Coeliac disease and inflammatory bowel disease Flashcards
What is coeliac disease?
Gluten sensitive enteropathy or coeliac sprue
An auto-immune mediated disease of the small intestine triggered by the ingestion of gluten in genetically predisposed individuals leading to malabsorption with cessation of symptoms on gluten free diet
What is gluten?
Gluten is a protein compound of wheat, rye and barley which is left behind after washing off the starch
Gluten consists of gliadin and glutenins
What genes are associated with coeliac disease?
Associated with HLA-DQ2 and HLA-DQ8 in 95% and 5% of the patients respectively
Which chromosome are the genes associated with coeliac disease located on?
Chr 6p21
What percentage approximately are genetically predisposed to coeliac disease
around 10% if first degree relatives
Where is coeliac disease most prevalent?
Most prevalent in western europe and US in patients of irish and scandinavian descent
Increasing incidence in Africa and Asia
What conditions do patients have that coincide with a high incidence of coeliac disease?
Down’s syndrome, Type 1 diabetes mellitus, auto-immune hepatitis and thyroid gland abdnormalities
How can coeliac disease be diagnosed?
Can present with abnormal liver function tests due to auto-immune hepatitis
How does gluten cause coeliac disease?
Gluten in wheat + small bowel mucosa –> tissue transglutaminase –> diamidates glutamine in gliadin –> negatively charged protein –> IL-15 –> Natural killer cells + intraepithelial T lymphocytes –> tissue destruction + villous atrophy
How does the microscopic appearance of the small bowel lining change as a result of coeliac disease?
Normal small bowel lining shows finger-like appearance.
Coeliac disease causes inflammation + flat lining
How does coeliac disease present?
Malabsorption of nutrients
Short stature and failure to thrive in children
Diarrhoea - smelly and bulky stool, rich in fat(steatorrhoea)
Weight loss and fatigue
Anaemia - folate and Fe deficiency
Osteopenia and osteoporosis - calcium and vitamin D deficiency
Classes of coeliac disease
Classical - malabsorption symptoms
Non-classical including symptoms outside the GI tract:
- constipation, bloating alternate bowel habits
- Heartburn, nausea, vomiting and dyspepsia(indigestion)
- Recurrent miscarriage/infertility
Sub-clinical - detected with blood tests
What are general investigations for coeliac disease?
FBC, U and Es(urea and electrolytes, LFTs(liver function tests)
What compounds are measured for in serology for diagnosis of coeliac disease?
- Tissue transglutaminase IgA(TTGA); 98% sensitive, 96% specific
- Endomysial IgA - connective tissue covering the smooth muscle fibres; 100% specificity, 90% sensitivity
- Deamidated gliadin peptide IgA and IgG
- For monitoring compliance to gluten free diet
- Sero-negative coeliac disease reported in 6.4-9% of patients
How do routine coeliac disease tests work?
They are tissue damage tests
There is overreaction of the immune system to produce antibodies to the proteins involved in tissue damage i.e antbodies to:
- tissue transglutaminase
- Endomysium
- Deamidated gliadin peptide
What are the microscopic features of coeliac disease?
At least four biopsies to be sampled from the duodenum at upper GIT endoscopy as changes can be patchy
On microscopy, there is:
- villous atrophy (VA)
- Crypt hyperplasia
- Increase in lymphocytes in the lamina propria/chronic inflammation
- Increase in intrapeithelial lymphocytes (IEL)
Recovery of villous abnormality on gluten-free diet
What are the complications of coeliac disease?
- Enteropathy associated T-cell lymphoma
- High risk of adenocarcinoma of small bowel and other organs - large bowel, oesophagus, pancreas
- May be associated with dermatitis hepetiformis (very itchy skin condition)
- Infertility and miscarriage
- Refractory coeliac disease despite strict adherence to gluten free diet