HLA-B~*5801基因多态性与别嘌醇致皮肤不良反应的文献分析
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摘要
目的探讨HLA-B~*5801等位基因变异与别嘌醇致皮肤不良反应之间的关联性,预测服用别嘌醇潜在的不良反应,为临床安全合理用药提供参考。方法检索2005年3月～2018年5月中国学术期刊(网络版)、万方数字化期刊全文库、中文科技期刊全文数据库(维普)及Pub Med等数据库,收集HLA-B~*5801等位基因变异与别嘌醇致皮肤不良反应(cutaneous adverse reactions,CAR)的文献进行统计和分析。结果共检索到46篇文献,别嘌醇致CAR病例342例,HLA-B~*5801等位基因阳性310例,阳性率90.64%,其中男性188例,女性122例,男性多于女性,年龄分布为18～91岁,以61～75岁患者多见。310例HLA-B~*5801等位基因阳性患者发生CAR中,重度皮肤不良反应(severe cutaneous adverse reactions,SCAR)256例,占82.58%,轻度CAR 54例,占17.42%。服用100 mg别嘌醇与服药时间在21～30天患者不良反应发生率较高。结论别嘌醇致CAR与HLA-B~*5801等位基因有较强的关联性,另外患者性别、年龄、用药时间、用药剂量亦是不良反应的影响因素,在别嘌醇临床使用中应关注这些因素,并加强药学监护,以避免不良反应的发生,确保患者用药安全。
Obje ctive To investigate the association between alleles of HLA-B~*5801 and cutaneous adverse reactions induced by allopurinol, and predict potential adverse effects of allopurinol, so as to provide references for clinical safe and rational use of drugs. Methods Chinese Academic Journal(online), Wanfang Database, Chinese Science and Technology Journal Full-text Database(VIP), and PubMed databases were retrieved from March 2005 to May 2018, and then the documents of alleles of HLA-B~*5801 and cutaneous adverse reactions(CAR) induced by allopurinol were collected for statistical analysis. Re s ults A total of 46 literatures with 342 cutaneous adverse reactions patients were retrieved. There are 310 cases with positive allele of HLA-B~*5801, with a positive rate of 90.64%. The males(188)are more than females(122) and the age distribution was 18 ～91 years old, especially 61 ～75 years old patients were more. Among the 310 patients with HLA-B~*5801 positive allele, 256 cases were severe cutaneous adverse reactions(SCAR), accounting for 82.58%, and 54 cases were mild cutaneous adverse reactions, accounting for17.42%. In addition, patients taking 100 mg allopurinol and taking it for 21 ～30 days had a higher incidence of adverse reactions. Conclus ion There was strong association between alleles of HLA-B~*5801 and cutaneous adverse reactions induced by allopurinol. In addition, gender, age, duration and dosage of medication were also influence factors of the adverse reactions. In clinical use of allopurinol, we should pay attention to these factors, and pharmaceutical care should be strengthened to avoid the occurrence of adverse reactions to ensure medication safety.
Obje ctive To investigate the association between alleles of HLA-B~*5801 and cutaneous adverse reactions induced by allopurinol, and predict potential adverse effects of allopurinol, so as to provide references for clinical safe and rational use of drugs. Methods Chinese Academic Journal(online), Wanfang Database, Chinese Science and Technology Journal Full-text Database(VIP), and PubMed databases were retrieved from March 2005 to May 2018, and then the documents of alleles of HLA-B~*5801 and cutaneous adverse reactions(CAR) induced by allopurinol were collected for statistical analysis. Re s ults A total of 46 literatures with 342 cutaneous adverse reactions patients were retrieved. There are 310 cases with positive allele of HLA-B~*5801, with a positive rate of 90.64%. The males(188)are more than females(122) and the age distribution was 18 ～91 years old, especially 61 ～75 years old patients were more. Among the 310 patients with HLA-B~*5801 positive allele, 256 cases were severe cutaneous adverse reactions(SCAR), accounting for 82.58%, and 54 cases were mild cutaneous adverse reactions, accounting for17.42%. In addition, patients taking 100 mg allopurinol and taking it for 21 ～30 days had a higher incidence of adverse reactions. Conclus ion There was strong association between alleles of HLA-B~*5801 and cutaneous adverse reactions induced by allopurinol. In addition, gender, age, duration and dosage of medication were also influence factors of the adverse reactions. In clinical use of allopurinol, we should pay attention to these factors, and pharmaceutical care should be strengthened to avoid the occurrence of adverse reactions to ensure medication safety.
引文
[1]曾大勇,王长连,黄品芳,等.别嘌醇引发严重皮肤不良反应标志基因HLA-B*5801的检测方法研究[J].中国现代应用药学,2015,32(6):700-704.
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[3] Cao Z H,Wei Z Y,Zhu Q Y,et al.HLA-B*5801 allele is associated with augmented risk for both mild and severe cutaneous adverse reation induced by allopurinol in Han Chinese[J].Pharmacogenomics,2012,13(10):1193-1201.
[4] Jung J W,Song W J,Kim Y S,et al.HLA-B58 can help the clinical decision on starting allopurinol in patients with chronic renalinsufficiency[J]. Nephrol Dial Transplant,2011,26(11):3567-3572.
[5] Ramasamy S N,Korb-Wells C S,Kannangara D R,et al. Allopurinol hypersensitivity:a systematic review of all published cases,1950-2012[J]. Drug Saf,2013,36(10):953-980.
[6] Chung W H,Hung S I,Hong H S, et al. A marker for StevensJohnson syndrome[J]. Nature,2004,428(6982):248-486.
[7] Khanna D,Fitzgerald J D,Khanna P P,et a1.2012 American college of rheumatology guidelines for management of gout. Part1:systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia[J]. Arthritis Care Res(Hoboken),2012,64(10):1431-1446.
[8]云雄,吴丹娜,韩方璇,等.海南省汉族人群HLA-B*5801基因多态性与别嘌醇所致不良反应的相关性研究[J].中国药房,2018,29(9):1256-1259.
[9]罗阳,韩悦,王宝玺,等.别嘌醇引起发疹型药疹8例及相关基因HLA-B*5801检测[J].中华临床免疫和变态反应杂志,2016,10(2):87-90.
[10] Kannangara D R,Ramasamy S N,Ray J E,et al. An audit of a therapeutic drug monitoring service for allopurinol therapy[J].Ther Drug Monit,2013,35(6):863-866.
[11] Thurston M M,Phillips B B,Bourg C A. Safety and efficacy of allopurinol in chronic kidney disease[J]. Ann Pharmacother,2013,47(11):1507-1516.
[12] Yeo S I. HLA-B*5801:utility and cost-effectiveness in the Asia-Pacific Region[J]. Int J Rheum Dis,2013,16(3):254-257.
[2]高杰,张晶晶,王进,等.别嘌醇致严重皮肤不良反应与江苏汉族人HLA-B*5801等位基因的相关性研究[J].药物不良反应杂志,2013,10(15):258-259.
[3] Cao Z H,Wei Z Y,Zhu Q Y,et al.HLA-B*5801 allele is associated with augmented risk for both mild and severe cutaneous adverse reation induced by allopurinol in Han Chinese[J].Pharmacogenomics,2012,13(10):1193-1201.
[4] Jung J W,Song W J,Kim Y S,et al.HLA-B58 can help the clinical decision on starting allopurinol in patients with chronic renalinsufficiency[J]. Nephrol Dial Transplant,2011,26(11):3567-3572.
[5] Ramasamy S N,Korb-Wells C S,Kannangara D R,et al. Allopurinol hypersensitivity:a systematic review of all published cases,1950-2012[J]. Drug Saf,2013,36(10):953-980.
[6] Chung W H,Hung S I,Hong H S, et al. A marker for StevensJohnson syndrome[J]. Nature,2004,428(6982):248-486.
[7] Khanna D,Fitzgerald J D,Khanna P P,et a1.2012 American college of rheumatology guidelines for management of gout. Part1:systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia[J]. Arthritis Care Res(Hoboken),2012,64(10):1431-1446.
[8]云雄,吴丹娜,韩方璇,等.海南省汉族人群HLA-B*5801基因多态性与别嘌醇所致不良反应的相关性研究[J].中国药房,2018,29(9):1256-1259.
[9]罗阳,韩悦,王宝玺,等.别嘌醇引起发疹型药疹8例及相关基因HLA-B*5801检测[J].中华临床免疫和变态反应杂志,2016,10(2):87-90.
[10] Kannangara D R,Ramasamy S N,Ray J E,et al. An audit of a therapeutic drug monitoring service for allopurinol therapy[J].Ther Drug Monit,2013,35(6):863-866.
[11] Thurston M M,Phillips B B,Bourg C A. Safety and efficacy of allopurinol in chronic kidney disease[J]. Ann Pharmacother,2013,47(11):1507-1516.
[12] Yeo S I. HLA-B*5801:utility and cost-effectiveness in the Asia-Pacific Region[J]. Int J Rheum Dis,2013,16(3):254-257.