Severe Cutaneous Adverse Reactions to Antiepileptic Drugs: A Nationwide Registry-Based Study in Korea

Abstract

Purpose Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) to antiepileptic drug (AED), are rare, but result in significant morbidity and mortality. We investigated the major culprit drugs, clinical characteristics, and clinical course and outcomes of AED-induced SCARs using a nationwide registry in Korea. Methods A total of 161 patients with AED-induced SCARs from 28 referral hospitals were analyzed. The causative AEDs, clinical characteristics, organ involvements, details of treatment, and outcomes were evaluated. We compared the clinical and laboratory parameters between SJS/TEN and DRESS according to the leading causative drugs. We further determined risk factors for prolonged hospitalization in AED-induced SCARs. Results Carbamazepine and lamotrigine were the most common culprit drugs causing SCARs. Valproic acid and levetiracetam also emerged as the major causative agents. The disease duration and hospital stay in carbamazepine-induced SJS/TEN were shorter than those in other AEDs ( P < 0.05, respectively). In younger patients, lamotrigine caused higher incidences of DRESS than other drugs ( P = 0.045). Carbamazepine, the most common culprit drug for SCARs, was associated with a favorable outcome related with prolonged hospitalization in SJS (odds ratio, 0.12; 95% confidence interval, 0.02-0.63, P = 0.12), and thrombocytopenia was found to be a risk factor for prolonged hospitalization in DRESS. Conclusion This was the first large-scale epidemiological study of AED-induced SCARs in Korea. Valproic acid and levetiracetam were the significant emerging AEDs causing SCARs in addition to the well-known offending AEDs such as carbamazepine and lamotrigine. Carbamazepine was associated with reduced hospitalization, but thrombocytopenia was a risk factor for prolonged hospitalization. Our results suggest that the clinical characteristics and clinical courses of AED-induced SCARs might vary according to the individual AEDs.

Adverse drug reaction profile in Amravati region of India: A pharmacovigilance study

“…[ 49 ] We found reddish pruritic macular rash all over the body with the use of divalporex sodium (coordination compound of valproic acid with sodium valproate). Park et al [ 50 ] investigated antiepileptic drug-induced severe cutaneous adverse reactions using a nationwide registry in Korea. They found valproic acid as the major causative agent in severe cutaneous adverse reaction, indicating its role in skin reactions.…”

“…They found valproic acid as the major causative agent in severe cutaneous adverse reaction, indicating its role in skin reactions. [ 50 ]…”

Drug rash with eosinophilia and systemic symptoms syndrome in an adolescent - efficiency of immunoglobulin G in a corticosteroid resistant case

“…In conclusion, we join the authors [6,[10][11][12][13][14][15][16][17][18]20] of who favor the treatment of DRESS sy using IVIG, and we point out to the need to change the order of recommendations in the current treatment recommendations for DRESS sy [5,9] in favor of IVIG. IVIG should be considered as a second-line treatment as soon as possible in patients in whom corticosteroid treatment failed.…”

“…HLA-B*15:02) which indicates the need for genetic testing [19]. Korea authors published results of national study and consideration that IVIG monotherapy or the combination of corticosteroids and IVIG might reduce the mortality rate in severe DRESS sy related to antiepileptic drugs [20].…”

Incidence rates of severe cutaneous adverse reactions due to antiseizure medication: A nationwide study using health claims data in Korea

“…SCARs are rare but sometimes lead to multiorgan failure, prolonged hospitalization, and an elevated risk of mortality 6 . Recently, two nationwide studies in Korea reported on the risk of SCARs due to ASM use based on spontaneous reporting systems 7,8 . However, spontaneous reporting systems tend to be less reliable due to possible underreporting 9 .…”