A Single Center Experience of Treatment of

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A Single Center Experience of Treatment of Refractory Celiac Disease Type 2 Nasr I1, Donnelly SC1, Ho-Yen C2, Mitchell T3, Chang F2, Ciclitira PJ1 Gastroenterology Department, Division of Nutritional Sciences, Kings College London1, Pathology Department2, Molecular Diagnostic Services3, St Thomas Hospital, Westminster Bridge Road, London SE1 7EH Introduction Refractory celiac disease (RCD) is a persistent malabsorption and villous atrophy despite adhering to a strict gluten-free diet (GFD) for at least 6–12 months in the absence of other cause. It is a rare complication of celiac disease (CD). RCD is classified based on the T-cells in the intraepithelial lymphocyte (IEL) morphology into type 1 with normal IEL and type 2 with aberrant IEL. RCD1 is managed with strict nutritional and pharmacological management. RCD2 can be complicated by ulcerative jejunitis or enteropathy associated lymphoma (EATL), the latter having a 5-year mortality of 8-20%. It is therefore necessary to investigate and manage RCD2 which has a less predicted response and has a poor prognosis due to the associated complications. Treatment options vary due to the low incidence of RCD2 and hence the small numbers of randomized control trials. Conclusions Prednisolone combined with azathioprine can be used successfully to treat RCD type 2. Our experience shows it is a safe and successful approach to improve prognosis. We successfully treated 7 out of 10 patients with RCD type 2 with this regimen. Results Fourteen out of twenty patients with RCD2 were successfully treated with prednisolone and azathioprine to become either type 1 refractory celiac disease, in 12 patients, or celiac disease, in 2 patients, with a better 5-year survival. None of the type 2 refractory patients developed lymphoma on this treatment. Table 1: Baseline characteristics at time of type 2 refractory celiac disease patients Table 2: Follow-up data RCD2 patients on treatment: azathioprine & prednisolone Patient Sex Age Hb (g/dl) Albumin (g/l) Vitamin B12 (ng/l) Folate (µg/l) Histology Marsh grade IEL phenotype T-cell Receptor status HLA 1 M 62 16.1 47 140 2.0 3a CD8-ve Clonal DQ8 2 F 75 10.1 41 105 1.8 3b DQ2 3 64 14.7 48 333 3.6 4 44 13.8 43 177 15.4 5 14.9 141 1.9 6 15.0 144 2.3 7 61 13.7 46 134 >20.0 3c CD8+ve 8 50 11.4 40 203 4.7 9 54 12.5 39 559 10 70 36 114 NA 11 77 14.8 279 12 67 9.7 297 13 80 12.4 38 81 12.3 14 78 15.1 332 4.3 15 65 13.3 485 10.4 16 63 12.1 237 17 82 11.7 35 294 17.3 18 14.5 164 19 14.3 127 7.8 20 49 13.5 118 9.1 Patient Time from treatment (months) Hb (g/dl) Albumin (g/l) Vitamin B12 (ng/l) Folate (µg/l) Histology Marsh grade IEL phenotype T-cell receptor status 1 36 15.9 47 195 3.1 3a CD8–ve Clonal 2 60 13.9 44 188 6.2 3 26 14.9 50 500 3.4 Polyclonal 4 28 12.1 46 203 13.8 CD8+ve 5 29 13.3 48 349 3.2 6 8 16.1 51 185 14.2 7 12 13.2 103 >20.0 3b 20 12.9 294 6.4 9 62 13.5 446 8.6 10 33 41 >1500 16.0 CD8-ve 11 49 >1000 7.2 18 12.8 595 6.9 13 14.1 40 210 >20 14 43 407 3.8 15 12.7 679 16 232 2.7 17 54 11.6 495 14.6 379 4.8 19 37 339 7.8 208 Aim To present a single center’s experience in the treatment of type 2 refractory celiac disease (RCD2). Method We performed a single centre retrospective study of all cases of RCD2 using the celiac database in a single center between 2000 and 2013. Case notes, biological and histological data were reviewed for patients with a diagnosis of RCD2 diagnosed between 2000 and 2013. All patients were treated with prednisolone, 20mg, and azathioprine, 2mg/kg/day with repeat small bowel biopsy and T cell receptor analysis by PCR at 4 monthly intervals. IEL intra-epithelial lymphocyte , HLA human leukocyte antigen, Hb normal value 12.0-15.0g/dL, Albumin normal values 40-52g/L, Vitamin B12 normal value 145-1000ng/L, Folate normal value 2.5-16.0µg/L, NA not available IEL intra-epithelial lymphocyte, Hb normal value 12.0-15.0g/dL, Albumin normal values 40-52g/L, Vitamin B12 normal value 145-1000ng/L, Folate normal value 2.5-16.0µg/L References: 1. Alberto Rubio-Tapia, Joseph A Murray. Classification and Management of Refractory Celiac Disease. Gut. 2010 April; 59(4): 547–557.