Coeliac Disease
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Direct answer
Total IgA must accompany every tissue transglutaminase-IgA you send, because selective IgA deficiency (present in roughly one in 40 coeliac patients) silently renders the usual test falsely negative and forces the switch to tTG-IgG or deamidated gliadin peptide-IgG. Adult diagnosis rests on positive serology plus duodenal histology — Marsh 3 villous atrophy with crypt hyperplasia and over 25–30 intraepithelial lymphocytes per 100 enterocytes — on biopsies taken from both the bulb and distal duodenum while the patient is still on gluten. Treatment is a lifelong gluten-free diet with serological follow-up (tTG falling towards normal by 6–12 months), and persistence of symptoms or serology beyond a year triggers the non-responsive coeliac workup: dietitian-verified gluten exposure first, then refractory coeliac disease and its complications. In children, a no-biopsy pathway exists for very high titre serology; in adults it does not.
What you must remember
- Serology pair: tTG-IgA (sensitivity around 90–95 per cent on gluten) plus total serum IgA; if IgA is low, use tTG-IgG or DGP-IgG; anti-endomysial antibody is the highly specific confirmatory test.
- Biopsy discipline: a minimum of four distal duodenal biopsies plus at least one from the bulb (where villous atrophy is patchy and a duodenal fold pathology is common); the patient must be eating gluten — roughly three slices of bread daily for the duration of a 2–6 week pre-biopsy gluten challenge.
- Marsh-Oberhuber grading: Marsh 1 isolated intraepithelial lymphocytosis, Marsh 2 with crypt hyperplasia, Marsh 3a/3b/3c partial, subtotal and total villous atrophy; Marsh 3 defines the diagnostic lesion in the right serological context.
- HLA contribution: DQ2 in about 90 per cent and DQ8 in most of the rest; a negative DQ2/DQ8 effectively excludes coeliac disease — useful in ambiguous cases (already gluten-free, immunodeficiency, discordant serology and histology) rather than as a frontline test.
- Diet milestones: symptomatic improvement within weeks, serology falling substantially by 6 months and normalising by 12–24 months; persistent titres at 12 months most often mean ongoing gluten ingestion (cross-contamination, hidden gluten in Indian packaged foods and condiments is notorious).
- Non-responsive coeliac disease: first exclude inadvertent gluten (60 per cent or more of cases), then reconsider — microscopic colitis, small intestinal bacterial overgrowth, lactose intolerance, pancreatic insufficiency and irritable bowel; only then refractory coeliac disease.
- Refractory coeliac disease: type 1 (normal intraepithelial lymphocyte phenotype) has a comparatively benign course; type 2 (aberrant clonal intraepithelial lymphocytes on flow cytometry, loss of surface CD3/CD8) behaves as a low-grade lymphoma, complicated by ulcerative jejunitis and enteropathy-associated T-cell lymphoma, treated with immunosuppression or chemotherapy and monitored aggressively.
- Associations to recall: type 1 diabetes, autoimmune thyroid disease, IgA deficiency, Down and Turner syndromes; dermatitis herpetiformis presents with IgA deposition at the dermal papillae and warrants duodenal biopsies regardless of serology, with dapsone for the rash and diet for the gut.
Working through the diagnostic pathway
A 34-year-old woman has chronic diarrhoea, iron-deficiency anaemia and a tTG-IgA of 10 times the upper limit with normal total IgA. Distal and bulb biopsies show Marsh 3b villous atrophy. Diagnosis confirmed, gluten-free diet begun with a dietitian, and tTG rechecked at 6 and 12 months. At 14 months she remains anaemic with a persistently raised tTG: step one is a structured dietitian audit for hidden gluten (the commonest answer); step two, if truly gluten-free, is colonoscopy with random biopsies for microscopic colitis and consideration of capsule endoscopy to inspect the small bowel for ulcerative jejunitis; step three, repeat biopsies with intraepithelial lymphocyte phenotyping by flow cytometry to separate refractory type 1 from type 2. This is the sequence that converts a straightforward diagnosis question into the DM-level reasoning examiners actually reward — and the anaemia thread ties it to Indian outpatient reality where coeliac disease clusters in the wheat-belt north.
Where students slip
Two errors dominate. First, diagnosing coeliac disease on serology alone in adults — the no-biopsy pathway is a paediatric construct for very high titre tTG with confirmatory EMA in symptomatic children. Second, labelling every Marsh 3 lesion coeliac: tropical sprue (the classic Indian confounder, with folate and B12 deficiency both low and ileal involvement), giardiasis, bacterial overgrowth, NSAID enteropathy and HIV enteropathy all produce villous atrophy with intraepithelial lymphocytosis; the serology, the distribution and the response to a gluten-free diet separate them.
Frequently asked questions
Why measure total IgA with tTG-IgA?
Selective IgA deficiency is many-fold more common in coeliac disease and makes IgA-based serology falsely negative; a low IgA mandates tTG-IgG or DGP-IgG testing.
How many biopsies are needed to exclude coeliac disease?
At least four from the distal duodenum plus one or more from the bulb, taken while the patient is on a gluten-containing diet.
What is the commonest cause of non-responsive coeliac disease?
Ongoing gluten ingestion — usually inadvertent cross-contamination — accounting for well over half of persistent cases before refractory disease is considered.
How do refractory coeliac disease types 1 and 2 differ?
Type 1 retains a normal intraepithelial lymphocyte phenotype and benign behaviour; type 2 shows clonal aberrant T cells and carries a high risk of ulcerative jejunitis and enteropathy-associated T-cell lymphoma.
Which patients need a gluten challenge before testing?
Those already on a gluten-free diet without prior diagnostic workup: roughly 2–6 weeks of daily gluten with serology and biopsies at the end, longer if serology remains negative.