Coeliac Disease Bible Class Questions and Answers
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1 Coeliac Disease Bible Class Questions and Answers Jan Hendrik Niess
2 What is the definition of coeliac disease? Coeliac disease is an immune reaction to gluten (wheat, barely, rye) in an genetic predisposed individual that results into an (small intestinal) enteropathy - asymptomatic (subclinical) coeliac disease - symptomatic coeliac disease - refractory coeliac disease - potential coeliac disease What is the definition of non-coeliac gluten sensitivity (NCGS)? Non-coeliac gluten sensitivity is a disorder, in which gluten intakes results in clinical symptoms (no enteropathy, no elevated transglutaminase antibodies, no change in permeability) According to the Oslo classification gluten-intolerance, glutensensitivity, silent coeliac disease should not be used
3 What is the worldwide prevalence of coeliac disease? No CD in Burkina Faso (low freqenecy of HLA DQ2 /DQ8 ) High incidence of CD in Finland, Mexico, Algeria and North India Why is there a difference in prevalence of CD in Algeria and Tunisia? (neighbouring countries, same gluten Intake, same HLA DQ2 / DQ8 frequency) What is the prevalence of coeliac disease in Switzerland? Prevalence (children) in Switzerland 1:132 Swiss Med. Wkly 2002;132:43-47
4 Does the presence of HLA DQ2 / 8 alone explain the occurence of CD? 20-25% of the population are positive for HLA DQ2/8 Although mucosal immunological sensitization is an invariable feature of celiac disease, it is not the precipitating factor for the expression of the full intestinal lesion; a second factor drives the enteropathy from minimal (latent) to overt... Candidate factors include an episode of hyperpermeability, nutrient deficiency, increased dietary gluten, impaired intraluminal digestion of ingested gluten, adjuvant effects of intestinal infection and a non-hla associated gene. Anne Ferguson Annu Rev Immunol. 2011;29:
5 What are common symptoms of coeliac disease? Symptomatic malabsorption Diarrhea with weight loss Chronic diarrhoea with or without abdominal pain Chronic iron deficiency Metabolic bone disease; premature osteoporosis Unexplained weight loss Abnormal elevated liver enzymes Incidentally discovers villous atrophy Dermatitis herpetiformis Peripheral neuropathy Oral aphthous ulcers Growth failure Discoloured teeth or synchronous enamel loss With what diseases is coeliac disease often associated? Thyroid disease Down`s and Turner`s syndrome Type I diabetes Selective IgA deficiency
6 How do you diagnose coeliac diases? Serology (tissue transglutaminase IgA) At least 6 biopsies ( bulb: 9 and 12 o clock position; 4 biopsies distal duodenum) Patient A. M., 29/07/1940, referred to upper endoscopy, manifest osteoporosis TTGA IgA 111 U/l, 60 IEL /100 enterocytes Marsh-Oberhuber Stadium 3b If there is a disagreement between serology and biopsy then HLA DQ2 and DQ8 genotyping Consider selective IgA deficiency Other reasons for villous atrophy
7 How can the histological changes be classified? Marsh modified (Oberhuber) Increased intraepithelial lymphocytes a Histologic criterion Crypt hyperplasia Villous atrophy Corazza Type 0 No No No None Type 1 Yes No No Grade A Type 2 Yes Yes No Type 3a Yes Yes Yes (partial) Grade B1 Type 3b Yes Yes Yes (subtotal) Type 3c Yes Yes Yes (total) Grade B2 a >40 intraepithelial lymphocytes per 100 enterocytes for Marsh modified (Oberhuber); >25 intraepithelial lymphocytes per 100 enterocytes for Corazza.
8 What can cause villous atrophy? Tropical sprue Small bowel bacterial overgrowth Autoimmune enteropathy Drug-associated enteropathy (e.g. olmesartan) Whipple disease Eosinophilic enteritis Intestinal lymphoma Crohnn`s disease Graft versus host disease Malnutrition Acquired immune deficiency enteropathy
9 Why is HLADQ2 and DQ8 important? Why is the tissue transglutaminase important? A B Antigen Presenting Cell (APC) Gluten HLA DQ 2 or HLA DQ 8 Alpha / beta T Cell Receptor CD4 T Cell Proinflammatory cytokines IFNg, IL-21) Annu Rev Immunol. 2011;29:
10 Explain the patho-physiology of coeliac disease Gluten intake Presentation by HLA DQ2/8 Production of IL-15 Proliferation of the IEL Blood Mar 15;119(11):
11 Can you propose an animal model for coeliac disease? x wt Gluten + Retinol Tolerogenic immune response HLA DQ8 Gluten + Retinol IL-15tg Proinflammatory cytokines Breakdown of oral tolerance Nature Mar 10;471(7337):220-4
12 How do you treat coeliac disease? Gluten-free diet (avoid wheat, rye, spelt, barely)
13 Follow up of patients with coeliac disease Am J Gastroenterol May;108(5):656-76
14 What do you consider if patients do not respond to gluten free diet? Gluten intake Bacterial overgrowth Microscopic colitis Exokrine pancreas insufficiency Fructose / Lactose intolerance Refractory coeliac disease
15 How is refractory coeliac disease defined? Villous atrophy unresponsive to gluten-free diet (GFD) How do you distinguish refractory coeliac disease type I and II? Semin Immunopathol Jul;34(4):
16 What is the importance to distinguish refractory coeliac disease type I from II? Blood Mar 15;119(11):
17 Thank you
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