A double‐blind,randomized assessment of the irritant potential of sunscreen chemical dilutions used in photopatch testing*

Background: The maximum concentration of organic sunscreen filters in current usage that does not lead to irritant reactions when performing photopatch testing is not known. Such irritant reactions can be misinterpreted as positive photoallergic contact dermatitis reactions. Objective: To determine the frequency of irritant reactions to 19 organic sunscreen filters in current use. Patients/Methods: Ninety‐four healthy volunteers were photopatch tested using the European consensus methodology to three different concentrations (2%, 5%, and 10%) of 19 organic sunscreen filters at the Photobiology Unit in Dundee, UK. Results: Of the 94 subjects recruited, 80 were analysed after withdrawals and exclusions. Of the 19 organic sunscreen filters studied, only 2 compounds led to irritant reactions in ≥5% subjects. Five per cent and 10% benzophenone‐4 led to irritant reactions in four and six subjects, respectively. Five per cent methylene bis‐benzotriazolyl tetramethylbutylphenol led to irritant reactions in six subjects, but unlike benzophenone‐4, this was not in a dose‐dependent fashion. Conclusions: When performing photopatch testing according to the European consensus methodology with these 19 organic sunscreen filters, a 10% concentration is suitable for all filters, except benzophenone‐4, which should be tested at a concentration of 2%.     

A bioengineering study on the efficacy of a skin protectant lotion in preventing SLS-induced dermatitis

Background/aims: This study evaluated the efficacy of a dimethicone skin protectant lotion against sodium lauryl sulfate (SLS)-induced irritant contact dermatitis (ICD) by clinical visual grading and bioengineering techniques in 12 healthy humans.
Methods: The flexor aspects of both forearms of the subjects were used as test sites. Each test was duplicated to diminish the variations of the test sites. In a random order and a double-blind manner, two test sites were pretreated either with the testing protectant lotion or with its vehicle control prior to contact with SLS. Thirty minutes later, 0.2 ml of 0.5% SLS in a polypropylene chamber was applied to each pretreated site. One additional test site served as a positive control (without lotion), receiving the irritant only. After 24 h of exposure to the irritant, the chambers were removed. The efficacy of protective effect was determined by four parameters: visual scoring (VS), transepidermal water loss (TEWL), skin color ( a * value), and cutaneous blood flow volume (BFV). All test sites were assessed with the parameters daily for 5 days.
Results: The VS data showed a significant decrease on the site pretreated with protectant lotion in comparison with the SLS-only treated site ( P <0.01) and with the site pretreated with control vehicle ( P <0.05) (overall for 5 days). TEWL value was significantly decreased in comparison with the SLS-only treated site ( P =0.02 at day 2; P =0.008 at day 4; P =0.014 at day 5) and with the site pretreated with the control vehicle ( P <0.05) (day 2, 4 and 5). However, the BFV and a * values did not show a statistical difference between protectant lotion, vehicle, and SLS-only treated sites.
Conclusions: This study demonstrated that appropriate dimethicone skin protection products may provide certain benefits from surfactant ICD. The skin protectant lotion may be used to prevent ICD in home or work environments, where skin irritants may induce dermatitis or eczema.     

Superiority of a vitamin B12‐barrier cream compared with standard glycerol‐petrolatum‐based emollient cream in the treatment of atopic dermatitis: A randomized,left‐to‐right comparative trial

Atopic dermatitis (AD) is a result of complex genetic, epigenetic, environmental, and immunological interactions with an overlapping epidermal barrier defect. The study evaluates the efficacy and tolerability of topical Vitamin B12‐barrier cream (MB12) compared with standard glycerol‐petrolatum‐based emollient cream (GPC) used three times a day for mild AD. The study was conducted as a on one hemi‐body randomized, controlled, single‐blind, intra‐patient left‐to‐right comparative trial by patients with clinical diagnosis of mild AD measured with total SCORAD index over 4 months. MB12 was compared on one hemi‐body treated (GPC). The comparisons of score values were performed primarily by using non‐parametric procedures: Mann–Whitney‐U test (for independent samples) and Wilcoxon test (for dependent samples). All 22 patients were randomized (left or right side treated with MB12 or GPC). At week 12 a reduction from baseline in SCORAD index was assessed in both body sites with 77.6% SCORAD index reduction in the MB12 treated body sites versus 33.5% in the GPC treated body sites. These results suggest that MB12 could represent a new option in the treatment of mild AD.     

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.     

Skin barrier response to occlusion of healthy and irritated skin: Differences in trans‐epidermal water loss,erythema and stratum corneum lipids

Background. Occlusion of the skin is a risk factor for development of irritant contact dermatitis. Occlusion may, however, have a positive effect on skin healing. No consensus on the effect of occlusion has been reached. Objectives. To investigate skin barrier response to occlusion on intact and damaged skin. Methods. In study A, the response to occlusion (nitrile glove material) for either 8 hr daily for 7 days or for 72 consecutive hours, respectively, was determined and compared with that of non‐occluded skin. In study B, the response to occlusion of for 72 consecutive hours of skin that had been damaged by either sodium lauryl sulfate (SLS) or tape stripping, respectively, was determined and compared with that of to non‐occluded pre‐damaged skin. Skin barrier function was assessed by measurements of trans‐epidermal water loss (TEWL) and erythema. In study A, stratum corneum lipids were analysed. Results. Occlusion of healthy skin did not significantly influence skin barrier function, ceramide profile or the ceramide/cholesterol ratio. Occlusion of the skin after SLS irritation resulted in higher TEWL than in the control (P = 0.049). Occlusion of the skin after tape stripping resulted in lower TEWL than in control skin (P = 0.007). Conclusions. A week of occlusion did not significantly affect healthy skin, but was found to decrease healing of SLS‐damaged skin, and to improve healing of tape‐stripped skin.     

Topical antioxidants protect the skin from chemical-induced irritation in the repetitive washing test: a placebo-controlled, double-blind study

Background. There is increasing evidence that reactive oxygen species play an important role in the development of both irritant and allergic contact dermatitis. Objectives. To assess the potential of topical antioxidants to prevent the development of experimentally induced irritant contact dermatitis. Methods. We evaluated the effect of a cream containing a combination of antioxidants on sodium lauryl sulfate-induced irritant contact dermatitis in the repetitive washing test. As readout parameters for skin barrier function and cutaneous inflammation stratum corneum hydration, cutaneous blood flow and transepidermal water loss were assessed in 25 volunteers with bioengineering methods. Results. In comparison with the cream base and a frequently used barrier cream, the antioxidant cream had high radical scavenging activity and effectively protected the skin from chemical-induced irritation. Conclusions. The superiority of the cream with antioxidants to the cream base suggests that reactive oxygen species, at least in part, play a role in the development of irritant contact dermatitis.     

Combination of glucosamine and low‐dose cyclosporine for atopic dermatitis treatment: A randomized,placebo‐controlled,double‐blind,parallel clinical trial

Our recent pilot study showed better outcomes using a combination of low‐dose cyclosporine and glucosamine than cyclosporine alone in the treatment of atopic dermatitis (AD). Here, a randomized, placebo‐controlled, double‐blind, parallel‐designed study was planned to compare the efficacy and safety of low‐dose cyclosporine and glucosamine combination to low‐dose cyclosporine alone for the treatment of patients with moderate to severe AD. AD patients with a Severity Scoring of Atopic Dermatitis (SCORAD) index ≥30 were randomly assigned in a 1:1 ratio to receive either cyclosporine 2 mg/kg and glucosamine 25 mg/kg (group A) or cyclosporine and placebo (group B) for 8 weeks. SCORAD indices, serum levels of chemokine ligand 17 and interleukin‐31, eosinophil counts, and blood cyclosporine levels were examined before and after treatment. The SCORAD indices for group A (n = 19) were significantly reduced after the treatment and a significant correlation between the changes in the SCORAD indices and changes in the serum levels of chemokine ligand 17, but not interleukin‐31, was detected. Glucosamine combined with cyclosporine did not increase adverse events and serum cyclosporine levels compared with cyclosporine alone. Therefore, combination of low‐dose cyclosporine and glucosamine may be useful to allow the long‐term use of cyclosporine in the treatment of patients with moderate to severe AD.     

Effect of topical heparin and levomenol on atopic dermatitis: a randomized four‐arm,placebo‐controlled,double‐blind clinical study

Background The aim of the controlled double‐blind trial was to demonstrate the superiority of a topical combination product over its single constituents. Patients and Methods A total of 278 patients with atopic dermatitis were randomized into four groups: 79 patients were treated with a topical combination of levomenol and heparin (A), 80 patients with levomenol alone (B), 78 patients with heparin alone (C) and 41 patients with the cream base with no active substances (D). The medication was applied twice daily for 8 weeks. Efficacy criteria included the severity of pruritus (visual analogue scale, VAS) and the SCORing Atopic Dermatitis (SCORAD) index as well as the overall assessment of efficacy and tolerance by both physician and patient. Results The improvement of pruritus and SCORAD values in Group A was significantly higher compared with Groups B–D (ancova , P < 7 × 10^?8). The improvement of pruritus in Group A approximately corresponded to the cumulative effect of the two single active substances, with mean improvements of itching of ?41.3, ?13.3, ?21.3 and +0.6 mm VAS in Groups A–D, respectively (95% CI 7.1–13.5, 2.9–9.2 and 10.4–18.3 mm for the comparisons A vs. B, A vs. C and A vs. D). Conclusion The combination of levomenol and heparin proved to be significantly more efficacious in the treatment of pruritus and inflamed skin than the preparations of the single components.     

Probiotics in pregnant women to prevent allergic disease: a randomized,double‐blind trial

Background Previous reports have suggested that certain probiotics given to mothers and children at risk of atopy halves the incidence of atopic dermatitis (AD) at 2 years of age. Objectives To examine if probiotics given to pregnant women in a nonselected population could prevent atopic sensitization or allergic diseases during the child’s first 2 years. Methods In a randomized, double‐blind trial of children from a nonselected maternal population (ClinicalTrials.gov identifier: NCT00159523), women received probiotic milk or placebo from 36 weeks of gestation to 3 months postnatally during breastfeeding. The probiotic milk contained Lactobacillus rhamnosus GG, L. acidophilus La‐5 and Bifidobacterium animalis subsp. lactis Bb‐12. Children with an itchy rash for more than 4 weeks were assessed for AD. At 2 years of age, all children were assessed for atopic sensitization, AD, asthma and allergic rhinoconjunctivitis. The intention‐to‐treat (ITT) analysis was enabled by multiple imputations. Results Four hundred and fifteen pregnant women were computer randomized. At 2 years, 138 and 140 children in the probiotic and the placebo groups, respectively, were assessed. In the ITT analysis, the odds ratio (OR) for the cumulative incidence of AD was 0·51 in the probiotic group compared with the placebo [95% confidence interval (CI) 0·30–0·87; P = 0·013]. There were no significant effects on asthma (OR 0·68, 95% CI 0·26–1·80; P = 0·437) or atopic sensitization (OR 1·52, 95% CI 0·74–3·14; P = 0·254). Conclusions Probiotics given to nonselected mothers reduced the cumulative incidence of AD, but had no effect on atopic sensitization.     

Preventive effects of topical washing with miconazole nitrate‐containing soap to diaper candidiasis in hospitalized elderly patients: A prospective,double‐blind,placebo‐controlled study

The objective of the present randomized, double‐blind trial was to evaluate the efficacy and safety of daily washing with miconazole nitrate‐containing soap for candidiasis at diaper‐covered sites in elderly subjects under long‐term inpatient care. To confirm the onset and disappearance of candidiasis, we microscopically evaluated the existence of the pseudohyphae and/or blastoconidia of Candida spp. We enrolled 75 elderly patients who wore diapers all day in the hospital or nursing home. Patients were randomly assigned to receive treatment with either miconazole soap or miconazole‐free placebo soap, and 28 patients in the miconazole group and 27 patients in the placebo group were followed for 4 weeks. Although washing with miconazole soap did not affect the frequency of pseudohyphae/blastoconidia‐positive patients, it significantly inhibited the positive conversion of pseudohyphae/blastoconidia compared with the placebo group. As a result, the frequency of patients positive for pseudohyphae/blastoconidia was significantly lower in the miconazole group than in the control group at 4 weeks (17.9% vs 44.4%). Clinically apparent diaper candidiasis did not develop in either group. Washing with miconazole soap was a significant independent factor for reducing the cases positive for pseudohyphae/blastoconidia, while diarrhea and heart failure were significant factors associated with an increase in the positive rate at the end‐point. Severe adverse effects were not found in any patients. Thus, washing with miconazole soap is well‐tolerated and can inhibit the positive conversion of Candida in patients wearing diapers. Therefore, maintenance of genital hygiene using this soap may prophylactically decrease the overall prevalence of patients with diaper candidiasis.     

Phase 2a,randomized, double‐blind,placebo‐controlled,multicenter, parallel‐group study of a H4R‐antagonist (JNJ‐39758979) in Japanese adults with moderate atopic dermatitis

This trial was conducted to evaluate the safety and efficacy of the H₄R‐antagonist JNJ‐39758979 in adult Japanese patients with moderate atopic dermatitis (AD). Eligible patients were randomly assigned to JNJ‐39758979 300 mg, 100 mg or placebo once daily for 6 weeks in this phase 2a, double‐blind, multicenter, placebo‐controlled study. Primary efficacy was assessed via week‐6 Eczema Area and Severity Index (EASI) scores. Secondary efficacy assessments included Investigator's Global Assessment (IGA) and patient‐reported outcome (PRO) pruritus assessments (Pruritus Categorical Response Scale [PCRS], Pruritus Numeric Rating Scales [PNRS], Pruritus Interference Numeric Rating Scale [PINRS] and Subject's Global Impressions of Change in Pruritus [SGICP]). Eighty‐eight of 105 planned patients were randomized before the study was stopped and unblinded for safety reasons. The study did not meet the primary end‐point. However, numerical improvements (i.e. decreases) in median EASI were observed with JNJ‐39758979 100 mg (?3.7) and 300 mg (?3.0) versus placebo (?1.3) at week 6. Nominally significant improvements across PRO PCRS, PNRS and SGICP assessments were consistently observed, particularly with JNJ‐39758979 300 mg. Safety, including adverse events (AE), was comparable between JNJ‐39758979 and placebo with the exception of two patients (both receiving JNJ‐39758979 300 mg) with serious AE of neutropenia, leading to premature study discontinuation. No deaths were reported. Except for neutropenia, no clinically relevant changes in laboratory values were observed. Although not conclusive, findings suggest H₄R‐antagonism may be beneficial for AD, particularly in controlling pruritus. JNJ‐39758979 appears to be associated with drug‐induced agranulocytosis, likely an off‐target effect.     

Seemingly healthy skin in atopic dermatitis: observations with the use of high‐frequency ultrasonography,preliminary study

Background: Atopic dermatitis (AD) is a chronic, relapsing skin disorder which is strictly determined by the epidermal barrier function. In previous studies, there is conclusive evidence that normal‐looking, nonlesional skin presents meaningful barrier function defect and a sub‐clinical eczematous skin reaction. Aim: The authors intended to visualize nonlesional AD skin with the use of high frequency ultrasonography to show that the normal‐looking, nonlesional skin may present significant abnormalities in USG examination. Methods: We have performed analysis with the use of high‐frequency 20 MHz skin sonography in the cases of 15 AD patients of the Department of Dermatology, Medical University, Poznań, Poland. The clinical score has been evaluated on the basis of W‐AZS index and EASI. The results were presented in the form of ultrasonographic images. Results: High frequency ultrasonography revealed an echopoor band within nonlesional skin of six (40%) examined AD patients and in all cases within skin lesions. Conclusion: Our results indicate the significant role of skin ultrasonography in the complete clinical evaluation of patients with AD, which may serve as an element in selection of the most appropriate topical treatment. An echopoor band beneath the echo entry within nonlesional skin of some AD patients may reflect subclinical eczematous reaction and the readiness for the development of typical skin lesions. For this purpose, we suggest to name an intact skin in AD as seemingly healthy skin.     

Comparative study of skin sebum and elasticity level in patients with sulfur mustard‐induced dermatitis and healthy controls

Background: Sulfur mustard (SM) – a chemical agent – has both acute and chronic effects on skin. Xerosis, which is deemed to be due to the damage of hydrolipidic barrier of the skin, is the most common complaint of veterans exposed to the chemical. This study was designed to evaluate skin sebum and elasticity in veterans with a history of SM contact. Methods: Three hundred and ten subjects were enrolled in this study and were divided into four groups: SM‐exposed patients with current skin lesions (n=87); SM‐exposed patients without skin lesions (n=71); patients with dermatitis (n=78); and normal controls (n=74). The skin sebum and elasticity were measured in four areas (forehead, suprasternal, palm and back of the hands) using a Sebumeter and a Reviscometer. Results: Skin sebum was higher in participants who presented with dermatitis and had history of contact with SM than others; the difference was only statistically significant on the forehead. There was no significant difference in the skin elasticity between the four groups. Conclusion: While SM may increase skin sebum in long term, there is no evidence that it has a substantial effect on skin elasticity.     

Efficacy and safety of topical OPA‐15406, a new phosphodiesterase 4 inhibitor,in Japanese patients with atopic dermatitis for 8 weeks: A phase 2, randomized,double‐blind,placebo‐controlled study

The efficacy and safety of topical OPA‐15406, a new phosphodiesterase 4 inhibitor, were examined in Japanese patients aged 15–70 years with atopic dermatitis in a phase 2, randomized, double‐blind, vehicle‐controlled study. Two hundred patients were randomized to three treatment groups at a 1:1:1 ratio to receive OPA‐15406 0.3%, OPA‐15406 1% or vehicle ointment twice daily for 8 weeks. The OPA‐15406 1% group was superior to the vehicle group in terms of the incidence of success based on the Investigator Global Assessment score at week 4 (P = 0.0328), which was the primary end‐point, while the OPA‐15406 0.3% group showed a trend toward improvement in the primary end‐point. The mean Eczema Area and Severity Index total score and subscale (erythema, induration/papulation, excoriation and lichenification) scores, the Visual Analog Scale pruritus score and the Patient‐Oriented Eczema Measure score were significantly improved and the percentage of affected body surface area was significantly decreased in both OPA‐15406 groups relative to the vehicle group as early as week 1, and the improved scores and decreased percentages were generally maintained until week 8. No deaths or serious treatment‐emergent adverse events occurred in the OPA‐15406 treatment groups. Treatment‐emergent adverse events frequently observed across treatment groups were worsening of atopic dermatitis, viral upper respiratory tract infection and pruritus, all of which were mild or moderate in severity in the OPA‐15406 groups. OPA‐15406 1% ointment showed favorable efficacy and safety profiles, indicating a promising treatment option for patients with atopic dermatitis.     

Deficiency of n‐6 polyunsaturated fatty acids is mainly responsible for atopic dermatitis‐like pruritic skin inflammation in special diet‐fed hairless mice

Hairless mice fed a special diet, HR‐AD, develop atopic dermatitis (AD)‐like skin inflammation with skin barrier defects and itch‐related scratching; however, the ingredient(s) causing the dermatitis remains unclear. In this study, we examined whether deficiency of certain polyunsaturated fatty acids (PUFAs) is involved in HR‐AD‐induced AD. High‐purity PUFAs were given to HR‐AD‐fed mice by dietary supplementation or gavage. Fatty acid levels in the serum and skin were determined by using gas chromatography–mass spectrometry. In serum from HR‐AD‐fed mice, linoleic acid (LA, 18:2n‐6) and α‐linolenic acid (ALA, 18:3n‐3), as well as their metabolites, were markedly decreased. When mice were fed HR‐AD supplemented with LA or ALA in an amount equal to that contained in a normal diet, the development of AD‐like symptoms was completely prevented by supplementation with LA but not with ALA. Relatively high dose of ALA slightly alleviated skin barrier defects, but did neither itch‐related scratching nor skin inflammation. On the other hand, gavage administration of LA metabolites, such as γ‐linolenic acid and arachidonic acid (AA), significantly ameliorated established dermatitis without increasing LA in the serum and skin. Moreover, AA‐induced amelioration of dermatitis was not affected by pharmacological blockade of 5‐lipoxygenase (5‐LOX) and cyclooxygenase (COX), suggesting no involvement of 5‐LOX‐ or COX‐mediated AA metabolites in the amelioration. In conclusion, our results indicate that deficiency of n‐6 PUFAs is mainly responsible for AD‐like symptoms by HR‐AD feeding. Thus, this model could be useful for studying the pathomechanisms associated with deficiency of n‐6 PUFAs in AD.