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2.
Immunity ; 57(7): 1451-1453, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38986439

RESUMO

Skin inflammation is potentiated by coordinated epithelial and immune cell metabolism. In this issue of Immunity, Subudhi and Konieczny et al. delineate how HIF1α regulates epithelial cell glycolysis during psoriasis. In turn, lactate is a byproduct that augments type 17 γδ T cell responses to sustain inflammatory skin disease.


Assuntos
Células Epiteliais , Glicólise , Subunidade alfa do Fator 1 Induzível por Hipóxia , Psoríase , Pele , Humanos , Células Epiteliais/metabolismo , Células Epiteliais/imunologia , Pele/imunologia , Pele/patologia , Pele/metabolismo , Animais , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Psoríase/imunologia , Psoríase/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Doença Crônica
3.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39000125

RESUMO

TNF inhibitors (TNFi) have revolutionized the therapeutic management of various chronic immune-mediated inflammatory diseases. Despite their known benefits, these therapies are related to paradoxical adverse effects (PAEs), including paradoxical psoriasis (PP). Although the underlying mechanism remains somewhat unclear, some theories suggest that genetic factors, particularly certain single-nucleotide polymorphisms (SNPs), may play an important role. The present review aimed to research and analyze recent findings regarding the pathomechanisms involved in the appearance of PP and the association between various genetic factors and PP in individuals treated with TNFi. We performed a literature search and found that certain genes (IL23R, TNF, FBXL19, CTLA4, SLC12A8, TAP1) are strongly associated with the occurrence of PP in pediatric and adult patients during therapy with TNFi. The identification of the specific SNPs involved in the appearance of PP and other PAEs in patients treated with TNFi for various diseases and in different populations may later favor the recognition of those patients at a high risk of developing such adverse effects and could guide personalized therapeutic strategies in future years.


Assuntos
Polimorfismo de Nucleotídeo Único , Psoríase , Inibidores do Fator de Necrose Tumoral , Humanos , Psoríase/genética , Psoríase/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Predisposição Genética para Doença , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética
4.
Int J Mol Sci ; 25(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-39000456

RESUMO

Psoriasis is an autoimmune cutaneous condition that significantly impacts quality of life and represents a burden on society due to its prevalence. Genome-wide association studies (GWASs) have pinpointed several psoriasis-related risk loci, underlining the disease's complexity. Functional genomics is paramount to unveiling the role of such loci in psoriasis and disentangling its complex nature. In this review, we aim to elucidate the main findings in this field and integrate our discussion with gold-standard techniques in molecular biology-i.e., Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-and high-throughput technologies. These tools are vital to understanding how disease risk loci affect gene expression in psoriasis, which is crucial in identifying new targets for personalized treatments in advanced precision medicine.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genômica , Psoríase , Psoríase/genética , Humanos , Genômica/métodos
5.
Biol Aujourdhui ; 218(1-2): 33-39, 2024.
Artigo em Francês | MEDLINE | ID: mdl-39007775

RESUMO

Interleukin (IL)-17A and then IL-17F have been discovered through their roles in chronic inflammatory diseases. These cytokines share 50% of sequence homology and bind to the same receptor made of the IL-17RA et IL-17RC chains. While they have rather similar pro-inflammatory effects, slight differences exist depending on the cell type considered or whether there is TNF or not. Indeed, there is a synergistic effect of TNF and IL-17A or IL-17F on many cell types. In addition, the interactions between immune and stromal cells also modulate their effects which vary according to stromal cell subtype. The identification of IL-17A and IL-17F roles in inflammatory diseases, as psoriasis, has led to the development of inhibitors of those cytokines. Anti-IL-17A, then anti-IL-17A/F and now anti-IL-17RA have been approved for different diseases and are particularly efficient in psoriasis. Their use is expending to other diseases like psoriatic arthritis and spondyloarthritis. Last, the recent understanding of the importance of stromal cells during chronic inflammation explains the relative inefficacy of such inhibitors in some other diseases.


Title: IL-17A et IL-17F : de la découverte au ciblage thérapeutique - Un exemple de médecine translationnelle. Abstract: L'interleukine (IL)-17A puis l'IL-17F ont été découvertes tour à tour pour leur rôle joué dans les maladies inflammatoires chroniques. Elles ont une homologie de séquence d'environ 50 % et partagent le même récepteur formé des chaînes IL-17RA et IL-17RC. Si elles ont des effets pro-inflammatoires assez similaires, il existe néanmoins quelques différences selon le type cellulaire considéré et selon la présence ou non de TNF, autre cytokine avec laquelle elles ont une synergie d'action. La troisième variable venant moduler leurs effets réside dans les interactions entre cellules immunes et cellules stromales, qui, là encore, varient selon le type de cellules stromales. La mise en évidence de leur rôle dans le psoriasis a notamment conduit au développement d'inhibiteurs de l'IL-17A, puis à la fois de l'IL-17A et de l'IL-17F et enfin d'un de leurs récepteurs. Ces inhibiteurs sont utilisés avec succès dans cette pathologie, et leur indication a été étendue progressivement au rhumatisme psoriasique et à certaines formes de spondylarthrite. Enfin, la récente compréhension de l'importance des cellules stromales dans la réaction inflammatoire chronique permet d'expliquer l'efficacité variable de ces biothérapies dans certaines pathologies.


Assuntos
Produtos Biológicos , Interleucina-17 , Psoríase , Pesquisa Translacional Biomédica , Humanos , Interleucina-17/antagonistas & inibidores , Interleucina-17/fisiologia , Psoríase/tratamento farmacológico , Psoríase/imunologia , Animais , Produtos Biológicos/uso terapêutico , Produtos Biológicos/farmacologia , Inflamação/tratamento farmacológico , Descoberta de Drogas/tendências , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Receptores de Interleucina-17/fisiologia , Receptores de Interleucina-17/antagonistas & inibidores
6.
Arch Dermatol Res ; 316(7): 474, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007937

RESUMO

Psoriasis, a chronic and easily recurring inflammatory skin disease, causes a great economic burden to the patient's family because the etiology and mechanism are still unclear and the treatment cycle is long. In this study, the function and related mechanisms of Momordin Ic in psoriasis were investigated. The IMQ-induced mouse psoriasis model was constructed. The protective effects of different doses of Momordin Ic on psoriasis skin damage in mice were detected by PASI score, HE staining and Ki-67 staining. A psoriasis-like keratinocyte model was established at the cellular level using M5 (IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α) triggered HaCaT. The effects of Momordin Ic upon HaCaT cell biological behavior were examined using MTT and CCK-8 assays. In terms of mechanism, the expression level of each inflammatory factor was assessed using IHC staining and/or ELISA, qRT-PCR, the expression of oxidative stress-related indicators was detected biochemically, and western blot was performed to detect the levels of key proteins of the Wnt signaling and VEGF. As the results shown,  at the in vivo level, Momordin Ic significantly alleviated skin damage, reduced PASI score and inhibited hyperproliferation of keratinized cells in psoriasis mice. At the cellular level, Momordin Ic also significantly reversed M5-induced hyperproliferation of HaCaT keratinocytes. In terms of mechanism, Momordin Ic significantly inhibited the IL-23/IL-17 axis, dramatically elevated the levels of intracellular antioxidants including SOD, GSH-Px, and CAT, and significantly down-regulated the levels of the indicator of oxidative damage, malondialdehyde (MDA). In addition, Momordin Ic also significantly inhibited the level of ß-catenin, a pivotal protein of the Wnt signaling, C-Myc, a target gene of the Wnt signaling, and VEGF, a critical protein of angiogenesis. In conclusion, Momordin Ic can be involved in the skin-protective effects of psoriasis by multiple mechanisms, including inhibition of the Wnt signaling pathway and the IL-23/IL-17 axis, and suppression of oxidative damageand VEGF expression. Momordin Ic has been proven to be an underlying therapeutic drug for the treatment of psoriasis.


Assuntos
Modelos Animais de Doenças , Interleucina-17 , Interleucina-23 , Queratinócitos , Psoríase , Pele , Via de Sinalização Wnt , Animais , Psoríase/tratamento farmacológico , Psoríase/patologia , Psoríase/induzido quimicamente , Psoríase/imunologia , Interleucina-17/metabolismo , Camundongos , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Interleucina-23/metabolismo , Pele/patologia , Pele/efeitos dos fármacos , Pele/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Células HaCaT , Imiquimode , Camundongos Endogâmicos BALB C , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Proliferação de Células/efeitos dos fármacos
8.
Acta Dermatovenerol Croat ; 32(1): 7-16, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38946182

RESUMO

BACKGROUND: Although biologic agents are very effective, long-term comparative studies demonstrating their safety relative to one another are still lacking. METHODS: A total of 124 patients with psoriasis were followed up for 30 months; 74 received anti-TNF-alpha inhibitors (adalimumab, etanercept, infliximab), 33 were on ustekinumab, and 17 were treated with secukinumab. The rates of adverse events in these groups were recorded and statistically analyzed. RESULTS: Infliximab-treated patients showed a high occurrence of asymptomatic, but increased liver enzymes, fatigue, and respiratory as well as dermatologic infections. Adalimumab-treated patients were more often affected by musculoskeletal disorders and infections of all types. Patients treated with secukinumab presented with higher rates of cardiovascular disorders as well as respiratory and dermatologic infections. The group receiving etanercept was more often diagnosed with musculoskeletal and reproductive disorders, specifically menstrual disorders. The rates of therapy discontinuation and serious adverse events did not reach statistically significant values. CONCLUSION: A higher incidence of adverse events was observed among adalimumab-, and infliximab-treated patients, with ustekinumab found to have the safest profile. Our results demonstrate that a personalized approach, including evaluation of a patient's risk profile, is necessary before commencing a biologic. Further research is warranted to confirm the findings of our study.


Assuntos
Adalimumab , Anticorpos Monoclonais Humanizados , Etanercepte , Infliximab , Psoríase , Ustekinumab , Humanos , Psoríase/tratamento farmacológico , Feminino , Masculino , Ustekinumab/uso terapêutico , Ustekinumab/efeitos adversos , Estudos Prospectivos , Adalimumab/efeitos adversos , Adalimumab/uso terapêutico , Infliximab/efeitos adversos , Infliximab/uso terapêutico , Pessoa de Meia-Idade , Adulto , Etanercepte/efeitos adversos , Etanercepte/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Estudos de Coortes , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico
10.
Arch Dermatol Res ; 316(7): 443, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951247

RESUMO

Current genome-wide association studies (GWAS) of plasma proteomes provide additional possibilities for finding new drug targets for inflammatory dermatoses. We performed proteome-wide Mendelian randomization (MR) and colocalization analyses to identify novel potential drug targets for inflammatory dermatoses. We performed MR and colocalization analysis using genetic variation as instrumental variables to determine the causal relationship between circulating plasma proteins and inflammatory dermatoses. 5 plasma proteins were found to be causally associated with dermatitis eczematosa, SLE, urticaria and psoriasis using cis-pQTLs as instrumental variables, but not found in AD and LP. 19 candidate genes with high colocalization evidence were identified. These potential drug targets still require more research and rigorous validation in future trials.


Assuntos
Proteínas Sanguíneas , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Proteoma , Humanos , Análise da Randomização Mendeliana/métodos , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/análise , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Psoríase/genética , Psoríase/sangue , Psoríase/diagnóstico , Locos de Características Quantitativas
11.
Drug Des Devel Ther ; 18: 2775-2791, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38984208

RESUMO

Background: Psoriasis is a common chronic inflammatory skin condition. The emergence of psoriasis has been linked to dysbiosis of the microbiota on the skin surface and an imbalance in the immunological microenvironment. In this study, we investigated the therapeutic impact of topical thymopentin (TP5) on imiquimod (IMQ)-induced psoriasis in mice, as well as the modulatory influence of TP5 on the skin immune milieu and the skin surface microbiota. Methods: The IMQ-induced psoriasis-like lesion mouse model was used to identify the targets and molecular mechanisms of TP5. Immunofluorescence was employed to identify differences in T-cell subset expression before and after TP5 therapy. Changes in the expression of NF-κB signaling pathway components were assessed using Western blotting (WB). 16S rRNA sequencing and network pharmacology were used to detect changes in the skin flora before and after TP5 administration. Results: In vivo, TP5 reduced IMQ-induced back inflammation in mice. H&E staining revealed decreased epidermal thickness and inflammatory cell infiltration with TP5. Masson staining revealed decreased epidermal and dermal collagen infiltration after TP5 administration. Immunohistochemistry showed that TP5 treatment dramatically reduced IL-17 expression. Results of the immunoinfiltration analyses showed psoriatic lesions with more T-cell subsets. According to the immunofluorescence results, TP5 dramatically declined the proportions of CD4+, Th17, ROR+, and CD8+ T cells. WB revealed that TP5 reduced NF-κB pathway expression in skin tissues from IMQ-induced psoriasis model mice. 16S rRNA sequencing revealed a significant increase in Burkholderia and Pseudomonadaceae_Pseudomonas and a significant decrease in Staphylococcaceae_Staphylococcus, Aquabacterium, Herbaspirillum, and Balneimonas. Firmicutes dominated the skin microbial diversity after TP5 treatment, while Bacteroidetes, Verrucomicrobia, TM7, Proteobacteria, Actinobacteria, Acidobacteria, Gemmatimonadetes, and other species dominated in the IMQ group. Conclusion: TP5 may treat psoriasis by modulating the epidermal flora, reducing NF-κB pathway expression, and influencing T-cell subsets.


Assuntos
Imiquimode , Psoríase , Pele , Timopentina , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Psoríase/imunologia , Psoríase/patologia , Animais , Camundongos , Pele/efeitos dos fármacos , Pele/patologia , Imiquimode/farmacologia , Timopentina/farmacologia , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Feminino , Microbiota/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL
13.
Biomed Mater ; 19(5)2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38955335

RESUMO

This study aimed to develop and optimize karanjin-loaded ethosomal nanogel formulation and evaluate its efficacy in alleviating symptoms of psoriasis in an animal model induced by imiquimod. These karanjin-loaded ethosomal nanogel, were formulated to enhance drug penetration into the skin and its epidermal retention. Karanjin was taken to formulate ethosomes due to its potential ani-psoriatic activity. Ethosomes were formulated using the cold method using 32full factorial designs to optimize the formulation components. 9 batches were prepared using two independent variablesX1: concentration of ethanol andX2: concentration of phospholipid whereas vesicle size (Y1) and percentage entrapment efficiency (Y2) were selected as dependent variables. All the dependent variables were found to be statistically significant. The optimized ethosomal suspension (B3) exhibited a vesicle size of 334 ± 2.89 nm with an entrapment efficiency of 94.88 ± 1.24% and showed good stability. The morphology of vesicles appeared spherical with smooth surfaces through transmission electron microscopy analysis. X-ray diffraction analysis confirmed that the drug existed in an amorphous state within the ethosomal formulation. The optimized ethosome was incorporated into carbopol 934 to develop nanogel for easy application on the skin. The nanogel underwent characterization for various parameters including spreadability, viscosity, pH, extrudability, and percentage drug content. The ethosomal formulation remarkably enhanced the skin permeation of karanjin and increased epidermal retention of the drug in psoriatic skin compared to marketed preparation and pure drug. A skin retention study showed that ethosomal nanogel formulation has 48.33% epidermal retention in 6 h.In vivo,the anti-psoriatic activity of karanjin ethosomal nanogel demonstrated significant improvement in psoriasis, indicated by a gradual decrease in skin thickness and scaling as reflected in the Psoriasis Severity Index grading. Therefore, the prepared ethosomal nanogel is a potential vehicle for improved topical delivery of karanjin for better treatment of psoriasis.


Assuntos
Nanogéis , Psoríase , Absorção Cutânea , Psoríase/tratamento farmacológico , Psoríase/patologia , Animais , Nanogéis/química , Lecitinas/química , Pele/metabolismo , Pele/patologia , Tamanho da Partícula , Lipossomos/química , Polietilenoglicóis/química , Glycine max/química , Ratos , Masculino , Imiquimode/química , Portadores de Fármacos/química , Polietilenoimina/química , Difração de Raios X , Etanol/química , Acrilatos
14.
Skin Res Technol ; 30(7): e13795, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38995229

RESUMO

OBJECTIVE: This study is designed to explore the potential causal relationship between psoriasis and psoriatic arthritis (PsA) while investigating the genetic basis shared by these inflammatory diseases. METHODS: Significant single nucleotide polymorphisms (SNPs) associated with UC, psoriasis, and PsA were selected as genetic instrumental variables using Genome-Wide Association Study (GWAS) datasets. Additionally, Mendelian randomization (MR) methods, including inverse-variance weighting (IVW), MR-Egger regression, and Weighted Median (WME), were utilized to evaluate the causal relationships between these diseases. Moreover, sensitivity analysis and heterogeneity testing were conducted to validate the stability of the results. RESULTS: A total of 123 significant SNPs associated with psoriasis, PsA, and UC were identified as genetic instrumental variables based on GWAS datasets. The analysis revealed a 36% increased risk of UC with psoriasis (odds ratio [OR] = 1.350, 95% confidence interval [CI] = 1.065-1.729, P = 0.012) and a 32.9% increased risk of UC with PsA (OR = 1.329, 95% CI = 1.176-1.592, P < 0.001). Further analysis showed a 43.5% increased risk of psoriasis with UC (OR = 1.435, 95% CI = 1.274-1.831, P < 0.001) and a 45.8% increased risk of PsA with UC (OR = 1.458, 95% CI = 1.166-1.822, P = 0.0013). In addition, sensitivity analysis and heterogeneity testing demonstrated the high stability of these results. Particularly, neither MR-Egger regression analysis nor leave-one-out analysis revealed significant heterogeneity or pleiotropy bias, indicating the reliability of these causal estimates. Moreover, the use of the MR-PRESSO further confirmed the positive correlation between psoriasis and UC, and the corrected estimates remained consistent with IVW analysis results after excluding potential outlier SNPs, enhancing the credibility of the analysis. CONCLUSIONS: This study strengthens the understanding of the genetic and causal relationships among UC, psoriasis, and PsA through GWAS and MR methods, revealing the genetic basis they may share. These findings not only provide a novel perspective on the comorbidity mechanisms of these diseases but also offer a valuable reference for the development of future treatment strategies and intervention measures.


Assuntos
Artrite Psoriásica , Colite Ulcerativa , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Psoríase , Humanos , Artrite Psoriásica/genética , Artrite Psoriásica/epidemiologia , Psoríase/genética , Psoríase/epidemiologia , Colite Ulcerativa/genética , Colite Ulcerativa/epidemiologia , Predisposição Genética para Doença/genética , Fatores de Risco
15.
PeerJ ; 12: e17701, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006018

RESUMO

Background: Atopic dermatitis (AD), psoriasis, and drug reactions associated with erythroderma are frequently complicated by infections. However, bloodstream infection (BSI) have received less research attention. Objectives: This study aimed to investigate the clinical characteristics and risk factors associated with BSI in patients with erythroderma. Methods: A retrospective analysis was conducted on 141 erythroderma cases. Eleven cases were identified as having BSI. Clinical records of both BSI and non-BSI groups were reviewed and compared. Results: BSI was diagnosed in 7.80% (11/141) of erythroderma cases, with a breakdown of 7.14% in AD, 2.00% in psoriasis, and 17.14% in drug reactions. Notably, all positive skin cultures (7/7) showed bacterial isolates concordant with blood cultures. Univariate logistic regression analysis revealed several significant associations with BSI, including temperature (≤36.0 or ≥38.5 °C; odds ratio (OR) = 28.06; p < 0.001), chilling (OR = 22.10; p < 0.001), kidney disease (OR = 14.64; p < 0.001), etiology of drug reactions (OR = 4.18; p = 0.03), albumin (ALB) (OR = 0.86; p < 0.01), C-reaction protein (CRP) (OR = 1.01; p = 0.02), interleukin 6 (IL-6) (OR = 1.02; p = 0.02), and procalcitonin (PCT) (OR = 1.07; p = 0.03). Receiver operating characteristic (ROC) curves demonstrated significant associations with ALB (p < 0.001; the area under curve (AUC) = 0.80), PCT (p = 0.009; AUC = 0.74), and CRP (p = 0.02; AUC = 0.71). Conclusions: Increased awareness of BSI risk is essential in erythroderma management. Patients with specific risk factors, such as abnormal body temperature (≤36.0 or ≥38.5 °C), chilling sensations, kidney disease, a history of drug reactions, elevated CRP (≥32 mg/L), elevated PCT (≥1.00 ng/ml), and low albumin (≤31.0 g/L), require close monitoring for BSI development.


Assuntos
Dermatite Atópica , Dermatite Esfoliativa , Psoríase , Humanos , Estudos Retrospectivos , Masculino , Dermatite Atópica/sangue , Dermatite Atópica/epidemiologia , Feminino , Fatores de Risco , Pessoa de Meia-Idade , Adulto , Idoso , Bacteriemia/epidemiologia , Bacteriemia/sangue , Adulto Jovem
16.
Front Immunol ; 15: 1412470, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39007153

RESUMO

The etiology of Guillain-Barré syndrome (GBS) may be autoimmune. About two-thirds of patients typically experience their first symptoms within 5 days to 3 weeks after common infectious diseases, surgery, or vaccination. Infection is a triggering factor for over 50% of patients. In recent years, a growing number of studies have indicated that some immune checkpoint inhibitors and COVID-19 may also contribute to the occurrence of GBS. However, drugs are considered a rare cause of GBS. The patient in our case was a 70-year-old man who developed GBS after initiating secukinumab for psoriasis. Upon diagnosis suggesting a potential association between secukinumab and the development of GBS, as per the Naranjo adverse drug reaction (ADR) probability scale, we decided to discontinue the drug. Following this intervention, along with the administration of immunoglobulin, the patient exhibited a significant improvement in extremity weakness. The association of GBS with secukinumab treatment, as observed in this case, appears to be uncommon. The underlying mechanisms that may link secukinumab to the development of GBS are not yet fully understood and warrant further scientific inquiry and rigorous investigation. However, we hope that this report can raise greater awareness and vigilance among medical professionals to enhance the safety of patients' medication.


Assuntos
Anticorpos Monoclonais Humanizados , Síndrome de Guillain-Barré , Psoríase , Humanos , Síndrome de Guillain-Barré/induzido quimicamente , Síndrome de Guillain-Barré/etiologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Idoso , Masculino , Psoríase/tratamento farmacológico , Psoríase/complicações , SARS-CoV-2 , COVID-19/complicações
17.
JAMA Netw Open ; 7(7): e2421665, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39012635

RESUMO

Importance: Psoriasis is a common autoinflammatory disease influenced by complex interactions between environmental and genetic factors. The influence of long-term air pollution exposure on psoriasis remains underexplored. Objective: To examine the association between long-term exposure to air pollution and psoriasis and the interaction between air pollution and genetic susceptibility for incident psoriasis. Design, Setting, and Participants: This prospective cohort study used data from the UK Biobank. The analysis sample included individuals who were psoriasis free at baseline and had available data on air pollution exposure. Genetic analyses were restricted to White participants. Data were analyzed between November 1 and December 10, 2023. Exposures: Exposure to nitrogen dioxide (NO2), nitrogen oxides (NOx), fine particulate matter with a diameter less than 2.5 µm (PM2.5), and particulate matter with a diameter less than 10 µm (PM10) and genetic susceptibility for psoriasis. Main Outcomes and Measures: To ascertain the association of long-term exposure to NO2, NOx, PM2.5, and PM10 with the risk of psoriasis, a Cox proportional hazards model with time-varying air pollution exposure was used. Cox models were also used to explore the potential interplay between air pollutant exposure and genetic susceptibility for the risk of psoriasis incidence. Results: A total of 474 055 individuals were included, with a mean (SD) age of 56.54 (8.09) years and 257 686 (54.36%) female participants. There were 9186 participants (1.94%) identified as Asian or Asian British, 7542 (1.59%) as Black or Black British, and 446 637 (94.22%) as White European. During a median (IQR) follow-up of 11.91 (11.21-12.59) years, 4031 incident psoriasis events were recorded. There was a positive association between the risk of psoriasis and air pollutant exposure. For every IQR increase in PM2.5, PM10, NO2, and NOx, the hazard ratios (HRs) were 1.41 (95% CI, 1.35-1.46), 1.47 (95% CI, 1.41-1.52), 1.28 (95% CI, 1.23-1.33), and 1.19 (95% CI, 1.14-1.24), respectively. When comparing individuals in the lowest exposure quartile (Q1) with those in the highest exposure quartile (Q4), the multivariate-adjusted HRs were 2.01 (95% CI, 1.83-2.20) for PM2.5, 2.21 (95% CI, 2.02-2.43) for PM10, 1.64 (95% CI, 1.49-1.80) for NO2, and 1.34 (95% CI, 1.22-1.47) for NOx. Moreover, significant interactions between air pollution and genetic predisposition for incident psoriasis were observed. In the subset of 446 637 White individuals, the findings indicated a substantial risk of psoriasis development in participants exposed to the highest quartile of air pollution levels concomitant with high genetic risk compared with those in the lowest quartile of air pollution levels with low genetic risk (PM2.5: HR, 4.11; 95% CI, 3.46-4.90; PM10: HR, 4.29; 95% CI, 3.61-5.08; NO2: HR, 2.95; 95% CI, 2.49-3.50; NOx: HR, 2.44; 95% CI, 2.08-2.87). Conclusions and Relevance: In this prospective cohort study of the association between air pollution and psoriasis, long-term exposure to air pollution was associated with increased psoriasis risk. There was an interaction between air pollution and genetic susceptibility on psoriasis risk.


Assuntos
Poluição do Ar , Exposição Ambiental , Predisposição Genética para Doença , Material Particulado , Psoríase , Humanos , Psoríase/genética , Psoríase/epidemiologia , Feminino , Masculino , Poluição do Ar/efeitos adversos , Poluição do Ar/estatística & dados numéricos , Pessoa de Meia-Idade , Reino Unido/epidemiologia , Estudos Prospectivos , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Material Particulado/efeitos adversos , Adulto , Poluentes Atmosféricos/efeitos adversos , Idoso , Fatores de Risco , Incidência , Dióxido de Nitrogênio/efeitos adversos , Modelos de Riscos Proporcionais , Óxidos de Nitrogênio/efeitos adversos , Óxidos de Nitrogênio/análise
20.
J Dermatolog Treat ; 35(1): 2373826, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38964751

RESUMO

BACKGROUND: To evaluate the risk of neutropenia during treatment with anti-IL-23 antibodies in patients with psoriasis. METHOD: We conducted an observational study with cohort design using MID-NET® in Japan. We identified patients with psoriasis who were newly prescribed anti-IL-23 antibodies, anti-IL-17-antibodies, adalimumab, or apremilast between January 1, 2009, and March 31, 2021. We estimated the adjusted hazard ratio (aHR) of anti-IL-23 antibodies compared to that of anti-IL-17 antibodies, adalimumab, or apremilast, for the risk of grade 2 (neutrophil count < 1,500/µL) or grade 3 (neutrophil count < 1,000/µL) neutropenia. RESULTS: Overall, 287 patients on anti-IL-23 antibodies, 189 patients on anti-IL-17 antibodies, 293 patients on adalimumab, and 540 patients on apremilast were included. Compared with anti-IL-17 antibodies, the aHR (95% confidence interval (CI)) of anti-IL-23 antibodies was 0.83 (0.27-2.51) for grade 2 and 0.40 (0.02-7.60) for grade 3 neutropenia; that when compared with adalimumab was 0.76 (0.28-2.06) for grade 2 but was not calculated for grade 3 as no cases were found; and that compared with apremilast was 3.88 (0.62-24.48) for grade 2 and 0.43 (0.02-11.63) for grade 3 neutropenia. CONCLUSION: No clear increase in the risk of neutropenia with anti-IL-23 antibodies was observed.


Assuntos
Adalimumab , Interleucina-17 , Interleucina-23 , Neutropenia , Psoríase , Talidomida , Humanos , Adalimumab/efeitos adversos , Adalimumab/imunologia , Psoríase/tratamento farmacológico , Psoríase/imunologia , Feminino , Masculino , Neutropenia/induzido quimicamente , Neutropenia/imunologia , Neutropenia/epidemiologia , Pessoa de Meia-Idade , Japão , Adulto , Interleucina-17/antagonistas & inibidores , Interleucina-17/imunologia , Interleucina-23/antagonistas & inibidores , Interleucina-23/imunologia , Talidomida/efeitos adversos , Talidomida/análogos & derivados , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos
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