A 42-year-old woman presents with chronic diarrhoea, weight loss, and abdominal bloating for 8 months. Small bowel biopsy shows villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes. Anti-tissue transglutaminase IgA is markedly elevated. She is started on a gluten-free diet. After 12 months, she continues to have diarrhoea despite strict dietary compliance. What is the most important consideration?

• A Non-compliance with gluten-free diet as sole explanation
• B Concurrent lactose intolerance as the only cause
• C Microscopic colitis as a separate diagnosis
• D Refractory coeliac disease or complication such as enteropathy-associated T-cell lymphoma ✓

Explanation

Persistent symptoms despite strict gluten-free diet for ≥12 months should raise suspicion for refractory coeliac disease (RCD), which is classified as Type I (normal IEL phenotype) or Type II (aberrant clonal IEL population), the latter carrying high risk for enteropathy-associated T-cell lymphoma (EATL). Evaluation requires repeat duodenal biopsy, immunophenotyping of IELs by flow cytometry, PET-CT, and gastroenterology referral. While dietary non-compliance and small intestinal bacterial overgrowth are common causes of non-response, EATL must be excluded in persistent refractory cases.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.