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Coeliac disease

Definition
Risk Factors
  • Almost all coeliac patients have specific HLA alleles:
    • HLA-DQ2 common in Europe (95%)
    • HLA-DQ8 more common in Middle East
    • But both have very low penetrance
  • Autoimmune thyroid disease
  • IgA deficiency
  • Hypothetical factors:
    • timing of initial gluten exposure
    • type 1 diabetes
    • gastrointestinal infection leading to gluten antigen mimicry
    • direct damage to the intestinal-epithelial barrier leading to abnormal exposure of the mucosa to gluten peptides
Differential diagnosis
  • Peptic duodenitis
  • Crohn's disease
  • Giardiasis
  • Small-intestinal bacterial overgrowth
  • Post-gastroenteritis
  • Eosinophilic enteritis
  • Tropical sprue
  • CVID and other immunodeficiency states
  • GVHD
  • Autoimmune enteropathy
  • Chronic pancreatitis
  • Hypolactasia
  • Whipple's disease
Epidemiology
  • Prevalence between 1 in 67 and 1 in 250 with an approximate average of 1%
    • North and South America, eastern and western Europe, Turkey, the Middle East, and North Africa
  • Far less common in people from southeast Asia and sub-Saharan Africa
  • Men and women are roughly equally affected
    • But women tend to make up almost two-thirds of patients
  • First peak period of presentation is in infancy soon after the initial exposures to gluten
  • Second, larger peak in the fourth and fifth decades
  • Most common age at diagnosis in the US is about 40 years
Aetiology
  • Reaction to prolamins
  • Autoimmune reaction leads to a truncating of the villi lining the small intestine (villous atrophy)
  • This interferes with the absorption of nutrients
Clinical features
Pathophysiology
  • Reaction to gliadin, a prolamin found in wheat
    • Resistant to human proteases, allowing them to persist intact in the small intestinal lumen
    • Specifically to three peptides found in prolamins
  • Also to similar proteins found in the crops of the tribe Triticeae
    • includes other common grains such as barley and rye
  • Unknown how these peptides gain access to the lamina propria
    • Faulty tight junctions
    • Endothelial cell transcytosis
    • Sampling of the intestinal lumen by dendritic cells
    • Passage during resorption of apoptotic villous enterocytes
  • Gluten peptides stimulate interleukin-15 production by dendritic cells and macrophages
    • These then stimulate intra-epithelial lymphocytes, leading to epithelial damage. [13] [14]
  • In the submucosa, gluten peptides are de-amidated by tissue transglutaminase (tTG)
    • Enzyme normally involved in collagen cross-linking and tissue remodelling
  • Allows for high-affinity binding to the coeliac-associated HLA peptides and activation of helper T (Th) cells. [15] 
  • Stimulation of Th cells causes:
    • Cell death and tissue remodelling with villous atrophy and crypt hyperplasia (Th1-mediated)
    • Plasma cell maturation and subsequent anti-gliadin and anti-tTG antibody production (Th2-mediated). [16]
  • Link to IgA deficiency:
    • Lack of secretory IgA and Peyer patch malfunction allow for increased free gluten peptides in the submucosa??
File:Coeliac Disease.png

Investigations
  • FBC and blood smear with iron studies
  • IgA-tTG ELISA
  • Endomysial antibody (EMA)
    • More expensive alternative to IgA-tTG with greater specificity but lower sensitivity
    • Based on immunofluorescence
      • Operator-dependent
  • IgG-tTG
    • Useful in people who are IgA deficient
      • Relatively common in coeliac
  • IgG DGP or IgA/IgG DGP (deamidated gliadin peptide)
  • Upper endoscopy with biopsy of the duodenum (beyond the duodenal bulb) or jejunum
  • Folic acid and vitamin B12
  • hypocalcaemia
  • Thyroid function tests
  • HLA typing??
    • cf penetrance issues
    • Not useful for diagnosis
Management

a) conservative
  • The only known effective treatment is a lifelong gluten-free diet.[5]
  • Adherence is difficult
  • Dietary changes may lead to deficiencies in fibre and other nutrients
  • There is substantial evidence that oats that are not contaminated by wheat or barley are safe for the vast majority of patients with coeliac disease.[B Evidence] [44] [45] [46]
    • In practice, oats should be avoided until the patient is in clinical remission
    • Then wheat-free oats may be gradually added to the diet
b) medical
  • Steroids?
  • A number of agents are under investigation
  • Unlikely to replace the gluten-free diet
  • May be used to allow for laxity in situations of low-level gluten exposure--for example, in food additives
c) surgical

Prognosis
  • Most, up to 90% in some studies, will have complete and lasting resolution of symptoms on a gluten-free diet alone
  • For the 10% with persistent symptoms, most of these will be attributed to ongoing gluten exposure, lactose intolerance, and irritable bowel syndrome
  • Hyposplenism
  • Less than 1% can be expected to develop refractory coeliac disease. [51]
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