Case scenario: A 36 years old woman with chronic intermittent diarrhea from

2. Case scenario: A 36 years old woman with chronic intermittent diarrhea from childhood and weight loss,Abdominal distention and bloating, idiopathic peripheral neuropathy,weakness,fatigue,bone pain and with unexplained iron-deficiency anemia,Folat deficiency, Vitamin D deficiency, abnormal liver function tests that by serologic evaluation and small bowel biopsy and clinical-histologic response to gluten-free diet, established the diognosis of coeliac disease. The patient is worried about risk of malignancy and mortality. Is she in risk of overal mortality compared with the general population?

3. PICO: P:A 36 years old woman known case of coeliac disease. .I:Coeliac patient .C:Non- coeliac patient .O:Mortality and malignancy

4. Meta-analysis: coeliac disease and the risk of all-cause mortality any malignancy and lymphoid malignancyM. Tio, M. R. Cox & G. D. Eslick

5. Celiac Disease

6. Celiac disease is common autoimmunedisorderand common cause of malabsorption of one or more nutrients.

8. This picture shows the damage that is caused by gluten to the microvilli in someone who suffers from Celiac Disease. As you can see, the image on the left, a healthy intestine, has much greater surface area than the one on the right, damaged by gluten consumption.

10. Celiac disease is considered an "iceberg" disease with a small number of individuals with classical symptoms and manifestations related to nutrient malabsorption

11. The Celiac Iceberg Symptomatic Celiac Disease Manifest mucosal lesion Silent Celiac Disease Normal Mucosa Latent Celiac Disease Genetic susceptibility: - DQ2, DQ8 Positive serology

12. Classical Celiac Disease (1:4500) Atypical Silent Latent Detected by screening (1:250)

13. :EtiologyThe etiology of celiac disease is not known, but environmental, immunologic, and genetic factors all appear to contribute to the disease.

15. Environmental factor is the clear association of the disease with gliadin,acomponent of gluten that is present in wheat, barley, and rye. In addition to the role of gluten restriction in treatment, the instillation of gluten into both normal-appearing rectum and distal ileum of patients with celiac disease results in morphologic changes within hours.

16. OBVIOUS SOURCES Bread Bagels Cakes Cereal Cookies Pasta / noodles Pastries / pies Rolls Sources of Gluten

17. Sources of Gluten • POTENTIAL SOURCES • Candy • Communion wafers • Cured Pork Products • Drink mixes • Gravy • Imitation meat / seafood • Sauce • Self-basting turkeys • Soy sauce

18. An immunologic component in the pathogenesis of celiac disease is critical Serum antibodiesIgAantigliadin,IgAantiendomysial, IgAanti-tTG antibodies—are present. The antiendomysialantibody has 90–95% sensitivity and 90–95% specificity. patients with these antibodies should undergo with .deudenal biopsy

19. Genetic factor(s) are also involved in celiac disease. The incidence of symptomatic celiac disease is 10% in first-degree relatives of celiac disease patients. all patients with celiac disease express the HLA-DQ2or HLA-DQ8 allele, though only a minority of people expressing DQ2/DQ8 have celiac disease. Absence of DQ2/DQ8 excludes the diagnosis of celiac disease.

20. Be aware DR3 should now be referred to as DR17 DQ2 DQ8 DR5/DR7 DR3/DR3 DR3 { DQA1*0501 { DQA: Any DQA1*0201 DQ2 DQB1*03 DQB1*0201 Trans CIS CIS Gluten APC

21. Genetics Several genes are involved The most consistent genetic component depends on the .presence of HLA-DQ (DQ2 and / or DQ8) genes Other genes (not yet identified) account for 60 % of the .inherited component of the disease HLA-DQ2 and / or DQ8 genes are necessary (No DQ2/8, no Celiac Disease!) but not sufficient for the .development of the disease Genes ? ? ? HLA ? + Gluten Celiac Disease

22. :DiagnosisA biopsy should be performed in patients with symptoms and laboratory findings suggestive of nutrient malabsorption and/or deficiency and with a positive endomysial antibody test.

23. The diagnosis of celiac disease requires the presence of characteristic histologicchanges on small-intestinal biopsy together with a prompt clinical and histologic response following the institution of a gluten-free diet. If serologic studies have detected the presence of IgAantiendomysial or tTG antibodies, they too should disappear after a gluten-free diet is started.

24. The hallmark of celiac disease is the presence of an abnormal small-intestinal biopsy (Fig. 294-4) and the response of the condition—symptoms and the histologicchanges on the small-intestinal biopsy—to the elimination of gluten from the diet.The histologic changes have a proximal-to-distal intestinal distribution of severity, which probably reflects the exposure of the intestinal mucosa to varied amounts of dietary gluten.

25. Diagnosis 1st: Physical exam and blood testing 2nd: Duodenal biopsy 3rd: Implement gluten-free diet http://www.csaceliacs.org/celiac_diagnosis.php

26. The classical changes seen on duodenal/jejunalbiopsy:are restricted to the mucosa and include 1:an increase in the number of intraepithelial .lymphocytes2: absence or reduced height of villi, resulting in a flat appearance with increased crypt cell proliferation, resulting in crypt hyperplasia and loss of villous structure, with consequent villous, but not mucosal, .atrophy3:cuboidal appearance and nuclei that are no longer oriented basally in surface epithelial cells.4:increased lymphocytes and plasma cells in the lamina propria.

27. Histology of intestinal biopsy in CDModified Marsh score

28. Normal small intestine Normal villi Small intestine with villous atrophy Small intestine with scalloping

31. Damaged Healthy It Takes A Villi

32. Duodenum

33. CELIAC DISEASE ENDOSCOPY Scalloped Gluten-free diet Normal HISTOLOGY Increased IEL Villous atrophy Recovering

34. This is what the small intestine looks like under the microscope when the mucosa is injured like the left photo shows. The villi are essentially flat and numerous lymhocytes are near the surface lining.

35. This endoscopic photo of the small bowel (duodenum) shows the classic fissuring or cobblestoning of the surface as well as "scalloping" of the folds in Celiac disease.

36. This endoscopic photo was taken with special light technique called Narrow Band Imaging (NBI). It brings out some of features of atrophy, fissuring or cobblestone appearance of the mucosa (surface lining) and the "scalloping" of the folds seen in Celiac disease.

37. The folds are flattened and the mucosa in this patient with Celiac.

42. GI symptoms • diarrhea • weight loss • weakness • pedal edema - protein malabsorption • easy bruising - vitamin K malabsorption • classic steatorrhea • increase in stool mass in most patients

43. Extraintestinal features

44. Hematopoietic • anemia - iron or folate deficiency, but also increased blood loss • B12 deficiency in severe cases • hyposplenism - may resolve with dietary therapy • thrombocytosis with Howell-Jolly bodies • bleeding diathesis

45. Osteopenic bone disease • decrease Ca absorption • decrease in absorption fat-soluble vitamin D • binding of Ca and Mg in lumen by unabsorbed dietary fatty acids

46. Osteopenic bone disease • Osteoporosis with bone pain and pathologic fractures • paresthesia, muscle cramps and tetany if severe hypocalcemia • chronic can result in secondary and even tertiary hyperparthyroidism • problems with premenopausal bone mass

47. Neurologic symptoms • peripheral neuropathy • myopathy • cerebellar ataxia • myoclonus • cerebral atrophy and dementia • cerebral vasculitis • brain-stem encephalitis • epilepsy and cerebral calcifications

48. Renal and liver disease • Glomerulonephritis • IgA nephropathy may respond to gluten-free diet • PBC, PSC and chronic active hepatitis • elevated transaminases

49. Autoimmune and Connective tissue disease • Vasculitis • cryoglobulinemia • Sjogren’s syndrome • SLE • selective IgA deficiency • thyroid disease • IDDM- and celiac both have HLA-DR3 and DQB1*0201 alleles

50. OB-GYN • Impaired fertility in women • high incidence of spontaneous abortion • low birth-weight babies • reduced breast milk production • paripartum exacerbation or first presentation • correctable with gluten-free diet