Coeliac disease — diagnosis, mechanism and management viva

Interpretation

The examiner presents a duodenal biopsy showing flattened, blunt villi with hyperplastic crypts and a marked intraepithelial lymphocytosis, and a positive anti-tissue transglutaminase IgA at 8 times the upper limit of normal. "What is the diagnosis, what is the underlying mechanism, and how would you manage this patient?"

• Diagnosis: coeliac disease, Marsh 3c (subtotal villous atrophy with crypt hyperplasia and raised intraepithelial lymphocytes). The serology and histology are concordant.^[1][2]
• Diagnosis requires the patient to be on a gluten-containing diet — the work-up is destroyed by a premature gluten-free diet.

Key points

The examiner will probe each of these; be ready to defend them at viva depth:

1. Definition and spectrum — immune-mediated enteropathy of the proximal small bowel, HLA-DQ2/DQ8, gluten-triggered; classical, atypical/extraintestinal, silent, latent, potential, seronegative, refractory subtypes.
2. Mechanism (the molecular cascade) — gliadin resists digestion, reaches the lamina propria, is deamidated by tTG2, and is presented on HLA-DQ2/DQ8 to CD4+ T cells; Th1 (IFN-gamma) inflammation drives villous atrophy and crypt hyperplasia; B cells produce anti-tTG and anti-EMA antibodies (the diagnostic markers); IL-15 drives intraepithelial lymphocytes — the substrate of refractory type 2 and EATL.
3. Serology hierarchy — anti-tTG IgA most sensitive (~90-95%); anti-endomysial IgA most specific (~97-99%); total IgA always (2-3% have selective IgA deficiency); anti-DGP IgG if IgA-deficient; HLA-DQ2/DQ8 is a rule-OUT test (NPV over 99%).^[1][6]
4. Histology — Marsh 0 to 3c (and 4); the diagnostic flat lesion is Marsh 3 = villous atrophy + crypt hyperplasia + IEL over 30 per 100 enterocytes. Take at least 6 biopsies including the bulb.
5. Treatment — strict lifelong gluten-free diet (under 20 ppm; exclude wheat, barley, rye); correct deficiencies (ferrous sulphate 200 mg, folic acid 5 mg, hydroxocobalamin 1 mg IM, calcium + vitamin D); vaccinate against encapsulated organisms (functional hyposplenism); structured annual review.
6. Dermatitis herpetiformis — itchy symmetric vesicles on extensors; granular IgA at the dermal papillae on perilesional skin biopsy; treat with gluten-free diet + dapsone (check G6PD first, start 50 mg daily, titrate to 50-150 mg).
7. Complications — iron-deficiency anaemia, osteoporosis, infertility/miscarriage, functional hyposplenism, EATL (T-cell lymphoma from refractory type 2), small-bowel adenocarcinoma. Strict gluten-free diet substantially reduces malignancy risk.
8. Pitfalls — never start a gluten-free diet before diagnosis; never miss IgA deficiency; never label any villous atrophy as coeliac (consider olmesartan, tropical sprue, CVID, giardiasis, Crohn's, lymphoma).

References3ShowHide

1. [1]Rubio-Tapia A, Hill ID, Kelly CP, et al. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol, 2013.PMID 23609613
2. [2]Lebwohl B, Sanders DS, Green PHR. Coeliac disease. Lancet, 2018.PMID 28760445
3. [6]Husby S, Koletzko S, Korponay-Szabó IR, et al. European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020. Gastroenterology, 2020.PMID 31568151