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coeliac

coeliac disease

see also: gastroenterology

Newsbreak - new vaccine starting trials 2009 for Rx of coeliac - see here

introduction

  • now known as gluten enteropathy
  • results from an abnormal immune response to gliadin, a component of dietary gluten, found in wheat, barley, rye and possibly oats.
  • this causes villous atrophy of the small bowel mucosa, which in turn leads to malabsorption and a predisposition to gastrointestinal malignancy, particularly carcinoma of the oropharynx and oesophagus, and small bowel lymphoma.
  • the disease may present in either children or adults, but it is uncommon in adolescence and its manifestations may disappear at this age.
  • largely a disorder of Caucasians - in Australia it affects approximately 1 in 100 to 1 in 2000 people depending upon accuracy of diagnosis.
  • subclinical, or `silent', celiac disease, detected by antibody screening, may be up to ten times more frequent.

pathophysiology

  • Patients with coeliac disease typically have the HLA-B8, DR3, DQ2 or DQ8 haplotype
    • thus coeliac disease occurs in 10% of first-degree relatives, 30% of HLA-identical siblings and 70% of monozygotic twins.
    • however, approximately 20% of the general population have the same HLA alleles but do not develop coeliac disease.
  • When gliadin enters the small bowel mucosa, it undergoes enzymatic deamidation by tissue transglutaminase (tTG), an extracellular enzyme found in the connective tissue of the small bowel.
  • In susceptible people, the gliadin-tTG complex becomes antigenic, producing a local immune response. This leads to the characteristic villous atrophy of coeliac disease. As part of this immune reaction antibodies to tTG are produced and are recognised as endomysial antibodies.

clinical features

  • The classic presentation of a patient with abdominal distension, steatorrhoea, weight loss, bruising and other obvious features of malabsorption is now uncommon.
  • adults tend to present with milder symptoms such as:
    • diarrhoea, flatulence and bloating, or fatigue.
    • isolated iron and/or folate deficiency anaemia
  • the clinical features have also changed in children who now may present with:
    • growth or pubertal failure, recurrent abdominal pain, iron and/or folate deficiency or malaise.
    • irritability and poor school performance.
  • non-GIT presentations:
    • recurrent mouth ulcers
    • delayed menarche, infertility or repeated miscarriage
      • untreated coeliac disease is reported to have a 8-9x risk of recurrent miscarriages compared with treated patients but requires further study1)
    • most adults will have significant osteopenia at presentation.
      • 5% of adults diagnosed with osteoporosis will be found to have underlying coeliac disease as the cause
    • at least 75% of patients with dermatitis herpetiformis will be found to have typical villous atrophy on small bowel biopsy whilst most of the others will have more subtle changes.
  • other associations:
    • type 1 diabetes
    • autoimmune thyroid disease
    • IgA deficiency
    • atrophic gastritis
    • peripheral neuropathy
    • primary biliary cirrhosis
    • alopecia areata
    • Down's syndrome
    • hyposplenism
    • muscle weakness due to hypokalaemia
    • cryptogenic neurological illness, in particular epilepsy and ataxia (leading to the term `gluten ataxia')
    • non-Hodgkin's lymphoma in < 1% patients
    • NB. arthritis is a rare association although rheumatoid arthritis has increased prevalence

diagnosis

  • requires a high index of suspicion
  • NB. trial of gluten-free diet has NO place in diagnosis or Rx - gluten-free diet must be lifelong

antibody testing

  • if low index of suspicion but alone, these are not diagnostic
  • “coeliac disease serology”
    • deamidated gliadin IgG
      • now used instead of endomysial (EMA) antibodies
    • h-Transglutaminase (h-TTG) IgA recomb Ab
      • now used instead of IgA-TTG
      • false negatives may occur if:
        • patient on a gluten-free diet
        • patient has IgA deficiency - 3-5% of patients with coeliac disease
        • the total serum IgA concentration should therefore also be measured at the same time as antibody tests if this is suspected
  • useful in checking dietary compliance

small bowel biopsy

  • now taken from distal duodenum rather than jejunum
  • essential in all patients
  • repeat after 6 months on gluten free diet
  • if coeliac disease is a possibility, duodenal biopsies should be taken in patients undergoing endoscopy for unexplained iron deficiency anaemia.

treatment

  • lifelong gluten-free diet
    • gluten refers to two families of proteins (glutenens and gliadins) found in mature grains such as wheat, barley and rye, and thus in foods such as bread, cakes and pasta
    • gluten is sticky, stretchable, elastic, and can act as a thickening agent
    • gluten-free diets can cause deficiency in iron, folate, thiamine, calcium, vitamin B12, and zinc

References

1)
NEJM 2011 364:8 p783-4
coeliac.txt · Last modified: 2014/09/09 23:02 (external edit)