Lim Shi Yu Derek, Tan Yingrou, Zhang Yuning, Zhao Xiahong, Ng Lai Guan, Tey Hong Liang
National Skin Centre, Singapore, Singapore.
Singapore Immunology Network, Agency of Science and Technology, Singapore, Singapore.
Front Med (Lausanne). 2023 Sep 22;10:1265148. doi: 10.3389/fmed.2023.1265148. eCollection 2023.
Chronic pruritus of unknown origin (CPUO) is poorly understood and lacks effective treatment options.
We aimed to elucidate abnormalities in the sweat apparatus of patients with CPUO, and to assess efficacy and safety of treatment with systemic retinoids.
An initial case-control study included 20 affected patients and five healthy controls, for whom heat and sweating were induced, either through a standardized exercise protocol or ingestion of hot water. high-definition optical coherence tomography, whole-body starch-iodine testing, and skin biopsy for immunofluorescence staining were done to evaluate for sweat duct obstruction. A subsequent retrospective cohort analysis included 56 patients with CPUO, seen at an Itch subspecialty clinic of a single tertiary referral centre, who failed conventional treatments and were treated with isotretinoin and/or acitretin from May 2014 to November 2020. Treatment response to retinoids was defined as a sustained reduction in itch score of ≥2/10. Safety was assessed by proportion stopping treatment due to side effects.
imaging in 19 (95%) patients revealed features of partial keratinaceous sweat duct obstruction with statistically significant luminal dilatation compared to controls. Immunofluorescence studies of three patients' paired lesional/non-lesional biopsies revealed dermcidin accumulation within sweat glands coupled with dermcidin leakage in itchy skin. Fifty-six patients (mean [SD] age 55.2 [17.5] years, 69.6% male) were treated with systemic retinoids. Mean (SD) duration of itch was 116.3 (140.4) months and mean (SD) itch score was 8.2 (1.8). Forty-one (73.2%) initially received isotretinoin, and 15 (26.8%) acitretin. At three months, mean itch score reduced by 2.38 (95% CI -3.2 to -1.6, < 0.0001). Thirty-eight (67.9%) had a sustained response. Eight (14.81%) achieved an itch score of 0 or 1, with four stopping treatment for a mean (SD) of 318.5 (291.2) days without relapse. Eight (14.3%) stopped or switched retinoid due to adverse effects, with similar incidences between both retinoids, the commonest being dryness.
Based on novel findings from physiological imaging studies identifying partial keratinaceous sweat duct obstruction in CPUO, we instituted systemic retinoid treatment to address the underlying pathology. In patients who failed conventional therapies, the treatment appears effective and safe.
不明原因的慢性瘙痒（CPUO）的发病机制尚不明确，且缺乏有效的治疗方案。
我们旨在阐明CPUO患者汗腺的异常情况，并评估系统性维甲酸治疗的疗效和安全性。
最初的病例对照研究纳入了20例患病患者和5名健康对照者，通过标准化运动方案或饮用热水诱导他们发热和出汗。采用高分辨率光学相干断层扫描、全身淀粉碘试验以及皮肤活检进行免疫荧光染色，以评估汗腺导管阻塞情况。随后的一项回顾性队列分析纳入了56例CPUO患者，这些患者均在一家三级转诊中心的瘙痒专科门诊就诊，他们对传统治疗无效，并于2014年5月至2020年11月期间接受了异维甲酸和/或阿维A治疗。维甲酸治疗反应定义为瘙痒评分持续降低≥2/10。通过因副作用而停止治疗的比例来评估安全性。
19例（95%）患者的影像学检查显示存在部分角质化汗腺导管阻塞的特征，与对照组相比，管腔扩张具有统计学意义。对3例患者的配对病变/非病变活检组织进行免疫荧光研究发现，汗腺内有皮肤杀菌素积聚，且瘙痒皮肤处有皮肤杀菌素渗漏。56例患者（平均[标准差]年龄55.2[17.5]岁，69.6%为男性）接受了系统性维甲酸治疗。瘙痒的平均（标准差）持续时间为116.3（140.4）个月，平均（标准差）瘙痒评分为8.2（1.8）。41例（73.2%）患者最初接受异维甲酸治疗，15例（26.8%）接受阿维A治疗。三个月时，平均瘙痒评分降低了2.38（95%置信区间-3.2至-1.6，<0.0001）。38例（67.9%）患者有持续反应。8例（14.81%）患者的瘙痒评分为0或1，其中4例停止治疗，平均（标准差）为318.5（291.2）天，无复发。8例（14.3%）患者因不良反应停止或更换维甲酸治疗，两种维甲酸的不良反应发生率相似，最常见的是皮肤干燥。
基于生理影像学研究的新发现，即CPUO存在部分角质化汗腺导管阻塞，我们采用系统性维甲酸治疗以解决潜在病理问题。对于传统治疗无效的患者，该治疗方法似乎有效且安全。
