Severe cutaneous adverse reactions to antiepileptic drugs: A nationwide registry-based study in Korea

Korean Registry of Severe Cutaneous Adverse Reactions Consortium

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)709-722
Number of pages14
JournalAllergy, Asthma and Immunology Research
Volume11
Issue number5
DOIs
Publication statusPublished - 2019 Sep 1

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Korea
Anticonvulsants
Registries
Drug Hypersensitivity Syndrome
Skin
Carbamazepine
Stevens-Johnson Syndrome
etiracetam
Hospitalization
Pharmaceutical Preparations
Valproic Acid
Thrombocytopenia
Epidemiologic Studies
Length of Stay
Referral and Consultation
Odds Ratio
Confidence Intervals
Morbidity
Mortality
Incidence

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pulmonary and Respiratory Medicine

Cite this

Korean Registry of Severe Cutaneous Adverse Reactions Consortium. / Severe cutaneous adverse reactions to antiepileptic drugs : A nationwide registry-based study in Korea. In: Allergy, Asthma and Immunology Research. 2019 ; Vol. 11, No. 5. pp. 709-722.
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title = "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.",
author = "{Korean Registry of Severe Cutaneous Adverse Reactions Consortium} and Park, {Chan Sun} and Kang, {Dong Yoon} and Kang, {Min Gyu} and Sujeong Kim and Ye, {Young Min} and Kim, {Sae Hoon} and Park, {Hye Kyung} and Park, {Jung Won} and Nam, {Young Hee} and Yang, {Min Suk} and Jee, {Young Koo} and Jung, {Jae Woo} and Kim, {Sang Hyon} and Kim, {Cheol Woo} and Kim, {Mi Yeong} and Kim, {Joo Hee} and Jaechun Lee and Lee, {Jun Gyu} and Kim, {Sang Hyun} and La, {Hyen O.} and Kim, {Min Hye} and Park, {Seoung Ju} and Koh, {Young Il} and Lee, {Sang Min} and Kwon, {Yong Eun} and Jin, {Hyun Jung} and Kim, {Hee Kyoo} and Kang, {Hye Ryun} and Choi, {Jeong Hee}",
year = "2019",
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Severe cutaneous adverse reactions to antiepileptic drugs : A nationwide registry-based study in Korea. / Korean Registry of Severe Cutaneous Adverse Reactions Consortium.

In: Allergy, Asthma and Immunology Research, Vol. 11, No. 5, 01.09.2019, p. 709-722.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Severe cutaneous adverse reactions to antiepileptic drugs

T2 - A nationwide registry-based study in Korea

AU - Korean Registry of Severe Cutaneous Adverse Reactions Consortium

AU - Park, Chan Sun

AU - Kang, Dong Yoon

AU - Kang, Min Gyu

AU - Kim, Sujeong

AU - Ye, Young Min

AU - Kim, Sae Hoon

AU - Park, Hye Kyung

AU - Park, Jung Won

AU - Nam, Young Hee

AU - Yang, Min Suk

AU - Jee, Young Koo

AU - Jung, Jae Woo

AU - Kim, Sang Hyon

AU - Kim, Cheol Woo

AU - Kim, Mi Yeong

AU - Kim, Joo Hee

AU - Lee, Jaechun

AU - Lee, Jun Gyu

AU - Kim, Sang Hyun

AU - La, Hyen O.

AU - Kim, Min Hye

AU - Park, Seoung Ju

AU - Koh, Young Il

AU - Lee, Sang Min

AU - Kwon, Yong Eun

AU - Jin, Hyun Jung

AU - Kim, Hee Kyoo

AU - Kang, Hye Ryun

AU - Choi, Jeong Hee

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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.

AB - 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.

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