Coeliac Disease Flashcards
What is Coeliac Disease?
systemic autoimmune condition triggered by dietary gluten peptides.
What is the cause of Coeliac disease?
Coeliac develops due to intolerance to proteins called prolamins. Gliadin is an example of a prolamin found within wheat. Other prolamins may be identified in other cereal grains including hordeins (barley) and secalins (rye). Prolamins possess high proline and glutamate content which makes them resistant to digestive gastric enzymes.
what is gluten?
Gluten is a general term for the proteins found within wheat and other cereal grains. It is a complex mixture of many proteins, particularly gliadin and glutenin.
Explain the pathophysiology of Coeliac.
Ingestion of prolamins can result in immune-mediated damage of the intestinal mucosa. Mucosal damage reduces in severity moving distally towards the terminal ileum. Persistent inflammation of the intestinal mucosa leads to damage and failure of its normal absorptive functions.
The development of sensitivity to dietary prolamins is thought to be multifactorial, and due to a complex interaction between prolamins and the patients’ genetics, immune system and the environment.
Prolamins (e.g. gliadin) are ingested within the diet. These may cross the epithelial surface into the lamina propria. Here, the enzyme tissue transglutaminase is able to deaminate gliadin.
Deamination makes gliadin more immunogenic and it subsequently binds to antigen-presenting cells (APCs) of the innate immune system. Gliadin is then presented to T helper cells via the HLA molecules DQ2/DQ8.
Activated T helper cells secrete pro-inflammatory cytokines and activate B lymphocytes. The activation of B lymphocytes leads to the formation of auto-antibodies.
Furthermore, gliadin may irritate endothelial cells leading to the release of cytokines (e.g. IL-15), which can activate intraepithelial lymphocytes (IEL) causing direct epithelial damage.
Collective activation of both the innate and adaptive immune responses leads to chronic inflammation and damage to enterocytes, resulting in three classical features:
1) Villous atrophy (reduced absorptive surface).
2) Crypt hyperplasia (increased cellular proliferation).
3) Inflammatory infiltration (increased IEL, influx of immune cells into lamina propria)
Which genes are involved in Coeliac’s Disease?
There is a strong association between coeliac disease and two type II human leukocyte antigens (HLAs):
1) HLA-DQ2 - present in ~95%.
2) HLA-DQ8 - present in ~5%.
HLA testing has a strong negative predictive value. This means an absence of the gene is strongly associated with not having the disease. However, having the gene does not mean patients will develop the disease
Explain the immune response to prolamins in Coeliac.
Both the innate and adaptive immune systems are involved in the inappropriate response to dietary prolamins.
Activation of T helper cells leads to stimulation of B cells and the release of pro-inflammatory cytokines. The activation of the immune system leads to the recruitment of inflammatory cells in the lamina propria (infiltration) and subsequent hyperplasia in the crypts of Lieberkühn.
What are some environmental factors that are implicated in Coeliac?
- recurrent rotavirus infection during childhood increase the risk of developing the disease.
- breastfeeding is thought to be protective.
What are the signs and symptoms of Coeliac disease?
Symptoms:
- weight loss
- fatigue
- weakness
- abdominal pain
- bloating
- flatulence
- loose stools
- steatorrhea (oily stools)
- faltering growth
Signs:
- mouth ulcers
- angular stomatitis
- abdominal distension
- contusion
- muscle wasting
- neuropathy
what are some extra-intestinal manifestations of Coeliac?
- anaemia- due to malabsorption of iron and folate
- osteoporosis- malabsorption of calcium, vit D
- Dermatitis herpetiformis- blistering skin condition (can be managed with dapsone and a gluten free diet.
- bruising- secondary to failure to absorb vit K
- neurological sequelae- secondary to hypocalcaemia or vit B12 deficiency
What are some investigations that can be done after diagnosing Coeliac to assess the severity & monitor the development of complications?
- ECG
- Stool culture, microscopy & sensitivities+ ova, cysts and parasites
- FBC
- Blood film (microcytes- iron, macrocytes- B12/folate, hypersegmented neutrophils- B12/folate, Howell-Jolly bodies- splenic atrophy)
- LFTs
- U&Es
- Lipids
- Mg
- Haematinics
- Bone profile
- Clotting
- serology
- genetic testing
Imaging:
- Small bowel imaging can help assess for complications (lymphoma)
Which invasive imaging technique confirms diagnosis of Coeliac, and how does it work?
Upper GI endoscopy (at least 4 biopsy specimens to be taken)- the samples are taken from the second part of the duodenum and duodenal bulb.
How is coeliac disease diagnosed?
serology and histology
What are the indications for testing for Coeliac disease?
Based on clinical features:
- Sudden or unexpected
-weight loss.
-Chronic or intermittent diarrhoea.
-Recurrent abdominal pain, cramping, or distension.
-Unexplained gastrointestinal symptoms (e.g. nausea and diarrhoea).
-Prolonged fatigue.
-Unexplained anaemia (e.g. iron-deficiency, megaloblastic).
Those at increased risk:
-Dermatitis herpetiformis
-Autoimmune thyroid disease.
-Irritable bowel syndrome.
-Type 1 diabetes
-Family history (first degree relative)
What do you check for in serology?
Patients should be tested for the presence of two auto-antibodies:
1) IgA Anti-tissue transglutaminase (tTGA)
2) IgA Anti-endomysial (EMA)
What do you direct patients to after recieving a positive serological test?
- referred for upper GI endoscopy and intestinal biopsy and histological investigation of that.
