Gastrointestinal Malabsorption & Coeliac Disease

Question 1

Name the common causes of malabsorption.

What are some other causes?

Answer 1

• Coeliac
• Chrons / UC
• Chronic pancreatitis

1. Insufficient absorptive area
   - Chrons & coeliac
2. Extensive surface parasitisation
   - Giardia
3. Small intestinal resection or bypass
   - Procedure done on obese patients, those with chrons or those with infarcted small bowel
4. Lack of digestive enzymes
   - Lactose intolerance
5. Lymphatic obstruction
   - Lymphoma or tuberculosis

Question 2

What are the signs and symptoms of malabsorption?

Answer 2

Symptoms

• Fatigue
• Weight loss
• Diarrhoea
• Steatorrhea
• Bloating

Signs

• Anaemia (B12, iron, folate)
• Bleeding disorders (decreased vit K)
• Oedema (decreased protein)
• Neurological features (neuropathy)

Question 3

What percentage of the population is affected by coeliac disease? What percentage are made up by women?

Answer 3

1% of the population - 2/3rds are women.

Question 4

What is happening to the prevalence of coeliac disease?

Answer 4

It is increasing - doubled over the last 20 years.

Question 5

When is the most common age of presentation for coeliac disease?

Answer 5

Before age of 1 and then between 40-60.

Question 6

If a patient has a first degree relative with coeliac disease, how much more likely is the patient to suffer from coeliac disease?

Answer 6

6x more likely.

Question 7

Almost all patients with coeliac disease carry one of 2 major histocompatibility complex class II molecules. What are these? 
Why do we think there is also environmental factors influencing coeliac disease?

Answer 7

HLA DQ2 (95%) and HLA DQ8 (5%)

40% of caucasians are also positive for DQ2 and DQ8 and do not have coeliac despite exposure to gluten.

Question 8

Describe the pathophysiology of coeliac disease

Answer 8

There is a loss of immune tolerance to peptides derived from prolamins in wheat (gliadin), rye (secalin), barley (hordein), spelt and related grains.

These peptides are resistant to human proteases which allows them to persist intact in the SI lumen.

In the intestinal submucosa, these peptides trigger innate and adaptive immune activation.
→ Gluten peptides stimulate IL-15 production which leads to epithelial damage.
→ Gluten peptides are then de-amidated by tissue transglutaminase (tTG)

→ De-amidating leads to high affinity binding to the coeliac-associated HLA peptides (DQ2, DQ8) on APCs and activation of helper T cells.

→ Stimulation of T helper cells causes cell death and tissue remodelling with villous atrophy and crypt hyperplasia and th2 (B cell) cells triggers production of anti-gliadin and anti-tTG antibody production.

Question 9

What are the 3 classifications of coeliac disease?

What are the symptoms for each of these types?

Answer 9

1. Classical
   - diarrhoea
   - steatorrheoa
   - weight loss
   - failure to thrive
2. Non-classical
   - IBS type symptoms
   - iron deficiency anaemia
   - osteoporosis
   - chronic fatigue
   - dermatitis herpetiformis
   - ataxia
   - peripheral neuropathy
   - amenorrhoea
   - infertility
3. Silent
   - first degree relatives
   - neglected coeliac disease

Question 10

What other conditions are associated with coeliac disease?

Answer 10

T1DM - 2-8%
Autoimmune thyroid disease 5%
Dermatitis hepetiformis 70%
IBS 3-5%

Question 11

How is coeliac disease diagnosed?

Answer 11

• IgA-tTG
• IgA EMA (more expensive, used if IgA tTG not available)
• Small bowel endoscopy and biopsy of duodenum while on gluten diet and histology showing villous atrophy, increased intra-epithelial WBC and crypt hyperplasia

Question 12

Treatment of coeliac disease

Answer 12

Life long gluten free diet
Might require vitamin and mineral supplementation
DEXA scans may be used for patients with high osteoporotic risk