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病例报告:使用度普利尤单抗治疗的特应性皮炎患儿皮损处银屑病样红斑的临床和组织病理学特征及IL-17A细胞因子表达

Case report: Clinical and histopathological characteristics of psoriasiform erythema and IL-17A cytokines expression on lesioned skin in atopic dermatitis children treated with dupilumab.

作者信息

Ali Kamran, Wu Liming, Qiu YunMi, Li Menghua

机构信息

Department of Dermatology, International Education College of Zhejiang Chinese Medical University, Hangzhou, China.

Department of Dermatology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Front Med (Lausanne). 2022 Jul 28;9:932766. doi: 10.3389/fmed.2022.932766. eCollection 2022.

Abstract

BACKGROUND

Atopic dermatitis (AD) is a chronic recurrent inflammatory disease, and dupilumab, a human monoclonal antibody, is the firstly approved biological drug for AD. Psoriasiform erythema (PE) during dupilumab treatment in adults has been reported. This study describes the risk of PE in children after initiation of dupilumab treatment.

OBJECTIVES

To evaluate the cytokines gene expression in the transition of atopic dermatitis symptoms to psoriasiform erythema during dupilumab treatment in children.

METHODS

Two 17-year-old teenage twin patients with AD were included in this study who developed psoriasiform erythema after initiation of dupilumab. The lesional skin biopsy specimens were obtained for the histopathological investigation and RNA Fluorescence Hybridization (RNA-FISH). Dermoscopy, cytometry (cytokine detection in the blood), and blood investigations were completed for the pedigree and the lesioned descriptions.

RESULTS

Two twin patients with AD presented with erythematic scaly plaques on the back, scalp, abdomen, and extensor extremities after 20 weeks of dupilumab treatment. The transitional change of AD to psoriasiform erythema treated with dupilumab was observed. Our subjects' dermoscopy showed pinpoint bleeding and white scales on pink background. Histopathology features showed psoriasiform hyperplasia, epidermal hyperplasia (acanthosis), ectatic capillaries, perivascular lymphocytes infiltration, and parakeratosis, with the absence of the granular cell layer. mRNA (RNA-FISH) cytokines gene expression showed a significantly high concentration of IL-17A. Blood investigation results showed a high concentration of (Immunoglobulin E) IgE and Eosinophils, and cytokines detection in blood showed IL-5,6 and IL-17 in one patient; however, only IL-5 in another patient. The dupilumab was discontinued and initiated with Baricitinib. Baricitinib showed a significant reduction in skin lesions.

CONCLUSION

Psoriasiform erythema can appear during dupilumab treatment in atopic dermatitis children. Potently, by suppressing skewed Th2 activation in patients with AD, the balance might shift toward Th1/Th17 predominance, and psoriasis develops. Baricitinib is a potential drug for psoriasiform erythema with significant therapeutic effects.

摘要

背景

特应性皮炎(AD)是一种慢性复发性炎症性疾病,度普利尤单抗,一种人源单克隆抗体,是首个被批准用于治疗AD的生物药物。已有报道称成人在使用度普利尤单抗治疗期间会出现银屑病样红斑(PE)。本研究描述了儿童开始使用度普利尤单抗治疗后发生PE的风险。

目的

评估儿童在使用度普利尤单抗治疗期间,特应性皮炎症状转变为银屑病样红斑过程中细胞因子基因的表达情况。

方法

本研究纳入了两名17岁患AD的青少年双胞胎患者,他们在开始使用度普利尤单抗后出现了银屑病样红斑。获取病变皮肤活检标本用于组织病理学检查和RNA荧光杂交(RNA-FISH)。对患者家族及病变情况进行了皮肤镜检查、细胞计数(血液中细胞因子检测)和血液检查。

结果

两名患AD的双胞胎患者在使用度普利尤单抗治疗20周后,背部、头皮、腹部和四肢伸侧出现了红斑鳞屑性斑块。观察到AD经度普利尤单抗治疗后转变为银屑病样红斑的变化。我们的研究对象皮肤镜检查显示在粉红色背景上有针尖样出血和白色鳞屑。组织病理学特征显示为银屑病样增生、表皮增生(棘层肥厚)、毛细血管扩张、血管周围淋巴细胞浸润和角化不全,且颗粒层缺失。mRNA(RNA-FISH)细胞因子基因表达显示白细胞介素-17A(IL-17A)浓度显著升高。血液检查结果显示免疫球蛋白E(IgE)和嗜酸性粒细胞浓度较高,血液中细胞因子检测显示一名患者有白细胞介素-5、6和白细胞介素-17;然而,另一名患者只有白细胞介素-(此处原文可能有误,推测应为白细胞介素-5)。停用度普利尤单抗并开始使用巴瑞替尼。巴瑞替尼使皮肤病变显著减轻。

结论

儿童特应性皮炎患者在使用度普利尤单抗治疗期间可能出现银屑病样红斑。强效抑制AD患者中偏向性的Th2激活后,平衡可能会向Th1/Th17占优势转变,进而发展为银屑病。巴瑞替尼是一种对银屑病样红斑有显著治疗效果的潜在药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b356/9366075/a18cf6ddf138/fmed-09-932766-g0001.jpg

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