Coeliac disease
Exam Tips
- Always test while the patient is still consuming gluten; starting a gluten-free diet first can produce false-negative serology/biopsy.
- A classic OSCE trap is isolated iron-deficiency anaemia with minimal GI symptoms: coeliac disease can present extra-intestinally.
- Positive tTG-IgA with low total IgA needs IgG-based serology, not dismissal of the diagnosis.
- Symptom improvement does not equal mucosal healing; ongoing follow-up is required.
- Differentiate non-responsive coeliac disease (usually gluten contamination) from refractory coeliac disease (persistent villous atrophy despite strict diet for at least 12 months).
- Type 2 refractory disease is a pre-lymphomatous state with markedly worse prognosis.
Definition
Coeliac disease is a chronic, immune-mediated systemic disorder triggered by dietary gluten (wheat, barley and rye) in genetically susceptible people, causing inflammatory small-bowel enteropathy. It is defined by a combination of compatible serology (coeliac-specific antibodies), characteristic duodenal histology (villous atrophy, crypt hyperplasia and increased intraepithelial lymphocytes), and clinical response to a strict gluten-free diet.
Pathophysiology
In people carrying HLA-DQ2 and/or HLA-DQ8, gluten-derived gliadin peptides are deamidated by tissue transglutaminase (tTG), increasing peptide binding to antigen-presenting cells and activating CD4+ T-cell responses in the lamina propria. This drives cytokine-mediated mucosal inflammation, crypt hyperplasia and villous atrophy, reducing absorptive surface area and causing malabsorption (iron, folate, vitamin B12, calcium and vitamin D deficiencies). Autoantibody formation (anti-tTG IgA, endomysial antibodies) reflects the adaptive immune process; epithelial injury is amplified by intraepithelial lymphocyte activation. Proximal small bowel is often most affected first, which explains early iron deficiency. See Figure: Marsh-Oberhuber histological spectrum (intraepithelial lymphocytosis to subtotal/total villous atrophy).
Risk Factors
- First-degree relative with coeliac disease (lifetime risk approximately 10-15%; higher in affected siblings)
- HLA-DQ2 or HLA-DQ8 haplotypes
- Personal autoimmune disease (especially type 1 diabetes mellitus, autoimmune thyroid disease)
- Female sex
- Any age can be affected, with peaks in early childhood (post-weaning) and early adulthood
- Possible environmental contributors: gastrointestinal infections, higher gluten exposure, microbiome perturbation
Clinical Features
Symptoms
- Chronic or intermittent diarrhoea
- Bloating, abdominal discomfort, excess flatus
- Weight loss or difficulty maintaining weight
- Fatigue (often from iron deficiency anaemia)
- Nausea or dyspepsia
- Constipation (less typical but possible)
- Aphthous mouth ulcers
- Symptoms of micronutrient deficiency (e. g, paraesthesia from B12 deficiency)
- Reduced fertility, recurrent miscarriage, menstrual disturbance
- Pruritic blistering rash suggestive of dermatitis herpetiformis
Signs
- Pallor (iron/folate/B12 deficiency anaemia)
- Weight loss or low BMI
- Abdominal distension
- Glossitis or angular cheilitis
- Bruising or osteomalacic bone tenderness in severe malabsorption
- Peripheral neuropathy or gait ataxia in extra-intestinal disease
- Dermatitis herpetiformis on extensor surfaces and buttocks
- In children: faltering growth and delayed puberty
Investigations
Management
Lifestyle Modifications
- Lifelong strict gluten-free diet with specialist dietitian input (avoid wheat, barley, rye; assess oats for contamination/tolerance)
- Do not start a gluten-free diet until diagnostic testing is completed unless specialist advice says otherwise
- Education on hidden gluten, cross-contamination, label reading, and eating-out risk reduction
- Screen and correct nutritional deficiencies; monitor weight, symptoms and psychosocial impact
- Vaccination review if hyposplenism/asplenia suspected (pneumococcal, meningococcal, Haemophilus influenzae type b as appropriate)
- Structured follow-up for adherence, persistent symptoms and risk of non-responsive/refractory disease
Pharmacological Treatment
Micronutrient replacement
- Ferrous sulfate 200 mg orally two to three times daily (each 200 mg tablet contains approximately 65 mg elemental iron)
- Folic acid 5 mg orally once daily (typically for around 4 months, then reassess)
- Hydroxocobalamin 1 mg intramuscularly on alternate days until improvement if symptomatic deficiency, then maintenance 1 mg every 2-3 months
- Colecalciferol loading regimens (e. g, total about 300,000 units over 6-10 weeks) followed by maintenance 800-2000 units daily if needed
- Calcium carbonate providing 1-1.2 g elemental calcium daily if intake is inadequate
Replace according to documented deficiency and local protocol; investigate persistent deficiency despite treatment for ongoing gluten exposure or alternative pathology.
Dermatitis herpetiformis symptom control
- Dapsone initially 25-50 mg once daily, titrated to lowest effective dose (commonly 50-100 mg daily)
Specialist initiation/monitoring recommended. Check G6PD before treatment; monitor FBC and LFTs due to risk of haemolysis, methaemoglobinaemia, agranulocytosis and hepatotoxicity. Use caution in significant cardiorespiratory disease and anaemia.
Refractory coeliac disease (specialist care)
- Prednisolone (for example 20-40 mg daily then taper according to response)
- Budesonide modified-release (specialist-selected in some centres)
- Azathioprine adjunct in selected type 1 refractory disease
Reserved for confirmed refractory disease after exclusion of ongoing gluten exposure and other causes; requires gastroenterology oversight and malignancy surveillance.
Complications
- Iron, folate and vitamin B12 deficiency anaemia
- Osteopenia/osteoporosis and fragility fractures
- Faltering growth and delayed puberty in children
- Dermatitis herpetiformis
- Neurological complications (peripheral neuropathy, gluten ataxia)
- Reproductive complications (subfertility, miscarriage, fetal growth restriction, preterm birth)
- Functional hyposplenism/asplenia with increased risk of severe infection by encapsulated organisms
- Non-responsive coeliac disease and refractory coeliac disease (type 1 and type 2)
- Ulcerative jejunitis (rare)
- Malignancy risk increase, particularly enteropathy-associated T-cell lymphoma and small bowel adenocarcinoma
Prognosis
Most patients improve clinically within weeks to months of a strict gluten-free diet, but histological recovery may lag behind symptoms and may remain incomplete in some adults despite good adherence. Children generally heal faster than adults. Persistent symptoms after 6-12 months are usually due to ongoing gluten exposure, while true refractory coeliac disease is uncommon; type 2 refractory disease carries poorer survival and a high risk of enteropathy-associated T-cell lymphoma.
Sources & References
🏥BMJ Best Practice(5)
✅NICE Guidelines(1)
- Coeliac disease[overview]
📖Textbook References(20)
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1246, 1247)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1806)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1247)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1323)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 694)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 705, 706)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 682, 683)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 686)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 652)[context]
- Guyton and Hall Textbook of Medical Physiology (John E. Hall, Michael E. Hall) (Z-Library).pdf(pp. 829)[context]
- Guyton and Hall Textbook of Medical Physiology (John E. Hall, Michael E. Hall) (Z-Library).pdf(pp. 830, 831)[context]
- Guyton and Hall Textbook of Medical Physiology (John E. Hall, Michael E. Hall) (Z-Library).pdf(pp. 829)[context]
- Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 357)[context]
- [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 343)[context]
- [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 874)[context]
- [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 261)[context]
- [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 343)[context]
- [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 342, 343)[context]
- [Williams, Bailey and Love's Short Practice of Surgery] Norman Williams, Christopher Bulstrode, P Ronan O'Connell - Bailey & Love's Short Practice of Surgery 26E (2013, CRC Press) - libgen.li.pdf(pp. 1194)[context]
- [Williams, Bailey and Love's Short Practice of Surgery] Norman Williams, Christopher Bulstrode, P Ronan O'Connell - Bailey & Love's Short Practice of Surgery 26E (2013, CRC Press) - libgen.li.pdf(pp. 1194)[context]