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Use of a stratified human keratinocyte model to predict skin irritation in subjects with sensitive skin
P8736
P8337
The impact of severe atopic dermatitis: Analysis of comorbidities
Up-regulation of epidermal differentiation markers filaggrin and claudins in dry skin Marius-Anton Ionescu, MD, PhD, Saint-Louis Hospital, Dermatology, Paris, France; Francine Joly, PhD, Laboratoire Sephrapharma, Puteaux, France; Luc Lefeuvre, PharmD, Laboratoires Dermatologiques d Uriage, Neuilly-sur-Seine, France
Hala Adil, MD, Saint Louis University, St. Louis, MO, United States; Elaine Siegfried, MD, Saint Louis University/Cardinal Glennon Pediatric Hospital, St. Louis, MO, United States; Eric Armbrecht, PhD, Saint Louis University, St. Louis, Missouri, United States Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition that may be associated with significant morbidity, including sleep disturbance, emotional distress and reduced quality of life. Well-recognized AD comorbidities include asthma and allergic rhinitis; however, new data suggest other previously unexplored associations. Objective: To identify associations between AD severity and various clinical and socioeconomic comorbidities, to compare comorbidity prevalence between study population versus standard norms. Methods: Retrospective chart review of children with AD seen at the Cardinal Glennon Children’s Hospital Dermatology Clinics in St. Louis, MO, identified by Immunocaps panel. Disease severity was defined using the 0-9 point RajkaeLangeland (RL) criteria, with 0 indicating no AD, and 9 indicating severe skin disease. A 3-group subset analysis was performed for the majority of parameters, to better assess trending. The groups were defined by the following scores: 4-5, 6-7, and 8-9. Results: 72 patients (33 females, 39 males), ages 3-18 were identified by computer search. AD was mild-moderate in 54% (n ¼ 39), and severe in 45.8% (n ¼ 33), a cohort with a higher prevalence of severe AD, as well as other allergic conditions, than other previously published AD cohorts. Nonallergic comorbidities included 8 (15%) with laboratory evidence of primary immunodeficiency, 8 (12% of the children ¼ age 4) with mental health disease (including depression, anxiety, ADHD and autism) and 11 (15%) with failure to thrive. A history of bacterial skin infection was associated with an increasing trend in AD severity. Laboratory evidence of primary immunodeficiency was significantly associated with AD severity: 0 with RL 4-5, 14% of those with RL 6-7, and 22% with RL 8-9. Vitamin D deficiency was detected in a large majority of patients, regardless of severity. Conclusion: Our cohort of children with AD featured a higher prevalence of severe skin disease as well as asthma and allergic rhinitis. Allergic comorbidities and laboratory evidence of primary immunodeficiency were highly associated with disease severity. We did not find an association between AD and failure to thrive or, unlike previous publications, mental health disease. Comorbidities that were not associated with disease severity included: sleep disturbance, vitamin D deficiency, and treatment nonadherence. Insurance type did not differ among groups with moderate or severe disease.
Background: Epidermal differentiation markers filaggrin and claudins (part of intercellular tight junctions) decrease in atopic dermatitis and in several skin conditions associated with dry skin. Objective: To compare the expression of epidermal differentiation factors filaggrin and claudins in dry skin ex vivo treated by 2 emulsions. Methods: Were compared 2 emulsions: emulsion A—an O/W emulsion with distilled water as continuous aqueous phase; emulsion B—an O/W emulsion with isotonic thermal water rich in trace elements and minerals (dispersed phases were identical in the emulsion A and B). Emulsion A or B were applied on human skin explants (cultured in medium DMEM) that were previously delipidated with ether/acetone mixture 1:1 (control untreated). After 5 days incubation were assessed the expressions of filaggrin, claudin-4, and claudin-6 by immunohistochemistry using antibodies coupled to fluorochromes (Alexa Fluor 488 for filaggrin, claudin-4 and claudin-6), nuclei were labeled with DAPI (dilution: 1/100) then observed with a fluorescence optical microscope (Olympus CK 40). Results: Keratinocytes’ nuclei were similar in all skin explants. Stratum corneum was altered and filaggrin labeling was discontinuous in delipidated explants. In explants treated by emulsion A after the delipidation with ether/acetone, filaggrin expression was poor and discontinuous. In skin explants treated by emulsion B after the delipidation with ether/acetone, filaggrin was continuous and more expressed compared to skin treated by emulsion A and to delipidated untreated skin. Claudins4 and 6 expressions were more important in delipidated skin treated by emulsion B compared to their expression in delipidated skin treated by emulsion A. Conclusion: In delipidated skin explants treated by 2 different O/W emulsions, containing same dispersed phase and different continuous aqueous phase (distilled vs isotonic thermal water) filaggrin and claudins-4/6 expressions were significantly more important in skin treated by the emulsion formulated with isotonic thermal water. Sponsored 100% by Laboratoires Dermatologiques d’Uriage.
Commercial support: None identified.
P8401
P8439 Treatment of atopic dermatitis with a steroid-free acute therapy emollient cream reduces eczema severity and the frequency, intensity, and impact of itch on life activities Teresa M. Weber, PhD, Beiersdorf Inc, Wilton, CT, United States; Alexander Filbry, PhD, Beiersdorf AG, Hamburg, Germany; Craig Arrowitz, Beiersdorf Inc, Wilton, CT, United States; Gitta Neufang, PhD, Beiersdorf AG, Hamburg, Germany; Ulrich Scherdin, PhD, Beiersdorf AG, Hamburg, Germany Atopic dermatitis (AD) is characterized by skin-irritating manifestations, including pruritus and xerosis that adversely impact the quality of life of affected individuals. This study tested the efficacy and tolerability of a novel steroid-free cream containing oatmeal, ceramide-3, licochalcone A, and menthoxypropanediol, a cooling agent, to reduce xerosis, pruritus intensity, frequency, and its influence on life quality. Thirtythree male and female subjects, ages 21-61, with mild to moderate AD active lesions participated in the 2-week study, with twice daily application of the test-product (TP). Efficacy was assessed by: a published 5-D itch questionnaire; expert grading of tolerability, improvement in AD symptoms (0-3 scale), and the AD Severity Index (ADSI, 15-pt scale); and instrumental measurement of skin hydration and TEWL. The 5-D itch questionnaire assessed frequency of itching, intensity, and impact on work, social activities, and sleep. Significant improvements in all parameters were observed. Before treatment with the TP 39% of subjects reported itching 6-18 hours daily and 12% experienced itch18-24 hours daily; at week 2 of treatment, 91% of subjects reported itching \6 hours if at all. Also at the baseline, 76% reported moderate to severe itch intensity; at week 2, 88% of subjects reported itch was either mild or not present. In addition, a high percentage of subjects reported occasional to frequent impact on their work (61%), and social activities (67%) before treatment. At the 2 week visit, 88% reported that their itch rarely or never affected their work and social activities. Lastly, before treatment, 60% reported that itching either delayed sleep or woke them occasionally to frequently; during treatment, 76% reported that sleep was not affected at all. Based on investigator’s assessments, statistically significant improvements in erythema, pruritus, excoriation, and lichenification were observed at week 2 compared to baseline. Pruritus was reduced from 1.89 at baseline to 0.83 at week 2. There was also significant improvement in the ADSI at week 2 (2.6) compared to baseline (5.0). After 2 weeks of treatment, skin lesions showed significant improvements in hydration (15.42 vs. 22.93) and reduced TEWL (26.79 vs. 21.11). In summary, the TP significantly improved skin hydration, barrier condition, AD severity, and demonstrated significant reduction in itch intensity, frequency, and improvements in life quality due to itch. Supported by Beiersdorf Inc.
AB66
J AM ACAD DERMATOL
Use of a stratified human keratinocyte model to predict skin irritation in subjects with sensitive skin Trisha Bonner, Johnson & Johnson Consumer Companies, Inc, Skillman, NJ, United States; Angelica Graves, Johnson & Johnson Consumer Companies, Inc, Skillman, NJ, United States; Anne-Sophie Brillouet, Johnson & Johnson Consumer Companies, Inc, Skillman, NJ, United States; Lauren Bernhofer, Johnson & Johnson Consumer Companies, Inc, Skillman, NJ, United States; Lorena Telofski, Johnson & Johnson Consumer Companies, Inc, Skillman, NJ, United States Background: Standard in vitro tests of products developed for application to the skin are not designed to predict sensory endpoints, such as stinging. Here we present results of a keratinocyte-based model originally designed for testing ocular products for predicting perceived skin irritation responses. Methods: In vitro models included 2 distinct types of 3-dimensional cultures, derived from human keratinocytes and structured to resemble either corneal tissue or epidermal tissue (MatTeK Corp, Ashland MA). In both culture types, irritation potential was estimated based on reduction in cell viability, using a standardized MTT-based cell viability assay, following exposure of the cells to test formulations for various time points up to 24 hours. Time to 50% survival (ET50) was calculated. No irritation potential was scored as ET50[24 hours. In vitro results were correlated to the findings from 2 in vivo evaluations in human subjects. In the sting test, lactic acid reactive subjects exposed the face to 758C steam for 5 min before application of test formulations to the nasolabial folds for 5 min. Subjects graded any reactions (stinging, itching, or burning) as mild, moderate, or severe. In the in-home use test, subjects were asked to use the test formulations at home for 2 weeks and the percent incidence of perceived irritation was reported. Values [10% indicate unacceptable irritation. Results: Four prototype skin care formulations (PSCF) were compared in the 2 in vitro models. The corneal model proved more sensitive (ET50 range,15-20 hours) than the epidermal model (ET50 [24 hours for 3 PSCF), and was selected to progress. Three PSCF previously evaluated by human testing and yielding mild to moderate sting and higher perceived irritation (range, 12-17%) were subsequently evaluated in vitro using the corneal model. Each PSCF tested yielded an ET50 ¼ 10 hours. An additional 4 PSCF, evaluated in vitro using the corneal model and yielding an ET50 [24 hours, were subsequently evaluated in the home use test and had no sting and low perceived irritation (range, 4-7%). Conclusions: Use of the corneal in vitro model should be considered as a tool to predict the potential to cause stinging and perceived skin irritation during use. ET50 values[24 hours were consistent with no sting and low human perceived irritation. ET50 values of 10 hours were associated with greater irritation potential. Sponsored 100% by Johnson & Johnson Consumer Companies, Inc.
MAY 2014
P8337
The impact of severe atopic dermatitis: Analysis of comorbidities
Up-regulation of epidermal differentiation markers filaggrin and claudins in dry skin Marius-Anton Ionescu, MD, PhD, Saint-Louis Hospital, Dermatology, Paris, France; Francine Joly, PhD, Laboratoire Sephrapharma, Puteaux, France; Luc Lefeuvre, PharmD, Laboratoires Dermatologiques d Uriage, Neuilly-sur-Seine, France
Hala Adil, MD, Saint Louis University, St. Louis, MO, United States; Elaine Siegfried, MD, Saint Louis University/Cardinal Glennon Pediatric Hospital, St. Louis, MO, United States; Eric Armbrecht, PhD, Saint Louis University, St. Louis, Missouri, United States Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition that may be associated with significant morbidity, including sleep disturbance, emotional distress and reduced quality of life. Well-recognized AD comorbidities include asthma and allergic rhinitis; however, new data suggest other previously unexplored associations. Objective: To identify associations between AD severity and various clinical and socioeconomic comorbidities, to compare comorbidity prevalence between study population versus standard norms. Methods: Retrospective chart review of children with AD seen at the Cardinal Glennon Children’s Hospital Dermatology Clinics in St. Louis, MO, identified by Immunocaps panel. Disease severity was defined using the 0-9 point RajkaeLangeland (RL) criteria, with 0 indicating no AD, and 9 indicating severe skin disease. A 3-group subset analysis was performed for the majority of parameters, to better assess trending. The groups were defined by the following scores: 4-5, 6-7, and 8-9. Results: 72 patients (33 females, 39 males), ages 3-18 were identified by computer search. AD was mild-moderate in 54% (n ¼ 39), and severe in 45.8% (n ¼ 33), a cohort with a higher prevalence of severe AD, as well as other allergic conditions, than other previously published AD cohorts. Nonallergic comorbidities included 8 (15%) with laboratory evidence of primary immunodeficiency, 8 (12% of the children ¼ age 4) with mental health disease (including depression, anxiety, ADHD and autism) and 11 (15%) with failure to thrive. A history of bacterial skin infection was associated with an increasing trend in AD severity. Laboratory evidence of primary immunodeficiency was significantly associated with AD severity: 0 with RL 4-5, 14% of those with RL 6-7, and 22% with RL 8-9. Vitamin D deficiency was detected in a large majority of patients, regardless of severity. Conclusion: Our cohort of children with AD featured a higher prevalence of severe skin disease as well as asthma and allergic rhinitis. Allergic comorbidities and laboratory evidence of primary immunodeficiency were highly associated with disease severity. We did not find an association between AD and failure to thrive or, unlike previous publications, mental health disease. Comorbidities that were not associated with disease severity included: sleep disturbance, vitamin D deficiency, and treatment nonadherence. Insurance type did not differ among groups with moderate or severe disease.
Background: Epidermal differentiation markers filaggrin and claudins (part of intercellular tight junctions) decrease in atopic dermatitis and in several skin conditions associated with dry skin. Objective: To compare the expression of epidermal differentiation factors filaggrin and claudins in dry skin ex vivo treated by 2 emulsions. Methods: Were compared 2 emulsions: emulsion A—an O/W emulsion with distilled water as continuous aqueous phase; emulsion B—an O/W emulsion with isotonic thermal water rich in trace elements and minerals (dispersed phases were identical in the emulsion A and B). Emulsion A or B were applied on human skin explants (cultured in medium DMEM) that were previously delipidated with ether/acetone mixture 1:1 (control untreated). After 5 days incubation were assessed the expressions of filaggrin, claudin-4, and claudin-6 by immunohistochemistry using antibodies coupled to fluorochromes (Alexa Fluor 488 for filaggrin, claudin-4 and claudin-6), nuclei were labeled with DAPI (dilution: 1/100) then observed with a fluorescence optical microscope (Olympus CK 40). Results: Keratinocytes’ nuclei were similar in all skin explants. Stratum corneum was altered and filaggrin labeling was discontinuous in delipidated explants. In explants treated by emulsion A after the delipidation with ether/acetone, filaggrin expression was poor and discontinuous. In skin explants treated by emulsion B after the delipidation with ether/acetone, filaggrin was continuous and more expressed compared to skin treated by emulsion A and to delipidated untreated skin. Claudins4 and 6 expressions were more important in delipidated skin treated by emulsion B compared to their expression in delipidated skin treated by emulsion A. Conclusion: In delipidated skin explants treated by 2 different O/W emulsions, containing same dispersed phase and different continuous aqueous phase (distilled vs isotonic thermal water) filaggrin and claudins-4/6 expressions were significantly more important in skin treated by the emulsion formulated with isotonic thermal water. Sponsored 100% by Laboratoires Dermatologiques d’Uriage.
Commercial support: None identified.
P8401
P8439 Treatment of atopic dermatitis with a steroid-free acute therapy emollient cream reduces eczema severity and the frequency, intensity, and impact of itch on life activities Teresa M. Weber, PhD, Beiersdorf Inc, Wilton, CT, United States; Alexander Filbry, PhD, Beiersdorf AG, Hamburg, Germany; Craig Arrowitz, Beiersdorf Inc, Wilton, CT, United States; Gitta Neufang, PhD, Beiersdorf AG, Hamburg, Germany; Ulrich Scherdin, PhD, Beiersdorf AG, Hamburg, Germany Atopic dermatitis (AD) is characterized by skin-irritating manifestations, including pruritus and xerosis that adversely impact the quality of life of affected individuals. This study tested the efficacy and tolerability of a novel steroid-free cream containing oatmeal, ceramide-3, licochalcone A, and menthoxypropanediol, a cooling agent, to reduce xerosis, pruritus intensity, frequency, and its influence on life quality. Thirtythree male and female subjects, ages 21-61, with mild to moderate AD active lesions participated in the 2-week study, with twice daily application of the test-product (TP). Efficacy was assessed by: a published 5-D itch questionnaire; expert grading of tolerability, improvement in AD symptoms (0-3 scale), and the AD Severity Index (ADSI, 15-pt scale); and instrumental measurement of skin hydration and TEWL. The 5-D itch questionnaire assessed frequency of itching, intensity, and impact on work, social activities, and sleep. Significant improvements in all parameters were observed. Before treatment with the TP 39% of subjects reported itching 6-18 hours daily and 12% experienced itch18-24 hours daily; at week 2 of treatment, 91% of subjects reported itching \6 hours if at all. Also at the baseline, 76% reported moderate to severe itch intensity; at week 2, 88% of subjects reported itch was either mild or not present. In addition, a high percentage of subjects reported occasional to frequent impact on their work (61%), and social activities (67%) before treatment. At the 2 week visit, 88% reported that their itch rarely or never affected their work and social activities. Lastly, before treatment, 60% reported that itching either delayed sleep or woke them occasionally to frequently; during treatment, 76% reported that sleep was not affected at all. Based on investigator’s assessments, statistically significant improvements in erythema, pruritus, excoriation, and lichenification were observed at week 2 compared to baseline. Pruritus was reduced from 1.89 at baseline to 0.83 at week 2. There was also significant improvement in the ADSI at week 2 (2.6) compared to baseline (5.0). After 2 weeks of treatment, skin lesions showed significant improvements in hydration (15.42 vs. 22.93) and reduced TEWL (26.79 vs. 21.11). In summary, the TP significantly improved skin hydration, barrier condition, AD severity, and demonstrated significant reduction in itch intensity, frequency, and improvements in life quality due to itch. Supported by Beiersdorf Inc.
AB66
J AM ACAD DERMATOL
Use of a stratified human keratinocyte model to predict skin irritation in subjects with sensitive skin Trisha Bonner, Johnson & Johnson Consumer Companies, Inc, Skillman, NJ, United States; Angelica Graves, Johnson & Johnson Consumer Companies, Inc, Skillman, NJ, United States; Anne-Sophie Brillouet, Johnson & Johnson Consumer Companies, Inc, Skillman, NJ, United States; Lauren Bernhofer, Johnson & Johnson Consumer Companies, Inc, Skillman, NJ, United States; Lorena Telofski, Johnson & Johnson Consumer Companies, Inc, Skillman, NJ, United States Background: Standard in vitro tests of products developed for application to the skin are not designed to predict sensory endpoints, such as stinging. Here we present results of a keratinocyte-based model originally designed for testing ocular products for predicting perceived skin irritation responses. Methods: In vitro models included 2 distinct types of 3-dimensional cultures, derived from human keratinocytes and structured to resemble either corneal tissue or epidermal tissue (MatTeK Corp, Ashland MA). In both culture types, irritation potential was estimated based on reduction in cell viability, using a standardized MTT-based cell viability assay, following exposure of the cells to test formulations for various time points up to 24 hours. Time to 50% survival (ET50) was calculated. No irritation potential was scored as ET50[24 hours. In vitro results were correlated to the findings from 2 in vivo evaluations in human subjects. In the sting test, lactic acid reactive subjects exposed the face to 758C steam for 5 min before application of test formulations to the nasolabial folds for 5 min. Subjects graded any reactions (stinging, itching, or burning) as mild, moderate, or severe. In the in-home use test, subjects were asked to use the test formulations at home for 2 weeks and the percent incidence of perceived irritation was reported. Values [10% indicate unacceptable irritation. Results: Four prototype skin care formulations (PSCF) were compared in the 2 in vitro models. The corneal model proved more sensitive (ET50 range,15-20 hours) than the epidermal model (ET50 [24 hours for 3 PSCF), and was selected to progress. Three PSCF previously evaluated by human testing and yielding mild to moderate sting and higher perceived irritation (range, 12-17%) were subsequently evaluated in vitro using the corneal model. Each PSCF tested yielded an ET50 ¼ 10 hours. An additional 4 PSCF, evaluated in vitro using the corneal model and yielding an ET50 [24 hours, were subsequently evaluated in the home use test and had no sting and low perceived irritation (range, 4-7%). Conclusions: Use of the corneal in vitro model should be considered as a tool to predict the potential to cause stinging and perceived skin irritation during use. ET50 values[24 hours were consistent with no sting and low human perceived irritation. ET50 values of 10 hours were associated with greater irritation potential. Sponsored 100% by Johnson & Johnson Consumer Companies, Inc.
MAY 2014