- Coeliac disease is an autoimmune disorder of the small bowel
- Occurs in genetically predisposed individuals
- Affects about 1% of the population
- Can present in either childhood or adulthood
- It is caused by a reaction to gliadin, a gluten protein found in
wheat
- Long term it leads to an increased risk of both adenocarcinoma and
lymphoma
- Coeliac disease has been linked with a number of conditions
including:
- IgA deficiency - present in 2% of patients with coeliac disease
- Dermatitis hepatiformis
- Other autoimmune diseases including autoimmune thyroiditis and
primary biliary cirrhosis
- Undefined neurological disorders and epilepsy
Pathophysiology
- The vast majority of coeliac patients have one of two types of HLA
DQ
- A gene that is part of the MHC class II antigen-presenting receptor
- There are 7 HLA DQ variants (DQ2 and D4 through 9)
- Two of these variants—DQ2 and DQ8—are associated with coeliac
disease
- The gene is located on the short arm of chromosome 6
- The receptors formed by these genes bind to gliadin peptides
- Coeliac disease shows incomplete penetrance
Clinical features
- Many patients are asymptomatic
- In those with symptoms they include
- Diarrhoea
- Weight loss
- Abdominal pain
- Fatigue
- There may also be features of malabsorption
- Anaemia can develop due to iron, folic acid or B12 deficiency
- Calcium and vitamin D malabsorption may cause osteopenia
- A mild coagulopathy may develop due to vitamin K malabsorption
Diagnosis
- Several tests that can be used to assist in diagnosis
- Many tests are only useful if patient is still on a normal diet
containing gluten
- Endoscopy with duodenal biopsies is the gold standard
- Multiple biopsies (4-8) are required
- Most patients with coeliac disease have a small bowel that appears
normal on endoscopy
- Endoscopy may show scalloping of the small bowel folds and a mosaic
pattern to the mucosa
- Serological tests have a high sensitivity and specificity
- Serological tests include
- IgA Antibodies against reticulin (ARA) or gliadin (AGA)
- IgA antibodies against endomysium (EMA) or tissue transglutaminase
(TTG)
Pathology
- The pathological changes of coeliac disease in the small bowel are
categorized by the Marsh classification
- Marsh stage 0 - normal mucosa
- Marsh stage 1 - increased number of intra-epithelial lymphocytes,
usually exceeding 20 per 100 enterocytes
- Marsh stage 2 - proliferation of the crypts of Lieberkuhn
- Marsh stage 3 - partial or complete villous atrophy
- Marsh stage 4 - hypoplasia of the small bowel architecture
- The changes classically improve or reverse after gluten is removed
from the diet
- Many guidelines recommend a repeat biopsy several (4–6) months after
commencement of gluten exclusion
Treatment
- The only effective treatment is a life-long gluten-free diet
- No medication exists that will prevent damage when gluten is present
- Adherence to the diet allows the intestines to heal
- Leads to the resolution of all symptoms in the vast majority of
cases
- A tiny minority of patients suffer from refractory disease
- Steroids or immunosuppressants (such as azathioprine) may be
considered in this scenario
Bibliography
Duggan J M. Coeliac disease: the great imitator.
Med J Aust 2004; 180: 524-526.
Goddard C J, Gillett H R. Complications of coeliac disease:
are all patients at risk? Postgrad Med J 2006; 82:
705-712.
Green P H. Jabri B. Coeliac disease. Lancet
2003; 362: 383-391.
van Heel D A, West J. Recent advances in coeliac disease.
Gut 2006; 55: 1037-1046. |