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土耳其人群中抗癫痫药物的皮肤药物反应及其与HLA等位基因的关系。

Cutaneous drug reactions to antiepileptic drugs and relation with HLA alleles in the Turkish population.

作者信息

Büyüköztürk S, Kekik Ç, Gökyiğit A Z, Tezer Filik F I, Karakaya G, Saygi S, Dursun A B, Kirbaş S, Tüfekçi A, Sin A Z, Aydoğdu I, Sorgun M H, Aydin N, Gelincik A, Çolakoğlu B, Çelik G, Oğuz F

机构信息

Istanbul University, Istanbul Faculty of Medicine, Department of Internal Medicine, Allergy and Clinical Immunology Unit, Istanbul, Turkey Phone: +90 212 5231241 E-mail:

Istanbul University, Istanbul Faculty of Medicine, Department of Medical Biology, Istanbul, Turkey.

出版信息

Eur Ann Allergy Clin Immunol. 2018 Jan;50(1):36-41. doi: 10.23822/EurAnnACI.1764-1489.23.

Abstract

Many studies have shown associations between HLAB15:02, HLA-A31:01 and carbamazepine (CBZ)-induced delayed cutaneous hypersensitivity reactions. The aim of this study is to evaluate a possible association between delayed cutaneous reactions to antiepileptic drugs (AEDs) and certain HLA-A and HLA-B alleles in the Turkish population. The study consisted of 3 groups: Group I (reactive group) included the patients who had documented delayed cutaneous reactions to any antiepileptic drug. Group II (non-reactive group) included the patients who have been on antiepileptic treatment at least for three months without any adverse reactions. Group III consisted of healthy subjects. The HLA-A and B alleles were analyzed in all groups. Forty patients (29 female) had experienced different hypersensitivity reactions due to AEDs: maculopapular exanthema (26 patients), Stevens-Johnson syndrome (6 patients), drug rash with eosinophilia and systemic symptoms (7 patients), toxic epidermal necrolysis (1 patient). Lamotrigine (11) and CBZ (10) were the most common culprit drugs involved in the reactions. The HLA-B15:02 was not present in any of the study groups. However, HLA-B35:02 was found in 4 patients from the reactive group, while it was not observed in non-reactive patients and was detected in only one healthy subject (p = 0.021). Although our preliminary results did not indicate a strong allele association with AED hypersensitivity, HLA-B*35:02 appears to be a candidate allele for MPE / DRESS / DIHSS induced by AED's in Turkish population. Further studies with a larger sample size may result in more comprehensive data about the genetic tendency for AED hypersensitivity in the Turkish population.

摘要

许多研究表明,人类白细胞抗原B15:02、人类白细胞抗原A31:01与卡马西平(CBZ)引起的迟发性皮肤过敏反应之间存在关联。本研究的目的是评估土耳其人群中抗癫痫药物(AEDs)引起的迟发性皮肤反应与某些人类白细胞抗原A和人类白细胞抗原B等位基因之间可能存在的关联。该研究包括3组:第一组(反应组)包括有记录显示对任何抗癫痫药物有迟发性皮肤反应的患者。第二组(无反应组)包括接受抗癫痫治疗至少3个月且无任何不良反应的患者。第三组由健康受试者组成。对所有组进行了人类白细胞抗原A和B等位基因分析。40名患者(29名女性)因AEDs出现了不同的过敏反应:斑丘疹(26名患者)、史蒂文斯-约翰逊综合征(6名患者)、伴有嗜酸性粒细胞增多和全身症状的药疹(7名患者)、中毒性表皮坏死松解症(1名患者)。拉莫三嗪(11例)和CBZ(10例)是反应中最常见的致病药物。研究组中均未发现人类白细胞抗原B15:02。然而,在反应组的4名患者中发现了人类白细胞抗原B35:02,而在无反应患者中未观察到,仅在1名健康受试者中检测到(p = 0.021)。虽然我们的初步结果并未表明等位基因与AED过敏反应有很强的关联,但人类白细胞抗原B*35:02似乎是土耳其人群中AEDs诱导的斑丘疹/药物反应伴嗜酸性粒细胞增多和全身症状/药物超敏综合征的候选等位基因。样本量更大的进一步研究可能会得出关于土耳其人群AED过敏反应遗传倾向的更全面数据。

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