Department of Pharmacology, Sri Manakula Vinayagar Medical College and Hospital, Puducherry-605017, India.
Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry- 605006, India.
Curr Drug Saf. 2022;17(1):40-46. doi: 10.2174/1574886316666210611160123.
BACKGROUND AND OBJECTIVE: Identification of the offending drug is crucial and challenging in cases of severe cutaneous adverse drug reactions (CADR) like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Poor reproducibility and varying levels of agreement have been observed among different causality assessment tools (CATs) in assessing severe CADRs. This study was conducted to examine the agreement among four different CATs in assessing cases of drug-induced SJS, TEN and SJS/TEN overlap. METHODS: All cases of drug-induced SJS, TEN and SJS/TEN overlap, which were reported between January 2012 and January 2020, were identified from the ADR register at an ADR monitoring centre. Causality assessment was done in these reported cases using the following CATs: The World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale, Naranjo algorithm, Liverpool algorithm and Algorithm of drug causality for epidermal necrolysis (ALDEN). Weighted kappa (κw) test was used to evaluate the agreement among four CATs. RESULTS: A total of 30 cases of drug-induced SJS, TEN and SJS/TEN overlap were included in our analyses. The most common offending groups of drugs were anticonvulsants (46.7%), antimicrobials (40%) and nonsteroidal anti-inflammatory drugs (13.3%). Of the anticonvulsants, phenytoin (13.3%), carbamazepine (10%), and valproate (10%) were the commonly reported offending drugs. Poor agreement was observed among the four different causality assessment scales. CONCLUSION: Discrepancies were observed among four different CATs in assessing drug-induced SJS and TEN. A CAT, which is more specific to drug-induced SJS and TEN, simple, user-friendly with limited subjective interpretation, incorporating new immunological and pharmacogenetic markers, is necessary.
背景与目的:在严重药物不良反应(CADR)病例中,如史蒂文斯-约翰逊综合征(SJS)和中毒性表皮坏死松解症(TEN),确定致敏药物至关重要且极具挑战性。不同因果关系评估工具(CAT)在评估严重 CADR 时,其重现性和一致性程度不一。本研究旨在评估四种不同 CAT 在评估药物诱导的 SJS、TEN 和 SJS/TEN 重叠病例中的一致性。
方法:从不良反应监测中心的 ADR 登记处,确定了 2012 年 1 月至 2020 年 1 月期间报告的所有药物诱导的 SJS、TEN 和 SJS/TEN 重叠病例。使用以下 CAT 对这些报告病例进行因果关系评估:世界卫生组织-乌普萨拉监测中心(WHO-UMC)量表、Naranjo 算法、利物浦算法和表皮坏死松解症药物因果关系算法(ALDEN)。使用加权 κ(κw)检验评估四种 CAT 之间的一致性。
结果:我们的分析共纳入 30 例药物诱导的 SJS、TEN 和 SJS/TEN 重叠病例。最常见的致敏药物类别为抗惊厥药(46.7%)、抗菌药物(40%)和非甾体抗炎药(13.3%)。在抗惊厥药中,苯妥英(13.3%)、卡马西平(10%)和丙戊酸(10%)是常见的致敏药物。四种不同因果关系评估量表之间观察到一致性较差。
结论:四种不同 CAT 在评估药物诱导的 SJS 和 TEN 时存在差异。需要一种更针对药物诱导的 SJS 和 TEN、简单、易于使用、主观解释有限、结合新的免疫和遗传标记的 CAT。
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