Coeliac disease — diagnosis, investigation and management

a) Clinical suspicion and diagnostic principle (2 marks)

The combination of chronic diarrhoea/bloating, weight loss, aphthous ulcers, iron + folate deficiency, hypocalcaemia and transaminitis is highly suggestive of coeliac disease — a chronic immune-mediated enteropathy triggered by gluten in HLA-DQ2/DQ8-positive individuals.^[1][2]

The diagnostic principle is that diagnosis must be made on a gluten-containing diet — the patient must NOT start a gluten-free diet first, because it sero-negatives the work-up and may normalise the biopsy, requiring an unpleasant 6-8 week gluten challenge to recover.

b) Investigations (3 marks)

First-line serology:

• Anti-tissue transglutaminase IgA (anti-tTG IgA) — most sensitive (~90-95%), quantitative.
• Anti-endomysial IgA (EMA) — most specific (~97-99%), confirmatory.
• TOTAL serum IgA — ALWAYS sent, because 2-3% of coeliac patients have selective IgA deficiency, which makes BOTH anti-tTG and EMA falsely negative. If IgA is low, use anti-DGP IgG instead.

Confirmatory histology (gold standard):

• OGD with at least 6 duodenal biopsies — 4 from the distal duodenum AND 2 from the duodenal bulb (disease may be patchy; bulb biopsies reduce the false-negative rate).
• Expected: Marsh 3 lesion — villous atrophy + crypt hyperplasia + intraepithelial lymphocytes over 30 per 100 enterocytes.

Adjunctive tests:

• HLA-DQ2/DQ8 typing — high negative predictive value (over 99%); a NEGATIVE result excludes coeliac. Useful if serology/biopsy discordant, patient already gluten-free, or screening first-degree relatives.
• DEXA scan at diagnosis (osteoporosis risk).
• Baseline bloods — FBC, ferritin, folate, B12, calcium, vitamin D, LFTs, TSH, coagulation.

c) Management — definitive and stepwise (3 marks)

1. Strict lifelong gluten-free diet — exclude wheat (gliadin), barley (hordein), rye (secalin), and triticale; oats tolerated if pure/uncontaminated. Threshold under 20 ppm (Codex). Refer to a dietitian and Coeliac Society; teach label-reading and cross-contamination avoidance.
2. Correct deficiencies: oral ferrous sulphate 200 mg one to three times daily until ferritin replete; folic acid 5 mg daily for 4 months; calcium 1000-1200 mg + colecalciferol 800-1000 IU daily; hydroxocobalamin 1 mg IM if B12-deficient.
3. Hyposplenism prevention — vaccinate against pneumococcus, Haemophilus influenzae type b, meningococcus, and influenza.
4. Structured annual review — symptoms, BMI, adherence; FBC, ferritin, folate, B12, calcium, vitamin D, LFTs, TSH, anti-tTG IgA titre (should normalise within 12-24 months).
5. Treat osteoporosis if DEXA-positive (bisphosphonate, e.g. alendronic acid 70 mg once weekly).

d) Complications to discuss (2 marks)

• Nutritional: iron-deficiency anaemia, osteoporosis/osteomalacia, fat-soluble vitamin deficiency.
• Reproductive: infertility, recurrent miscarriage, intrauterine growth restriction.
• Functional hyposplenism: encapsulated-organism sepsis (Howell-Jolly bodies).
• Malignant: enteropathy-associated T-cell lymphoma (EATL, from refractory coeliac type 2), small-bowel adenocarcinoma, oesophageal/pharyngeal carcinoma — risk substantially reduced by a strict gluten-free diet.^[2]
• Refractory coeliac disease: persistent villous atrophy despite a strict diet for over 12 months — type 1 (budesonide-responsive) vs type 2 (clonal IELs, pre-EATL, poor prognosis).^[6]

Prognosis — with strict adherence, prognosis is excellent: symptoms resolve in weeks, serology normalises within months, and mucosa heals within 1-2 years.