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Pruritus in the elderly and its impact on quality of life
PD06—AESTHETIC & AGING Physiological changes in skin barrier function due to intrinsic aging: A quantitative analysis of 150 female subjects
(Poster reference number 5534)
Stefanie Luebberding, University of Hamburg, Hamburg, Germany; Martina Kerscher, MD, University of Hamburg, Hamburg, Germany; Nils Krueger, University of Hamburg, Hamburg, Germany Background: Specific signs of aging are apparent on the body and more markedly on the skin. The change in physiological properties of the skin remains a controversial issue. Objective: To investigate the effects of aging on skin regarding transepidermal waterloss (TEWL), stratum corneum hydration, surface pH, and sebum production in 150 adult healthy females ranging 20-80 years in age. Methods: All subjects were distributed evenly to five age groups (group I: 18-29 yrs, group II: 30-39 yrs, group III: 40-49 yrs, group IV: 50-59 yrs, group V: 60-80 yrs). Women recruited in age groups I-III were in the follicular phase of their menstrual cycle. Woman in age group IV were postmenopausal. Hormone replacement therapies, treatments with phytohormones, history of smoking, and extensive sun exposure were excluded from the study. Areas studied were forehead, cheek, neck, cleavage, volar forearm, and dorsal hand under standardized conditions at 20 8C (688F) and 50% relative humidity. Results: The mean age in the four groups was 24.7 (group I), 33.1 (group II), 43.7 (group III), 55.2 (group IV), and 67.4 (group V). A nonsignificant increase in TEWL, stratum corneum hydration and pH (r\ 0.2) was observed in all age groups. With the exception of cleavage and hand, the hydration in stratum corneum increased with aging. Decrease of sebum excretion correlates significant with increasing age (r ¼ -0.355; P ¼.001). Conclusion: The maintenance of stratum corneum hydration, skin pH, and TEWL in the five age groups suggests that with intrinsic aging the stratum corneum maintains its physiologic function as skin barrier for hydrophobic substances. A decrease in sebum production in the older age groups can be attributed to a decrease in the activity of the sebaceous glands. The results of this study are useful for a better understanding of the physiological signs of intrinsic aging of the skin and its barrier function. Commercial support: None identified.
NF-kB inhibition of collagen synthesis in aging human dermal fibroblasts
(Poster reference number 4990)
Nicolas Bigot, PhD, Laboratoire Matrice Extracellulaire et Pathologie, IFR ICORE Cedex, France, Caen, France; Karim Boumediene, PhD, Laboratoire Matrice Extracellulaire et Pathologie, IFR ICORE 146, Universite de Caen/BasseNormandie, Caen, France; Philippe Galera, PhD, Laboratoire Matrice Extracellulaire et Pathologie, IFR ICORE 146, Universite de Caen/BasseNormandie, Caen, France; Thierry Oddos, PhD, Johnson & Johnson, Val de reuil, France Skin aging is accompanied by changes in the dermal structure and a slow-down in the collagen synthesis potential of the dermal fibroblasts. We studied the mechanisms by which collagen transcription is regulated in aging fibroblasts with a special focus on the role of NF-kB. NF-kB is a dimeric protein present in the cell cytoplasm which is translocated in nucleus where it regulates expression of multiple genes under activation by different type of aggressions (UV light, oxidative stress). The role of NF-kB was assessed by overexpression of p50 and p65 proteins or by gene silencing using specific siRNA. Collagen secretion in the culture medium was assessed by ELISA method. Gene expression was measured by real time PCR. NF-kB transcriptional activity was measured either using gel retardation assay or after transfection of a luciferase reporter gene under the control of a NF-kB responsive element. We first investigated the effect of aging on collagen synthesis and NF-kB activation. Dermal fibroblast cultures were prepared from skin biopsies obtained from healthy donors of different ages. In the fibroblasts originated from older donors we showed a decrease the level of COL1A1 gene expression measured by real time PCR and collagen secretion assessed by ELISA method. In parallel, an increase in the transcriptional activity of NF-kB was demonstrated in fibroblast from aged donors either using either gel retardation assay method or after transfection of a luciferase reporter gene under the control of a NF-kB responsive element. Overexpression of NF-kB p65 subunit in dermal fibroblast decreased COL1A1 gene expression as well as collagen type 1 secretion in the culture medium. On the other hand, p65 siRNA increased COL1A1 gene transcription. Overexpression of p50 subunit or use of p50 specific mRNA did not show any effect on either COL1A1 expression or collagen synthesis. We demonstrated that NF-kB transcriptional activity is increased in aging fibroblasts and that it correlates with a decrease in COL1A1 transcription and collagen synthesis. This negative regulation could be attributed to the p65 subunit of NF-kB. Stimulation of collagen synthesis by p65 siRNA suggests that inhibition of NFkB transcriptional activity may be a good way to counteract the decrease of collagen synthesis in aging fibroblasts. In conclusion, our results demonstrate that inhibition of NF-kB can counterbalance the skin’s age-dependent loss of collagen synthesis, thereby mitigating the appearance of skin aging signs. Commercial support: 50% is paid by Johnson & Johnson Sante Beaute France.
Reduction of submental fat with ATX-101: A pooled analysis of two international multicenter, double-blind, randomized, placebo-controlled studies
(Poster reference number 5168)
Greg Goodman, MBBS, Dermatology Institute of Victoria, South Yarra, Victoria, Australia; Daniel Lee, MS, Kythera Biopharmaceuticals, Inc, Calabasas, CA, United States; Kevin Smith, MD, Niagara Falls Dermatology & Skin Care Centre, Niagara Falls, Ontario, Canada; Patricia Walker, MD, PhD, Kythera Biopharmaceuticals, Inc, Calabasas, CA, United States Background: Many individuals have submental fat (SMF) that is aesthetically unappealing. Currently, the only treatment options for reducing SMF are liposuction and surgical neck lifts and there are no approved pharmacologic therapies. ATX-101 is an investigational drug with adipolytic properties that is based on an endogenous bile acid. Methods: 155 subjects were enrolled into one of two phase II studies (ATX-101-0603 and ATX-101-07-07). Subjects had to be 25-65 years of age, with Fitzpatrick skin type I-III, prominent or marked SMF that they considered undesirable, and no prior interventions for the reduction of SMF. Subjects were randomly assigned to receive injections of one of the following directly into the submental area at baseline and weeks 4, 8, and 12: ATX-101 (1 mg/cm2, 2 mg/cm2, or 4 mg/cm2) or placebo. The configuration and volume of SMF determined the number of injections. At baseline and weeks 4, 8, 12, 16 (4 weeks after final dose) and 24 (12 weeks after final dose), investigators evaluated the severity of SMF and the degree of laxity in the submental area (using a 5-point Clinician-Reported Submental Fat Rating Scale [CR-SMFRS] and a 4-point Skin Laxity Rating Scale [SLRS], respectively). Subject satisfaction (with face and chin appearance) was evaluated at baseline and week 16 (using a 7-point Subject Satisfaction Rating Scale [SSRS]). Results: The subjects had a mean age of 46 years. In each ATX-101 dose group, investigator evaluations of SMF showed a statistically significant improvement in reduction of SMF versus placebo at weeks 16 and 24 (P \.05). Similarly, subject satisfaction was significantly greater in all ATX-101 groups than placebo at week 16 (P \.05). Mean skin laxity scores remained unchanged across all evaluation time points, even with fat reduction. Adverse events (AE) were limited to the injection site and included most commonly pain, swelling, anesthesia, bruising, and induration. The majority of these were mild or moderate in severity, temporally associated with treatment, and resolved within the treatment interval of 28 days. No treatmentrelated systemic AE were observed. Conclusions: ATX-101 may offer a novel minimally invasive treatment option for reducing SMF. ATX-101 treatment was associated with reductions in SMF, and improvements in subject satisfaction, that were significantly greater than those attained with placebo. At the doses evaluated, ATX-101 was well tolerated with no treatment-related systemic AE. Commercial support: Kythera Biopharmaceuticals, Inc
APRIL 2012
Pruritus in the elderly and its impact on quality of life
(Poster reference number 5327)
Yee Leng Teoh, MBBS, Changi General Hospital, Singapore, Singapore; Benson Koon-Wee Yeo, MBBS, Changi General Hospital, Singapore, Singapore; Mark JeanAan Koh, MBBS, Changi General Hospital, Singapore, Singapore; Rachael Yu-Lin Teo, MBBS, Changi General Hospital, Singapore, Singapore Background: Pruritus is a common complaint among the elderly. It may have a significant impact on quality of life, but may be underestimated and poorly addressed by doctors. Aims: We aim to assess the prevalence and severity of itch and its impact on the quality of life in a group of geriatric patients admitted to a tertiary geriatric ward. Methods: From March to May 2010, patients admitted to a geriatric ward in a tertiary hospital were interviewed using a structured questionnaire including the Dermatology Life Quality Index (DLQI). Information obtained include presence and severity of itch, and its impact on quality of life. Patients’ hospital records were reviewed and information regarding comorbid conditions, prior skin disease, medications, and social background were recorded and analyzed. Results: A total of 194 patients were enrolled, with a mean age of 85.4 years (range, 75-103 years). 94 patients (48.5%) reported having a problem with itch, with a mean duration of 15.3 months. Itching caused sleep disruption in 35.1% and affected concentration levels in 30.9% of patients. The mean DLQI score was 6.7 in these patients. 60.6% of them had informed a doctor about the problem and 26.3% of these felt that the problem was not sufficiently addressed. Twenty patients were diagnosed with a specific dermatological condition, with the commonest being eczema and dermatophyte infection. Of the participants who had informed their doctor about the problem, 57.9% were treated only with topicals, 3.5% with only oral antihistamines, 33.3% with topicals and oral antihistamines, and 5.3% were not provided with any treatment. 17% of patients self-medicated with over the counter medications, and 28.7% used traditional medications. Patients with diabetes were 2.2 times more likely to have itch (95% confidence interval [CI] 1.197-4.189, P ¼ .012) than those without diabetes. Similarly, participants with a history of cerebrovascular accidents (CVA) or transient ischaemic attacks (TIA) were 3.5 times (95% CI 1.378-8.986, P ¼ .009) more likely to have itch. Conversely, patients who were on laxatives were 2.1 times (95% CI 1.152-3.809, P ¼.015) more likely not to have itch than those who were not taking laxatives. Conclusion: Itch is common among the elderly and can significantly affect their quality of life. Diabetes and previous CVA or TIA were statistically significant predictors of itch while patients who were on laxatives were significantly less likely to have itch. Commercial support: None identified.
J AM ACAD DERMATOL
AB11
(Poster reference number 5534)
Stefanie Luebberding, University of Hamburg, Hamburg, Germany; Martina Kerscher, MD, University of Hamburg, Hamburg, Germany; Nils Krueger, University of Hamburg, Hamburg, Germany Background: Specific signs of aging are apparent on the body and more markedly on the skin. The change in physiological properties of the skin remains a controversial issue. Objective: To investigate the effects of aging on skin regarding transepidermal waterloss (TEWL), stratum corneum hydration, surface pH, and sebum production in 150 adult healthy females ranging 20-80 years in age. Methods: All subjects were distributed evenly to five age groups (group I: 18-29 yrs, group II: 30-39 yrs, group III: 40-49 yrs, group IV: 50-59 yrs, group V: 60-80 yrs). Women recruited in age groups I-III were in the follicular phase of their menstrual cycle. Woman in age group IV were postmenopausal. Hormone replacement therapies, treatments with phytohormones, history of smoking, and extensive sun exposure were excluded from the study. Areas studied were forehead, cheek, neck, cleavage, volar forearm, and dorsal hand under standardized conditions at 20 8C (688F) and 50% relative humidity. Results: The mean age in the four groups was 24.7 (group I), 33.1 (group II), 43.7 (group III), 55.2 (group IV), and 67.4 (group V). A nonsignificant increase in TEWL, stratum corneum hydration and pH (r\ 0.2) was observed in all age groups. With the exception of cleavage and hand, the hydration in stratum corneum increased with aging. Decrease of sebum excretion correlates significant with increasing age (r ¼ -0.355; P ¼.001). Conclusion: The maintenance of stratum corneum hydration, skin pH, and TEWL in the five age groups suggests that with intrinsic aging the stratum corneum maintains its physiologic function as skin barrier for hydrophobic substances. A decrease in sebum production in the older age groups can be attributed to a decrease in the activity of the sebaceous glands. The results of this study are useful for a better understanding of the physiological signs of intrinsic aging of the skin and its barrier function. Commercial support: None identified.
NF-kB inhibition of collagen synthesis in aging human dermal fibroblasts
(Poster reference number 4990)
Nicolas Bigot, PhD, Laboratoire Matrice Extracellulaire et Pathologie, IFR ICORE Cedex, France, Caen, France; Karim Boumediene, PhD, Laboratoire Matrice Extracellulaire et Pathologie, IFR ICORE 146, Universite de Caen/BasseNormandie, Caen, France; Philippe Galera, PhD, Laboratoire Matrice Extracellulaire et Pathologie, IFR ICORE 146, Universite de Caen/BasseNormandie, Caen, France; Thierry Oddos, PhD, Johnson & Johnson, Val de reuil, France Skin aging is accompanied by changes in the dermal structure and a slow-down in the collagen synthesis potential of the dermal fibroblasts. We studied the mechanisms by which collagen transcription is regulated in aging fibroblasts with a special focus on the role of NF-kB. NF-kB is a dimeric protein present in the cell cytoplasm which is translocated in nucleus where it regulates expression of multiple genes under activation by different type of aggressions (UV light, oxidative stress). The role of NF-kB was assessed by overexpression of p50 and p65 proteins or by gene silencing using specific siRNA. Collagen secretion in the culture medium was assessed by ELISA method. Gene expression was measured by real time PCR. NF-kB transcriptional activity was measured either using gel retardation assay or after transfection of a luciferase reporter gene under the control of a NF-kB responsive element. We first investigated the effect of aging on collagen synthesis and NF-kB activation. Dermal fibroblast cultures were prepared from skin biopsies obtained from healthy donors of different ages. In the fibroblasts originated from older donors we showed a decrease the level of COL1A1 gene expression measured by real time PCR and collagen secretion assessed by ELISA method. In parallel, an increase in the transcriptional activity of NF-kB was demonstrated in fibroblast from aged donors either using either gel retardation assay method or after transfection of a luciferase reporter gene under the control of a NF-kB responsive element. Overexpression of NF-kB p65 subunit in dermal fibroblast decreased COL1A1 gene expression as well as collagen type 1 secretion in the culture medium. On the other hand, p65 siRNA increased COL1A1 gene transcription. Overexpression of p50 subunit or use of p50 specific mRNA did not show any effect on either COL1A1 expression or collagen synthesis. We demonstrated that NF-kB transcriptional activity is increased in aging fibroblasts and that it correlates with a decrease in COL1A1 transcription and collagen synthesis. This negative regulation could be attributed to the p65 subunit of NF-kB. Stimulation of collagen synthesis by p65 siRNA suggests that inhibition of NFkB transcriptional activity may be a good way to counteract the decrease of collagen synthesis in aging fibroblasts. In conclusion, our results demonstrate that inhibition of NF-kB can counterbalance the skin’s age-dependent loss of collagen synthesis, thereby mitigating the appearance of skin aging signs. Commercial support: 50% is paid by Johnson & Johnson Sante Beaute France.
Reduction of submental fat with ATX-101: A pooled analysis of two international multicenter, double-blind, randomized, placebo-controlled studies
(Poster reference number 5168)
Greg Goodman, MBBS, Dermatology Institute of Victoria, South Yarra, Victoria, Australia; Daniel Lee, MS, Kythera Biopharmaceuticals, Inc, Calabasas, CA, United States; Kevin Smith, MD, Niagara Falls Dermatology & Skin Care Centre, Niagara Falls, Ontario, Canada; Patricia Walker, MD, PhD, Kythera Biopharmaceuticals, Inc, Calabasas, CA, United States Background: Many individuals have submental fat (SMF) that is aesthetically unappealing. Currently, the only treatment options for reducing SMF are liposuction and surgical neck lifts and there are no approved pharmacologic therapies. ATX-101 is an investigational drug with adipolytic properties that is based on an endogenous bile acid. Methods: 155 subjects were enrolled into one of two phase II studies (ATX-101-0603 and ATX-101-07-07). Subjects had to be 25-65 years of age, with Fitzpatrick skin type I-III, prominent or marked SMF that they considered undesirable, and no prior interventions for the reduction of SMF. Subjects were randomly assigned to receive injections of one of the following directly into the submental area at baseline and weeks 4, 8, and 12: ATX-101 (1 mg/cm2, 2 mg/cm2, or 4 mg/cm2) or placebo. The configuration and volume of SMF determined the number of injections. At baseline and weeks 4, 8, 12, 16 (4 weeks after final dose) and 24 (12 weeks after final dose), investigators evaluated the severity of SMF and the degree of laxity in the submental area (using a 5-point Clinician-Reported Submental Fat Rating Scale [CR-SMFRS] and a 4-point Skin Laxity Rating Scale [SLRS], respectively). Subject satisfaction (with face and chin appearance) was evaluated at baseline and week 16 (using a 7-point Subject Satisfaction Rating Scale [SSRS]). Results: The subjects had a mean age of 46 years. In each ATX-101 dose group, investigator evaluations of SMF showed a statistically significant improvement in reduction of SMF versus placebo at weeks 16 and 24 (P \.05). Similarly, subject satisfaction was significantly greater in all ATX-101 groups than placebo at week 16 (P \.05). Mean skin laxity scores remained unchanged across all evaluation time points, even with fat reduction. Adverse events (AE) were limited to the injection site and included most commonly pain, swelling, anesthesia, bruising, and induration. The majority of these were mild or moderate in severity, temporally associated with treatment, and resolved within the treatment interval of 28 days. No treatmentrelated systemic AE were observed. Conclusions: ATX-101 may offer a novel minimally invasive treatment option for reducing SMF. ATX-101 treatment was associated with reductions in SMF, and improvements in subject satisfaction, that were significantly greater than those attained with placebo. At the doses evaluated, ATX-101 was well tolerated with no treatment-related systemic AE. Commercial support: Kythera Biopharmaceuticals, Inc
APRIL 2012
Pruritus in the elderly and its impact on quality of life
(Poster reference number 5327)
Yee Leng Teoh, MBBS, Changi General Hospital, Singapore, Singapore; Benson Koon-Wee Yeo, MBBS, Changi General Hospital, Singapore, Singapore; Mark JeanAan Koh, MBBS, Changi General Hospital, Singapore, Singapore; Rachael Yu-Lin Teo, MBBS, Changi General Hospital, Singapore, Singapore Background: Pruritus is a common complaint among the elderly. It may have a significant impact on quality of life, but may be underestimated and poorly addressed by doctors. Aims: We aim to assess the prevalence and severity of itch and its impact on the quality of life in a group of geriatric patients admitted to a tertiary geriatric ward. Methods: From March to May 2010, patients admitted to a geriatric ward in a tertiary hospital were interviewed using a structured questionnaire including the Dermatology Life Quality Index (DLQI). Information obtained include presence and severity of itch, and its impact on quality of life. Patients’ hospital records were reviewed and information regarding comorbid conditions, prior skin disease, medications, and social background were recorded and analyzed. Results: A total of 194 patients were enrolled, with a mean age of 85.4 years (range, 75-103 years). 94 patients (48.5%) reported having a problem with itch, with a mean duration of 15.3 months. Itching caused sleep disruption in 35.1% and affected concentration levels in 30.9% of patients. The mean DLQI score was 6.7 in these patients. 60.6% of them had informed a doctor about the problem and 26.3% of these felt that the problem was not sufficiently addressed. Twenty patients were diagnosed with a specific dermatological condition, with the commonest being eczema and dermatophyte infection. Of the participants who had informed their doctor about the problem, 57.9% were treated only with topicals, 3.5% with only oral antihistamines, 33.3% with topicals and oral antihistamines, and 5.3% were not provided with any treatment. 17% of patients self-medicated with over the counter medications, and 28.7% used traditional medications. Patients with diabetes were 2.2 times more likely to have itch (95% confidence interval [CI] 1.197-4.189, P ¼ .012) than those without diabetes. Similarly, participants with a history of cerebrovascular accidents (CVA) or transient ischaemic attacks (TIA) were 3.5 times (95% CI 1.378-8.986, P ¼ .009) more likely to have itch. Conversely, patients who were on laxatives were 2.1 times (95% CI 1.152-3.809, P ¼.015) more likely not to have itch than those who were not taking laxatives. Conclusion: Itch is common among the elderly and can significantly affect their quality of life. Diabetes and previous CVA or TIA were statistically significant predictors of itch while patients who were on laxatives were significantly less likely to have itch. Commercial support: None identified.
J AM ACAD DERMATOL
AB11