Drug hypersensitivity: Pharmacogenetics and clinical syndromes

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:127

Article; Proceedings Paper

Phillips, Elizabeth J.^1,2,3,4,5  Chung, Wen-Hung⁶  Mockenhaupt, Maja⁷  Roujeau, Jean-Claude⁸  Mallal, Simon A.^1,2 

[1] Murdoch Univ, Inst Immunol & Infect Dis, Murdoch, WA 6150, Australia

[2] Royal Perth Hosp, Dept Clin Immunol & lmmunogenet, Perth, WA, Australia

[3] Sir Charles Gairdner Hosp, Dept Clin Immunol Infect Dis & Clin Pharmacol Tox, Nedlands, WA 6009, Australia

[4] Univ Western Australia, Sch Pathol, Crawley, WA, Australia

[5] Univ Western Australia, Lab Med & Biomed Biomol & Chem Sci, Crawley, WA, Australia

[6] Chang Gung Univ, Coll Med, Chang Gung Mem Hosp, Dept Dermatol, Taipei, Taiwan

[7] Univ Med Ctr, Dept Dermatol, Dokumentat Zentrum Schewerer Hautreaktionen dZh, Freiburg, Germany

[8] Univ Paris 12, Dept Dermatol, Creteil, France

关键词: Drug hypersensitivity;    drug reaction with eosinophilia and systemic symptoms;    drug-induced hypersensitivity syndrome;    Stevens-Johnson syndrome/toxic epidermal necrolysis;    pharmacogenetics;    severe cutaneous adverse reaction;    abacavir;    nevirapine;    carbamazepine;    allopurinol;   

DOI  :  10.1016/j.jaci.2010.11.046

来源: Elsevier

【 摘 要 】

Severe cutaneous adverse reactions include syndromes such as drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). An important advance has been the discovery of associations between HLA alleles and many of these syndromes, including abacavir-associated hypersensitivity reaction, allopurinol-associated DRESS/DIHS and SJS/TEN, and SJS/TEN associated with aromatic amine anticonvulsants. These HLA associations have created the promise for prevention through screening and have additionally shed further light on the immunopathogenesis of severe cutaneous adverse reactions. The rollout of HLA-B*5701 into routine clinical practice as a genetic screening test to prevent abacavir hypersensitivity provides a translational roadmap for other drugs. Numerous hurdles exist in the widespread translation of several other drugs, such as carbamazepine, in which the positive predictive value of HLA-B*1502 is low and the negative predictive value of HLA-B*1502 for SJS/TEN might not be 100% in all ethnic groups. International collaborative consortia have been formed with the goal of developing phenotypic standardization and undertaking HLA and genome-wide analyses in diverse populations with these syndromes. (J Allergy Clin Immunol 2011;127:S60-6.)

【 授权许可】

Free