OBJECTIVES: Allopurinol, a uric acid lowering drug commonly used for hyperuricemia and gouty arthritis, has been reported as a common cause of severe cutaneous adverse drug reactions (SCAR) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). A strong association between allopurinol-induced SCAR and HLA-B*5801 was observed in a Han Chinese population with high frequency of this allele, whereas only a moderate association was observed in populations with low frequency (i.e. European and Japanese). This study investigated the relationship between SJS/TEN and HLA-B*5801 in a Thai population that has a high allelic frequency of this allele. METHODS: Twenty-seven allopurinol-induced SJS/TEN and 54 allopurinol-tolerant patients were enrolled in the study. The presence of HLA-B*5801 and HLA-B genotypes in these patients were analyzed using a PG5801 DNA detection kit and sequence-based typing, respectively. RESULTS: All of the 27 (100%) allopurinol-induced SJS/TEN patients who were examined carried HLA-B*5801 whereas only seven (12.96%) of the control patients had this allele. The risk of allopurinol-induced SJS/TEN was significantly greater in patients with HLA-B*5801 when compared with those who did not carry this allele, with an odds ratio of 348.3 (95% confidence interval=19.2-6336.9, P = 1.6 x10). The sensitivity and specificity of the HLA-B*5801 allele for prediction of allopurinol-induced SJS/TEN were 100 and 87%, respectively. By assuming a 0.2% prevalence rate, the positive predictive value and the negative predictive value of the HLA-B*5801 allele was 1.52 and 100%, respectively. CONCLUSION: A strong association of allopurinol-induced SJS/TEN with the HLA-B*5801 allele was observed in a Thai population. The results suggest that HLA-B*5801 is a valid genetic marker for screening Thai individuals who may be at risk for allopurinol-induced life-threatening SJS and TEN.
OBJECTIVES:Allopurinol, a uric acid lowering drug commonly used for hyperuricemia and gouty arthritis, has been reported as a common cause of severe cutaneous adverse drug reactions (SCAR) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). A strong association between allopurinol-induced SCAR and HLA-B*5801 was observed in a Han Chinese population with high frequency of this allele, whereas only a moderate association was observed in populations with low frequency (i.e. European and Japanese). This study investigated the relationship between SJS/TEN and HLA-B*5801 in a Thai population that has a high allelic frequency of this allele. METHODS: Twenty-seven allopurinol-induced SJS/TEN and 54 allopurinol-tolerant patients were enrolled in the study. The presence of HLA-B*5801 and HLA-B genotypes in these patients were analyzed using a PG5801 DNA detection kit and sequence-based typing, respectively. RESULTS: All of the 27 (100%) allopurinol-induced SJS/TEN patients who were examined carried HLA-B*5801 whereas only seven (12.96%) of the control patients had this allele. The risk of allopurinol-induced SJS/TEN was significantly greater in patients with HLA-B*5801 when compared with those who did not carry this allele, with an odds ratio of 348.3 (95% confidence interval=19.2-6336.9, P = 1.6 x10). The sensitivity and specificity of the HLA-B*5801 allele for prediction of allopurinol-induced SJS/TEN were 100 and 87%, respectively. By assuming a 0.2% prevalence rate, the positive predictive value and the negative predictive value of the HLA-B*5801 allele was 1.52 and 100%, respectively. CONCLUSION: A strong association of allopurinol-induced SJS/TEN with the HLA-B*5801 allele was observed in a Thai population. The results suggest that HLA-B*5801 is a valid genetic marker for screening Thai individuals who may be at risk for allopurinol-induced life-threatening SJS and TEN.
Authors: Daniel F B Wright; Stephen B Duffull; Tony R Merriman; Nicola Dalbeth; Murray L Barclay; Lisa K Stamp Journal: Br J Clin Pharmacol Date: 2015-12-29 Impact factor: 4.335
Authors: Yan Jia; Tao Su; Yanghui Gu; Cui Li; Xujie Zhou; Jianqun Su; Pingping Sun; Jiawei Tang; Liu Yang; Gang Liu; Li Yang Journal: J Immunol Date: 2018-06-01 Impact factor: 5.422
Authors: Sarah F Keller; Na Lu; Kimberly G Blumenthal; Sharan K Rai; Chio Yokose; Jee Woong J Choi; Seoyoung C Kim; Yuqing Zhang; Hyon K Choi Journal: Ann Rheum Dis Date: 2018-04-13 Impact factor: 19.103
Authors: Dinesh Khanna; John D Fitzgerald; Puja P Khanna; Sangmee Bae; Manjit K Singh; Tuhina Neogi; Michael H Pillinger; Joan Merill; Susan Lee; Shraddha Prakash; Marian Kaldas; Maneesh Gogia; Fernando Perez-Ruiz; Will Taylor; Frédéric Lioté; Hyon Choi; Jasvinder A Singh; Nicola Dalbeth; Sanford Kaplan; Vandana Niyyar; Danielle Jones; Steven A Yarows; Blake Roessler; Gail Kerr; Charles King; Gerald Levy; Daniel E Furst; N Lawrence Edwards; Brian Mandell; H Ralph Schumacher; Mark Robbins; Neil Wenger; Robert Terkeltaub Journal: Arthritis Care Res (Hoboken) Date: 2012-10 Impact factor: 4.794