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.
Mulder
C J
CJ
Depts. of Gastroenterology and Pathology, Rijnstate Hospital, P.O. Box 5555, 6800 TA Arnhem, The Netherlands.
Wahab
P J
PJ
Moshaver
B
B
Meijer
J W
JW
D016827:CD8 Antigens / Q000276:immunology; D002446:Celiac Disease / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000628:therapy; D000075202:Contraindications; D003937:Diagnosis, Differential; D004032:Diet; D019674:Genes, T-Cell Receptor beta / Q000235:genetics / Q000276:immunology; D005983:Glutens; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D007414:Intestinal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000628:therapy; D016399:Lymphoma, T-Cell / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000628:therapy; D010641:Phenotype; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D016827:CD8 Antigens; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D007166:Immunosuppressive Agents; D005983:Glutens