E5dc Coeliac Disease, Worcester University

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E5dc Coeliac Disease, Worcester University

  1. 1. Coeliac Disease Kamran Rostami Honorary Clinical Lecturer School of Medicine University of Birmingham
  2. 2. Objectives <ul><li>What is coeliac disease? </li></ul><ul><li>What is the prevalence of CD in UK and the rest of the world? </li></ul><ul><li>Symptoms, Clinical presentation and associated conditions with CD. </li></ul><ul><li>What is the differences between Microcytic and Macrocytic Anaemia? </li></ul><ul><li>What do you know about lactose intolerance? </li></ul><ul><li>Pathogenesis and Complications of untreated CD. </li></ul><ul><li>How do you diagnose CD and what are the pitfalls? </li></ul><ul><li>What is the treatment of CD </li></ul>
  3. 3. Definition <ul><li>immune-mediated enteropathy </li></ul><ul><ul><li>caused by a permanent sensitivity to gluten </li></ul></ul><ul><ul><li>in genetically susceptible individuals. </li></ul></ul><ul><li>A unique autoimmune disorder: </li></ul><ul><ul><li>environmental trigger (gluten) and the </li></ul></ul><ul><ul><li>autoantigen (tissue Transglutaminase) </li></ul></ul>
  4. 4. Diagnosis of Coeliac Disease and pitfalls <ul><li>Clinical </li></ul><ul><li>Serological </li></ul><ul><li>Histological </li></ul><ul><li>Rostami K, Danciu M. Endoscopy and small-bowel biopsy in celiac disease: indications and implications. Endoscopy 2007;39:573 </li></ul><ul><li>Green PH, Rostami K, Marsh MN. Diagnosis of coeliac disease. Best Pract Res Clin Gastroenterol. 2005;19:389-400 </li></ul>
  5. 5. Serology in Coeliac Disease <ul><li>High estimation of sensitivity in the most studies </li></ul><ul><ul><ul><li>Biopsy only seropositive </li></ul></ul></ul><ul><ul><ul><li>Rolling out the diagnosis </li></ul></ul></ul><ul><li>Serologic tests, in clinical practice, lack the sensitivity reported in the literature. </li></ul><ul><li>Rostami K, Mulder CJ et al. What a clinician should know about coeliac disease autoantibodies. Eur J Gastroenterol Hepatol. 2004;16:715-6. </li></ul><ul><li>Abrams JA, Green PH. Seronegative celiac disease: increased prevalence with lesser degrees of villous atrophy. Dig Dis Sci. 2004;49:546-50. </li></ul>
  6. 6. Elderly and antibodies <ul><li>Negative serology should not necessarily reassure the clinician </li></ul><ul><li>Elderly patients following a gluten-free diet will see improvements in their symptoms and be committed to the diet despite their age </li></ul><ul><li>David S Sanders et al Antibody negative coeliac disease presenting in elderly people—an easily missed diagnosis BMJ 2005; 330: 775-776 </li></ul>
  7. 7. Serology sensitivity Rostami, Mulder et al. American J Gastroenterol 1999;94:888-894
  8. 8. Modified Marsh Classification <ul><li>Rostami, Mulder et al. American J Gastroenterol 1999;94:888-894 </li></ul>
  9. 9. Marsh I or Infiltrative lesion <ul><li>Non specific </li></ul><ul><li>Known as lymphocytic enteritis </li></ul><ul><li>Occasionally positive serology </li></ul><ul><li>Common presentation in latent Coeliac Disease </li></ul><ul><li>Often missed by pathologist as they do not count </li></ul>Rostami K, Mulder C et al. Modified Marsh Classification THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 94, No. 4, 1999 © 1999 by Am. Coll. of Gastroenterology ISSN 0002-9270/99/$20.00 Published by Elsevier Science Inc.
  10. 10. Marsh II Hyperplastic lesion Rostami K, Mulder C et al. Modified Marsh Classification THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 94, No. 4, 1999 © 1999 by Am. Coll. of Gastroenterology ISSN 0002-9270/99/$20.00 Published by Elsevier Science Inc. <ul><li>Very common </li></ul><ul><li>IBS </li></ul><ul><li>Could present with symptoms </li></ul><ul><li>Do you treat this? </li></ul>
  11. 11. Marsh IIIa or Partial Villous Atrophy (Destructive) Should the relatives of coeliacs -with clinical compliants undergo a small bowel biopsy, in spite of their negative serology ? A complex and prevalent variety of coeliac subgroups Easily missed Negative in serology 60-70% Common presentation in First degree relatives other at high risk 20% of first degree relatives had coeliac disease Rostami K,Mulder C. et al Eur.J.Gastroenterol.Hepatol 2000; 12:51-56 Rostami K, Mulder C et al. Modified Marsh Classification THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 94, No. 4, 1999 © 1999 by Am. Coll. of Gastroenterology ISSN 0002-9270/99/$20.00 Published by Elsevier Science Inc.
  12. 12. Marsh IIIb or Subtotal Villous Atrophy Rostami K, Mulder C et al. Modified Marsh Classification THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 94, No. 4, 1999 © 1999 by Am. Coll. of Gastroenterology ISSN 0002-9270/99/$20.00 Published by Elsevier Science Inc. Less common and easier to recognise About 70% present with positive serology Very closed to the classical presentation
  13. 13. Marsh IIIc or Total Villous Atrophy Rostami K, Mulder C et al. Modified Marsh Classification THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 94, No. 4, 1999 © 1999 by Am. Coll. of Gastroenterology ISSN 0002-9270/99/$20.00 Published by Elsevier Science Inc. <ul><li>Classical Coeliac Disease </li></ul><ul><li>Serology positive in almost 100% if not IgA-deficient </li></ul>
  14. 14. Correlation between sero-sensitivity, endoscopy and Histology Dickey W. Endoscopic markers for celiac disease. Nat Clin Pract Gastroenterol Hepatol. 2006;3:546-51. 31% sensitivity for serology 100% sensitivity for serology
  15. 15. Coeliac disease IgG/IgA  -gliadin IgA  -tTG/EMA Mucosal biopsy 3-4 samples Gluten Free Diet Childeren < 2 yrs (-> IgG/IgA  -gliadin Symptoms but no antibodies =>DQ2/8 and biopsy IgA deficiency (prevalence 2% in CD vs 0.2% in normal population) Gluten Free Diet Repeat biopsy Schuppan et al Dig Liv Dis October 2004;10:358-360
  16. 16. Seropositive with normal histology <ul><li>Atypical localisation </li></ul><ul><ul><ul><li>Bulb </li></ul></ul></ul><ul><ul><ul><li>Terminal ileum </li></ul></ul></ul><ul><li>False positive </li></ul><ul><ul><ul><li>Liver dis </li></ul></ul></ul><ul><ul><ul><li>Autoimmune </li></ul></ul></ul><ul><li>Brocchi et al. Adult coeliac disease diagnosed by endoscopic biopsies in the duodenal bulb. Eur J Gastroenterol Hepatol. 2005;17:1413-5. </li></ul><ul><li>Villanacci V et al. Histological aspects of the terminal ileum: a windows on coeliac disease too? Dig Liver Dis. 2006;38:820-2. </li></ul><ul><li>Microenteropathy </li></ul>
  17. 17. Endoscopy <ul><li>Entire small bowels </li></ul><ul><li>Normal Duodenal biopsy do not exclude diagnosis </li></ul><ul><li>Segmental biopsy would be required </li></ul>Green PH, Rostami K, Marsh MN. Diagnosis of coeliac disease. Best Pract Res Clin Gastroenterol. 2005;19:389-400
  18. 18. Pitfalls <ul><li>If the symptoms persist </li></ul><ul><ul><li>Repeat serology </li></ul></ul><ul><ul><li>Repeat biopsy </li></ul></ul><ul><li>Serology does not exclude Diagnosis </li></ul>
  19. 19. Which of the following is the most common reason for failing to respond to a gluten free diet? <ul><li>A The diagnosis was wrong </li></ul><ul><li>B Non-concordance with diet </li></ul><ul><li>C Lactose intolerance </li></ul><ul><li>D Pancreatic insufficiency </li></ul><ul><li>E Small bowel lymphoma </li></ul>
  20. 20. Coeliac Keystone <ul><li>The enzymatic degradation of gluten might become an alternative to the gluten-free diet </li></ul><ul><li>Exogenous prolyl-endopeptidases </li></ul>Vora H et al. A scaleable manufacturing process for pro-EP-B2, a cysteine protease from barley indicated for celiac sprue. Biotechnol Bioeng. 2007 Mar 26; [Epub ahead of print]
  21. 21. Summary and conclusion <ul><li>Coeliac Disease is a common condition </li></ul><ul><li>Atypical cases are predominant </li></ul><ul><li>Seronegative are under-diagnosed </li></ul><ul><ul><li>Look for them and you find them </li></ul></ul><ul><li>Duodenal biopsy do not exclude the diagnosis </li></ul><ul><ul><li>Segmental biopsy in difficult cases </li></ul></ul><ul><li>FU and repeating the tests is a key to diagnosis </li></ul><ul><li>GFD improve life qualities at any age </li></ul>
  22. 22. <ul><li>Thank you! </li></ul><ul><li>Any question? </li></ul>

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