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LB762 Distinctive miRNA expression profiles in primary extramammary Paget’s disease
| ABSTRACTS LB762
Distinctive miRNA expression profiles in primary extramammary Paget’s disease H Guo, X Gao and H Chen Dermatology, No.1 Hospital of China Medical University, Shenyang, China MicroRNAs (miRNAs) are small noncoding RNAs involved in cancer development. Extramammary Paget’s disease (EMPD) is a rare cutaneous malignancy and the role of miRNAs in EMPD remains unknown. Here, we used TaqMan miRNA arrays to characterize miRNA expression profile in EMPD and further validated the candidates by single RT-PCR.. Total 12 cases EMPD were involved in this study. Using laser capture micro-dissection technique, we collected EMPD tumor cells (ET, n¼12), normal epidermal cells (NE, n¼12) and normal apocrine glands cells (NA, n¼7). miRNA arrays from two pairs of EMPD cells and corresponding normal epidermal cells showed that miR-375, miR-10b, miR-31, miR-31* were differentially expressed. The single RT-PCR further confirmed that miR-375, miR-31 and miR-31* were upregulated in in EMPD cells than those of the normal epidermis and apocrine glands (p<0.0001). Our preliminary study suggested that these miRNAs could be involved in EMPD development and may serve as potential biomarkers for early EMPD diagnosis.
LB764
LB763
Risk of melanoma after chronic exposure to aspirin: A large, single center, retrospective study A Cices, N Guido, S Majewski, E Ibler, T Huynh, S Rangel, AE Laumann, M Martini, D West and B Nardone Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL Aspirin use has been reported to be protective against development of several cancers. The aim of this study is to evaluate the association of aspirin use and melanoma in a large, urban, single academic center electronic medical record repository, the Northwestern Medicine Enterprise Data Warehouse (NMEDW) (>4.4 million patients, 01/2001 e 12/2015) to detect data for all patients, age 18-89, with a follow-up encounter 1 year. Aspirin exposure was 1 year with subsequent cutaneous melanoma diagnosis (ICD-9 172.0-172.9 and ICD10:C43.0-C43.9), occurring 6 months after initial aspirin exposure. Data on age, gender, and race were collected. Adjusted Odds Ratio (OR) was determined per logistic regression analysis. The total study population consisted of 802,963 individuals. Of these, 7,227 aspirin users were detected, of whom 93 had a subsequent diagnosis of cutaneous melanoma (mean age 73.85 years, range 34-89; 64M/ 29F; 69% Caucasian). Median follow-up was 163 months (interquartile range (IQR) 134.5-177); length of exposure 36 months (IQR 21.5-66.5); time from first exposure to melanoma 69 months (IQR 32.5-86.5). After adjusting for age, race, and gender an increased risk for melanoma in aspirin-exposed patients (OR: 1.25; 95%CI 1.011.54; p¼0.037) was detected. These findings serve to delineate the association between aspirin use and subsequent development of melanoma.
LB765
Reverting dermal and epidermal alterations associated to photo-aging: Extracellular matrix rebuilding and decreasing DNA-damage markers K Kadoya1, C Mazur2, T Fleck1, RC Mehta1, VL Vega1 and D McDaniel2 1 R&D, SkinMedica, an Allergan Company, Irvine, CA and 2 McDaniel Institute of Anti-Aging Research and Laser & Cosmetic Center, Virginia Beach, VA Intrinsic skin aging results in progressive loss of structural integrity and physiological function which is aggravated by unprotected exposure to solar radiation the most common source of extrinsic aging. Clinical signs for these aging are different with the latter characterized by dryness, irregular pigmentation, sallowness, laxity, telangiectasia and leathery appearance. Sunscreen actives minimize the effects of ultraviolet (UV) A and B rays, but have no effects on pre-existent alterations. Topically applied antioxidants are commonly used by the cosmetic industry due to their great tolerability profile broad efficacy spectrum and stability. The goal of this study was to investigate the benefits of a cosmetic formulation (TDR SPF34) in which SPF actives were mixed with a unique blend of antioxidants to provide protection against solar UV and infrared rays as well as evaluating its ability to repair and/or revert pre-existent damage. Study was conducted on volunteers with facial photo-damage (n¼24). TDR SPF34 was applied once daily in the morning up to 12 weeks. Investigator assessment and standardized digital photographs were obtained at week 4, 8 and 12. Punch biopsies (n¼5) were obtained at baseline and week 12. Investigator assessments showed statistically significant improvements at week 12 when compared to baseline. Also histological observations reported improvement in the thickening of epidermis, increased deposit of collagen I in dermis and collagen IV in the DEJ also enhanced levels of hyaluronic acid in dermis and epidermis. Reduction in the expression of MMP1 and mutant (m)p53 were also observed in epidermis. These observations suggest that the unique blend of antioxidants present in TDR SPF34 is able to revert clinical and histological signs of photo-aging. These changes are associated to repairing and rebuilding of extracellular matrix components as well as decreasing in DNAdamage markers expression.
Whole-genome sequence of S. aureus strains from infant skin e its utility to discover bacterial target to control atopic dermatitis onset in childhood Y Nakamura1, Y Inoue2, A Takaya3, H Takahashi4, Y Kusuya4, Y Katayama1, G Nunez5, N Shimojo2 and H Matsue1 1 Dermatology, Chiba University, Chiba, Japan, 2 Pediatrics, Chiba University, Chiba, Japan, 3 Microbiology and Molecular Genetics, Chiba University, Chiba, Japan, 4 Division of Bio-resources, Medical Mycology Research Center, Chiba University, Chiba, Japan and 5 Pathology and Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI Atopic dermatitis (AD) is commonly accompanied by S. aureus colonization in the affected skin. However, it is not known how the colonization is involved in the disease onset. We performed whole-genome sequencing of S. aureus strains isolated from the cheek skin of 270 infants at 6 months old who received a regular health checkup in Chiba, Japan. At a 2-yearold checkup, doctors evaluated whether they had AD or not. This study revealed that 6-month-old infants with S. aureus colonization (more than 50% of infants) had significantly higher AD odds ratio compared with bacteria negative infants (odds ratio 4.203, p¼0.008). Multilocus sequence typing (MLST) based on whole-genome sequencing identified ST8 and ST188 as frequent colonizers (23 and 24, respectively out of 132 S. aureus strains). Among the 132 strains, 100% had RNAIII (encoding d-toxin) and agr genes (that control the bacterial virulence); 64% had agr I, 24% agr II, 8% agr III, and 4% agr IV. The frequencies of the agr subtype genes showed no significant differences between AD and non-AD groups. However, some agr mutations in S. aureus were found to be related to markedly downregulate or not to detect RNAIII expression assessed by qPCR. Interestingly, infants colonized with RNAIII negative S. aureus strains had not developed AD by 2-year-old checkup. Therefore, we believe that whole-genome sequence of S. aureus may provide a useful and helpful technique to find out the bacterial factors to control AD disease onset.
LB766
LB767
Parkinson’s disease association with rosacea: A large, single center, retrospective study S Lyon, S Majewski, N Guido, E Ibler, T Huynh, S Rangel, AE Laumann, BJ Schlosser, D West and B Nardone Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL Rosacea is a common inflammatory condition characterized by transient or persistent central facial erythema, telangiectasias, papules or pustules. Recently, an increased incidence of Parkinson’s disease (PD) in patients with rosacea has been reported within a large population. However, the association between rosacea and PD has not been well-characterized. We sought to determine if an association exists between rosacea and PD in a large, urban, single center, electronic medical record (EMR) repository by searching the Northwestern Medicine Enterprise Data Warehouse (NMEDW) (> 4 million patients) for patients data on those who had an in-person encounter between 2001 and March 2016 and with 1 year documentation of follow-up encounter. Of these, we selected all patients diagnosed with rosacea (ICD-9 codes: 372.31; 695.3, ICD-10 codes: L71.8; L71.9) and a subsequent diagnosis of PD (ICD-9 code: 332; ICD-10 code: G20). Patients diagnosed with PD prior to rosacea diagnosis were excluded. Data on age, gender and race were also collected. Adjusted odds ratio (OR) was obtained by using logistic regression analysis. A total of 803,005 patients were identified. 17,682 were diagnosed with rosacea, of which 47 were subsequently diagnosed with PD (mean age: 74.3 years, range 53-89; 24F/23M; 77% White). A significant association between rosacea and PD was detected in this population after adjusting for age, gender and race (OR ¼ 1.7; 95%CI 1.27-2.28; p<0.001). These findings are supportive of a previously reported association between rosacea and PD. Further exploration of the association between these two conditions is essential to fully characterizing this important issue in order to optimally counsel patients.
Vitamin D deficiency and atopic dermatitis: Consider disease, race, and body mass K Darji1, Z Bryan2, C Tobin3, M Janssen1, A Eric4 and E Siegfried5 1 Saint Louis University School of Medicine, St. Louis, MO, 2 Dermatology, U Kansas SOM, Kansas City, MO, 3 Dermatology, Saint Louis University, St. Louis, MO, 4 Center for Outcomes Research, Saint Louis University, St. Louis, MO and 5 Pediatric Dermatology, Cardinal Glennon Children’s Hospital/Saint Louis University School of Medicine, St. Louis, MO Background/Objectives: Vitamin D deficiency is a well-recognized cause of rickets, but has been implicated in a variety of diseases, including atopic dermatitis (AD). This study analyzes serum vitamin D in children with respect to atopic dermatitis and several potentially confounding factors. Methods: This study was conducted at Cardinal Glennon Children’s Hospital, an urban-based tertiary care center. Charts of 665 children with serum 25hydroxyvitamin D levels taken between 2009 and 2013 were retrospectively reviewed. Results: Defining vitamin D deficiency as <20 ng/ml, neither average 25-hydroxyvitamin D nor deficiency prevalence varied among disease groups, except cystic fibrosis (CF), which was associated with a significantly higher average vitamin D and lower prevalence of deficiency. Children with AD had the lowest prevalence of vitamin D sufficiency; this was not significantly associated with disease severity. No seasonal variation was detected across all patients or the subgroup of white patients. Strong correlations were identified only between 25-hydroxyvitamin D levels, BMI and race. Conclusions: Our data does not support a strong association between vitamin D levels in children and AD or AD severity. We did observe a strong association with skin type and BMI. The lower prevalence of vitamin D deficiency among children with CF likely reflects a predominance of light skin and low BMI in this cohort. A very high prevalence of vitamin D insufficiency and deficiency as currently defined among children with dark skin and high BMI suggests a need to reevaluate normal vitamin D levels in these populations, especially with respect to comorbidities.
www.jidonline.org B3
Distinctive miRNA expression profiles in primary extramammary Paget’s disease H Guo, X Gao and H Chen Dermatology, No.1 Hospital of China Medical University, Shenyang, China MicroRNAs (miRNAs) are small noncoding RNAs involved in cancer development. Extramammary Paget’s disease (EMPD) is a rare cutaneous malignancy and the role of miRNAs in EMPD remains unknown. Here, we used TaqMan miRNA arrays to characterize miRNA expression profile in EMPD and further validated the candidates by single RT-PCR.. Total 12 cases EMPD were involved in this study. Using laser capture micro-dissection technique, we collected EMPD tumor cells (ET, n¼12), normal epidermal cells (NE, n¼12) and normal apocrine glands cells (NA, n¼7). miRNA arrays from two pairs of EMPD cells and corresponding normal epidermal cells showed that miR-375, miR-10b, miR-31, miR-31* were differentially expressed. The single RT-PCR further confirmed that miR-375, miR-31 and miR-31* were upregulated in in EMPD cells than those of the normal epidermis and apocrine glands (p<0.0001). Our preliminary study suggested that these miRNAs could be involved in EMPD development and may serve as potential biomarkers for early EMPD diagnosis.
LB764
LB763
Risk of melanoma after chronic exposure to aspirin: A large, single center, retrospective study A Cices, N Guido, S Majewski, E Ibler, T Huynh, S Rangel, AE Laumann, M Martini, D West and B Nardone Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL Aspirin use has been reported to be protective against development of several cancers. The aim of this study is to evaluate the association of aspirin use and melanoma in a large, urban, single academic center electronic medical record repository, the Northwestern Medicine Enterprise Data Warehouse (NMEDW) (>4.4 million patients, 01/2001 e 12/2015) to detect data for all patients, age 18-89, with a follow-up encounter 1 year. Aspirin exposure was 1 year with subsequent cutaneous melanoma diagnosis (ICD-9 172.0-172.9 and ICD10:C43.0-C43.9), occurring 6 months after initial aspirin exposure. Data on age, gender, and race were collected. Adjusted Odds Ratio (OR) was determined per logistic regression analysis. The total study population consisted of 802,963 individuals. Of these, 7,227 aspirin users were detected, of whom 93 had a subsequent diagnosis of cutaneous melanoma (mean age 73.85 years, range 34-89; 64M/ 29F; 69% Caucasian). Median follow-up was 163 months (interquartile range (IQR) 134.5-177); length of exposure 36 months (IQR 21.5-66.5); time from first exposure to melanoma 69 months (IQR 32.5-86.5). After adjusting for age, race, and gender an increased risk for melanoma in aspirin-exposed patients (OR: 1.25; 95%CI 1.011.54; p¼0.037) was detected. These findings serve to delineate the association between aspirin use and subsequent development of melanoma.
LB765
Reverting dermal and epidermal alterations associated to photo-aging: Extracellular matrix rebuilding and decreasing DNA-damage markers K Kadoya1, C Mazur2, T Fleck1, RC Mehta1, VL Vega1 and D McDaniel2 1 R&D, SkinMedica, an Allergan Company, Irvine, CA and 2 McDaniel Institute of Anti-Aging Research and Laser & Cosmetic Center, Virginia Beach, VA Intrinsic skin aging results in progressive loss of structural integrity and physiological function which is aggravated by unprotected exposure to solar radiation the most common source of extrinsic aging. Clinical signs for these aging are different with the latter characterized by dryness, irregular pigmentation, sallowness, laxity, telangiectasia and leathery appearance. Sunscreen actives minimize the effects of ultraviolet (UV) A and B rays, but have no effects on pre-existent alterations. Topically applied antioxidants are commonly used by the cosmetic industry due to their great tolerability profile broad efficacy spectrum and stability. The goal of this study was to investigate the benefits of a cosmetic formulation (TDR SPF34) in which SPF actives were mixed with a unique blend of antioxidants to provide protection against solar UV and infrared rays as well as evaluating its ability to repair and/or revert pre-existent damage. Study was conducted on volunteers with facial photo-damage (n¼24). TDR SPF34 was applied once daily in the morning up to 12 weeks. Investigator assessment and standardized digital photographs were obtained at week 4, 8 and 12. Punch biopsies (n¼5) were obtained at baseline and week 12. Investigator assessments showed statistically significant improvements at week 12 when compared to baseline. Also histological observations reported improvement in the thickening of epidermis, increased deposit of collagen I in dermis and collagen IV in the DEJ also enhanced levels of hyaluronic acid in dermis and epidermis. Reduction in the expression of MMP1 and mutant (m)p53 were also observed in epidermis. These observations suggest that the unique blend of antioxidants present in TDR SPF34 is able to revert clinical and histological signs of photo-aging. These changes are associated to repairing and rebuilding of extracellular matrix components as well as decreasing in DNAdamage markers expression.
Whole-genome sequence of S. aureus strains from infant skin e its utility to discover bacterial target to control atopic dermatitis onset in childhood Y Nakamura1, Y Inoue2, A Takaya3, H Takahashi4, Y Kusuya4, Y Katayama1, G Nunez5, N Shimojo2 and H Matsue1 1 Dermatology, Chiba University, Chiba, Japan, 2 Pediatrics, Chiba University, Chiba, Japan, 3 Microbiology and Molecular Genetics, Chiba University, Chiba, Japan, 4 Division of Bio-resources, Medical Mycology Research Center, Chiba University, Chiba, Japan and 5 Pathology and Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI Atopic dermatitis (AD) is commonly accompanied by S. aureus colonization in the affected skin. However, it is not known how the colonization is involved in the disease onset. We performed whole-genome sequencing of S. aureus strains isolated from the cheek skin of 270 infants at 6 months old who received a regular health checkup in Chiba, Japan. At a 2-yearold checkup, doctors evaluated whether they had AD or not. This study revealed that 6-month-old infants with S. aureus colonization (more than 50% of infants) had significantly higher AD odds ratio compared with bacteria negative infants (odds ratio 4.203, p¼0.008). Multilocus sequence typing (MLST) based on whole-genome sequencing identified ST8 and ST188 as frequent colonizers (23 and 24, respectively out of 132 S. aureus strains). Among the 132 strains, 100% had RNAIII (encoding d-toxin) and agr genes (that control the bacterial virulence); 64% had agr I, 24% agr II, 8% agr III, and 4% agr IV. The frequencies of the agr subtype genes showed no significant differences between AD and non-AD groups. However, some agr mutations in S. aureus were found to be related to markedly downregulate or not to detect RNAIII expression assessed by qPCR. Interestingly, infants colonized with RNAIII negative S. aureus strains had not developed AD by 2-year-old checkup. Therefore, we believe that whole-genome sequence of S. aureus may provide a useful and helpful technique to find out the bacterial factors to control AD disease onset.
LB766
LB767
Parkinson’s disease association with rosacea: A large, single center, retrospective study S Lyon, S Majewski, N Guido, E Ibler, T Huynh, S Rangel, AE Laumann, BJ Schlosser, D West and B Nardone Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL Rosacea is a common inflammatory condition characterized by transient or persistent central facial erythema, telangiectasias, papules or pustules. Recently, an increased incidence of Parkinson’s disease (PD) in patients with rosacea has been reported within a large population. However, the association between rosacea and PD has not been well-characterized. We sought to determine if an association exists between rosacea and PD in a large, urban, single center, electronic medical record (EMR) repository by searching the Northwestern Medicine Enterprise Data Warehouse (NMEDW) (> 4 million patients) for patients data on those who had an in-person encounter between 2001 and March 2016 and with 1 year documentation of follow-up encounter. Of these, we selected all patients diagnosed with rosacea (ICD-9 codes: 372.31; 695.3, ICD-10 codes: L71.8; L71.9) and a subsequent diagnosis of PD (ICD-9 code: 332; ICD-10 code: G20). Patients diagnosed with PD prior to rosacea diagnosis were excluded. Data on age, gender and race were also collected. Adjusted odds ratio (OR) was obtained by using logistic regression analysis. A total of 803,005 patients were identified. 17,682 were diagnosed with rosacea, of which 47 were subsequently diagnosed with PD (mean age: 74.3 years, range 53-89; 24F/23M; 77% White). A significant association between rosacea and PD was detected in this population after adjusting for age, gender and race (OR ¼ 1.7; 95%CI 1.27-2.28; p<0.001). These findings are supportive of a previously reported association between rosacea and PD. Further exploration of the association between these two conditions is essential to fully characterizing this important issue in order to optimally counsel patients.
Vitamin D deficiency and atopic dermatitis: Consider disease, race, and body mass K Darji1, Z Bryan2, C Tobin3, M Janssen1, A Eric4 and E Siegfried5 1 Saint Louis University School of Medicine, St. Louis, MO, 2 Dermatology, U Kansas SOM, Kansas City, MO, 3 Dermatology, Saint Louis University, St. Louis, MO, 4 Center for Outcomes Research, Saint Louis University, St. Louis, MO and 5 Pediatric Dermatology, Cardinal Glennon Children’s Hospital/Saint Louis University School of Medicine, St. Louis, MO Background/Objectives: Vitamin D deficiency is a well-recognized cause of rickets, but has been implicated in a variety of diseases, including atopic dermatitis (AD). This study analyzes serum vitamin D in children with respect to atopic dermatitis and several potentially confounding factors. Methods: This study was conducted at Cardinal Glennon Children’s Hospital, an urban-based tertiary care center. Charts of 665 children with serum 25hydroxyvitamin D levels taken between 2009 and 2013 were retrospectively reviewed. Results: Defining vitamin D deficiency as <20 ng/ml, neither average 25-hydroxyvitamin D nor deficiency prevalence varied among disease groups, except cystic fibrosis (CF), which was associated with a significantly higher average vitamin D and lower prevalence of deficiency. Children with AD had the lowest prevalence of vitamin D sufficiency; this was not significantly associated with disease severity. No seasonal variation was detected across all patients or the subgroup of white patients. Strong correlations were identified only between 25-hydroxyvitamin D levels, BMI and race. Conclusions: Our data does not support a strong association between vitamin D levels in children and AD or AD severity. We did observe a strong association with skin type and BMI. The lower prevalence of vitamin D deficiency among children with CF likely reflects a predominance of light skin and low BMI in this cohort. A very high prevalence of vitamin D insufficiency and deficiency as currently defined among children with dark skin and high BMI suggests a need to reevaluate normal vitamin D levels in these populations, especially with respect to comorbidities.
www.jidonline.org B3