Coeliac disease

Question 1

What is coeliac disease?

Answer 1

A gluten-sensitive enteropathy: permanent sensitivity of the intestinal lumen to gliadin contained in gluten in wheat/rye.

Question 2

What causes intestinal sensitivity to gliadin?

Answer 2

Inappropriate T cell mediated immune response in genetically susceptible individuals.

Question 3

What is the characteristic histological appearance of intestine in coeliac disease?

Answer 3

Small intestinal villous atrophy, which resolves when gluten is removed from the diet.

Question 4

Who is most likely to get coeliac disease?

Answer 4

Females more than males.
Any age at diagnosis (20%>60)
1% of people in UK, 10% in 1st degree relatives

Question 5

What gene is involved in CD?

Answer 5

HLA-DQ2 in 95%

HLA-DQ8 in 5%

Question 6

What theories are there about the causes CD?

Answer 6

Infectious hypothesis: adenovirus 12 infection in genetically susceptible individuals.
- A peptide on alpha-gliadin is similar to that within the E1b portion of the adenovirus which leads to cross reactivity

Question 7

How does alpha-gliadin contribute to CD onset?

Answer 7

Alpha-gliadin is digested to give a stable peptide and is absorbed into the lamina propria where it is exposed to transglutaminase from damaged epithelium. Glutamine residues on gliadin are deaminated, making it recognisable as antigenic to CD4 T cells via HLA DQ2

Question 8

How does CD present in infants?

Answer 8

Aged 4-24 months once cereals are introduced.
Infants: Impaired growth, D&V, abdominal distension
Children (older): anaemia, pubertal delay, abdominal pain

Question 9

How does CD present in adults?

Answer 9

Diarrhoea, flatulence and abdominal pain.
Provoked by infection, pregnancy and surgery
Chronic IDA: 50% of presentations
Nutritional deficiency
Osteoporosis
Unexplained increased AST/ALT

Question 10

What are the main pathophysiological mechanisms in CD?

Answer 10

Sub-total villous atrophy due to infiltration of lymphocytes which decreases villous height and surface area of small intestine.

Crypt hypertrophy means there is no change in total mucosal thickness.

Question 11

Why is there loss in villous height?

What effect does flattened villous surface have?

Answer 11

Stem cells can’t keep up with the rate of enterocyte loss.

Reduced absorption

Question 12

Why does lactose intolerance occur?

Answer 12

Due to secondary disaccharide deficiency, due to loss of epithelial cells.

Question 13

What small bowel symptoms are present in CD?

Answer 13

Diarrhoea (watery, high volume)
Steathorrhoea (reduced fat absorption)
Malabsorption
Weight loss, abdominal pain, vomiting

Question 14

What electrolyte imbalances are present in SB disease?

Answer 14

Folate
Calcium and vit D
Vit K = coagulopathy 
Magnesium
Vit B12 (rare)

Question 15

What factors can enhance and inhibit iron absorption?

Answer 15

Vitamin C, citric acid and alcohol enhance.

Phylates and tannins inhibit

Question 16

How is CD diagnosed by serology?

Answer 16

IgA TTG antibodies by immunofluorescence (more sensitive in adults)

IgA EMA antibodies: 93% sensitive and >99% specific (more specific in adults)

Question 17

How is CD diagnosed by endoscopy?

Answer 17

Duodenal biopsy (gold standard)

• Scalloping of folds
• Mosaic, cracked mud pattern
• Prominent submucosal blood vessels
• Nodular pattern to mucosa

Question 18

How many biopsies are needed to show patchy changes on a gluten rich diet?

Answer 18

4

Question 19

What is the Marsh classification?

Answer 19

Types 0-3c, depending on:

• how many inflammatory leucocytes are in the enterocytes (1 = >40)
• if there is crypt hypertrophy (2= increased)
• if there is villous atrophy (3a-3c, mild to absent)

Question 20

What should you do if there is villous atrophy, but negative coeliac serology?

Answer 20

Check IgA: selective deficiency in 2-5%

Could be Giardisis: common parasitic infection in humans

Question 21

What diseases are associated with CD?

Answer 21

Dermatitis herpetiformis: itchy rash on extensor surfaces which is gluten sensitive; 90% villous atrophy

Type 1 diabetes: 3-8% CDs
Thyrotoxicosis
Addison’s disease (not enough cortisol)

Question 22

How is CD managed?

Answer 22

Not eating gluten, improvement in 2 weeks

Keep eating dairy to avoid secondary hypolactasia (50%)

Question 23

What are complications of CD?

Answer 23

1. Infection: functional hyposplenism
2. Osteoporosis: 25% due to Ca/D deficiency
3. Malignancy: enteropathy associated T cell lymphoma; advanced, GI bleeding, weight loss; poor response to chemo and 8-20% 5yr survival

Question 24

What is refractory CD?

Answer 24

Recurrent malabsorptive symptoms and villous atrophy, despite gluten free diet for > 6-12 months.

RCD1: persistent villous atrophy, normal immunophenotype. 96% 5yr survival. Treat with steroids and azathioprine

RCD2: same, but with abnormal immunophenotypes (cD3/CD8 negative). Ulcerative jejunitis with only 58% 5yr survival and can progress to EATL in 60-80%.