The Frequency and Clinical Features of Hypersensitivity Reactions to Antiepileptic Drugs in Children: A Prospective Study

J Allergy Clin Immunol Pract. 2018 Nov-Dec;6(6):2043-2050. doi: 10.1016/j.jaip.2018.02.018. Epub 2018 Mar 6.


Background: Antiepileptic drugs (AEDs) can cause hypersensitivity reactions during childhood. Studies report a wide clinical spectrum of reactions with AED use, ranging from a mild rash to severe cutaneous reactions.

Objective: To determine the prevalence and clinical features of AED hypersensitivity reactions during childhood.

Methods: Patients in our pediatric neurology clinic who were prescribed an AED for the first time between November 2015 and November 2016 were monitored and those who developed skin rash during this period were evaluated.

Results: A total of 570 patients were evaluated. The median age of the patients was 8.86 (interquartile range, 4.2-13.7) years, and 55.8% (318) of patients were male. The most frequently used AEDs were valproic acid (42%, n = 285) and carbamazepine (20.4%, n = 116). Hypersensitivity reactions to AEDs developed in 5.4% of patients. Of these patients, 71% (29) had cutaneous drug reactions and 29% (9) had severe cutaneous drug reactions; 61.3% (19) were using aromatic AEDs, and the leading suspected AED was carbamazepine (45.2%). Comparison of patients who did and did not develop AED hypersensitivity showed that hypersensitivity was more frequent among patients who were younger than 12 years, who used aromatic AEDs, or who used multiple AEDs. In addition, according to regression analysis results, aromatic AED use significantly increased the risk of AED hypersensitivity (P < .001).

Conclusions: Although allergic reactions to AEDs are rare, they are of significance because they can cause life-threatening severe cutaneous drug reactions. Therefore, patients receiving AEDs, especially aromatic AEDs, must be monitored closely.

Keywords: Antiepileptic drugs; Child; DRESS; Epilepsy; Hypersensitivity; Patch test; SJS.

MeSH terms

  • Adolescent
  • Allergens / immunology
  • Anticonvulsants / immunology
  • Anticonvulsants / therapeutic use*
  • Carbamazepine / immunology
  • Carbamazepine / therapeutic use*
  • Child
  • Child, Preschool
  • Drug Hypersensitivity / epidemiology*
  • Female
  • Humans
  • Male
  • Prevalence
  • Prospective Studies
  • Skin / pathology*
  • Turkey / epidemiology
  • Valproic Acid / immunology
  • Valproic Acid / therapeutic use*


  • Allergens
  • Anticonvulsants
  • Carbamazepine
  • Valproic Acid