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.