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.
Epidemiology
largely an inherited disorder of Caucasians
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.
overall seroprevalence of coeliac disease is 1.4%, both globally and in Australia 1)
1st degree relatives of index case screened for HLA‐DQ2/8/7 and serum anti‐tissue transglutaminase (tTG) IgA and anti‐deamidated gliadin peptide (DGP) IgG:
86% had susceptibility haplotypes
11% of child 1st degree relatives had biopsy‐confirmed disease 2)
1.4% of adult 1st degree relatives had biopsy‐confirmed disease
pathophysiology
Patients with coeliac disease typically have the HLA-B8, DR3, DQ2 or DQ8 haplotype
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.
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 study3)
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.
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