Coeliac Disease Flashcards
What is coeliac disease?
Autoimmune condition - inflammation of the mucosa of the upper small bowel that improves with gluten withdrawal from the diet.
In which foods is gluten found?
Gluten in the main protein in cereals, wheat, barley and rye.
How common is it?
1% of population affected; mostly a clinically silent disease
What is the pathophysiology of this disease?
Both genetics and environmental factors needed
Prolamins (gliadin from wheat, hordeins from barley, secalins from rye) are resistant to digestion by pepsin and chymotrypsin.
They remain in the gut lumen, triggering immune response resulting in coeliac’s disease.
How does gliadin in particular trigger an immune response?
Gliadin peptides pass through the epithelium and are deaminated by tissue transglutaminase - increasing its immunogenicity.
Gliadin peptides bind to APC which interact with CD4+ T-cells in the lamina propria via HLA class II molecules.
These T-cells produce pro-inflammatory cytokines (interferon-y)
CD4+ T-cell also interact with B cells to produce endomysial and tissue transglutaminase antibodies.
Gliadin peptides also cause release of metalloproteinases and other inflammatory markers leading to villous atrophy and crypt hyperplasia => malabsorption
Which part of the bowel is predominantly affected in Coeliac disease?
Proximal small bowel mucosa -
Severity decreases toward ileum as gluten is digested into smaller non-toxic parts.
How do genetics and environmental factors increase the risk of coeliac disease?
Increased incidence of coeliac disease within families.
HLA-DQ2 assoc. with coeliac disease.
Breast-feeding and the age of introduction of gluten into diet is important.
Rotavirus infection in infancy also increases the risk
Who does coeliac disease affect?
Coeliac disease can present at any age but most common in 5th decade.
More common in women
What are the clinical features of coeliac disease?
Mostly asymptomatic May mimic IBS - always check for coeliac
Tiredness, malaise assoc. with iron deficiency anaemia
Angular stomatitis & aphthous ulcers
Nausea & vomiting
Severe disease:
Diarrhoea ; steatorrhoea
Abdominal pain
Weight loss
In children:
Osteomalasia
Failure to thrive
What are the complications of coeliac disease?
Osteoporosis (even in patients with long-term gluten free diet)
Rare complications: tetany, osteomalacia, gross malnutrition
Which other diseases is coeliac disease associated with?
Coeliac’s increases incidence of other autoimmune diseases.
Thyroid disease
Type 1 Diabetes
Sjögren’s syndrome
Other associated diseases:
IBD Primary biliary cholangitis Chronic liver disease Interstitial lung disease Epilepsy IgA deficiency e
How do you diagnose coeliac disease?
Gold standard for +ve diagnosis : small bowel (duodenal) biopsy
Histology:
Crypt hyperplasia
Villous atrophy
Serological tests:
endomysial and tissue transglutaminase antibodies (most sensitive)
HLA typing:
HLA-DQ2 in 90% of coeliac patients
HLA-DQ8 in 8% of coeliac patients
Which investigations are carried out for coeliac disease?
Haematology:
Mild-moderate anaemia is present in 50% cases. Folate & iron deficiency is common - due to malabsorption.
Blood film will show a microcytes and macrocytes (dimorphic picture)
Biochemistery:
Severe case: osteomalacia
Low calcium ; high phosphate
Hypoalbuminaemia
Imaging:
Small bowel barium or MRI
Bone densitometery - on patients at risk of osteoporosis
How do you manage coeliac disease?
Replacement minerals & vitamins (iron, folic acid, calcium, vitamin D)
Gluten free diet for life (no wheat, barley, rye). Clinical improvement seen within weeks. Morphological improvements seen within months.
How can a gluten-free dietary compliance monitored?
Through endomysial and tissue transglutaminase antibodies
