A study of HLA class I and class II 4-digit allele level in Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are represented by rare but life-threatening cutaneous adverse reactions to different drugs. Previous studies have found that in a Han Chinese population from Taiwan and other Asian Countries, a strong genetic association between HLA-class I alleles (B*15:02, B*58:01) and SJS and TEN was induced by carbamazepine and allopurinol, respectively. To identify genetic markers that covered the MHC region, we carried out a case-control association enrolling 20 Caucasian patients with SJS/TEN. Our patient series included 10 cases related to paracetamol, 7 to allopurinol and 3 to different drugs (plaquenil, itraconazol, nabumetone). Healthy controls were represented by 115 Caucasian bone marrow or stem cell donors. The HLA-A*, B*, C*, DRB1*, DQB1*, DQA1* and DPB1* genotyping were determined. The frequencies of HLA-A*33:03 as well as C*03:02 and C*08:01 were significantly higher in SJS/TEN patient subgroup showing allopurinol drug-induced severe cutaneous adverse reactions (SCAR) as compared to controls (28.6% vs 0%, P=0.00002, Pc=0.0011; 28.6% vs 0%, P=0.00002, Pc=0.001; 28.6% vs 0%, P=0.00002, Pc=0.001, respectively). In the same subgroup the frequencies of B*58:01, DRB1*15:02 and DRB1*13:02 alleles, although considerably higher than in control group (42.8% vs 5.2%, P=0.003; 28.6% vs 1.7%, P=0.005; 28.6% vs 3.5%, P=0.037, respectively), appeared no more statistically different after P correction (Pc=0.248; Pc=0.29; Pc=1.00, respectively). In addition, in 10 of the 20 SJS/TEN patient subgroup with paracetamol-induced SCAR no statistically significant association with HLA alleles could be found. However, in the same SJS/TEN patient subgroup showing allopurinol drug-induced SCAR, haplotype analysis indicated that B*58:01, DRB1*13:02 and DRB1*15:02 alleles, that in a single allele analysis lost statistical significance after P correction, may still confer susceptibility, because the B*58:01-DRB1*13:02 and DRB1*15:02-DQB1*05:02 are positively associated with the disease (14.2% vs 0.43%, P= 0.00001, Pc=0.00028; 14.2% vs 0.43%, P=0.00001, Pc=0.00028, respectively). Our results show that in contrast to SCAR-related to paracetamol, where HLA alleles do not appear to be involved, HLA molecules behave as a strong risk factor for SCAR-related to allopurinol even when a limited number of patients are considered.

Cristallo AF ，Schroeder J ，Citterio A ，Santori G ，Ferrioli GM ，Rossi U ，Bertani G ，Cassano S ，Gottardi P ，Ceschini N ，Barocci F ，Ribizzi G ，Cutrupi V ，Cairoli R ，Rapisarda V ，Pastorello EA ，Barocci S ... -  《-》

Strong association between HLA-B*5801 and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in a Thai population.

Tassaneeyakul W ，Jantararoungtong T ，Chen P ，Lin PY ，Tiamkao S ，Khunarkornsiri U ，Chucherd P ，Konyoung P ，Vannaprasaht S ，Choonhakarn C ，Pisuttimarn P ，Sangviroon A ，Tassaneeyakul W ... -  《Pharmacogenetics and Genomics》

A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs.

Lonjou C ，Borot N ，Sekula P ，Ledger N ，Thomas L ，Halevy S ，Naldi L ，Bouwes-Bavinck JN ，Sidoroff A ，de Toma C ，Schumacher M ，Roujeau JC ，Hovnanian A ，Mockenhaupt M ，RegiSCAR study group ... -  《Pharmacogenetics and Genomics》

HLA-B*1502 strongly predicts carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Thai patients with neuropathic pain.

Carbamazepine (CBZ) is one of the standard pharmacological treatments for neuropathic pain. However, its serious adverse drug reactions include Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Recently, HLA-B*1502 allele was implicated as a genetic marker of CBZ-induced SJS/TEN in some Asian epilepsy populations. This is a case control study to describe the clinical characteristics of SJS/TEN in Thai patients with neuropathic pain who were treated with CBZ, and to determine the association of HLA-B*1502 in these patients, comparing with those who exposed to CBZ for at least 6 months without any cutaneous reactions. Thirty-four SJS/TEN patients and 40 control patients were included in this study. Mean age of SJS/TEN patients was 47 years. SJS/TEN was developed in 10.8 ± 1.4 days after initiation of CBZ. HLA-B*1502 allele was found in 32 of 34 SJS/TEN patients (94.1%) but it was found only in 7 of 40 control patients (17.5%). The association was very strong with an odds ratio of 75.4. Sensitivity and specificity of this HLA-B*1502 genotype test were 94.1% and 82.5%, respectively, while the positive predictive value and negative predictive value were 1.43% and 99.98%, respectively. Positive and negative likelihood ratios were 5.37 and 0.07, respectively. HLA-B*1502 is a strong genetic marker for CBZ-induced SJS/TEN in Thai patients with neuropathic pain. The screening for this marker should be performed prior to initiation of CBZ treatment to assess the risk of this serious side effect.

Kulkantrakorn K ，Tassaneeyakul W ，Tiamkao S ，Jantararoungtong T ，Prabmechai N ，Vannaprasaht S ，Chumworathayi P ，Chen P ，Sritipsukho P ... -  《-》

HLA class I (A, B, C) and class II (DRB1, DQA1, DQB1, DPB1) alleles and haplotypes in the Han from southern China.

Trachtenberg E ，Vinson M ，Hayes E ，Hsu YM ，Houtchens K ，Erlich H ，Klitz W ，Hsia Y ，Hollenbach J ... -  《-》