title: Spectrum of Cutaneous Adverse Reactions to Levetiracetam and Human Leukocyte Antigen Typing in North-Indian Patients.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Bhargavi
authors.initials: B
authors.lastname: Ramanujam
authors.affiliation: Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Kavish
authors.initials: K
authors.lastname: Ihtisham
authors.affiliation: Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Gurvinder
authors.initials: G
authors.lastname: Kaur
authors.affiliation: Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Shivani
authors.initials: S
authors.lastname: Srivastava
authors.affiliation: Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Narinder Kumar
authors.initials: NK
authors.lastname: Mehra
authors.affiliation: Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Neena
authors.initials: N
authors.lastname: Khanna
authors.affiliation: Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Mahip
authors.initials: M
authors.lastname: Singh
authors.affiliation: Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Manjari
authors.initials: M
authors.lastname: Tripathi
keywords: Human leukocyte antigen (HLA); Levetiracetam; Maculo-papular exanthem; Stevens-Johnson syndrome; Toxic Epidermal Necrolysis