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193 Reproductive and hormonal factors and risk of rosacea in US women
Clinical Research: Epidemiology of Skin Diseases | ABSTRACTS 192
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NOS1AP is associated with impaired healing of diabetic foot ulcer DJ Margolis1, OJ Hoffstad1, M Yang2 and S Thom2 1 University of Pennsylvania, Philadelphia, PA and 2 University of Maryland, Baltimore, MD Many patients with diabetes will develop a foot ulcer (DFU) during their lifetime and most who have a lower extremity amputation (LEA) will have had a DFU. We have demonstrated that Nitric oxide synthase 1 adaptor protein (NOS1AP) variation was associated with LEA in diabetics. We recently demonstrated an association between circulating endothelial stem cell (SPC), at baseline and after one week of care, and DFUs that fail to heal by the 16th week of care (impaired healing). The goal of this study was to determine if NOS1AP variation was associated with DFU impaired healing and whether this might be associated with SPC. We conducted a prospective study of 47 subjects with DFU who received standard therapy for 16 weeks. We evaluated two NOS1AP variants previously associated with LEA, rs16849113 (African Americans) and rs1963645 (White), and created an ancestry-based composite variable. We used a proportional hazards model and assumed an additive relationship between the composite variable and healing. NOS1AP variation was significantly associated with impaired healing (HR 0.30(0.16,0.82) p¼0.015). Using linear regression, the number of SPCs was also significantly associated with NOS1AP variation (enrollment p¼0.003; week 1 p¼0.002). The SPC was also associated with actual genotype (WT: 0.96(SD 0.63), Heterozygote: 0.60(SD 0.26) and homozygote: 0.67(SD 0.48, p¼0.001). The NOS1AP protein is called capon and has a C-terminal PDZ-binding domain that was previously thought to bind only to neuronal nitric oxide synthase (nNOS) prolonging its activity. The NOS classes of proteins synthesize. NO that is a cell signaling molecule with respect to angiogenesis and wound repair. NNOS is structurally related to iNOS (NOS2) and eNOS (NOS3), which are proteins involved in angiogenesis, an important aspect of wound repair, and the likely mechanism of action of NOS1AP variation.
Reproductive and hormonal factors and risk of rosacea in US women H Geng, E Cho, A Drucker, I Parulkar, A Qureshi and W Li Brown University, Providence, RI Rosacea in women is often diagnosed perimenopausally, and has also been reported to occur during pregnancy and in women taking oral contraceptive pills. These data raise potential connections between hormonal and reproductive factors and risk of rosacea. In a prospective cohort study, we evaluated the association between menstrual, reproductive, and exogenous hormonal factors and risk of rosacea in women. Our population consisted of 89062 women based on the Nurses’ Health Study II. Information on menstrual cycle, menopausal status, parity, and exogenous hormone use was collected during the follow-up (1991-2005). Lifetime diagnosis of rosacea and diagnosis year was asked in 2005. Cox regression models were used to calculate the age- and multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 4425 rosacea cases were identified during the follow-up. Compared with premenopausal women, postmenopausal women had a lower risk of rosacea (HR¼0.73, 95% CI: 0.58-0.92). No significant association with risk of rosacea was found for other menstrual factors. Risk of rosacea was significantly increased for nulliparous women (HR¼1.23, 95% CI: 1.14-1.32) and women with age at first birth < 22 years or 25 years (compared with 22-24 years). Exogenous hormone use was also positively associated with risk of rosacea, with an HR of 1.37 (95% CI: 1.15-1.64) for ever use of postmenopausal hormone (PMH) and an HR of 1.17 (95% CI: 1.06-1.28) for ever use of oral contraceptive. Compared with non-users of PMH, risk of rosacea was significantly increased with longer duration of use (HR¼1.59, 95% CI: 1.14-2.20 for use 10 years) and with use of estrogen-containing PMH (HR¼1.31, 95% CI: 1.07-1.60). Risk of rosacea was significantly decreased in postmenopausal women and increased in women taking exogenous hormones. Nulliparous women and women with an early or late age at first birth may also have an increased risk of rosacea.
Decreasing prevalence of tanning bed use in the US: Data from the 2010, 2013, and 2015 National Health Interview Surveys AH Fischer, S Kang and A Chien Dermatology, Johns Hopkins Univ, Baltimore, MD Recent strides in policy, legislation, and interventions have been undertaken to decrease tanning bed use in the US; however, studies examining national trends in tanning bed use and correlates of persistent tanning bed use are limited in recent literature. We examined recent tanning bed use reported in the last year by individuals aged 18-60 in the 2010 (N¼20,053), 2013 (N¼24,701), and 2015 (N¼23,073) National Health Interview Surveys. Risk factor analysis was conducted using multivariable logistic regression. Prevalence of recent tanning bed use in the general population decreased (6.8%, 5.3%, and 4.5% in 2010, 2013, and 2015, respectively; p-trend < 0.001). Among non-Hispanic white females aged 18-24, a marked decrease in recent tanning bed use was observed (19.0%, 16.3%, and 9.7% in 2010, 2013, and 2015, respectively; p-trend < 0.001), however, the proportion of recent indoor tanners reporting 10+ recent sessions did not significantly change from 2010-2015 (p-trend¼0.70). Among individuals who reported ever tanning indoors (N¼4,003; 2015 data), significant independent factors associated with recent tanning bed use included female sex (adjusted odds ratio [aOR]¼1.7; 1.3-2.2), single marital status (aOR¼1.6; 1.3-2.0), high school diploma or less (aOR¼1.6; 1.3-2.0), residence outside of the West (aOR¼1.6; 1.2-2.1), no history of cancer (aOR¼1.8; 1.1-3.0), younger age (p-trend < 0.001), and increasing ability to tan (p-trend < 0.001). These findings suggest that while the prevalence of indoor tanning in the US is decreasing, the relative proportion of individuals frequently tanning indoors has not changed in young non-Hispanic white women, a group with markedly high prevalence of tanning bed use. The correlates of recent tanning bed use among those who had ever tanned indoors may help identify subpopulations that continue to demonstrate a relatively poor tendency toward tanning bed cessation, and could therefore benefit from targeted policy and interventions.
The burden of childhood atopic dermatitis in U.S. primary care settings J Al-naqeeb1, S Danner1, L Fagnan1, K Ramsey1, L Michaels2, J Mitchell1, K Branca1, C Morris1, D Nease3, L Zittleman3, B Levy4, J Daly4, D Hahn5, R Dolor6, J Hanifin1, S Tofte1, K Zuckerman1, K Hansis5, M Gundersen2, K Dillon7, J Block8, F Karr7, S Dunbrasky9, J Lapidus1, K Siebe10 and E Simpson1 1 Oregon Health and Science University, Portland, OR, 2 Meta-network Learning and Research Center (Meta-LARC), Portland, OR, 3 Meta-network Learning and Research Center (Meta-LARC), Denver, CO, 4 Meta-network Learning and Research Center (Meta-LARC), Iowa City, IA, 5 Meta-network Learning and Research Center (Meta-LARC), Madison, WI, 6 Meta-network Learning and Research Center (Meta-LARC), Durham, NC, 7 Meta-network Learning and Research Center (Meta-LARC), Hood River, OR, 8 Meta-network Learning and Research Center (Meta-LARC), San Rafael, CA, 9 Metanetwork Learning and Research Center (Meta-LARC), Ontario, OR and 10 Meta-network Learning and Research Center (Meta-LARC), Enterpprise, OR Little is known about the atopic dermatitis (AD) burden encountered in primary care practices and the frequency and type of skin care practices used on children in U.S. communities. We measured the prevalence of parent-reported childhood AD in 10 primary care practices located in Oregon, Iowa, Wisconsin, Colorado and North Carolina using a convenience sample of children 0-5 years old. To better understand current skin care practices among the general pediatric population, we surveyed parents regarding current skin care used on their children. The prevalence of AD was 24% (95% CI¼ 21-28) ranging from 15% among those under the age of one to 38% among those aged 4-5 years. Emollient use was very common even in those children without AD (74%) with the majority of users applying it 4 or more days per week (61%) . Lotions were the most frequently used product in children without AD. Of those we surveyed without AD, 60% received a bath/shower 4 or more days a week. Our study found a large burden of AD in the primary care practice setting in the U.S. The majority of households use skin care practices that may be detrimental to the skin barrier such as frequent bathing and the routine use of products with high water: oil ratios. Clinical trials will allow us to identify which skin care practices are optimal for reducing the significant burden of AD in the community.
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Perceived magnitude of skin cancer risk reduction predicts sunscreen use TR Sharma1, V Yeh2, S Debanne3 and JS Bordeaux4 1 University Hospitals Cleveland Medical Center, Cleveland, OH, 2 Case Western Reserve University School of Medicine, Cleveland, OH, 3 Case Western Reserve University, Cleveland, OH and 4 University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH Wearing sunscreen with sun protection factor (SPF) 30+ is recommended to prevent skin cancer; however, most Americans do not practice this behavior. Understanding factors that influence sunscreen use would allow dermatologists to counsel their patients in a way that is well-received and impactful. The perceived efficacy of sunscreen in reducing the risk of skin cancer has been found to correlate with sunscreen use. However, it is not clear whether the perceived magnitude of risk reduction has an impact on sunscreen use. We hypothesized that larger perceived magnitude of risk reduction of skin cancer would correlate with increased sunscreen use. To investigate this, we surveyed 131 patients at a Mohs micrographic surgery clinic about their perceptions of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma, and sunscreen. Participants thought sunscreen would reduce their risk of BCC by 61.1% [95% CI ¼ 56.4-65.9], SCC by 59.4% [95% CI ¼ 54.6-64.2], and melanoma by 59.5% [95% CI ¼ 54.8-64.3]. There was no difference in perceived risk reduction among these three cancers. Perceived magnitude of risk reduction of BCC, SCC, and melanoma was a significant independent predictor of sunscreen use (p¼ 0.038, p¼ 0.050, p¼0.002 respectively). These data suggest that larger perceived magnitude of skin cancer risk reduction promotes sunscreen use. Although sunscreen’s absolute impact on skin cancer risk reduction is not well established, our findings suggest that physicians should not undermine sunscreen’s potential efficacy when counseling patients, as it may be a critical motivational factor.
Influence of FLG mutations and TSLP polymorphisms on atopic dermatitis onset age J Wan, N Mitra, OJ Hoffstad and DJ Margolis University of Pennsylvania, Philadelphia, PA It has been proposed that genetic factors drive early onset atopic dermatitis (AD) while environmental exposures drive late onset AD. Mutations in filaggrin (FLG) increase the odds of AD, and single-nucleotide polymorphisms in thymic stromal lymphopoietin (TSLP) are linked to less persistent AD. Our aim was to examine the impact of FLG mutations and TSLP polymorphisms on the timing of AD onset. We performed a cross-sectional study using the Pediatric Eczema Elective Registry, a cohort of children with physician-confirmed diagnosis of AD. A total of 798 subjects were genotyped for 4 common FLG null mutations (R501X, 2282del4, R2447X, S3247X) and 770 subjects were genotyped for TSLP rs1898671. Age of AD onset was self-reported by the subject or caregiver. Logistic regression was performed to compare the odds of early onset AD (defined as 2 years old) with respect to FLG and TSLP status under an additive genetic model. The median ages of AD onset were 0.75 (IQR 0.252.0), 0.75 (IQR 0.25-1.0), and 0.25 (IQR 0.25-0.75) years for subjects with 0, 1, and 2 FLG mutations, respectively (test for trend p < 0.001). The odds of early onset AD was significantly higher among subjects with 1 FLG mutation (OR 1.74, 95% CI 1.02-2.96) and over 3-fold higher among subjects with 2 mutations (OR 3.03, 95% CI 0.70-13.16). The median AD onset age and odds of early onset AD did not vary by TSLP status. There was no interaction between FLG and TSLP variants on the odds of early onset AD, and analysis by race did not alter the findings. In distinguishing subjects with 1 FLG mutation versus 2 mutations, we found that common FLG mutations are associated with earlier AD onset in a dose-dependent manner. However, TSLP rs1898671 appears unrelated to the timing of AD onset. Our findings support the notion that early onset and late onset AD may differ in their genetic underpinnings. Further genetic and clinical studies are needed to better distinguish these forms of AD.
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NOS1AP is associated with impaired healing of diabetic foot ulcer DJ Margolis1, OJ Hoffstad1, M Yang2 and S Thom2 1 University of Pennsylvania, Philadelphia, PA and 2 University of Maryland, Baltimore, MD Many patients with diabetes will develop a foot ulcer (DFU) during their lifetime and most who have a lower extremity amputation (LEA) will have had a DFU. We have demonstrated that Nitric oxide synthase 1 adaptor protein (NOS1AP) variation was associated with LEA in diabetics. We recently demonstrated an association between circulating endothelial stem cell (SPC), at baseline and after one week of care, and DFUs that fail to heal by the 16th week of care (impaired healing). The goal of this study was to determine if NOS1AP variation was associated with DFU impaired healing and whether this might be associated with SPC. We conducted a prospective study of 47 subjects with DFU who received standard therapy for 16 weeks. We evaluated two NOS1AP variants previously associated with LEA, rs16849113 (African Americans) and rs1963645 (White), and created an ancestry-based composite variable. We used a proportional hazards model and assumed an additive relationship between the composite variable and healing. NOS1AP variation was significantly associated with impaired healing (HR 0.30(0.16,0.82) p¼0.015). Using linear regression, the number of SPCs was also significantly associated with NOS1AP variation (enrollment p¼0.003; week 1 p¼0.002). The SPC was also associated with actual genotype (WT: 0.96(SD 0.63), Heterozygote: 0.60(SD 0.26) and homozygote: 0.67(SD 0.48, p¼0.001). The NOS1AP protein is called capon and has a C-terminal PDZ-binding domain that was previously thought to bind only to neuronal nitric oxide synthase (nNOS) prolonging its activity. The NOS classes of proteins synthesize. NO that is a cell signaling molecule with respect to angiogenesis and wound repair. NNOS is structurally related to iNOS (NOS2) and eNOS (NOS3), which are proteins involved in angiogenesis, an important aspect of wound repair, and the likely mechanism of action of NOS1AP variation.
Reproductive and hormonal factors and risk of rosacea in US women H Geng, E Cho, A Drucker, I Parulkar, A Qureshi and W Li Brown University, Providence, RI Rosacea in women is often diagnosed perimenopausally, and has also been reported to occur during pregnancy and in women taking oral contraceptive pills. These data raise potential connections between hormonal and reproductive factors and risk of rosacea. In a prospective cohort study, we evaluated the association between menstrual, reproductive, and exogenous hormonal factors and risk of rosacea in women. Our population consisted of 89062 women based on the Nurses’ Health Study II. Information on menstrual cycle, menopausal status, parity, and exogenous hormone use was collected during the follow-up (1991-2005). Lifetime diagnosis of rosacea and diagnosis year was asked in 2005. Cox regression models were used to calculate the age- and multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 4425 rosacea cases were identified during the follow-up. Compared with premenopausal women, postmenopausal women had a lower risk of rosacea (HR¼0.73, 95% CI: 0.58-0.92). No significant association with risk of rosacea was found for other menstrual factors. Risk of rosacea was significantly increased for nulliparous women (HR¼1.23, 95% CI: 1.14-1.32) and women with age at first birth < 22 years or 25 years (compared with 22-24 years). Exogenous hormone use was also positively associated with risk of rosacea, with an HR of 1.37 (95% CI: 1.15-1.64) for ever use of postmenopausal hormone (PMH) and an HR of 1.17 (95% CI: 1.06-1.28) for ever use of oral contraceptive. Compared with non-users of PMH, risk of rosacea was significantly increased with longer duration of use (HR¼1.59, 95% CI: 1.14-2.20 for use 10 years) and with use of estrogen-containing PMH (HR¼1.31, 95% CI: 1.07-1.60). Risk of rosacea was significantly decreased in postmenopausal women and increased in women taking exogenous hormones. Nulliparous women and women with an early or late age at first birth may also have an increased risk of rosacea.
Decreasing prevalence of tanning bed use in the US: Data from the 2010, 2013, and 2015 National Health Interview Surveys AH Fischer, S Kang and A Chien Dermatology, Johns Hopkins Univ, Baltimore, MD Recent strides in policy, legislation, and interventions have been undertaken to decrease tanning bed use in the US; however, studies examining national trends in tanning bed use and correlates of persistent tanning bed use are limited in recent literature. We examined recent tanning bed use reported in the last year by individuals aged 18-60 in the 2010 (N¼20,053), 2013 (N¼24,701), and 2015 (N¼23,073) National Health Interview Surveys. Risk factor analysis was conducted using multivariable logistic regression. Prevalence of recent tanning bed use in the general population decreased (6.8%, 5.3%, and 4.5% in 2010, 2013, and 2015, respectively; p-trend < 0.001). Among non-Hispanic white females aged 18-24, a marked decrease in recent tanning bed use was observed (19.0%, 16.3%, and 9.7% in 2010, 2013, and 2015, respectively; p-trend < 0.001), however, the proportion of recent indoor tanners reporting 10+ recent sessions did not significantly change from 2010-2015 (p-trend¼0.70). Among individuals who reported ever tanning indoors (N¼4,003; 2015 data), significant independent factors associated with recent tanning bed use included female sex (adjusted odds ratio [aOR]¼1.7; 1.3-2.2), single marital status (aOR¼1.6; 1.3-2.0), high school diploma or less (aOR¼1.6; 1.3-2.0), residence outside of the West (aOR¼1.6; 1.2-2.1), no history of cancer (aOR¼1.8; 1.1-3.0), younger age (p-trend < 0.001), and increasing ability to tan (p-trend < 0.001). These findings suggest that while the prevalence of indoor tanning in the US is decreasing, the relative proportion of individuals frequently tanning indoors has not changed in young non-Hispanic white women, a group with markedly high prevalence of tanning bed use. The correlates of recent tanning bed use among those who had ever tanned indoors may help identify subpopulations that continue to demonstrate a relatively poor tendency toward tanning bed cessation, and could therefore benefit from targeted policy and interventions.
The burden of childhood atopic dermatitis in U.S. primary care settings J Al-naqeeb1, S Danner1, L Fagnan1, K Ramsey1, L Michaels2, J Mitchell1, K Branca1, C Morris1, D Nease3, L Zittleman3, B Levy4, J Daly4, D Hahn5, R Dolor6, J Hanifin1, S Tofte1, K Zuckerman1, K Hansis5, M Gundersen2, K Dillon7, J Block8, F Karr7, S Dunbrasky9, J Lapidus1, K Siebe10 and E Simpson1 1 Oregon Health and Science University, Portland, OR, 2 Meta-network Learning and Research Center (Meta-LARC), Portland, OR, 3 Meta-network Learning and Research Center (Meta-LARC), Denver, CO, 4 Meta-network Learning and Research Center (Meta-LARC), Iowa City, IA, 5 Meta-network Learning and Research Center (Meta-LARC), Madison, WI, 6 Meta-network Learning and Research Center (Meta-LARC), Durham, NC, 7 Meta-network Learning and Research Center (Meta-LARC), Hood River, OR, 8 Meta-network Learning and Research Center (Meta-LARC), San Rafael, CA, 9 Metanetwork Learning and Research Center (Meta-LARC), Ontario, OR and 10 Meta-network Learning and Research Center (Meta-LARC), Enterpprise, OR Little is known about the atopic dermatitis (AD) burden encountered in primary care practices and the frequency and type of skin care practices used on children in U.S. communities. We measured the prevalence of parent-reported childhood AD in 10 primary care practices located in Oregon, Iowa, Wisconsin, Colorado and North Carolina using a convenience sample of children 0-5 years old. To better understand current skin care practices among the general pediatric population, we surveyed parents regarding current skin care used on their children. The prevalence of AD was 24% (95% CI¼ 21-28) ranging from 15% among those under the age of one to 38% among those aged 4-5 years. Emollient use was very common even in those children without AD (74%) with the majority of users applying it 4 or more days per week (61%) . Lotions were the most frequently used product in children without AD. Of those we surveyed without AD, 60% received a bath/shower 4 or more days a week. Our study found a large burden of AD in the primary care practice setting in the U.S. The majority of households use skin care practices that may be detrimental to the skin barrier such as frequent bathing and the routine use of products with high water: oil ratios. Clinical trials will allow us to identify which skin care practices are optimal for reducing the significant burden of AD in the community.
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Perceived magnitude of skin cancer risk reduction predicts sunscreen use TR Sharma1, V Yeh2, S Debanne3 and JS Bordeaux4 1 University Hospitals Cleveland Medical Center, Cleveland, OH, 2 Case Western Reserve University School of Medicine, Cleveland, OH, 3 Case Western Reserve University, Cleveland, OH and 4 University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH Wearing sunscreen with sun protection factor (SPF) 30+ is recommended to prevent skin cancer; however, most Americans do not practice this behavior. Understanding factors that influence sunscreen use would allow dermatologists to counsel their patients in a way that is well-received and impactful. The perceived efficacy of sunscreen in reducing the risk of skin cancer has been found to correlate with sunscreen use. However, it is not clear whether the perceived magnitude of risk reduction has an impact on sunscreen use. We hypothesized that larger perceived magnitude of risk reduction of skin cancer would correlate with increased sunscreen use. To investigate this, we surveyed 131 patients at a Mohs micrographic surgery clinic about their perceptions of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma, and sunscreen. Participants thought sunscreen would reduce their risk of BCC by 61.1% [95% CI ¼ 56.4-65.9], SCC by 59.4% [95% CI ¼ 54.6-64.2], and melanoma by 59.5% [95% CI ¼ 54.8-64.3]. There was no difference in perceived risk reduction among these three cancers. Perceived magnitude of risk reduction of BCC, SCC, and melanoma was a significant independent predictor of sunscreen use (p¼ 0.038, p¼ 0.050, p¼0.002 respectively). These data suggest that larger perceived magnitude of skin cancer risk reduction promotes sunscreen use. Although sunscreen’s absolute impact on skin cancer risk reduction is not well established, our findings suggest that physicians should not undermine sunscreen’s potential efficacy when counseling patients, as it may be a critical motivational factor.
Influence of FLG mutations and TSLP polymorphisms on atopic dermatitis onset age J Wan, N Mitra, OJ Hoffstad and DJ Margolis University of Pennsylvania, Philadelphia, PA It has been proposed that genetic factors drive early onset atopic dermatitis (AD) while environmental exposures drive late onset AD. Mutations in filaggrin (FLG) increase the odds of AD, and single-nucleotide polymorphisms in thymic stromal lymphopoietin (TSLP) are linked to less persistent AD. Our aim was to examine the impact of FLG mutations and TSLP polymorphisms on the timing of AD onset. We performed a cross-sectional study using the Pediatric Eczema Elective Registry, a cohort of children with physician-confirmed diagnosis of AD. A total of 798 subjects were genotyped for 4 common FLG null mutations (R501X, 2282del4, R2447X, S3247X) and 770 subjects were genotyped for TSLP rs1898671. Age of AD onset was self-reported by the subject or caregiver. Logistic regression was performed to compare the odds of early onset AD (defined as 2 years old) with respect to FLG and TSLP status under an additive genetic model. The median ages of AD onset were 0.75 (IQR 0.252.0), 0.75 (IQR 0.25-1.0), and 0.25 (IQR 0.25-0.75) years for subjects with 0, 1, and 2 FLG mutations, respectively (test for trend p < 0.001). The odds of early onset AD was significantly higher among subjects with 1 FLG mutation (OR 1.74, 95% CI 1.02-2.96) and over 3-fold higher among subjects with 2 mutations (OR 3.03, 95% CI 0.70-13.16). The median AD onset age and odds of early onset AD did not vary by TSLP status. There was no interaction between FLG and TSLP variants on the odds of early onset AD, and analysis by race did not alter the findings. In distinguishing subjects with 1 FLG mutation versus 2 mutations, we found that common FLG mutations are associated with earlier AD onset in a dose-dependent manner. However, TSLP rs1898671 appears unrelated to the timing of AD onset. Our findings support the notion that early onset and late onset AD may differ in their genetic underpinnings. Further genetic and clinical studies are needed to better distinguish these forms of AD.
www.jidonline.org S33