Association of cutaneous adverse drug reactions due to antiepileptic drugs with HLA alleles in a North Indian population

• Published in: Seizure (London, England) England), 2019-03, Vol.66, p.99-103
• Main Authors: Ihtisham, Kavish, Ramanujam, Bhargavi, Srivastava, Shivani, Mehra, Narinder Kumar, Kaur, Gurvinder, Khanna, Neena, Jain, Satish, Kumar, Sachin, Kaul, Bhavna, Samudrala, Raghavan, Tripathi, Manjari
• Format: Article
• Language: English
• Subjects: Antiepileptic drugs; Drug reaction eosinophilia and systemic symptoms (DRESS); Human leukocyte antigen (HLA); Maculopapular exanthema (MPE); Stevens-Johnson syndrome (SJS); Toxic Epidermal Necrolysis (TEN)
• ISSN: 1059-1311; 1532-2688
• DOI: 10.1016/j.seizure.2019.02.011

•North Indian subjects with cADRs to AEDs were studied for HLA associations.•HLA-A*31:01 and B*51:01 were associated with MPE due to CBZ and PHT; p = 0.01,0.002.•HLA-DRB1*07:01 was associated with CBZ-induced SJS/TEN; p = 0.01.•HLA-B *51:01 was associated with DRESS caused by PHT; p = 0.007.•HLA-B*15:02 was not significantly associated with any AED-related cADR. Aromatic antiepileptic drugs (AEDs) are frequently implicated in cutaneous adverse drug reactions (cADRs), a few of which are associated with certain human leukocyte antigen (HLA) alleles in some populations. We aimed to find HLA-associations with AED-related cADRs among North Indians. North Indian subjects with cADR due to an AED, and those who were AED-tolerant were recruited as cases and controls, respectively. Genotyping for HLA-A, B and DRB1 were performed. Statistical analysis to compare carrier-rates and allele-frequencies between cases and controls (and healthy population, where necessary), was done for HLA-alleles occurring more than twice in either group. 120 cases {11 - Lamotrigine (LTG), 14 -Valproic acid (VPA), 8 -Levetiracetam (LEV), 35 -Carbamazepine (CBZ) and 52 - Phenytoin (PHT)}, and 250 controls were recruited. Presence of HLA-A*31:01 and HLA-B*51:01 were found to increase the risk of Maculopapular exanthema (MPE) due to CBZ and PHT (OR = 6.38; 95% CI: 1.46–27.75; OR = 4.60; 95% CI: 1.54–13.72, respectively). 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). We found significant associations of some HLA alleles with specific cADRs to CBZ and PHT in North Indians, which may need to be tested before AED-initiation; only screening for HLA-B*15:02 may not help in this population.