The HLA-B*15:02 allele is associated with an increased risk of developing carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
Previously, we have reported the association of HLA-A*02:06 and HLA-B*44:03 with cold medicine (CM)-related SJS/TEN with severe ocular complications (SOCs) in the Japanese population.
However, it did assess an outcome of (characteristically severe) hypersensitivity reaction which included (but was not limited to) our secondary outcomes of HSS and SJS/TEN.The study demonstrated that prospective HLA-B*57:01 screening probably reduces the incidence of hypersensitivity reaction to abacavir.
Among the severe cADRs, HLA-B*57:01(OR = 11.00 95% CI: 1.41-85.81) and HLA-DRB1*07:01 (OR = 7.25; 95% CI: 1.09-48.18) were noted to be significantly associated with CBZ-induced Stevens Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN); HLA-B *51:01 was associated with drug reaction eosinophilia and systemic symptoms (DRESS) caused by PHT (OR = 6.90; 95% CI: 1.38-34.29).
Allergic drug reactions are unpredictable; nevertheless, there is increased risk of drug hypersensitivity in (1) patients with cystic fibrosis who receive antibiotics; (2) patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) who receive trimethoprim-sulfamethoxazole or if human leukocyte antigen (HLA)-B*5701+ and receive the antiretroviral agent abacavir; (3) other genetically susceptible populations, e.g., Han-Chinese with HLA-B*1502+ who develop Stevens-Johnson syndrome and toxic epidermal necrolysis from carbamazepine, with HLA-B*5801+ who are at increased risk for such reactions from allopurinol, those with HLA-A*32:01 and receive vancomycin and develop drug reaction with eosinophilia and systemic symptoms syndrome; and (4) patients with a history of compatible allergic reactions to the same medication, similar class, or potentially unrelated medication.
The HLA-B*15:02 polymorphism was also strongly associated with the CBZ-SJS subgroup (OR: 152.089, 95% CI: 34.737-665.901) and significantly associated with the CBZ-SJS/TEN subgroup (OR: 13.993, 95% CI: 7.291-26.856).
Due to the significant risk of developing Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), the use of carbamazepine is not recommended in patients carrying the human leukocyte antigen B (HLA-B) *15:02 allele.
The presence of HLA-B*15:02 and CYP2C9 *2 or *3 in the same patient increases the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis; hence, PHT should not be prescribed in these patients.
Additionally, 17 of 49 patients with CM-SJS/TEN with SOC (34.7%) significantly harboured the HLA-B*44:03 and HLA-C*07:01 haplotype compared with only 11 of 159 healthy controls (6.9%) (OR=7.1, p=5.5×10<sup>-6</sup>).
The variant allele HLA-B*15:02 is strongly associated with greater risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients treated with carbamazepine or oxcarbazepine.
HLA-A*31: 01 and HLA-B*15:02 association with Stevens-Johnson syndrome and toxic epidermal necrolysis to carbamazepine in a multiethnic Malaysian population.
We also confirmed HLA-B*15:02 association with PHT-SJS/TEN (61.5%, 8/13 cases vs 21.9%, 7/32 controls; OR 5.71, P=0.016) when compared with PHT-tolerant controls.
Positive HLA-B*5801 carriers are at greater risk of experiencing rare but severe allopurinol hypersensitivity syndrome (AHS) [i.e., Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)]; however, HLA-B*5801 prevalence and AHS risk vary by race/ethnicity.
For example, it is well-established that HLA-B*15:02 and HLA-B*57:01 are associated with carbamazepine-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and abacavir-induced hypersensitivity/flucloxacillin-induced liver injury, respectively.
This study suggests that HLA-A*66:01 might be a marker for CM-SJS/TEN with SOCs in Brazilian individuals of Pardo and European ancestry and that HLA-B*44:03 and HLA-C*12:03 might be markers only in those of European ancestry.
Screening for <i>HLA-B*15:02</i> is mandated in patients from South East Asia because of a strong association with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
We also found that the haplotypes consisting of HLA-B*44:03 and HLA-C*07:01 were strongly associated with SJS/TEN with SOC in our Indian population (p = 1.1 × 10<sup>-7</sup>, odds ratio = 11.0).
HLA-B*15:02 and HLA-B*15:21 are members of the HLA-B75 serotype, for which a greater frequency was observed in CBZ-induced SJS/TEN (vs tolerant control [p = 0.0078; OR: 12; 95% CI: 1.90-75.72] and vs normal control [p = 0.0018; OR: 8.56; 95% CI: 1.83-40]).