Effect of rosmarinic acid on atopic dermatitis

Rosmarinic acid is known to have anti‐inflammatory and immunomodulatory activities. This study was performed to evaluate the effect of rosmarinic acid on atopic dermatitis (AD), one of the inflammatory disorders of the skin. Twenty‐one subjects (14 women and seven men, 5–28 years of age) with mild AD participated in this study. Rosmarinic acid (0.3%) emulsion was topically applied to the elbow flexures of AD patients twice a day (once in the morning and once in the evening). All subjects were evaluated for skin conditions before treatment at the first visit, and then at 4 and 8 weeks after treatment. According to local Severity Scoring of Atopic Dermatitis index results, erythema on antecubital fossa was significantly reduced at 4 and 8 weeks (P < 0.05). Transepidermal water loss of the antecubital fossa was significantly reduced at 8 weeks compared to before treatment (P < 0.05). The results from self‐questionnaires on the efficacy of rosmarinic acid indicated that dryness, pruritus and general AD symptoms improved. Our investigation into the AD‐mitigating effect of rosmarinic acid through in vivo experiments demonstrated the possible clinical use of rosmarinic acid as a therapeutic agent for AD.     

Genetics of atopic dermatitis

Atopic dermatitis (AD) is a multifactorial disease, with a strong genetic predisposition. Genome‐wide studies as well as candidate gene studies revealed several susceptibility loci. Since the observation of a strong association of “loss of function” mutations in the filaggrin gene with AD, the epidermal barrier was rediscovered as important pathophysiological co‐factor of this disease.     

The use of selective Th2 blocker dupilumab for the treatment of atopic dermatitis in a heart transplant patient: Case report

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by relapsing eczematous rash with severe pruritus and recurrent infection. Topical emollients and immune‐modulators (e.g., corticosteroids and calcineurin inhibitor) are first‐line therapies for acute flares. In severe refractory cases, systemic immunosuppression may be required. Increased incidence of AD has been documented in heart‐transplant children who receive their transplant or thymectomy before the age of 1 year. The treatment of these patients remains a conundrum for dermatologists. We present a case report of a chronically immunosuppressed transplant patient with severe AD treated with dupilumab and in remission for over 2 years with minimal side effects. We will also discuss impact of transplant immunosuppression in the pathogenesis of AD.     

特应性皮炎与丝聚蛋白研究进展

丝聚蛋白(FLG)基因的失功能突变可使表皮FLG含量减少或缺失,进而引起表皮屏障功能发生改变,增加特应性皮炎(AD)的患病风险。本文对FLG在表皮屏障形成中的作用、FLG基因结构、FLG基因在AD患者中的突变情况及FLG基因突变与AD临床表型的相关性进行综述。     

Omalizumab for treatment of refractory severe atopic dermatitis. A pediatric perspective

Omalizumab is a monoclonal antibody, targeting Fc receptor of IgE, approved for the treatment of allergic asthma and chronic spontaneous urticaria. Its utility in atopic dermatitis appears controversial from data in literature since the molecule is well tolerated but it seems less effective than other medications used in adult patients (eg, Dupilumab). At present, the use of Dupilumab is not approved in pediatric patients therefore there are no second level treatments available in this age group. Here we report two clinical cases of patients (15 and 16 years old) suffering from both atopic dermatitis and asthma, treated with Omalizumab. Our experience suggests that atopic eczema of young patients with allergic comorbidities can benefit from asthma treatment with Omalizumab observing improvement on both conditions.     

迟发型特应性皮炎的研究进展

特应性皮炎（AD）是一种炎症性皮肤病,与皮肤屏障功能受损密切相关。遗传因素、生活方式、环境因素的暴露都可导致该病的发生。尽管AD常见于婴幼儿,仍有成年后首次出现AD症状,被称为迟发型AD（AOAD）。与儿童期始发的AD相比,AOAD在分型、免疫学机制及与其他疾病的关联方面都存在着显著的差异。皮损分布与婴幼儿期初发的AD相似,但以亚急性和慢性皮炎为主要表现,呈现干燥的、肥厚的皮炎损害,少见渗出。Th1/Th2失衡及抗原提呈细胞的功能亢进是AD发生的免疫学基础。FLG基因突变会影响AD的发生,IL-13升高使FLG存在获得性的表达缺陷仅发生于成年人,提示了AOAD不同于婴幼儿期初发并迁延至成年期的AD。感染、皮肤及肠道菌群改变、吸烟等均可成为诱发AOAD的重要因素,因此在诊断AOAD时询问相关疾病史和吸烟史有助于AOAD的诊断。     

皮肤屏障功能与特应性皮炎

目前认为特应性皮炎发病机制不清,可能具有遗传缺陷的个体,在环境等因素的作用下皮肤的蛋白、脂质等的代谢出现异常,进而出现皮肤屏障结构的异常,导致天然保湿因子、抗菌肽减少、经皮失水率增加和pH值的升高等病理生理改变。本文将对皮肤屏障结构异常与特应性皮炎的关系进行综述。     

富含亚油酸-神经酰胺的保湿剂在特应性皮炎鼠模型中的作用研究

目的：明确外用富含亚油酸-神经酰胺（Linoleic acid-ceramide, LA-Cer）的保湿剂对特应性皮炎（AD）鼠模型皮肤炎症和屏障的影响。方法：将18只BALB/c小鼠分为疾病组、治疗组和对照组,每组6只。疾病组以卡泊三醇（MC903）涂抹小鼠耳朵2周,诱导特应性皮炎模型;治疗组在诱导特应性皮炎的同时外用富含LA-Cer的保湿剂;对照组以无水乙醇外涂小鼠耳朵。比较各组间临床表型、组织病理、皮肤水含量的改变,通过实时荧光定量PCR检测炎症相关因子（TSLP,IL-4,IL-10,IL-1β,IL-33,IFNγ）的表达。结果：卡泊三醇诱导出较典型的小鼠AD模型。治疗组的鼠耳厚度（0.375±0.015）cm较疾病组（0.510±0.035）cm改善,治疗组皮肤含水量（22.500±2.081）au较疾病组（6.750±1.258）au高。与疾病组比较,治疗组皮损中炎症因子TSLP和IL-1β的表达含量明显降低。结论：外用富含LA-Cer的保湿剂可以减轻卡泊三醇诱导的特应性皮炎小鼠模型皮肤炎症,修护皮肤屏障。     

Evaluation of efficacy of a skin lipid mixture in patients with irritant contact dermatitis, allergic contact dermatitis or atopic dermatitis: a multicenter study

Disturbances of skin barrier function occur in several skin diseases, e.g., atopic dermatitis (AD), irritant/allergic contact dermatitis (ICD, ACD). Skin barrier damage triggers the production of cytokines that stimulate lipogenesis which may also cause inflammatory processes. The aim of this study was to evaluate the efficacy of a topical skin lipid mixture in the treatment of ICD, ACD and AD. 580 consecutive patients suffering from ICD, ACD or AD were treated with a skin lipid mixture containing ceramide-3 and patented nanoparticles. Patients received the lipid mixture alone or in combination with topical corticosteroids until clearance or for 8 weeks. Both treatment groups statistically improved all parameters considered at week 4 and 8 as compared to baseline. Between the 2 treatment groups, there was a statistically significant difference in favour of combined therapy for (ICD, ACD, AD, respectively): erythema, pruritus and overall disease severity; erythema and pruritus; erythema, pruritus, fissuring and overall disease severity. No statistically significant difference was found for (ICD, ACD, AD, respectively): dryness, scaling and fissuring; scaling, fissuring and overall disease severity; dryness and scaling. Between the 2 ACD treatment groups, there was a statistically significant difference in favour of the skin lipid mixture for dryness. In conclusion, the study shows that balanced lipid mixtures are effective in improving barrier properties and the clinical condition of the skin in contact dermatitis.     

213例儿童特应性皮炎临床及病理特点分析

本研究对213例AD儿童患者临床及组织病理学特点进行分析,患儿平均发病年龄为0.88±1.73岁,约85.9%的患者表现为慢性皮炎;约78.9%的患者有个人或家族遗传过敏史。组织病理学示角化过度、微水疱形成、棘层肥厚、海绵水肿、浅层血管周围炎症及嗜酸性粒细胞浸润。     

Effect of standard medication on quality of life of patients with atopic dermatitis

Patients with atopic dermatitis present with debilitating symptoms, including pruritus and subsequent excoriation, which significantly reduces their quality of life (QOL). At present, the standard therapy for atopic dermatitis constitutes a topical steroid and/or a topical immunomodulator, an emollient and an oral antihistamine, although few studies have reported the effect of this treatment regimen on QOL. The current study aimed to verify the efficacy of the standard therapy for both clinical symptom severity and patient QOL, assessed using the validated Skindex-16 questionnaire. Atopic dermatitis patients receiving the standard therapy (n=771) were enrolled in the current phase IV, multicenter, 12-week, open-label study. The Rajka and Langeland scale (used to rate the severity of atopic dermatitis symptoms) and the Skindex-16 QOL questionnaire were completed at weeks 0 (baseline), 4 and 12. Of 415 patients completing the questionnaire at all time points (per-protocol population), 95.2% were prescribed the antihistamine fexofenadine HCl 60 mg. There were significant improvements in symptoms, emotions and functioning scale scores at weeks 4 and 12 compared with baseline (P<0.005). Discomfort associated with itching, as assessed by item 1 on the Skindex-16, improved over the treatment period (score decreased by >or=1 and >or=2 in 75.2% and 50.9% of patients, respectively). Significant (P<0.005) improvements from baseline in global scores were also observed at weeks 4 and 12, and for week 12 compared with week 4. Severity scores improved significantly (P<0.005) from weeks 0-4 and from weeks 4-12. The standard therapy was generally well tolerated with only mild adverse events reported (0.5%). These data suggest that patients with atopic dermatitis and associated pruritus experience significant improvements in both symptom severity and QOL when receiving standard therapy.     

Phenotypes of atopic dermatitis identified by cluster analysis in early childhood

Atopic dermatitis is a chronic, relapsing, inflammatory skin disease that usually appears in early childhood and develops into a heterogeneous disease during childhood. The clinical course and treatment for atopic dermatitis can differ according to its phenotype and/or endotype. This study aimed to identify clinical phenotypes of atopic dermatitis in early childhood. Data were obtained from 572 children under 3 years of age with atopic dermatitis. Cluster analysis applied to 11 variables, and we identified four clusters of atopic dermatitis. Children in cluster A (n = 141) had early‐onset atopic dermatitis with high blood eosinophil counts, serum total immunoglobulin E and rates of sensitization to food allergens. Children in cluster B (n = 218) had early‐onset atopic dermatitis with low blood eosinophil counts, serum total immunoglobulin E and rates of sensitization to both food and inhalant allergens. Children in cluster C (n = 53) had early‐onset atopic dermatitis with high C‐reactive protein levels and white blood cell counts. Children in cluster D (n = 160) had middle‐onset atopic dermatitis with high serum total immunoglobulin E and rates of sensitization to inhalant allergens. Cluster A had the highest Scoring for Atopic Dermatitis and transepidermal water loss values. Age at onset, age at diagnosis, white blood cell count, eosinophil count, C‐reactive protein and serum total immunoglobulin E level were the strongest predictors of cluster assignment. Analysis of these six variables alone resulted in correct classification of 95.5% of the subjects. These results support the heterogeneity of atopic dermatitis, even in early childhood.     

Comparison of skin barrier function and sensory nerve electric current perception threshold between IgE-high extrinsic and IgE-normal intrinsic types of atopic dermatitis

Background  Two types of atopic dermatitis (AD) have been proposed, with different pathophysiological mechanisms underlying this seemingly heterogeneous disorder. The extrinsic type shows high IgE levels presumably as a consequence of skin barrier damage and feasible allergen permeation, whereas the intrinsic type exhibits normal IgE levels and is not mediated by allergen-specific IgE.
Objectives  To investigate the relationship between pruritus perception threshold and skin barrier function of patients with AD in a comparison between the extrinsic and intrinsic types.
Methods  Enrolled in this study were 32 patients with extrinsic AD, 17 with intrinsic AD and 24 healthy individuals. The barrier function of the stratum corneum was assessed by skin surface hydration and transepidermal water loss (TEWL), and pruritus perception was evaluated by the electric current perception threshold (CPT) of sensory nerves upon neuroselective transcutaneous electric stimulation.
Results  Skin surface hydration was significantly lower and TEWL was significantly higher in extrinsic AD than intrinsic AD or normal controls. Although there was no statistically significant difference in CPT among extrinsic AD, intrinsic AD and normal controls, CPT was significantly correlated with skin surface hydration and inversely with TEWL in intrinsic AD and normal controls, but not extrinsic AD. Finally, CPT was correlated with the visual analogue scale of itch in the nonlesional skin of patients with extrinsic but not intrinsic AD.
Conclusions  Patients with extrinsic AD have an impaired barrier, which increases the pre-existing pruritus but rather decreases sensitivity to external stimuli. In contrast, patients with intrinsic AD retain a normal barrier function and sensory reactivity to external pruritic stimuli.     

Pathophysiology of pruritus in atopic dermatitis: an overview

Pruritus is an essential feature of atopic dermatitis (AD) and the diagnosis of active AD cannot be made without the history of itching. Because of the high impact on life quality, most of the patients measure the severity of eczema by the intensity of pruritus rather than appearance of skin lesions. However, although pruritus is a cardinal symptom of AD, its mechanism and association with the cutaneous nervous system is not completely understood. Recently, a considerable progress has been achieved in clarifying the complex pathophysiology of pruritus in AD. As a cutaneous sensory perception, itch requires excitation of neuropeptide-containing free nerve endings of unmyelinated nociceptor fibers. It is well known that histamine and acetylcholine provoke itch by direct binding to 'itch receptors' and several mediators such as neuropeptides, proteases or cytokines indirectly via histamine release. Interestingly, some variations of these complex mechanisms could be demonstrated in patients with AD. This review highlights the recent knowledge of different mechanisms which may be involved in regulating pruritus in patients with AD potentially leading to new therapeutic applications for the treatment of itch in AD.     

The effect of wet-wrap dressing on epidermal barrier in patients with atopic dermatitis

BACKGROUND: Wet-wrap dressing has been shown to be effective for atopic dermatitis; however, the therapeutic mechanism of wet-wrap dressing is only the hypothesis based on the recovery of decreased epidermal barrier function. OBJECTIVES: To examine the therapeutic efficacy as well as the mechanism of wet-wrap dressing in atopic dermatitis patients. METHODS: To examine the difference of non-lesional and lesional atopic skin and to evaluate the change between epidermal barrier function before and after the treatment, SCORAD, epidermal water content, transepidermal water loss, the lipid amount of skin surface, immunohistochemical staining of filaggrin and loricrin, transmission electron microscopic examination, and calcium ion capture cytochemistry method were done in 10 severe form atopic dermatitis patients. RESULTS: In atopic dermatitis patients, SCORAD was clearly decreased, epidermal water content was increased, and transepidermal water loss was decreased after wet-wrap dressing. After wet-wrap dressing, increased release of lamellar body and the recovery of the damaged lamellar structure of intercellular lipid were observed; nevertheless, neither the change in keratinocyte differentiation nor the change of calcium ion gradient was detected. A week after the termination of wet-wrap dressing, increased water content and decreased transepidermal water loss were still maintained. CONCLUSION: We confirmed the abnormality of the epidermal barrier in atopic dermatitis, and the effects of wet-wrap were associated with the recovery of epidermal barrier. In atopic lesions, wet-wrap dressing induced clinical improvement by the release of lamellar body and the restoration of intercellular lipid lamellar structure.     

Biologics in atopic dermatitis

Atopic dermatitis (AD) accounts for a significant share of chronic inflammatory skin disorders. There is a niche for the development of biologics to treat recalcitrant autoinflammatory stage AD seen mostly in adults. The heterogeneity of patient response to various existing biotherapies points to involvement of various immune responses and suggests that therapies must preferably target early development of allergen‐specific B‐ and T‐cell clones. In addition to immune targets, tissue factors that help restore the normal epidermal environment constitute interesting therapeutic tools. Several approaches are needed to find the appropriate targets in a field where so many have been investigated without definitive proof of concept for human systemic therapy. The keys to success are probably (1) to influence the inflammatory skin pattern towards less pruritogenic effects, requiring us to better understand pruritogenic inflammation and (2) to limit the amplification loop of disease by attacking abnormal regulatory mechanisms which perpetuate skin autoinflammation.     

Epithelial barrier function and atopic diathesis in rosacea and perioral dermatitis

BACKGROUND: Rosacea and perioral dermatitis (PD) are common dermatoses, the aetiology and pathogenesis of which remain speculative. Objectives To investigate skin barrier function and features of atopy in both diseases. METHODS: We studied 75 patients with rosacea and 75 with PD. Transepidermal water loss (TEWL) was measured in three regions of the face (lateral chin, perinasal cheek, side of the nose) and the patients were assessed for atopy by clinical criteria, prick tests and specific IgE against a mixture of aeroallergens (CAP SX1). The control group consisted of 125 individuals with no history of rosacea, PD or active atopic disease. RESULTS: In patients with PD, TEWL was significantly increased (P < 0.001) at all measurement points in comparison with the rosacea and control groups. Significantly (P < 0.001) higher values were also found regarding history and clinical signs of an atopic diathesis, prick test reactivity and specific IgE against aeroallergens. CONCLUSIONS: PD is characterized by a skin barrier disorder of facial skin. It differs from rosacea in that it involves a significantly increased TEWL and features of an atopic diathesis. However, it remains disputed as to whether PD is an individual skin disease or a subtype of rosacea in atopic patients.