Background Information
Definition
Coeliac disease is a chronic immune-mediated systemic disorder which occurs in genetically predisposed people and is triggered by exposure to dietary gluten.
Gluten is the major protein component of wheat, barley, and rye.
Aetiology
Coeliac disease develops as a result of a complex immune response to the ingestion of gluten. The exact cause is not fully understood.
Genetic predisposition plays a major role:
- Coeliac disease is strongly associated with HLA-DQ2 and/or HLA-DQ8 (seen >90% patients with coeliac disease vs 40-50% of the general population)
- The lifetime risk of developing coeliac disease is 10–15% in people with a family history
- Concordance rate in monozygotic twins is high (50–80%)
Coeliac disease often coexists with other autoimmune conditions:
- Type 1 diabetes
- Autoimmune thyroid disease (Graves’ disease and Hashimoto’s thyroiditis)
- Addison’s disease
- Pernicious anaemia
- Rheumatoid arthritis, SLESystemic lupus erythematosus, Sjogren’s syndrome
- Autoimmune hepatitis, PBCPrimary biliary cholangitis
It is worth noting that the following factors do NOT reduce the risk of developing coeliac disease:
- Breastfeeding (any amount / any duration / exclusive)
- Introduction of gluten into an infant’s diet at 4-12 m/o (it may only lead to earlier seroconversion and coeliac disease)
Clinical Manifestation
Bimodal age of onset:
- <2 y/o (after weaning and followed by exposure to gluten)
- 20-30 y/o
| GI manifestation | Patients typically present with chronic, recurring GI symptoms that typically manifest hours to days after gluten ingestion
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| Extra-GI manifestation |
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| Complications |
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The most common deficiencies in coeliac disease are iron (most common overall), vitamin D and calcium. This is because these nutrients are primarily absorbed in the duodenum and proximal jejunum, which are the segments of the small intestine most affected in coeliac disease.
Folate (absorbed in the jejunum) and vitamin B12 (absorbed in the terminal ileum) deficiencies may also occur but are less common, in keeping with their sites of absorption.
Diagnosis
Indications for Testing
Apart from those with suspected coeliac disease (based on clinical features NICE specifically outlined:
), NICE also recommends coeliac testing in the following patients:
- 1st degree relative with coeliac disease
- Suspected IBSIrritable bowel syndrome in adults
- Type 1 diabetes or autoimmune thyroid disease (perform coeliac screening at diagnosis)
- Unexplained iron, vitamin B12 or folate deficiency
NICE also recommends considering coeliac testing in individuals with ANY of the following:
- Metabolic bone disorder (reduced bone mineral density or osteomalacia)
- Unexplained neurological symptoms (particularly peripheral neuropathy or ataxia)
- Unexplained subfertility or recurrent miscarriage
- Persistently raised liver enzymes with an unknown cause
- Dental enamel defects
- Down syndrome
- Turner syndrome
Coeliac Testing and Diagnosis
Approach:
- Initial screening test: serological testing
- If serological testing +ve → refer all patients for endoscopic intestinal biopsy (definitive test)
Serological Testing
The patient must follow a gluten-containing diet (>1 meal every day) for at least 6 weeks before testing
- Explain that the test is only accurate if a gluten-containing diet is eaten during the process, otherwise may result in false negative
- If the patient has already restricted their gluten intake or excluded gluten, advise re-introducing gluten into their diet before testing
Choice of serology testing:
- 1st line: IgA tTGTissue transglutaminase + total IgA
- ↑ IgA tTG with a normal total IgA count is highly suggestive of coeliac disease
- 2nd line
- If IgA tTGTissue transglutaminase is weakly +ve (but no IgA deficiency) → test for IgA EMAEndomysial antibodies
- If there is IgA deficiency (indicated by low total IgA) → test for IgG tTGTissue transglutaminase or IgG DGPDeamidated gliadin peptide
IgA deficiency is the most common primary antibody deficiency in the UK, and is often asymptomatic in most patients.
Coeliac patients with IgA deficiency can result in false negatives in IgA tTG, therefore IgA tTG should always be tested together with total IgA levels to exclude underlying IgA deficiency.
Do not use HLA DQ2/DQ8 testing in non-specialist settings. It needs careful interpretation, as HLA DQ2/DQ8 haplotypes are seen in over 90% of people with coeliac disease, but also seen in 40–50% of the general population. This makes it a good exclusion test (high sensitivity but poor specificity)
Definitive Testing – Biopsy
Endoscopic duodenal biopsy is the definitive test for coeliac disease. It is necessary in ALL patients with +ve serology to confirm the diagnosis
Characteristic histological findings:
- Villous atrophy
- Crypt hyperplasia
- Intraepithelial lymphocytic infiltration
A biopsy is taken from the duodenum in coeliac disease, because coeliac disease primarily affects the proximal small intestine, especially the duodenum and proximal jejunum.
Other Tests
Blood test findings in coeliac disease:
| Functional hyposplenism → |
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| Malabsorption → |
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Management
Definitive Management
Long-term gluten-free diet – the only effective treatment
- Refer to a dietitian to educate the patient about dietary changes
- Advise on the importance of reading food labels to check if products are suitable. Manufacturers of packaged foods are required by law to list on the product’s label any product containing gluten that is used as an ingredient
Key gluten-containing foods (i.e. those based on wheat, barley and rye – not an exhaustive list):
- Breast
- Cereals
- Flour
- Pasta
- Cakes, pastries
- Biscuits
- Beer / lager / ale / malt-based drinks
Alternative starch sources that do NOT contain gluten (not an exhaustive list):
- Rice
- Potatoes
- Corn (maize)
- Fruit and vegetables, dairy (e.g. milk, cheese), and protein foods (e.g. meat, eggs, fish)
- Buckwheat (despite the name, it is gluten-free)
Monitoring
Consider annual blood monitoring:
| Test | Purpose |
|---|---|
| Coeliac serology |
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| FBC and ferritin |
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| TFT |
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| LFT |
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| Calcium, vitamin D, vitamin B12, folate |
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Complication Management
| Malabsorption problems |
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| Hyposplenism | Offer the following vaccinations:
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| Dermatitis herpetiformis |
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References
NICE guideline Coeliac disease: recognition, assessment and management
NICE CKS Coeliac disease