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Immunopathogenesis and risk factors for allopurinol severe cutaneous adverse reactions

Immunopathogenesis and risk factors for allopurinol severe cutaneous adverse reactions Purpose of review The article reviews the immunopathogenesis and risk factors related to allopurinol-induced severe cutaneous adverse reactions (SCARs). Recent findings For years, allopurinol remains one of the leading cause for SCARs worldwide. The pathogenesis of allopurinol-induced SCARs have been discovered in recent years. HLA-B ∗ 58 : 01 has been found to be strongly associated with allopurinol-SCARs with functional interactions between allopurinol/its metabolite-oxypurinol and the T-cell receptor (TCR). However, the genetic strength of HLA-B ∗ 58 : 01 may vary among different ethnic populations. In addition to HLA-B ∗ 58 : 01, specific T cells with preferential TCR clonotypes, which have no cross-reactivity with new xanthine oxidase inhibitors structurally different from allopurinol, are found to play a crucial role for allopurinol-induced SCARs. Furthermore, other nongenetic factors such as renal impairment are also found to be an important factor resulting in allopurinol-induced SCARs of greater severity and poorer prognosis. Summary There are multiple risk factors for allopurinol-induced SCARs, including genetic and nongenetic factors. Activation of specific T cells with preferential TCR and its functional interaction of HLA-B ∗ 58 : 01 molecule and allopurinol/oxypurinol are involved in the immune mechanism of allopurinol-induced SCAR. Patients with allopurinol-induced SCARs with renal impairment have significantly higher risk of mortality. A structurally different new generation xanthine oxidase inhibitor can provide a safer alternative for patients intolerant to allopurinol. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Current Opinion in Allergy and Clinical Immunology Wolters Kluwer Health

Immunopathogenesis and risk factors for allopurinol severe cutaneous adverse reactions

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References (65)

Copyright
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Subject
DRUG ALLERGY: Edited by Bernard Y-H. Thong and Miguel Blanca
ISSN
1528-4050
eISSN
1473-6322
DOI
10.1097/ACI.0000000000000286
pmid
27362322
Publisher site
See Article on Publisher Site

Abstract

Purpose of review The article reviews the immunopathogenesis and risk factors related to allopurinol-induced severe cutaneous adverse reactions (SCARs). Recent findings For years, allopurinol remains one of the leading cause for SCARs worldwide. The pathogenesis of allopurinol-induced SCARs have been discovered in recent years. HLA-B ∗ 58 : 01 has been found to be strongly associated with allopurinol-SCARs with functional interactions between allopurinol/its metabolite-oxypurinol and the T-cell receptor (TCR). However, the genetic strength of HLA-B ∗ 58 : 01 may vary among different ethnic populations. In addition to HLA-B ∗ 58 : 01, specific T cells with preferential TCR clonotypes, which have no cross-reactivity with new xanthine oxidase inhibitors structurally different from allopurinol, are found to play a crucial role for allopurinol-induced SCARs. Furthermore, other nongenetic factors such as renal impairment are also found to be an important factor resulting in allopurinol-induced SCARs of greater severity and poorer prognosis. Summary There are multiple risk factors for allopurinol-induced SCARs, including genetic and nongenetic factors. Activation of specific T cells with preferential TCR and its functional interaction of HLA-B ∗ 58 : 01 molecule and allopurinol/oxypurinol are involved in the immune mechanism of allopurinol-induced SCAR. Patients with allopurinol-induced SCARs with renal impairment have significantly higher risk of mortality. A structurally different new generation xanthine oxidase inhibitor can provide a safer alternative for patients intolerant to allopurinol.

Journal

Current Opinion in Allergy and Clinical ImmunologyWolters Kluwer Health

Published: Aug 1, 2016

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