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Khusru Asadullah - One of the best experts on this subject based on the ideXlab platform.
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shortened treatment duration of glucocorticoid induced Skin Atrophy in rats
Experimental Dermatology, 2011Co-Authors: Stefanie Schoepe, Khusru Asadullah, Heike Schacke, Richardus Vonk, Thomas M Zollner, Lars RoseAbstract:Abstract: Glucocorticoids (GCs) belong to the most widely used anti-inflammatory drugs at all. However, their topical use is limited by their side effect potential, with Skin Atrophy being the most prominent one. Thus, determining the atrophogenic potential of novel compounds is of importance for drug development. Currently, the most frequently performed model in the base and pharmaceutical research is the hr/hr rat model of GC-induced Skin Atrophy that lasts for 19 days. In this study, we analysed statistically Skin Atrophy experiments retrospectively to ascertain (i) the earliest time-point, at which Skin Atrophy is significantly induced; and (ii) whether the differences between the GC treatment groups change until the end of the experiment. We show here that the treatment duration of rat Skin Atrophy models might be reduced to 5 days for economical and ethical reasons.
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test systems for the determination of glucocorticoid receptor ligand induced Skin Atrophy
Dermato-endocrinology, 2011Co-Authors: Stefanie Schoepe, Heike Schacke, Khusru AsadullahAbstract:Topical glucocorticoids are highly anti-inflammatory effective but limited by their side effect potential, with Skin Atrophy being the most prominent one. Thus, determining the atrophogenic potential of novel compounds targeting the glucocorticoid receptor is important. Significant progress in the understanding of glucocorticoid receptor mediated molecular action has been made providing the basis for novel glucocorticoid receptor ligands with a potentially superior effect/side effect profile. Such compounds, however, need to be tested. The present gold standard for the reliable prediction of glucocorticoid induced Skin Atrophy are still in vivo models, however, in vitro models may replace them to some extent in the future. Indeed, advances in technologies to determine the atrophogenic potential of compounds in vitro has been made recently and promising novel test models like the human full thickness Skin models are emerging. Their full predictive value, however, needs to be further evaluated. Currently, a...
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superior nuclear receptor selectivity and therapeutic index of methylprednisolone aceponate versus mometasone furoate
Experimental Dermatology, 2007Co-Authors: Parham Mirshahpanah, Wolfdietrich Docke, Udo Merbold, Khusru Asadullah, Lars Rose, Heike Schacke, Thomas Matthias ZollnerAbstract:: Although introduced more than 50 years ago, topical glucocorticoids are still the first line therapy for many inflammatory Skin disorders such as atopic eczema, contact dermatitis and many others. Recently, significant improvements have been made to optimize the ratio of desired to unwanted effects. While with early compounds such as triamcinolone, topical side effects such as Skin Atrophy and telangiectasias can be observed rather frequently, newer drugs such as methylprednisolone aceponate or mometasone furoate have a significantly improved therapeutic index. The present study compared these two modern topical glucocorticoids, which possess the highest therapeutic index currently found, in terms of nuclear receptor selectivity in vitro and induction of the most important local side effects (Skin Atrophy and telangiectasias) in a relevant rodent model in vivo. We demonstrate that methylprednisolone aceponate displays higher specificity in nuclear receptor binding compared with mometasone furoate. Methylprednisolone aceponate was also markedly superior in terms of minimizing induction of Skin Atrophy or telangiectasias when compared with mometasone furoate. Based on these observations, methylprednisolone aceponate is expected to have a greater therapeutic index as compared with mometasone furoate, at least in the test systems used here. The degree to which this observation may translate into a clinical setting requires confirmation.
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glucocorticoid therapy induced Skin Atrophy
Experimental Dermatology, 2006Co-Authors: Stefanie Schoepe, Heike Schacke, Ekkehard May, Khusru AsadullahAbstract:Glucocorticoids (GCs) are highly effective for the topical treatment of inflammatory Skin diseases. Their long-term use, however, is often accompanied by severe and partially irreversible adverse effects, with Atrophy being the most prominent limitation. Progress in the understanding of GC-mediated molecular action as well as some advances in technologies to determine the atrophogenic potential of compounds has been made recently. It is likely that the detailed mechanisms of GC-induced Skin Atrophy will be discovered and in vitro models for the reliable prediction of Atrophy will be established in the foreseeable future. This knowledge will not only facilitate safety profiling of established drugs but will also foster further drug discovery by improving compound characterization processes. New insights into GC modes of action will guide optimization strategies aiming at novel GC receptor ligands with improved effect/side effect profile.
Stefanie Schoepe - One of the best experts on this subject based on the ideXlab platform.
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shortened treatment duration of glucocorticoid induced Skin Atrophy in rats
Experimental Dermatology, 2011Co-Authors: Stefanie Schoepe, Khusru Asadullah, Heike Schacke, Richardus Vonk, Thomas M Zollner, Lars RoseAbstract:Abstract: Glucocorticoids (GCs) belong to the most widely used anti-inflammatory drugs at all. However, their topical use is limited by their side effect potential, with Skin Atrophy being the most prominent one. Thus, determining the atrophogenic potential of novel compounds is of importance for drug development. Currently, the most frequently performed model in the base and pharmaceutical research is the hr/hr rat model of GC-induced Skin Atrophy that lasts for 19 days. In this study, we analysed statistically Skin Atrophy experiments retrospectively to ascertain (i) the earliest time-point, at which Skin Atrophy is significantly induced; and (ii) whether the differences between the GC treatment groups change until the end of the experiment. We show here that the treatment duration of rat Skin Atrophy models might be reduced to 5 days for economical and ethical reasons.
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test systems for the determination of glucocorticoid receptor ligand induced Skin Atrophy
Dermato-endocrinology, 2011Co-Authors: Stefanie Schoepe, Heike Schacke, Khusru AsadullahAbstract:Topical glucocorticoids are highly anti-inflammatory effective but limited by their side effect potential, with Skin Atrophy being the most prominent one. Thus, determining the atrophogenic potential of novel compounds targeting the glucocorticoid receptor is important. Significant progress in the understanding of glucocorticoid receptor mediated molecular action has been made providing the basis for novel glucocorticoid receptor ligands with a potentially superior effect/side effect profile. Such compounds, however, need to be tested. The present gold standard for the reliable prediction of glucocorticoid induced Skin Atrophy are still in vivo models, however, in vitro models may replace them to some extent in the future. Indeed, advances in technologies to determine the atrophogenic potential of compounds in vitro has been made recently and promising novel test models like the human full thickness Skin models are emerging. Their full predictive value, however, needs to be further evaluated. Currently, a...
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identification of novel in vitro test systems for the determination of glucocorticoid receptor ligand induced Skin Atrophy
Skin Pharmacology and Physiology, 2010Co-Authors: Stefanie Schoepe, H Schacke, A Bernd, N Zoller, K AsadullahAbstract:Topical glucocorticoids (GCs) demonstrate good anti-inflammatory effects but are limited by their side effect potential, with Skin Atrophy being the most prominent one. Thus, determining the atrophogenic potential of novel compounds is important. The aim of this study was to establish an in vitro Skin Atrophy model. A screening cascade was applied and GCs with a known atrophogenic potential were used as tool compounds. Five rodent and human cutaneous cell types/cell lines and 2 human Skin equivalents were tested. Known and suspected Atrophy markers related to collagen metabolism and epidermal thickness were measured. Altogether, a combination of 7 different cellular assays with up to 16 markers each were investigated. A reproducible, more than 2-fold, regulation of the candidate markers by dexamethasone or clobetasol was found for: (a) matrix metalloproteinase (MMP) 1, 2, 3 and 9 expression in human keratinocytes, (b) COL1A1 and COL3A1 expression in 3T3 fibroblasts, and (c) epidermal thickness, collagen and MMP synthesis in the full-thickness Skin model (FTSM). These 3 models were further investigated with a panel of 4-5 GCs, demonstrating dose dependency and correlation with the atrophogenic potential of the tool compounds, qualifying them as potentially suitable. Finally, the predictability of these models for the in vivo situation was analyzed, testing a novel selective GC receptor agonist (SEGRA) in comparison to clobetasol. The results from the in vitro models suggested less atrophogenic effects for the SEGRA compound, which indeed was confirmed in the hr/hr rat Skin Atrophy model. In conclusion, a combination of 3 in vitro models based on 3T3 cells, human keratinocytes and FTSM with several readouts is recommended to determine atrophogenicity of GC receptor ligands. Further experiments are necessary to eventually reduce this panel and to demonstrate the true predictability for the clinic.
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glucocorticoid therapy induced Skin Atrophy
Experimental Dermatology, 2006Co-Authors: Stefanie Schoepe, Heike Schacke, Ekkehard May, Khusru AsadullahAbstract:Glucocorticoids (GCs) are highly effective for the topical treatment of inflammatory Skin diseases. Their long-term use, however, is often accompanied by severe and partially irreversible adverse effects, with Atrophy being the most prominent limitation. Progress in the understanding of GC-mediated molecular action as well as some advances in technologies to determine the atrophogenic potential of compounds has been made recently. It is likely that the detailed mechanisms of GC-induced Skin Atrophy will be discovered and in vitro models for the reliable prediction of Atrophy will be established in the foreseeable future. This knowledge will not only facilitate safety profiling of established drugs but will also foster further drug discovery by improving compound characterization processes. New insights into GC modes of action will guide optimization strategies aiming at novel GC receptor ligands with improved effect/side effect profile.
Takahiko Shimizu - One of the best experts on this subject based on the ideXlab platform.
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syringaresinol reverses age related Skin Atrophy by suppressing foxo3a mediated matrix metalloproteinase 2 activation in copper zinc superoxide dismutase deficient mice
Journal of Investigative Dermatology, 2019Co-Authors: Juewon Kim, Si Young Cho, Toshihiko Toda, Kenji Watanabe, Shuichi Shibuya, Yusuke Ozawa, Naotaka Izuo, Dae Bang Seo, Koutaro Yokote, Takahiko ShimizuAbstract:Aging is characterized by accumulation of chronic and irreversible oxidative damage, chronic inflammation, and organ dysfunction. Superoxide dismutase (SOD) serves as a major enzyme for cellular superoxide radical metabolism and physiologically regulates cellular redox balance throughout the body. Copper/zinc superoxide dismutase–deficient (SOD1–/–) mice showed diverse phenotypes associated with enhanced oxidative damage in whole organs. Here, we found that oral treatment with syringaresinol (also known as lirioresinol B), which is the active component in the berries of Korean ginseng (Panax ginseng C.A. Meyer), attenuated the age-related changes in Sod1–/– Skin. Interestingly, syringaresinol morphologically normalized Skin Atrophy in Sod1–/– mice and promoted fibroblast outgrowth from Sod1–/– Skin in vitro. These protective effects were mediated by the suppression of matrix metalloproteinase-2 overproduction in Sod1–/– Skin, but not by increased collagen expression. Syringaresinol also decreased the oxidative damage and the phosphorylation of FoxO3a protein, which was a transcriptional factor of matrix metalloproteinase–2, in Sod1–/– Skin. These results strongly suggest that syringaresinol regulates the FoxO3–matrix metalloproteinase-2 axis in oxidative damaged Skin and exhibits beneficial effects on age-related Skin involution in Sod1–/– mice.
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resveratrol derivative rich melinjo seed extract attenuates Skin Atrophy in sod1 deficient mice
Oxidative Medicine and Cellular Longevity, 2015Co-Authors: Kenji Watanabe, Shuichi Shibuya, Yusuke Ozawa, Naotaka Izuo, Takahiko ShimizuAbstract:The oxidative damages induced by a redox imbalance cause age-related changes in cells and tissues. Superoxide dismutase (SOD) enzymes play a pivotal role in the antioxidant system and they also catalyze superoxide radicals. Since the loss of cytoplasmic SOD (SOD1) resulted in aging-like phenotypes in several types of murine tissue, SOD1 is essential for the maintenance of tissue homeostasis. Melinjo (Gnetum gnemon Linn) seed extract (MSE) contains trans-resveratrol (RSV) and resveratrol derivatives, including gnetin C, gnemonoside A, and gnemonoside D. MSE intake also exerts no adverse events in human study. In the present studies, we investigated protective effects of MSE on age-related Skin pathologies in mice. Orally MSE and RSV treatment reversed the Skin thinning associated with increased oxidative damage in the Sod1−/− mice. Furthermore, MSE and RSV normalized gene expression of Col1a1 and p53 and upregulated gene expression of Sirt1 in Skin tissues. In vitro experiments revealed that RSV significantly promoted the viability of Sod1−/− fibroblasts. These finding demonstrated that RSV in MSE stably suppressed an intrinsic superoxide generation in vivo and in vitro leading to protecting Skin damages. RSV derivative-rich MSE may be a powerful food of treatment for age-related Skin diseases caused by oxidative damages.
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palladium and platinum nanoparticles attenuate aging like Skin Atrophy via antioxidant activity in mice
PLOS ONE, 2014Co-Authors: Shuichi Shibuya, Toshihiko Toda, Kenji Watanabe, Yusuke Ozawa, Naotaka Izuo, Koutaro Yokote, Takahiko ShimizuAbstract:Cu-Zn superoxide dismutase (Sod1) loss causes a redox imbalance as it leads to excess superoxide generation, which results in the appearance of various aging-related phenotypes, including Skin Atrophy. Noble metal nanoparticles, such as palladium (Pd) and platinum (Pt) nanoparticles, are considered to function as antioxidants due to their strong catalytic activity. In Japan, a mixture of Pd and Pt nanoparticles called PAPLAL has been used to treat chronic diseases over the past 60 years. In the present study, we investigated the protective effects of PAPLAL against aging-related Skin pathologies in mice. Transdermal PAPLAL treatment reversed Skin thinning associated with increased lipid peroxidation in Sod1−/− mice. Furthermore, PAPLAL normalized the gene expression levels of Col1a1, Mmp2, Has2, Tnf-α, Il-6, and p53 in the Skin of the Sod1−/− mice. Pt nanoparticles exhibited marked SOD and catalase activity, while Pd nanoparticles only displayed weak SOD and catalase activity in vitro. Although the SOD and catalase activity of the Pt nanoparticles significantly declined after they had been oxidized in air, a mixture of Pd and Pt nanoparticles continued to exhibit SOD and catalase activity after oxidation. Importantly, a mixture of Pd and Pt nanoparticles with a molar ratio of 3 or 4 to 1 continued to exhibit SOD and catalase activity after oxidation, indicating that Pd nanoparticles prevent the oxidative deterioration of Pt nanoparticles. These findings indicate that PAPLAL stably suppresses intrinsic superoxide generation both in vivo and in vitro via SOD and catalase activity. PAPLAL is a potentially powerful tool for the treatment of aging-related Skin diseases caused by oxidative damage.
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collagen peptide and vitamin c additively attenuate age related Skin Atrophy in sod1 deficient mice
Bioscience Biotechnology and Biochemistry, 2014Co-Authors: Shuichi Shibuya, Toshihiko Toda, Kenji Watanabe, Yusuke Ozawa, Chisa Tometsuka, Takayuki Ogura, Yohichi Koyama, Takahiko ShimizuAbstract:Age-related Skin thinning is correlated with a decrease in the content of collagen in the Skin. Accumulating evidence suggests that collagen peptide (CP) and vitamin C (VC) transcriptionally upregulate type I collagen in vivo. However, the additive effects of CP and VC on age-related Skin changes remain unclear. We herein demonstrate that CP and a VC derivative additively corrected age-related Skin thinning via reduced oxidative damage in superoxide dismutase 1 (Sod1)-deficient mice. Co-treatment with these compounds significantly normalized the altered gene expression of Col1a1, Has2, and Ci1, a proton-coupled oligopeptide transporter, in Sod1−/− Skin. The in vitro analyses further revealed that collagen oligopeptide, a digestive product of ingested CP, significantly promoted the bioactivity of the VC derivative with respect to the migration and proliferation of Sod1−/− fibroblasts. These findings suggest that combined treatment with CP and VC is effective in cases of age-related Skin pathology.
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Skin Atrophy in cytoplasmic SOD-deficient mice and its complete recovery using a vitamin C derivative.
Biochemical and biophysical research communications, 2009Co-Authors: Kazuma Murakami, Jun Inagaki, Mitsuru Saito, Yasutaka Ikeda, Chizuru Tsuda, Yoshihiro Noda, Satoru Kawakami, Takuji Shirasawa, Takahiko ShimizuAbstract:Intrinsic Skin ageing is characterized by Atrophy and loss of elasticity. Although the Skin hypertrophy induced by photoageing has been studied, the molecular mechanisms of Skin Atrophy during ageing remain unclear. Here, we report that copper/zinc superoxide dismutase (CuZn-SOD)-deficient mice show atrophic morphology in their Skin. This Atrophy is accompanied by the degeneration of collagen and elastic fibers, and Skin hydroxyproline is also significantly reduced in deficient mice. These imply that the dysfunction of collagen and elastin biosynthesis are involved in the progression of Skin thinning. Furthermore, transdermal administration of a vitamin C derivative which can permeate through the membrane, completely reversed the Skin thinning and deterioration of collagen and elastin in the mutant mice. These indicate that the vitamin C derivative is a powerful agent for alleviating Skin ageing through regeneration of collagen and elastin. The CuZn-SOD-deficient mice might be applicable to evaluation of therapeutic medicines against Skin ageing.
Heike Schacke - One of the best experts on this subject based on the ideXlab platform.
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shortened treatment duration of glucocorticoid induced Skin Atrophy in rats
Experimental Dermatology, 2011Co-Authors: Stefanie Schoepe, Khusru Asadullah, Heike Schacke, Richardus Vonk, Thomas M Zollner, Lars RoseAbstract:Abstract: Glucocorticoids (GCs) belong to the most widely used anti-inflammatory drugs at all. However, their topical use is limited by their side effect potential, with Skin Atrophy being the most prominent one. Thus, determining the atrophogenic potential of novel compounds is of importance for drug development. Currently, the most frequently performed model in the base and pharmaceutical research is the hr/hr rat model of GC-induced Skin Atrophy that lasts for 19 days. In this study, we analysed statistically Skin Atrophy experiments retrospectively to ascertain (i) the earliest time-point, at which Skin Atrophy is significantly induced; and (ii) whether the differences between the GC treatment groups change until the end of the experiment. We show here that the treatment duration of rat Skin Atrophy models might be reduced to 5 days for economical and ethical reasons.
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test systems for the determination of glucocorticoid receptor ligand induced Skin Atrophy
Dermato-endocrinology, 2011Co-Authors: Stefanie Schoepe, Heike Schacke, Khusru AsadullahAbstract:Topical glucocorticoids are highly anti-inflammatory effective but limited by their side effect potential, with Skin Atrophy being the most prominent one. Thus, determining the atrophogenic potential of novel compounds targeting the glucocorticoid receptor is important. Significant progress in the understanding of glucocorticoid receptor mediated molecular action has been made providing the basis for novel glucocorticoid receptor ligands with a potentially superior effect/side effect profile. Such compounds, however, need to be tested. The present gold standard for the reliable prediction of glucocorticoid induced Skin Atrophy are still in vivo models, however, in vitro models may replace them to some extent in the future. Indeed, advances in technologies to determine the atrophogenic potential of compounds in vitro has been made recently and promising novel test models like the human full thickness Skin models are emerging. Their full predictive value, however, needs to be further evaluated. Currently, a...
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superior nuclear receptor selectivity and therapeutic index of methylprednisolone aceponate versus mometasone furoate
Experimental Dermatology, 2007Co-Authors: Parham Mirshahpanah, Wolfdietrich Docke, Udo Merbold, Khusru Asadullah, Lars Rose, Heike Schacke, Thomas Matthias ZollnerAbstract:: Although introduced more than 50 years ago, topical glucocorticoids are still the first line therapy for many inflammatory Skin disorders such as atopic eczema, contact dermatitis and many others. Recently, significant improvements have been made to optimize the ratio of desired to unwanted effects. While with early compounds such as triamcinolone, topical side effects such as Skin Atrophy and telangiectasias can be observed rather frequently, newer drugs such as methylprednisolone aceponate or mometasone furoate have a significantly improved therapeutic index. The present study compared these two modern topical glucocorticoids, which possess the highest therapeutic index currently found, in terms of nuclear receptor selectivity in vitro and induction of the most important local side effects (Skin Atrophy and telangiectasias) in a relevant rodent model in vivo. We demonstrate that methylprednisolone aceponate displays higher specificity in nuclear receptor binding compared with mometasone furoate. Methylprednisolone aceponate was also markedly superior in terms of minimizing induction of Skin Atrophy or telangiectasias when compared with mometasone furoate. Based on these observations, methylprednisolone aceponate is expected to have a greater therapeutic index as compared with mometasone furoate, at least in the test systems used here. The degree to which this observation may translate into a clinical setting requires confirmation.
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glucocorticoid therapy induced Skin Atrophy
Experimental Dermatology, 2006Co-Authors: Stefanie Schoepe, Heike Schacke, Ekkehard May, Khusru AsadullahAbstract:Glucocorticoids (GCs) are highly effective for the topical treatment of inflammatory Skin diseases. Their long-term use, however, is often accompanied by severe and partially irreversible adverse effects, with Atrophy being the most prominent limitation. Progress in the understanding of GC-mediated molecular action as well as some advances in technologies to determine the atrophogenic potential of compounds has been made recently. It is likely that the detailed mechanisms of GC-induced Skin Atrophy will be discovered and in vitro models for the reliable prediction of Atrophy will be established in the foreseeable future. This knowledge will not only facilitate safety profiling of established drugs but will also foster further drug discovery by improving compound characterization processes. New insights into GC modes of action will guide optimization strategies aiming at novel GC receptor ligands with improved effect/side effect profile.
P Joly - One of the best experts on this subject based on the ideXlab platform.
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Topical corticosteroids in plaque psoriasis: a systematic review of risk of adrenal axis suppression and Skin Atrophy.
Journal of the European Academy of Dermatology and Venereology, 2012Co-Authors: E Castela, E Archier, S Devaux, A Gallini, S Aractingi, B Cribier, D Jullien, F Aubin, H Bachelez, P JolyAbstract:BACKGROUND: Topical steroids have been used for more than 50 years in mild-to-moderate plaque psoriasis and carry a theoretical risk of adverse events. OBJECTIVES: The aim of this systematic literature review was to evaluate the risk of hypothalamo-pituitary-adrenal (HPA) axis suppression and the risk of Skin Atrophy with topical steroids in the treatment of plaque psoriasis. METHODS: A systematic search between 1980 and January 2011 in Medline, Embase and Cochrane databases (English, French language, adults), using the keywords 'psoriasis'/exp/mj AND 'corticosteroid'/exp/mj, RESULTS: Altogether 1269 references were found. Of these 1124 articles were excluded by reading the abstract and 123 by reading the article. A total of 22 randomized trials were selected. Effects on HPA axis: Thirteen studies, with a sample size varying from 7 to 341 patients, were selected. The effect on HPA axis was evaluated by the morning cortisol level (11 studies), the 24 h urine steroid levels (five studies) and/or by the Synacthen test (three studies). Reduction of morning cortisol was observed in 0-25% of patients in 10 short-term studies (two in scalp psoriasis, eight in body psoriasis) and in 48% of patients in the remaining short-term study (body psoriasis). Only four of these studies with three on body psoriasis evaluated the effect of long-term treatment defined as 6-month treatment duration or longer and did not identify HPA axis suppression by cortisol level measurement. The Synacthen test, considered as the gold standard to assess HPA axis, was always normal. There was no evidence of clinically significant HPA axis suppression due to absorption of topical steroids even when treating the scalp or in patients with extensive disease. Risk of Skin Atrophy: Thirteen studies with topical steroid evaluating treatment durations from 4 weeks to 1 year were analysed. The frequency of Skin Atrophy assessed clinically, varied from 0% to 5% of patients. CONCLUSIONS: The literature analysis on topical steroids in psoriasis is reassuring although the quality of safety studies is limited with a majority of short-term studies. Although short-term biological effects of topical steroids on the HPA axis were observed in several clinical studies, they were not associated with clinical signs. Adequately designed long-term studies would be necessary to better determine the risk of Skin Atrophy using modern methods of evaluation such as dermoscopy and echography.
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topical corticosteroids in plaque psoriasis a systematic review of risk of adrenal axis suppression and Skin Atrophy
Journal of The European Academy of Dermatology and Venereology, 2012Co-Authors: E Castela, E Archier, S Devaux, A Gallini, S Aractingi, B Cribier, D Jullien, F Aubin, H Bachelez, P JolyAbstract:Background Topical steroids have been used for more than 50 years in mild-to-moderate plaque psoriasis and carry a theoretical risk of adverse events. Objectives The aim of this systematic literature review was to evaluate the risk of hypothalamo-pituitary-adrenal (HPA) axis suppression and the risk of Skin Atrophy with topical steroids in the treatment of plaque psoriasis. Methods A systematic search between 1980 and January 2011 in Medline, Embase and Cochrane databases (English, French language, adults), using the keywords ‘psoriasis’/exp/mj AND ‘corticosteroid’/exp/mj, Results Altogether 1269 references were found. Of these 1124 articles were excluded by reading the abstract and 123 by reading the article. A total of 22 randomized trials were selected. Effects on HPA axis: Thirteen studies, with a sample size varying from 7 to 341 patients, were selected. The effect on HPA axis was evaluated by the morning cortisol level (11 studies), the 24 h urine steroid levels (five studies) and/or by the Synacthen® test (three studies). Reduction of morning cortisol was observed in 0–25% of patients in 10 short-term studies (two in scalp psoriasis, eight in body psoriasis) and in 48% of patients in the remaining short-term study (body psoriasis). Only four of these studies with three on body psoriasis evaluated the effect of long-term treatment defined as 6-month treatment duration or longer and did not identify HPA axis suppression by cortisol level measurement. The Synacthen® test, considered as the gold standard to assess HPA axis, was always normal. There was no evidence of clinically significant HPA axis suppression due to absorption of topical steroids even when treating the scalp or in patients with extensive disease. Risk of Skin Atrophy: Thirteen studies with topical steroid evaluating treatment durations from 4 weeks to 1 year were analysed. The frequency of Skin Atrophy assessed clinically, varied from 0% to 5% of patients. Conclusions The literature analysis on topical steroids in psoriasis is reassuring although the quality of safety studies is limited with a majority of short-term studies. Although short-term biological effects of topical steroids on the HPA axis were observed in several clinical studies, they were not associated with clinical signs. Adequately designed long-term studies would be necessary to better determine the risk of Skin Atrophy using modern methods of evaluation such as dermoscopy and echography.
