Coeliac Disease

Question 1

What is the most toxic part of gluten?

Answer 1

a-gliadin.

Question 2

Are females or males more likely to suffer from coeliac disease?

Answer 2

Females.

Question 3

What gene is the most commonly affected in coeliac disease?

Answer 3

HLA-DQ2.

Question 4

What other gene can give rise to coeliac?

Answer 4

HLA-DQ8.

Question 5

What is the infection hypothesis?

Answer 5

Infection with adenovirus 12 in genetically susceptible individuals may cause coeliac as the peptide on a-gliadin is similar to that within the E1b portion of the virus. This leads to cross-reactivity with a-gliadin and development of coeliac disease.

Question 6

How can a-gliadin cause coeliac disease in genetically susceptible individuals?

Answer 6

Exposure to TTG (IgG and IgA) from damaged epithelium causes deamination of glutamine residues.
This enables bonding to HLADQ2 and activation of pro-inflammatory T cell response.

Question 7

How does coeliac disease present in infants?

Answer 7

Usually presents aged 4-24 months, after cereals have been introduced.
Impaired growth, diarrhoea, vomiting and abdominal distension.

Question 8

How does coeliac disease present in older children?

Answer 8

Anaemia, short stature, pubertal delay, recurrent abdominal pain or behavioural disturbance.

Question 9

How does coeliac disease present in adults?

Answer 9

Symptomatic
Chronic/recurrent IDA
Nutritional deficiency
Reduced fertility/amenorrhoea 
Osteoporosis
Unexplained AST and ALT.
Neurological/psychiatric symptoms.

Question 10

What histological changes occur in coeliac disease?

Answer 10

Mucosal inflammation.
Loss of villous height (completely flat or short and broad).
Hypertrophy of crypts.
Increased plasma cells and intraepithelial lymphocytes (IELs).

Question 11

How can coeliac disease be diagnosed?

Answer 11

Serology

• IgA tTG
• IgA EMA

Endoscopy

• Scalloping of folds
• Cracked mud pattern
• Prominent submucosal blood vessels
• Nodular pattern to the mucosa.

Question 12

What is the Marsh Classification and what does it determine?

Answer 12

The severity of inflammation.

Marsh 3a-3c shows mild atrophy-absence of villi.

Question 13

What diseases are associated with coeliac?

Answer 13

Dermatitis herpetiformis

- itchy rash and 90% villous atrophy.

Question 14

What are complications of coeliac?

Answer 14

Infection - functional hyposplenism.

Osteoporosis as low BMI and potential Ca/vit D deficiency

Refractory coeliac disease

• RCD I - persistent villous atrophy and normal immunophenotype
• RCD II - persistent villous atrophy and abnormal immunophenotype

Malignancy

• enteropathy-associated T-cell lymphoma (EATL)
• small bowel adenocarcinoma

Question 15

What are other causes of villous atrophy?

Answer 15

Giardisis - parasitic infection.
HIB
Crohn's 
NSAIDs
T1DM