Journal of Pediatric Epilepsy 2022; 11(04): 097-102
DOI: 10.1055/s-0042-1749344
Original Article

Antiepileptic Drug Adverse Cutaneous Reaction in Childhood

1   Department of Pediatric Neurology, Health Ministry Eskişehir City Hospital, Eskişehir, Turkey
,
2   Department of Pediatric Neurology, Health Ministry Bursa Yüksek İhtisas Eğitim Araştirma Hastanesi, Bursa, Turkey
,
3   Department of Pediatric Immunology and Allergy, Health Ministry Kütahya Health Science University, Kütahya, Turkey
,
4   Department of Pediatrics, Health Ministry Eskisehir City Hospital, Eskisehir, Turkey
› Author Affiliations

Abstract

Antiepileptic drug (AED) side effects can result in treatment failure, morbidity, and mortality. Adverse cutaneous drug reactions (ACRs) frequently occur within the first 2 to 3 months of drug use. We wanted to discuss antiepileptic ACRs in childhood in this study. This was a study of 37 pediatric patients who were diagnosed with ACR and treated with AED in the last 5 years. Over a 5-year period, 37 (1.8%) of the 2,064 epilepsy patients had ACRs. There were 23 (62%) male patients and 14 (38%) female patients. Patients had a median age of 6 years (interquartile range: [IQR]: 3.5–10). The ACRs occurred in a median of 20 (IQR: 14–30) days. There were 28 (75%) patients receiving monotherapy and 9 (25%) patients receiving polytherapy. Overall, 22 (59.5%) of the 37 patients used aromatic drugs (AD), while 15 (40.5%) used nonaromatic drugs (NAD). Morbilliform eruptions accounted for the majority of ACRs (84%). Valproic acid (54%) was the most frequently used AED that resulted in ACRs. There was no significant difference in terms of eruption time, gender, or age between AD and NAD. Within 1 to 2 months of initiating a new AED, patients should be closely monitored for ACRs. If an ACR develops for one AED, greater caution should be taken when initiating the other AED. Although it is well established that ADs cause more skin reactions, we found that one of the NADs, valproic acid, causes more skin reactions.



Publication History

Received: 20 February 2022

Accepted: 14 April 2022

Article published online:
27 June 2022

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  • References

  • 1 Thong B, Vervloet D. Drug allergies. Accessed January 23, 2021 at: https://www.worldallergy.org/education-and-programs/education/allergic-disease-resource-center/professionals/drug-allergies
  • 2 Philp JR. Allergic drug reactions. In: Walker HK, Hall WD, Hurst JW. eds. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Boston, MA: Butterworths; 1990: 956-967
  • 3 Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med 1994; 331 (19) 1272-1285
  • 4 Mockenhaupt M. Epidemiology of cutaneous adverse drug reactions. Allergol Select 2017; 1 (01) 96-108
  • 5 Beghi E, Shorvon S. Antiepileptic drugs and the immune system. Epilepsia 2011; 52 (suppl 3): 40-44
  • 6 Błaszczyk B, Lasoń W, Czuczwar SJ. Antiepileptic drugs and adverse skin reactions: an update. Pharmacol Rep 2015; 67 (03) 426-434
  • 7 Mani R, Monteleone C, Schalock PC, Truong T, Zhang XB, Wagner ML. Rashes and other hypersensitivity reactions associated with antiepileptic drugs: a review of current literature. Seizure 2019; 71: 270-278
  • 8 Krauss G. Current understanding of delayed anticonvulsant hypersensitivity reactions. Epilepsy Curr 2006; 6 (02) 33-37
  • 9 Handoko KB, van Puijenbroek EP, Bijl AH. et al. Influence of chemical structure on hypersensitivity reactions induced by antiepileptic drugs: the role of the aromatic ring. Drug Saf 2008; 31 (08) 695-702
  • 10 Wang XQ, Lang SY, Shi XB, Tian HJ, Wang RF, Yang F. Antiepileptic drug-induced skin reactions: a retrospective study and analysis in 3793 Chinese patients with epilepsy. Clin Neurol Neurosurg 2012; 114 (07) 862-865
  • 11 Arif H, Buchsbaum R, Weintraub D. et al. Comparison and predictors of rash associated with 15 antiepileptic drugs. Neurology 2007; 68 (20) 1701-1709
  • 12 Park CS, Kang DY, Kang MG. et al; Korean Registry of Severe Cutaneous Adverse Reactions Consortium. Severe cutaneous adverse reactions to antiepileptic drugs: a nationwide registry-based study in Korea. Allergy Asthma Immunol Res 2019; 11 (05) 709-722
  • 13 Guvenir H, Dibek Misirlioglu E, Civelek E. et al. The frequency and clinical features of hypersensitivity reactions to antiepileptic drugs in children: a prospective study. J Allergy Clin Immunol Pract 2018; 6 (06) 2043-2050
  • 14 Hung SI, Chung WH, Liu ZS. et al. Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics 2010; 11 (03) 349-356
  • 15 Tangamornsuksan W, Chaiyakunapruk N, Somkrua R, Lohitnavy M, Tassaneeyakul W. Relationship between the HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. JAMA Dermatol 2013; 149 (09) 1025-1032
  • 16 Zaccara G, Franciotta D, Perucca E. Idiosyncratic adverse reactions to antiepileptic drugs. Epilepsia 2007; 48 (07) 1223-1244
  • 17 Ye YM, Thong BY, Park HS. Hypersensitivity to antiepileptic drugs. Immunol Allergy Clin North Am 2014; 34 (03) 633-643 , ix
  • 18 Gomes ER, Demoly P. Epidemiology of hypersensitivity drug reactions. Curr Opin Allergy Clin Immunol 2005; 5 (04) 309-316
  • 19 Thong BY, Tan TC. Epidemiology and risk factors for drug allergy. Br J Clin Pharmacol 2011; 71 (05) 684-700
  • 20 Błaszczyk B, Szpringer M, Czuczwar SJ, Lasoń W. Single centre 20 year survey of antiepileptic drug-induced hypersensitivity reactions. Pharmacol Rep 2013; 65 (02) 399-409
  • 21 Hsu DY, Brieva J, Silverberg NB, Paller AS, Silverberg JI. Pediatric Stevens-Johnson syndrome and toxic epidermal necrolysis in the United States. J Am Acad Dermatol 2017; 76 (05) 811-817.e4
  • 22 Jenson NO, Dam M, Jakobsen K. Oxcarbazepine in patients hypersensitive to carbamazepine. Isr J Med Sci 1986; 155 (08) 297
  • 23 Sofi FA, Koul PA, Mufti SA, Dhobi GN. Lamotrigine-induced toxic epidermal necrolysis in a young epileptic. BMJ Case Rep 2011; 2011: bcr0420114149