Refractory celiac disease and lymphomagenesis

While most adult patients with celiac disease (CD) respond clinically and histologically to a gluten-free diet, a substantial proportion may have symptoms and/or histopathological duodenal lesions after 12–24 months of diet. In such clinical scenario, it is essential to discriminate between those who have “nonresponsive” CD, that is, conditions other than CD causing symptoms, and “refractory” CD, that is, persistent villous atrophy despite the diet. Additionally, causes of “false refractory” CD, such as diet nonadherence, must be excluded. Refractory CD is further classified into type I, with a good prognosis, and type II, which is considered a prelymphoma with poor prognosis. Refractory CD type II may complicate into enteropathy-associated T-cell lymphoma, a rare but highly lethal intestinal lymphoma. We herein critically discuss from a clinical perspective how to manage a patient with nonresponsive CD, refractory CD, and enteropathy-associated T-cell lymphoma, also highlighting the epidemiological, histopathological, pathogenetic, diagnostic, and treatment issues and controversies. © 2024 Elsevier Inc. All rights reserved.