Improvement in skin barrier function in patients with atopic dermatitis after treatment with a moisturizing cream (Canoderm)

Patients with atopic skin show a defective barrier function both in rough and in clinically normal skin, with an increasing risk of developing contact dermatitis. Moisturizing creams are often used in the treatment of dry skin. The purpose of this study was to investigate the influence of treatment with a urea-containing moisturizer on the barrier properties of atopic skin. Fifteen patients with atopic dermatitis treated one of their forearms twice daily for 20 days with a moisturizing cream. Skin capacitance and transepidermal water loss (TEWL) were measured at the start of the study and after 10 and 20 days. On day 21 the skin was exposed to sodium lauryl sulphate (SLS) and on day 22 the irritant reaction was measured non-invasively. Skin capacitance was significantly increased by the treatment, indicating increased skin hydration. The water barrier function, as reflected by TEWL values, tended to improve (P = 0.07), and the skin susceptibility to SLS was significantly reduced, as measured by TEWL and superficial skin blood flow (P < 0.05). Thus, it seems that certain moisturizers could improve skin barrier function in atopics and reduce skin susceptibility to irritants. The mechanism and the clinical relevance need further investigation.     

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.     

特应性皮炎动物模型表皮脂合成的研究

目的:探讨特应性皮炎(AD)皮肤生理改变(包括表皮水分丢失量和角质层水分含量)是否与表皮脂的代谢有关。方法:在小鼠的背部和躯干外涂2,4-二硝基氟苯(DNFB),建立小鼠特应性皮炎模型,利用14[C]乙酸对AD模型表皮脂的代谢进行研究,并用电子显微镜对AD皮肤的超微结构进行观察。结果:AD表皮的胆固醇和脂肪酸的合成速度明显低于对照组,正常对照组的角质细胞间均为正常的复层板层膜结构。而皮炎组的深层角质细胞间虽可见正常的复层板层结构,但有许多没有加工完全的膜结构存在。结论:推测AD皮肤生理的异常改变可能是由于表皮脂的合成减少和角质细胞间膜异常所致。     

Intermittent dosing of fluticasone propionate cream for reducing the risk of relapse in atopic dermatitis patients

BACKGROUND: One of the most troublesome features of atopic dermatitis (AD) is its chronic relapsing nature, and there is a lack of published evidence on the best treatment strategy for long-term management of the disease. OBJECTIVE: To compare an intermittent dosing regimen of fluticasone propionate (FP) cream 0.05% (twice per week) with its vehicle base in reducing the risk of relapse when added to regular daily emollient in adult and paediatric subjects with stabilized AD. METHODS: Subjects (aged 3 months to 65 years) with moderate or severe AD were enrolled into an open-label Stabilization Phase of up to 4 weeks on daily emollients plus FP twice daily. Those subjects who achieved 'treatment success' (Global Assessment Score 相似文献   

Daily intake of Jeju groundwater improves the skin condition of the model mouse for human atopic dermatitis

Drinking water is an important nutrient for human health. The mineral ingredients included in drinking water may affect the physical condition of people. Various kinds of natural water are in circulation as bottled water in developed countries; however, its influence on clinical conditions of patients with certain diseases has not been fully evaluated. In this study, effects of the natural groundwater from Jeju Island on clinical symptoms and skin barrier function in atopic dermatitis (AD) were evaluated. NC/Tnd mice, a model for human AD, with moderate to severe dermatitis were used. Mice were given different natural groundwater or tap water for 8 weeks from 4 weeks of age. Clinical skin severity scores were recorded every week. Scratching analysis and measurement of transepidermal water loss were performed every other week. The pathological condition of the dorsal skin was evaluated histologically. Real‐time polymerase chain reaction analysis was performed for cytokine expression in the affected skin. The epidermal hyperplasia and allergic inflammation were reduced in atopic mice supplied with Jeju groundwater when compared to those supplied with tap water or other kinds of natural groundwater. The increase in scratching behavior with the aggravation of clinical severity of dermatitis was favorably controlled. Moreover, transepidermal water loss that reflects skin barrier function was recovered. The early inflammation and hypersensitivity in the atopic skin was alleviated in mice supplied with Jeju groundwater, suggesting its profitable potential on the daily care of patients with skin troubles including AD.     

The management of moderate to severe atopic dermatitis in adults with topical fluticasone propionate

This study was designed to investigate a long-term therapeutic strategy for the management of recurring atopic dermatitis (AD) in adults using fluticasone propionate (FP) ointment (Cutivate^TM) whereby FP could help to prevent a relapse of AD once symptoms were under control. Adult patients with chronic, moderate to severe AD entered this multicentre study. All patients were initially treated with FP 0.005% (g/g) ointment in two different regimens. Patients whose AD had been completely healed by these treatments then entered a long-term treatment phase applying FP or placebo ointment once daily, two times per week for 16 weeks to 'known' healed lesions. By the end of the initial treatment period, mean SCORAD values had significantly ( P  < 0.0005) improved from baseline. Patients who entered the maintenance phase and were treated with intermittent FP for up to 16 weeks, demonstrated its superior efficacy ( P  = 0.018) over placebo, maintaining the improvements achieved after the initial treatment phase, reducing risk of relapse and delaying time to relapse ( P  = 0.013). No significant changes were detected in either treatment group in serum cortisol levels or in skin thickness measurements. Intermittent FP applied two times per week maintained a significant level of control, and delayed relapse of AD by comparison with placebo.     

Economic evaluation of maintenance treatment with tacrolimus 0.1% ointment in adults with moderate to severe atopic dermatitis

Background Rational health care decision‐making based on outcomes and economic evidence is essential to provide the best possible care for individual patients with atopic dermatitis (AD). Objectives To describe treatment outcomes and to evaluate resource utilization and associated cost of maintenance use of tacrolimus ointment (MU) vs. standard use of tacrolimus ointment (SU) in adults with AD. Methods A pan‐European, phase III multicentre randomized clinical trial was conducted. Patients with mild to severe AD were randomized to tacrolimus 0·1% ointment (MU) or vehicle (SU) twice per week for 12 months. Disease exacerbations were treated by using open‐label tacrolimus 0·1% ointment twice daily. Resource utilization data were collected prospectively alongside the clinical trial. Costs of pooled resource data were determined using German unit cost data. Direct and indirect costs were considered from third party payer, patient and societal perspectives. Results All patients with moderate and severe AD were included in a subanalysis, 75 patients in the MU arm (57% moderately affected) and 59 patients in the SU arm (59% moderately affected). In patients with moderate AD, the number of disease exacerbations in the MU arm was 2·4 vs. 5·5 in the SU arm (P < 0·001); in patients with severe AD corresponding figures were 2·3 vs. 7·4 (P < 0·001), respectively. Mean ± SD total annual cost per patient was €1525 ± 1081 (MU) vs. €1729 ± 1209 (SU) in patients with moderate AD and €2045 ± 2013 (MU) vs. €2904 ± 1510 (SU) in patients with severe AD. Conclusions Maintenance treatment with 0·1% tacrolimus ointment is more effective and leads to cost savings and improved health‐related quality of life in comparison with standard use of 0·1% tacrolimus ointment, especially in patients with severe AD.     

Treatment of patients with atopic dermatitis using wet-wrap dressings with diluted steroids and/or emollients. An expert panel''s opinion and review of the literature

BACKGROUND: The use of dampened bandages to reduce inflamed eczema (synonyme dermatitis) is an old remedy. In order to evaluate the current indications for so-called wet-wrap treatment (WWT) for atopic dermatitis (AD), and to compare the different currently recognized methods, a group of experts critically reviewed their own expertise on WWT in respect to the existing literature on the subject. RESULTS: WWT is well tolerated in eczema due to the cooling effect on the skin and the rapid improvement in skin inflammation. It has been shown to be an extremely effective treatment for acute erythrodermic dermatitis, therapy-resistant AD and intolerable pruritus. Advantages of WWT include rapid response to therapy, reduction in itch and sleep disturbance, and potential for reduction in usage of topical corticosteroids (TCS). However, disadvantages include high cost, the necessity for special training in usage, potential for increased TCS absorption, increased cutaneous infections and folliculitis, and poor tolerability. Precautions to reduce the risks of long-term treatment should include education, monitoring of weight and height and, if necessary, serum cortisol levels. In adolescents the risk of striae from TCS absorption around puberty is high, and WWT with TCS in this age group should be used as a short-term therapy only and with extreme caution. To reduce risks, dilutions of steroids may be used ranging from 5 to 10%. In the maintenance phase this treatment can be rotated with the use of emollients only. Low potency TCS should be used on the face (with a mask). CONCLUSION: WWT using diluted steroids is a relatively safe addition to the therapeutic treatment options for children and adults with severe and/or refractory AD. Explanation and education is extremely important in the treatment of AD and WWT should only be employed by practitioners trained in its use. Specialized nursing care is essential, especially when using WWT for prolonged periods.     

Skin and systemic pharmacokinetics of tacrolimus following topical application of tacrolimus ointment in adults with moderate to severe atopic dermatitis

Background  Systemic exposure to tacrolimus following topical application of tacrolimus ointment is minimal. There are, however, no data on the distribution of tacrolimus in the skin.
Objectives  To assess the distribution of tacrolimus in the skin and the systemic pharmacokinetics of tacrolimus in adults with moderate to severe atopic dermatitis after first and repeated application of tacrolimus ointment.
Methods  We investigated skin distribution of topically applied tacrolimus and systemic pharmacokinetics of percutaneously absorbed tacrolimus in adults with atopic dermatitis after topical application of tacrolimus 0·1% ointment twice daily for 2 weeks. Tacrolimus concentrations were assessed in full-thickness skin biopsies and blood samples.
Results  Of 14 patients, 11 completed treatment and were analysed. Mean ± SD tacrolimus concentrations in the skin at 24 h after first and last ointment applications were 94 ± 20 and 595 ± 98 ng cm⁻³, respectively. At 168 h after stopping treatment, values were 97% lower than at 24 h after last application. Tacrolimus concentration decreased with increasing skin depth. Systemic tacrolimus exposure after ointment application was low and highly variable, with 31% of samples below the limit of quantification (0·025 ng mL⁻¹) and 94% below 1 ng mL⁻¹. Blood concentrations at 24 h after the first and last ointment applications were 750 and 1800 times lower, respectively, than those in skin. Physicians' assessments showed that tacrolimus ointment was effective and well tolerated.
Conclusions  Tacrolimus was primarily partitioned in the skin, with minimal systemic absorption after topical application, in patients with atopic dermatitis.     

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.     

他克莫司软膏治疗成人特应性皮炎

目的研究他克莫司软膏治疗成人特应性皮炎(AD)的疗效与安全性.方法采用随机、双盲、赋形剂对照临床研究方法,将44例成人AD患者随机分为3组,按111比例分别接受0.1%(0.1%组)、0.03%(0.03%组)他克莫司软膏和赋形剂(赋形剂组)治疗.观察治疗第1、2和3周的临床疗效和不良反应.结果他克莫司软膏0.1%组和0.03%组的有效率分别为86.7%(13/15)和78.6%(11/14),均明显高于赋形剂组(42.9%,6/14),差异非常显著(P＜0.001).总体疗效比较0.1%组优于0.03%组,差异显著(P=0.043).治疗后第1、2、3周0.1%组和0.03%组的主要症状-体征指标平均值均明显低于赋形剂组,组间差异显著(P＜0.05～P＜0.001).治疗后患者的生活质量明显改善.药物相关不良反应主要为一过性局部刺激,但组间比较无统计学意义(P＞0.05),3组均未出现严重不良反应.结论他克莫司软膏治疗成人特应性皮炎安全有效.     

Efficacy and safety of 'wet-wrap' dressings as an intervention treatment in children with severe and/or refractory atopic dermatitis: a critical review of the literature

BACKGROUND: During the last two decades wet-wrap treatment (WWT) has been advocated as a relatively safe and effective treatment modality in children with severe and/or refractory atopic dermatitis (AD). Unfortunately, there are still many unsolved issues concerning the use of wet-wrap dressings in patients with AD. OBJECTIVES: To make an inventory of the different methodologies and to evaluate the currently available evidence for the use of WWT as an intervention treatment in children with severe and/or refractory AD. METHODS: We performed a search of the literature via the online PubMed database. Reference lists from relevant articles were scanned for additional publications. Publications describing a treatment modality for children with severe and/or refractory AD, which included the application of wet dressings, were collected and evaluated using the guidelines of the NHS Centre for Reviews and Dissemination, University of York. RESULTS: Twenty-four publications were included for evaluation. Eleven of the publications detailed original clinical studies (study design level 2-4), while 13 revealed expert opinions (study design level 5). Evidence levels did not exceed level 4. CONCLUSIONS: Large prospective studies evaluating the efficacy and safety profile of WWT are lacking. We were able to formulate the following conclusions with a grade C of recommendation. (i) WWT using cream or ointment and a double layer of cotton bandages, with a moist first layer and a dry second layer, is an efficacious short-term intervention treatment in children with severe and/or refractory AD. (ii) The use of wet-wrap dressings with diluted topical corticosteroids is a more efficacious short-term intervention treatment in children with severe and/or refractory AD than wet-wrap dressings with emollients only. (iii) The use of wet-wrap dressings with diluted topical corticosteroids for up to 14 days is a safe intervention treatment in children with severe and/or refractory AD, with temporary systemic bioactivity of the corticosteroids as the only reported serious side-effect. (iv) Lowering the absolute amount of applied topical corticosteroid to once daily application and further dilution of the product can reduce the risk of systemic bioactivity.     

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.     

Oral administration of persimmon leaf extract ameliorates skin symptoms and transepidermal water loss in atopic dermatitis model mice, NC/Nga

BACKGROUND: We have previously shown that persimmon leaf extract and its major flavonoid constituent, astragalin, inhibited histamine release by basophils and that oral administration of these substances prior to the onset into an atopic dermatitis (AD) model mouse, NC/Nga, prevented development of dermatitis. OBJECTIVES: This study was designed to assess the clinical therapeutic effect of persimmon leaf extract and astragalin in NC/Nga mice suffering from dermatitis and the dose-response preventive effects of persimmon leaf extract on dermatitis and transepidermal water loss (TEWL). METHODS: The efficacy of persimmon leaf extract or astragalin in NC/Nga mice was judged by measurement of skin severity, scratching behaviour, serum IgE levels or TEWL. RESULTS: Oral administration of persimmon leaf extract (250 mg kg(-1)) or astragalin (1.5 mg kg-1) for 4 weeks into NC/Nga mice with overt dermatitis resulted in a decrease in the severity of the condition. The preventive effect of persimmon leaf extract on the dermatitis was dose-dependent and continuous intake of persimmon leaf extract significantly decreased its onset and development. In addition, TEWL was also suppressed at a persimmon leaf extract dose of 250 mg kg(-1). No significant adverse reaction by these substances could be observed. CONCLUSIONS: These observations suggest that persimmon leaf extract or the flavonoid astragalin may be alternative substances for the management of AD.     

Scratching behavior in spontaneous- or allergic contact-induced dermatitis in NC/Nga mice

NC/Nga mice have pathological and behavioral features similar to those seen in human atopic dermatitis. There are two known dermatitis models in NC/Nga mice, one being spontaneous-induced dermatitis under conventional conditions and the other 2,4,6-trinitrochlorobenzene (TNCB)-induced allergic contact dermatitis. However, there are significant differences in time course on development of dermatitis. We studied the role of scratching behavior (sign of itch) on the development of dermatitis on spontaneous- and TNCB-induced dermatitis. We measured scratching counts, transepidermal water loss (TEWL), and skin inflammation score, under conventional conditions or by applying 5% TNCB once a week for 6 weeks in NC/Nga mice. In spontaneous-induced dermatitis, scratching counts increased with the passage of time. The scratching counts were significantly increased only 1 week after housing the mice under conventional conditions, but no changes were observed in cases of TNCB-induced dermatitis. In spontaneous-induced dermatitis, TEWL and skin-inflammation score were gradually increased, time-dependently. On the other hand, in TNCB-induced dermatitis, these dependent values rapidly increased and reached a maximum only after 24 h TNCB application. These data suggest that pathogenesis of spontaneous- and allergic contact-induced dermatitis was clearly different. It will be of major interest to identify the pruritic mediators causing profound scratching behavior and scratching-induced aggravation of inflammation in the spontaneous-induced dermatitis, as opposed to the inflammatory mediators that cause contact allergic dermatitis without major scratching.     

0.03%他克莫司软膏治疗儿童特应性皮炎的疗效观察及生活质量评价

目的:评价0.03%他克莫司软膏治疗儿童特应性皮炎的疗效和安全性。方法:采用随机、双盲、平行对照方法,分别对两组儿童特应性皮炎患者外用0.03%他克莫司软膏和赋形剂,疗程为3周。每周对患儿进行随访观察,并在治疗前、后对5～17岁患者作皮肤病学生活质量指数(DLQI)问卷调查。结果:0.03%他克莫司软膏组和对照组的有效率分别为85.0%和33.3%,两组疗效比较差异有非常显著性(P<0.001)。问卷调查表明患者治疗后生活质量明显改善。结论:0.03%他克莫司软膏治疗儿童特应性皮炎安全、有效,治疗后患者的生活质量明显改善。     

COX-1 inhibition enhances scratching behaviour in NC/Nga mice with atopic dermatitis

NC/Nga (NC) mice, spontaneously develop an eczematous atopic dermatitis (AD)-like skin lesion when kept under conventional condition (Conv), but not under specific pathogen-free (SPF) conditions, have been thought to be an animal model of AD. We have previously shown that PGD(2) and arachidonic acid inhibited the scratching behaviour of NC mice, while indomethacin enhanced it. This study was designed to assess the role of cyclooxygenase (COX)-1 and COX-2 in the itch-related scratching behaviour of NC mice. We examined the expression of COX in the skin using real-time PCR and Western blotting and the effects of SC-560 (a COX-1 selective inhibitor) or NS-398 (a COX-2 selective inhibitor) on scratching behaviour in relation to skin prostaglandin (PG) levels in NC mice. COX-1 mRNA expression was unchanged and protein expression decreased in Conv NC mice compared with that of SPF mice. By contrast, COX-2 mRNA and protein expression increased in Conv NC mice. SC-560 increased scratching behaviour and significantly reduced skin PGD(2), PGE(2) and PGF(2alpha) levels, but NS-398 did not have effects on scratching and skin PG level. Moreover, the topical application of PGD(2), which might be the endogenous inhibitor of itching, suppressed the SC-560-induced enhancement of scratching behaviour by NC mice. These results suggest COX-1-coupled skin PGD(2) biosynthesis plays a physiological role in inhibiting regulation of pruritus in NC mice with AD.     

An open study of efficacy and safety of long-term treatment with mometasone furoate fatty cream in the treatment of adult patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis is a severe chronic skin disease often deteriorated by the presence of microorganisms and often responds well to treatment with potent corticosteroids. However, the long-term use of potent topical corticosteroids are accompanied by side-effects such as skin atrophy. OBJECTIVE: To study the effect and safety of prophylactic treatment with mometasone furoate fatty cream (contains hexylene glycol) for 6 months in patients with atopic dermatitis. RESULTS: Sixty-one of 68 (90%) patients were still free of their disease after 6 months of twice weekly treatment and only one showed possible treatment related signs of skin atrophy. The number of Staphylococcus aureus and Pityrosporum ovale were significantly reduced in cleared patients. CONCLUSIONS: Mometasone furoate fatty cream is effective and safe both for treatment and as a prophylaxis in patients with atopic dermatitis.