Coeliac Disease Flashcards
What specific molecule is responsible for coeliac disease?
Alpha-gliadin
What happens to the immune system during coeliac disease?
There is an inappropriate T-cell mediated response
What is the epidemiology for coeliac disease?
It’s more common in females, can occur at any age, 1% prevalence in the UK (rare in Africa and Asia) and 10% prevalence in 1st degree relatives
What are 95% of coeliac disease cases due to?
A HLA-DQ2 mutation
What is the relevance of the infection hypothesis to this disease?
Infection with adenovirus 12 in genetically susceptible people can trigger the disease. The peptide on alpha-gliadin is similar to that in the E1b portion of the virus. This leads to cross reaction and triggers the disease.
How is alpha-gliadin absorbed?
It’s absorbed intact into the lamina propria.
What happens to the alpha-gliadin in coeliac disease?
It’s exposed to TTG from damaged epithelium, leading to deamination of glutamine residues. This enables bonding to HLA-DQ2 and activates the pro-inflammatory T-cell response.
How does coeliac disease present in infants?
Presents aged 2-4 months (after cereal introduction). Causes DIVA; diarrhoea, impaired growth, vomiting and abdominal distension
How does coeliac disease present in older children?
Anaemia, short stature, puberty delay, recurrent abdominal pain or behavioural disturbance
Coeliac disease presents in seven ways in adults.
Symptomatic Chronic/recurrent IDA Nutritional deficiency Reduced fertility Osteoporosis Unexplained increase in AST/ALT Neurological symptoms (epilepsy)
What are the symptoms of coeliac disease in adults?
Diarrhoea Bloating Abdominal discomfort Flatulence - only 50% have diarrhoea, some have constipation
How common is IDA in coeliac disease in adults?
50% of coeliac’s have it
1-2% of all IDA cases also have coeliac
Name four intestinal consequences of coeliac disease.
Mucosal inflammation - mild and proximal - causes patchy mucosal damage Loss of villus height - either completely flat or short and broad (sub-total villus atrophy) Increased plasma cells and intraepithelial lymphocytes Reduced surface area - less absorptive capacity
What vitamins and food stuffs are malabsobed in coeliac disease?
Fats Proteins Carbohydrates Folate Vitamin D/calcium Vitamin K Magnesium Vitamin B12
How do we lose iron from the body?
Shedding of skin and mucosal cells including the lining of the GI tract
- 1mg is lost a day
What serology results indicate coeliac disease?
IgA tTG - more sensitive
IgA EMA - more specific
What can be seen in an endoscopy of a coeliac?
Scalloping of the folds Paucity of folds Mosaic pattern Distinct sub-mucosal blood vessels Modular patterns on the mucosa
What must be done to validate a diagnosis based off a small bowel biopsy?
Minimum of four biopsies (at least eight one from the duodenal bulb)
Person must be on a gluten rich diet
Differential diagnosis if there is negative coeliac serology.
Double check IgA Rarer causes - Crohn's disease - lymphoma - whipples disease - HN entropy - NSAIDs - chronic ischemia - giardiasis (most common parasitic infection)
Name three diseases associated with coeliac.
Dermatitis herpetiforms - an itchy rash - 90% villus atrophy T1 diabetes - 3-8%, so all patients are screened Thyrotoxicosis Addison's disease
Treatment of coeliac disease?
Gluten free diet
- can eat rice, oats and maize
- 70% of cases see a symptomatic improvement
- most of the rest improve after they also stop eating dairy
Histology taken after 3-12 months to check healing
What are the complications of coeliac disease?
- functional hyposplenism
- encapsulates organisms, vaccines, meningococcus and pneumococcal
Osteoporosis (25%) - low BMI and vitamin D/calcium deficiency
- DEXA
- vitamin D and calcium supplements
What is refractory coeliac disease?
Recurrent malabsorptive symptoms and villus atrophy despite gluten free diet (6-12 months) and in the absence of other non-responsive coeliac disease or overt malignancy
What is the difference between refractory coeliac diseases one and two?
They both have persistent villous atrophy, but RCD II has an abnormal immunophentype
What’s the treatment for refractory coeliac disease one?
Over 75% of patients respond to steroids.
95% 5 year survival
What’s the prognosis for refractory coeliac disease two?
Can cause ulcerative jejunitis
58% 5 year survival rate
60-80% progression to EATL by 5 years
What is entropy associated T-cell lymphoma (EATL)?
Often advanced and incurable Symptoms - weight loss - night sweats - itch - GI bleed - venous thrombosis-embolism
How do you treat EATL?
Chemotherapy and autologous stem cell treatment
- poor response; 8-20% 5 year survival
Name two more small bowel malignancies associated with coeliac disease.
Small bowel adenocarcinoma - rare - symptoms develop over 14 months - 58% survival rate at 30 months Oesophageal and colonic adenocarcinoma
What is coeliac disease?
A gluten-sensitive entropy with small intestinal villus atrophy that resolves when gluten is withdrawn from the diet
