89-92. Coeliac disease

Question 1

What is coeliac disease? What are the features of the disease?

Answer 1

Gluten sensitive enteropathy
Small intestinal villous atrophy that resolves when gluten is withdrawn from the diet
Inappropriate T cell response in genetically susceptible individuals

Question 2

What is the most toxic moiety of gliadin (present in wheat)?

Answer 2

alpha-gliadin

Question 3

What is the gene which genetically predisposes people to coeliac disease?

Answer 3

HLA-DQ2 (95%)

The rest are HLA-DQ8

Question 4

What causes coeliac disease?

Answer 4

Infection with adenovirus 12 in genetically susceptible individuals

Peptide on alpha-gliadin is similar to that within the Eb1 portion of the virus

This leads to cross reactivity with alpha-gliadin and development of coeliac disease

Question 5

How does alpha-gliadin produce an inflammatory response in coeliac patients?

Answer 5

Digestion of alpha-gliadin produces a stable peptide, which is absorbed intact to the lamina propria

Exposure to TTG (an autoantibody) from damaged epithelium leads to deamination of glutamine residues

This enables bonding to HLA-DQ2 and the activation of pro-inflammatory T cell responses

Question 6

What are the 7 main presentations associated with coeliac disease?

Answer 6

1. Symptomatic (may be provoked by infection, pregnancy or surgery)
   - diarrhoea, bloating, flatulence, abdominal discomfort
2. Chronic or recurrent iron deficiency anaemia (50% of coeliacs present with this)
3. Nutritional deficiency (i.e. vit B12, folate)
4. Reduced fertility/amenorrhoea
5. Osteoporosis
6. Unexplained raised AST/ALT
7. Neurological/psychiatric symptoms

Question 7

How many litres of fluid does the small intestine absorb daily?

Answer 7

6 litres

Question 8

What is the surface area of the small intestine?

Answer 8

200m^2

Question 9

What are the pathological changes of the small intestine in coeliac disease?

Answer 9

Mucosal inflammation - can vary based on severity & extent
Mild proximal disease typically occurs
Mucosal damage may be patchy
Loss of villous height
- villi may be completely flat or short and broad (sub total villous atrophy)

No change in total mucosal thickness as crypts become elongated (hypertrophy)

Increased plasma cells and intraepithelial lymphocytes (IELs)

Question 10

Describe the clinical features related to the small bowel in coeliac disease

Answer 10

Diarrhoea - steatorrhoea, watery and high volume, rarely bloody
Weight loss
Malabsorption
abnormal pain/vomiting

Question 11

What are the indicators of small bowel disease?

Answer 11

Malabsorption/electrolyte imbalances

• folate
• vit D/ calcium —–> osteoporosis
• Vit K/ coagulopathy
• magnesium
• vit B12

Chronic/recurrent IDA

Question 12

What 80% of iron is incorporated into red cell haemoglobin?

Answer 12

80%

Question 13

How many mg of iron is required daily for the rate of renewal of RBCs?

Answer 13

20mg

Question 14

What is the RDA of iron, including pregnant women?

Answer 14

8-18mg

27 in pregnancy

Question 15

How many mg of iron is lost per day and what causes this loss?

Answer 15

1mg lost through sloughing of cells from skin and mucosal surfaces, including the lining of the GI tract

In menstruation, this increases to 2mg per day

Question 16

Where is iron absorption most predominant?

Answer 16

Duodenum and proximal jejunum

Question 17

Why is more iron absorbed in the duodenum and upper jejunum than other areas?

Answer 17

At physiological pH, iron is rapidly oxidised from the ferrous iron into insoluble ferric iron

Gastric acid lowers the pH, and when present in the duodenum this increases the solubility of iron for enhanced uptake

Question 18

What enhances uptake of iron?

Answer 18

Vitamin C and citric acid

Question 19

What inhibits the uptake of iron?

Answer 19

Phytates and tannins (tea)

Question 20

What are tested in serology for the diagnosis of coeliac disease?

Answer 20

IgA tTG (tissue transglutaminase antibody)
IgA EMA (antiendomysial Ab)

TTG more sensitive in adults, with EMA more specific

Question 21

What can be used to monitor patient compliance?

Answer 21

Seroconversion (the length of time it takes for an antibody to develop) with gluten free diet

Question 22

What may appear on endoscopy of a patient with coeliac disease?

Answer 22

Scalloping of the folds
Insufficient amount of folds
Music pattern "cracked mud"
Prominent submucosal blood vessels
Nodular pattern to the mucosa

May also appear NORMAL

Question 23

How are biopsies used to diagnose coeliac disease?

Answer 23

Taken from distal duodenum
Minimum of 4 biopsies
Biopsies from duodenal bulb may improve diagnosis
Must be on gluten rich diet

Question 24

If there is villous atrophy with no coeliac serology, what do you check for?

Answer 24

IgA selective deficiency (in 2-5%)

Question 25

What are rarer causes of villous atrophy without coeliac serology?

Answer 25

``` Giardiasis (parasitic disease) - most common parasite infection in humans CVID (common variable immune deficiency) Radiation enteritis Crohn's disease lymphoma Whipple's disease Tropical Sprue HIV enteropathy Chronic ischaemia NSAIDs ```

Question 26

What are the coeliac related diseases?

Answer 26

Dermatitis herpetiformis T1DM - NICE advise to screen all patients Thyrotoxicosis (hyperthyroidism) Addison's disease (not enough cortisol)

Question 27

What are features of dermatitis herpetiformis?

Answer 27

Itchy rash on exterior surfaces 90% villous atrophy Gluten sensitive/dapsone

Question 28

What foods should coeliacs avoid and what foods can they eat?

Answer 28

Avoid: wheat, barley, rhye Can eat: Oats*, rice and maize Should continue to eat dairy to avoid hypolactasia (50%) *Debate as to whether or not coeliacs can eat oats

Question 29

What % show symptomatic improvement within 2-52 weeks?

Answer 29

70%

Question 30

How long does it take to show improvement in histology?

Answer 30

3-12 months

Question 31

What are the 4 main complications of coeliac disease?

Answer 31

Osteoporosis Malignancy Recurrent coeliac disease Infection

Question 32

What may cause infection in coeliacs?

Answer 32

``` Functional hyposplenism - defective immune responses to: Encapsulated organisms Pneumococcal Haemophilus influenzae Meningococcus Vaccinations ```

Question 33

What % of coeliacs develop osteoporosis and why?

Answer 33

25% Low BMI Calcium and vitamin D deficiency (consider DEXA at diagnosis and supplementation)

Question 34

What is refractory coeliac disease?

Answer 34

Recurrent malabsorptive symptoms and villous atrophy despite strict adherence to a gluten free diet for at least 6-12 months in the absence of other causes of non-responsive treated coeliac disease and overt malignancy.

Question 35

What are the outcomes and treatment for patients with refractory coeliac disease 1 (RCD1) - villous atrophy with normal immunophenotype?

Answer 35

96% 5 year survival rate | Treated with steroids/azathiopine (over 75% response)

Question 36

What are the outcomes for RCD2 - villous atrophy with abnormal immunophenotype?

Answer 36

58% 5 year survival rate | 60-80% progression onto EATL (enteropathy associated T cell lymphoma) at 5 years

Question 37

What are the clinical features of EATL, the treatment and survival rate?

Answer 37

Weight loss, night sweats, itch, overt/occult GI bleeding, venous thromboembolism Often advanced and incurable Chemotherapy and autologous stem cell Tx Poor response, 8-20% 5 year survival

Question 38

What are the main features of small bowel adenocarcinoma?

Answer 38

``` Rare -13% coeliac, 7% Crohns 58% survival at 30 months Male more than female 55% present with obstruction Mean time from symptoms to diagnosis - 14 months ```