A study of matrix metalloproteinase expression and activity in atopic dermatitis using a novel skin wash sampling assay for functional biomarker analysis

Background Atopic dermatitis (AD) is a chronic inflammatory skin condition that is characterized by a defective skin barrier. Despite the well‐recognized role of proteases in skin barrier maintenance, relatively little is known of the contribution made by matrix metalloproteinases (MMPs) to the inflammatory process in AD. Objectives To test a simple, novel ex vivo bioassay technique in an analysis of the MMPs present in wash samples taken from the skin surface of patients with AD. Methods Saline wash samples were collected from eczematous and unaffected areas of the skin of patients with AD and from the skin of normal controls. Wash samples were analysed for their MMP content using a functional peptide cleavage assay, gelatin zymography and an antibody array. Results Using a functional substrate cleavage assay, skin wash samples from AD lesions were shown to contain 10‐ to 24‐fold more MMP activity than those from normal control skin (P < 0·02) and fivefold more than those from unaffected AD skin (P < 0·05); this activity was inhibited by a broad‐spectrum MMP inhibitor Ro 31‐9790. Gelatin zymography and antibody array analysis revealed substantial levels of MMP‐8 (neutrophil collagenase) and MMP‐9 (92‐kDa gelatinase) in AD skin wash samples as well as lower levels of MMP‐10 (stromelysin 2) and tissue inhibitor of metalloproteinases (TIMP)‐1 and TIMP‐2; low levels of MMP‐1 (fibroblast collagenase), MMP‐3 (stromelysin 1) and TIMP‐4 were also detected. Conclusions A simple skin wash technique suitable for the quantitative and functional analysis of biomolecules in AD is described. Using this method we show that MMPs, and in particular MMP‐8 and MMP‐9, represent an important potential component of the pathology of AD. The method is expected to prove useful in advancing our understanding of AD and in identifying biomarkers for the evaluation of new therapies.     

Therapeutic patient education in children with moderate to severe atopic dermatitis: A multicenter randomized controlled trial in China

Background

Therapeutic patient education is a continuous, systematic, patient‐centered learning process to help patients and their families acquire and maintain the skills they need to manage their lives with a chronic disease. It has been proven effective in increasing treatment adherence and improving quality of life for patients with atopic dermatitis (AD) in Western countries. We introduce the first multicenter, randomized controlled clinical trial of therapeutic patient education in Chinese children with AD.

Objectives

To evaluate the effects of therapeutic patient education on the severity of AD, quality of life, and understanding and successful use of emollients in Chinese children with eczema.

Methods

We recruited 580 children, ages 2‐14 years, with moderate to severe AD from six hospitals in China. Participants were randomized (1:1) to an intervention (n = 293) or control (n = 249) group. In addition to the severity of AD, data on quality of life and a questionnaire on family and patient knowledge of emollients were evaluated at the 6‐month follow‐up.

Results

On study completion, we found that the intervention group showed a significantly greater reduction in mean SCORing Atopic Dermatitis (P < .001) and Infant's Dermatology Life Quality Index (P = .030) scores than the control group. In addition, knowledge about the use of emollients improved significantly in the intervention group. There was no significant difference between groups in Children's Dermatology Life Quality Index scores.

Conclusions

The first randomized controlled trial of a therapeutic patient education program in China had positive long‐term effects on decreasing eczema severity and improvement of quality of life in children 2‐4 years of age with AD, as well as in promoting greater understanding of the use of emollients.     

Cognitive functioning in children with atopic dermatitis: Pilot observations

Atopic dermatitis (AD) is a common and chronic inflammatory skin disease that can adversely affect quality of life and carry significant burdens on physical, emotional, and social health. Recent evidence suggests that AD may also impair cognition, including attention and memory. In a pilot study of six children with AD, we administered a comprehensive battery of assessments to evaluate cognition and behavior and found that this approach was feasible and practical, which will enable the conduct of future larger-scale studies to characterize the impact of AD on cognitive function.     

Well being,psychopathology and coping strategies in psoriasis compared with atopic dermatitis: a controlled study

Background There is a vast literature describing the association between psoriasis, atopic dermatitis (AD) and psychological distress. Some of these studies were uncontrolled and others used non‐dermatological diseases as control, but only a few used chronic skin diseases as controls. Objective To compare well being, psychopathology and coping strategies of psoriatic, AD and healthy controls in a prospective case‐control study. Methods Thirty‐seven psoriatic patients and 31 AD patients were recruited from the Hadassah Ein Karem Hospital, Jerusalem, Israel, outpatient and inward clinic. The participants in the control group were 31 healthy workers and volunteers with no dermatological diseases from Kaplan Hospital, Rehovot, Israel. We used self‐report questionnaires [Mental Health Inventory (MHI) and Adjustment to Chronic Skin Diseases Questionnaire (ACSD)], a projective technique (Hand Test) and assessment tools (Clinical Global Impression). Results Psoriatic patients experienced reduced well being (P = 0.007) and more anxiety and depression (P = 0.018) than normal controls. Psoriatic patients also displayed more severe psychopathology (P = 0.039) a more passive attitude towards life, and loss of meaning in life (P = 0.001) as measured by the projective technique compared with AD patients and normal controls. Conclusions We propose two explanations, derived from the psychological and the psycho‐neuro‐immunological domains. First, greater mental distress in psoriasis is because of the greater stigma it bears compared with AD. Alternatively, we hypothesize that the psoriatic inflammatory process may possibly have a direct central nervous system effect.     

Evaluation of lens clarity in children with atopic dermatitis: A densitometric analysis with Pentacam

The association of atopic dermatitis (AD) with a wide variety of ocular complications is known; however, there is no study in the literature that measured lens densitometry in pediatric patients with AD. This study aimed to investigate lens densitometry in children with AD. In order to examine ocular complications in AD, 31 pediatric patients (13 males, 18 females; mean age 12 ± 3 years) with AD and 20 healthy children (9 males, 11 females; mean age 12 ± 2 years), who presented to the dermatology clinic of Istanbul Medipol Mega University between December 2018 and May 2019 were included in this study. The diagnosis of AD was based on the UK Working Party's Diagnostic Criteria for AD. Patients receiving inhaler and systemic steroids were excluded from the study. All children were examined by the same dermatologist and ophthalmologist. The mean values of best‐corrected visual acuity, refractive error, and axial length were similar between both groups (P > .05). The lens densitometry values of zone 1, zone 2, and zone 3, as well as the average lens densitometry measurements were found statistically significantly higher in children with AD compared to the controls (P < .05 for all). This is the first study to demonstrate an increase in treatment‐independent lens densitometry in children with AD.     

Benefits of an emollient body wash for patients with chronic winter dry skin

This randomized 5-week study assessed the clinical benefits of a high-emollient body wash versus a regular bar cleanser in terms of improving chronic winter dry skin condition. After 4 weeks, subjects who washed daily with a high-emollient body wash exhibited a significant reduction in all dermatologist-assessed dry skin attributes and improvements in self-evaluated skin condition when compared with baseline measures. Those subjects who washed with a regular bar cleanser experienced a minimal to marked increase in dermatologist-assessed and self-assessed dry skin attributes when compared with baseline. These findings suggested that bathing with a high-emollient body wash, as opposed to a regular bar cleanser, can reduce xerosis symptoms and improve skin health and appearance without the additional use of a moisturizer.     

基于ARNE项目的多元化健康教育对特应性皮炎患儿家长的干预研究

目的：明确基于ARNE项目的多元化健康教育对特应性皮炎患儿和家长的干预效果。方法：选取0~2岁AD患儿和家长为研究对象,共计120例,随机分为干预组和对照组,每组60例。对照组患儿和家长接受常规诊疗活动并由接诊医生进行健康指导和答疑,干预组在接受门诊医生常规健康指导和答疑基础上由3名接受过统一培训的护师实施基于ARNE项目的多元化健康教育方案,两组干预前后使用SCORAD评分、DFI、IDQOL及《特应性皮炎防治知识调查问卷》评价干预效果。结果：干预组有效例数59例,对照组有效例数57例,干预后干预组SCORAD 评分、IDQOL评分、DFI评分分别为21.57±2.42,8.20±2.54,6.67±1.52,低于对照组的26.46±3.84,13.79±1.73,10.28±2.21,差异均有统计学意义（P<0.05),干预组知识问卷得分20.75±1.67高于对照组的16.28±2.39,差异有统计学意义（P=0.029）。结论：本研究基于ARNE项目制定的多元化健康教育方案在改善AD患儿和家属生活质量方面有重要意义。     

Skin physiological parameters confirm the therapeutic efficacy of pimecrolimus cream 1% in patients with mild-to-moderate atopic dermatitis

Abstract:  In this double-blind, within-patient vehicle-controlled study, patients with mild-to-moderate atopic dermatitis (AD) were treated for 3 weeks twice daily with pimecrolimus cream 1% on one forearm and with vehicle cream on the other forearm. Efficacy of treatment was assessed clinically using the Atopic Dermatitis Severity Index (ADSI), the Investigators Global Assessment (IGA) and the pruritus visual analogue scale. In parallel, blood microcirculation in the skin was measured as an objective parameter for skin inflammation. Skin hydration and transepidermal water loss (TEWL) were monitored as parameter relevant for the barrier function. Treatment with pimecrolimus cream 1% resulted in a quick and marked improvement of signs and symptoms of AD and a significant reduction of microcirculation from 33.90 to 15.55 AU ( P  < 0.0001). Skin hydration increased continually from 42.86 to 52.69 AU ( P  = 0.002) and TEWL decreased from 35.30 to 21.50 g/m²/h ( P  = 0.001), indicating restoration of skin barrier. At vehicle-treated sites changes of skin physiological parameters were less pronounced and observed only initially with later plateau or even reversal. At the end of the study, there were significant differences for all measured skin physiological parameters between pimecrolimus cream 1% and vehicle: microcirculation 12.15 AU ( P  = 0.004), skin hydration 7.12 AU ( P  = 0.002), TEWL 11.38 g/m²/h ( P  = 0.004). Non-invasive evaluation of microcirculation and barrier functionality thus represent a valuable tool for the objective assessment of treatment response to pimecrolimus cream 1%.     

Contact allergy to aeroallergens in children with atopic dermatitis: comparison with allergic contact dermatitis

Immediate and delayed cutaneous hypersensitivity are believed to be implicated in the physiopathology atopic dermatitis (AD). The purpose of this study was to evaluate Type I and Type IV allergy to aeroallergens in children with AD. 59 children (mean age 5.2 years), presenting with AD according to Hanifin and Rajka's criteria, were skin tested (patch and corresponding prick tests) with common environmental aeroallergens and a restricted panel of the European standard series over a 1-year period. History and clinical data were carefully recorded using a standardized evaluation sheet: total and specific IgE serum levels were evaluated 17 of 59 patients (28.8%) had at least 1 positive patch test, 32 of 59 patients (54.2%) had at least 1 positive prick test. Corresponding patch and prick tests were observed in 8 out of 17 patients. 5 children with positive patch tests had negative prick tests. Irritant pustular reactions (2/59, i.e. 3%), "angry back" reactions (6/59, i.e. 10%) and doubtful reactions (3/59, i.e. 5%) were excluded from the positive group. Positive patch tests observed included, in decreasing order: D. pteronyssinus and D. farinæ (26.8%) garden trees (12.2%), plantain (9.8%), timothy grass, mugwort and damp area trees (4.9% each), and orchard grass (2.44%). 6 children with positive aeroallergen patch tests and 11 children with negative aeroallergen patch tests had at least 1 positive patch test to standard allergens. All children with an irritant reaction to aeroallergens had no reaction to standard patch tests. The relevance of aeroallergens in upgrading the severity of AD lesions has still to be explored by challenge studies and by long-term follow-up.     

Managing sleep disturbances in children with atopic dermatitis

Atopic dermatitis is a chronic, pruritic inflammatory disease that often disrupts sleep in severely affected children, but there are limited studies to guide clinical management of these sleep problems. Disease control is crucial in improving sleep, but additional sleep aids may sometimes be helpful in decreasing scratching during the night. This review discusses the benefits and limitations of potential therapeutic agents available to manage sleep disturbances in children with atopic dermatitis.     

Cutaneous pH in children affected by atopic dermatitis and in healthy children: a multicenter study

Background/aims: Several studies have been conducted in order to assess, objectively and non-invasively, atopic skin parameters. Since little is known about clinically uninvolved, perilesional and lesional skin pH in atopic children at different stages of the disease, we studied cutaneous pH in atopic and healthy children and investigated possible relationships among different sites, phases of the disease and main symptoms.
Methods: Two hundred and eighty-four children of both sexes, 143 atopic and 141 healthy children, aged 3 months to 11 years, examined in 10 different Italian dermatological centres were included in the study and subjected to clinical examinations and pH measurements.
Results: Atopic children presented statistically significant higher pH values than controls, not only at the level of eczematous lesions (P=0.004) and of perilesional skin (P=0.003) but also at the level of apparently healthy skin (P=0.002). A progressive statistically significant increase in pH values was observed from healthy to perilesional to lesional skin. In acute dermatitis, children affected by moderate itching (considering itching complaints and scratching lesions) presented, at the level of lesional and perilesional skin, statistically significant higher pH values than children affected by mild itching.
Conclusion: The correlation found in this study between severity of itch and skin surface alkalinity, far from demonstrating a therapeutic role of acidic substances against itching in atopic children, deserves new epidemiological studies on a large scale in order to identify new strategies of treatment of atopic skin.     

真实世界度普利尤单抗治疗儿童中重度特应性皮炎15例疗效观察

目的:评估真实世界下度普利尤单抗治疗儿童中重度特应性皮炎的有效性和安全性。方法:收集2020年11月至2022年3月于我院使用度普利尤单抗治疗的15例1～12岁儿童中重度AD患者信息,比较药物治疗前、治疗4周、12周、16周的SCORAD、EASI、瘙痒NRS的评分变化,记录治疗过程中的不良反应。结果:本研究共纳入15例患者。研究结果表明,与基线相比,治疗后第4、12和16周时SCORAD评分分别下降了43.4%、63.3%、72.6%;EASI评分分别下降了52.8%、73.2%、86.7%;瘙痒NRS评分下降了52.8%、72.2%、83.8%。在第12周随访时,有50.0%的患者达到了EASI-75,10.0%的患者达到了EASI-90。在16周时,达到这两项指标的比例增加到75.0%和50.0%。随访期间所有患者均未出现不良反应及严重不良事件。结论:度普利尤单抗对儿童中重度特应性皮炎具有良好的疗效,且安全性较高。     

Occupational dermatitis in bakers: a clue for atopic contact dermatitis

6 patients are described who developed contact dermatitis after cereal contact on atopic skin for periods of 2 to 20 years. 2 patients were wheat flour patch-test-positive. They had punch biopsies taken for standard histological and immunohistochemical investigation by labeling with monoclonal antibodies, anti-DR and anti-IgE. Sections showed features of contact dermatitis. There were many dendritic cells located perivascularly in the papilla and in the epidermidis, intensely positive for monoclonal anti-IgE antibody. In control atopic subjects, there were a few perivascular IgE positive cells, probably mastocytes. This study shows that there may be a relationship between some allergens and atopic eczema in patients exposed to them in the course of their work. In some cases, there was a true allergic contact dermatitis, seen through the clinical and histological characteristics, and the results of immunohistochemical study.     

饮食和环境因素与儿童特应性皮炎的相关性研究进展

特应性皮炎(AD)是一种慢性复发性炎症性皮肤病,遗传因素的作用已被证实,近年研究发现饮食、环境因素也可影响AD的发病,孕期和产后母亲饮食及儿童自身对食物的过敏情况可影响AD发病。环境因素如空气污染和紫外线照射在AD发生、发展中也起着重要作用。本文对不同饮食、环境因素与儿童AD发病间的相关性作一综述。     

Hand dermatitis among university hospital nursing staff with or without atopic eczema: assessment of risk factors

Background. Nurses are prone to develop hand dermatitis. Although an atopic constitution has been identified as a genetic risk factor, the behavioural risk factors associated with hand dermatitis in wet work conditions have not been fully explored. Objectives. This study aimed to clarify the impact of atopic eczema (fulfilling the diagnostic criteria during the past 1 year) on the occurrence of hand dermatitis and to identify the behavioural risk factors among non‐atopic nurses with hand dermatitis. Methods. From August 2007 to July 2009, nurses from Kaohsiung Medical University Hospital were recruited. The associations between different risk factors and hand dermatitis were documented. In addition, the behavioural risk factors among non‐atopic nurses were evaluated via observational study. Results. One thousand one hundred and thirty‐two nurses participated in the first part of the study, which revealed that individuals with atopic eczema had a 3.76‐fold increased risk for hand dermatitis. However, among 248 nurses with hand dermatitis, only 43 had atopic eczema. The observational study performed on 140 non‐atopic nurses identified frequency of hand washing as the behavioural risk factor associated with hand dermatitis. Conclusions. Although atopic eczema is the major risk factor for hand dermatitis, those with atopic eczema constitute only 17% of nurses with hand dermatitis. Decreasing hand washing frequency is the most effective strategy to reduce the occurrence of hand dermatitis among non‐atopic nurses.