Combined Therapy of Prednisone and Cyclosporine as Treatment Option for Refractory Coeliac Disease and Clonal T Cell Receptor (TCR) Gene Rearrangement

Abstract

Effective therapy of refractory coeliac disease is still under debate. The necessity for such treatment is underlined by the potential risk of the development of an enteropathy-associated T-cell lymphoma. We report of a male patient with coeliac disease first diagnosed in 1991. Under subsequent gluten-free diet, clinical symptoms of the disease necessitated only intermittent treatment with prednisone. A recent deterioration was treated with azathioprine which had to be stopped because of side effects. When we first saw the patient in August 2004, he had experienced a weight loss of 16 kg within 14 months and suffered from diarrhea, hypoalbuminia and impaired nutritional state. The diagnostic work-up (blood/stool/x-ray/CT) did not result in any other diagnoses explaining the clinical symptoms. GI endoscopy showed intraepithelial lymphocytosis, villous atrophy with crypt hyperplasia and ulcerative lesions in the small bowel. All biopsies (duodenum/jejunum/ileum/bone marrow/liver/lymph node) but not blood were characterized by monoclonal T-cell receptor-gamma gene rearrangement. Total parenteral nutrition resulted in a weight gain of 14 kg but administration of prednisone at different doses (20–60mg iv/die) was not associated with improved enteral resorption. Therefore, cyclosporine (initially 5mg/kg iv/die) was added to prednisone (60mg iv/die). Consequently, a stepwise reduction of parenteral nutrition was feasible. Within 4 months, the patient gained another 8 kg. A shift from parenteral to oral drug administration was successful under cyclosporine plasma levels between 65 and 96ng/ml (limitation of daily cyclosporine dosage to 2mg/kg because of developing renal insufficiency). The histological analysis of duodenal/jejunal biopsies did not show any change in the modified Marsh classification (IIIb). Conclusion: The combined administration of prednisone plus cyclosporine represents a clinically effective treatment option in patients with refractory celiac disease who are unresponsive to steroids alone and do not tolerate azathioprine.