Coeliac Disease Flashcards
What is Coeliac Disease?
Coeliac disease = gluten sensitivity enteropathy:
- A T-cell mediated autoimmune condition, in which there is inflammation of the mucosa of the upper small bowel that improves when gluten is withdrawn from the diet, and relapses when gluten is reintroduced
What is the triggering element of Coeliac disease?
Prolamin as a component of gluten protein
- Alcohol-soluble protein in wheat, barley, rye + oats
- Prolamins: gliadin in wheat, hordeins in barley and secalins in rye
What is the prevalence of coeliac disease?
1%.
Describe the pathophysiology of coeliac disease.
Type 4 hypersensitivity reaction mediated by T cells
- Gluten breaks down to gliadin
- Gliadin (product of gluten digestion) = immunogenic
- Gliadin → triggers the immune system to produce autoantibodies like:
- Anti-tissue transglutaminase (anti-tTG)
- Anti-endomysial (anti-EMA)
- The gliadin peptides then bind to APCs, which interact with CD4+ T cells in the lamina propria via HLA class II molecules, DQ2 or DQ8
- These 2 HLA class II molecules DQ2 (95%) or DQ8 (5%) ACTIVATE the gluten-sensitive T cells.
- T cells produce pro-inflammatory cytokines and initiate an inflammatory cascade.
- The cascade releases metaloproteinkinases and other mediators, which target the epithelial cells of the small intestine causing:
- Villous atrophy
- Crypt hyperplasia
- Intraepithelial lymphocytes - Result in malabsorption.
Give 2 risk factors of Coeliac disease.
- Other autoimmune diseases since having one will increase risk of others:
* Type 1 diabetes
* Thyroid disease
* Sjorgrens - IgA deficiency
- Breast feeding
- Age of introduction to gluten into diet
- Rotavirus infection in infancy increases risk
Give 5 symptoms of coeliac disease.
- Dermatitis herpetiformis (elbows, knees, buttocks)
- Angular stomatitis
- Mouth ulcers
- Steatorrhoea (pale floating stools)
- Diarrhoea
- Weight loss
- Bloating
- Failure to thrive (children)
- Anaemia secondary to iron, folate, B12 deficiency
What are the genetic associations for Coeliac disease?
- HLA-DQ2 gene (90%)
- HLA-DQ8 gene
What are the main auto-antibodies related to Coeliac disease?
Auto-antibodies:
- Tissue transglutaminase antibodies (anti-TTG)
- Endomysial antibodies (EMAs)
- Deaminated gliadin peptides antibodies (anti-DGPs)
Name the break down product of gluten that can trigger coeliac disease.
Gliadin.
What part of the small intestine is mainly affected by coeliac disease?
Duodenum.
What disorders might be associated with coeliac disease?
Other autoimmune disorders:
- T1 diabetes.
- Thyroxoicosis.
- Hypothyroidism.
- Addisons disease.
Osteoporosis is also commonly seen in people with coeliac disease.
What 3 histological features are needed in order to make a diagnosis of coeliac disease?
- Raised intraepithelial lymphocytes.
- Crypt hyperplasia.
- Villous atrophy.
In someone with coeliac disease, what are they most likely to be deficient in - iron, folate, or B12?
Iron.
Coeliac disease mainly affects the duodenum and iron is absorbed in the duodenum. Folate is absorbed in the jejunum and B12 in the terminal ileum.
What investigations might you do in someone who you suspect to have coeliac disease?
- Serology - look for auto-antibodies - TTG and EMA.
- Gastroscopy - duodenal biopsies.
1st line: Raised anti-tTG
AND for total IgA
2nd line: Raised anti-EMA
Gold standard: Endoscopy and duodenal biopsy (villous atrophy, crypt hyperplasia, intraepithelial lymphocytes)
What does the patient have to do before carrying out the investigations for Coeliac Disease?
Investigations must be carried out whilst the patient remains on a diet containing gluten otherwise it may not be possible to detect antibodies or inflammation in the bowel.
