1. 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 Case notes, biological and histological data were reviewed for patients with a diagnosis of RCD2 diagnosed between 2000 and 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 g/dL, Albumin normal values 40-52g/L, Vitamin B12 normal value ng/L, Folate normal value µg/L, NA not available
IEL intra-epithelial lymphocyte, Hb normal value g/dL, Albumin normal values 40-52g/L, Vitamin B12 normal value ng/L, Folate normal value µg/L
References: 1. Alberto Rubio-Tapia, Joseph A Murray. Classification and Management of Refractory Celiac Disease. Gut April; 59(4): 547–557.