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1.
Expert Opin Drug Saf ; : 1-12, 2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39365557

ABSTRACT

OBJECTIVE: The study aims to thoroughly assess the adverse events related to infections and infestations associated with biological agents used for psoriasis using the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) database. METHODS: We analyzed FAERS data from the first quarter of 2004 to the fourth quarter of 2023. The study included TNF-α inhibitors (etanercept, infliximab, adalimumab), IL-12/23 inhibitors (ustekinumab), IL-23p19 inhibitors (guselkumab), and IL-17 inhibitors (secukinumab, ixekizumab). We used disproportionality analysis and Bayesian methods to quantify the related adverse event (AE) signals. RESULTS: Most AEs related to infections and infestations are already listed on the drug packaging labels. Notably, TNF-α inhibitors are associated with a significantly higher incidence of tuberculosis-related diseases compared to other biological agents. In contrast, IL-17 inhibitors show a greater variety and number of fungal infection-related AEs than their counterparts. Furthermore, our study has identified new potential AEs that require the attention of clinicians. CONCLUSION: In clinical practice, it is advisable to monitor the risks of infections and infestations in patients receiving biological agents for psoriasis to enable early detection and intervention. Our findings highlight the need for further epidemiological investigations to establish causality and guide clinical practice in managing these risks effectively.

2.
Arch Dermatol Res ; 316(9): 661, 2024 Oct 05.
Article in English | MEDLINE | ID: mdl-39369132

ABSTRACT

Psoriasis, an inflammatory disease, is largely mediated by T-helper 17 cytokines. We have previously identified the immune system-released activating agent (Israa) as a novel gene that connects the nervous and immune systems. This research aims to investigate the role of the Israa gene in psoriasis in vivo using the imiquimod-induced psoriasis model. We established the model in C57BL/6 wildtype mice, which were then treated with 200 pg/mouse, 400 pg/mouse, or 800 pg/mouse of recombinant ISRAA compared to methotrexate. Subsequently, we also induced psoriasis in Israa-knockout mice to confirm the effect of Israa. Results consistently showed improvement in psoriasis in all groups receiving recombinant ISRAA. The 200 pg/mouse dose eliminated the disease, reduced the cutaneous release of IL-17 to one-third and TNF-α to one-sixth, increased IL-10 release to over 500 pg, completely resolved parakeratosis, decreased epidermal thickness to one-half, and reduced the expression of CD4 and neutrophil elastase in the skin (all p < 0.05). Israa-knockout mice exhibited less severe psoriasis in all scoring, biochemical, and histological parameters compared to wild-type mice (p < 0.05). This study highlights Israa as a crucial molecule in psoriasis and confirms its immunomodulatory role in inflammatory diseases.


Subject(s)
Disease Models, Animal , Imiquimod , Psoriasis , Animals , Humans , Mice , CD4 Antigens/metabolism , CD4 Antigens/genetics , Imiquimod/administration & dosage , Interleukin-10/genetics , Interleukin-10/metabolism , Interleukin-17/metabolism , Interleukin-17/genetics , Leukocyte Elastase/metabolism , Leukocyte Elastase/genetics , Methotrexate , Mice, Inbred C57BL , Mice, Knockout , Psoriasis/chemically induced , Psoriasis/drug therapy , Psoriasis/pathology , Psoriasis/genetics , Psoriasis/immunology , Recombinant Proteins/administration & dosage , Skin/pathology , Skin/drug effects , Skin/immunology , Tumor Necrosis Factor-alpha/metabolism
3.
Curr Health Sci J ; 50(2): 215-222, 2024.
Article in English | MEDLINE | ID: mdl-39371054

ABSTRACT

Our observational study included on 54 patients with PsO, evaluated into the Dermatology Department of the Emergency County Hospital Craiova, Romania, between August 2023 and January 2024, and 40 controls. Our research proposed determining the prevalence of MetS in a cohort of PsO patients, and its relationship to subclinical atherosclerosis, evaluated by carotid ultrasound. Metabolic syndrome (MetS) was established according to National Cholesterol Education Program (NCP) Adult Treatment Panel (ATP) III criteria for MetS for 35 of the patients (64.81%) vs. 11 of the control group (27.5%), p=0.0003. An overview of each component of MetS depending on the diagnostic criteria for MetS showed that waist and total cholesterol exerted significant differences. Carotid ultrasound evaluation revealed an increased ITM, of over 0.9mm, for 19 (35.18%) or PsO patients, significantly increased compared to controls, as well as the presence of carotid plaques in significantly different percentages (37.03% PsO vs. 17.5% controls, p=0.001). We also noted that for patients with MetS, US examination displayed increased results for IMT compared to those without MetS. The prevalence of carotid atheroma plaque was augmented in patients with MetS and PsO. In our PsO group IMT exerted a positive inter-relation with: age, MetS, blood glucose, disease duration, and PASI. Important to note is that after multiple linear regression analysis, age and MetS were independent indicators of IMT (p=0.02 for age and p=0.001 for MetS). Our findings sustain a firm relationship between MetS and psoriasis and the major consequence of this observation is the inherent risk of cardiovascular events.

4.
Eur J Pharm Sci ; : 106925, 2024 Oct 05.
Article in English | MEDLINE | ID: mdl-39374744

ABSTRACT

Psoriasis is an immune-mediated chronic inflammatory disease that causes major psychosocial impact. Topical corticosteroids represent the standard pharmacological treatment for mild-to-moderate disease, but their local and systemic adverse effects reinforce the need for treatment innovations. Here we developed lamellar phase-based formulations for topical delivery of a hybrid dexamethasone and hydrogen sulfide (H2S) donor molecule (Dexa-TBZ), aiming to potentiate the effects of the glucocorticoid with H2S. They offer the possibility to obtain precursor formulations free of water that originate lamellar phases upon water addition, preventing drug hydrolysis during storage. Two groups of formulations were developed varying the surfactants and oil phase types and content. Systems containing 20 and 70% of water formed, respectively, bulk lamellar phase and a more fluid formulation consisting of dispersed droplets (< 1000 nm) stabilized by lamellar phase. Both presented pseudoplastic behavior. Dexa-TBZ was incorporated at 1%, remaining stable for 8 h. Drug content decreased to ∼80% after 1 week in precursor formulations free of water, but remained stable after that. Without causing changes to the cutaneous barrier function ex vivo or to the histological structure of the skin in vivo, the formulation containing phosphatidylcholine as surfactant and 70% of water promoted 1.8- and 2.7-fold increases in Dexa-TBZ penetration in the stratum corneum and epidermis+dermis, respectively, compared to a control solution, demonstrating their potential applicability as topical delivery systems.

5.
Int J Dermatol ; 2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39375798

ABSTRACT

BACKGROUND: Despite advancements in psoriasis treatment, a gap remains in aligning patient satisfaction with clinical outcomes. Our study aimed to evaluate which clinical and psychological factors may impact treatment satisfaction in psoriatic patients undergoing long-term biological therapies. METHODS: We performed an observational, cross-sectional, single-center study involving adult patients with moderate-to-severe psoriasis treated with biologics for at least 12 months. We collected sociodemographic characteristics and data on the course of the psoriasis. We also assessed the absolute (residual) Psoriasis Area and Severity Index (PASI), the site of the residual disease, and the severity of pruritus through the Visual Analogue Scale (VAS). Satisfaction was evaluated using the Treatment Satisfaction Questionnaire for Medication (TSQMv.II). The Type D Personality Scale (DS14 questionnaire and Patient Health Questionnaire-9 assessed the psychological profile. RESULTS: Overall, 146 patients were included, and 82.1% were globally satisfied (global satisfaction TSQM score >75). Linear regression analysis showed a negative correlation between global satisfaction scoring and residual PASI. The multivariable analysis found a higher VAS-pruritus score (OR = 1.20, 95% CI = 1.01-1.44; P = 0.043) and not reaching a residual PASI < 2 (OR = 0.30, 95% CI = 0.09-0.94, P = 0.039) as the strongest predictors of global unsatisfied patients (TSQM < 75%). Other factors unrelated to residual disease, such as gender, class of biologic agent, and type D personality, have also been found to impact patient satisfaction. CONCLUSIONS: Our study's findings underscore the complexity of patient satisfaction in psoriasis management and highlight the multifactorial nature of treatment success beyond traditional clinical measures.

6.
Small ; : e2405927, 2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39375985

ABSTRACT

Methotrexate is successfully used as the gold standard for managing moderate-to-severe psoriasis. However, the low bioavailability and short half-life of the oral pills and the invasiveness of the parenteral injections make these suboptimal therapeutic options. Microneedles, bridging the advantages of the former forms, are successfully used to deliver methotrexate for different therapeutic purposes. However, the utilized dissolving microneedles demand frequent administration, potentially compromising patients' compliance. Additionally, the high toxicity of methotrexate prompts a quest for safer alternatives. Phloretin, a natural compound with confirmed antipsoriatic potential, emerges as a promising candidate. Herein, microneedle patches with separable, slow-degrading tips are developed for the sustained delivery of methotrexate and phloretin, as a comprehensive solution for long-term psoriasis management. Both compounds are individually loaded at varying doses and display sustained-release profiles. The developed microneedle patches demonstrate high mechanical strength, favorable drug delivery efficiency, and remarkable antipsoriatic potential both in vitro in keratinocytes and in vivo in a psoriasis mouse model. Comparative analysis with two subcutaneous injections reveals a similar antipsoriatic efficacy with a single patch of either compound, with prominent phloretin safety. Therefore, the developed patches present a superior alternative to methotrexate's current marketed forms and provide a viable alternative (phloretin) with comparable antipsoriatic efficacy and higher safety.

7.
Clin Cosmet Investig Dermatol ; 17: 2197-2213, 2024.
Article in English | MEDLINE | ID: mdl-39376789

ABSTRACT

Background: Psoriasis, a chronic and recurrent inflammatory skin disease, current treatments can only alleviate its symptoms. There is still no complete cure. Although increasing research supports the therapeutics to be better, the common mechanism of its occurrence is still not fully elucidated. Our study is about further explore the molecular mechanism of the occurrence of this disease. Methods: The gene expression profiles of psoriasis (GSE151177, GSE41664, GSE30999) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) of psoriasis using R software, three kinds of analyses were performed, namely WGCNA, GWAS Analysis, Drug Target Prediction. Results: A total of 14 common DEGs was selected for subsequent analyses. Our Drug Target Prediction analysis revealed that the expression profiles influenced by certain drugs, including methotrexate, budesonide, amino purvalanol-a, and selumetinib, exhibited negative correlations with the disease-perturbed expression profiles. Finally, It was found that S100A4, JAML, TRAF3IP3, MIAT, IL7R, and KLRB1 were prominently expressed in the immune pathway related to allograft rejection. In the metabolic pathway, oxidative phosphorylation showed high expression levels, while the reactive oxygen species pathway was notably expressed in the signaling pathways domain. Conclusion: Our study reveals the potential drugs and pathogenesis of psoriasis. These potential pathway and hub genes may provide new ideas for further mechanism research.

8.
J Cutan Pathol ; 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39377573

ABSTRACT

BACKGROUND: There are limited surrogate biomarkers to identify the active inflammatory pathway in psoriasis to direct treatment with targeted biologic therapies. We investigated the association of interleukin (IL)-36 epidermal expression, a diagnostic marker of psoriasis, with response to biologic therapy in patients with psoriasis. METHODS: Retrospective immunohistochemical and chart review pilot study. RESULTS: Patients with psoriasis with low (scores 0-2) vs. high (scores 3-4) IL-36 expression did not have significantly different response rates to tumor necrosis factor α (TNFα), IL-17, and IL-12/23 or IL-23 inhibitors; and similarly, mean IL-36 expression scores did not significantly differ among responders vs. non-responders to each treatment mechanism. However, in patients with psoriasis treated with IL-12/23 or IL-23 inhibitors, there was a marked absolute difference in response rates in those with high vs. low IL-36 (84% vs. 50%, p = 0.12) and in mean IL-36 scores in responders vs. non-responders (3.35 vs. 2.57, p = 0.19). CONCLUSIONS: Patients with psoriasis with high IL-36 expression were more likely to respond to IL-12/23 and IL-23 inhibition than those with low IL-36, though these findings were not statistically significant. Additional studies with larger sample sizes are needed to validate and expand upon these findings.

9.
Article in English | MEDLINE | ID: mdl-39354758

ABSTRACT

AIM: Psoriasis is an immune-mediated skin disease that occurs worldwide and is characterized by high prevalence and chronicity. Psoriasis has a complex pathogenesis and is difficult to cure. Therefore, continuous exploration of the pathogenesis of psoriasis and the search for new drug treatment methods are crucial for improving treatment efficiency and reducing psychological damage to psoriasis patients. The active ingredients in Dihuang Zicao granules (DHZCG) can effectively treat psoriasis. Therefore, this study aimed to analyze the active ingredients of DHZCG and their potential mechanisms for treating psoriasis. METHODS: The effective components of DHZCG were screened via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Genetic information for psoriasis was retrieved from the GeneCards, OMIM and DisGENET databases. Protein-Protein Interaction (PPI) analysis was performed, and component‒target‒disease networks were constructed. Important molecular biological processes and signaling pathways were screened via GO and KEGG analyses. Molecular docking of the active ingredients and key targets was performed via AutoDock Vina (1.1.2). A mouse model of psoriasis was established and divided into a control group, model group, low-dose DHZCG group (L-DHZCG), medium-dose DHZCG group (M-DHZCG), and high-dose DHZCG group (H-DHZCG). Hematoxylin and Eosin (HE) staining was performed to determine the pathological changes in the skin of each group of mice, and the Psoriasis Area Severity Index (PASI) score was used to assess skin damage. ELISA and RT‒ PCR were used to measure the levels of the inflammatory factors TNF-a, IL-17A, and IL-23 in the serum and skin tissue of the mice, respectively. Western blotting was used to analyze the expression of proteins related to the AGE/RAGE signaling pathway. Immunofluorescence was used to examine the expression of the inflammatory factor NF-kB. Immunohistochemistry was used to measure IL-1ß and TNF-a expression in skin tissues. RESULTS: Sixty genes associated with psoriasis treatment by DHZCG, including core genes encoding IL-6, TNF-a, AKT1, IL-1ß, TP53, NFKB1, BCL2, and MAPK3, were identified. Through the construction of a psoriasis mouse model, DHZCG treatment effectively reduced skin damage and significantly decreased the levels of the validated factors TNF-a, IL-17A, IL- 23, IL-1b, and NF-kB in the serum and damaged skin. Furthermore, the reduction in the levels of these inflammatory factors by DHZCG is associated with the downregulation of the AGE/RAGE signaling pathway. CONCLUSION: DHZCG reduces inflammation and alleviates psoriasis by downregulating the AGE/RAGE/NF-kB signaling pathway. This study is beneficial for providing a theoretical basis for the development of drugs for psoriasis and for offering personalized treatment strategies for the clinical management of psoriasis.

10.
Pol Merkur Lekarski ; 52(4): 439-444, 2024.
Article in English | MEDLINE | ID: mdl-39360725

ABSTRACT

OBJECTIVE: Aim: The purpose of this article is to review the literature on the applicability of biologic agents, their mechanism of action, safety and factors affecting their choice in selected chronic conditions: asthma, psoriasis, ankylosing spondylitis and ulcerative colitis. PATIENTS AND METHODS: Materials and Methods: The electronic databases MEDLINE/PubMed and ScienceScholar were searched for studies published in English and Polish and indexed from 2018 to April 2024. Dodatkowo uwzgledniono Stanowisko Polskiego Towarzystwa Alergologicznego i Polskiego Towarzystwa Chorób Ukladu Oddechowego, rekomendacje Polskiego Towarzystwa Dermatologicznego, wytyczne Polskiego Towarzystwa Gastroenterologii i konsultanta krajowego w dziedzinie gastroenterologii oraz wytyczne Global Initiative for Asthma (GINA). CONCLUSION: Conclusions: 1. Biological therapy demonstrates a significant reduction in the severity of clinical symptoms and complications associated with a variety of disease entities. An additional value of this therapy is its effectiveness among patients who do not respond to traditional treatment strategies. 2. In the perspective of the future of biologic treatment, it is important to study potential interactions between biologic drugs and other therapeutic methods. 3. To maximize benefits while minimizing complications, requires an individualized approach for each patient.


Subject(s)
Asthma , Colitis, Ulcerative , Humans , Colitis, Ulcerative/therapy , Colitis, Ulcerative/drug therapy , Asthma/drug therapy , Asthma/therapy , Chronic Disease , Psoriasis/drug therapy , Psoriasis/therapy , Spondylitis, Ankylosing/drug therapy , Spondylitis, Ankylosing/therapy , Biological Therapy , Biological Products/therapeutic use
12.
Front Med (Lausanne) ; 11: 1451069, 2024.
Article in English | MEDLINE | ID: mdl-39359925

ABSTRACT

Introduction: Plaque psoriasis is a persistent skin disorder that necessitates efficient management. This study investigates the therapeutic effectiveness and timeline for skin lesion resolution in plaque psoriasis patients treated with combined biologic agents compared to standard therapies. Methods: Conducted retrospectively between March 2020 and March 2023, the study included 162 patients with moderate to severe plaque psoriasis. Participants were divided into two groups: the Control Group, which received standard treatments, and the Combined Biologic Agent Group, which received additional biologic therapy with secukinumab. Participants in the Control Group received standard treatments, while those in the Combined Biologic Agent Group received standard treatments plus secukinumab. Results: The results showed that the Combined Biologic Agent Group experienced a significantly faster onset of therapeutic effects, with an average time of 3.04 ± 2.25 days compared to 6.12 ± 2.06 days in the Control Group. Additionally, skin lesion resolution occurred more rapidly in the biologic agent group (7.04 ± 2.13 days) than in the control group (14.56 ± 4.73 days). By week 24, the Psoriasis Area and Severity Index (PASI) scores demonstrated a more substantial reduction in the biologic agent group, decreasing from 26.98 ± 11.28 to 2.48 ± 3.01, whereas the control group showed a reduction from 25.82 ± 10.47 to 10.40 ± 7.63. The overall effectiveness rate was higher in the biologic agent group, with no cases of ineffectiveness, compared to a 20.99% ineffectiveness rate in the control group. Furthermore, there was no recurrence of the disease in the biologic agent group, while the control group experienced an 11.11% recurrence rate. Both groups had a similar incidence of adverse reactions, indicating that the addition of biologic agents does not significantly increase the risk of adverse events. Discussion: These findings suggest that combined biologic agent therapy offers a more effective and faster treatment option for plaque psoriasis without compromising safety. However, larger-scale clinical trials are necessary to validate these results and establish the long-term benefits and safety of this treatment approach in diverse patient populations.

13.
Article in English | MEDLINE | ID: mdl-39361844

ABSTRACT

Objectives Tofacitinib is used as an oral Janus-associated kinase (JAK) inhibitor acting on JAK1 and JAK3, in treating psoriatic disease. However, there is still no consensus on the optimal dosage and duration of tofacitinib. In this study, we aimed to evaluate the effects of tofacitinib in treating psoriatic disease. Methods and Materials A literature search was done utilising Cochrane library, Medline, EMBASE, Wiley Online library, Web of Science and BIOSIS Previews through December 18, 2022. We performed a meta-analysis of published original studies to assess the impact of tofacitinib in plaque psoriasis or psoriatic arthritis therapy based on seven randomised controlled trials (RCTs) involving 2,672 patients (receiving tofacitinib) and 853 controls (receiving placebo). Results Compared with placebo, the treatment of 5 mg twice-daily (BID) tofacitinib for 12 weeks is sufficient to significantly alleviate the main clinical manifestations of psoriasis [≥75% decrease in Psoriasis Area and Severity Index score (PASI 75): Risk ratio (RR)=4.38 (95% Confidence interval (CI) 2.51 to 7.64); ≥90% decrease in PASI score (PASI 90): RR=21.68 (95% CI 4.20 to 111.85); Physician's Global Assessment of 'clear' or 'almost clear' (PGA 0/1): RR=3.93 (95%CI 3.03 to 5.09)]. Interestingly, there was no significant difference in improvement in PGA 0/1 with 5 mg BID tofacitinib given for 16 weeks when compared with 5 mg BID tofacitinib for 12 weeks [RR=1.11 (95%CI 0.98 to 1.25)]. Additionally, the 5 mg BID tofacitinib for 16 weeks treatment schedule significantly increased the incidence of upper respiratory tract infection (URTI) [RR=1.89 (95%CI 1.06 to 3.38)] as compared to 5 mg BID tofacitinib for 12 weeks treatment schedule [RR=1.15 (95%CI 0.60 to 2.20)]. Conclusion The 5 mg BID tofacitinib for 12 weeks treatment significantly improved psoriasis without causing too many specific adverse events. This indicated that tofacitinib is an effective treatment plan for psoriatic disease by reasonably controlling dosage and dosing time.

14.
Article in English | MEDLINE | ID: mdl-39361841

ABSTRACT

Background Psoriatic arthritis (PsA) is seen in almost 30-40% cases of psoriasis. Psoriasis precedes the onset of PsA in 85% of cases. Delay in the diagnosis of PsA may lead to poor functional outcomes and morbidity. Screening psoriasis patients with high-frequency ultrasound helps to diagnose arthritis at an early stage leading to prompt intervention and possible reduction in the morbidity associated with the disease. Objectives To determine the role of high frequency ultrasonography (USG) in the detection of subclinical PsA. Methods A cross-sectional study was conducted in a dermatology and radiology department of Armed Forces Medical College, Pune between July 2021 and December 2022. Patients of chronic plaque psoriasis with no clinical evidence of arthritis were assessed using high-frequency USG. Various parameters such as bony erosions, synovial thickening, tendon thickening, tendon hypo-echogenicity, calcifications and power doppler signals were assessed. Results A total of 117 patients were included in the study. The distal interphalangeal joint (DIP) and Achilles tendon were the most commonly affected sites. Synovial thickening in DIP was observed in 67 (57%) patients and Achilles tendon thickening was observed in 39 (33%) patients. Limitations of the study The cross-sectional nature of the study is the major limitation. A longitudinal study will be required to understand the clinical relevance of ultrasonographic changes in these patients. Another limitation of the study is the lack of age and gender-matched controls. Future research should include such controls to ensure more accurate results. Conclusion Subclinical arthritis is common in patients with chronic plaque psoriasis. High-frequency ultrasound is a useful tool for detecting subclinical synovitis and enthesitis in asymptomatic patients. The DIP joint and Achilles tendon ultrasound can be used for screening for early detection of PsA.

15.
Article in English | MEDLINE | ID: mdl-39361853

ABSTRACT

Generalised pustular psoriasis (GPP) is a chronic, multisystemic, autoinflammatory disease with predominantly cutaneous manifestations, characterised by recurrent episodes of widespread, macroscopic and aseptic pustules. It has a highly unpredictable, heterogeneous and unstable clinical course. There are no consensus guidelines in India for the management of GPP. The objective of this Delphi panel study was to achieve consensus on problem areas in the understanding and management of GPP. Based on the inputs from an expert panel, 19 topics across six domains were identified as being important regarding the understanding and management of GPP. Statements were developed for these 19 topics, and consensus for the statements was sought using the modified Delphi method. Twelve experts evaluated the statements, indicating their agreement or disagreement. Consensus was considered to be reached when ≥80% of experts agreed with a statement. After two rounds of discussion, consensus was reached for 17 out of 19 (89%) statements and no consensus was achieved for two (11%) statements. We have presented the statements along with the respective degrees of consensus. Wherever relevant, clarifications or additional comments by experts are provided in the document.

17.
Article in English | MEDLINE | ID: mdl-39365309

ABSTRACT

Berberine (BBR), a Rhizoma Coptis-sourced isoquinoline alkaloid, is an effective drug for psoriasis treatment with its therapeutic mechanism remaining unclear. We delved into the mechanism of BBR affecting psoriatic skin inflammation by regulating keratinocyte pyroptosis. A psoriasis-like skin inflammation mouse model was induced by imiquimod (IMQ) and treated with BBR and a p38 activator anisomycin. Human epidermal keratinocytes (HEKs) were stimulated with five chemokines (M5) [interleukin (IL)-17A, IL-22A, oncostatin M, tumor necrosis factor-α, IL-1α] to simulate psoriasis immune microenvironment, then treated with BBR and anisomycin. Psoriasis skin lesions, skin tissue damage, cell viability and death, and gasdermin D-N (GSDMD-N) and NOD-like receptor protein 3 (NLRP3) positive cell numbers were assessed. The p38 mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) pathway and levels of the NLRP3/GSDMD pathway-related proteins and inflammatory factors were determined. BBR alleviated M5-induced HEK pyroptosis by inactivating NLRP3 inflammasomes. BBR inhibited the p38 MAPK/NF-κB pathway, and its effects on HEKs were partly averted by activating the p38 MAPK/NF-κB pathway. BBR repressed NLRP3 inflammasome activation and pyroptosis by inhibiting the p38 MAPK/NF-κB pathway. Collectively, BBR suppressed keratinocyte NLRP3/GSDMD pathway pyroptosis by suppressing the p38 MAPK/NF-κB pathway, thereby affecting psoriasis skin inflammation.

18.
Article in English | MEDLINE | ID: mdl-39365432

ABSTRACT

INTRODUCTION: Psoriasis is a chronic immune-mediated skin disease with several comorbidities and a considerable influence on quality of life. Many patients with moderate-to-severe psoriasis are undertreated and have a substantial disease duration before effective treatment is started. This study analyzed patient and disease characteristics and time to effective treatment of patients with psoriasis who consulted PsoPlus. It also examined whether a treat-to-target (T2T) approach, which is implemented in PsoPlus, has an impact on treatment choice and disease progression. METHODS: Through a single center, retrospective study, 170 patients in the PsoPlus dedicated clinic were compared at moment of enrollment in PsoPlus and at the last recorded consultation in 2021. RESULTS: Median disease duration at the first PsoPlus consultation was 16.0 (interquartile range (IQR) 19.0) years. There was a significant difference in Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) between the first and the last recorded PsoPlus consultation (PASI 6.0 (IQR 6.4) vs. 0.6 (IQR 2.6); DLQI 11 (IQR 11) vs. 2 (IQR 6); p < 0.001). A weak positive Spearman correlation (rs) was found between disease duration and PASI at the first PsoPlus consultation (rs = 0.175; p = 0.034), while a weak negative correlation (rs = - 0.2; p = 0.013) was found at the last registered PsoPlus consultation. Patients with a disease duration of more than 20 years had significantly more switches of treatment than those with a shorter disease duration (p < 0.001). Median time from psoriasis onset until PASI ≤ 2 was 16.0 years. Median time from the first PsoPlus consultation until PASI ≤ 2 was 7.0 months. CONCLUSION: The PsoPlus program with its T2T approach effectively improves clinical outcomes and quality of life for patients with psoriasis in a relatively short period, emphasizing the value of a structured, personalized treatment plan for long-term management.

19.
Int J Circumpolar Health ; 83(1): 2412378, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39363155

ABSTRACT

Cold climate and unique genetic and environmental factors may influence the prevalence of skin diseases in Greenland. However, there is a lack of epidemiological studies on skin diseases in the adult Greenlandic population. To address this unmet need a cross-sectional study, run by dermatologists from Denmark, the UK, and Switzerland estimated the prevalence and clinical manifestations of skin diseases among adults in East Greenland in May 2022. All adults ≥18 years in the town of Tasiilaq were invited, and 295 individuals aged 18-78 years participated (22.5% of the overall adult population in Tasiilaq). Two-hundred and three participants (69%) had visible signs of current skin disease, and among these, 242 cases of dermatoses were identified. The most common skin diseases were hand eczema (22.4%), lichen simplex (9.5%), discoid eczema (7.1%), psoriasis, atopic dermatitis and acne vulgaris (5.8% each). Scabies was the most frequent infectious skin disease (4.4%). No cases of skin cancer were identified. Atopic dermatitis and psoriasis presented with disease that was of limited extent and different from the classical presentations. Skin diseases showed a high prevalence among adults in East Greenland, and some of them were severe. This indicates a noteworthy public health problem that warrants better access to dermatologist support.


Subject(s)
Skin Diseases , Humans , Greenland/epidemiology , Adult , Middle Aged , Skin Diseases/epidemiology , Male , Female , Cross-Sectional Studies , Young Adult , Aged , Prevalence , Adolescent
20.
Cureus ; 16(9): e68510, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39364469

ABSTRACT

Objective In this study, we aimed to investigate the correlation between the clinical diagnosis, histological diagnosis, and patch test positivity among patients with foot dermatoses receiving treatment at the Department of Dermatology, MES Medical College, Perinthalmanna. Methodology A hospital-based cross-sectional observational diagnostic evaluation was carried out from January 1, 2019, to December 31, 2019, among 44 patients with foot dermatoses who met the inclusion criteria. A thorough general physical and cutaneous examination was performed to determine the type, extent, and morphology of lesions after obtaining the written informed consent; sociodemographic information and a thorough recording of patient history were gathered. In all cases, a potassium hydroxide (KOH) mount, skin biopsy, and patch testing were performed. Additionally, pus culture and sensitivity tests were conducted in pertinent cases. Results Our study found that the most prevalent foot dermatosis, based on clinical diagnosis, was allergic contact dermatitis (ACD) foot, affecting 26 patients (59.0%). This was followed by plantar psoriasis, observed in 13 patients (29.5%), and lichen planus, present in two patients (4.5%). The predominant histological diagnosis was ACD foot in 11 patients (25.0%), followed by plantar psoriasis in 10 patients (22.7%), spongiotic dermatitis in seven patients (15.9%), atopic dermatitis (AD) and psoriasiform dermatitis in four patients (9.1%) each, and tinea pedis in two patients (4.5%). The sensitivity of patch testing in detecting ACD foot was 90.91%, whereas its specificity was 57.58%. The positive and negative predictive values (PPV and NPV) were 41.67% and 95.0% respectively.  Conclusions Based on our findings, histopathological evaluation is a highly effective diagnostic technique for foot dermatoses, as it demonstrated exceptional diagnostic accuracy (p<0.001). The sensitivity of patch testing in identifying ACD of the foot was 90.91% (p<0.05). This highlighted the usefulness of patch testing as a confirmatory diagnostic tool along with histopathological evaluation for precise diagnosis of ACD of the foot. While laboratory testing can increase diagnostic precision, it cannot replace a clinical examination.

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