史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症的因果关系归因

Attribution of causality in Stevens-Johnson syndrome/toxic epidermal necrolysis.

作者信息

Parvathaneni Asha, Benchetrit Liliya, Metcalfe Derek, Kwan James T, Bian Yandong, Van Zyl Tavé, Saeed Hajirah N, Chodosh James

机构信息

University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA.

Department of Otolaryngology-Head and Neck Surgery Boston University Medical Center Boston, Massachusetts, USA.

出版信息

Ocul Surf. 2025 Jun 18;38:104-112. doi: 10.1016/j.jtos.2025.06.004.

Abstract

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is an acute, severe immunobullous disorder of skin and mucous membranes that is most commonly induced by exposure to drugs. Causation of SJS/TEN is most often determined by the "algorithm of drug causality for epidermal necrolysis" (ALDEN) tool. However, concerns remain regarding the precision of ALDEN and causality assessment tools, potentially impacting ongoing studies attempting to link specific genotypes with specific drug classes as causes. To determine whether a standard of care exists in attribution of causation in SJS/TEN, we performed a narrative review of current concepts on causation in SJS/TEN, and available clinical and laboratory assessment tools for attributing causation. We found that current SJS/TEN causality attribution tools, including ALDEN, are somewhat limited by underlying assumptions. The utility of ex vivo tests proposed for determining causation in SJS/TEN, specifically the lymphocyte transformation test and cytokine stimulation assays, remain under investigation and are either not tractable for acute SJS/TEN or are not yet validated. In summary, a critical unmet need exists in the care of SJS/TEN patients, namely the difficulty in determining a precise cause in any specific individual. This shortfall limits the clinician's ability to discontinue only the causal agent in the acute phase, confounds studies of pathogenesis, and leaves affected patients in the chronic phase without knowing which drug or drug class is safe to use in the future. Further studies are needed to close this critical gap in the care of this devastating disease.

摘要

史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症(SJS/TEN)是一种急性、严重的皮肤和黏膜免疫性大疱性疾病,最常见的诱因是接触药物。SJS/TEN的病因通常由“表皮坏死松解症药物因果关系算法”(ALDEN)工具来确定。然而,人们对ALDEN及因果关系评估工具的准确性仍存在担忧,这可能会影响正在进行的试图将特定基因型与特定药物类别作为病因联系起来的研究。为了确定SJS/TEN病因归因是否存在护理标准,我们对SJS/TEN病因的当前概念以及用于归因的现有临床和实验室评估工具进行了叙述性综述。我们发现,当前包括ALDEN在内的SJS/TEN因果关系归因工具在一定程度上受到潜在假设的限制。为确定SJS/TEN病因而提出的体外试验,特别是淋巴细胞转化试验和细胞因子刺激试验的效用仍在研究中,对于急性SJS/TEN来说,要么难以操作,要么尚未得到验证。总之,SJS/TEN患者护理中存在一个关键的未满足需求,即在任何特定个体中难以确定确切病因。这一不足限制了临床医生在急性期仅停用致病药物的能力,混淆了发病机制的研究,并使处于慢性期的患者不知道未来哪种药物或药物类别使用起来是安全的。需要进一步研究来填补这种毁灭性疾病护理中的这一关键空白。

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