Godfrey Hannah, Jedlowski Patrick, Thiede Rebecca
University of Arizona College of Medicine-Tucson, Tucson, AZ, USA.
Division of Dermatology, University of Arizona College of Medicine-Tucson, Tucson, AZ, USA.
J Cutan Med Surg. 2024 Jan-Feb;28(1):51-58. doi: 10.1177/12034754231220931. Epub 2024 Jan 8.
Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) are potentially life-threatening severe cutaneous adverse reactions (SCARs). Although the classical causal agents of SCARs (antibiotics, anticonvulsants, nonsteroidal anti-inflammatory drugs, and allopurinol) are well characterized, there has been little update to this list to account for newly marketed medications.
To provide an updated and stratified list of medications with significant reporting odds ratios (RORs) of SCARs.
A case/non-case analysis using the United States FDA Adverse Event Reporting System was performed.
As expected, the prototypical medication classes made up the majority of reported cases of SJS, TEN, AGEP, and DRESS (77%, 64%, 75%, and 72%, respectively). In addition, several infrequently or previously undescribed classes/medications implicated in SCARs were identified to have significant ROR signals, including acetylcysteine, anticoagulants, diuretics, immunotherapies, proton pump inhibitors, antivirals, and antifungals. Among these reported for SJS were acetylcysteine (ROR: 64.38) and fluconazole (ROR: 17.13). For TEN, we identified furosemide (ROR: 26.32), spironolactone (ROR: 14.45), fluconazole (ROR: 30.21), amphotericin B (39.06), and acetylcysteine (ROR: 93.12). For AGEP, we identified acyclovir (ROR: 61.72), valacyclovir (ROR: 30.76), and enoxaparin (ROR: 27.37). For DRESS, we identified vemurafenib (ROR: 17.35), acyclovir (ROR: 30.63), abacavir (ROR: 26.62), raltegravir (ROR: 23.27), and valacyclovir (ROR: 21.77) to have strong reporting odds.
Our analysis provides an updated tool for physicians to reference when identifying suspected SCARs and a basis for future studies to investigate atypical medication causality.
史蒂文斯 - 约翰逊综合征（SJS）、中毒性表皮坏死松解症（TEN）、伴有嗜酸性粒细胞增多和全身症状的药物反应（DRESS）以及急性泛发性脓疱病（AGEP）是潜在危及生命的严重皮肤不良反应（SCARs）。虽然SCARs的经典致病药物（抗生素、抗惊厥药、非甾体抗炎药和别嘌醇）已得到充分表征，但该清单几乎没有更新以纳入新上市药物。
提供一份具有显著SCARs报告比值比（RORs）的药物更新分层清单。
使用美国食品药品监督管理局不良事件报告系统进行病例/非病例分析。
正如预期的那样，典型药物类别构成了SJS、TEN、AGEP和DRESS报告病例的大多数（分别为77%、64%、75%和72%）。此外，还确定了几种与SCARs相关的不常见或先前未描述的类别/药物具有显著的ROR信号，包括乙酰半胱氨酸、抗凝剂、利尿剂、免疫疗法、质子泵抑制剂、抗病毒药物和抗真菌药物。在报告的SJS病例中，有乙酰半胱氨酸（ROR：64.38）和氟康唑（ROR：17.13）。对于TEN，我们确定呋塞米（ROR：26.32）、螺内酯（ROR：14.45）、氟康唑（ROR：30.21）、两性霉素B（39.06）和乙酰半胱氨酸（ROR：93.12）。对于AGEP，我们确定阿昔洛韦（ROR：61.72）、伐昔洛韦（ROR：30.76）和依诺肝素（ROR：27.37）。对于DRESS，我们确定维莫非尼（ROR：17.35）、阿昔洛韦（ROR：30.63）、阿巴卡韦（ROR：26.62）、拉替拉韦（ROR：23.27）和伐昔洛韦（ROR：21.77）具有较强的报告比值。
我们的分析为医生在识别疑似SCARs时提供了一个更新的参考工具，并为未来研究调查非典型药物因果关系提供了基础。
