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Celiac Disease & Non Celiac Gluten Sensitivity Chanda K. Ho, MD MPH March 23, 2013.

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Presentation on theme: "Celiac Disease & Non Celiac Gluten Sensitivity Chanda K. Ho, MD MPH March 23, 2013."— Presentation transcript:

1 Celiac Disease & Non Celiac Gluten Sensitivity Chanda K. Ho, MD MPH March 23, 2013

2 Objectives Gluten Free Diet Diagnosis and Management of Celiac Disease Irritable Bowel Syndrome and Celiac Disease Non-Celiac Gluten Sensitivity Recommendations

3 Wheat (Triticum spp) 1 st cultivated approximately 10,000 years ago in fertile crescent Relatively novel to mans diet 2010 world production 651 million tons 3 rd most-produced cereal after maize (844 million tons) & rice (672 million tons) Major diet component b/c need to increase agricultural production Wheat, Barley, Rye

4 Wheat Gluten- main structural protein complex Gluten- main structural protein complex Primary proteins are gliadin and glutenin. Primary proteins are gliadin and glutenin. Gliadin contains bulk of toxic complements- contains repeating patterns of AA that GI tract cannot break down Gliadin contains bulk of toxic complements- contains repeating patterns of AA that GI tract cannot break down

5 Gluten The New Diet Villain High profile celebrities New Diet Fad Public has adopted this concept quite readily Google: PubMed searches- 4,598: 1 Springen K. Newsweek. 2 Dec 2008

6 www.nytimes.com

7 Gluten Free Diet 15-30 million Americans are buying gluten free products $2 billion of gluten free products sold in 1 year Public awareness of non celiac gluten sensitivity in US has been shown to be higher than that of celiac disease Di Sabatino et al. Ann Intern Med 2012

8 Gluten-Free Diet Foods containing wheat, rye, and barley OK to eat: soybean/tapioca flours, rice, corn, buckwheat, potatoes Read labels on prepared foods/condiments, may contain stabilizers/emulsifies that have gluten Wine is gluten free. Avoid beers, ales, lagers, and malt vinegars. Dairy may be not well tolerated given secondary lactose intolerance Limit oat consumption

9 Diagnosing Celiac Disease

10 Celiac Disease (CD): definition Chronic immune-mediated disease in genetically susceptible individuals Environmental precipitant- gliadin (toxic fraction of gluten protein) Found in wheat, rye, barley Improvement with gluten withdrawal Clinical manifestations are variable

11 Classical CD Symptoms of malabsorption such as steatorrhea, weight loss, or other signs of nutrient or vitamin deficiency [12].12 The presence of characteristic histologic changes (including villous atrophy) on small intestinal biopsy. Resolution of the mucosal lesions and symptoms upon withdrawal of gluten-containing foods, usually within a few weeks to months.

12 The Celiac Iceberg Symptomatic Celiac Disease Silent Celiac Disease Latent Celiac Disease Genetic susceptibility: - DQ2, DQ8 Positive serology Manifest mucosal lesion Normal Mucosa Potential Asymptomatic/ Non-classical CD

13 Definitions of Celiac Disease CLASSIC: malabsoprtion, fully developed villous atrophy, GI symptoms ATYPICAL: no GI symptoms but evaluated for IDA, anemia, short stature, osteoporosis, etc SILENT: no symptoms, no features/complications, found incidentally LATENT: CD pts who responded to have a GRD and have normal histology OR pts with normal histology now on GFD who go on to develop CD (normal mucosa, +Ab test) AGA Technical Review, Gastro, 2006.

14 Who Should Be Tested? GI symptoms including chronic/recurrent diarrhea, malabsoption, distension, bloating Symptoms suggestive of IBS and/or Lactose Intolerance Patients with Type 1 DM, Autoimmune disorders, 1 st /2 nd degree relatives of individuals with CD, Down, Turner, or Williams syndromes

15 Who Should Be Tested? Iron Deficiency Anemia Folate/B12 deficiency Persistent elevation in AST/ALT Short Stature Delayed puberty Recurrent migraines Recurrent fetal loss Low Birthweight Infants

16 Serologic Testing Serologic Test Sensitivity % Specificity % Features IgA AGA 85-9090ELISA False positive with mucosal damage Replaced by other markers IgA EMA 97.499.6 Immunofluorescence with human umbilical cord or monkey esophagus Subjective, time consuming, expensive IgA TTG 95.198.3 ELISA, human recombinant or RBC- derived Nonsubjective, less expensive Loss of specificity with autoimmunity IgA DGP 9597ELISA Positive in 80% of cases w/ IgA def Deamidated gliadin peptides Rostom et al. Gastroenterol 2006

17 Guidelines for Diagnosis of Celiac Disease Typical symptoms of CD Typical symptoms of CD Positivity of serum CD IgA class autoantibodies at high titer Positivity of serum CD IgA class autoantibodies at high titer HLA-DQ2 and/or HLA DQ8 genotypes HLA-DQ2 and/or HLA DQ8 genotypes Celiac enteropathy found on small bowel biopsy Celiac enteropathy found on small bowel biopsy Crypt hyperplasia Crypt hyperplasia Villous atrophy Villous atrophy Intraepithelial lymphocytosis Intraepithelial lymphocytosis Response to a GFD Response to a GFD ESPGHAN Guidelines for Diabnosis of Celiac Disease

18 Monitoring Response to GFD 70% with noticeable clinical improvement within 2 weeks. Symptoms > Histology Patients should be evaluated 4-6 weeks after starting GFD Use of serologic testing to monitor response Normal levels do not necessarily mean histologic recovery Levels which do not fall, however, indicate ongoing gluten ingestion (intentional or inadvertent) Requires pre-treatment elevated levels to be clinically useful

19 Genetic Testing for Celiac Sprue Human leukocyte antigen (HLA) alleles associated with celiac disease Sensitive but NOT specific 30% Caucasians carry DQ2 or DQ8 A negative test excludes celiac disease with 99% confidence Schuppan D. Gastroenterology. 2000: 119: 234-242 Kaukinen, K, e al. Am J Gastroenterol. 2002: 97: 695-699

20 ?Repeating Small Bowel Biopsies If nonresponder to GFD Confirm mucosal healing

21 Nonresponders Patients with poor compliance or inadvertent ingestion of gluten May have histologic features that overlap with CD but due to another undiagnosed disorder Concurrent IBS, lactose intolerance, SIBO, pancreatic insufficiency, microscopic colitis Refractory sprue Ulcerative jejunitis or intestinal lymphoma

22 Other factors to consider in CD management Nutritional Deficiencies: iron, folic acid, calcium, Vit D Constipation (GFD are low in fiber)- Rx with psyllium Prevention of bone loss evaluate with DEXA scan Pneumovax Dermatitis herpetiformis

23 IBS and Celiac

24 Rome III Criteria for IBS Recurrent abdominal pain or discomfort, at least 3 days/month in the last 3 months associated with 2 or more of the following Improvement with defecation Onset associated with a change in frequency of stool Onset associated with a change in form of stool Longstreth et al, Gastroenterology 2006: 130: 1480-1491.

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26 IBS and diet Individuals with IBS complain of subjective food intolerance twice as much as controls Up to 25% of general US pop believe they have a food allergy True FA 4-8% children, 1-4% adults 50-90% presumed food allergies are food intolerance or aversion (non-immune mediated) Eswaran et al Gastro Clin N Am 2011

27 IBS and Celiac Disease EventIBS patients %Gen Pop % Colitis/IBD0.51-0.980.3-1.2 CRC0-0.510-6 (age dep) Thyroid dysfxn4.25-9 Celiac sprue3.60.7 Lactose intol3826 Cash et al. Am J Gastroenterol 2002; 97:2812.

28 Date of download: 8/6/2012 Copyright © 2012 American Medical Association. All rights reserved. From: Yield of Diagnostic Tests for Celiac Disease in Individuals With Symptoms Suggestive of Irritable Bowel Syndrome: Systematic Review and Meta-analysis Arch Intern Med. 2009;169(7):651-658. doi:10.1001/archinternmed.2009.22

29 Screening for Celiac Disease Routine serologic screening for celiac sprue should be pursued in patients with diarrhea predominant IBS and mixed IBS (Grade 1B recommendation) ACG Functional Bowel Disorders Task Force 2009

30 What is Non-Celiac Gluten Sensitivity?

31 Definitions Encompasses a collection of medical conditions where gluten has an adverse effect Can be clinically indistinguishable from celiac sprue but testing often negative or inconclusive Improves with a gluten free diet Murray et al. Am J Gastroenterol 2009

32 Gluten Sensitivity Celiac Disease IBS Verdu EF, et al. Am J Gastroenterol 2009: 104: 1587-94.

33 Non-Celiac Gluten Sensitivity Cases of gluten reactions in which neither allergic nor autoimmune mechanisms can be identified. Cases of gluten reactions in which neither allergic nor autoimmune mechanisms can be identified. Diagnosis by exclusion Diagnosis by exclusion Prevalence of extraintestinal symptoms such as behavioral changes, bone or joint pain, muscle cramps, leg numbness, weight loss and chronic fatigue Prevalence of extraintestinal symptoms such as behavioral changes, bone or joint pain, muscle cramps, leg numbness, weight loss and chronic fatigue

34 Non-Celiac Gluten Sensitivity Still not a well-defined clinical entity There are data to suggest improvement in symptoms on a GFD in non-celiac patients Di Sabatino, J Clin Gastoenterol 2013

35 Non-Celiac Gluten Sensitivity Abdominal pain 68% Abdominal pain 68% Eczema/rash 40% Eczema/rash 40% Headache 35% Headache 35% Foggy mind 34% Foggy mind 34% Fatigue 33% Fatigue 33% Diarrhea 33% Diarrhea 33% Depression 22% Depression 22% Joint pain 11% Joint pain 11%

36 Non-Celiac Gluten Sensitivity Only recently has this been formerly studied Strongest evidence of this entity- DBRC trial of FODMAP-depleted gluten in 34 patients who had celiac dz excluded.. Gibson et al. Am J Gastroenterol 2012: 657-665

37 Effect of Gluten on Symptoms in IBS Patients Biesiekierski et al Am J Gastroenterol 2011;10:1038

38 Effect of Gluten on Pain/Bloating in IBS patients Biesiekierski et al Am J Gastroenterol 2011;10:1038

39 Effect of Gluten on Fatigue on IBS patients Biesiekierski et al Am J Gastroenterol 2011;10:1038

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41 Proposed Management for Patients with IBS-like symptoms and minimal histology SymptomLDHLASerologyTreatment IBS+++GFD IBS+Consider other cause IBS-++Consider GFD IBS---Tx IBS Eswaran et al Gastro Clin N Am 2011 Verdu Am J Gastro 2009

42 FODMAP diet in the management of Functional GI symptoms Fermentable Oligo-di and Mono Saccharides and Polyols Induce luminal distension, food chemicals that stimulate the Enteric Nervous System and gluten may trigger symptoms in non- celiacs via an unknown mechanism Fermentable readily by bacteria, slowly or poorly absorbed by small intestine

43 FODMAPS Fruits with fructose > glucose Fructan containing vegetables Wheat based products Sorbitol and lactose containing foods Raffinose containing foods Increasingly being recommended to manage patients with functional GI symptoms

44 Remaining questions Is this just potential celiac disease? Do patients without evidence of celiac disease who are interested in GFD need to be on a strictly GFD or just decrease gluten? Are other components of wheat causing symptoms? Nocebo effect?

45 Conclusions Non-celiac gluten sensitivity currently encompasses a broad array of disorders ranging from potential CD to food hypersensitivity to IBS with identified food trigger. Several proposed mechanisms but pathogenesis is not clearly understood. Non-celiac gluten sensitivity needs to be better defined and an optimal diagnostic algorithm is needed. Larger double-blind RCT studies are needed. Gluten free diet may be reasonable to try in motivated patients.

46 Celiac Disease Management Recommendations Consultation with a skilled dietician Education about the disease Lifelong adherence to a GFD Identification and treatment of nutritional deficiencies Access to an advocacy group Continuous long-term follow-up by a multidisciplinary team

47 Thank you!


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