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. 2016 Dec 31;6(2):87-92.
doi: 10.14581/jer.16016. eCollection 2016 Dec.

Spectrum of Cutaneous Adverse Reactions to Levetiracetam and Human Leukocyte Antigen Typing in North-Indian Patients

Bhargavi Ramanujam  1 , Kavish Ihtisham  1 , Gurvinder Kaur  2 , Shivani Srivastava  1 , Narinder Kumar Mehra  2 , Neena Khanna  3 , Mahip Singh  1 , Manjari Tripathi  1
Affiliations

Spectrum of Cutaneous Adverse Reactions to Levetiracetam and Human Leukocyte Antigen Typing in North-Indian Patients

Bhargavi Ramanujam et al. J Epilepsy Res. .

Abstract

Background and purpose: Aromatic antiepileptic drugs are frequently implicated for cutaneous adverse drug reactions (cADRs); there are case-reports of even severe reactions like drug reaction eosinophilia and systemic symptoms (DRESS) and Stevens Johnson syndrome (SJS)-toxic epidermal necrolysis with Levetiracetam (LEV). Certain human leukocyte antigen (HLA)-alleles have strong association with cADRs due to specific drugs - HLA-B*15:02 and HLA-A*31:01 in Carbamazepine (CBZ)-related SJS in Han-Chinese and European populations, respectively. Here, the spectrum of cADRs to LEV was studied, and HLA-typing in patients with cADRs due to LEV and some who were LEV-tolerant was performed, in an attempt to find an association between HLA and such reactions.

Methods: 589 patients taking LEV were screened for skin reactions, and eight patients with LEV-related cADRs and 25 LEV-tolerant controls were recruited - all 33 of North Indian ethnicity, their HLA-A, B, DRB1 genotyping done. Statistical analysis was done to compare carrier-rates and allele-frequencies of HLA-alleles between cases and controls (and healthy population, where necessary) for alleles occurring more than two times in either group.

Results: Out of 589 patients on LEV screened, there were 8 cases of cADR: 5 with maculopapular exanthema (MPE), 2 of SJS, and 1 with DRESS. Although HLA-A*33:01 was seen to occur more in MPE cases as compared to tolerant controls, the difference was not statistically significant (odds ratio [OR] 6.00, 95% confidence interval [CI] 0.30-116.6; p = 0.31). HLA A*11:01 and 24:02 were found to occur more in LEV-tolerant controls than in cases (OR 0.23 [95% CI 0.02-2.36, p = 0.33] and 1.00 [95% CI 0.09-11.02, p = 1.00] respectively).

Conclusions: Cutaneous reactions to LEV are very unusual, and their association with HLA in North-Indian population was not statistically significant.

Keywords: Human leukocyte antigen (HLA); Levetiracetam; Maculo-papular exanthem; Stevens-Johnson syndrome; Toxic Epidermal Necrolysis.

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