Accelerated barrier recovery and enhancement of the barrier integrity and properties by topical application of a pH 4 vs. a pH 5·8 water-in-oil emulsion in aged skin.

BACKGROUND: Increased skin-surface pH is an important host-related factor for deteriorated barrier function in aged skin. OBJECTIVES: We investigated whether restoration of skin pH through topical application of a water-in-oil emulsion with pH 4 improved the barrier homeostasis in aged skin, and compared the effects with an identical galenic formulation with pH 5·8. METHODS: The effects of the test formulations on barrier recovery were investigated by repeated measurements of transepidermal water loss (TEWL) and skin pH 3 h, 6 h and 24 h after acetone-induced impairment of barrier function in aged skin. The long-term effects of the pH 4 and pH 5·8 emulsions were analysed by investigation of the barrier integrity and cohesion, the skin-surface pH and the skin roughness and scaliness before and after a 4-week, controlled application of the formulations. RESULTS: The application of the pH 4 emulsion accelerated barrier recovery in aged skin: 3 h and 6 h after acetone-induced barrier disruption the differences in the TEWL recovery between the pH 4 treated and acetone control fields were significant. Furthermore, long-term application of the pH 4 formulation resulted in significantly decreased skin pH, enhanced barrier integrity and reduced skin-surface roughness and scaliness. At the same time points, the pH 5·8 formulation exerted only minor effects on the barrier function parameters. CONCLUSIONS: Exogenous acidification through topical application of a water-in-oil emulsion with pH 4 leads to improvement of the skin barrier function and maintenance of the barrier homeostasis in aged skin.

A randomized, investigator-blinded efficacy assessment study of stand-alone emollient use in mild to moderately severe atopic dermatitis flares.

BACKGROUND: Whereas emollients are integral to the long-term management of atopic dermatitis (AD), the evidence for their efficacy in disease flares is limited. OBJECTIVE: We aimed to investigate the stand-alone efficacy of an emollient formulation with regard to improvement of the clinical symptoms, skin barrier function and reduction of pathogenic bacterial colonization in acute stage of AD. MATERIALS AND METHODS: Twenty AD volunteers aged 12-65 years with symmetric, mild to moderately severe inflammatory lesions on the forearms/arms were recruited for the study. At inclusion, the forearms/arms of each volunteer were randomized to receive for 1 week either an o/w formulation containing licochalcone A (Glycyrrhiza Inflata root extract), decanediol, menthoxypropanediol and ω-6-fatty acids (emollient arm) or 1% hydrocortisone (HC arm); after 1 week, the application of the emollient and HC were discontinued and the volunteers applied a w/o emollient containing licochalcone A and ω-6-fatty acids on both arms for further 3 weeks. The outcomes included reduction of the clinical and itch severity, decrease in S.aureus colonization, improvement of the barrier function, skin hydration and skin tolerability assessed after 1 week (D7) and after 4 weeks (D28) respectively. RESULTS: In both arms, there was a significant decrease in the severity score, itch intensity, erythema and TEWL on D7 and D28 compared to baseline. In addition, emollient use resulted in pronounced decrease in S.aureus colonization and significant increase of skin hydration on D7. The comparison of the outcomes, based on percentage change from baseline, showed no significant differences between the emollient and HC arm at any time point. CONCLUSIONS: The results of the study indicate that the 1-week stand-alone application of an emollient, tailored to target inflammation, pruritus, compromised barrier function and pathogenic bacterial colonization may offer benefit for the improvement of mild to moderately severe localized flares of AD.

A double-blind, randomized, vehicle-controlled efficacy assessment study of a skin care formulation for improvement of mild to moderately severe acne.

BACKGROUND: Inflammation, increased sebum production and P. acnes colonization are key factors in acne pathogenesis. Cosmetic formulations based on a combination of active compounds with in vitro proven anti-inflammatory, sebum regulating and P. acnes reducing properties may therefore contribute to improve the clinical signs and associated burden of disease. OBJECTIVE: To provide in vivo proof-of-concept, we performed a 9-week, double-blind, randomized, vehicle-controlled study to assess the stand-alone efficacy of a skin care formulation containing licochalcone A, l-carnitine and 1,2-decanediol in volunteers with mild to moderately severe acne (10-25 inflammatory lesions) involving the face. MATERIALS AND METHODS: After enrolment followed by a 1-week standardization of the cleansing procedure, 60 volunteers aged 14-40 years (40 women and 20 men, mean age 22.4 years) were randomized into two groups of 30 volunteers each, to apply either the active formulation or the vehicle twice daily on the face for 8 weeks. Reduction in the lesion count, P. acnes and sebum levels, stratum corneum hydration, Dermatology Life Quality Index (DLQI) and skin tolerability, assessed after 4 and 8 weeks were defined as outcomes. RESULTS: Compared to baseline, the active formulation group showed at the end of the study a reduction in the mean total lesions count and papular lesions, significant reduction in the pustules (P < 0.05) and sebum levels (P < 0.01), marked reduction in P. acnes and improvement of DLQI. No significant changes in the respective parameters were found in the vehicle group. At the end of the study, greater reduction in the total lesion count, papules and pustules, P. acnes colonization, sebum production and more pronounced improvement of life quality in the active formulation group compared to the vehicle were found. CONCLUSIONS: Our results provide evidence for improved outcomes in result of the application of the active formulation compared to the vehicle from both physician's and patient's perspective.

Tandem repeated irritation in aged skin induces distinct barrier perturbation and cytokine profile in vivo.

BACKGROUND: The barrier perturbation pattern and molecular markers of inflammation upon tandem repeated irritation in chronologically aged skin have not been previously studied. OBJECTIVES: We aimed to investigate the barrier impairment kinetic and in vivo cytokine profile following sequential irritation with sodium lauryl sulfate (SLS) and undiluted toluene (Tol) in aged compared with young skin. METHODS: Four fields on the volar forearm of healthy aged and young volunteers (median age, respectively, 63.9 and 32.6 years) were sequentially exposed to 0.5% SLS and undiluted toluene in a controlled tandem repeated irritation test; an adjacent nontreated field served as control. The permeability barrier function was monitored by repeated measurements of transepidermal water loss (TEWL), capacitance and erythema every 24 h up to 96 h. The stratum corneum cytokines were harvested by sequential tape stripping and quantified by multiplex bead array and enzyme-linked immunosorbent assay. RESULTS: Compared with young skin, aged skin was characterized by delayed and/or less pronounced alterations in the visual irritation score, TEWL, chromametry a*-value and capacitance, assessed by the respective Δ-values for each parameter and monitoring time point. In both groups, exposure to SLS/SLS, SLS/Tol and Tol/SLS resulted in decreased interleukin (IL)-1α levels, whereas the application of Tol/Tol induced an increase in IL-1α. Furthermore, decreased IL-1 receptor antagonist (IL-1RA) levels and a lower IL-1RA/IL-1α ratio were found following repeated exposure to the irritants. CONCLUSIONS: Our results provide evidence for selective alterations in the cytokine profile and distinct barrier impairment kinetic following tandem repeated irritation with SLS and Tol in aged compared with young skin in vivo.

Noninvasive bioengineering assessment of the skin barrier function in patients with chronic venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) comprises all symptoms caused by permanent venous and capillary hypertension. While the clinical manifestations of the disease have been well characterized, there is little knowledge on the skin barrier function in the affected patients. OBJECTIVES: The aim of the study was to assess noninvasively the barrier function in patients with CVI stage C2 and stage C4 according to the CEAP classification in comparison with healthy controls (stage C0). METHODS: Thirty patients with CVI without concomitant diseases and 15 healthy, aged-matched controls were recruited for the study. The skin barrier function was assessed by measuring transepidermal water loss (TEWL), capacitance and skin colour symmetrically on the calf, medial and lateral malleolus, posterior arch (arcus venosus) and volar forearm. RESULTS: Compared with the forearm, there was a tendency for increased TEWL and significant reduction of capacitance on all measurement sites on the lower limb. Compared with the control group, the patients with CVI had significantly higher TEWL values on all measurement sites on the lower extremities while no difference in capacitance between patients and controls was observed. CONCLUSIONS: Changes in the epidermal barrier function in patients with CVI are readily detectable by bioengineering methods as early as stage C2 and are manifested by significantly increased TEWL. Our results suggest that the reduced stratum corneum hydration in patients with CVI is due to anatomical differences rather than venous disease. These findings may help better understand the factors contributing to disease progression and its complications.

In vivo confocal laser scanning microscopy for non-invasive diagnosis of pemphigus foliaceus.

BACKGROUND/PURPOSE: In vivo confocal laser scanning microscopy (CLSM) is a modern non-invasive method for investigation of the skin that allows real-time visualization of individual cells and sub-cellular structures at resolution similar to the one provided by routine histopathology. Our aim was to investigate the potential of CLSM for non-invasive diagnosis of pemphigus foliaceus (PF). METHODS: Pre-existing and mechanically induced lesions in two cases of PF were examined by means of CLSM, parallel to routine histology, direct immunofluorescence microscopy and enzyme-linked immunosorbent assay performed in the same patients. RESULTS: The morphological features characteristic for PF, namely an intraepidermal blister with acantholytic cells in the blister cavity, were readily detectable by means of CLSM. The findings were consistent in both patients and across the investigated lesions. The confocal images were consistent with the routine histology of the pre-existing lesions. No differences in the confocal images of pre-existing lesions compared with mechanically induced ones were observed. CONCLUSIONS: Our findings suggest the potential of CLSM as a non-invasive tool for the diagnosis of pemphigus and differentiation of its subtype. Although at present the method cannot replace the current diagnostic standards for pemphigus, it may be successfully used as in vivo non-invasive screening tool to facilitate the diagnosis and point to the need for further investigation of the patient.

Skin irritation and sensitization: mechanisms and new approaches for risk assessment. 1. Skin irritation.

Cutaneous irritation presents a major health problem with serious social and occupational impact. The interaction between an irritant and the human skin depends on multiple factors: the intrinsic properties and the nature of the irritant itself, and specific individual- and environment-related variables. The main pathological mechanisms of irritancy include skin barrier disruption, induction of a cytokine cascade and involvement of the oxidative stress network; all of them resulting in a visible or subclinical inflammatory reaction. In vivo, different non-invasive parameters for the evaluation of skin irritation and irritant potential of compounds and their specific formulations have been introduced, such as epidermal barrier function, skin hydration, surface pH, lipid composition, skin colour and skin blood flow. The diverse physiological changes caused by irritating agents require implementation of a multiparametric approach in the evaluation of cutaneous irritancy.

Significance of interleukin-16, macrophage-derived chemokine, eosinophil cationic protein and soluble E-selectin in reflecting disease activity of atopic dermatitis--from laboratory parameters to clinical scores.

BACKGROUND: The search for the ideal clinical score reflecting atopic dermatitis (AD) severity has developed in parallel with unveiling key events in disease pathogenesis and finding laboratory parameters for monitoring disease activity. A major difficulty in assessing the relevance of reported serum markers of AD severity is the use of nonvalidated referent tools, which compromises comparison of results across studies. OBJECTIVES: The aim of our study was to compare the significance of serum levels of interleukin (IL)-16, macrophage-derived chemokine (MDC), soluble E-selectin (sE-selectin) and eosinophil cationic protein (ECP) in reflecting AD severity and identify the most relevant parameter for monitoring the course of disease. Serum levels were tested against the same referent severity score in the same time frame and group of patients. METHODS: The Severity Scoring of Atopic Dermatitis (SCORAD) index was used for assessment of disease severity in 21 adult patients in acute stage of AD and after complete resolution of clinical findings. Serum levels of IL-16, MDC, ECP and sE-selectin were measured at the same time points in 18 patients and compared with healthy nonatopic controls. The correlation between SCORAD and each laboratory parameter was tested for significance and compared. RESULTS: Serum levels of IL-16, MDC, ECP and sE-selectin were significantly higher in patients in acute stage of AD compared with controls and decreased significantly after treatment, in parallel with clinical improvement. All monitored parameters reflected disease severity assessed by the clinical score. We found the highest significance level of correlation with SCORAD for IL-16 (r = 0.68, P =0.0019), followed by ECP (r = 0.65, P = 0.0032) and MDC (r = 0.55, P =0.0326). There was significant correlation between serum levels of IL-16 and MDC (r = 0.53, P = 0.0443) and ECP and sE-selectin (r = 0.48, P = 0.0427). CONCLUSIONS: The study established a significant correlation between serum levels of IL-16 and SCORAD in adult AD patients. We report a significant correlation between IL-16 and MDC, both T-helper 2 activation markers. Our data suggested that IL-16 reflects most convincingly disease severity and may be used as a marker in clinical studies preferentially in combination with a clinical activity score.

The objective severity assessment of atopic dermatitis (OSAAD) score: validity, reliability and sensitivity in adult patients with atopic dermatitis.

BACKGROUND: The Objective Severity Assessment of Atopic Dermatitis (OSAAD) score is a recently developed scale for evaluation of severity of atopic dermatitis, constructed from the assessment of epidermal barrier function, and properties using noninvasive bioengineering methods and computer-assisted estimates of disease extent. The method has been validated for use in infants and children with atopic dermatitis and compared with a referent scoring system. OBJECTIVES: The aim of the present study was to test the validity, reliability and sensitivity of the OSAAD score as an objective tool for the assessment of the severity of atopic dermatitis in adult patients. METHODS: Thirty-two adult patients with atopic dermatitis were included in the study. To assess the validity of the OSAAD score we tested it against the Severity Scoring of Atopic Dermatitis (SCORAD) index of the European Task Force on Atopic Dermatitis as a referent clinical severity scale, and the serum levels of interleukin (IL)-16 as a laboratory variable for monitoring the activity of atopic dermatitis. Responsiveness to change was assessed in a longitudinal study comparing OSAAD, SCORAD and serum levels of IL-16 before and after treatment. To test the reliability of the OSAAD score we studied the interobserver variability of the score recorded by three independent board-certified dermatologists in 16 patients and compared it with SCORAD. RESULTS: We report a significant correlation between the OSAAD and the SCORAD index as an acknowledged referent severity scale. The OSAAD score correlated significantly with the serum levels of IL-16 in the acute stage of atopic dermatitis. In a longitudinal study, the OSAAD score decreased significantly, parallel with improvement of the skin findings and a significant decrease in the SCORAD score and IL-16 serum levels. We report improved interobserver variability for the OSAAD score compared with SCORAD. CONCLUSIONS: This is the first study validating the OSAAD score as a sensitive and reliable tool for the assessment of the severity of atopic dermatitis in adult patients.