Allergy Asthma Immunol Res.  2019 Sep;11(5):709-722. 10.4168/aair.2019.11.5.709.

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

• Park CS
• Kang DY
• Kang MG
• Kim S
• Ye YM
• Kim SH
• Park HK
• Park JW
• Nam YH
• Yang MS
• Jee YK
• Jung JW
• Kim SH
• Kim CW
• Kim MY
• Kim JH
• Lee J
• Lee JG
• Kim SH
• La HO
• Kim MH
• Park SJ
• Koh YI
• Lee SM
• Kwon YE
• Jin HJ
• Kim HK
• Kang HR
• Choi JH
• Korean Registry of Severe Cutaneous Adverse Reactions Consortium

• KMID: 2452760
• DOI: http://doi.org/10.4168/aair.2019.11.5.709

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.

Keyword

Antiepileptic drugs; Stevens-Johnson syndrome; toxic epidermal necrolysis

MeSH Terms

Anticonvulsants*
Carbamazepine
Cicatrix
Drug Hypersensitivity Syndrome
Epidemiologic Studies
Hospitalization
Humans
Incidence
Korea*
Length of Stay
Mortality
Referral and Consultation
Risk Factors
Stevens-Johnson Syndrome
Thrombocytopenia
Valproic Acid
Anticonvulsants
Carbamazepine
Valproic Acid

Figure

• 

  Figure Causative drugs of SJS, TEN + SJS/TEN overlap, and DRESS. SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis; DRESS, drug reaction with eosinophilia and systemic symptoms.

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