Squamometry in rating the efficacy of topical corticosteroids in atopic dermatitis

Objective: Squamometry is a non-invasive test allowing a reproducible rating of cutaneous xerosis including atopic dermatitis lesions. The method was used to compare the efficacy of proprietary topical corticosteroids in alleviating signs of atopic xerosis. Results: The steroid compounds and their vehicles improve the texture of the stratum corneum at different rates after treatment for 1 week. Some differences in efficacy may be explained by the nature of the vehicle, which enhances the basic pharmacological activity of the corticosteroid itself. Received: 26 April 1996/Accepted in revised form 16 July 1996     

Safety of topical calcineurin inhibitors for the treatment of atopic dermatitis

Atopic dermatitis is a chronic, highly pruritic, and frequently recurring inflammatory skin disease that can be burdensome to affected individuals as well as to their family members, the health care system, and society as a whole. Immunomodulatory agents, such as topical corticosteroids and topical calcineurin inhibitors (TCIs), target the underlying immunopathology of atopic dermatitis and are the foundation of pharmacologic treatment for disease exacerbations. Recent recommendations from the United States Food and Drug Administration prompted the addition of a black-box warning and medication guide for tacrolimus ointment and pimecrolimus cream (both TCIs). The recommendations were based on a theoretical risk of malignancy derived from safety profiles, animal data, and reported cases of malignancy from clinical trials and postmarketing safety surveillance of oral calcineurin inhibitors. We know of no data that suggest that TCI use increases the risk of malignancy. Several dermatologic associations have issued statements supporting the safety of TCIs, and independent oncology experts have concluded that reported lymphomas were not related to TCI use. The black-box warning added to the TCI prescribing information also states that no causal link has been established. Effective treatment of atopic dermatitis can help alleviate the burden this disease imposes, and TCIs remain important treatment options.     

Calcineurin inhibitors for the treatment of atopic dermatitis

Background: Atopic dermatitis (AD) is a chronic disease characterized by periods of remission and relapse. Therapeutic objectives for AD should be to quickly reduce disease symptoms by targeting pathophysiological pathways, and to provide long-term management by reducing recurrences. Objective: Calcineurin inhibitors currently appear to be one of the most promising alternative systemic and topical compounds to treat AD. This review focuses on new developments of topical calcineurin inhibitors, therapeutic regimens including long-term management, and prophylaxis of AD. Methods: The published clinical studies that present data on treatment of AD with calcineurin inhibitors were assessed. Results/conclusion: Topical calcineurin inhibitors such as tacrolimus and pimecrolimus provide an effective treatment for AD. They are useful for long-term management and prophylaxis of AD. Safety concerns with regard to increased risk for lymphomas or skin cancer could not be confirmed but will remain under careful observation.     

Effective topical delivery systems for corticosteroids: dermatological and histological evaluations

Abstract

Atopic dermatitis (AD) is a chronic and relapsing skin disease with severe eczematous lesions. Long-term topical corticosteroid treatment can induce skin atrophy, hypopigmentation and transepidermal water loss (TEWL) increase. A new treatment approach was needed to reduce the risk by dermal targeting. For this purpose, Betamethasone valerate (BMV)/Diflucortolone valerate (DFV)-loaded liposomes (220–350?nm) were prepared and incorporated into chitosan gel to obtain adequate viscosity (～13?000 cps). Drugs were localized in stratum corneum?+?epidermis of rat skin in ex-vivo permeation studies. The toxicity was assessed on human fibroblast cells. In point of in-vivo studies, pharmacodynamic responses, treatment efficacy and skin irritation were evaluated and compared with previously prepared nanoparticles. Liposome/nanoparticle in gel formulations produced higher paw edema inhibition in rats with respect to the commercial cream. Similar skin blanching effect with commercial creams was obtained via liposome in gels although they contain 10 times less drug. Dermatological scoring results, prognostic histological parameters and suppression of mast cell numbers showed higher treatment efficiency of liposome/nanoparticle in gel formulations in AD-induced rats. TEWL and erythema measurements confirmed these results. Overview of obtained results showed that liposomes might be an effective and safe carrier for corticosteroids in skin disease treatment.     

An update on the topical and oral therapy options for treating pediatric atopic dermatitis

Introduction: Atopic dermatitis (AD) is one of the most common childhood skin disorders. Multiple mechanisms contribute to the pathology of AD and treatment approaches are directed at these processes.

Areas covered: The purpose of this review is to discuss the chemical treatment options for pediatric atopic dermatitis, including immunomodulators and small molecule inhibitors. A systematic literature search was conducted, and publications were reviewed for applicable treatment guidelines.

Expert opinion: Topical therapy is first-line for pediatric atopic dermatitis. Providers should work closely with patients and caregivers to promote the success of topical treatments. In disease refractory to topical treatments, systemic agents may be considered. Clinical trials are ongoing for the use of biologics in the treatment of pediatric AD. When choosing the most appropriate treatment, physicians should consider the drug efficacy, potential adverse effects, patient adherence, and quality of life for both patients and caregivers. Additional studies are required to determine the safest and most effective doses for systemic therapy in childhood AD.     

Atopic dermatitis: understanding the disease and its management

ABSTRACT

Objective: Atopic dermatitis (AD) is a common, chronic, inflammatory skin disease that can significantly reduce the quality of life of not only patients but also entire families. This review will focus on the currently available non-pharmacologic and pharmacologic treatments for the control and management of AD.

Research design and methods: A review of English-language articles from January 1953 to May 2006 was performed within the MEDLINE database. Search terms included, but were not limited to, atopic dermatitis, topical corticosteroids, and topical calcineurin inhibitors. Studies evaluating the diagnosis, physical and psychological burden, and underlying pathophysiology of AD were included. Particular focus was placed on literature presenting key safety and efficacy data from clinical trials involving AD treatment.

Results: Although good skin care and trigger avoidance are fundamental to AD management, most patients also require pharmacologic intervention. Topical therapies comprise the foundation of AD treatment. In particular, topical corticosteroids have been a mainstay in AD treatment for several decades and the newer topical calcineurin inhibitors have become a valuable addition to the therapeutic armamentarium. TCIs are a safe and effective AD treatment; they limit the number of disease flares, extend the time between flares, and provide a steroid-sparing option that may be of particular benefit in the pediatric population. The use of more potent therapies, such as systemic (oral/injected) agents or phototherapy, is typically limited to the treatment of severe, refractory disease. Additionally, owing to the increased risk for bacterial, viral, and fungal infections in patients with AD, topical or systemic antimicrobials are an important component of treatment.

Limitations: Case reports and small-scale studies were typically not included in this analysis and owing to the limited number of trials evaluating TCSs, consensus statements and comprehensive review articles were used to obtain information pertaining to the use of this treatment in AD.

Conclusions: AD is a common, chronic disease requiring a long-term management strategy that incorporates preventive measures and a multipronged treatment approach.     

Efficacy and safety of silver textile in the treatment of atopic dermatitis (AD)

ABSTRACT

Background: Patients with atopic dermatitis (AD) have an increased tendency to develop bacterial skin infections. Colonization with Staphylococcus aureus is known to be a major trigger and might also play a pathophysiological role. Because of their antiseptic action, silver-coated textiles suppress S. aureus colonization and toxin formation, thus damping the inflammatory reaction.

Objectives: To evaluate the clinical effectiveness and safety of a special silver textile in the treatment of patients suffering from acute AD.

Methods: In a randomized phase II monocenter parallel-group comparative study 30 patients were recruited (average age 25.5 years, min. 4 years, max. 70 years) who were affected by AD in an acute phase. During the first study phase from Day 1 to Day 14, 10 patients received a silver textile (Group 1), 10 a silver-free textile (Group 2), and 10 prednicarbate ointment (Group 3). In the second phase from Day 15 to Day 28 all patients wore the silver textile, and during the follow-up period from Day 28 to Day 56 no textiles were used. Prednicarbate ointment was allowed as emergency medication, but ointment consumption was measured. The overall severity of the disease was evaluated using the SCORAD index as the primary efficacy parameter. Secondary parameters included severity of pruritus and the patients’ assessment of their disease control (uncontrolled, limited, good or complete). Safety tests included hematology, blood chemistry, urinalysis for silver, and physical examination for silver deposits in the skin and mucous membranes.

Results: The initial SCORAD was 61.6 (IQR 26.6, min. 30.6, max. 99.9). At the end of the Study Phase 1 the SCORAD had improved significantly in the patients of Groups 1 (74.6–29.9, p = 0.005) and 3 (57.8–24.0, p = 0.009). During Study Phase 2 healing of eczema continued in Group 1 (SCORAD 29.9–18.1, p = 0.037), was observed in Group 2 (48.2–24.1, p = 0.015), and remained at an improved level in Group 3 (SCORAD 24–23.5). Consumption of prednicarbate ointment (Phase 1, Phase 2, follow-up period, medians are given): Group 1: 135?g, 10?g, 45?g; Group 2: 13?g, 0?g, 0?g; Group 3: 145?g, 30?g, 90?g. Silver textiles reduced the severity of the pruritus (p = 0.031); silver-free textiles (n.s.) and prednicarbate (n.s.) were less effective. No undesired events were observed.

Conclusion: The elastic silver textile worn directly against the skin led to an impressive improvement of AD and a reduction in the use of prednicarbate ointment.     

A proposal for the use of new silver-seaweed-cotton fibers in the treatment of atopic dermatitis

Abstract

Background: Atopic dermatitis (AD) is a disease with multifactorial etiology. Staphylococcus aureus is one of the predominant environmental factors acting on the course and intensity of the disease.

Objectives: The aims of the study were to evaluate the efficacy and safety of clothing made of cellulose fibers with seaweed enriched with silver ions in the treatment of children with AD.

Methods: A prospective, randomized and double-blinded controlled selection was done to recruit 19 children with diagnosis of AD. This sample was divided in two groups with similar demographic and clinical characteristics (the “control” group of seven children who wore placebo clothing and the “trial textile” group of 12 children who wore clothing with the new textile). The severity of AD and clinical response were assessed by the SCORAD index, the intensity of pruritus and the changes in sleep characteristics, at the start of the study and after 7 and 90?d.

Results: The SCORAD index improvement in the group with the fiber under study was statistically significant after the first 7?d of treatment (p?<?0.001) and was reduced by about 45% after 90?d. There was also a statistically relevant reduction of the intensity of pruritus and an improvement in the sleep quality after the initial 7?d and at day 90.

Conclusion: The results showed that the textile clothing with seaweed enriched with silver ions brings a quicker improvement of the patients in the first days in opposition to the use of standard all-cotton clothes. The results also reinforce the importance of non-pharmacological measures, like clothing, in the management of patients with a diagnosis of AD.     

69例儿童特应性皮炎治疗及随访体会

目的：探讨儿童特应性皮炎的临床治疗方法和疗效。方法：回顾本院2007年6月～2009年1月收集诊治的69例患儿的临床资料,其分别采用常规治疗（对照组）与医学护肤品辅助治疗（试验组）的方法进行治疗。结果：试验组和对照组有效率分别为95.00%和75.86%,两组比较差异有统计学意义（P〈0.05）,试验组疗效明显优于对照组。结论：对抗皮肤干燥的关键在于保湿润肤,并减少长期外用糖皮质激素导致的皮肤萎缩变薄、毛细血管扩张等不良反应,可减轻症状,减少复发且使用安全方便。     

A safety review of the medications used to treat atopic dermatitis

Introduction: Atopic dermatitis (AD) is a common disease in children and adults which causes severe physical discomfort and psychosocial distress. Recently novel therapies for AD have been FDA approved for use which creates the need to review the safety surrounding current FDA approved AD medications.

Areas covered: Published clinical studies involving topical and oral FDA approved medications for AD are included in this review. Authors used PubMed research database to search for clinical trials involving AD patients.

Expert opinion: AD is a common disease which currently has limited FDA approved medications. Given the chronicity of this disease, medications are needed which control disease while minimizing side effects to allow for long term use. Newer approved medications show promise but safety data is limited given their relatively new utilization for AD.     

A systematic review of tacrolimus ointment compared with corticosteroids in the treatment of atopic dermatitis

Abstract

Objective:

A systematic review and meta-analysis was conducted to determine the efficacy and tolerability of tacrolimus ointment for the treatment of atopic dermatitis (AD) compared with topical corticosteroids.     

曲安奈德鼻喷雾剂治疗过敏性皮炎疗效观察

目的观察曲安奈德鼻喷雾剂治疗过敏性皮炎的临床疗效和安全性。方法 92例患者分为观察组和对照组各46例。观察组给予曲安奈德鼻喷雾剂治疗;对照组给予丁酸氢化可的松乳膏治疗。观察2组病情积分、起效时间、临床疗效及不良反应。结果 治疗中脱落8例,其中观察组3例,对照组5例。2组治疗后病情积分、起效时间及临床疗效比较差异均无统计学意义(P>0.05)。2组治疗后病情积分均低于治疗前,差异有统计学意义(P<0.01)。观察组发生不良反应4例占9.30%,对照组发生4例占9.76%。结论曲安奈德鼻喷雾剂治疗过敏性皮炎安全、有效,值得临床推广使用。     

Inhibition of skin inflammation and atopic dermatitis by topical application of a novel ceramide derivative, K112PC-5, in mice

PC-9S (N-Ethanol-2-mirystyl-3-oxo-stearamide) is a synthetic ceramide and has been known to be effective in atopic and psoriatic patients. K112PC-5 (2-Acetyl-N-(1,3-dihydroxyisopropyl)-tetradecanamide) is a novel ceramide derivative of PC-9S. In the present study, we examined the effect of K112PC-5 on macrophage and T lymphocyte function in primary macrophages and splenocytes, respectively, as well as the effect of topical application of K112PC-5 on skin inflammation and atopic dermatitis (AD) in mouse models. K112PC-5 inhibited lipopolysaccharide-induced nitrite generation in mouse peritoneal macrophages in a dose-dependent manner. However, K112PC-5 did not affect concanavalin A-induced proliferation, interleukin (IL)-2 secretion and IL-4 secretion in mouse splenocytes. In addition, K112PC-5 significantly suppressed the increase in phorbol ester-induced ear thickness in BALB/c mice. Further study demonstrated that topical application of K112PC-5 also inhibited AD induced by extracts of dust mites, Dermatophagoides pteronyssinus and Dermatophagoides farinae, in NC/Nga mice. Taken together, these results showed that K112PC-5 exerted an anti-inflammatory effect both in vitro and in vivo and proved to be beneficial in an animal model of AD. Our results suggest that K112PC-5 might be beneficial as a topical agent for the treatment of AD.     

Pharmacological management of atopic dermatitis in the elderly

ABSTRACT

Introduction

The prevalence of atopic dermatitis (AD) in geriatric populations of industrialized countries is currently estimated at 3-4% and continues to increase. AD is associated with significant morbidity, increased susceptibility to infection, and symptoms of pruritus and pain. Treatments may negatively affect elderly patients; thus, plans should be optimized for this population.     

Emerging small-molecule compounds for treatment of atopic dermatitis: a review

Introduction: Atopic dermatitis is a chronic, relapsing, pruritic inflammatory skin disease. Both skin barrier defects and abnormal immune reactions contribute to this complex disease. Current therapeutic guidelines recommend the use of moisturizers, good skin care and allergen avoidance as the first-line approach. In patients who do not respond well to these measures, topical corticosteroids, calcineurin inhibitors, and, in severe cases, systemic immunosuppressive agents are mostly used.

Areas covered: This review summarizes the patent applications for small-molecule compounds for the treatment of atopic dermatitis from 2009 to date. These substances include compounds targeting the skin barrier (filaggrin production promoters, filaggrin breakdown products and compounds improving stratum corneum lipid barrier including pseudoceramides), anti-inflammatory compounds (PDE4/7 inhibitors, CRTH2 inhibitors, chemokine receptor antagonists, inhibitors of chymase and other) and compounds specifically targeting itch (TRP agonists, opioid ligands, serotonin 7 and histamine 4 antagonists).

Expert opinion: Recent advances in understanding the pathogenic mechanisms of atopic dermatitis have created a strong rationale for the design of targeted therapeutics. Most emerging compounds target inflammation and/or pruritus, probably because of the broader therapeutic utility of such compounds. Specific skin barrier-corrective therapies are much fewer but bear strong potential to actually prevent inflammation.     

特应性皮炎患儿外周血DC1／DC2亚群的检测及临床意义

目的:探讨特应性皮炎(AD)患儿外周血树突状细胞亚群(DC1/DC2)的其临床意义。方法:采用免疫荧光三标记流式细胞术检测38例AD患儿外周血DC亚群(DC1/CD11c+和DC2/CD123+),并以35例正常儿童作为对照。结果:AD患儿外周血CD123+DC百分率(1.28±0.59)%,比对照组(0.69±0.25)%明显增高(P<0.05),CD11c+DC百分率(2.81±1.44)%与对照组(2.56±0.78)%相比,差异无显著性(P>0.05);AD患儿CD11c+DC和CD123+DC与疾病严重程度无关(P>0.05)。结论:特应性皮炎患儿外周血中DC2亚群占优势,导致Th1/Th2细胞向Th2类方向偏移,可能与特应性皮炎的发病机制有关。     

本维莫德治疗特应性皮炎及银屑病作用机制的研究进展（英文）

特应性皮炎(atopic dermatitis,AD)和银屑病是常见的慢性、复发性、炎症性皮肤病。Th2和Th17细胞介导的细胞免疫分别被认为是AD和银屑病发病机制中必不可少的环节。本维莫德是一种芪类小分子化合物,自从1965年被发现至今,已成为国家一类新药,在临床上用于成人轻中度银屑病的治疗。临床研究表明,本维莫德对特应性皮炎也有积极的治疗作用。尽管目前对本维莫德作用机制的研究还处于探索阶段,但是越来越多的证据显示,本维莫德对皮肤中的芳香烃受体(aryl hydrocarbon receptor,AhR)和核转录因子Nrf2起着重要的调控作用。近年来发现本维莫德调节相关免疫因子的同时,也广泛参与皮肤微环境中抗氧化途径的激活与皮肤屏障的修复。本文就本维莫德治疗AD和银屑病作用机制的相关研究进展做综述。     

特应性皮炎患者外周血辅助性T细胞22的表达及意义

[目的]检测特应性皮炎(AD)患者外周血辅助性T细胞22(Th22)的表达,探讨其在AD发病机制中的作用.[方法]以湿疹面积及严重度指数(EASI)评分评估患者病情,采用流式细胞术检测46例AD患者和28例健康对照者外周血Th22(IL-22)细胞,ELISA法检测血清中IL-22、IFN-γ、IL-4水平.[结果]AD患者外周血Th22细胞(2.35±0.64)％,明显高于对照组的(0.94±0.43)％(P＜ 0.01); Th22细胞与血清中IL-22呈正相关(r=0.48,P＜0.05),而与IFN-γ、IL-4无相关(r=- 0.105,P＞0.05;r=- 0.267,P＞0.05),Th22细胞与疾病的EASI评分呈正相关(r=0.53,P＜0.05).[结论]Th22细胞有可能作为监测AD严重程度或病情波动的指标.     

人体肘窝部皮肤菌群培养方法的建立及其在特应性皮炎疾病辅助诊断中的应用探索

目的　建立一种肘窝部皮肤菌群的分离培养方法,探讨其在特应性皮炎（atopic dermatitis,AD）疾病辅助诊断中的应用价值。方法　采用前瞻性试验性研究方法,选取符合Williams诊断标准的AD患者8例和健康者8例,采集其肘窝部皮肤刷洗标本进行皮肤菌群的分离培养,探讨生长温度、气体环境、pH值、盐浓度和培养基等条件对皮肤细菌生长的影响,建立人体皮肤菌群培养的方法。基于该方法,选取2019年9月至2020年3月就诊于广东省中医院皮肤科的AD患者34例［年龄（14.43±8.03）岁,男21例,女13例］和健康志愿者者26例［年龄（29.38±7.47）岁,男12例,女14例］,对其肘窝部皮肤菌群进行定量培养,采用MALDI-TOF质谱技术和16S rRNA基因测序技术进行菌种鉴定和菌落计数。采用Kruskal-Wallis H检验比较AD患者和健康者肘窝部皮肤菌群结构差异,以及AD患者中肘部皮损者与肘部非皮损者的皮肤菌群结构差异。最终,结合AD患者的菌群培养结果及其局部皮肤损伤严重程度,探讨金黄色葡萄球菌定量计数在AD诊断中的应用价值。结果　人体肘窝部皮肤菌群培养的最适宜生长温度为28～32 ℃,最适pH值为6～7,最适盐浓度范围为0.5%～5.0%,其中以血平板和巧克力平板检出细菌种类和数量最多。定量细菌培养结果比较发现：健康对照组肘部皮肤菌群在种属上的多样性比AD组（AD皮损组和AD非皮损组）高,而AD患者中AD皮损组肘窝部皮肤细菌的总体分布密度明显高于AD非皮损组和健康对照组（H=24.25,P<0.05;H=13.41,P<0.05）,且从AD皮损组中检出的金黄色葡萄球菌的占比与AD的严重程度呈显著正相关（r=0.411,P<0.05）。结论　基于上述培养方法,采用定量培养获得的皮肤菌群多样性数据,尤其是血平板上金黄色葡萄球菌的占比,可作为评估AD患者皮损严重程度的微生物学指标,对指导AD疾病的临床治疗及预后判断有重要意义。