Risk-factors Associated with Poor Outcomes in VEO-IBD Secondary to XIAP Deficiency: A Case Report and Literature Review

Very early onset inflammatory bowel disease (VEO-IBD) represents a diagnostic and treatment challenge. Here we present a case of VEO-IBD secondary to a mutation in BIRC4 gene, which encodes X-linked inhibitor of apoptosis protein (XIAP), in a 17 month-old male with severe failure to thrive, intractable diarrhea and hepatosplenomegaly. Endoscopy and histology identified only mild duodenitis and ileitis, but severe pancolitis with crypt abscesses and epithelium apoptosis. Minimal improvement in symptoms was achieved with total parenteral nutrition (TPN), intravenous (IV) corticosteroids and tacrolimus, whereas induction and maintenance therapy with adalimumab led to complete remission. After 6 months, the patient developed hemophagocytic lymphohistiocytosis (HLH) and eventually died due to multi-system organ failure. A review of the literature revealed that some patients with VEO-IBD secondary to XIAP deficiency develop symptoms that are refractory to medical and surgical management, while initial reports suggest that allogeneic hematopoietic stem cell transplantation (HSCT), with reduced intensity conditioning, can successfully induce long lasting remission and may even be curative. We propose that in patients with XIAP deficiency a constellation of symptoms including colitis at an early age, severe failure to thrive and splenomegaly/hepatosplenomegaly can identify a subgroup of patients at high-risk of experiencing medically-refractory IBD phenotype and increased mortality. Hematopoietic stem cell transplant should be considered early in these high-risk patients, as it may resolve both their intestinal inflammation and a risk of developing life threatening HLH. Address correspondence and reprint requests to Samir Softic, MD, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02215 (e-mail: samir.softic@childrens.harvard.edu). Received 3 October, 2018 Accepted 30 December, 2018 Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). The authors report no conflicts of interest. © 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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