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Noninvasive dermal measurement of carotenoid levels inversely associated with anxiety and stress in breast cancer patients
5794
4587
Nodular colloid milium mimicking keloid Seyyede Zeinab Azimi, Guilan University of Medical Sciences
Noninvasive dermal measurement of carotenoid levels inversely associated with anxiety and stress in breast cancer patients David Li, BS, David Li; Gabrielle LeCompte, MD, Gabrielle LeCompte; Lihong Mo, MD, Lihong Mo; Miranda Weintraub, PhD, Miranda Weintraub; David Irwin, MD, David Irwin; Gary Cecchi, MD, Gary Cecchi Background: Breast cancer is the most prevalent malignancy among women worldwide. Increased levels of oxidative stress are associated with lower levels of dermal carotenoids and increased breast cancer incidence. This study assesses physical, behavioral, and subjective health correlates of oxidative stress as quantified by dermal biomarkers and associations between oxidative stress and breast cancer stage.
Colloid milium (CM) is a degenerative cutaneous condition with deposition of colloid in dermis, producing small rounded lesions, which can be single or multiple. The pathogenesis is unknown, although it is assumed to be due to degeneration of cutaneous elastic fibers as a result of excess sun exposure. There is some evidence to suggest a genetic predisposition, and some cases have been felt to be due to exposure to petroleum products or hydroquinone. Clinically, CM is characterized by multiple yellow or flesh colored, dome shaped papules. The areas most commonly affected are on the sun-exposed areas of the head and neck, as well as the dorsal aspects of the hands and forearms. The back can be involved in some patients. Squeezing the lesions between thumb and forefinger can sometimes extrude a lightly colored gelatinous material. A 52-year-old man presented with an asymptomatic slowly growing lesion on his upper lip, which had gradually developed over a year. He had sustained a very minor trauma to the area and afterward a dome shape papule developed. It gradually increased in size over a period of 4 months and remained unchanged until presentation almost a year later. The lesion had been diagnosed as a keloid by a dermatologist, but failed to respond to several intralesional triamcinolone injections. Physical examination revealed a well-defined, red, firm nodule on the central area of the upper lip. The nodule was noted to be pushing the vermilion border down, but did not actually involve it. Milia like areas were observed under high power magnification. There were no other similar lesions on the lips, in the oral cavity, or anywhere else on skin examination. Histopathologic examination with hematoxylin and eosin (H&E) staining showed a flattened epidermis with a large deposition of amorphous eosinophilic material containing horizontal fissures, which expanded the dermal papillae, with extension into deep dermis. Congo red, crystal violet and periodic acideSchiff (PAS) stains were positive, but polarized microscopy was negative for any signs of amyloid or birefringence, and there was no sign of foreign body material. The differential diagnosis of CM includes a variety of entities, which can exhibit multiple small light colored papules. These include systemic and primary cutaneous amyloidosis, common milium, erythropoietic protoporphyria, syringomata, steatocystoma multiplex, lipoid proteinosis, retention cysts, sarcoidosis, molluscum contagiosum, papular mucinosis, and sebaceous hyperplasia. Nodular colloid degeneration has sometimes been classified as a form of nodular amyloidosis. Histochemistry and immunohistochemistry examinations are often necessary to distinguish CM from amyloidosis. Colloid can be differentiated from amyloid since the colloid material does not react with Pagoda red and other cotton dyes, and immunohistochemically, colloid does not react with light-chain immunoglobulin while amyloid frequently reacts. Negative reactivity with cytokeratin also distinguishes colloid from amyloid. There are limited treatment options for CM. Modalities such as dermabrasion and ablation with the Er:YAG laser, as well as destructive procedures such as diathermy and cryotherapy have been reported to be useful in treatment. Our patient has been treated with CO2 laser which led to satisfactory outcome after two sessions. Colloid milium needs to be kept in mind when a patient is seen with a single firm skin-colored lesion, or with multiple such lesions, and the important diseases included in the above differential diagnoses, which can be associated with such cutaneous displays, must be considered by the clinician.
Methods: Current and previous breast cancer patients were asked to participate in this cross-sectional study approved by the Institutional Review Board of Highland Hospital in affiliation with UCSF. After assessing Electronic Medical Records (EMR), a sample of 149 patients met the inclusion criteria. A final sample of 102 (68%) were enrolled. Each participant’s skin carotenoid score (SCS), a dermal measure of oxidative stress, was recorded via Raman spectroscopy. Patient demographics, physical health (breast cancer stage, treatment status, weight, height) health behaviors (smoking status, diet) and subjective health (anxiety and self-rated health) were ascertained. Results: No correlation between breast cancer stage and SCS was found. SCS was associated with behavioral health, weight and height (P \.05), a finding consistent with previous research. A multivariate linear regression analysis, controlling for all covariates, found the two subjective health measures to be associated with SCS scores; the presence of anxiety was associated with lower SCS scores, a novel finding (b ¼ -0.48, 95%CI -0.93, -0.035). Moreover, self-rated health was inversely correlated with SCS, showing those with lower self-reported quality levels paradoxically had higher levels of SCS (b ¼ 19.89, 95% CI 6.12, 33.67). Conclusions: Although oxidative stress as measured by dermal carotenoid biomarkers may not be associated with breast cancer staging, future research should explore the causal relationship between oxidative stress and subjective stress. Results suggest an unknown biochemical mechanism linking increased levels of oxidative stress with lower subjective health scores. Findings of the study indicate the possibility of utilizing skin carotenoid levels as an objective correlate to gauge an individual’s subjective stress levels in order to optimize cancer treatment. Commercial support: None identified.
Commercial support: None identified.
4805 Noncosmetic prescription medication prices are increasing at a higher rate than cosmetic prescription medication prices Zachary Eyre, BS, University of Utah Department of Dermatology; Mark Eliason, MD, University of Utah Department of Dermatology; Richard Nelson, PhD, University of Utah School of Medicine; Aaron Secrest, MD, University of Utah Department of Dermatology Background: Escalating U.S. health care costs have come under increasing scrutiny, particularly prescription drug costs. The pharmaceutical industry has argued that market forces exist to keep the prices of prescription drugs in check. Dermatology has a unique opportunity to explore this argument, due to a handful of purely cosmetic prescription medications. Health insurance companies do not include these medications on any of their formularies, so patients must pay the entire cost of these out of pocket. In this study we explored differences between the rates at which prices have increased between prescription cosmetic vs non-cosmetic medications in dermatology. Methods: All dermatologic cosmetic prescription medications that are currently FDAapproved were included in our analyses. The 20 most frequently prescribed medications within the University of Utah Department of Dermatology in 2015 were selected as the control group of noncosmetic medications, based on the active drug ingredient. Any brand name or generic medication (1) containing the same active ingredient, (2) currently in production, and (3) with at least 12 years of pricing data since the year 2000, was included in the analysis. All pricing data came from the Truven Health Analytics Red Book, using the historical average wholesale price (AWP) for each medication. Results: The overall average price increase since 2000 was 450% for all medications in our analysis. Noncosmetic prescription medications saw an average price increase of 460%, while cosmetic medications increased only an average of 96% over roughly the same period. The average generic price increase was 202%, while the increase for brand name medications was 635%. Brand name topical steroids saw the largest price increase (1670%), while generic oral medications saw the smallest (85%). Health carespecific consumer price index (CPI) increased 58% from 2000 to 2016. Discussion: Prescription cosmetic medications have not experienced the same dramatic price increases seen with other brand name and generic dermatologic medications. Although many reasons for this difference exist, the lack of a thirdparty payer may help market forces keep the price increases lower and closer to the CPI for cosmetic medications. Future research is needed to isolate the effect of a third-party payer’s presence from other factors that could influence drug prices, including differences in patient demand and competition from other producers. Commercial support: None identified.
AB180
J AM ACAD DERMATOL
5382 Noninvasive gene expression analysis for psoriasis Gerald Krueger, MD, Department of Dermatology, University of Utah School of Medicine; Burkhard Jansen, MD, DermTech; Zuxu Yao, PhD, DermTech Background: Significant progress has been made in the treatment of moderate to severe psoriasis by blocking TNF alpha, IL-17A and IL-23. Biosimilars as well as further improved targeted treatment options are on the horizon. However, disease monitoring, prediction of flare-ups and treatment selection remain challenging. A robust, noninvasive option to assess gene expression in psoriasis and potentially predict treatment response appears highly desirable. Approach: Using our adhesive patch e based skin biopsy platform, we established such an assay. The modular structure of the qRT-PCR assay allows it to be employed in a number of inflammatory skin conditions including psoriasis, atopic dermatitis or lupus. In psoriasis, it focuses on 20 targets involved in expanded TH17 pathways. Results: Initial findings from an ongoing analysis effort of over 500 lesional and nonlesional adhesive patch biopsy samples from patients with moderate to severe psoriasis demonstrate reliable detection of all 20 selected targets by qRT-PCR and significant differences in gene expression signatures of lesional, non-lesional and non-psoriasis control skin (P \.001, n ¼ 24). Analyses from non-lesional samples avoid the need to control for disease activity in individual psoriasis lesions and may provide the clinically most useful information. In non-lesional psoriatic compared to normal skin, gene expression levels of IL-17A, IL-17C, IL-17F, IL-17 receptors, IL-23A, IL-22, IL-24, IL-6, IL-8, CXCL1, CXCL5, DEFB4A, LCN2, S100A7 as well as TNF-a and its receptor were altered by 2 to 200 fold. Therapeutic intervention with targeted therapeutics such as ixekizumab significantly (P \ .001) reduced target gene expression (including IL-17A and 17F, TNF- a and CXCL1 and CXCL5) compared to baseline after 2 weeks. Conclusion: Noninvasive gene expression analysis of lesional, and possibly even more importantly of nonlesional epidermal skin samples, is a robust approach to monitor disease activity with the potential to predict flare-ups and treatment failure in psoriasis. Commercial support: Supported by DermTech, Inc.
JUNE 2017
4587
Nodular colloid milium mimicking keloid Seyyede Zeinab Azimi, Guilan University of Medical Sciences
Noninvasive dermal measurement of carotenoid levels inversely associated with anxiety and stress in breast cancer patients David Li, BS, David Li; Gabrielle LeCompte, MD, Gabrielle LeCompte; Lihong Mo, MD, Lihong Mo; Miranda Weintraub, PhD, Miranda Weintraub; David Irwin, MD, David Irwin; Gary Cecchi, MD, Gary Cecchi Background: Breast cancer is the most prevalent malignancy among women worldwide. Increased levels of oxidative stress are associated with lower levels of dermal carotenoids and increased breast cancer incidence. This study assesses physical, behavioral, and subjective health correlates of oxidative stress as quantified by dermal biomarkers and associations between oxidative stress and breast cancer stage.
Colloid milium (CM) is a degenerative cutaneous condition with deposition of colloid in dermis, producing small rounded lesions, which can be single or multiple. The pathogenesis is unknown, although it is assumed to be due to degeneration of cutaneous elastic fibers as a result of excess sun exposure. There is some evidence to suggest a genetic predisposition, and some cases have been felt to be due to exposure to petroleum products or hydroquinone. Clinically, CM is characterized by multiple yellow or flesh colored, dome shaped papules. The areas most commonly affected are on the sun-exposed areas of the head and neck, as well as the dorsal aspects of the hands and forearms. The back can be involved in some patients. Squeezing the lesions between thumb and forefinger can sometimes extrude a lightly colored gelatinous material. A 52-year-old man presented with an asymptomatic slowly growing lesion on his upper lip, which had gradually developed over a year. He had sustained a very minor trauma to the area and afterward a dome shape papule developed. It gradually increased in size over a period of 4 months and remained unchanged until presentation almost a year later. The lesion had been diagnosed as a keloid by a dermatologist, but failed to respond to several intralesional triamcinolone injections. Physical examination revealed a well-defined, red, firm nodule on the central area of the upper lip. The nodule was noted to be pushing the vermilion border down, but did not actually involve it. Milia like areas were observed under high power magnification. There were no other similar lesions on the lips, in the oral cavity, or anywhere else on skin examination. Histopathologic examination with hematoxylin and eosin (H&E) staining showed a flattened epidermis with a large deposition of amorphous eosinophilic material containing horizontal fissures, which expanded the dermal papillae, with extension into deep dermis. Congo red, crystal violet and periodic acideSchiff (PAS) stains were positive, but polarized microscopy was negative for any signs of amyloid or birefringence, and there was no sign of foreign body material. The differential diagnosis of CM includes a variety of entities, which can exhibit multiple small light colored papules. These include systemic and primary cutaneous amyloidosis, common milium, erythropoietic protoporphyria, syringomata, steatocystoma multiplex, lipoid proteinosis, retention cysts, sarcoidosis, molluscum contagiosum, papular mucinosis, and sebaceous hyperplasia. Nodular colloid degeneration has sometimes been classified as a form of nodular amyloidosis. Histochemistry and immunohistochemistry examinations are often necessary to distinguish CM from amyloidosis. Colloid can be differentiated from amyloid since the colloid material does not react with Pagoda red and other cotton dyes, and immunohistochemically, colloid does not react with light-chain immunoglobulin while amyloid frequently reacts. Negative reactivity with cytokeratin also distinguishes colloid from amyloid. There are limited treatment options for CM. Modalities such as dermabrasion and ablation with the Er:YAG laser, as well as destructive procedures such as diathermy and cryotherapy have been reported to be useful in treatment. Our patient has been treated with CO2 laser which led to satisfactory outcome after two sessions. Colloid milium needs to be kept in mind when a patient is seen with a single firm skin-colored lesion, or with multiple such lesions, and the important diseases included in the above differential diagnoses, which can be associated with such cutaneous displays, must be considered by the clinician.
Methods: Current and previous breast cancer patients were asked to participate in this cross-sectional study approved by the Institutional Review Board of Highland Hospital in affiliation with UCSF. After assessing Electronic Medical Records (EMR), a sample of 149 patients met the inclusion criteria. A final sample of 102 (68%) were enrolled. Each participant’s skin carotenoid score (SCS), a dermal measure of oxidative stress, was recorded via Raman spectroscopy. Patient demographics, physical health (breast cancer stage, treatment status, weight, height) health behaviors (smoking status, diet) and subjective health (anxiety and self-rated health) were ascertained. Results: No correlation between breast cancer stage and SCS was found. SCS was associated with behavioral health, weight and height (P \.05), a finding consistent with previous research. A multivariate linear regression analysis, controlling for all covariates, found the two subjective health measures to be associated with SCS scores; the presence of anxiety was associated with lower SCS scores, a novel finding (b ¼ -0.48, 95%CI -0.93, -0.035). Moreover, self-rated health was inversely correlated with SCS, showing those with lower self-reported quality levels paradoxically had higher levels of SCS (b ¼ 19.89, 95% CI 6.12, 33.67). Conclusions: Although oxidative stress as measured by dermal carotenoid biomarkers may not be associated with breast cancer staging, future research should explore the causal relationship between oxidative stress and subjective stress. Results suggest an unknown biochemical mechanism linking increased levels of oxidative stress with lower subjective health scores. Findings of the study indicate the possibility of utilizing skin carotenoid levels as an objective correlate to gauge an individual’s subjective stress levels in order to optimize cancer treatment. Commercial support: None identified.
Commercial support: None identified.
4805 Noncosmetic prescription medication prices are increasing at a higher rate than cosmetic prescription medication prices Zachary Eyre, BS, University of Utah Department of Dermatology; Mark Eliason, MD, University of Utah Department of Dermatology; Richard Nelson, PhD, University of Utah School of Medicine; Aaron Secrest, MD, University of Utah Department of Dermatology Background: Escalating U.S. health care costs have come under increasing scrutiny, particularly prescription drug costs. The pharmaceutical industry has argued that market forces exist to keep the prices of prescription drugs in check. Dermatology has a unique opportunity to explore this argument, due to a handful of purely cosmetic prescription medications. Health insurance companies do not include these medications on any of their formularies, so patients must pay the entire cost of these out of pocket. In this study we explored differences between the rates at which prices have increased between prescription cosmetic vs non-cosmetic medications in dermatology. Methods: All dermatologic cosmetic prescription medications that are currently FDAapproved were included in our analyses. The 20 most frequently prescribed medications within the University of Utah Department of Dermatology in 2015 were selected as the control group of noncosmetic medications, based on the active drug ingredient. Any brand name or generic medication (1) containing the same active ingredient, (2) currently in production, and (3) with at least 12 years of pricing data since the year 2000, was included in the analysis. All pricing data came from the Truven Health Analytics Red Book, using the historical average wholesale price (AWP) for each medication. Results: The overall average price increase since 2000 was 450% for all medications in our analysis. Noncosmetic prescription medications saw an average price increase of 460%, while cosmetic medications increased only an average of 96% over roughly the same period. The average generic price increase was 202%, while the increase for brand name medications was 635%. Brand name topical steroids saw the largest price increase (1670%), while generic oral medications saw the smallest (85%). Health carespecific consumer price index (CPI) increased 58% from 2000 to 2016. Discussion: Prescription cosmetic medications have not experienced the same dramatic price increases seen with other brand name and generic dermatologic medications. Although many reasons for this difference exist, the lack of a thirdparty payer may help market forces keep the price increases lower and closer to the CPI for cosmetic medications. Future research is needed to isolate the effect of a third-party payer’s presence from other factors that could influence drug prices, including differences in patient demand and competition from other producers. Commercial support: None identified.
AB180
J AM ACAD DERMATOL
5382 Noninvasive gene expression analysis for psoriasis Gerald Krueger, MD, Department of Dermatology, University of Utah School of Medicine; Burkhard Jansen, MD, DermTech; Zuxu Yao, PhD, DermTech Background: Significant progress has been made in the treatment of moderate to severe psoriasis by blocking TNF alpha, IL-17A and IL-23. Biosimilars as well as further improved targeted treatment options are on the horizon. However, disease monitoring, prediction of flare-ups and treatment selection remain challenging. A robust, noninvasive option to assess gene expression in psoriasis and potentially predict treatment response appears highly desirable. Approach: Using our adhesive patch e based skin biopsy platform, we established such an assay. The modular structure of the qRT-PCR assay allows it to be employed in a number of inflammatory skin conditions including psoriasis, atopic dermatitis or lupus. In psoriasis, it focuses on 20 targets involved in expanded TH17 pathways. Results: Initial findings from an ongoing analysis effort of over 500 lesional and nonlesional adhesive patch biopsy samples from patients with moderate to severe psoriasis demonstrate reliable detection of all 20 selected targets by qRT-PCR and significant differences in gene expression signatures of lesional, non-lesional and non-psoriasis control skin (P \.001, n ¼ 24). Analyses from non-lesional samples avoid the need to control for disease activity in individual psoriasis lesions and may provide the clinically most useful information. In non-lesional psoriatic compared to normal skin, gene expression levels of IL-17A, IL-17C, IL-17F, IL-17 receptors, IL-23A, IL-22, IL-24, IL-6, IL-8, CXCL1, CXCL5, DEFB4A, LCN2, S100A7 as well as TNF-a and its receptor were altered by 2 to 200 fold. Therapeutic intervention with targeted therapeutics such as ixekizumab significantly (P \ .001) reduced target gene expression (including IL-17A and 17F, TNF- a and CXCL1 and CXCL5) compared to baseline after 2 weeks. Conclusion: Noninvasive gene expression analysis of lesional, and possibly even more importantly of nonlesional epidermal skin samples, is a robust approach to monitor disease activity with the potential to predict flare-ups and treatment failure in psoriasis. Commercial support: Supported by DermTech, Inc.
JUNE 2017