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-l ong adherence to a gluten-free diet. However, in a small subgroup of patien ts, the clinical and histological abnormalities persist or recur. This non- responsiveness leaves a poorly understood syndrome known as refractory coel iac disease (RCD). A specific definition of RCD is lacking in the literatur e. We speculate that RCD may appear in a subgroup of coeliacs with persisti ng histologic abnormalities. In all patients screened for RCD we look for D Q2 and DQ8. In non-DQ2/DQ8 patients we reconsider the diagnosis of CD and o f auto-immune enteropathy. Most of the patients referred to us because of s uspicion of RCD are affected by other diseases. Probably the commonest caus e of non-responsiveness is continued gluten intake. Exocrine pancreas insuf ficiency, hyperthyroid disease, collagenous colitis are other common explan ations. RCD and enteropathy-associated T cell lymphomas (EATL) can be disti nguished by intra-epithelial lymphocyte phenotyping and TCR-gamma gene rear rangements. In RCD, an unexplained sustained stimulation of T cell cytotoxi c activity is present. Immunosuppressive treatment might moderate this. Cyc losporine has been reported as a resounding success in case reports; howeve r, our results were disappointing. We suggest azathioprine and steroids in RCD without aberrant T-lymphocytes in their mucosa. However, in RCD with ab errant T-lymphocytes we suggest chemotherapy. As the prognosis of EATLs is extremely poor the early detection of RCD with aberrant T cells is crucial.