e5dc coeliac disease, worcester university
TRANSCRIPT
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?