Coeliac Disease Coeliac Disease

Kamran RostamiKamran RostamiHonorary Clinical LecturerHonorary Clinical Lecturer

School of MedicineSchool of MedicineUniversity of BirminghamUniversity of Birmingham

ObjectivesObjectives

What is coeliac disease?What is coeliac disease?What is the prevalence of CD in UK and the rest of the What is the prevalence of CD in UK and the rest of the world?world?Symptoms, Clinical presentation and associated Symptoms, Clinical presentation and associated conditions with CD.conditions with CD.What is the differences between Microcytic and What is the differences between Microcytic and Macrocytic Anaemia?Macrocytic Anaemia?What do you know about lactose intolerance?What do you know about lactose intolerance?Pathogenesis and Complications of untreated CD.Pathogenesis and Complications of untreated CD.How do you diagnose CD and what are the pitfalls?How do you diagnose CD and what are the pitfalls?What is the treatment of CDWhat 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 Diagnosis of Coeliac Disease and pitfallsand pitfalls

ClinicalClinicalSerologicalSerologicalHistologicalHistological

Rostami K, Danciu M. Endoscopy and small-bowel biopsy in celiac disease: indications Rostami K, Danciu M. Endoscopy and small-bowel biopsy in celiac disease: indications and implications. Endoscopy 2007;39:573and 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 DiseaseSerology in Coeliac Disease

High estimation of sensitivity in the most studiesHigh estimation of sensitivity in the most studiesBiopsy only seropositiveBiopsy only seropositiveRolling out the diagnosisRolling out the diagnosis

Serologic tests, in clinical practice, lack the Serologic tests, in clinical practice, lack the sensitivity reported in the literature.sensitivity reported in the literature.

Rostami K, Mulder CJ et al. What a clinician should know about coeliac Rostami K, Mulder CJ et al. What a clinician should know about coeliac disease autoantibodies. Eur J Gastroenterol Hepatol. 2004;16:715-6.disease autoantibodies. Eur J Gastroenterol Hepatol. 2004;16:715-6.

Abrams JA, Green PH. Seronegative celiac disease: increased Abrams JA, Green PH. Seronegative celiac disease: increased prevalence with lesser degrees of villous atrophy. Dig Dis Sci. prevalence with lesser degrees of villous atrophy. Dig Dis Sci. 2004;49:546-50.2004;49:546-50.

Elderly and antibodiesElderly and antibodies

Negative serology should not necessarily Negative serology should not necessarily reassure the clinicianreassure the clinician Elderly patients following a gluten-free diet will Elderly patients following a gluten-free diet will see improvements in their symptoms and be see improvements in their symptoms and be committed to the diet despite their agecommitted to the diet despite their age

David S SandersDavid S Sanders et al et al Antibody negative coeliac disease presenting in Antibody negative coeliac disease presenting in elderly people—an easily missed diagnosiselderly people—an easily missed diagnosisBMJ 2005; 330: 775-776BMJ 2005; 330: 775-776

Serology sensitivitySerology sensitivity

0

10

20

30

40

50

60

70

80

90

100

Marsh I-II Marsh IIIa Marsh IIIb Marsh IIIc

EMA

Rostami, Mulder et al. American J Gastroenterol 1999;94:888-894

Modified Marsh ClassificationModified Marsh Classification

Rostami, Mulder et al. American J Gastroenterol 1999;94:888-894

Marsh I or Infiltrative lesionMarsh 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 lesionMarsh 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 commonIBS•Could present with symptoms

Do you treat this?

Marsh IIIa Marsh IIIa or Partial Villous Atrophy (Destructive)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 subgroupsEasily 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 Marsh IIIb or Subtotal Villous AtrophySubtotal Villous Atrophy

Rostami K, Mulder C et al. Modified Marsh ClassificationTHE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 94, No. 4, 1999© 1999 by Am. Coll. of Gastroenterology ISSN 0002-9270/99/$20.00Published 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 Marsh IIIc or Total Villous AtrophyTotal Villous Atrophy

Rostami K, Mulder C et al. Modified Marsh ClassificationTHE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 94, No. 4, 1999© 1999 by Am. Coll. of Gastroenterology ISSN 0002-9270/99/$20.00Published by Elsevier Science Inc.

•Classical Coeliac Disease•Serology positive in almost 100% if not IgA-deficient

Correlation between sero-sensitivity, Correlation between sero-sensitivity, endoscopy and Histologyendoscopy 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 biopsy3-4 samples

Gluten Free Diet

Childeren < 2 yrs (-> IgG/IgA -gliadinSymptoms but no antibodies =>DQ2/8 and biopsyIgA deficiency (prevalence 2% in CD vs 0.2% in normal population)

Gluten Free DietRepeat biopsy

Schuppan et al Dig Liv Dis October 2004;10:358-360

Seropositive with normal histologySeropositive with normal histology

Atypical localisationAtypical localisationBulbBulbTerminal ileumTerminal ileum

False positiveFalse positiveLiver disLiver disAutoimmuneAutoimmune

Brocchi et al. Adult coeliac disease diagnosed by endoscopic biopsies in the Brocchi et al. Adult coeliac disease diagnosed by endoscopic biopsies in the duodenal bulb. Eur J Gastroenterol Hepatol. 2005;17:1413-5.duodenal bulb. Eur J Gastroenterol Hepatol. 2005;17:1413-5.

Villanacci V et al. Histological aspects of the terminal ileum: a windows on Villanacci V et al. Histological aspects of the terminal ileum: a windows on

coeliac disease too? Dig Liver Dis. 2006;38:820-2.coeliac disease too? Dig Liver Dis. 2006;38:820-2.

MicroenteropathyMicroenteropathy

EndoscopyEndoscopy

•Entire small Entire small bowelsbowels

•Normal Normal Duodenal biopsy Duodenal biopsy do not exclude do not exclude diagnosisdiagnosis

•Segmental Segmental biopsy would be biopsy would be requiredrequired

Green PH, Rostami K, Marsh MN. Diagnosis of coeliac disease. Best Pract Res Clin Gastroenterol. 2005;19:389-400

Pitfalls

If the symptoms persistIf the symptoms persist

– Repeat serologyRepeat serology

– Repeat biopsyRepeat biopsy

Serology does not exclude DiagnosisSerology does not exclude Diagnosis

Which of the following is the most common reason Which of the following is the most common reason for failing to respond to a gluten free diet?for failing to respond to a gluten free diet?

A The diagnosis was wrong A The diagnosis was wrong

B Non-concordance with diet B Non-concordance with diet

C Lactose intolerance C Lactose intolerance

D Pancreatic insufficiency D Pancreatic insufficiency

E Small bowel lymphomaE Small bowel lymphoma

Coeliac Keystone

The enzymatic The enzymatic degradation of gluten degradation of gluten might become an might become an alternative to the alternative to the gluten-free dietgluten-free diet

Exogenous prolyl-Exogenous prolyl-endopeptidasesendopeptidases

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 conclusionSummary and conclusion

Coeliac Disease is a common condition Coeliac Disease is a common condition

Atypical cases are predominant Atypical cases are predominant

Seronegative are under-diagnosed Seronegative are under-diagnosed – Look for them and you find themLook for them and you find them

Duodenal biopsy do not exclude the diagnosisDuodenal biopsy do not exclude the diagnosis– Segmental biopsy in difficult casesSegmental biopsy in difficult cases

FU and repeating the tests is a key to diagnosisFU and repeating the tests is a key to diagnosis

GFD improve life qualities at any ageGFD improve life qualities at any age

Thank you!Thank you!

Any Any question?question?