Refractory coeliac disease: a window between coeliac disease and enteropathy associated T cell lymphoma

The treatment of coeliac disease (CD) is straightforward and simple: life-long adherence to a gluten-free diet. However, in a small subgroup of patients, the clinical and histological abnormalities persist or recur. This non-responsiveness leaves a poorly understood syndrome known as refractory coeliac disease (RCD). A specific definition of RCD is lacking in the literature. We speculate that RCD may appear in a subgroup of coeliacs with persisting histologic abnormalities. In all patients screened for RCD we look for DQ2 and DQ8. In non-DQ2/DQ8 patients we reconsider the diagnosis of CD and of auto-immune enteropathy. Most of the patients referred to us because of suspicion of RCD are affected by other diseases. Probably the commonest cause of non-responsiveness is continued gluten intake. Exocrine pancreas insufficiency, hyperthyroid disease, collagenous colitis are other common explanations. RCD and enteropathy-associated T cell lymphomas (EATL) can be distinguished by intra-epithelial lymphocyte phenotyping and TCR-gamma gene rearrangements. In RCD, an unexplained sustained stimulation of T cell cytotoxic activity is present. Immunosuppressive treatment might moderate this. Cyclosporine has been reported as a resounding success in case reports; however, our results were disappointing. We suggest azathioprine and steroids in RCD without aberrant T-lymphocytes in their mucosa. However, in RCD with aberrant T-lymphocytes we suggest chemotherapy. As the prognosis of EATLs is extremely poor the early detection of RCD with aberrant T cells is crucial.