Coeliac disease

Question 1

Define coeliac disease.

Answer 1

Systemic autoimmune disease triggered by dietary gluten-peptides found in wheat, rye and barley.

Question 2

What is the epidemiology for coeliac disease?

Answer 2

· Men and women are equally affected, but in practice, women make up 2/3 of patients.
· First peak period of presentation is in infancy, soon after initial exposures to gluten.
· Second and larger peak in the 4th and 5th decades.

Question 3

What is the pathophysiology of coeliac disease?

Answer 3

· Loss of immune tolerance is gliadin peptide antigens.
· These peptides are resistant to human proteases, allowing them to persist intact in the small intestinal lumen.
· In the intestinal submucosa, these peptides trigger both innate and adaptive immune activation.
· Gluten peptides can stimulate IL-15 production, which stimulate IEL’s, leading to epithelial damage.

Question 4

What is the prognosis for coeliac disease?

Answer 4

· 90% have complete and lasting resolution of symptoms on a gluten-free diet alone.
· 10% with persistent symptoms is attributed to ongoing gluten exposure, lactose intolerance and IBS.

Question 5

What are the 5 types of classification for coeliac disease?

Answer 5

1. Classic coeliac disease.
2. Atypical coeliac disease.
3. Silent coeliac disease.
4. Non-responsive coeliac disease.
5. Refractory coeliac disease.

Question 6

How is classic coeliac disease characterised?

Answer 6

· Diarrhoea, weight loss, abdominal pain and fatigue.

· Found in <50% of patients.

Question 7

How is atypical coeliac disease characterised?

Answer 7

· Lacks typical GI symptoms of malnutrition.
· Presents with deficiency states (iron deficiency) or extra-intestinal manifestations (fatigue, elevated liver enzymes or infertility).
· Largest proportion of patients.

Question 8

How is silent coeliac disease characterised?

Answer 8

· Serological and histological evidence of coeliac disease.
· No evident symptoms, signs or deficiency states.
· 20% of cases.

Question 9

How is non-responsive coeliac disease characterised?

Answer 9

· Clinical symptoms and serology fail to improve within 6 months of gluten withdrawal.
· Or symptoms recur while the patient is on a gluten-free diet.

Question 10

How is refractory coeliac disease characterised?

Answer 10

· Persistence of symptoms and histological abnormalities after at least 6 months on a gluten-free diet and in the absence of other evident causes or of overt lymphoma.
· 1% of cases.

Question 11

List the risk factors for coeliac disease.

Answer 11

· Family history of coeliac disease.
· IgA deficiency - lack of secretory IgA and Peyer’s patch malfunction allow for increased free gluten peptides in the submucosa.
· Type 1 diabetes.
· Autoimmune thyroid disease.

Question 12

What is the aetiology of coeliac disease?

Answer 12

· Systemic autoimmune disease triggered by dietary gluten-peptides found in wheat, rye and barley.

· Almost all people with coeliac disease carry 1 or 2 major histocompatibility complex class-II molecules (HLA-DQ2 or HLA-DQ8) that are required to present gluten peptides in a manner that activates an antigen-specific T cell response.

· Most DQ2 or DQ8 positive people never develop coeliac disease despite daily exposure to gluten.

· Unknown additional environmental or genetic factors are required for loss of immune tolerance. Theories include:

• Timing of initial gluten exposure.
• GI infection leading to gluten antigen mimicry.
• Direct damage to the intestinal-epithelial barrier leading to abnormal exposure of mucosa to gluten peptides.

Question 13

What are the typical signs and symptoms of coeliac disease?

Answer 13

· Unexplained GI symptoms.
· Chronic diarrhoea.
· Bloating.
· Abdominal pain.
· Unexplained iron deficiency anaemia.
· Skin rash consistent with dermatitis herpetiformis.
· Others - failure to thrive, short stature, vitamin deficiency (B12, D or folate), recurrent severe aphthous stomatitis, recurrent spontaneous abortion or infertility.

Question 14

What is it crucial to do when undertaking investigations on a suspected coeliac patient?

Answer 14

Ensure that the patient is ingesting gluten, because tests will normalise on a gluten-free diet.

Question 15

What 3 investigations can be done to confirm coeliac disease?

Answer 15

1. Serology.
2. Histology.
3. Endoscopy.

Question 16

What does a serology investigation involve?

Answer 16

· FBC and blood smear: iron deficiency anaemia is the most common presentation&raquo_space; low Hb and microcytic red cells. Folate deficiency can lead to macrocytic anaemia.

· IgA-tTG: if elevated, advise to remain on a gluten-containing diet and referred for duodenal biopsies. It’s also reasonable to proceed to duodenal biopsy in patients with IgA deficiency.

· IgA/IgG DGP - elevated.

· A normal IgA-tTG and total IgA result excludes the diagnosis in patients with a low index of clinical suspicion.

Question 17

What does a histology investigation involve?

Answer 17

· Small intestinal biopsies should be obtained regardless of IgA-tTG result in patients with a high index of clinical suspicion.

· For diagnosis - IEL’s increased and villous-to-crypt ratio decreased.

· If clinical improvement after gluten-free diet, a repeat biopsy is no longer necessary.

· SMALL BOWEL – HISTOLOGY: gold standard and is essential to confirm the diagnosis&raquo_space;> presence of intra-epitehlial lymphocytes, villous atrophy and crypt hyperplasia.

Question 18

List some differential diagnoses.

Answer 18

· Peptic duodenitis.
· Crohn’s disease.
· Giardiasis.

Question 19

What is the treatment for coeliac disease?

Answer 19

· 1st line - Gluten-free diet.
· Plus - check for common deficiencies such as vit D or iron - all pts should take Calcium and Vitamin D supplementation +/- iron.

Question 20

What is the treatment for refractory coeliac disease?

Answer 20

Plus - Referral to nutritionist or gastroenterologist

Question 21

What is the treatment for coeliac crisis?

Answer 21

· Plus - Rehydration and correction of electrolyte abnormalities.
· Adjunct - Corticosteroid.

Question 22

What complications can occur?

Answer 22

· Osteoporosis/Osteopenia.
· Dermatitis Herpetiformis.
· Malignancy
· Idiopathic recurrent acute pancreatitis/chronic pancreatitis.
· Pneumococcal infection.
· Villous atrophy - villi disappear if untreated.