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特应性皮炎患者度普利尤单抗相关的眼表疾病:临床特征、眼部治疗反应和结膜杯状细胞分析。

Dupilumab-associated ocular surface disease in atopic dermatitis patients: Clinical characteristics, ophthalmic treatment response and conjunctival goblet cell analysis.

机构信息

Department of Dermatology and Allergology, National Expertise Center for Atopic Dermatitis, University Medical Center Utrecht, Utrecht, the Netherlands.

Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

出版信息

Allergy. 2023 Aug;78(8):2266-2276. doi: 10.1111/all.15717. Epub 2023 Mar 29.

Abstract

BACKGROUND

Dupilumab-associated ocular surface disease (DAOSD) is frequently reported as side effect in atopic dermatitis (AD) patients. Therefore, the aim of this study was to investigate the frequency and severity of DAOSD, ophthalmic treatment response and to learn more about the effect of dupilumab on conjunctival goblet cells (GC).

METHODS

This prospective study included dupilumab-treated AD patients between February 2020 and June 2022 from the University Medical Centre Utrecht. Patients were examined by an ophthalmologist and a dermatologist before start (baseline), and after 4 and 28 weeks of dupilumab treatment. Ophthalmological examination was assessed by the Utrecht Ophthalmic Inflammatory and Allergic disease (UTOPIA) score. DAOSD was defined as an increase in UTOPIA score of ≥3 points from baseline. To quantify conjunctival GCs and to investigate the percentage of Cytokeratin 19 (CK19)-CD45-Mucin 5 AC (MUC5AC)+ cells, conjunctival impression cytology samples were analysed.

RESULTS

Ocular surface disease (OSD) was present in 91.3% (n = 63/69) patients at baseline. DAOSD was observed in 28.9% (n = 20/69) patients, in whom GC numbers remained stable and the percentage of CK19-CD45-MUC5AC+ cells decreased at onset of DAOSD compared with baseline. After 28 weeks of dupilumab treatment, DAOSD was seen in 14.5% (n = 10/69) patients. Of the 85.5% (n = 59/69) patients without DAOSD or with controlled DAOSD at Week 28, 40.7% (n = 24/59) patients received anti-inflammatory ophthalmic drugs.

CONCLUSIONS

Ocular surface disease is common in moderate-to-severe AD patients before starting dupilumab. During treatment with dupilumab DAOSD severity improves with early ophthalmic treatment. The decrease in percentage of CK19-CD45-MUC5AC+ cells during dupilumab treatment suggests an impairment of the GC function due to dupilumab treatment.

摘要

背景

在特应性皮炎(AD)患者中,度普利尤单抗相关的眼表疾病(DAOSD)常被报道为副作用。因此,本研究旨在调查 DAOSD 的频率和严重程度、眼部治疗反应,并更多地了解度普利尤单抗对结膜杯状细胞(GC)的影响。

方法

这项前瞻性研究纳入了 2020 年 2 月至 2022 年 6 月乌得勒支大学医学中心接受度普利尤单抗治疗的 AD 患者。患者在开始治疗前(基线)、治疗后 4 周和 28 周时分别由眼科医生和皮肤科医生进行检查。眼科检查采用乌得勒支眼科炎症和过敏性疾病(UTOPIA)评分进行评估。DAOSD 的定义为基线时 UTOPIA 评分增加≥3 分。为了定量评估结膜 GC,并研究细胞角蛋白 19(CK19)-CD45-粘蛋白 5AC(MUC5AC)+细胞的百分比,对结膜印迹细胞学样本进行了分析。

结果

91.3%(n=63/69)的患者在基线时存在眼表疾病(OSD)。28.9%(n=20/69)的患者出现了 DAOSD,在出现 DAOSD 时,GC 数量保持稳定,而 CK19-CD45-MUC5AC+细胞的百分比与基线相比下降。在接受度普利尤单抗治疗 28 周后,14.5%(n=10/69)的患者出现了 DAOSD。在 28 周时无 DAOSD 或 DAOSD 得到控制的 85.5%(n=59/69)的患者中,40.7%(n=24/59)接受了抗炎性眼科药物治疗。

结论

在开始度普利尤单抗治疗前,中重度 AD 患者的眼表疾病较为常见。在接受度普利尤单抗治疗期间,DAOSD 的严重程度随着早期眼部治疗而改善。在度普利尤单抗治疗期间,CK19-CD45-MUC5AC+细胞的百分比下降提示 GC 功能因度普利尤单抗治疗而受损。

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