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P815 Clinical and endoscopic features of XIAP deficiency mimicking refractory Crohn’s disease in paediatric patients

N. Toita*1, A. Kamada1, S-i. Fujiwara1, M. Takahashi1, M. Konno1, S. S. Abdrabou2, Y. Tozawa2, M. Ueki2, S. Takezaki2, M. Yamada2, T. Ariga2, H. Kanegane3

1Sapporo Kosei General Hospital, Pediatrics, Sapporo, Japan, 2Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Pediatrics, Sapporo, Japan, 3Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Pediatrics and Developmental Biology, Tokyo, Japan

Background

X-linked inhibitor of apoptosis protein (XIAP) deficiency is a rare immunodeficiency that is characterised by recurrent haemophagocytic lymphohistiocytosis (HLH) and splenomegaly and often associated with refractory inflammatory bowel disease (IBD). We report on four patients with childhood-onset XIAP deficiency who were initially diagnosed with Crohn’s disease (CD) and had been treated with frequent relapse.

Methods

We aimed to investigate clinical characteristics and endoscopic features of paediatric patients diagnosed with XIAP deficiency at Sapporo Kosei General Hospital, Sapporo, Japan. Symptoms, complications, endoscopic images and genetic data were reviewed.

Results

At onset four male patients were between the age of 8 and 11 years. They were then histopathologically diagnosed with CD and underwent treatment with prednisolone, several immunosuppressants, and thereafter with infliximab. All of them responded to treatment partially and relapsed frequently. Three of the four patients were complicated with HLH. Serum interleukin (IL)-18 levels (normal range: 0–300 pg/ml) of three patients were elevated. western blot analysis demonstrated absent XIAP expressions and genetic analyses definitely confirmed XIAP deficiency in all the four patients. Three patients underwent haematopoietic stem cell transplantation (HSCT) and the fourth one is planning to undergo HSCT.

Table. Summary of patients with XIAP deficiency.

Figure. Endoscopic images of the wide and longitudinal ulcers with scooped-out appearance in the colon.

Conclusion

CD like inflammatory bowel disease associated with recurrent HLH, splenomegaly and anal fistula is a characteristic clinical feature of patients with XIAP deficiency. We presented here a characteristic endoscopic finding of wide and ‘scooped-out’ multiple longitudinal ulcer lesions in all the four XIAP deficiency patients. We propose that XIAP deficiency should be suspected for those with characteristic clinical features and unique endoscopic findings as described above. We recommend flow-cytometric analysis or western blot of XIAP expression followed by whole-exome sequencing analysis as soon as possible. CD-like inflammatory bowel disease in our three cases was improved remarkably after HSCT and has been maintained remission without any further treatments. We should not postpone the timing of performing genetic analysis because HSCT is the only curative treatment for XIAP deficiency patients.