Association of cutaneous adverse drug reactions due to antiepileptic drugs with HLA alleles in a North Indian population. (March 2019)

• Record Type: Journal Article
• Authors: Ihtisham, Kavish; Ramanujam, Bhargavi; Srivastava, Shivani; Mehra, Narinder Kumar; Kaur, Gurvinder; Khanna, Neena; Jain, Satish; Kumar, Sachin; Kaul, Bhavna; Samudrala, Raghavan; Tripathi, Manjari
• Is Part Of: Seizure. Volume 66(2019)
• Page Start: 99
• Page End: 103
• Publication Date: 2019-03
• Subjects: Antiepileptic drugs -- Maculopapular exanthema (MPE) -- Stevens-Johnson syndrome (SJS) -- Toxic Epidermal Necrolysis (TEN) -- Human leukocyte antigen (HLA) -- Drug reaction eosinophilia and systemic symptoms (DRESS); Epilepsy -- Periodicals; Epilepsy -- Periodicals; Seizures -- Periodicals; Épilepsie -- Périodiques; Electronic journals; Electronic journals; 616.853
• DOI: 10.1016/j.seizure.2019.02.011
• Languages: English
• ISSNs: 1059-1311

Abstract

Highlights: 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. Abstract: Purpose: 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. Methods: 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. Results: 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). Conclusions: 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.