中华皮肤科杂志 ›› 2026, Vol. 59 ›› Issue (11): 1083-1091.doi: 10.35541/cjd.20260252

• 论著·慢性皮肤瘙痒 • 上一篇    下一篇

特应性皮炎患者皮肤疼痛及机械感觉异常的临床特征和蛋白质组学分析

张睿文1，2    唐睿1    王芳1   

  1. 1南方医科大学皮肤病医院皮肤内科，广州  510091；2南方医科大学第一临床医学院，广州  510515
  • 收稿日期:2026-05-08 修回日期:2026-10-08 发布日期:2026-11-03
  • 通讯作者: 王芳 E-mail:wangf78@smu.edu.cn
  • 基金资助:
    国家自然科学基金（82525056）；广州市科技计划科技菁英“领航”项目（2025A04J7157）

Skin pain and mechanical sensory abnormalities in patients with atopic dermatitis: clinical characteristics and proteomic analysis

Chang Juiwen1,2, Tang Rui1, Wang Fang1   

  1. 1Department of Dermatology, Dermatology Hospital, Southern Medical University, Guangzhou 510091, China; 2The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
  • Received:2026-05-08 Revised:2026-10-08 Published:2026-11-03
  • Contact: Wang Fang E-mail:wangf78@smu.edu.cn
  • Supported by:
    National Natural Science Foundation of China （82525056）; Guangzhou Science and Technology Program Tech Elite Pioneer Project （2025A04J7157）

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摘要： 【摘要】 目的 探讨特应性皮炎（AD）患者皮肤疼痛特征及机械痛阈变化，分析疼痛与疾病严重程度及瘙痒的关系，并分析与机械痛阈升高相关的蛋白特征。方法 前瞻性收集2023年3月1日至2026年3月31日分别在南方医科大学皮肤病医院和中山大学附属第一医院皮肤科门诊就诊的82例和20例AD患者，另外于中山大学附属第一医院同期招募20例健康对照。记录两组受试者的年龄、性别等资料。采用疼痛问卷调查82例AD患者的疼痛发生情况，采用电子von Frey测痛仪测定47例AD患者皮损部位、非皮损部位及20例健康对照者皮肤的机械痛阈。按疾病严重程度分层比较疼痛负担及机械痛阈差异，并采用Spearman秩相关分析湿疹面积及严重程度指数（EASI）、峰值瘙痒数字分级评分（PP-NRS）、疼痛视觉模拟评分（pVAS）与机械痛阈的相关性。基于受试者操作特征（ROC）曲线探索机械痛阈升高的最佳截断值，并通过皮肤贴片蛋白质组学分析机械痛阈升高相关的蛋白特征。结果 接受机械痛阈检查的受试者中，AD组47例，男27例，女20例，年龄24.0（18.0，33.0）岁；健康对照组20例，男8例，女12例，年龄25.0（21.3，32.0）岁；两组间性别及年龄差异无统计学意义（均P > 0.05）。与健康对照组［（56.6 ± 37.6） g］相比，AD组皮损及非皮损部位机械痛阈均升高［皮损：（100.2 ± 39.8） g，t = 4.17，P < 0.001；非皮损：（89.2 ± 36.9） g，t = 3.29，P = 0.002］，且AD组皮损部位机械痛阈高于非皮损部位（配对t = 2.74，P = 0.009）。接受问卷调查的82例AD患者中，58例（70.7%）患者报告存在皮肤疼痛，73例（89.0%）能够明确区分疼痛与瘙痒。中重度AD患者疼痛程度高于轻度AD患者（P = 0.035）；两组在皮损和非皮损部位机械痛阈的组间比较中，差异均无统计学意义（均P > 0.05）；组内比较显示，中重度 AD 组皮损部位机械痛阈高于非皮损部位（配对t = 2.25，P = 0.031）。相关性分析显示，EASI评分与PP-NRS评分呈弱正相关（rs = 0.42，P = 0.030），与pVAS评分及机械痛阈的相关性无统计学意义（均P > 0.05）；PP-NRS评分与pVAS评分的相关性亦无统计学意义（P > 0.05）；AD皮损与非皮损部位的机械痛阈呈正相关（rs = 0.54，P = 0.004）。ROC曲线分析显示，皮损及非皮损部位机械痛阈区分AD患者与健康对照的最佳截断值分别为70.54 g和73.62 g，曲线下面积分别为0.830（95% CI：0.692 ~ 0.968）和0.802（95% CI：0.650 ~ 0.955）。基于上述截断值并结合皮肤贴片样本的可用情况，最终纳入健康对照组15例、AD皮损组17例及AD非皮损组16例进行蛋白质组学分析，结果显示，机械痛阈升高的AD患者表皮中白细胞介素（IL）-18、IL-36A、S100钙结合蛋白A9等炎症相关蛋白上调，而AD皮损中突触相关蛋白（如突触蛋白1、突触小体相关蛋白29）下调，差异表达蛋白主要富集于神经调控及炎症免疫通路。结论 皮肤疼痛在AD患者中较常见，AD患者皮损及非皮损部位机械痛阈均升高，机械痛阈、疼痛评分与瘙痒评分及AD疾病严重程度评分均未见明显相关性。机械痛阈升高的AD患者表皮蛋白谱呈现神经及炎症免疫相关蛋白表达特征。

关键词: 皮炎, 特应性, 疼痛, 机械痛阈, 瘙痒, 蛋白质组学

Abstract: 【Abstract】 Objective To investigate the characteristics of skin pain and the changes in mechanical pain thresholds in patients with atopic dermatitis （AD）, to analyze the relationship of pain with disease severity and pruritus, and to identify the protein profiles associated with elevated mechanical pain thresholds. Methods Between March 1, 2023, and March 31, 2026, 82 and 20 patients with AD were prospectively enrolled from outpatient departments of the Dermatology Hospital, Southern Medical University, and the First Affiliated Hospital, Sun Yat-sen University, respectively; additionally, 20 healthy controls were recruited from the First Affiliated Hospital, Sun Yat-sen University. Data on age, sex, and other characteristics of the subjects were recorded. A questionnaire survey was conducted to assess pain in 82 AD patients. Mechanical pain thresholds were measured with an electronic von Frey aesthesiometer at lesional and non-lesional skin sites in 47 patients with AD and at normal skin sites in 20 healthy controls. Pain burden and mechanical pain thresholds were compared among patients stratified by disease severity. Spearman rank correlation analysis was performed to assess the correlations of the Eczema Area and Severity Index （EASI） score, Peak Pruritus Numerical Rating Scale （PP-NRS） score, and pain Visual Analogue Scale （pVAS） score with the mechanical pain threshold. The optimal cutoff values for elevated mechanical pain thresholds were determined by receiver operating characteristic （ROC） curve analysis, and the protein profiles associated with elevated mechanical pain thresholds were identified by tape-strip proteomic analysis. Results Among the subjects who underwent mechanical pain threshold testing, 47 patients were in the AD group, including 27 males and 20 females, aged 24.0 （18.0, 33.0） years, and 20 subjects were in the healthy control group, including 8 males and 12 females, aged 25.0 （21.3, 32.0） years; there were no significant differences in gender or age between the two groups （both P > 0.05）. Mechanical pain thresholds were significantly elevated at both lesional （100.2 ± 39.8 g; t = 4.17, P < 0.001） and non-lesional sites （89.2 ± 36.9 g; t = 3.29, P = 0.002） in the AD group compared with the healthy control group （56.6 ± 37.6 g）; in the AD group, the mechanical pain threshold was significantly higher at lesional sites than at non-lesional sites （paired t = 2.74, P = 0.009）. Of the 82 patients with AD who completed the questionnaire, 58 （70.7%） reported skin pain, and 73 （89.0%） could clearly distinguish pain from pruritus. Pain intensity was significantly higher in the patients with moderate-to-severe AD than in those with mild AD （P = 0.035）; no significant differences in mechanical pain thresholds were observed between the two groups at either lesional or non-lesional sites （both P > 0.05）; however, in the moderate-to-severe AD group, the mechanical pain threshold was significantly higher at lesional sites than at non-lesional sites （paired t = 2.25，P = 0.031）. Correlation analysis showed that the EASI score was weakly positively correlated with the PP-NRS score （rs = 0.42, P = 0.030）, but was not significantly correlated with the pVAS score or the mechanical pain threshold （both P > 0.05）; there was no significant correlation between PP-NRS and pVAS scores （P > 0.05）; the mechanical pain thresholds at lesional and non-lesional sites were positively correlated （rs = 0.54, P = 0.004）. ROC curve analysis identified optimal cutoff values of 70.54 g and 73.62 g for mechanical pain thresholds at lesional and non-lesional sites, respectively, for distinguishing patients with AD from healthy controls, with corresponding areas under the curve of 0.830 （95% CI: 0.692 - 0.968） and 0.802 （95% CI: 0.650 - 0.955）. Based on these cutoff values and the availability of skin tape-strip samples, 15 samples from the healthy control group, 17 lesional samples and 16 non-lesional samples from the AD group were finally included in the tape-strip proteomic analysis. The results showed that inflammation-related proteins such as interleukin （IL）-18, IL-36A, and S100 calcium-binding protein A9 were upregulated in the epidermis of AD patients with elevated mechanical pain thresholds, whereas synapse-related proteins such as synaptogyrin 1 and synaptosome-associated protein 29 were downregulated in skin lesions of AD patients with elevated mechanical pain thresholds; the differentially expressed proteins were mainly enriched in neuromodulatory and inflammatory immune pathways. Conclusions Skin pain was common in patients with AD. Mechanical pain thresholds were elevated at both lesional and non-lesional sites in patients with AD, and mechanical pain thresholds and pain scores showed no significant correlation with pruritus scores or disease severity scores. AD patients with elevated mechanical pain thresholds exhibited a distinct expression profile of neural and inflammatory immune-related proteins.

Key words: Dermatitis, atopic, Pain, Mechanical pain threshold, Pruritus, Proteomics

引用本文

张睿文 唐睿 王芳. 特应性皮炎患者皮肤疼痛及机械感觉异常的临床特征和蛋白质组学分析[J]. 中华皮肤科杂志, 2026,59(11):1083-1091. doi:10.35541/cjd.20260252

Chang Juiwen, Tang Rui, Wang Fang. Skin pain and mechanical sensory abnormalities in patients with atopic dermatitis: clinical characteristics and proteomic analysis [J]. Chinese Journal of Dermatology, 2026, 59(11): 1083-1091.doi:10.35541/cjd.20260252