Gluten Catastrophe: A Fatal Case of Refractory Celiac Disease Type 2

ABSTRACT Celiac disease (CeD) is an immune-mediated enteropathy triggered by gluten, while refractory CeD (RCD) represents a severe form with persistent villous atrophy despite adherence to a gluten-free diet. RCD type 2 (RCD2) is characterized by aberrant clonal intraepithelial lymphocytes and carries a poor prognosis. We report a fatal case of RCD2 in a 55-year-old man who initially presented with abdominal pain, weight loss, and chronic diarrhea. Despite negative celiac serologies, duodenal biopsies demonstrated villous atrophy, and human leukocyte antigen (HLA)-DQ2 positivity supported CeD. He developed steroid-refractory disease, with immunophenotypic and molecular findings consistent with RCD2, complicated by concomitant microscopic colitis and severe malnutrition. Extensive surveillance showed no evidence of lymphoma. He later presented with septic shock following Mycobacterium avium complex pneumonia and experienced progressive diarrhea and nutritional decline despite aggressive management. He ultimately elected for palliative care and died. This case highlights the diagnostic challenges, morbidity, and high mortality associated with RCD2.