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

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??

Investigations

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]