A 50-year-old man has a 6-month history of diarrhoea, weight loss, and iron deficiency anaemia. Duodenal biopsy on upper GI endoscopy shows villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes. IgA anti-tissue transglutaminase (tTG) antibodies are elevated. He is started on a gluten-free diet. After 12 months, diarrhoea persists. The MOST important next step to diagnose refractory coeliac disease is:
- A Repeat duodenal biopsy and flow cytometry of intraepithelial lymphocytes (IELs) for aberrant CD3+CD8- T-cell phenotype ✓
- B Repeat anti-tTG antibodies to assess compliance
- C Start immunosuppression empirically with budesonide
- D Test for HLA-DQ2/DQ8 status
Explanation
Refractory coeliac disease (RCD) is defined as persistent or recurrent villous atrophy and malabsorptive symptoms despite strict adherence to a gluten-free diet for >12 months, after excluding other causes and inadvertent gluten exposure. Distinguishing RCD type I (normal IEL phenotype) from type II (aberrant clonal IEL phenotype: surface CD3+, cytoplasmic CD3+, but CD8-) is critical because type II is a premalignant condition (risk of enteropathy-associated T-cell lymphoma, EATL) requiring specialist management. Flow cytometry on IEL is the key diagnostic test. Anti-tTG normalisation confirms dietary compliance; if tTG remains elevated, dietary non-adherence is more likely than true RCD.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.