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BACKGROUND: Mesenchymal stem cells (MSCs) play important roles in therapeutic applications by regulating immune responses. OBJECTIVE: We investigated the safety and efficacy of allogenic human bone marrow-derived clonal MSCs (hcMSCs) in subjects with moderate to severe atopic dermatitis (AD). METHODS: The study included a phase 1 open-label trial followed by a phase 2 randomized, double-blind, placebo-controlled trial that involved 72 subjects with moderate to severe AD. RESULTS: In phase 1, intravenous administration of hcMSCs at 2 doses (1 × 106 and 5 × 105 cells/kg) was safe and well tolerated in 20 subjects. Because there was no difference between the 2 dosage groups (P = .9), it was decided to administer low-dose hcMSCs only for phase 2. In phase 2, subjects receiving 3 weekly intravenous infusions of hcMSCs at 5 × 105 cells/kg showed a higher proportion of an Eczema Area and Severity Index (EASI)-50 response at week 12 compared to the placebo group (P = .038). The differences between groups in the Dermatology Life Quality Index and pruritus numeric rating scale scores were not statistically significant. Most adverse events were mild or moderate and resolved by the end of the study period. CONCLUSIONS: The hcMSC treatment resulted in a significantly higher rate of EASI-50 at 12 weeks compared to the control group in subjects with moderate to severe AD. The safety profile of hcMSC treatment was acceptable. Further larger-scale studies are necessary to confirm these preliminary findings.
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Skin barrier dysfunction induces skin inflammation. Signal transducer and activator of transcription 3 (STAT3) is known to be involved in Th17-mediated immune responses and barrier integrity in the cornea and intestine; however, its role in the skin barrier remains largely unknown. In this study, we elucidated the potential role of STAT3 in the skin barrier and its effect on kallikrein-related peptidase 5 (KLK5) and serine protease inhibitor Kazal-type 5 (SPINK5) expression using a mouse model with keratinocyte-specific ablation of STAT3. Keratinocyte-specific loss of STAT3 induced a cutaneous inflammatory phenotype with pruritus and intense scratching behaviour in mice. Transcriptomic analysis revealed that the genes associated with impaired skin barrier function, including KLK5, were upregulated. The effect of STAT3 on KLK5 expression in keratinocytes was not only substantiated by the increase in KLK5 expression following treatment with STAT3 siRNA but also by its decreased expression following STAT3 overexpression. Overexpression and IL-17A-mediated stimulation of STAT3 increased the expression of SPINK5, which was blocked by STAT3 siRNA. These results suggest that the expression of SPINK5 and KLK5 in keratinocytes could be dependent on STAT3 and that STAT3 might play an essential role in the maintenance of skin barrier homeostasis.
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Calicreínas , Fator de Transcrição STAT3 , Calicreínas/genética , Calicreínas/metabolismo , Queratinócitos/metabolismo , RNA Interferente Pequeno/genética , Fator de Transcrição STAT3/metabolismo , Inibidor de Serinopeptidase do Tipo Kazal 5/genéticaRESUMO
Environmentally hazardous substances and exposure to these can cause various diseases. Volatile organic compounds can easily evaporate into the atmosphere, thereby exerting toxic effects through either the skin or respiratory tract exposures. Toluene, a neurotoxin, has been widely used in various industries. However, it has a detrimental effect on the nervous system (such as hallucinations or memory impairment), while data on the mechanism underlaying its harmful effects remain limited. Therefore, this study investigates the effect of toluene on the nervous system via epigenetic and genetic changes of toluene-exposed individuals. We identified significant epigenetic changes and confirmed that the affected abnormally expressed genes negatively influenced the nervous system. In particular, we confirmed that the miR-15 family, upregulated by toluene, downregulated ABL2, which could affect the R as signaling pathway resulting in neuronal structural abnormalities. Our study suggests that miR-15a-5p, miR-15b-5p, miR-16-5p, miR-301a-3p, and lncRNA NEAT1 may represent effective epigenomic markers associated with neurodegenerative diseases caused by toluene.
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MicroRNAs , Doenças do Sistema Nervoso , RNA Longo não Codificante , Epigênese Genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Doenças do Sistema Nervoso/genética , RNA Longo não Codificante/genética , Transdução de SinaisRESUMO
Humans are easily exposed to environmentally hazardous factors in industrial sites or daily life. In addition, exposure to various substances and not just one harmful substance is common. However, research on the effects of combined exposure on humans is limited. Therefore, this study examined the effects of combined exposure to volatile organic compounds (VOCs) on the human body. We separated 193 participants into four groups according to their work-related exposure (nonexposure, toluene exposure, toluene and xylene exposure, and toluene, ethylbenzene, and xylene exposure). We then identified the methylation level and long noncoding RNA (lncRNA) levels by omics analyses, and performed an integrated analysis to examine the change of gene expression. Thereafter, the effects of combined exposure to environmental hazards on the human body were investigated and analyzed. Exposure to VOCs was found to negatively affect the development and maintenance of the nervous system. In particular, the MALAT1 lncRNA was found to be significantly reduced in the complex exposure group, and eight genes were significantly downregulated by DNA hypermethylation. The downregulation of these genes could cause a possible decrease in the density of synapses as well as the number and density of dendrites and spines. In summary, we found that increased combined exposure to environmental hazards could lead to additional epigenetic changes, and consequently abnormal dendrites, spines, and synapses, which could damage motor learning or spatial memory. Thus, lncRNA MALAT1 or FMR1 could be novel biomarkers of neurotoxicity to identify the negative health effects of VOC complex exposure.
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Poluentes Atmosféricos , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , Metilação de DNA , Exposição Ambiental/análise , Monitoramento Ambiental , Epigênese Genética , Proteína do X Frágil da Deficiência Intelectual , Humanos , Tolueno/análise , Tolueno/toxicidade , Compostos Orgânicos Voláteis/toxicidade , XilenosRESUMO
Hypoxia-inducible factor-1α (HIF-1α) has been reported to be up-regulated in psoriatic epidermis, resulting in increased proliferation and abnormal differentiation of human keratinocytes (KCs). However, the role of HIF-1α in psoriatic epidermis, which is mainly composed of KCs, is poorly understood. Here, we show that morphogenic protein 6 (BMP6) is down-regulated when HIF-1α is upregulated in patients with psoriasis skin lesions. HIF-1α overexpression in primary human KCs promoted proliferation and inhibited terminal differentiation. Furthermore, HIF1-α repressed the expression of BMP6 by binding directly to the hypoxia-response element (HRE) in the BMP6 promotor region, which shows that BMP6 is a novel target gene of HIF-1α. We also found that HIF-1α-mediated BMP6 suppression could alter the proliferation status by modulating the expression levels of cell cycle regulatory proteins and also affect the early differentiation of KCs. Therefore, we suggest that HIF-1α-dependent BMP6 suppression has a critical role in the induction of hyper-proliferation and abnormal differentiation in psoriatic KCs.
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Proteína Morfogenética Óssea 6/metabolismo , Diferenciação Celular/genética , Proliferação de Células/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Psoríase/genética , Antígenos de Neoplasias/metabolismo , Proteína Morfogenética Óssea 6/farmacologia , Anidrase Carbônica IX/metabolismo , Ciclo Celular/genética , Diferenciação Celular/efeitos dos fármacos , Hipóxia Celular , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Regulação para Baixo , Transportador de Glucose Tipo 1/metabolismo , Humanos , Queratinócitos/fisiologia , Cultura Primária de Células , Regiões Promotoras Genéticas , Psoríase/metabolismo , TransfecçãoRESUMO
The receptor-interacting protein kinase 4 (RIP4), a serine/threonine kinase, is an important modulator of epidermal growth and cutaneous inflammation. We found that RIP4 expression was significantly increased in the lesional skin of psoriasis. However, the role and regulatory mechanism of RIP4 in psoriasis have not been characterized. After treatment with IL-17, RIP4 mRNA and protein levels were increased in HaCaT cells. IL-17 also activated the RIP4 promoter. To understand the functional role of RIP4 in keratinocyte and to investigate the genes regulated by RIP4, RNA-based microarray analysis was performed. Among immune response-related genes, CCL20 expression was significantly changed by RIP4. To identify RIP4-interacting protein, an immunoprecipitation assay was performed. As a result, STAT3 was identified as a new protein that interacts with RIP4. The interaction of RIP4 and STAT3 enhanced STAT3 phosphorylation. In addition, the transcriptional activity of STAT3 induced by RIP4 regulated IL-17-mediated CCL20 expression in HaCaT cells. Taken together, these findings indicate that IL-17 increased RIP4-mediated STAT3 phosphorylation by directly interacting with STAT3. Thus, transcriptional activation of STAT3 promotes the expression of CCL20. Thus, activations of these signalling pathways by RIP4 may contribute to epithermal inflammation in psoriatic keratinocytes.
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Quimiocina CCL20/genética , Interleucina-17/farmacologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Psoríase/genética , Fator de Transcrição STAT3/metabolismo , Adulto , Células HEK293 , Humanos , Queratinócitos , Análise de Sequência com Séries de Oligonucleotídeos , Fosforilação , Regiões Promotoras Genéticas/efeitos dos fármacos , Psoríase/metabolismo , Psoríase/patologia , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Fator de Transcrição STAT3/genética , Transcrição Gênica , Regulação para Cima/efeitos dos fármacosRESUMO
Quantum dots (QDs) have shown great potential for biomedical use in a broad range including diagnostic agents. However, the regulatory mechanism of dermal toxicity is poorly understood. In this study, we investigated how QDs-induced apoptosis is regulated in human keratinocytes. We also examined the effect of carboxylic acid-coated QDs (QD 565 and QD 655) on reactive oxygen species (ROS) production and apoptosis-related cellular signalling. The viability of keratinocyte was inhibited by two types of QDs in a concentration-dependent manner. QDs induce ROS production and blockade of AKT phosphorylation. Moreover, the cleavage of AKT-dependent pro-apoptotic proteins such as poly (ADP-ribose) polymerase, caspases-3 and caspases-9 was significantly increased. We also found that a decrease in cellular ROS level by ROS scavenger, N-acetylcysteine (NAC), resulting in the abolishment of QDs-induced AKT de-phosphorylation and cellular apoptosis. Interestingly, QD 655 had a more cytotoxic effect including oxidative stress and AKT-dependent apoptosis than QD 565. In addition, QD 655 had the cytotoxic potential in the human skin equivalent model (HSEM). These data show that QD-induced intracellular ROS levels may be an important parameter in QD-induced apoptosis. These findings from this study indicate that intracellular ROS levels might determine the apoptotic potential of keratinocyte by QD via blockade of AKT phosphorylation.
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Apoptose , Epiderme/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pontos Quânticos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Acetilcisteína/farmacologia , Apoptose/efeitos dos fármacos , Ácidos Carboxílicos , Caspase 3/metabolismo , Caspase 9/metabolismo , Sobrevivência Celular , Células Cultivadas , Humanos , Queratinócitos/metabolismo , Fosforilação , Poli(ADP-Ribose) Polimerases/metabolismo , Pontos Quânticos/química , Transdução de SinaisRESUMO
The emission of volatile organic compounds (VOCs) resulting from outdoor air pollution can contribute to major public health problems. However, there has been limited research on the health effects in humans from the inhalation of VOCs. Therefore, this study conducted an in vivo analysis of the effects of toluene, one of the most commonly used chemicals in many industries, on gene expression and methylation over time using the high-throughput technique of microarray analysis. We separated participants into three groups (control, short-term exposure, and long-term exposure) to investigate the influence of toluene exposure time on gene expression. We then comprehensively analyzed and investigated the correlation between variations in gene expression and the occurrence of methylation. Twenty-six genes were upregulated and hypomethylated, while 32 genes were downregulated and hypermethylated. The pathways of these genes were confirmed to be associated with cell survival and the immune system. Based on our findings, these genes can help predict the effects of time-dependent exposure to toluene on human health. Thus, observations from our data may have implications for the identification of biomarkers of toluene exposure.
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Poluentes Atmosféricos/análise , Exposição Ambiental , Regulação da Expressão Gênica/efeitos dos fármacos , Exposição por Inalação , Metilação/efeitos dos fármacos , Exposição Ocupacional , Tolueno/análise , Adulto , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , República da Coreia , Fatores de Tempo , Adulto JovemRESUMO
Volatile organic compounds (VOCs) can be easily taken up by humans, leading to various diseases, such as respiratory system and central nervous system disorders. Environmental risk assessment is generally conducted using traditional tests, which may be time-consuming and technically challenging. Therefore, analysis of the effects of VOCs, such as toluene, ethylbenzene, and xylene, may be improved by use of novel, high-throughput methods, such as microarray analysis. In this study, we examined the effects of VOCs exposure in humans on gene expression and methylation using microarray analysis. We recruited participants who had short-term exposure, long-term exposure, or no exposure. We then analyzed changes in gene expression in blood samples from these participants. A total of 866 genes were upregulated, while 366 genes were downregulated in the short-term exposure group. Similarly, in the long-term exposure group, a total of 852 and 480 genes were up- or downregulated, respectively. Hierarchical clustering analysis was used to divide the clustered genes into nine clusters to investigate the expression of variations in accordance with the exposure period. And the methylation microarray was performed at the same time to see whether this expression variation is related to the epigenetic study. Finally, we have 5 genes that were upregulated and 12 genes that were downregulated, gradually and respectively, so these genes are expected to function as biomarkers of the duration of exposure to VOCs. Further research is required to determine the time-dependent effects of VOCs on epigenetic regulation of gene expression. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1563-1570, 2016.
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Poluentes Ambientais/toxicidade , Compostos Orgânicos Voláteis/toxicidade , Biomarcadores/análise , Epigênese Genética/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Ensaios de Triagem em Larga Escala , Humanos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Fatores de TempoRESUMO
Atopic dermatitis (AD) is a chronic inflammatory skin disease in which T-helper type 2 (Th2)-type immune responses are dominant. Th2 cytokine, interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) have been suggested to have an important role in AD. IL-33 is highly expressed in AD, but its role in AD has not yet been fully understood. To further identify the role of IL-33 in AD, we investigated the expression of TSLP induced by IL-33 in keratinocytes. This study revealed that IL-33 induced TSLP expression in human keratinocytes. Early growth response protein 1 (Egr)-1, which is an inflammatory transcriptional factor, is induced by IL-33. IL-33-mediated TSLP induction in keratinocytes was suppressed by treatment with mitogen-activated protein kinase (MAPK) inhibitors or small interfering RNA against Egr-1. Chromatin immunoprecipitation (ChIP) assay indicated the direct involvement of Egr-1 in IL-33-mediated TSLP induction. Taken together, these findings indicate that IL-33 may increase TSLP expression through an Egr-1-dependent mechanism via ERK1/2, JNK and p38 activation in keratinocytes. These data suggest that the IL-33-ERK/JNK/p38/Egr-1/TSLP axis is involved in allergic skin Th2 inflammation, and it may be a novel therapeutic target.
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Citocinas/metabolismo , Dermatite Atópica/metabolismo , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Interleucina-33/fisiologia , Queratinócitos/metabolismo , Sistema de Sinalização das MAP Quinases , Células Cultivadas , Dermatite Atópica/etiologia , Humanos , Linfopoietina do Estroma do TimoRESUMO
We conducted a 16-week double-blind randomized controlled single-center trial to evaluate the safety and efficacy of dermal rice bran supercritical CO2 extract (RB-SCE) in the treatment of androgenic alopecia. Fifty alopecia patients were randomly assigned to the experimental and placebo groups. The experimental group received a dermal application of 0.5% RB-SCE (8 mL/d) to the head skin for 16 weeks while the control group received a dermal application of placebo. Changes in hair count, diameter, and density were evaluated with a Folliscope(®). Patient satisfaction was evaluated via questionnaire and clinical photographs were rated by dermatologists. The results showed that RB-SCE significantly increased hair density and hair diameter in male subjects. Patient satisfaction and the evaluation of photographs by dermatologists also confirmed the effectiveness of RB-SCE in the treatment of alopecia. No adverse reactions related to RB-SCE were reported. Therefore, RB-SCE shows promise for use in functional cosmetics and pharmaceuticals.
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Alopecia/tratamento farmacológico , Cabelo/efeitos dos fármacos , Oryza , Fitoterapia , Extratos Vegetais/uso terapêutico , Sementes/química , Adulto , Método Duplo-Cego , Feminino , Cabelo/crescimento & desenvolvimento , Humanos , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/farmacologiaRESUMO
The early growth response (Egr)-1 is a transcriptional factor which plays an important role in the regulation of cell growth, differentiation, cell survival and immune responses. Emerging evidences including our data demonstrate that the Egr-1 expression is up-regulated in the psoriatic skin lesions. The purpose of this study was to investigate the significance and regulatory mechanism of Egr-1 in the pathogenesis of psoriasis. Through microarray analysis, we found out that psoriasin (S100A7) expression was increased in the Egr-1 overexpressed cells. Our results showed that IL-17A increased Egr-1 expression in the skin of psoriatic patients and cultured human keratinocytes. We then investigated activation of mitogen-activated protein kinase as an upstream signal regulator of Egr-1 expression. IL-17A-induced Egr-1 expression was suppressed by ERK inhibitor. In addition, IL-17A induced psoriasin expression in cultured keratinocytes and the skin of IL-17A intradermally injected mouse. IL-17A-mediated psoriasin upregulation was reduced after treatment of small interfering RNAs against Egr-1. Furthermore, the results of chromatin immunoprecipitation assays demonstrated that Egr-1 directly binds the psoriasin promoter. Our findings present a novel signalling mechanism by which IL-17A can induce the Egr-1-dependent psoriasin expression via the ERK pathway in human keratinocytes. This study suggests that Egr-1 may be a novel and important modulator in IL-17A-mediated immune response in psoriasis.
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Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Interleucina-17/metabolismo , Psoríase/etiologia , Proteínas S100/genética , Animais , Linhagem Celular , Proteína 1 de Resposta de Crescimento Precoce/antagonistas & inibidores , Proteína 1 de Resposta de Crescimento Precoce/genética , Feminino , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Queratinócitos/imunologia , Queratinócitos/metabolismo , Queratinócitos/patologia , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos BALB C , Psoríase/imunologia , Psoríase/metabolismo , Proteína A7 Ligante de Cálcio S100 , Regulação para CimaAssuntos
Carcinoma Basocelular/etnologia , Carcinoma Basocelular/patologia , Hiperpigmentação/patologia , Neoplasias Cutâneas/etnologia , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/estatística & dados numéricos , Carcinoma Basocelular/cirurgia , Estudos de Coortes , Feminino , Humanos , Hiperpigmentação/etnologia , Hiperpigmentação/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Cirurgia de Mohs/métodos , Análise Multivariada , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Medição de Risco , Neoplasias Cutâneas/cirurgia , Carga TumoralRESUMO
The potential hair growth-promoting activity of rice bran supercritical CO2 extract (RB-SCE) and major components of RB-SCE, linoleic acid, policosanol, γ-oryzanol, and γ-tocotrienol, were evaluated with the histological morphology and mRNA expression levels of cell growth factors using real-time reverse transcriptase-polymerase chain reaction (PCR) in C57BL/6 mice. RB-SCE showed hair growth-promoting potential to a similar extent as 3% minoxidil, showing that the hair follicles were induced to be in the anagen stage. The numbers of the hair follicles were significantly increased. In addition, mRNA expression levels of vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and keratinocyte growth factor (KGF) were also significantly increased and that of transforming growth factor-ß (TGF-ß) decreased in RB-SCE-treated groups. Among the major components of RB-SCE, linoleic acid and γ-oryzanol induced the formation of hair follicles according to examination of histological morphology and mRNA expression levels of cell growth factors. In conclusion, our results demonstrate that RB-SCE, particularly linoleic acid and γ-oryzanol, promotes hair growth and suggests RB-SCE can be applied as hair loss treatment.
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Alopecia/metabolismo , Folículo Piloso/efeitos dos fármacos , Cabelo/efeitos dos fármacos , Ácido Linoleico/farmacologia , Oryza/química , Fenilpropionatos/farmacologia , Extratos Vegetais/farmacologia , Alopecia/tratamento farmacológico , Alopecia/genética , Animais , Fator 7 de Crescimento de Fibroblastos/genética , Fator 7 de Crescimento de Fibroblastos/metabolismo , Cabelo/crescimento & desenvolvimento , Ácido Linoleico/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Fenilpropionatos/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , RNA Mensageiro/metabolismo , Sementes/química , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Autologous fat injection is widely used procedure for various functional and aesthetic purposes. However, it could result in many immediate or delayed complications including dystrophic calcifications. Almost all of the case reports about dystrophic calcification after autologous fat injection were result from the iatrogenic tissue trauma of breast augmentation. This is a report of a 30-year-old patient who developed pathologically proven multiple dystrophic calcifications on the face after autologous fat injection.
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Tecido Adiposo , Calcinose/etiologia , Técnicas Cosméticas/efeitos adversos , Face , Complicações Pós-Operatórias/etiologia , Adulto , Calcinose/radioterapia , Feminino , Humanos , Lasers de Gás/uso terapêutico , Terapia com Luz de Baixa Intensidade , Complicações Pós-Operatórias/radioterapia , Transplante AutólogoRESUMO
Dupilumab is a biologic medication that is used for the treatment of moderate-to-severe atopic dermatitis (AD). Long-term data on dupilumab drug survival in Asia patients with AD are limited. A single-center, retrospective study was performed to assess drug survival between March 2019 and March 2023. Drug survival and associated characteristics were analyzed using Kaplan-Meier survival curves and multivariate Cox regression analysis, respectively. A total of 124 patients with AD (Mean age [standard deviation], 26.0 [8.6] years) with a 4 years-overall dupilumab drug survival rate of 87.9%, were included in this study. Characteristics associated with shorter drug survival were the low eczema area and severity index (EASI) scores at baseline (hazard ratio [HR] 0.84; 95% confidence interval [CI] 0.75-0.94, p-value = 0.003) and non-insurance coverage of dupilumab (HR 11.87; 95% CI 3.28-42.99, p-value = 0.001). This retrospective study demonstrated good overall 4-year dupilumab survival (87.6%) in South Korea. Patients with low baseline EASI scores and those who did not have insurance for dupilumab treatment discontinued the therapy frequently. To the best of our knowledge, this is the first long-term dupilumab drug survival study conducted in Asia with predictors.
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Anticorpos Monoclonais Humanizados , Dermatite Atópica , Humanos , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/mortalidade , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Masculino , Estudos Retrospectivos , Adulto , República da Coreia , Adulto Jovem , Índice de Gravidade de Doença , Adolescente , Estimativa de Kaplan-Meier , Resultado do Tratamento , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Cyclosporine (CS) is a first-line immunosuppressive agent used to manage moderate to severe atopic dermatitis (AD). To date, the risk of developing hypertension associated with the long-term use of low-dose CS in AD patients is understudied. OBJECTIVE: To determine the cumulative dose-dependent effect of CS on the risk of developing hypertension in patients with AD. METHODS: A nationwide population-based retrospective cohort with 1,844,009 AD patients was built from the Korean National Health Insurance System database from 2005 to 2009. A Cox proportional-hazard regression analysis was performed according to patients' CS treatment history adjusted for potential confounders. RESULTS: Current use of CS was associated with an increased risk of developing hypertension (adjusted hazard ratio, 4.442; 95% confidence interval, 3.761-5.247). Among the current CS users, a higher cumulative dose of CS (≥39,725 mg) or longer cumulative use of CS (≥182 days), was significantly associated with an increased risk of developing hypertension. CONCLUSION: The incidence of CS-associated hypertension is very low when using low-dose treatment regimens for AD. However, the current use or a high cumulative dose of CS for treating patients with AD increases the risk of developing hypertension. Precaution is needed when prescribing CS for long-term treatment of AD.
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INTRODUCTION: The burden of atopic dermatitis (AD) is significant, with a substantial impact on quality of life (QoL). This cross-sectional study aimed to ascertain the burden of AD, its impact on QoL, and associated costs. METHODS: Patients with moderate-to-severe AD were enrolled from eight territories, namely Hong Kong, India, Japan, Mainland China, Singapore, South Korea, Taiwan, and Thailand. After screening was performed and informed consent was obtained, eligible participants were asked to provide responses on their AD symptoms, severity, treatment, and out-of-pocket costs via an online survey. QoL was assessed using EQ-5D-5L and Dermatology Life Quality Index (DLQI), while productivity loss was quantified using the Work Productivity and Activity Impairment (WPAI) questionnaire. Data from completed submissions were analyzed using descriptive statistics. The study was reviewed by the institutional review board in each territory. RESULTS: Median age of enrolled patients (N = 1103) was 41.0 years (interquartile range, IQR 16.0). The majority of patients reported that their head/neck, trunk, upper limbs, and lower limbs were affected during a flare. Topical (74.2%) and oral steroids (58.7%) were frequently prescribed to manage AD. Common atopic comorbidities were allergic urticaria (64.2%), allergic rhinitis (61.8%), and allergic conjunctivitis (51.5%). Median DLQI score was 13.0 (IQR 11.0), while median EQ-5D-5L (based on China value set) score was 0.8 (IQR 0.4); 87.2% and 77.2% of patients reported pain/discomfort and anxiety/depression on the EQ-5D-5L domains, respectively. Median total annual costs associated with AD were USD 10,128.52 (IQR 12,963.26) per patient, with indirect costs being the largest component. Findings from WPAI indicated that presenteeism is a major contributor to productivity loss. CONCLUSION: This multinational survey study showed that AD is associated with substantial QoL impairment and economic burden among Asian adult patients with moderate-to-severe AD. To alleviate burden of AD, clinicians should be more proactive in managing other concomitant conditions including psychological issues, and advocate for increased reimbursement for AD treatments.
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INTRODUCTION: Limited evidence is available on real-world management of atopic dermatitis (AD) among Asian adults. This cross-sectional study aimed to assess current approaches in AD diagnosis and management in Asia. METHODS: Practising dermatologists regularly treating patients with moderate-to-severe AD were recruited from eight Asia-Pacific territories, namely Mainland China, Hong Kong, India, Japan, Singapore, South Korea, Taiwan, and Thailand. A survey was administered to eligible dermatologists after screening and taking informed consent. Data from fully completed submissions were analysed using descriptive statistics. The study was reviewed by the institutional review board in each territory. RESULTS: Data from 271 dermatologists were included for analysis. About one-third (31.7%) reported that they referred to the Hanifin and Rajka criteria during diagnosis. The majority of dermatologists used clinical impression when assessing AD severity and treatment response. Reduction of eczema and pruritus was the primary treatment objective when managing both acute (98.1%) and chronic (69.1%) AD. More than half of dermatologists preferred adding systemic anti-inflammatory medication for patients who did not respond to maximized topical treatment, while 43.6% would switch to another systemic medication for those failing to respond to maximized systemic treatment. Topical corticosteroids were frequently selected by dermatologists. For systemic therapies, oral corticosteroids were most frequently used, followed by cyclosporin and dupilumab. Narrow-band ultraviolet B was the most common phototherapy reported (84.9%). There was considerable variation in estimated average and maximum durations of therapies used to treat AD. CONCLUSION: This study has provided insights on the real-world management of moderate-to-severe AD in the Asia-Pacific region. The diverse approaches in diagnosis and treatment highlight the multifactorial nature of AD, reliance on clinical judgement, and importance of personalized care. To improve outcomes in patients with AD, it will be crucial to develop biomarkers for diagnosis, reduce subjectivity in assessment, as well as promote access to newer and effective therapies.
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INTRODUCTION: It remains unclear how patients with atopic dermatitis (AD) and clinicians perceive the level of patient-clinician communication and if there could be potential lapses. This cross-sectional study aims to compare perspectives between patients with AD and dermatologists regarding communication and treatment expectations in Asia. METHODS: Moderate-to-severe patients with AD and practicing dermatologists were recruited from eight Asia-Pacific territories, including Mainland China, Hong Kong, India, Japan, Singapore, South Korea, Taiwan, and Thailand. Patients and dermatologists completed separate surveys designed to elicit their expectations regarding AD management, and their perceived level of patient-clinician communication. Patients were also asked about their treatment satisfaction and whether they prefer additional treatment beyond what was prescribed. Demographic information and responses were analyzed using descriptive statistics. The study was reviewed by the institutional review board in each territory, and all participants provided informed consent. RESULTS: A total of 1103 patients and 271 dermatologists completed the surveys. Both patients and dermatologists were largely aligned in their top treatment goals in AD management. However, greater proportions of patients prioritized the prevention of exacerbation (78.0% versus 47.2%), minimization of treatment adverse effects (46.4% versus 9.1%), and improvement in mental health (16.0% versus 4.9%), compared with dermatologists. Although patient-clinician communication was observed to be generally good, 10.9% of patients reported dissatisfaction with communication in AD management. The majority of patients were either "very satisfied" or "satisfied" with their latest acute AD treatment, but 65.5% of patients still desired additional treatment. CONCLUSIONS: This multinational study has provided insights on the perspectives of Asian patients and dermatologists in treatment goals, AD management, and communication. In general, both patients and dermatologists were aligned in treatment goals and there was satisfactory patient-clinician communication in most aspects. However, potential areas of improvement have been identified to further enhance patient-centered care.