabetes Mellitus type I ~8% positive rate in asymptomatic DM I children Autoimmune Thyroiditis

19. Associated Conditions Seizure Disorder Occipital calcification IgA nephropathy IgA deficiency Sjogren’s syndrome/ Rheumatoid Arthritis/ Collagen Disorders Down’s Syndrome

20. Diagnosis One study showed that a subset of patients with adult-onset celiac disease had symptoms and were followed by a physician for 28 years before Dx 43% of Canadian celiac disease patients misdiagnosed previously (IBS, stress, anemia, colitis, food allergy, PUD)

21. Diagnosis Routine tests that can suggest celiac disease Anemia (microcytic, hypochromic or normocytic, normochromic with  RDW)  AST  Albumin/plasma protein Low or “too good” cholesterol (total, LDL, HDL)  alkaline phosphatase

22. Diagnosis Currently, Ontario laboratories screen with IgA antiendomysial antibody and tissue transglutimase antibody If positive other tests can be ordered MDS charges, in hospital does not May want to test for IgA deficiency before writing off a false test

23. Tests Sens SpecPPVNPV IgA antigliadin Ab’s 75-9082-9528-10065-100 IgG antigliadin Ab’s69-8573-9020-9541-88 IgA Antiendomysial Ab (indirect)85-9897-10098-10080-95 IgA Antiendomysial Ab (ELISA with tissue transglutaminase) 95-9894=9591-9596-98 IgA Antiendomysial Ab (dot blot with tissue transglutaminase) 9399 93

24. Diagnosis Presence of IgA antiendomysial and gliadin antibodies were predictive of positive villous atrophy in 99.1% of patients If both negative, normal mucosa in 99.1% of patients

25. Small Intestine Biopsy Required for diagnosis before start of gluten-free diet Panendoscopy/OGD with biopsies from 2 nd or 3 rd portion of the duodenum Absent villi, hyperplastic crypts, increased numbers of intraepithelial lymphocytes Reserve 2 nd biopsy to unresponsive patients

28. Treatment Strict Gluten-free diet for life Avoid all foods with wheat, rye, barley Avoid oats initially until remission Avoid lactose initially until remission Try foods containing wheat starch with gluten removed Read all labels of foods, medications, etc Avoid beer, ales, lagers, stouts Wine, liquors, whiskey, brandy, spirits okay

29. Treatment 70% improve within first two weeks Full resolution of histology more common in children; 2-3 months after start of diet Vitamin supplementation initially May require IV corticosteroids if critically ill with celiac crisis especially if after a gluten challenge

30. The Masters

31. References Farrell and Kelly. “Celiac Sprue” NEJM. Vol 346 #3 January 17, 2002 Hin et al. “Celiac Disease in Primary Care.” BMJ Vol 318 January 16, 1999 Pruessner. “Detecting Celiac Disease in Your Patients.” Am Fam Phys March 1/98 Gillett et al. “High Prevalence of Celiac Disease in Pts with Type I DM Detected by Antibodies to Endomysium and Tissue Transglutaminase.” Can Jour Gastroenterology May 2001