Background: Infliximab (IFX), an established therapy for pediatric Crohn disease (CD), is also efficacious in treating psoriasis, a skin disorder, in which tumor necrosis factor-α is implicated pathogenically. Paradoxically, there have been numerous reports of new-onset psoriasis following tumor necrosis factor-α antagonist therapy in adult patients with inflammatory bowel disease, but pediatric data are sparse.
Methods: A retrospective review of all IFX-treated patients with CD, who subsequently developed psoriasis, at a single pediatric inflammatory bowel disease center, was performed. A subset of affected patients (10/18) and CD controls (147 of 172) treated with IFX but without the development of psoriasis were genotyped for polymorphisms in the interleukin-23 receptor (IL-23R) gene, which has been identified as conferring susceptibility to both CD and psoriasis.
Results: Eighteen (10.5%) of 172 IFX-treated patients with CD developed new-onset psoriasis (n = 17) or worsening of existing psoriasis (n = 1). The duration of IFX exposure was variable, ranging from 1 to 25 infusions. Three patients discontinued IFX because of this complication. Most patients responded well to topical steroid therapy. In comparison to disease-matched controls, patients with CD developing psoriasis following IFX therapy were more likely to be homozygous for specific polymorphisms in the IL-23R gene (rs10489628, rs10789229, and rs1343151).
Conclusions: As in adults, the development of psoriasis or psoriasiform skin lesions occurs in pediatric patients with CD treated with IFX. Adequately powered studies are required to further explore the preliminary findings reported here to determine whether polymorphisms in the IL-23R gene have a role in the pathogenesis of this paradoxical process, which presently remains unexplained.
*Division of Gastroenterology, and Nutrition, McMaster Children's Hospital, Hamilton
†Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Canada
‡Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Amsterdam, The Netherlands
§Division of Dermatology, The Hospital for Sick Children, Toronto, Canada.
Address correspondence and reprint requests to Dr Mary Sherlock, Division of Gastroenterology and Nutrition, McMaster University, Hamilton Health Sciences, HSC 3A, Hamilton, Ontario, Canada, L8S 4K1 (e-mail: email@example.com).
Received 4 May, 2012
Accepted 17 December, 2012
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M.E.S. was supported by an Inflammatory Bowel Disease fellowship grant from Schering-Plough Canada (manufacturers of infliximab) from July 2008 to June 2009, and by an Inflammatory Bowel Diseases fellowship grant from CAG/CIHR/UCB Pharma from July 2009 to June 2011.
M.E.S. has been an advisory board member for Merck and Janssen (manufacturers of infliximab). T.W. has been an advisory board member for Merck and Janssen. A.M.G. has been a consultant for Merck and Janssen and has received speaker's honoraria from Merck and Janssen in addition to research support for investigator-initiated research from Schering Canada. The other authors report no conflicts of interest. The study described in this manuscript was independent of these pharmaceutical companies who had no role in the study design or manuscript preparation. The final manuscript was not reviewed by any pharmaceutical company.