<i>HLA-B*58:01</i>
            Allele is Associated with Augmented Risk for Both Mild and Severe Cutaneous Adverse Reactions Induced by Allopurinol in Han Chinese

Cao, Zhi-Hao; Wei, Zengxin; Zhu, Qian; Zhang, Jun-yu; Yang, Lun; Qin, Shengying; Shao, Li‐Hua; Zhang, Yiting; Xuan, Jiekun; Li, Qiaoli; Xu, Jinhua; Xu, Feng; Ma, Li; Huang, Huei Li; Xing, Qinghe; Luo, Xiaoqun

doi:10.2217/pgs.12.89

Cited by 89 publications

(83 citation statements)

References 40 publications

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“…In addition, an association was found between BL allergy and 2 variants in the HLA-DRA/HLA-DRB5 region (rs7754768 and rs9268832) [24]. Our results agree with those of various studies showing a link between increased IgE levels and HLA alleles [30,31] and a potential effect of NOD2 polymorphisms on HLA-DRA expression [32,33]. Our genome-wide study also revealed that the C5 missense variant rs17612 predicted BL allergy in both populations, albeit to a lower extent in the Italian patients [24].…”

Section: Immediate Reactions To Bl Antibioticssupporting

confidence: 92%

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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: Immediate Reactions To Bl Antibioticssupporting

confidence: 92%

“…This allele is also a risk factor for other severe and mild DHRs in Han Chinese patients [32]. Thus, screening for the HLA-B*5801 allele has been proposed to reduce the incidence of these nonimmediate DHRs [33][34][35].…”

Section: Allopurinolmentioning

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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“…In Han Chinese, 9Á9-14Á8% (mean 10Á9%) of the 741 of allopurinol-tolerant controls also carry this HLA molecule. [21][22][23][35][36][37] As is the case for carbamazepine, 44 in addition to a predisposing HLA type, T cells with high-affinity T-cell receptor are needed to recognize and proliferate on exposure to allopurinol/oxypurinol. Otherwise, when affinity is less strong, either more drug/metabolite molecules or a state of preactivation of T cells is needed for a significant T-cell proliferation and a CADR to develop.…”

Section: Discussionmentioning

confidence: 99%

HLA-B58:01*is a risk factor for allopurinol-induced DRESS and Stevens-Johnson syndrome/toxic epidermal necrolysis in a Portuguese population

et al. 2013

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“…Because HLA-B*58:01 is not only a risk factor for severe cutaneous reactions, but also for mild cutaneous adverse reactions, such as maculopapular exanthema in the Han Chinese population 19 , broad criteria of any allopurinol-related skin reactions were used to minimize underestimation of incidence. The total number of incident cases over the study period was consistent with the documented reports in the national reporting center of adverse drug reactions in Taiwan between 1999 and 2010 4 .…”

Section: Analysis Of Incidence Of Scarmentioning

confidence: 99%

Cost-effectiveness Analysis for Genotyping before Allopurinol Treatment to Prevent Severe Cutaneous Adverse Drug Reactions

Chung

Wen

et al. 2017

J Rheumatol

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Objective.Patients with an HLA-B*58:01 allele have an increased risk of developing severe cutaneous adverse drug reactions (SCAR) when treated with allopurinol. Although one-off pharmacogenetic testing may prevent life-threatening adverse drug reactions, testing prior to allopurinol initiation incurs additional costs. The study objective was to evaluate the cost-effectiveness of HLA-B*58:01 screening compared with using other available urate-lowering agents (ULA).Methods.A decision-analytical model was used to compare direct medical costs and effectiveness [including lifetime saved, quality-adjusted life-yrs (QALY) gained] in treating new patients with the following options: (1) genetic screening followed by allopurinol prescribing for noncarriers of HLA-B*58:01, (2) prescribing benzbromarone without screening, (3) prescribing febuxostat without screening, and (4) prescribing allopurinol without screening. A 1-year time frame and third-party payer perspective were modeled for both the entire cohort (base-case) and for the subgroup of patients with chronic kidney disease (CKD).Results.The incremental cost-effectiveness ratio of genetic screening prior to ULA therapy was estimated as New Taiwan (NT) $234,610 (US$7508) per QALY gained in the base-case cohort. For patients with CKD, it was estimated as NT$230,925 (US$7390) per QALY. The study results were sensitive to the probability of benzbromarone/febuxostat-related hypersensitivity, and a negative predicted value of genotyping.Conclusion.HLA-B*58:01 screening gave good value for money in preventing allopurinol-induced SCAR in patients indicated for ULA therapy. In addition to the costs of genotyping, it is important to monitor ULA safety closely in adopting HLA-B*58:01 screening in practice.

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HLA-B58:01* Allele is Associated with Augmented Risk for Both Mild and Severe Cutaneous Adverse Reactions Induced by Allopurinol in Han Chinese

Cited by 89 publications

References 40 publications

Update on the Genetic Basis of Drug Hypersensitivity Reactions

Update on the Genetic Basis of Drug Hypersensitivity Reactions

HLA-B58:01*is a risk factor for allopurinol-induced DRESS and Stevens-Johnson syndrome/toxic epidermal necrolysis in a Portuguese population

Cost-effectiveness Analysis for Genotyping before Allopurinol Treatment to Prevent Severe Cutaneous Adverse Drug Reactions

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HLA-B*58:01 Allele is Associated with Augmented Risk for Both Mild and Severe Cutaneous Adverse Reactions Induced by Allopurinol in Han Chinese

Cited by 89 publications

References 40 publications

Update on the Genetic Basis of Drug Hypersensitivity Reactions

Update on the Genetic Basis of Drug Hypersensitivity Reactions

HLA-B*58:01is a risk factor for allopurinol-induced DRESS and Stevens-Johnson syndrome/toxic epidermal necrolysis in a Portuguese population

Cost-effectiveness Analysis for Genotyping before Allopurinol Treatment to Prevent Severe Cutaneous Adverse Drug Reactions

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HLA-B58:01* Allele is Associated with Augmented Risk for Both Mild and Severe Cutaneous Adverse Reactions Induced by Allopurinol in Han Chinese

HLA-B58:01*is a risk factor for allopurinol-induced DRESS and Stevens-Johnson syndrome/toxic epidermal necrolysis in a Portuguese population