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A case-control study of rosacea subjects compared to control subjects
P1028 A novel approach to enhance mildness of cleansers using organic ions Lin Yang, Unilever R&D, Trumbull, CT, United States; Jaime O’Leary, Unilever R&D, Trumbull, CT, United States; K. P. Ananthapadmanabhan, Unilever R&D, Trumbull, CT, United States; Prem Chandar, Unilever R&D, Trumbull, CT, United States The skin irritation potential of surfactants has been investigated extensively in the past, and the available results in the literature show that the irritation potential can be correlated with the ability of surfactants to cause swelling or denaturation of proteins. We have also recently shown that the protein/enzyme denaturation potential of surfactants increases with an increase in the charge density of the surfactant micelle. This shows that the common practice of using a blend of anionic and nonionic surfactants to increase surfactant mildness involves reducing the charge density of anionic micelles. Another method to reduce micelle charge density involves the use of large organic cations, and our in vitro results show that protein denaturation tendency of anionic surfactants can be reduced significantly by using a cation such as a hydroxyl propyl quaternary ammonium salt. We have also shown in in vivo studies that these organic cations applied to skin before surfactant exposure can reduce the intensity of protein damage. Insights derived from these studies of the physicochemical interactions of surfactant systems and stratum corneum components provide a means to develop more effective products to address dry skin conditions. Commercial support: 100% sponsored by Unilever HPC.
CLINICAL DERMATOLOGY AND OTHER CUTANEOUS DISORDERS P1100 Infliximab in the treatment of refractory chronic urticaria Norbert Reider, MS, Clinical Department of Dermatology, Medical University, Innsbruck, Austria; Cornelia Egger, MD, Clinical Department of Dermatology, Medical University, Innsbruck, Austria Chronic urticaria is defined as appearance of hives for at least 6 weeks. In 80% of cases, no causal trigger can be found. Adequate evidence for the effect of symptomatic treatment only exists for antihistamines. Other options, among them intravenous immunoglobulin (IVIG), have been suggested in mostly uncontrolled case series. We report on the effect of infliximab (IFX), a monoclonal IgG-antibody directed against tumor necrosis factor-alfa (TNFa), in four patients with chronic refractory urticaria. To exclude an effect of the Ig per se, we compared our results to those with IVIG in five other cases. The mean age in the IFX group was 34.8 years, with a duration of urticaria of 49 months. The patients had been examined for infections, autoimmune disorders (including autoreactive urticaria), physical and cholinergic urticaria, and food or drug allergy. Five other patients with similar characteristics were selected to receive IVIG. All patients had daily urticaria and been treated with various combinations of H1- and H2-antihistamines, ketotifen, montelukast, hydroxychloroquine, dapsone, mirtazapin, cyclosporine, and naltrexon without success for at least 1 year. We then decided to administer IFX 5 mg/kg in weeks 0, 2, and 6 in one group and a mean of 6.6 series of IVIG at a dose of 0.5 mg/kg divided over 5 days each in the other group. In three of four IFX patients, urticaria was suspended before the second infusion. All three have been in full remission for a mean of 10 months (range, 6-12 mos) now. The only male patient did not show any benefit. A complete response was achieved in four of five IVIG subjects and a partial response in the fifth already during the first days of administration. However, this persisted for 1 to 3 weeks only. Further series proved to be similarly effective. No sustained remissions were observed. We suggest a mainly antiidiotype effect of IVIG as relapses occurred after a maximum of 3 weeks, the half-life of IVIG. If this were also the case for IFX, no sustained remissions could be expected. Elevated levels of TNFa have been demonstrated in chronic urticaria, including endothelial and perivascular cells of the epidermis and upper dermis. TNFa induces E-selectin, which is elevated in urticaria and is an important mediator of neutrophil and eosinophil adherence. Because urticaria involves mast cell activation and infiltration of neutrophils and eosinophils into the dermis, a specific anti-TNFa effect of IFX in chronic urticaria may be suggested. Commercial support: None identified.
P1101
P1029
A case-control study of rosacea subjects compared to control subjects Maryanne Kazanis, Brigham and Women’s Hospital, Boston, MA, United States; Alexandra B. Kimball, MPH, MD, Massachusetts General Hospital, Boston, MA, United States; April W. Armstrong, MD, Brigham and Women’s Hospital, Boston, MA, United States; Jason Frangos, Massachusetts General Hospital, Boston, MA, United States; Lynn Drake, MD, Massachusetts General Hospital, Boston, MA, United States Background: Rosacea is a common disease characterized by inflammation and vascular abnormalities of the facial skin and ocular surface. It is considered to be a syndrome encompassing various combinations of cutaneous signs including flushing, erythema, telangiectasia, papules, pustules, edema, ocular lesions, and rhinophyma. The exact etiology of cutaneous rosacea is unknown, but is thought to be characterized in part by persistent vasodilatation, increased vascular permeability and vascular hyperreactivity of the microcirculation of the central part of the face.
A virtual cell system prototyping for development and validation of skin lightening actives: Correlation with ex vivo and in vivo results N. Domloge, Vincience, Montard, Sophia Antipolis, France; E. Bauza, Vincience, Montard, Sophia Antipolis, France; G. Oberto, Vincience, Montard, Sophia Antipolis, France; R. McMullen, ISP, Wayne, NJ, United States; S. Vali, Cellworks Group, Saratoga, CA, United States Reducing uneven pigmentation, a hallmark of aging changes in ethnic population, is of interest to dermatologists and their patients. For the cosmetic industry, meeting consumers’ expectations in this area requires more efficacy than that provided by currently marketed tyrosinase inhibitors. The discovery of new actives is greatly aided by employing a virtual cell system of interacting melanocytes and keratinocytes (a proprietary skin pigmentation platform) which has multiple triggers and more than 4000 biomolecules that can be assayed by simulation in silico. This provides unprecedented visibility and the ability to understand and drive experimental work efficiently while predicting the beneficial clinical or even toxicologic impact of the targets and actives being designed. We have experimentally tested and compared the effects of 1% Brassicacea extract and 1% arbutin, and combinations of both, on ex vivo skin. FontanaeMasson (FM) staining of histologic sections showed that the Brassicasea extract and Arbutin treatment decreased the skin melanin content. Quantitative image analysis of the FM-stained histologic sections indicated a 49% decrease in melanin for Brassicasea compared to 32% for arbutin. A combination of two actives did not increase the efficacy of the Brassicacea extract. A blinded clinical study with the Brassicasea extract showed a significant decrease in the melanin index. Image analysis of clinical photographs of age spots supported the clinical findings. A comparison of the experimental results with that of the in silico results will be presented and the implications discussed in the poster.
Results: Sixty-five rosacea subjects and 65 controls were enrolled. On average, rosacea subjects had moderately severe global disease. All rosacea subjects in this study had the erythematotelangiectatic subtype, and many had an additional subtype: 38.4% (n ¼ 25) had papulopustular, 10.8% (n ¼ 7) had phymatous, and 23% (n ¼ 15) had ocular rosacea. Rosacea subjects were much more likely to have a family member with rosacea compared with controls (R ¼ 34% vs C ¼ 10.5%). In reported dermatologic and medical conditions, rosacea subjects had significantly higher rates of blistering sunburns (R ¼ 44% and C ¼ 5.2%; P \.05), and increased prevalence of hypercholesterolemia (R ¼ 22%, C ¼ 7% and R ¼ 24%, C ¼ 7%, respectively; P \.05).
Commercial support: 100% sponsored by ISP.
Commercial support: None identified.
MARCH 2009
Objective: To prospectively confirm previous epidemiologic associations of rosacea with demographic characteristics versus controls. Methods: Eligible subjects with and without rosacea underwent a facial skin exam, completed a questionnaire, and had their height, weight, and blood pressure measured. Blood pressure measurements, body mass indices, and questionnaire results of the two groups were compared.
J AM ACAD DERMATOL
AB39
CLINICAL DERMATOLOGY AND OTHER CUTANEOUS DISORDERS P1100 Infliximab in the treatment of refractory chronic urticaria Norbert Reider, MS, Clinical Department of Dermatology, Medical University, Innsbruck, Austria; Cornelia Egger, MD, Clinical Department of Dermatology, Medical University, Innsbruck, Austria Chronic urticaria is defined as appearance of hives for at least 6 weeks. In 80% of cases, no causal trigger can be found. Adequate evidence for the effect of symptomatic treatment only exists for antihistamines. Other options, among them intravenous immunoglobulin (IVIG), have been suggested in mostly uncontrolled case series. We report on the effect of infliximab (IFX), a monoclonal IgG-antibody directed against tumor necrosis factor-alfa (TNFa), in four patients with chronic refractory urticaria. To exclude an effect of the Ig per se, we compared our results to those with IVIG in five other cases. The mean age in the IFX group was 34.8 years, with a duration of urticaria of 49 months. The patients had been examined for infections, autoimmune disorders (including autoreactive urticaria), physical and cholinergic urticaria, and food or drug allergy. Five other patients with similar characteristics were selected to receive IVIG. All patients had daily urticaria and been treated with various combinations of H1- and H2-antihistamines, ketotifen, montelukast, hydroxychloroquine, dapsone, mirtazapin, cyclosporine, and naltrexon without success for at least 1 year. We then decided to administer IFX 5 mg/kg in weeks 0, 2, and 6 in one group and a mean of 6.6 series of IVIG at a dose of 0.5 mg/kg divided over 5 days each in the other group. In three of four IFX patients, urticaria was suspended before the second infusion. All three have been in full remission for a mean of 10 months (range, 6-12 mos) now. The only male patient did not show any benefit. A complete response was achieved in four of five IVIG subjects and a partial response in the fifth already during the first days of administration. However, this persisted for 1 to 3 weeks only. Further series proved to be similarly effective. No sustained remissions were observed. We suggest a mainly antiidiotype effect of IVIG as relapses occurred after a maximum of 3 weeks, the half-life of IVIG. If this were also the case for IFX, no sustained remissions could be expected. Elevated levels of TNFa have been demonstrated in chronic urticaria, including endothelial and perivascular cells of the epidermis and upper dermis. TNFa induces E-selectin, which is elevated in urticaria and is an important mediator of neutrophil and eosinophil adherence. Because urticaria involves mast cell activation and infiltration of neutrophils and eosinophils into the dermis, a specific anti-TNFa effect of IFX in chronic urticaria may be suggested. Commercial support: None identified.
P1101
P1029
A case-control study of rosacea subjects compared to control subjects Maryanne Kazanis, Brigham and Women’s Hospital, Boston, MA, United States; Alexandra B. Kimball, MPH, MD, Massachusetts General Hospital, Boston, MA, United States; April W. Armstrong, MD, Brigham and Women’s Hospital, Boston, MA, United States; Jason Frangos, Massachusetts General Hospital, Boston, MA, United States; Lynn Drake, MD, Massachusetts General Hospital, Boston, MA, United States Background: Rosacea is a common disease characterized by inflammation and vascular abnormalities of the facial skin and ocular surface. It is considered to be a syndrome encompassing various combinations of cutaneous signs including flushing, erythema, telangiectasia, papules, pustules, edema, ocular lesions, and rhinophyma. The exact etiology of cutaneous rosacea is unknown, but is thought to be characterized in part by persistent vasodilatation, increased vascular permeability and vascular hyperreactivity of the microcirculation of the central part of the face.
A virtual cell system prototyping for development and validation of skin lightening actives: Correlation with ex vivo and in vivo results N. Domloge, Vincience, Montard, Sophia Antipolis, France; E. Bauza, Vincience, Montard, Sophia Antipolis, France; G. Oberto, Vincience, Montard, Sophia Antipolis, France; R. McMullen, ISP, Wayne, NJ, United States; S. Vali, Cellworks Group, Saratoga, CA, United States Reducing uneven pigmentation, a hallmark of aging changes in ethnic population, is of interest to dermatologists and their patients. For the cosmetic industry, meeting consumers’ expectations in this area requires more efficacy than that provided by currently marketed tyrosinase inhibitors. The discovery of new actives is greatly aided by employing a virtual cell system of interacting melanocytes and keratinocytes (a proprietary skin pigmentation platform) which has multiple triggers and more than 4000 biomolecules that can be assayed by simulation in silico. This provides unprecedented visibility and the ability to understand and drive experimental work efficiently while predicting the beneficial clinical or even toxicologic impact of the targets and actives being designed. We have experimentally tested and compared the effects of 1% Brassicacea extract and 1% arbutin, and combinations of both, on ex vivo skin. FontanaeMasson (FM) staining of histologic sections showed that the Brassicasea extract and Arbutin treatment decreased the skin melanin content. Quantitative image analysis of the FM-stained histologic sections indicated a 49% decrease in melanin for Brassicasea compared to 32% for arbutin. A combination of two actives did not increase the efficacy of the Brassicacea extract. A blinded clinical study with the Brassicasea extract showed a significant decrease in the melanin index. Image analysis of clinical photographs of age spots supported the clinical findings. A comparison of the experimental results with that of the in silico results will be presented and the implications discussed in the poster.
Results: Sixty-five rosacea subjects and 65 controls were enrolled. On average, rosacea subjects had moderately severe global disease. All rosacea subjects in this study had the erythematotelangiectatic subtype, and many had an additional subtype: 38.4% (n ¼ 25) had papulopustular, 10.8% (n ¼ 7) had phymatous, and 23% (n ¼ 15) had ocular rosacea. Rosacea subjects were much more likely to have a family member with rosacea compared with controls (R ¼ 34% vs C ¼ 10.5%). In reported dermatologic and medical conditions, rosacea subjects had significantly higher rates of blistering sunburns (R ¼ 44% and C ¼ 5.2%; P \.05), and increased prevalence of hypercholesterolemia (R ¼ 22%, C ¼ 7% and R ¼ 24%, C ¼ 7%, respectively; P \.05).
Commercial support: 100% sponsored by ISP.
Commercial support: None identified.
MARCH 2009
Objective: To prospectively confirm previous epidemiologic associations of rosacea with demographic characteristics versus controls. Methods: Eligible subjects with and without rosacea underwent a facial skin exam, completed a questionnaire, and had their height, weight, and blood pressure measured. Blood pressure measurements, body mass indices, and questionnaire results of the two groups were compared.
J AM ACAD DERMATOL
AB39