Genotype–phenotype association between HLA and carbamazepine-induced hypersensitivity reactions: Strength and clinical correlations

Hsiao, Yi-Hsin; Hui, Rosaline Chung‐Yee; Wu, Tony; Chang, Wen Han; Hsih, Mo-Song; Yang, Chih-Hsun; Ho, Hung‐Yao; Chang, Ya-Ging; Chen, Mingjing; Lin, Jingyi; Chen, Ding‐Ping; Chang, Pi-Yueh; Wu, Tsu‐Lan; Hung, Shuen‐Iu; Chung, Wen‐Hung

doi:10.1016/j.jdermsci.2013.10.003

Cited by 82 publications

(63 citation statements)

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“…Multiple studies have found an association between the HLA-B*1502 allele and carbamazepine-induced SJS/TEN in Han Chinese [38][39][40][41] and other Asian populations [42][43][44][45]. The strength of such associations has led to the recommendation to screen for this variant in patients with Asian ancestry before starting treatment [46,47].…”

Section: Anticonvulsantsmentioning

confidence: 99%

Update on the Genetic Basis of Drug Hypersensitivity Reactions

Jurado‐Escobar¹,

Perkins²,

García‐Martín³

et al. 2017

J Investig Allergol Clin Immunol

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Drug hypersensitivity reactions (DHRs) are unpredictable, complex responses to medicines in predisposed individuals. They represent a major health problem owing to the number of patients affected and the severity of the clinical conditions they can induce. In addition to environmental factors, the underlying mechanisms of DHRs are also influenced by genetic factors, although considerable gaps remain in our knowledge. Therefore, further study of the genetics of DHRs is necessary to shed light on their underlying mechanisms. In this manuscript, we provide an update on the genetic basis of the most frequent types of DHRs, including those mediated by immunological and nonimmunological mechanisms. For the first group, we will focus on immediate reactions to β-lactam antibiotics, which are associated mainly with the IgE pathway (IL13, IL4R, LGALS3, and NOD2) and antigen presentation (HLA-DRA), and nonimmediate reactions to allopurinol, anticonvulsants, antibiotics, and antiretrovirals, which are often associated with polymorphisms in the HLA system. For the second group, we will focus on nonsteroidal anti-inflammatory drugs, which are mostly associated with genetic variants in enzymes and receptors from the arachidonic acid pathway (eg, ALOX5, ALOX5AP, PTGDR, and CYSLTR1). The information provided here will be of interest for medical practitioners from a range of disciplines who come across these reactions in their clinical practice, as well as for allergologists. Key words: Drug hypersensitivity. Immunologically-mediated reactions. Cross-hypersensitivity. Single-nucleotide polymorphisms. Genomewide association study. ResumenLas reacciones de hipersensibilidad a fármacos (RHFs) son respuestas no predecibles que se producen en algunos sujetos y que representan un serio problema de salud pública debido al número de pacientes implicados y a su potencial gravedad. Además de factores ambientales, en estas reacciones también participan factores genéticos, cuya influencia está, en la mayoría de los casos, aún por dilucidar. En este manuscrito describiremos la información disponible sobre la base genética de los tipos más frecuentes de RHFs, tanto de las mediadas inmunológicamente como de aquellas en las que no se requiere reconocimiento antigénico. En el primer grupo nos ocuparemos de las reacciones inmediatas a antibióticos β-lactámicos, que han sido asociadas con variantes relacionadas con la IgE (IL13, IL4R, LGALS3 y NOD2) y la presentación antigénica (HLA-DRA), y de las reacciones no inmediatas a diferentes grupos de medicamentos (alopurinol, anticonvulsivos, antibióticos y antiretrovirales), relacionadas fundamentalmente con polimorfismos en el sistema HLA. En el segundo grupo nos centraremos en las reacciones inducidas por antiinflamatorios no esteroideos (AINE), que han sido asociadas básicamente con variantes en enzimas y receptores de la vía del ácido araquidónico (ALOX5, ALOX5AP, PTGDR y CYSLTR1, entre otros). Esta revisión puede ser de interés no sólo para alergólogos, sino para los profesionales de otras ...

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Section: Anticonvulsantsmentioning

confidence: 99%

Update on the Genetic Basis of Drug Hypersensitivity Reactions

Jurado‐Escobar¹,

Perkins²,

García‐Martín³

et al. 2017

J Investig Allergol Clin Immunol

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“…Our patient had inherited several 'at-risk' HLA alleles for severe drug reactions (Table 2 outlines the drugs and HLA alleles associated with DIHS), [26][27][28][29][30][31][32][33][34][35][36][37]. It is possible that herpes virus reactivation, most notably HHV-6, was the common underlying factor for the multiple drug reactions [38][39][40][41][42], although that was not proven in our case.…”

Section: Discussionmentioning

confidence: 73%

Multiple Drug Induced Hypersensitivity Syndrome Reactions in a Patient with Drugs that Have Known HLA Associations for Reactions

Khan¹,

Bhartia²,

S³

2014

General Med

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We report a rare case of a patient with chronic myeloid leukaemia (CML) who had severe drug hypersensitivity reactions with not only allopurinol and imatinib therapies for the CML, but also to a non-steroidal anti-inflammatory drug and an antibiotic. Each of the drugs (allopurinol and imatinib) when used alone, and in combination, had caused various combinations of fever (hyperpyrexia), rash and/or generalized edema. The patient had the HLA-B*58 haplotype that is associated with allopurinol induced Steven-Johnson syndrome. However, in our case, imatinib alone also caused a similar reaction. We discuss the other 'at-risk' HLA alleles and known drug reactions and that our patient was unfortunate to have all of these HLA alleles. Further studies are required to confirm whether the HLA-B*58 haplotype is a risk factor for imatinib induced adverse cutaneous drug reactions.

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“…Both small sample size for each SCAR and the heterogeneity of the responsible AEDs were the main limiting factors. The many previous studies on CBZ hypersensitivity reactions suffered from the low incidences, difficulty of patient's enrollment, and small sample sizes (17). Focusing on a specific drug and analyzing HLA genotype-phenotype correlations in the clinical spectrum, could provide more comprehensive pharmacogenetic data in AED-induced hypersensitivity reactions.…”

Section: Discussionmentioning

confidence: 99%