Refractory Celiac Disease

A small subset of celiac disease (CD) patients becomes refractory to a gluten-free diet with persistent symptoms of malabsorption and intestinal villous atrophy. Diagnosis of this condition, defined as refractory celiac disease (RCD), is made after exclusion of other small bowel diseases with villous atrophy. RCD has been subdivided into two subgroups according to the normal (type 1 RCD [RCDI]) or abnormal phenotype of intraepithelial lymphocytes (IEL) (type II RCD [RCDII]). The latter condition, called clonal refractory celiac sprue, is considered a low-grade intraepithelial lymphoma and has a very poor prognosis, leading to intractable ulcerative duodenojejunitis, gastrointestinal and extraintestinal dissemination of the abnormal IEL, and to their frequent transformation into a high-grade lymphoma. We review here the clinical and pathological features of RCD as well as the recent pathogenic findings in RCDII, which offers a model to study how inflammation can drive T-cell lymphomagenesis.