Coeliac Disease

Question 1

What specific molecule is responsible for coeliac disease?

Answer 1

Alpha-gliadin

Question 2

What happens to the immune system during coeliac disease?

Answer 2

There is an inappropriate T-cell mediated response

Question 3

What is the epidemiology for coeliac disease?

Answer 3

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

Question 4

What are 95% of coeliac disease cases due to?

Answer 4

A HLA-DQ2 mutation

Question 5

What is the relevance of the infection hypothesis to this disease?

Answer 5

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.

Question 6

How is alpha-gliadin absorbed?

Answer 6

It’s absorbed intact into the lamina propria.

Question 7

What happens to the alpha-gliadin in coeliac disease?

Answer 7

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.

Question 8

How does coeliac disease present in infants?

Answer 8

Presents aged 2-4 months (after cereal introduction). Causes DIVA; diarrhoea, impaired growth, vomiting and abdominal distension

Question 9

How does coeliac disease present in older children?

Answer 9

Anaemia, short stature, puberty delay, recurrent abdominal pain or behavioural disturbance

Question 10

Coeliac disease presents in seven ways in adults.

Answer 10

Symptomatic 
Chronic/recurrent IDA
Nutritional deficiency 
Reduced fertility 
Osteoporosis
Unexplained increase in AST/ALT
Neurological symptoms (epilepsy)

Question 11

What are the symptoms of coeliac disease in adults?

Answer 11

Diarrhoea 
Bloating
Abdominal discomfort
Flatulence 
- only 50% have diarrhoea, some have constipation

Question 12

How common is IDA in coeliac disease in adults?

Answer 12

50% of coeliac’s have it

1-2% of all IDA cases also have coeliac

Question 13

Name four intestinal consequences of coeliac disease.

Answer 13

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

Question 14

What vitamins and food stuffs are malabsobed in coeliac disease?

Answer 14

Fats
Proteins
Carbohydrates
Folate
Vitamin D/calcium
Vitamin K
Magnesium
Vitamin B12

Question 15

How do we lose iron from the body?

Answer 15

Shedding of skin and mucosal cells including the lining of the GI tract
- 1mg is lost a day

Question 16

What serology results indicate coeliac disease?

Answer 16

IgA tTG - more sensitive

IgA EMA - more specific

Question 17

What can be seen in an endoscopy of a coeliac?

Answer 17

Scalloping of the folds
Paucity of folds
Mosaic pattern
Distinct sub-mucosal blood vessels
Modular patterns on the mucosa

Question 18

What must be done to validate a diagnosis based off a small bowel biopsy?

Answer 18

Minimum of four biopsies (at least eight one from the duodenal bulb)
Person must be on a gluten rich diet

Question 19

Differential diagnosis if there is negative coeliac serology.

Answer 19

Double check IgA
Rarer causes
- Crohn's disease
- lymphoma
- whipples disease
- HN entropy 
- NSAIDs
- chronic ischemia
- giardiasis (most common parasitic infection)

Question 20

Name three diseases associated with coeliac.

Answer 20

Dermatitis herpetiforms 
- an itchy rash
- 90% villus atrophy
T1 diabetes
- 3-8%, so all patients are screened
Thyrotoxicosis
Addison's disease

Question 21

Treatment of coeliac disease?

Answer 21

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

Question 22

What are the complications of coeliac disease?

Answer 22

• functional hyposplenism
• encapsulates organisms, vaccines, meningococcus and pneumococcal
  Osteoporosis (25%)
• low BMI and vitamin D/calcium deficiency
• DEXA
• vitamin D and calcium supplements

Question 23

What is refractory coeliac disease?

Answer 23

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

Question 24

What is the difference between refractory coeliac diseases one and two?

Answer 24

They both have persistent villous atrophy, but RCD II has an abnormal immunophentype

Question 25

What’s the treatment for refractory coeliac disease one?

Answer 25

Over 75% of patients respond to steroids.

95% 5 year survival

Question 26

What’s the prognosis for refractory coeliac disease two?

Answer 26

Can cause ulcerative jejunitis
58% 5 year survival rate
60-80% progression to EATL by 5 years

Question 27

What is entropy associated T-cell lymphoma (EATL)?

Answer 27

Often advanced and incurable
Symptoms 
- weight loss
- night sweats
- itch
- GI bleed
- venous thrombosis-embolism

Question 28

How do you treat EATL?

Answer 28

Chemotherapy and autologous stem cell treatment

- poor response; 8-20% 5 year survival

Question 29

Name two more small bowel malignancies associated with coeliac disease.

Answer 29

Small bowel adenocarcinoma
- rare
- symptoms develop over 14 months 
- 58% survival rate at 30 months
Oesophageal and colonic adenocarcinoma

Question 30

What is coeliac disease?

Answer 30

A gluten-sensitive entropy with small intestinal villus atrophy that resolves when gluten is withdrawn from the diet