P8424Improving the quality of skin barrier function with PPAR-activatingtechnology

Stacey Demento, PhD, Unilever R&D, Trumbull, CT, United States; BrianDobkowski, Unilever R&D, Trumbull, CT, United States; Hasiba Pehratovic, MS,Unilever R&D, Trumbull, CT, United States; Jaime O’Leary, Unilever R&D,Trumbull, CT, United States; Jennifer Huertas, MS, Unilever R&D, Trumbull,CT, United States; Kristopher Kalleberg, Unilever R&D, Trumbull, CT, UnitedStates; Stacy Hawkins, PhD, Unilever R&D, Trumbull, CT, United States

The nuclear hormone receptors, peroxisome proliferator-activated receptors(PPARs), have been shown to play a major role in processes related to overallbarrier maintenance including: homeostasis, keratinocyte differentiation, andinflammation. Once activated by ligands consisting of fatty acids and theirderivatives, PPARs form heterodimers with retinoid X receptors and regulate theexpression of profilaggrin and genes related to lipidmetabolism, among others. Herewe identified 12-hydroxystearic acid (12-HSA) as a pan-agonist of the 3 distinct PPARisoforms, all of which are expressed in the epidermis. The goal of this research wasto study the in vivo improvements to skin barrier after topical treatment with12-HSA. White female subjects with moderately dry skin, ages 18-65 years, wereprovided informed consent to participate in institutional review boardeapproved,double-blind, vehicle-controlled paired application studies. Study personnel appliedthe test product daily for 4 weeks, followed by 1 week of regression with nomoisturizers applied. Significant improvements in the skin barrier condition wereobserved after product application and regression from 12-HSA in full moisturizingformulations over the occlusive and humectant effects of petrolatum and glycerin(without 12-HSA), respectively. The permeability of the skin decreased 1.3 timesover the vehicle control and 3.6 time over no treatment after 3 weeks of use. Higherlevels of NMFs were measured in the stratum corneum after treatment with the 12-HSA formulation. In a separate study, 12-HSA in a simple formulation was appliedunder occlusive patches over 3 weeks, and was found to result in an increase in thethickness of the granular layer over the vehicle control, as analyzed by histology ofthe epidermis after treatment. Lastly, the percutaneous absorption of 12-HSA and thedelivery into the viable epidermis showed good agreement with in vivo clinicalbenefits in skin barrier condition.

AB64

d 100% by Unilever R&D.

Sponsore

P8289Oat (Avena sativa) oil activates the PPAR? and PPARb/d pathways,resulting in keratinocyte differentiation and upregulation of ceramidesynthesis

Michael Southall, PhD, Johnson & Johnson Consumer Companies, Inc, Skillman,NJ, United States; Apostolos Pappas, PhD, Johnson & Johnson ConsumerCompanies, Inc, Skillman, NJ, United States; Chon Suhyoun, Johnson &Johnson Consumer Companies, Inc, Skillman, NJ, United States; Ruth Earland,Johnson & Johnson Consumer Companies, Inc, Skillman, NJ, United States

Oat (Avena sativa) extracts are frequently used in dermatologic treatments toreduce irritation and improve dry skin. Extensive clinical trials have demonstratedthe efficacy of formulations containing oats for skin; however, few studies havedetermined the mechanisms for how oats produce these benefits for skin. In thepresent study, we demonstrate that a lipid extract isolated from oats was able toinduce activation of the peroxisome proliferator-activated receptors (PPAR) PPAR?and b/d receptors in human keratinocyte cell. PPARs are transcription factorswhich, upon activation increase the expression of differentiation proteins and lipidsynthesizing enzymes in skin. The PPAR activity was confirmed by the increasedexpression of the PPAR direct target genes, such as ANGPTL4, PLIN2, and CPT1A inprimary human keratinocytes treated with oat oil. Consistent with previous studieson PPAR activation, treatment with oat oil resulted in a significant upregulation ofdifferentiation marker genes, such as involucrin and transglutaminse-1. In addition,we confirmed the increased ceramide synthetic gene expression as b-glucocere-brosidase (GBA) and sphingomyelinases3 (SMPD3) and the intracellular ceramidetransporter, ABCA12. Finally, treating human keratinocytes with oat oil was found toincrease production of ceramide levels up to 3 fold compared to untreated, which isconsistant with PPAR activation. In summary, we found a novel mechanism thatexplains the skin benefits of oat oil via stimulation of keratinocyte PPAR? and b/d,which could increase differentiation and ceramide synthesis resulting in animproved epidermal barrier.

d 100% by Johnson & Johnson Consumer Companies, Inc.

Sponsore

J AM ACAD DERMATOL

P8032Oral tacrolimus in treatment of severe atopic dermatitis

Jack Short, MD, George Washington University, Washington, DC, United States;Alison Ehrlich, MD, MHS, George Washington University, Washington, DC,United States; Kerian Dodds, George Washington University, Washington, DC,United States

Objective: To exhibit a case of oral tacrolimus used in a patient with refractoryatopic dermatitis.

Background: Tacrolimus, a calcineurin inhibitor immunosuppressant, is a drugwidely used in the prevention of organ transplant rejection. Off-label, it has seen avariety of uses, including the treatment of psoriasis, Behcet disease, and pyodermagangrenosum. In its topical ointment form, tacrolimus is approved for the treatmentof moderate to severe atopic dermatitis, and has become a well-known nonsteroidtherapy. Oral drugs, such as cyclosporine, are effective in atopic dermatitis, butcarry a long-term risk of nephrotoxicity.

Case report: A 25-year-old white woman presented with chronic severe atopicdermatitis of the hands, upper arms, and upper thighs. Patch testing was conductedto rule out allergic contact dermatitis. She had previously used topical steroids withlittle relief. Before consultation, outside dermatologists had treated her with pulseoral corticosteroids. Her medical history was significant for seasonal allergies andsinusitis. Oral cyclosporine therapy was initiated, but then switched to oraltacrolimus for long-term therapy. Dosing was calculated using 0.15 mg/kg/day.Tacrolimus was initiated at 3 mg po BID and then titrated up after 5 weeks to 3 mgqAM and 4 mg qhs. Significant clearance at the 5-week and 2-month appointmentswas noted, and patient reported no adverse effects.

Discussion: Oral tacrolimus has a more desirable side effect profile than previousdrugs used in the systemic treatment of atopic dermatitis. Cyclosporine hasconsistent evidence of effectiveness in atopic dermatitis, but is significantly morenephrotoxic than tacrolimus. While there are little data addressing the dose of oraltacrolimus for dermatologic use, previous studies for psoriasis used dosing of 0.05 to0.15 mg/kg/day, significantly less than the 0.1 to 0.4 mg/kg/day used for transplantpatients. With such an improvement in our case, who had previously failed topicaltherapies, tacrolimus may be a promising nonsteroidal systemic treatment for atopicdermatitis.

Conclusion: Tacrolimus may yield promising results in patients with severe atopicdermatitis, while avoiding the adverse effects of oral corticosteroids and cyclo-sporine.While less nephrotoxic, the lack of use of tacrolimus in dermatologymay berelated to limited experience with this drug in dermatology training programs.

cial support: None identified.

Commer

P8407Quality of life impact from a skin care regimen on adult eczema sufferers

Vickie Foy, Unilever R&D, Trumbull, CT, United States; Jeff Wolcheski, UnileverR&D, Trumbull, CT, United States; Jessica Krisiak, Unilever R&D, Trumbull, CT,United States; Lara Rafiee, Unilever R&D, Trumbull, CT, United States; StacyHawkins, PhD, Unilever R&D, Trumbull, CT, United States

Atopic eczema is an intensely pruritic cutaneous inflammatory condition that isexacerbated by irritants, such as cleansing surfactants. Typical skin care recom-mendations for eczema sufferers include using a mild cleanser followed by a goodmoisturizer. It was therefore of interest to understand the impact on quality of life(QOL) with a daily skin care regimen comprised of a mild, moisturizing body washand lotion specifically designed for eczema sufferers. Thirty-two adult panelists(9 male/23 female) with mild to moderate eczema were enrolled in a multisite,IRB-approved 4-week body wash and lotion regimen compatibility study, withdermatologist assessment of eczema condition using the standardized Eczema Areaand Severity Index (EASI). Eligible panelists must have been on their currenttreatments for eczema for at least 3 months, and daily moisturizer users. Panelistsreplaced their normal cleansers and lotions with the test products in unbrandedpackages. Self-perception surveys and a validated QOL survey were completed bypanelists (Dermatology Life Quality Index, or DLQI Score) at baseline and after 2 and4 weeks. The DLQI survey is comprised of 9 individual questions, and an overallscore is tabulated to indicate total impact on quality of life factors related to impacton work, social, self-consciousness, and leisure activities (from no effect toextremely large effect). The moisturizing body wash and lotion were found to besuitable for use in panelists with mild to moderate eczema and compatible with theirtreatments, as assessed by the EASI score. The clinical visual dryness on lesion siteswas also significantly reduced. The regimen was perceived by the panelists tosignificantly improve sensations caused by eczema, such as itch, soreness, sting,roughness, overall feel, etc. at all weeks. The DLQI survey results showed significantimprovement in 7 out of 9 attributes. At baseline, 55% of subjects felt their eczemasymptoms had a moderate to extreme impact on overall DLQI score, and 32% werein the very large to extreme range. After 4 weeks of using the skin care regimen, theDLQI score was significantly reduced to 6% and 3% in the moderate to extreme andvery large to extreme ranges, respectively. The results provide quantitative evidenceof the positive impact to QOL factors in eczema sufferers, using a mild cleanser andlotion.

d 100% by Unilever R&D.

Sponsore

MAY 2014