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E5dc Coeliac Disease, Worcester University
 

E5dc Coeliac Disease, Worcester University

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    E5dc Coeliac Disease, Worcester University E5dc Coeliac Disease, Worcester University Presentation Transcript

    • Coeliac Disease Kamran Rostami Honorary Clinical Lecturer School of Medicine University of Birmingham
    • Objectives
      • What is coeliac disease?
      • What is the prevalence of CD in UK and the rest of the world?
      • Symptoms, Clinical presentation and associated conditions with CD.
      • What is the differences between Microcytic and Macrocytic Anaemia?
      • What do you know about lactose intolerance?
      • Pathogenesis and Complications of untreated CD.
      • How do you diagnose CD and what are the pitfalls?
      • What is the treatment of CD
    • Definition
      • immune-mediated enteropathy
        • caused by a permanent sensitivity to gluten
        • in genetically susceptible individuals.
      • A unique autoimmune disorder:
        • environmental trigger (gluten) and the
        • autoantigen (tissue Transglutaminase)
    • Diagnosis of Coeliac Disease and pitfalls
      • Clinical
      • Serological
      • Histological
      • Rostami K, Danciu M. Endoscopy and small-bowel biopsy in celiac disease: indications and implications. Endoscopy 2007;39:573
      • Green PH, Rostami K, Marsh MN. Diagnosis of coeliac disease. Best Pract Res Clin Gastroenterol. 2005;19:389-400
    • Serology in Coeliac Disease
      • High estimation of sensitivity in the most studies
          • Biopsy only seropositive
          • Rolling out the diagnosis
      • Serologic tests, in clinical practice, lack the sensitivity reported in the literature.
      • Rostami K, Mulder CJ et al. What a clinician should know about coeliac disease autoantibodies. Eur J Gastroenterol Hepatol. 2004;16:715-6.
      • Abrams JA, Green PH. Seronegative celiac disease: increased prevalence with lesser degrees of villous atrophy. Dig Dis Sci. 2004;49:546-50.
    • Elderly and antibodies
      • Negative serology should not necessarily reassure the clinician
      • Elderly patients following a gluten-free diet will see improvements in their symptoms and be committed to the diet despite their age
      • David S Sanders et al Antibody negative coeliac disease presenting in elderly people—an easily missed diagnosis BMJ 2005; 330: 775-776
    • Serology sensitivity Rostami, Mulder et al. American J Gastroenterol 1999;94:888-894
    • Modified Marsh Classification
      • Rostami, Mulder et al. American J Gastroenterol 1999;94:888-894
    • Marsh I or Infiltrative lesion
      • Non specific
      • Known as lymphocytic enteritis
      • Occasionally positive serology
      • Common presentation in latent Coeliac Disease
      • Often missed by pathologist as they do not count
      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.
    • 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.
      • Very common
      • IBS
      • Could present with symptoms
      • Do you treat this?
    • 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.
    • 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
    • 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.
      • Classical Coeliac Disease
      • Serology positive in almost 100% if not IgA-deficient
    • 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
    • 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
    • Seropositive with normal histology
      • Atypical localisation
          • Bulb
          • Terminal ileum
      • False positive
          • Liver dis
          • Autoimmune
      • Brocchi et al. Adult coeliac disease diagnosed by endoscopic biopsies in the duodenal bulb. Eur J Gastroenterol Hepatol. 2005;17:1413-5.
      • Villanacci V et al. Histological aspects of the terminal ileum: a windows on coeliac disease too? Dig Liver Dis. 2006;38:820-2.
      • Microenteropathy
    • Endoscopy
      • Entire small bowels
      • Normal Duodenal biopsy do not exclude diagnosis
      • Segmental biopsy would be required
      Green PH, Rostami K, Marsh MN. Diagnosis of coeliac disease. Best Pract Res Clin Gastroenterol. 2005;19:389-400
    • Pitfalls
      • If the symptoms persist
        • Repeat serology
        • Repeat biopsy
      • Serology does not exclude Diagnosis
    • Which of the following is the most common reason for failing to respond to a gluten free diet?
      • A The diagnosis was wrong
      • B Non-concordance with diet
      • C Lactose intolerance
      • D Pancreatic insufficiency
      • E Small bowel lymphoma
    • Coeliac Keystone
      • The enzymatic degradation of gluten might become an alternative to the gluten-free diet
      • Exogenous prolyl-endopeptidases
      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]
    • Summary and conclusion
      • Coeliac Disease is a common condition
      • Atypical cases are predominant
      • Seronegative are under-diagnosed
        • Look for them and you find them
      • Duodenal biopsy do not exclude the diagnosis
        • Segmental biopsy in difficult cases
      • FU and repeating the tests is a key to diagnosis
      • GFD improve life qualities at any age
      • Thank you!
      • Any question?