Yonsei Med J. 2019;60(2):208-215.

Analysis of Individual Case Safety Reports of Severe Cutaneous Adverse Reactions in Korea.

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제1저자 강민규 · 교신저자 강혜련

PMID 30666843 PMC6342723 DOI 10.3349/ymj.2019.60.2.208 IF 3.1 알레르기내과

소속 (10)

Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea.
Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea.
Regional Pharmacovigilance Center, Chungbuk National University Hospital, Cheongju, Korea.
Department of Internal Medicine, Kyung-Hee University Hospital, Seoul, Korea.
Regional Pharmacovigilance Center, Seoul National University Hospital, Seoul, Korea.
Drug Safety Monitoring Center, Seoul National University Hospital, Seoul, Korea.
Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Korea.
Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.
College of Pharmacy, Seoul National University, Seoul, Korea.
Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. helenmed@snu.ac.kr.

Abstract

PURPOSE Despite morbidities and fatalities, nationwide epidemiologic data for severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), are not widely available. We aimed to investigate SCAR epidemiology over the last two decades in Korea.

MATERIALS AND METHODS We analyzed individual case safety reports (ICSRs) of SCARs in the Korea Adverse Event Reporting System from 1988 to 2013. Administered drugs, demographic profiles, and causality assessment according to the World Health Organization-Uppsala Monitoring Center system were analyzed.

RESULTS A total of 755 SCAR cases (508 SJS/TEN, 247 DRESS) were reported. The number of SCAR ICSRs has been increasing with increasing ICSRs for overall adverse drug events. Since 2010, the number of SCAR ICSRs has increased up to 100 cases/year. Allopurinol was the most common causative drug (SJS/TEN: 10.2%; DRESS: 11.3%; SCAR ICSRs: 10.6%), followed by carbamazepine (SJS/TEN: 8.7%; DRESS: 9.7%; SCAR ICSRs: 8.6%). Regarding drug groups, antiepileptics (19.5%) and antibiotics for systemic use (12.7%) were common causative drug groups. Twenty SCAR-related deaths were recorded. Antibacterials were the most common causes of deaths (8 cases), followed by antiepileptics (5 cases). The potential risk of SCARs was not specified in the drug information leaflet for 40.2% of drugs causing SJS/TEN and 82.5% causing DRESS syndrome in Korea.

CONCLUSION The number of SCAR ICSRs has increased rapidly with recent active pharmacovigilance programs in Korea. Allopurinol and antiepileptics are the most common individual and categorical causative agents, respectively.

Keywords

PharmacovigilanceStevens-Johnson syndromedrug hypersensitivity syndrometoxic epidermal necrolysis

Figures

**Fig. 1** Scheme of the selection process for ICSRs of SCARs in the KIDS-KD. ICSRs, individual case safety reports; SCARs, severe cutaneous adverse reactions; KIDS-KD, Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System database; ADE, adverse drug event; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis; DRESS syndrome, drug reaction with eosinophilia and systemic symptoms syndrome; DHS, drug hypersensitivity syndrome; WHO-ART, World Health Organization Adverse Reactions Terminology.

**Fig. 2** Trends in annual numbers of ICSRs of SCARs in KAERS. ICSRs, individual case safety reports; SCARS, severe cutaneous adverse reactions; KAERS, Korea Adverse Event Reporting System; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis; DRESS syndrome, drug reaction with eosinophilia and systemic symptoms syndrome.

**Fig. 3** Proportion of causative drugs for SCARs categorized by the main therapeutic group (second level) per ATC classification. (A) Total, (B) SJS/TEN, (C) DRESS syndrome. SCARs, severe cutaneous adverse reactions; ATC, anatomical therapeutic chemical; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis; DRESS syndrome, drug reaction with eosinophilia and systemic symptom syndrome. ATC code: B01 (antithrombotic agents), H02 (corticosteroids for systemic use), J01 (antibacterials for systemic use), J04 (antimycobacterials), L01 (antineoplastic agents), M01 (anti-inflammatory and antirheumatic products), M04 (anti-gout preparations), N02 (analgesics), N03 (antiepileptics), S01 (ophthalmologicals), and undetermined (cases in which two or more drugs were simultaneously reported as a causative agent so that the culprit drug could not be identified).

그림 출처: PubMed Central 공개 논문 (PMC6342723)

Conflict of interest statement

The authors have no potential conflicts of interest to disclose.

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