回顾性研究人类疱疹病毒再激活与严重 DRESS 的关系：血液和皮肤再激活的描述。

Retrospective study on the association of human herpesvirus reactivation with severe DRESS: A description of blood and skin reactivations.

机构信息

Department of Dermatology, AP-HP, Bichat Hospital, Paris, France.

Department of Dermatology, AP-HP, Henri-Mondor Hospital, Créteil, France.

出版信息

J Eur Acad Dermatol Venereol. 2023 Dec;37(12):2550-2557. doi: 10.1111/jdv.19425. Epub 2023 Aug 28.

DOI:10.1111/jdv.19425

PMID:37591509

Abstract

BACKGROUND

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a severe adverse event (mortality of 10%). Its pathophysiology involves herpesviruses, particularly HHV-6, but the exact mechanisms are still poorly understood.

OBJECTIVE

To describe severe cases of DRESS and especially their association with herpesvirus reactivation.

METHODS

This study was a multicentre case series conducted between 2007 and 2021 at five University Hospital Centres in France. The study included patients who had severe DRESS, which was defined as death, transfer to the intensive care unit (ICU), or severe damage to internal organs. We excluded patients without blood PCR sample, without a drug formally attributed or with RegiSCAR score < 6. We collected data on severity, causative drug, associated visceral damage and results of viral blood PCRs. HHV-6 reactivation was studied in skin biopsies by detection of small non-coding transcripts (HHV-6 miR-aU14) and a late viral protein (GP82/105).

RESULTS

Fifty-two patients were included (29 female, median age 62, interquartile range (IQR) [37;72]). Eight patients (15%) died, 13 (27%) were admitted to ICU. Most patients (n = 34; 65%) had multisystem involvement: most frequent was liver (n = 46; 88%), then renal failure (n = 24; 46%). Forty patients (77%) had at least one blood viral reactivation among HHV-6, EBV or CMV, of which 21 (53%) had at least two. Median time of blood HHV-6 reactivation was 24 days (IQR [20;35]). HHV-6 reactivation was demonstrated in 15 out of 20 skin biopsies, with a median time of 11 days [9;17].

CONCLUSIONS

We confirmed the high rate of HHV-6 reactivation in severe DRESS and demonstrated cutaneous HHV-6 reactivation using small non-coding transcripts (HHV-6 miR-aU14), which preceded viral PCR positivity in blood. These results suggest that HHV-6 reactivation during DRESS may start in skin. Furthermore, search for miR-aU14 in skin biopsy could become a useful diagnostic tool for early detection of HHV-6 reactivation.

摘要

背景

药物反应伴嗜酸性粒细胞增多和全身症状（DRESS）是一种严重的不良反应（死亡率为 10%）。其病理生理学涉及疱疹病毒，特别是 HHV-6，但确切机制仍知之甚少。

目的

描述严重的 DRESS 病例，特别是它们与疱疹病毒再激活的关系。

方法

这是一项多中心病例系列研究，于 2007 年至 2021 年在法国五所大学医院中心进行。该研究纳入了患有严重 DRESS 的患者，严重 DRESS 定义为死亡、转入重症监护病房（ICU）或严重内脏损伤。我们排除了没有血液 PCR 样本、没有正式归因于药物或 RegiSCAR 评分<6 的患者。我们收集了严重程度、致病药物、相关内脏损伤和病毒血液 PCR 结果的数据。通过检测小非编码转录物（HHV-6 miR-aU14）和晚期病毒蛋白（GP82/105），在皮肤活检中研究了 HHV-6 的再激活。

结果

共纳入 52 例患者（29 例女性，中位年龄 62 岁，四分位间距[IQR] [37；72]）。8 例（15%）患者死亡，13 例（27%）患者入住 ICU。大多数患者（n=34；65%）有多个系统受累：最常见的是肝脏（n=46；88%），其次是肾功能衰竭（n=24；46%）。40 例（77%）患者至少有一种血液病毒再激活，其中 21 例（53%）至少有两种。血液 HHV-6 再激活的中位时间为 24 天（IQR [20；35]）。20 例皮肤活检中有 15 例证实 HHV-6 再激活，中位时间为 11 天[9；17]。

结论

我们证实了严重 DRESS 中 HHV-6 再激活的高发生率，并通过小非编码转录物（HHV-6 miR-aU14）证实了皮肤 HHV-6 再激活，该转录物在血液病毒 PCR 阳性之前出现。这些结果表明，DRESS 期间的 HHV-6 再激活可能始于皮肤。此外，在皮肤活检中寻找 miR-aU14 可能成为早期检测 HHV-6 再激活的有用诊断工具。