RESUMO
Inflammation resolution is an essential process for preventing the development of chronic inflammatory diseases. However, the mechanisms that regulate inflammation resolution in psoriasis are not well understood. Here, we report that ANKRD22 is an endogenous negative orchestrator of psoriasiform inflammation because ANKRD22-deficient mice are more susceptible to IMQ-induced psoriasiform inflammation. Mechanistically, ANKRD22 deficiency leads to excessive activation of the TNFRII-NIK-mediated noncanonical NF-κB signaling pathway, resulting in the hyperproduction of IL-23 in DCs. This is due to ANKRD22 being a negative feedback regulator for NIK because it physically binds to and assists in the degradation of accumulated NIK. Clinically, ANKRD22 is negatively associated with IL-23A expression and psoriasis severity. Of greater significance, subcutaneous administration of an AAV carrying ANKRD22-overexpression vector effectively hastens the resolution of psoriasiform skin inflammation. Our findings suggest ANKRD22, an endogenous supervisor of NIK, is responsible for inflammation resolution in psoriasis, and may be explored in the context of psoriasis therapy.
Assuntos
Modelos Animais de Doenças , Interleucina-23 , Psoríase , Transdução de Sinais , Psoríase/metabolismo , Psoríase/patologia , Psoríase/terapia , Psoríase/etiologia , Psoríase/imunologia , Psoríase/genética , Psoríase/induzido quimicamente , Animais , Camundongos , Interleucina-23/metabolismo , Interleucina-23/genética , Humanos , Inflamação/metabolismo , Inflamação/patologia , Camundongos Knockout , Pele/patologia , Pele/metabolismo , Quinase Induzida por NF-kappaB , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , NF-kappa B/metabolismoRESUMO
BACKGROUND: High salt intake may play a critical role in the etiology of psoriasis. Yet, evidence on the association of high salt intake with risk of psoriasis is limited. OBJECTIVE: To estimate the association between frequency of adding salt to foods and risk of psoriasis. METHODS: We conducted a prospective cohort study of 433,788 participants from the UK Biobank. Hazard ratios (HRs) and their 95 % confidence intervals (CIs) for risk of psoriasis in relation to frequency of adding salt to foods were estimated using multivariable Cox proportional hazards models. We further evaluated the joint association of adding salt to foods and genetic susceptibility with risk of psoriasis. We conducted a mediation analysis to assess how much of the effect of adding salt to foods on risk of psoriasis was mediated through several selected mediators. RESULTS: During a median of 14.0 years of follow-up, 4279 incident cases of psoriasis were identified. In the multivariable-adjusted model, a higher frequency of adding salt to foods was significantly associated with an increased risk of psoriasis ("always" versus "never/rarely" adding salt to foods, HR = 1.25, 95 % CI: 1.10, 1.41). The observed positive association was generally similar across subgroups. In the joint association analysis, we observed that participants with a high genetic risk (above the second tertile) and the highest frequency of adding salt to foods experienced 149 % higher risk of psoriasis, when compared with participants with a low genetic risk (below the first tertile) and the lowest frequency of adding salt to foods (HR = 2.49, 95 % CI: 2.05, 3.02). Mediation analysis revealed that 1.8 %-3.2 % of the positive association between frequency of adding salt and risk of psoriasis was statistically significantly mediated by obesity and inflammatory biomarkers such as C-reactive protein and systemic immune-inflammation index (all P values < 0.004). CONCLUSIONS: Our study demonstrated a positive association between frequency of adding salt to foods and risk of psoriasis. The positive association was independent of multiple other risk factors, and may be partially mediated through obesity and inflammation.
Assuntos
Psoríase , Cloreto de Sódio na Dieta , Humanos , Psoríase/epidemiologia , Psoríase/etiologia , Estudos Prospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Cloreto de Sódio na Dieta/efeitos adversos , Adulto , Fatores de Risco , Idoso , Modelos de Riscos Proporcionais , Reino Unido/epidemiologia , Predisposição Genética para Doença , Incidência , SeguimentosRESUMO
BACKGROUND: Smoking is a known risk factor for psoriasis; however, the impact of smoking cessation on psoriasis has seldom been evaluated. OBJECTIVES: We aimed to examine the effects of smoking cessation on the development of psoriasis vulgaris (PsV), palmoplantar pustulosis (PPP) and generalized pustular psoriasis (GPP). METHODS: Using the Korean National Health Insurance Service database, we retrospectively compiled a cohort of 5 784 973 participants without psoriasis, analysed their changes in smoking status from 2004 to 2007 and followed up new cases of psoriasis until 2021. The psoriasis risks were compared with those of sustained smokers, smoking quitters, sustained ex-smokers and never smokers using multivariate Cox proportional hazard models. RESULTS: The mean age of the participants was 47.1â years (SD 13.5) and 3 092 426 (53.5%) were male. During 77 990 688 person-years, 67 364 psoriasis cases were identified. Compared with sustained smokers, smoking quitters showed a reduced risk of developing psoriasis [adjusted hazard ratio (aHR) 0.91; 95% confidence interval (CI) 0.87-0.95], specifically PsV (aHR 0.92; 95% CI 0.88-0.97) and PPP (aHR 0.71; 95% CI 0.63-0.79). The reduction in risk due to smoking cessation was more prominent in sustained ex-smokers (psoriasis: aHR 0.77, 95% CI 0.74-0.79; PsV: aHR 0.76, 95% CI 0.73-0.79; PPP: aHR 0.56, 95% CI 0.51-0.61; GPP: aHR 0.64; 95% CI 0.52-0.78). When conducting sensitivity analyses to address the potential for changes in smoking habits after 2007, the results and trends were consistent with the main findings, and a more pronounced significance was observed. CONCLUSIONS: Compared with continuous smoking, smoking cessation was associated with a decreased risk of developing psoriasis. The risk-reducing effect of smoking cessation was more pronounced in those maintaining a smoke-free status. Smoking cessation and the maintenance of a smoke-free status should be encouraged to prevent the development of psoriasis and all other smoking-related diseases.
Psoriasis vulgaris (PsV) is a chronic inflammatory skin condition that causes scaly plaques on the body. Pustular psoriasis [including palmoplantar pustulosis (PPP) and generalized pustular psoriasis (GPP)] is a variant characterized by sterile pustules. Limited evidence exists on how quitting smoking affects psoriasis and its subtypes. In this study conducted in South Korea, we aimed to investigate how changes in smoking habits, especially quitting smoking, could impact the development of psoriasis. We used medical claims records from the Korean National Health Insurance Service database, which included data from over 5.7 million people participating in health checkups between 2004 and 2007. We divided people into four groups based on their smoking habits: sustained smokers, smoking quitters, sustained ex-smokers and never smokers. We found that smoking quitters had a lower risk of developing psoriasis, especially PsV and PPP. Even people who had quit smoking and remained smoke-free for an extended period (sustained ex-smokers) showed a more pronounced reduction in the risk of psoriasis, including PsV, PPP and GPP. Our findings remained consistent across various groups of people, considering factors such as age, sex, weight and overall health. The results suggest that encouraging people to quit smoking and maintain a smoke-free lifestyle may help to prevent the onset of psoriasis. In conclusion, this large-scale study from South Korea provides real-world evidence to suggest that quitting smoking could reduce the risk of developing psoriasis. These findings are valuable for public health initiatives, emphasizing the benefits of quitting smoking for skin health.
Assuntos
Psoríase , Abandono do Hábito de Fumar , Humanos , Psoríase/etiologia , Psoríase/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Abandono do Hábito de Fumar/estatística & dados numéricos , Adulto , República da Coreia/epidemiologia , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Ex-Fumantes/estatística & dados numéricosRESUMO
Phototherapy is broadly utilized for treatment of inflammatory skin conditions affecting pediatric patients. However, there are no specific guidelines or recommendations for implementing phototherapy in pediatric populations leading to variability in treatment procedures. Here, we present findings from a cross-sectional, survey-based study investigating the implementation of phototherapy in pediatric patients across the United States. A total of 39 sites from 19 different states identified via the National Psoriasis Foundation (NPF) Health Care Provider Directory responded. Common practices included a signed informed consent prior to performing phototherapy (86.4%, n = 32), no minimum age requirement for pediatric patients (91.8%, n = 34), the use of Fitzpatrick skin type to determine dosing protocol (100%, n = 37), and allowing parents to accompany their children into the lightbox (65%, n = 20). Our results provide insights into current common practices and themes for further study.
Assuntos
Dermatite Atópica , Psoríase , Terapia Ultravioleta , Humanos , Criança , Estados Unidos , Estudos Transversais , Terapia Ultravioleta/métodos , Fototerapia , Psoríase/radioterapia , Psoríase/etiologia , Dermatite Atópica/terapiaRESUMO
Members of the C-X-C motif chemokine receptor (CXCR) superfamily play central roles in initiating the innate immune response in mammalian cells by orchestrating selective cell migration and immune cell activation. With its multilayered structure, the skin, which is the largest organ in the body, performs a crucial defense function, protecting the human body from harmful environmental threats and pathogens. CXCRs contribute to primary immunological defense; these receptors are differentially expressed by different types of skin cells and act as key players in initiating downstream innate immune responses. While the initiation of inflammatory responses by CXCRs is essential for pathogen elimination and tissue healing, overactivation of these receptors can enhance T-cell-mediated autoimmune responses, resulting in excessive inflammation and the development of several skin disorders, including psoriasis, atopic dermatitis, allergic contact dermatitis, vitiligo, autoimmune diseases, and skin cancers. In summary, CXCRs serve as critical links that connect innate immunity and adaptive immunity. In this article, we present the current knowledge about the functions of CXCRs in the homeostasis function of the skin and their contributions to the pathogenesis of allergic contact dermatitis and psoriasis. Furthermore, we will examine the research progress and efficacy of therapeutic approaches that target CXCRs.
Assuntos
Dermatite Alérgica de Contato , Psoríase , Humanos , Animais , Cisteína , Receptores de Quimiocinas , Psoríase/etiologia , Dermatite Alérgica de Contato/etiologia , Homeostase , MamíferosRESUMO
A key principle of clinical studies and case reports is that they should reflect the demographics and epidemiology of the patient population concerned. Here, we have compiled a diverse group of clinical cases of generalized pustular psoriasis (GPP) to showcase the differences in GPP presentation in patients worldwide. We attempt to capture the broad spectrum of clinical presentations of GPP and showcase the diversity of the patient population. The patients included in this series are diverse in age, genetic background, skin phototype and medical history. Moreover, they present with a variety of clinical courses of GPP and different degrees of systemic involvement, and experience flares triggered by different inciting factors. The key learnings from this case series may support physicians in identifying and managing patients with this rare and multifaceted disease that can affect patients both physically and psychologically.
Assuntos
Psoríase , Humanos , Psoríase/etiologia , Pele , Doença Aguda , Doença CrônicaRESUMO
BACKGROUND: Few studies have reported the burden of generalized pustular psoriasis (GPP), a severe and potentially life-threatening skin disease, especially at a national level. OBJECTIVES: The aim of this study is to estimate the nationwide burden of GPP in China and make a systemic review of the published data. METHODS: We conducted a population-based study using Urban Basic Medical Insurance in China from 2012 to 2016. GPP cases were identified by primary diagnoses including the international classification of Diseases codes (ICD-10: L40.1 and ICD-9: 694.3). A systematic review was conducted using relevant databases up to January 2022. RESULTS: The crude prevalence and incidence of GPP in 2016 were 1.403 (95% confidence interval [CI]: 1.115-1.691) and 0.629 (95% CI: 0.483-0.775) per 100,000 person-years, respectively. The rates were higher in males than in females for both prevalence (1.429 vs. 1.135) and incidence (0.635 vs. 0.520). The prevalence and incidence showed a bimodal age distribution, with the first peak occurring in the 0- to 3-year age-group and the second peak occurring in the 30- to 39-year age-group. The per capita total cost per year for 1 patient with GPP was 609.26 (± 45.77) US dollars. Seven studies were identified in a systematic review, according to which the prevalence (per 100,000) of GPP tended to be higher in Asian countries (0.746-8.178 in Japan and 12.230 in Korea) than in France (0.176), Sweden (6.25), and Brazil (0.7). CONCLUSIONS: This is the largest study concerning the disease burden of GPP, and in this study, the prevalence seemed to be higher in Asia. Although the direct economic burden of GPP did not seem high during the study period, the future usage of biologics and the humanistic burden should also be considered for policy-related decision-making.
Assuntos
Psoríase , Masculino , Feminino , Humanos , Prevalência , Psoríase/epidemiologia , Psoríase/etiologia , China/epidemiologia , Ásia/epidemiologia , FrançaRESUMO
Blue light has garnered attention because of its ability to penetrate more deeply into the skin layers, and induce cellular dysfunction and DNA damage. Photoageing, hyperpigmentation and melasma are some of the cutaneous changes that develop on exposure to blue light. To date, the therapeutic roles of blue light have been evaluated in dermatological conditions like psoriasis, eczema, acne vulgaris, actinic keratosis and cutaneous malignancies, among others. In this review, we have attempted to present an evidence-based compilation of the effects of blue light on the skin.
Assuntos
Acne Vulgar , Hiperpigmentação , Ceratose Actínica , Psoríase , Humanos , Pele , Ceratose Actínica/tratamento farmacológico , Luz , Psoríase/etiologia , Acne Vulgar/etiologia , Acne Vulgar/tratamento farmacológico , Hiperpigmentação/etiologia , Hiperpigmentação/tratamento farmacológicoRESUMO
Discordance between patient and clinician treatment goals and expectations can present a challenge to implementation of effective therapeutic plans. Because topical treatments are commonly used for plaque psoriasis, both as monotherapy and adjuncts to other treatment modalities, providers need to understand the concerns of patients with psoriasis regarding use of topical products. Psoriasis is a complex and chronic disease with treatment needs that may change over time, influencing patient treatment goals and expectations of efficacy. When these expectations are not met and patient concerns are unaddressed, dissatisfaction may lead to nonadherence, which in turn can prevent patients from achieving relief from the signs and symptoms of psoriasis that affect their quality of life. Here, we detail how current topical treatments meet patient expectations and needs, with particular attention given to combination regimens using corticosteroids. This review shows that once-daily application of halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) not only has a rapid onset of treatment effect and proven efficacy, but also has a remittive effect. In addition, HP/TAZ has a favorable safety profile, with low rates of irritation and local skin reactions in clinical studies. The dual mechanisms of action related to 2 active ingredients, once-daily use, and the favorable clinical findings suggest that HP/TAZ may address patient concerns and promote treatment adherence.J Drugs Dermatol. 2023;22(2):132-138. doi:10.36849/JDD.7367.
Assuntos
Fármacos Dermatológicos , Ácidos Nicotínicos , Psoríase , Humanos , Combinação de Medicamentos , Motivação , Qualidade de Vida , Resultado do Tratamento , Índice de Gravidade de Doença , Creme para a Pele , Clobetasol , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Psoríase/etiologia , Emolientes/uso terapêutico , Emulsões/uso terapêuticoRESUMO
Psoriasis is a chronic multifactorial skin disorder with an immune basis. It is characterized by patches of skin that are usually red, flaky and crusty, and that often release silvery scales. The patches appear predominantly on the elbows, knees, scalp and lower back, although they may also appear on other body areas and severity may be variable. The majority of patients (about 90%) present small patches known as "plaque psoriasis". The roles of environmental triggers such as stress, mechanical trauma and streptococcal infections are well described in psoriasis onset, but much effort is still needed to unravel the genetic component. The principal aim of this study was to use a next-generation sequencing technologies-based approach together with a 96 customized multigene panel in the attempt to determine if there are germline alterations that can explain the onset of the disease, and thus to find associations between genotypes and phenotypes. To this aim, we analyzed a family in which the mother showed mild psoriasis, and her 31-year-old daughter had suffered from psoriasis for several years, whereas an unaffected sister served as a negative control. We found variants already associated directly to psoriasis in the TRAF3IP2 gene, and interestingly we found a missense variant in the NAT9 gene. The use of multigene panels in such a complex pathology such as psoriasis can be of great help in identifying new susceptibility genes, and in being able to make early diagnoses especially in families with affected subjects.
Assuntos
Predisposição Genética para Doença , Psoríase , Adulto , Feminino , Humanos , Mutação , Fenótipo , Psoríase/etiologia , Psoríase/genética , Infecções Estreptocócicas/complicaçõesRESUMO
Psoriasis is the most common chronic inflammatory skin disease with a genetic basis. It is characterised by keratinocyte hyperproliferation, parakeratosis and inflammatory cell infiltration. Psoriasis negatively affects a patient's physical and emotional quality of life. Sirtuins (SIRTs; silent information regulators) are an evolutionarily conserved group of enzymes involved in the post-translational modification of proteins, including deacetylation, polyADP-ribosylation, demalonylation and lipoamidation. SIRTs are involved in a number of cellular pathways related to ageing, inflammation, oxidative stress, epigenetics, tumorigenesis, the cell cycle, DNA repair and cell proliferation, positioning them as an essential component in the pathogenesis of many diseases, including psoriasis. Activation of SIRT1 counteracts oxidative-stress-induced damage by inhibiting the mitogen-activated protein kinases (MAPK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways and may mitigate pathological events in psoriasis. There is a significant reduction in the expression of SIRT1, SIRT2, SIRT3, SIRT4 and SIRT5 and an increase in the expression of SIRT6 and SIRT7 in psoriasis. The aim of the review is to draw the attention of physicians and scientists to the importance of SIRTs in dermatology and to provide a basis and impetus for future discussions, research and pharmacological discoveries to modulate SIRT activity. In light of the analysis of the mode of action of SIRTs in psoriasis, SIRT1-SIRT5 agonists and SIRT6 and SIRT7 inhibitors may represent new therapeutic options for the treatment of psoriasis.
Assuntos
Psoríase , Sirtuínas , Dermatopatias , Humanos , Sirtuína 1 , Sirtuínas/metabolismo , Qualidade de Vida , Envelhecimento , Psoríase/etiologiaRESUMO
Psoriatic arthritis (PsA), a heterogeneous chronic inflammatory immune-mediated disease characterized by musculoskeletal inflammation (arthritis, enthesitis, spondylitis, and dactylitis), generally occurs in patients with psoriasis. PsA is also associated with uveitis and inflammatory bowel disease (Crohn's disease and ulcerative colitis). To capture these manifestations as well as the associated comorbidities, and to recognize their underlining common pathogenesis, the name of psoriatic disease was coined. The pathogenesis of PsA is complex and multifaceted, with an interplay of genetic predisposition, triggering environmental factors, and activation of the innate and adaptive immune system, although autoinflammation has also been implicated. Research has identified several immune-inflammatory pathways defined by cytokines (IL-23/IL-17, TNF), leading to the development of efficacious therapeutic targets. However, heterogeneous responses to these drugs occur in different patients and in the different tissues involved, resulting in a challenge to the global management of the disease. Therefore, more translational research is necessary in order to identify new targets and improve current disease outcomes. Hopefully, this may become a reality through the integration of different omics technologies that allow better understanding of the relevant cellular and molecular players of the different tissues and manifestations of the disease. In this narrative review, we aim to provide an updated overview of the pathophysiology, including the latest findings from multiomics studies, and to describe current targeted therapies.
Assuntos
Artrite Psoriásica , Psoríase , Humanos , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/etiologia , Comorbidade , Citocinas , Psoríase/tratamento farmacológico , Psoríase/etiologiaRESUMO
Psoriasis is a chronic and immune-mediated skin condition characterized by pro-inflammatory cytokines and keratinocyte hyperproliferation. Dendritic cells, T lymphocytes, and keratinocytes represent the main cell subtypes involved in the pathogenesis of psoriasis, while the interleukin-23 (IL-23)/IL-17 pathway enhances the disease progression. Human adipose tissue is an endocrine organ, which secretes multiple proteins, known as adipokines, such as adiponectin, leptin, visfatin, or resistin. Current evidence highlights the immunomodulatory roles of adipokines, which may contribute to the progression or suppression of psoriasis. A better understanding of the complexity of psoriasis pathophysiology linked with adipokines could result in developing novel diagnostic or therapeutic strategies. This review aims to present the pathogenesis of psoriasis and the roles of adipokines in this process.
Assuntos
Adipocinas , Psoríase , Humanos , Adipocinas/metabolismo , Leptina/uso terapêutico , Psoríase/etiologia , Psoríase/tratamento farmacológico , Resistina , Adiponectina/uso terapêutico , Tecido Adiposo/metabolismoRESUMO
Atopic dermatitis (AD) is a chronic inflammatory skin disease of very high prevalence, especially in childhood, with no specific treatment or cure. As its pathogenesis is complex, multifactorial and not fully understood, further research is needed to increase knowledge and develop new targeted therapies. We have recently demonstrated the critical role of NAD+ and poly (ADP-ribose) (PAR) metabolism in oxidative stress and skin inflammation. Specifically, we found that hyperactivation of PARP1 in response to DNA damage induced by reactive oxygen species, and fueled by NAMPT-derived NAD+, mediated inflammation through parthanatos cell death in zebrafish and human organotypic 3D skin models of psoriasis. Furthermore, the aberrant induction of NAMPT and PARP activity was observed in the lesional skin of psoriasis patients, supporting the role of these signaling pathways in psoriasis and pointing to NAMPT and PARP1 as potential novel therapeutic targets in treating skin inflammatory disorders. In the present work, we report, for the first time, altered NAD+ and PAR metabolism in the skin of AD patients and a strong correlation between NAMPT and PARP1 expression and the lesional status of AD. Furthermore, using a human 3D organotypic skin model of AD, we demonstrate that the pharmacological inhibition of NAMPT and PARP reduces pathology-associated biomarkers. These results help to understand the complexity of AD and reveal new potential treatments for AD patients.
Assuntos
Dermatite Atópica , Psoríase , Animais , Humanos , Inflamação , NAD/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli Adenosina Difosfato Ribose/metabolismo , Poli ADP Ribosilação , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Psoríase/etiologia , Peixe-Zebra/metabolismoRESUMO
BACKGROUND: Alcohol consumption and smoking have been reported to be associated with psoriasis risk. However, a conclusion with high-quality evidence of causality could not be easily drawn from regular observational studies. OBJECTIVES: This study aims to assess the causal associations of alcohol consumption and smoking with psoriasis. METHODS: Genome-wide association study (GWAS) summary-level data for alcohol consumption (N = 941 280), smoking initiation (N = 1 232 091), cigarettes per day (N = 337 334) and smoking cessation (N = 547 219) was obtained from the GSCAN consortium (Sequencing Consortium of Alcohol and Nicotine use). The GWAS results for lifetime smoking (N = 462 690) were obtained from the UK Biobank samples. Summary statistics for psoriasis were obtained from a recent GWAS meta-analysis of eight cohorts comprising 19 032 cases and 286 769 controls and the FinnGen consortium, comprising 4510 cases and 212 242 controls. Linkage disequilibrium score regression was applied to compute the genetic correlation. Bidirectional Mendelian randomization (MR) analyses were conducted to determine casual direction using independent genetic variants that reached genome-wide significance (P < 5 × 10-8 ). RESULTS: There were genetic correlations between smoking and psoriasis. MR revealed a causal effect of smoking initiation [odds ratio (OR) 1·46, 95% confidence interval (CI) 1·32-1·60, P = 6·24E-14], cigarettes per day (OR 1·38, 95% CI 1·13-1·67, P = 0·001) and lifetime smoking (OR 1·96, 95% CI 1·41-2·73, P = 7·32E-05) on psoriasis. Additionally, a suggestive causal effect of smoking cessation on psoriasis was observed (OR 1·39, 95% CI 1·07-1·79, P = 0·012). We found no causal relationship between alcohol consumption and psoriasis (P = 0·379). The reverse associations were not statistically significant. CONCLUSIONS: Our findings provide causal evidence for the effects of smoking on psoriasis risk. What is already known about this topic? Alcohol consumption and smoking have been reported to be associated with psoriasis risk. Whether alcohol consumption and smoking have a causal effect on psoriasis risk remains unclear. What does this study add? This Mendelian randomization study shows a causal association between smoking, but not alcohol consumption, and the risk of developing psoriasis. Restricting smoking could be helpful in reducing the burden of psoriasis.
Assuntos
Psoríase , Fumar , Humanos , Fumar/efeitos adversos , Fumar/genética , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/genética , Psoríase/etiologia , Psoríase/genéticaRESUMO
Psoriasis is a common chronic inflammatory skin disease with a prevalence of about 2% in the Caucasian population. Tumor necrosis factor (TNF) plays an essential role in the pathogenesis of psoriasis, but its mechanism of action remains poorly understood. Here we report that the development of psoriasis-like skin inflammation in mice with epidermis-specific inhibition of the transcription factor NF-κB was triggered by TNF receptor 1 (TNFR1)-dependent upregulation of interleukin-24 (IL-24) and activation of signal transducer and activator of transcription 3 (STAT3) signaling in keratinocytes. IL-24 was strongly expressed in human psoriatic epidermis, and pharmacological inhibition of NF-κB increased IL-24 expression in TNF-stimulated human primary keratinocytes, suggesting that this mechanism is relevant for human psoriasis. Therefore, our results expand current views on psoriasis pathogenesis by revealing a new keratinocyte-intrinsic mechanism that links TNFR1, NF-κB, ERK, IL-24, IL-22R1, and STAT3 signaling to disease initiation.
Assuntos
Citocinas/fisiologia , Queratinócitos/patologia , Psoríase/etiologia , Receptores Tipo I de Fatores de Necrose Tumoral/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , Animais , Células Cultivadas , Cruzamentos Genéticos , Citocinas/biossíntese , Citocinas/genética , Modelos Animais de Doenças , Epiderme/patologia , Regulação da Expressão Gênica/fisiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/biossíntese , Humanos , Quinase I-kappa B/deficiência , Quinase I-kappa B/fisiologia , Interleucinas/fisiologia , Queratinócitos/metabolismo , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Knockout , Camundongos Transgênicos , NF-kappa B/metabolismo , Psoríase/patologia , Psoríase/fisiopatologia , Espécies Reativas de Oxigênio/metabolismo , Receptores de Interleucina/fisiologia , Receptores Tipo I de Fatores de Necrose Tumoral/deficiência , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Fator de Transcrição STAT3/fisiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
The cutaneous side effects of COVID-19 vaccines are being studied and their immunogenicity is most likely linked to the pathophysiology of psoriasis. Although uncommon, several cases of exacerbation and new onset of psoriasis have been reported globally after vaccination. To contribute to the literature on this intriguing topic, we present three cases of de novo psoriasis in adult patients following COVID-19 vaccination. Our observations and a literature review show that this occurrence is independent of the type and brand of vaccines.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Psoríase , Vacinas , Adulto , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Psoríase/diagnóstico , Psoríase/epidemiologia , Psoríase/etiologia , Vacinação/efeitos adversosRESUMO
BACKGROUND: Particulate matter (PM) is a mixture of solid and liquid particles suspended in air, which originates from industrial plants or vehicle emissions. Although the skin is the primary body area of contact with air pollutants, the associations between PM and chronic inflammatory skin diseases has not been well established. AIM: To investigate associations between PM and atopic dermatitis (AD) and between PM and other chronic inflammatory dermatoses, using data from the Korean Health Insurance Review and Assessment Service. METHODS: Monthly disease statistics from the seven largest cities in South Korea (Seoul, Busan, Daegu, Incheon, Gwangju, Daejeon, Ulsan) and from Jeju Island (in total, a population of 23 288 000 for all eight areas) were included. Based on daily air pollution level and weather forecast from 2015 to 2019, multivariate negative binomial regression analysis was conducted to estimate monthly visits of AD with respect to outdoor air pollutants: coarse PM with a diameter of ≤ 10 µm (PM10) and fine PM with a diameter of ≤ 2.5 µm (PM2.5) ozone (O3 ), nitrogen dioxide (NO2 ), sulphur dioxide (SO2 ) and carbon monoxide (CO). RESULTS: Increases in the levels of PM2.5, PM10, SO2 and CO were associated with significant increases in monthly patient visits for AD. Every 10 µg/m3 increase in PM2.5 and PM10 resulted in patient visit increases of 2.71% (95% CI 0.76-4.71; P < 0.01) and 2.01% (95% CI 0.92-3.11, P < 0.001), respectively, while every 1 part per billion (ppb) increase in SO2 and every 100 ppb increase in CO resulted in visit increases of 2.26% (95% CI 1.35-3.17; P < 0.001) and 2.86% (95% CI 1.35-4.40; P < 0.001), respectively. O3 and NO2 were not associated with increased patient visits for AD. Increases in PM2.5 and PM10 concentrations were also significantly associated with increases in patient visits for psoriasis, seborrhoeic dermatitis and rosacea. CONCLUSION: Our data suggest that PM is associated with AD and other chronic inflammatory skin diseases.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Dermatite Atópica/etiologia , Exposição Ambiental/efeitos adversos , Material Particulado/efeitos adversos , Poluentes Atmosféricos/análise , Doença Crônica , Dermatite Seborreica/etiologia , Humanos , Material Particulado/análise , Psoríase/etiologia , República da Coreia , Rosácea/etiologiaRESUMO
INTRODUCTION: Childhood psoriasis is not uncommon, and its prevalence is estimated to be 128 per 100,000 children. There are sparse data regarding intrauterine and environmental tobacco smoke exposure and the development of psoriasis in childhood. In this study, we aimed to investigate these parameters in the Turkish pediatric population. MATERIALS AND METHODS: We included 130 children with psoriasis and 390 children as controls. For each risk factor, odds ratios of psoriasis as an estimate of relative risks and corresponding 95% confidence interval were calculated. Univariate conditional logistic regression analysis was used to determining the crude odds ratio. Subsequently, to evaluate the effects of potential confounding factors, multivariate conditional logistic regression analysis was used. RESULTS: Childhood psoriasis (CP) was found to be associated with environmental tobacco smoke exposure irrespective of intrauterine smoking exposure, family history of psoriasis, and obesity (OR: 2.23, 95% CI = 1.39-3.58), whereas multiple logistic regression analysis did not show a relationship between CP and intrauterine tobacco exposure (OR: 1.61, 95% CI = 0.75-3.43). CONCLUSIONS: Environmental tobacco smoke exposure at home denotes an important preventable risk factor for developing CP. Further studies are needed to elucidate the relationship between CP and environmental tobacco exposure investigating a large cohort of CP patients who have been diagnosed by expert dermatologists.
Assuntos
Psoríase , Poluição por Fumaça de Tabaco , Estudos de Casos e Controles , Criança , Exposição Ambiental/efeitos adversos , Humanos , Psoríase/epidemiologia , Psoríase/etiologia , Fatores de Risco , Nicotiana , Poluição por Fumaça de Tabaco/efeitos adversosRESUMO
BACKGROUND: IL-17A-producing CD4+ T helper (TH17) cells play a critical role in autoimmune and chronic inflammatory diseases, such as crescentic GN. The proinflammatory effects of IL-17 are mediated by the activation of the IL-17RA/IL-17RC complex. Although the expression of these receptors on epithelial and endothelial cells is well characterized, the IL-17 receptor expression pattern and function on hematopoietic cells, e.g., CD4+ T cell subsets, remains to be elucidated. METHODS: Crescentic GN (nephrotoxic nephritis) was induced in IL-17A, IFNγ, and Foxp3 triple-reporter mice for sorting of renal CD4+ T cell subsets and subsequent single-cell RNA sequencing. Moreover, we generated TH17 cell-specific IL-17RA and IL-17RC gene-deficient mice and studied the functional role of IL-17 signaling in TH17 cells in crescentic GN, imiquimod-induced psoriasis, and in the CD4+CD45RBhigh T cell transfer colitis model. RESULTS: We identified a specific expression of the IL-17 receptor A/C complex on CD4+ TH17 cells. Single-cell RNA sequencing of TH17 cells revealed the activation of the IL-17 receptor signaling pathway in experimental crescentic GN. Disruption of the IL-17RC signaling pathway in CD4+ T cells and, most importantly, specifically in CD4+ TH17 cells, potentiates the IL-17 cytokine response and results in an accelerated course of experimental crescentic GN. Comparable results were observed in experimental models of psoriasis and colitis. CONCLUSIONS: Our findings indicate that IL-17 receptor C signaling has a previously unrecognized function in the regulation of CD4+ TH17 cells and in the control of organ-specific autoimmunity and might provide new insights into the development of more efficient anti-TH17 treatment strategies.