背景:在艾滋病毒高流行环境中,一线抗结核药物(FLTD)相关DRESS提出了治疗挑战.FLTDs的序贯和加性药物挑战(SADC)最好地识别有问题的药物,避免不必要的排除,并优化非违规药物的重新启动。然而,SADC相关的反应复杂性限制了其效用。
目的:我们旨在描述FLTD相关DRESS患者的特征,他们的治疗限制性SADC反应和相关结局。
方法:2013-2023年在南非一家三级医院接受FLTD相关DRESS住院并在现有登记处登记(回顾性或前瞻性)的患者符合资格。
结果:在41例患者中进行了SADC。总的来说,发生了47个可分类的反应,29/41(71%)患者中的34/47(72%),治疗受限,12/41(29%)顺利重启FLTD。确定了15个单个和8个多个药物反应器。利福平,在13/23(57%)反应堆中,最常见的个人犯罪者。乙胺丁醇最常参与多个药物反应器。可检测反应的中值(IQR)时间为24(12-120)小时,6/34(18%)立即(<6小时)。瘙痒(65%),嗜酸性粒细胞增多症(56%),发烧(41%),非典型淋巴细胞增多症(41%),皮疹(38%),转氨酶(32%)和面部水肿(18%),单独或组合是最常见的特征。三个反应,一次表皮坏死松解和两次肝脏紊乱,是CTCAE4级(危及生命)事件。没有确定多种药物反应性的预测因子,但是多个反应堆住院的时间明显更长,125(100-134)天与60(45-80)天。
结论:SADC优化了FLTD的重新启动。然而,定时,FLTD相关DRESS后SADC相关反应的临床表现和严重程度明显不均匀.此外,多个药物反应器是一个复杂的群体,需要更长的住院时间,并且没有常规生物标志物来区分真正的多药物超敏反应和非特异性发作,并指导长期药物回避策略。
BACKGROUND: In high HIV prevalence settings, first-line antituberculosis drug (FLTD)-associated drug reaction with eosinophilia and systemic symptoms (DRESS) poses therapeutic challenges. A sequential and additive drug challenge (SADC) of FLTDs best identifies offending drug(s), avoids unnecessary exclusions, and optimizes reinitiation of nonoffending drugs. However, SADC-associated reaction complexities limit its utility.
OBJECTIVE: We aimed to describe the characteristics of patients with FLTD-associated DRESS, their treatment-limiting SADC reactions, and related outcomes.
METHODS: Patients hospitalized with FLTD-associated DRESS from 2013 to 2023 in a South African tertiary hospital and enrolled (retrospectively or prospectively) in an existing registry were eligible.
RESULTS: SADC was undertaken in 41 patients. Overall, 47 classifiable reactions occurred. 34/47 (72%) reactions in 29/41 (71%) patients were treatment-limiting and 12 of 41(29%) patients reinitiated FLTDs uneventfully. Fifteen single and 8 multiple drug reactors were identified. Rifampicin in 13 of 23(57%) reactors was the most common individual offender. Ethambutol was most frequently involved in multiple drug reactors. The median (interquartile range) time to a detectable reaction was 24(12-120) hours, 6 of 34(18%) being immediate (<6 hours). Itch (65%), eosinophilia (56%), fever (41%), atypical lymphocytosis (41%), rash (38%), transaminitis (32%), and facial edema (18%) singly or in combination were the most common features. Three reactions, 1 epidermal necrolysis and 2 liver derangements, were Common Terminology Criteria for Adverse Events grade 4 (life-threatening) events. No predictors of multiple drug reactivity were identified, but multiple reactors were hospitalized significantly longer, 125(100-134) days versus 60(45-80) days.
CONCLUSIONS: SADC optimizes FLTD reinitiation. However, timing, clinical presentation, and severity of SADC-associated reactions after FLTD-associated DRESS are markedly heterogeneous. Additionally, multiple drug reactors are a complex group that require longer hospitalization. There are no routine biomarkers available to distinguish true multiple drug hypersensitivity from nonspecific flare-ups and to guide long-term drug avoidance strategies.