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与表皮生长因子受体抑制剂相关的紫癜性药疹抗生素治疗相关的微生物群的时间变化。

Temporal shifts of the microbiome associated with antibiotic treatment of purpuric drug eruptions related to epidermal growth factor receptor inhibitors.

作者信息

Hsieh Paul-Chen, Chang Chi-Sheng, Chen Kai-Lung, Cho Yung-Tsu, Chu Chia-Yu, Chen Kuan-Yu

机构信息

Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

Department of Dermatology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan.

出版信息

J Eur Acad Dermatol Venereol. 2023 Feb;37(2):382-389. doi: 10.1111/jdv.18640. Epub 2022 Oct 19.

Abstract

BACKGROUND

Epidermal growth factor receptor (EGFR) inhibitors are selective and effective treatments for cancers with relevant mutations. Purpuric drug eruptions are an uncommon but clinically significant dermatological side effect related to EGFR inhibitor use that are associated with positive bacterial cultures and responsive to antibiotic treatment. However, the longitudinal temporal shifts in the skin microbiome that occur before and after antibiotic treatment of purpuric drug eruptions remain largely unknown.

OBJECTIVES

To characterize temporal changes in the skin and mucosal microbiomes before and after antibiotic treatment of EGFR inhibitor-related purpuric drug eruptions.

METHODS

Twelve patients who experienced EGFR inhibitor-related purpuric drug eruptions were recruited from a dermato-oncology clinic in Taiwan from May 2017 to April 2018. Swabs were obtained from skin lesions and the nasal mucosa before and after antibiotic treatment of purpuric drug eruptions. After the amplification and sequencing of bacterial 16S rRNA genes, the diversity and compositions of microbiomes sampled at different time points were compared.

RESULTS

The alpha diversity (represented by the Shannon index) of the skin microbiome increased significantly in the recovered phase of purpuric drug eruptions compared with that of the active phase. By contrast, the nasal microbiome showed no significant change in alpha diversity. The relative abundance of Staphylococcus significantly decreased in samples from skin of the recovered phase, which was confirmed by analysis of compositions of microbiomes (ANCOM) and the ALDEx2 analysis packages in R.

CONCLUSIONS

The cutaneous microbiome of purpuric drug eruptions showed a significant increase in alpha diversity and a decrease in the relative abundance of Staphylococcus following antibiotic treatment. These findings may help guide antimicrobial therapy of this EGFR inhibitor-related condition.

摘要

背景

表皮生长因子受体(EGFR)抑制剂是治疗具有相关突变癌症的选择性有效疗法。紫癜性药疹是一种与使用EGFR抑制剂相关的罕见但具有临床意义的皮肤副作用,与细菌培养阳性有关且对抗生素治疗有反应。然而,紫癜性药疹抗生素治疗前后皮肤微生物群的纵向时间变化仍 largely未知。

目的

描述EGFR抑制剂相关紫癜性药疹抗生素治疗前后皮肤和黏膜微生物群的时间变化。

方法

2017年5月至2018年4月从台湾一家皮肤肿瘤诊所招募了12例经历EGFR抑制剂相关紫癜性药疹的患者。在紫癜性药疹抗生素治疗前后,从皮肤病变和鼻黏膜获取拭子。对细菌16S rRNA基因进行扩增和测序后,比较不同时间点采样的微生物群的多样性和组成。

结果

与活动期相比,紫癜性药疹恢复期皮肤微生物群的α多样性(以香农指数表示)显著增加。相比之下,鼻微生物群的α多样性没有显著变化。恢复期皮肤样本中葡萄球菌的相对丰度显著降低,这通过微生物群组成分析(ANCOM)和R中的ALDEx2分析软件包得到证实。

结论

紫癜性药疹的皮肤微生物群在抗生素治疗后α多样性显著增加,葡萄球菌相对丰度降低。这些发现可能有助于指导这种EGFR抑制剂相关疾病的抗菌治疗。

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