Coeliac disease Flashcards
What is Coeliac disease?
systemic autoimmune condition triggered by dietary gluten peptides.
People with Coeliac disease have an intolerance to which protein? Where can these proteins be found?
prolamins
found within the seeds of cereal grains such as wheat (gliadin), barley (hordeins) and rye (secalins).
Which genes are associated with Coeliac disease? What is the strength of the predictive value with ese genes?
two type II human leukocyte antigens
HLA-DQ2 - present in 95%.
HLA-DQ8 - present in 5%.
has a strong negative predictive value. absence of the gene is strongly associated with not having the disease.
However, having the gene does not mean patients will develop the disease
Which environmental factor predisposes someone to Coeliac disease and which is protective?
Recurrent rotavirus infection infections during childhood increase the risk of developing the disease.
Breastfeeding = protective.
Describe the pathophysiology of Coeliac disease?
- 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 (e.g. anti-endomysial and anti-tissue transglutaminase).
gliadin may irritate endothelial cells leading to the release of cytokines (e.g. IL-15) which can lead to causing direct epithelial damage.
Which immune responses are used in coeliac disease?
innate and adaptive immune responses
What are the 3 classic features of coeliac disease?
Villous atrophy (reduced absorptive surface).
Crypt hyperplasia (increased cellular proliferation).
Inflammatory infiltration (increased IEL, influx of immune cells into lamina propria)
What are the signs and symptoms of coeliac disease?
Symptoms - bloating abdominal pain loose stools and steatorrhoea Weight loss Fatigue Weakness Abdominal pain Bloating Flatulence
Signs Mouth ulcers Angular stomatitis Abdominal distension Ecchymosis (discoloration of the skin resulting from bleeding underneath) Muscle wasting Neuropathy
What are the Extra-intestinal manifestations of coeliac disease? What is the main reason for the manifestations of these conditions?
Occur as a secondary consequence of malabsorption
Anaemia
- due to malabsorption of iron and folate
a mixed megaloblastic/microcytic picture may be seen (may present as nomocytic)
- In severe disease affecting the ileum, B12 malabsorption may occur.
Osteoporosis
- Malabsorption of calcium and vitamin D deficiency
- Calcium may sequestered to poorly absorbed fatty acids
- Assess with DEXA scan
Dermatitis herpetiformis
- blistering skin condition
- The rash is intensely pruritic
may be managed with dapsone and a gluten free diet.
Bruising:
- secondary to failure to absorb vitamin K.
Neurological sequelae:
- secondary to hypocalcaemia - vitamin B12 deficiency.
Which investigations (non images) are conducted for those suspected of having coeliac disease?
Observations
ECG
Stool culture, microscopy & sensitivities + ova, cysts & parasites
Bloods- FBC Blood films Liver function tests (LFTs) Urea & electrolytes (U&Es) Lipids Magnesium Haematinics Bone profile Clotting Serology (discussed below) Genetic testing
Which imaging techniques are used in the diagnosis of Coeliac disease?
Small bowel imaging can help to assess for complications (e.g. lymphoma).
- barium imaging
- capsule endoscopy.
Upper GI endoscopy helps to confirm the diagnosis of coeliac disease (minimum 6 biopsies).
It can also be used to assess the response to treatment.
How is coeliac disease ultimately diagnosed?
both serological and histological evidence of disease activity.
Biopsy taken on Go endoscopy
When should individuals under go serology 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)
Other:
Multiple diseases associated with coeliac disease.
What are the 2 auto-antibodies which are often present in coeliac disease?
When testing for these autoantibodies, which other immune related test should you take?
IgA Anti-tissue transglutaminase (tTGA)
IgA Anti-endomysial (EMA)
Typically, anti-tTGA is assessed first. Anti-EMA should be tested for if the initial anti-tTGA test result is equivocal.
Total IgA levels should be checked at the same time
If IgA deficiency is found then tests specific for IgG anti-tTGA/anti-EMA are required
How many biopsies should be taken in GI endoscopy for coeliac disease?
6 or more
