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Cyclosporine for treatment of acute generalized exanthematous pustulosis: A retrospective analysis.
Journal of the American Academy of Dermatology ( IF 12.8 ) Pub Date : 2020-03-07 , DOI: 10.1016/j.jaad.2020.02.069
Daniel Yanes 1 , Emily Nguyen 1 , Sotonye Imadojemu 2 , Daniela Kroshinsky 1
Affiliation  

Background

Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction, typically to a medication, that is characterized by fever, neutrophilia, and a disseminated non-follicular pustular eruption. AGEP is typically self-resolving upon withdrawal of the offending agent, however it is not without complications and distributive shock due to systemic inflammatory response can lead to hemodynamic instability and organ failure1-2. These patients have been successfully treated with systemic corticosteroids3. Cyclosporine use in patients with AGEP has been limited to only a few case reports4, 5. To date, no studies have evaluated the utility of cyclosporine in the management of AGEP. We report the largest cohort of patients with AGEP treated with cyclosporine and compare them to patients treated with systemic glucocorticoids.

Methods

This was a retrospective study of adults admitted to Massachusetts General Hospital or Brigham and Women’s Hospital with a diagnosis of AGEP from 2009-2019. The patients were identified via a query of electronic medical record systems at both hospitals, and their records were reviewed to find those who received cyclosporine, matched to approximately 3 age- (+/- 5 years) and sex-matched controls per case that received systemic glucocorticoids, amounting to a total of 23 controls. The patients were followed daily while inpatient, and within 2 weeks of discharge. Time from treatment initiation to first noted improvement (defined by defervescence, or symptomatic improvement), time to cessation of pustule formation, time to resolution of erythema, and length of hospital stay were analyzed.

Results

The data from patients who received cyclosporine and systemic glucocorticoids was analyzed, with characteristics of the study population presented in Table 1. There was a high prevalence of patients who met SIRS criteria in patients treated with cyclosporine (62.5%), as well as in those with glucocorticoids (61%), implying that this cohort consisted of more severe cases of AGEP. The time from drug eruption onset to cessation of pustule formation was similar in both the cyclosporine group (2.5 days) and corticosteroid group (3 days). Patients treated with cyclosporine were able to achieve initial noted clinical improvement in 1.5 days, and had comparable durations of hospitalization and time to resolution of erythema as patients who received glucocorticoids. No patients had major adverse side effects from cyclosporine or glucocorticoids.

Discussion

To date, this represents the largest cohort of patients with AGEP successfully treated with cyclosporine. Cyclosporine appears to be non-inferior to glucocorticoids with regards to cessation of the eruption and providing clinical improvement. In this cohort, the patients who received cyclosporine were those with relative contraindications to systemic corticosteroids, such as diabetes, history of steroid use with poor tolerance (i.e. delirium, emotional lability, etc.). As cyclosporine was administered primarily based on provider preferences in the setting of the aforementioned comorbidities, some selection bias was unavoidable in this cohort. The small sample size and retrospective nature also limit this study. Nevertheless, cyclosporine appears to be a non-inferior therapeutic alternative to glucocorticoids in the appropriate patient who presents with AGEP, and future prospective studies are needed to further examine its utility in AGEP.



中文翻译:

环孢素治疗急性全身性皮疹性脓疱病的回顾性分析。

背景

急性全身性皮疹性脓疱病(AGEP)是一种严重的皮肤不良反应,通常是针对药物的,其特征是发烧,中性粒细胞增多和弥漫性非小疱性脓疱疹。AGEP通常会在撤消违规药物后自行解决,但并非并非没有并发症,由于全身性炎症反应而引起的分布性休克会导致血液动力学不稳定和器官衰竭1-2。这些患者已成功接受全身性激素治疗3。AGEP患者使用环孢菌素仅限于少数病例报告4、5。迄今为止,尚无研究评估环孢菌素在AGEP管理中的效用。我们报告了环孢素治疗的AGEP患者的最大队列,并将其与全身性糖皮质激素治疗的患者进行比较。

方法

这是一项回顾性研究,研究对象是2009年至2019年在马萨诸塞州总医院或布里格姆妇女医院住院的成人,诊断为AGEP。通过查询两家医院的电子病历系统对患者进行了识别,并对其病历进行了审查,以查找接受环孢霉素治疗的患者,每例患者与大约3个年龄(+/- 5岁)和性别匹配的对照者相匹配全身性糖皮质激素,总计23个对照。每天在住院期间和出院后2周内对患者进行随访。分析了从治疗开始到首次出现明显改善的时间(定义为去热或症状改善),停止脓疱形成的时间,红斑消退的时间以及住院时间。

结果

分析了接受环孢霉素和全身性糖皮质激素的患者的数据,表1列出了研究人群的特征。在接受环孢霉素治疗的患者中,符合SIRS标准的患者(62.5%)的患病率很高,糖皮质激素(61%),这表明该队列由更严重的AGEP病例组成。在环孢素组(2.5天)和皮质类固醇组(3天)中,从药疹发作到脓疱形成停止的时间相似。接受环孢霉素治疗的患者能够在1.5天内实现最初的显着临床改善,并且住院时间和红斑消退时间与接受糖皮质激素治疗的患者相当。没有患者因环孢霉素或糖皮质激素而产生重大不良副作用。

讨论区

迄今为止,这是成功用环孢霉素治疗的AGEP患者的最大队列。就停止喷发和提供临床改善而言,环孢霉素似乎并不逊色于糖皮质激素。在该队列中,接受环孢霉素的患者是全身性皮质类固醇相对禁忌症的患者,例如糖尿病,耐受性差的类固醇使用史(即del妄,情绪不稳等)。由于在上述合并症中环孢素的使用主要是基于提供者的偏好而进行的,因此在该队列中不可避免地会有一些选择偏见。小样本量和回顾性也限制了这项研究。不过,

更新日期:2020-03-09
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