A 28-year-old woman presents with chronic diarrhea, weight loss, and anemia. Duodenal biopsy shows villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Anti-tissue transglutaminase IgA antibody is strongly positive. She is started on a gluten-free diet (GFD). After 12 months on strict GFD, she has persistent symptoms and ongoing villous atrophy on repeat biopsy. No dietary indiscretions found. What is the next diagnostic consideration?
- A Increase corticosteroid suppression of inflammation
- B Non-celiac gluten sensitivity — switch to low FODMAP diet
- C Refractory celiac disease type II (aberrant intraepithelial T-cell clones) — evaluate for enteropathy-associated T-cell lymphoma (EATL) ✓
- D Common variable immunodeficiency (CVID) mimicking celiac disease
Explanation
Refractory celiac disease (RCD) is defined as persistent malabsorption with villous atrophy despite strict GFD for >12 months, in the absence of other explanations. RCD Type II is characterized by a clonal population of aberrant intraepithelial lymphocytes lacking surface CD3/CD8 but expressing cytoplasmic CD3 — these represent a pre-lymphomatous condition with high risk (~50%) of progressing to enteropathy-associated T-cell lymphoma (EATL). Flow cytometry of duodenal biopsies and TCR gene rearrangement studies are essential. Steroids and cladribine are treatment options for RCD II but prognosis is poor. Early diagnosis is critical for surveillance.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.