A 45-year-old man has chronic diarrhoea with weight loss and macrocytic anaemia. Serum anti-TTG IgA is weakly positive. Duodenal biopsy shows subtotal villous atrophy (Marsh-Oberhuber grade 3b). He is started on a strict gluten-free diet but has persistent symptoms after 12 months. The MOST likely explanation is:
- A Refractory coeliac disease (RCD), particularly RCD type II with aberrant intraepithelial lymphocytes ✓
- B Microscopic colitis developing as a complication of coeliac disease
- C Small bowel bacterial overgrowth (SIBO) as co-existing complication
- D IgA deficiency causing false-negative baseline anti-TTG and inadequate response
Explanation
Refractory coeliac disease (RCD) is defined by persistent malabsorptive symptoms and villous atrophy despite strict GFD for >12 months, after exclusion of dietary gluten exposure and other causes. RCD type I has normal intraepithelial lymphocytes (IELs), while RCD type II has aberrant IELs (absent surface CD3/CD8 but positive intracytoplasmic CD3), representing a clonal T-cell expansion that carries risk of enteropathy-associated T-cell lymphoma (EATL). Microscopic colitis and SIBO can cause persistent symptoms but do not explain ongoing villous atrophy. IgA deficiency would cause false-negative anti-TTG but the biopsy is positive here.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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