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Objective: The relationship between systemic immune‐inflammation index (SII) and psoriasis and its prognosis is not yet clear. In this study, the correlation between SII and psoriasis, psoriasis comorbidities, and all‐cause mortality was investigated based on the National Health and Nutrition Examination Survey (NHANES). Methods: The study population was derived from five NHANES cycles: 2003–2006, 2009–2014, and survival follow‐up was as of December 31, 2019. The association between SII and psoriasis and its comorbidities was analyzed using weighted multivariate logistic regression models. Weighted COX regression was used to calculate hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). Restricted cubic spline, subgroup and sensitivity analyses were also used. Logarithmic conversion was performed on SII(log2SII) to reduce the impact of outliers. Results: A total of 21,431 participants were included in this study. As a continuous variable, log2SII was significantly associated with psoriasis in the fully adjusted model [OR = 1.20(1.04–1.39), p =.01]. log2SII remained positively associated with psoriasis after excluding participants with a history of cancer or cardiovascular disease (CVD), or non‐Hispanic black participants. Among psoriasis patients, log2SII was significantly associated with metabolic syndrome (MetS) [OR = 1.68(1.19,2.38), p =.004] and all‐cause mortality [HR = 1.48(1.09,1.99), p =.01]. Similar results were consistently observed when SII was analyzed as a categorical variable (in quartiles). Conclusion: This study suggested a positive association between SII and the prevalence of psoriasis. Among psoriasis patients, SII was positively correlated with MetS and all‐cause mortality. [ABSTRACT FROM AUTHOR]

Background/Objectives: Psoriasis is a chronic inflammatory condition mediated by the immune system with various manifestations. The increased prevalence of subclinical joint involvement has led to the development of early diagnostic methods for psoriatic arthritis, including several instruments that have been validated and used in clinical practice. The aim of this study was to perform the Romanian translation, cultural adaptation, and validation of three assessment tools: the Early Arthritis for Psoriatic Patients (EARP) Questionnaire, Psoriasis Epidemiology Screening Tool (PEST), and Toronto Psoriatic Arthritis Screen 2 (TOPAS 2), which are designed to evaluate early-stage arthritis in patients with psoriasis. Methods: All the activities were carried out in accordance with the internationally recognized methodology recommended by the International Society for Pharmacoeconomics and Outcome Research (ISPOR), the recommendations of the World Health Organization (WHO) regarding the translation process and the validation of instruments, and data from the international literature. These three questionnaires were administered to 29 patients with psoriasis diagnosed by biopsy. A descriptive study was conducted and the data were analyzed with appropriate statistical tests using the PSPP program. A reliability test was assessed using Cronbach's alpha coefficient. Results: The obtained values were significant for the first two questionnaires, with a value of 0.89 for the EARP and 0.63 for the PEST, but the value was not as significant for ToPAS2, at 0.40. Conclusions: This pilot study revealed that the Romanian and original versions of the three questionnaires are similar. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic autoimmune disease with a long disease course and frequent relapse characteristics. It is now recognised to be associated with epidermal environments of inflammatory cytokines. However, its pathogenesis is still not completely clear. We found the haemorheology of psoriatic patients to be abnormal, and ageing and deformed erythrocytes increased in the blood. The abnormal erythrocytes were more likely to induce psoriasis, which was confirmed in a mouse model induced by different blood components of psoriatic patients/healthy volunteers. Spleen filtration dysfunction, which caused abnormal erythrocytes, was also more likely to induce psoriasis, which was confirmed in a mouse model induced by splenectomy. The mechanism was the weakening of the 'eat me' function of spleen macrophages phagocytizing ageing and deformed erythrocytes, resulting in the dysfunction of spleen filtration and the increase of ageing and deformed erythrocytes in the body. Additionally, the decreased oxygen‐carrying capacity and the declined antioxidant capacity of those erythrocytes led to the hypoxia environment, making psoriasis more likely to be induced. These findings demonstrate that spleen filtration dysfunction contributes to the pathogenesis of psoriasis and suggest that improving it may be an effective therapy for psoriasis and control its relapse. [ABSTRACT FROM AUTHOR]

Psoriasis is an inflammatory skin disease associated with an impaired skin barrier. The skin barrier function is dependent on the extracellular lipid matrix which surrounds the corneocytes in the stratum corneum. Ceramides comprise essential components of this matrix. Alterations in the stratum corneum ceramide profile have been directly linked to barrier dysfunction and might be an underlying factor of the barrier impairment in psoriasis. In this study, we investigated the ceramide profile and barrier function in psoriasis. Lesional and non‐lesional skin of 26 patients and 10 healthy controls were analysed using in‐depth ceramide lipidomics by liquid chromatography‐mass spectrometry. Barrier function was assessed by measuring transepidermal water loss. Lesional skin showed a significant decrease in the abundance of total ceramides with significant alterations in the ceramide subclass composition compared to control and non‐lesional skin. Additionally, the percentage of monounsaturated ceramides was significantly increased, and the average ceramide chain length significantly decreased in lesional skin. Altogether, this resulted in a markedly different profile compared to controls for lesional skin, but not for non‐lesional skin. Importantly, the reduced barrier function in lesional psoriasis correlated to alterations in the ceramide profile, highlighting their interdependence. By assessing the parameters 2 weeks apart, we are able to highlight the reproducibility of these findings, which further affirms this connection. To conclude, we show that changes in the ceramide profile and barrier impairment are observed in, and limited to, lesional psoriatic skin. Their direct correlation provides a further mechanistic basis for the concomitantly observed impairment of barrier dysfunction. [ABSTRACT FROM AUTHOR]

(1) Introduction: Topical dithranol is still commonly used today as an effective treatment for psoriasis. Dithranol treatment is often supplemented with balneotherapy, which has been shown to increase effectiveness and reduce side effects. The inorganic salts (sulfhide, selenium, zinc) are usually thought to be responsible for the effect. The antioxidant effect of the waters is thought to be behind the therapeutic effect, for which inorganic substances (sulfides, selenium, zinc) are thought to be responsible. The organic matter content of medicinal waters is also particularly important, as humic acids, which are often found in medicinal waters, have antioxidant effects. (2) Methods: In this short-term experiment, we aimed to test the possible protective effect of Szigetvár medicinal water and its organic matter isolate on HaCaT cells exposed to dithranol. Malondialdehyde levels were measured, and RT-qPCR was used to investigate the gene expression of selected cytokines relevant in the oxidative stress response (IL-6, IL-8, TNF-α, GM-CSF) and the expression of microRNA-21. (3) Results: Szigetvár medicinal water and the organic isolate prevented the increase in malondialdehyde levels caused by dithranol treatment. The cytokine gene expressions elevated by dithranol exposure were reduced by the treatment. (4) Conclusions: Szigetvár medicinal water and organic substances alone may have a protective effect on patients' healthy skin surfaces against dithranol damage. We also demonstrated that the organic compounds are also responsible for the protective effect. [ABSTRACT FROM AUTHOR]

(1) Background: The purpose of this study is to compare the rate of COVID-19 vaccination among psoriasis patients internationally and to correlate it with their treatment regimens. (2) Methods: We conducted a cross-sectional study from January 2021 to October 2022 among adults in the United States (US), Chile, China, Switzerland, and Singapore using the Global Healthcare Study on Psoriasis survey. (3) Results: A total of 310 psoriasis patients in the US (98), Chile (32), China (80), Switzerland (39), and Singapore (61) were surveyed. Of these, 248 patients (80.0%) were vaccinated at least once for COVID-19 (Chile: 100%, Singapore: 100%, US: 93.9%, Switzerland: 69.2%, China: 45.0%). Compared with other countries, patients in China were 89% less likely to report at least one COVID-19 vaccination (1 − 0.11 = 0.89; OR 0.11; 95% CI: 0.03–0.48), and patients in Switzerland were 80% less likely (1 − 0.20 = 0.80; OR 0.20; 95% CI: 0.05–0.79). Compared with patients on biologics, patients on topicals were 10.9 (95% CI: 2.1–56.6) times more likely to report at least one COVID-19 vaccination, and patients on oral systemics were 7.2 times more likely (95% CI: 1.6–31.6). (4) Conclusions: Country of residence and treatment regimen are associated with different COVID-19 vaccination rates in psoriasis patients. [ABSTRACT FROM AUTHOR]

A literature search on the subject of botulinum toxin treatment in psoriasis found 15 relevant articles, 11 on human subjects and 4 on animal studies. Of the human data, eight were clinical trials and three were single case reports. Seven out of eight clinical trials, all open-label, reported improvement in psoriasis following intradermal or subcutaneous botulinum toxin injections. One double-blind, placebo-controlled study, which used a smaller dose than the open-label studies, did not note a healing effect. Animal studies have shown that injection of botulinum toxins in the skin heals psoriatic skin lesions and can reduce the level of interleukins (ILs) and cytokines as well as inflammatory cells in psoriatic plaques. There is a need for controlled, blinded studies conducted in larger numbers of patients with doses that have shown promise in open-label studies. [ABSTRACT FROM AUTHOR]

Background/Objectives: Implementing model-informed precision dosing (MIPD) strategies guided by population pharmacokinetic/pharmacodynamic (PK/PD) models could enhance the management of inflammatory diseases such as psoriasis. However, the extent of individual experimental data gathered during MIPD significantly influences the uncertainty in estimating individual PK/PD parameters, affecting clinical dose selection decisions. Methods: This study proposes a methodology to individualize ustekinumab (UTK) dosing strategies for 23 Spanish patients with moderate to severe chronic plaque psoriasis., considering the uncertainty of individual parameters within a population PK/PD model. Results: An indirect response model from previous research was used to describe the PK/PD relationship between UTK serum concentrations and the Psoriasis Area and Severity Index (PASI) score. A maximum inhibition drug effect (Imax) model was selected, and a first-order remission constant rate of psoriatic skin lesion (kout = 0.016 d−1) was estimated. Conclusions: The MIPD approach predicted that 35% and 26% of the patients would need an optimized and intensified dosage regimen, respectively, compared to the regimen typically used in clinical practice. This analysis demonstrated its utility as a tool for selecting personalized UTK dosing regimens in clinical practice in order to optimize the probability of achieving targeted clinical outcomes in patients with psoriasis. [ABSTRACT FROM AUTHOR]

Background: Baricitinib, commonly used for autoimmune diseases, is typically administered orally, which can lead to systemic adverse effects. A topical formulation could potentially offer localized therapeutic effects while minimizing these side effects. Objectives: This study focuses on developing a lipid-based topical formulation of baricitinib (BCT-OS) for treating psoriasis. Methods: The optimized formulation was then assessed for physical, chemical, and biopharmaceutical characterization. Furthermore, the anti-inflammatory efficacy of the formulation was tested in a model of psoriasis induced by imiquimod in mice, and its tolerance was determined by the evaluation of biomechanical skin properties and an inflammation test model induced by xylol in mice. Results: BCT-OS presented appropriate characteristics for skin administration in terms of pH, rheology, extensibility, and stability. The formulation also demonstrated a notable reduction in skin inflammation in the mouse model, and high tolerability without affecting the skin integrity. Conclusions: BCT-OS shows promise as an alternative treatment for psoriasis, offering localized therapeutic benefits with a potentially improved safety profile compared to systemic administration. [ABSTRACT FROM AUTHOR]

(1) Background/Objectives: Nail psoriasis (NP) is a chronic and difficult-to-treat disease, which causes significant social stigma and impairs the patients' quality of life. Moreover, nail psoriasis is a true therapeutic challenge for clinicians. The presence of nail psoriasis can be part of a severe form of psoriasis and can have predictive value for the development of psoriatic arthritis. Our real-world-evidence multicenter study aims to evaluate the efficacy of bimekizumab in nail psoriasis. (2) Methods: A retrospective analysis of a multicenter observational study included 834 patients affected by moderate-to-severe psoriasis, in 33 Dermatologic Units in Italy, treated with bimekizumab from December 2022 to September 2023. Clinimetric assessments were based on Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Physician's Global Assessment of Fingernail Psoriasis (PGA-F) for the severity of nail psoriasis at 0, 12, 24, and 36 weeks. (3) Results: Psoriatic nail involvement was present in 27.95% of patients. The percentage of patients who achieved a complete clearance of NP in terms of PGA-F 0 was 31.7%, 57%, and 88.5% at week 4, 16, and 36, respectively. PASI 100 was achieved by 32.03% of patients at week 4, by 61.8% at week 16, and by 78.92% of patients at week 36. The mean baseline PASI was 16.24. The mean DLQI values for the entire group of patients at baseline, at week 4, at week 16, and at week 36 were 14.62, 3.02, 0.83, and 0.5, respectively. (4) Conclusions: Therapies that promote the healing of both the skin and nails in a short time can also ensure a lower risk of subsequently developing arthritis which is disabling over time. Bimekizumab proved to be particularly effective to treat NP, with a fast response in terms of complete clearance, with over 88.5% of patients free from NP after 36 weeks. The findings of our real-world study showed that patients with moderate-to-severe PsO and concomitant NP had significantly faster and more substantial improvements in NP up to 36 weeks with respect to previous research findings. Considering the rapid healing of the nail, the dual inhibition of IL17 A and F might have a great value in re-establishing the dysregulation of keratin 17 at the nail level. [ABSTRACT FROM AUTHOR]

Psoriasis is a long-term inflammatory skin disorder that significantly affects a patient's quality of life in addition to having notable physical symptoms. Recent research has increasingly focused on the neuropsychiatric dimensions of psoriasis, recognizing the complex interplay between psychological health and dermatological disease. There is growing recognition of the correlation between psoriasis and neuropsychiatric conditions such as anxiety, depression, and cognitive decline, indicating the reciprocal interaction of the skin and brain. This study explores the prevalence and implications of neuropsychiatric disorders among 3,850 psoriasis patients, of whom 458 were diagnosed with neuropsychiatric conditions. The results emphasize the value of treating psoriasis with a multidisciplinary approach. Integrating care that addresses dermatological and neuropsychiatric health is crucial for improving patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Objectives: Cold plasma has shown efficacy in various dermatological applications by reduces inflammatory responses and modulating cytokine expression. Therefore, this study aimed to investigate the therapeutic effects of cold plasma on psoriasis. Methods: In psoriasis HaCaT cells with cold plasma, we confirmed the expression of inflammatory cytokines involved in psoriasis formation and MAPK pathway, cell cycle, and apoptosis‐related factors. In psoriasis‐like BALB/c mice model, the effects of cold plasma treatment on skin were visually assessed. The expression of psoriasis‐related factors was confirmed through qPCR, Western blotting, and Immunohistochemistry. Results: Cold plasma led to a reduction in inflammatory cytokines including IL‐17A, IL‐23A, IL‐24, IL‐1β, and TNF‐α in the psoriasis cell line. It also modulated factors involved in the MAPK pathway and the cell cycle. In the psoriasis‐like mice model, cold plasma resulted in improvements in skin thickness, erythema, scaling, and PASI. Additionally, decreases in inflammatory cytokines like INF‐γ, IL‐23, and S100a7 were observed, along with improvements in MAPK pathway activation, apoptosis, and other psoriasis‐related factors. Conclusion: Through in vitro and in vivo studies, our research highlights the potential of cold plasma as a novel therapeutic approach for psoriasis. Furthermore, cold plasma could serve as an adjunctive treatment for skin immunological diseases. [ABSTRACT FROM AUTHOR]

Background: Biologics are among the most effective therapies for psoriasis. However, many patients are only introduced to them at advanced stages of the disease course. Objectives: Our aim was to identify predictors of initiating biologic therapy in patients with psoriasis and compare patients initiating biologics early versus late in their disease course. Methods: Kaplan–Meier curves visualized time to biologic initiation, while Cox regression models further explored variables as predictors of biologic initiation. Mann–Whitney U and chi‐squared tests compared patients who started biologics early with those who began biologics later in the disease course. Results: Our primary analysis included 233 psoriasis patients. Cox regression showed that age at diagnosis (P = 0.007), general physical well‐being (P = 0.02), and nail psoriasis severity (P = 0.02) were significantly associated with time to biologic initiation. Our secondary analysis, the comparisons between patients starting biologics early versus later in the disease course, included a total of 378 patients. The median (interquartile range [IQR]) age at diagnosis was 34.5 (25.0–51.2) years for patients initiating biologics within 5 years, compared to 22.0 (15.0–32.8) years for patients initiating biologics later (P < 0.0001). The median (IQR) age at initiation was 37.0 (27.0–53.2) and 45.0 (36.0–55.0) years for patients initiating biologics earlier versus later than 5 years (P = 0.04). Conclusions: Age at diagnosis, general well‐being, and severity of nail psoriasis significantly predicted future initiation of biologic treatment. Patients initiating biologics early in their disease course were generally older at diagnosis but younger at the time of biologic initiation compared to patients initiating biologics later in their disease course. [ABSTRACT FROM AUTHOR]

The article discusses the real-world effectiveness and drug survival of guselkumab over a 3-year period in treating moderate-to-severe plaque psoriasis, including difficult-to-treat areas. Guselkumab, an anti-IL23 biologic, has shown superior efficacy compared to adalimumab in clinical trials, with sustained high levels of clinical response over 5 years of treatment. Real-life studies have confirmed the effectiveness and safety of guselkumab, particularly in difficult-to-treat areas like scalp, palmoplantar, and genital psoriasis. The study emphasizes the importance of being treatment-naive for achieving complete or almost complete clinical clearance at Week 52. [Extracted from the article]

Background: Device‐related infective endocarditis (IE) is associated with high mortality, resulting in a growing emphasis on identifying and managing comorbidities that increase the risk of IE in these patients. Psoriasis is increasingly being recognized as having multiple cardiovascular manifestations. However, little is known about the impact of psoriasis on IE risk in patients with permanent pacemakers (PPM). Our study aimed to assess whether psoriasis is associated with an increased risk of developing IE in patients with PPM. Methods: The National Inpatient Sample database was utilized to extract patients with PPM. The presence of psoriasis stratified patients. Demographic and comorbidity data were collected. 1:10,000 propensity matching for IE risk factors was performed to examine independent associations between psoriasis and IE. Results: Of 437,793 patients, 45 had psoriasis. Psoriasis patients had higher IE rates (4.4% vs. 0.6%; P < 0.01). On multivariate analysis, psoriasis was associated with a 7.2‐fold high IE risk (OR: 7.2 [1.7–30.2]; P < 0.01). Post‐match analysis showed an 8.3‐fold IE risk in psoriasis patients (OR: 8.3 [2.0–34.4]; P < 0.001). Conclusion: Psoriasis was independently associated with elevated IE risk in patients with PPM. Further studies are required to corroborate these findings, which will have implications for IE prophylaxis. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, relapsing inflammatory skin disorder that is associated with substantial physical and psychosocial comorbidity. Although biologic agents have offered transformative therapeutic advantages to those unresponsive to traditional treatments, data from recent literature indicate significant undertreatment of certain populations, highlighting potential barriers to access. This review aims to comprehensively elucidate barriers to biological therapy, addressing a recognized gap in the current literature. A search was conducted using MEDLINE, Embase, and Web of Science to investigate the obstacles and disparities that prevent access to biologic treatments in biologic‐naïve psoriatic patients. Emergent themes were then systematically categorized into five primary domains: patient‐level, prescriber‐level, medicine‐level, organizational‐, and external environment‐level factors. Our results demonstrate pronounced barriers and disparities encompassing increased age, race, socioeconomic status, rural location, cost and insurance, and insufficient knowledge that may hinder access to biologic treatments among psoriatic patients. Further research on how these barriers can be effectively addressed is needed to optimize treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: IL‐23 inhibitors were recently approved for the treatment of skin psoriasis and psoriatic arthritis (PsA). Risankizumab, a humanized monoclonal antibody that specifically binds the p19 subunit of IL‐23, has proven effective on PsA in two randomized controlled trials. To date, only a few real‐world data are available on this topic. Methods: Our study aimed to prospectively evaluate the effectiveness of risankizumab in patients with PsA in a real‐world setting. For this purpose, both rheumatologic and dermatologic assessments were performed at baseline and after 28–40 weeks of continuous risankizumab administration. Moreover, joint and entheses ultrasound assessment was performed at the mentioned time points. The rheumatologic assessment was carried out by means of the following scores: (i) clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA); (ii) Leeds Enthesitis Index (LEI); (iii) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and (iii) Bath Ankylosing Spondylitis Functional Index (BASFI). The degree of skin involvement was measured by both the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA). Quality of life was assessed by the Health Assessment Questionnaire (HAQ) and Dermatology Life Quality Index (DLQI). Ultrasound assessment of joints and entheses was performed on the basis of the EULAR‐OMERACT score. Results: After treatment, cDAPSA decreased from a mean value of 12.9 ± 7.6 to 7.0 ± 6.1 (P < 0.001), and the median PD score significantly decreased from baseline (3; range 1–8) to TP1 (1; range 0–7) (P < 0.001). PASI score also decreased from 8.4 ± 4.9 to 0.3 ± 0.5 (P < 0.001), and PGA from 3.1 ± 1.0 to 0.4 ± 0.5 (P < 0.001). Conclusion: We can conclude that risankizumab led to substantial improvement in both skin and joint involvement. [ABSTRACT FROM AUTHOR]

Background: Social comparison, the process of evaluating one's characteristics in relation to others, influences individuals' self‐perception and behavior. However, instruments are scarce for assessing social comparison in the medical setting. Objectives: Our aim was to develop and validate a new scale for assessing social comparison. Materials and methods: Seven statements were developed, encompassing the perceived normality of having rashes, the tendency to compare their situation with others, and the emotional response when seeing someone better or worse off than themselves. The instrument was piloted in 15 patients for readability and face validity, then prospectively validated using modern psychometric methods in 1,053 adult patients with eczema or psoriasis from three tertiary dermatological centers in Singapore. Results: Of 1,053 adult patients, 802 (76.2%) had eczema, and 251 (23.8%) had psoriasis. Exploratory factor analysis (using a 70% sample split) showed a single factor model comprising three questions (Eigenvalue: 1.4). Confirmatory factor analysis with the remaining 30% of the sample confirmed an excellent model fit. Cronbach's alpha was 0.7, and inter‐item correlations ranged from 0.42 to 0.46. In the Rasch analysis, item fit statistics and item characteristic curves showed appropriate discrimination between response options, although reliability was suboptimal with a person separation reliability of 0.63. Conclusions: Comprising 3 questions, the newly derived social comparison scale showed acceptable psychometrics as a measure of social comparison for clinical and research purposes in dermatology. Its brief nature likely results from its brevity and applicability to conditions beyond eczema and psoriasis, which warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a common skin disorder linked to systemic inflammation and immune dysregulation. It is believed to involve activated T cells and neutrophils. Recent research has highlighted the potential role of hematological ratios, such as neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), eosinophil‐to‐lymphocyte ratio (ELR), eosinophil‐to‐neutrophil ratio (ENR), and eosinophil‐to‐monocyte ratio (EMR), as markers for inflammatory skin diseases, including psoriasis. Objectives: We aimed to investigate hematological ratios between children and adults, patients and controls, and patients with moderate‐to‐severe and mild psoriasis. Materials and Methods: This national retrospective cohort study included over 16,000 psoriasis patients in Israel. Patients with comorbidities influencing blood counts were excluded. Ratios were calculated from blood counts taken within 30 days of diagnosis. Multivariable logistic regression, including age, gender, ethnicity, smoking status, and socioeconomic status, was performed. Results: Findings revealed age‐specific variations in blood counts, hematological ratios, and differences between mild and moderate–severe patients and patients versus controls. Moderate–severe psoriasis patients had elevated neutrophil and eosinophil counts (4.57 vs. 4.25, P < 0.001, and 0.24 vs. 0.22, P = 0.047, respectively), as well as increased NLR (2.46 vs. 2.29, P < 0.001). Multivariable logistic regression analysis confirmed the significance of neutrophil and platelet counts as well as NLR and PLR in predicting psoriasis severity. Limitations: This was a retrospective study without subjective data on disease severity. Conclusion: This study highlights hematologic ratios' diagnostic and prognostic potential in psoriasis. [ABSTRACT FROM AUTHOR]

Background: Psoriasis (Ps) and atopic dermatitis (AD) are chronic systemic immune‐mediated diseases that can coexist in an overlapping condition called psoriasis dermatitis (PD). PD patients have intermediate lesions with characteristics of both Ps and AD. PD is very rare in adults but much more frequent in children. Little is known, however, about the course of PD in the pediatric population. The aim of this study was to evaluate the percentage of PD cases in children that evolved to a definite form of Ps or AD and to identify any clinical or epidemiological variables that could predict the course of the disease. Methods: We performed a prospective multicenter cohort study of children diagnosed with PD between January 2018 and December 2020. We collected participants' clinical and epidemiological characteristics, and pediatric dermatologists determined the percentage of participants who developed Ps or AD. Results: The study included 24 children with PD, with a median age of 7.0 years. After a median follow‐up period of 31 months, 83.3% of cases had evolved to a definite form of Ps or AD (44.4% to Ps and 38.9% to AD). Younger age and family history of Ps were associated with progression to AD. Participants who progressed to AD or Ps had a longer follow‐up than those with an unchanged PD diagnosis. Conclusions: Given sufficient time, a large percentage of PD cases in children will evolve into Ps or AD. Long‐term clinical follow‐up is necessary for a correct diagnosis. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic inflammatory skin disorder with significant impact on quality of life. The evolving landscape of treatment modalities includes traditional therapies and newer biologic agents. This study systematically reviews the efficacy and safety of various psoriasis treatments to guide clinical decision-making. Methods: A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, and ClinicalTrials.gov, yielding 45 studies that met the inclusion criteria. These studies were categorized into four treatment groups: topical, phototherapy, systemic, and biologic therapies. Data on efficacy, measured by PASI score reduction, and safety were extracted and analyzed. Results: Biologic therapies targeting TNF-α, IL-12/23, and IL-17 demonstrated the highest efficacy with mean PASI reductions of 75%, 72%, and 78%, respectively. Systemic therapies such as methotrexate and cyclosporine showed mean PASI reductions of 65% and 70%. Topical treatments and phototherapy also proved effective but were less impactful compared to biologics. Safety profiles varied, with biologics associated with increased risk of infections and injection site reactions, while systemic therapies had notable risks of organ toxicity. Conclusion: Biologic therapies represent a significant advancement in psoriasis management, offering superior efficacy for moderate to severe cases. However, their high cost and potential side effects highlight the need for personalized treatment approaches. Traditional therapies remain valuable, particularly for milder forms or as adjunctive treatments. Future research should focus on long-term safety and efficacy, and strategies to optimize treatment outcomes. [ABSTRACT FROM AUTHOR]

Objective: Tildrakizumab, an anti–interleukin-23 p19 monoclonal antibody, is approved for the treatment of adults with moderate-to-severe plaque psoriasis. Limited evidence is available regarding the effects of tildrakizumab on patient-reported symptoms and satisfaction. This report describes the secondary endpoints of patient-reported symptoms and treatment satisfaction over 64 weeks in patients with moderate-to-severe plaque psoriasis treated with tildrakizumab in a Phase IV, real-world study. Methods: In this uncontrolled, open-label study (NCT03718299), patients received tildrakizumab 100 mg at baseline, Week (W)4, and every 12 weeks thereafter to W52, with the final assessment at W64. Patient-reported secondary endpoints included numerical rating scale (NRS) scores for itch, pain, and scaling, and treatment satisfaction measured by 3 rating scales (Treatment Satisfaction Questionnaire for Medication [TSQM], Tildrakizumab Overall Satisfaction, and Patient Happiness with Psoriasis Control instrument) through W64. Results: Of the 55 patients enrolled, 45 were assessed at W64. Mean NRS scores for itch, pain, and scaling all decreased from baseline beginning as early as W4 with maintenance through W64 (P≤0.001). Treatment satisfaction was positive throughout treatment based on all 3 measures. Mean±SD TSQM domain scores increased from 59.5±17.0 at W4 to 79.5±20.1 at W64 for Effectiveness and from 72.7±18.6 to 81.9±20.5 for Global Satisfaction. Limitations: The study is small and lacks a comparator arm. Conclusion: Tildrakizumab treatment improved patient-reported symptoms in patients with moderate-to-severe plaque psoriasis in a real-world setting and was associated with high levels of treatment satisfaction over 64 weeks. [ABSTRACT FROM AUTHOR]

It is often a goal of model development to predict data from which a variety of outcomes can be derived, such as threshold‐based categorization or change from baseline (CFB) transformations. This approach can improve power or support multiple decisions. Because these derivations are indirectly predicted from the model, they are valuable tests for misspecification when used in visual or numeric predictive checks (V/NPCs). However, derived outcome V/NPCs (especially if primary or key secondary) are often overly scrutinized and held to an uncommon standard when comparing model predictions to point estimates, even if by conventional standards both the directly and indirectly modeled data are captured well. Here, simulations of directly modeled data were used to determine where apparent issues in V/NPCs of derived outcomes are expected. Two types of datasets were simulated: (1) a simple pre–post study and (2) pharmacokinetic/pharmacodynamic data from a dose‐ranging study. A psoriasis exposure–response model case study was also assessed. V/NPCs were generated on the raw data, CFB data, and placebo‐corrected CFB (dCFB) data, and binned summary statistics of the observed data for each trial were graded as being strongly or weakly supportive of a predictive model (within the interquartile range or the 95% central distribution of all simulated trials, respectively). In all cases, the strength of support in direct data V/NPCs was minimally related to that in derived outcome V/NPCs. There are myriad benefits to modeling the underlying data of a derived measure, and these results support caution in discarding adequate models based on overly strict derived measure predictive checks. [ABSTRACT FROM AUTHOR]

Objective To construct a mouse model of psoriasis with spleen deficiency and dampness obstruction pattern and evaluate the model from multiple dimensions and directions, expects to provide research support for the study of traditional Chinese medicine (TCM) treatment of psoriasis with spleen deficiency and dampness obstruction pattern. Methods A mouse model of spleen deficiency and dampness obstruction pattern was established by feeding a high-fat diet, a mouse model of psoriasis vulgaris was established by externally applying imiquimod ointment, and a mouse model of psoriasis with spleen deficiency and dampness obstruction pattern was constructed by combining the above two models. Indications of spleen deficiency and dampness obstruction pattern were evaluated by comparing the body mass, food intake and water intake of mice in each group. The severity of psoriasis in mice was evaluated by comparing the area of skin lesions, PASI score, the value of transdermal water loss (TEWL), and histopathological morphological changes of skin under HE staining in each group. Flow cytometry was used to detect the expression in various cell types to evaluate the degree of inflammatory response of psoriasis in mice. Observation of adiposity index, changes in the histopathological morphology of liver tissue under HE staining, changes in the mRNA expression levels of related factors in liver tissue and adipose tissue of epididymis of mice detected by RT-qPCR, and changes of ABCA1 protein expression level of skin detected by Western Blot were used to evaluate the lipid metabolism disorders in mice. Results Compared with the mice in the psoriasis vulgaris model group, the mice in the model of psoriasis with pattern of spleen deficiency and dampness obstruction had significantly higher body mass (P＜0.001), significantly lower food intake (P＜0.005), and the symptoms of pattern of spleen deficiency and dampness obstruction such as greasy fur, mental fatigue, etc. appeared. The TWEL were significantly increased (P＜0.001), and the PASI scores also significantly increased (P＜0.001). HE results were found psoriasis-like manifestations including hypertrophy of the spinous layer and clubbed hyperplasia. The expression of CD11bhighLy6G+ neutrophil subpopulation, CD11binLy6Chigh monocyte subpopulation, CD11binCD11chigh classical dendritic cell subpopulation, F4/80-CD11c+ dendritic cell subpopulation was significantly increased (P＜ 0.001). HE staining suggested that the cellular morphology of liver showed obvious vacuolated degeneration, and the index of subcutaneous white adiposity and epididymal adiposity index were both significantly increased (P＜ 0.005). The mRNA levels of FABP4 and CD36 in liver tissue were significantly elevated (P＜0.005, P＜0.001), while the mRNA expression levels of ABCA1 and PPARγ in epididymal fat tissue were decreased (P＜0.05, P＜ 0.01). ABCA1 protein level in skin increased (P＞0.05). Conclusion The mouse model of psoriasis with spleen deficiency and dampness obstruction pattern can be used as a reliable animal model for combining disease and pattern, which can provide a reference for further exploration of TCM in the treatment of psoriasis with spleen deficiency and dampness obstruction pattern. [ABSTRACT FROM AUTHOR]

Background It is unknown if an unhealthy diet can affect the risk of developing psoriasis. Objectives To test the hypothesis that individuals with an unhealthy diet have an increased risk of prevalent and incident psoriasis. Methods We included 105 332 adults from the Copenhagen General Population Study, who were invited to participate between 2003 and 2015. The response rate was 43%. An unhealthy vs. healthy diet was defined according to adherence to general national dietary guidelines. The participants were grouped into three groups: low, intermediate and high adherence to general national dietary guidelines; this was based on information from a food frequency questionnaire. Identification of psoriasis was made using International Classification of Diseases codes. Results Of the 105 332 individuals, 580 had a diagnosis of psoriasis at the time of enrolment and 640 received a diagnosis during the median follow-up of 9 years. Risk of prevalent psoriasis increased according to nonadherence to general national dietary guidelines in a stepwise manner with an age- and sex-adjusted odds ratio of 1.70 (95% confidence interval 1.26–2.30) in individuals with low vs. high adherence to dietary guidelines. Results were similar in a multivariable-adjusted model. Prospective analyses adjusted for age and sex showed a weak association between nonadherence to dietary guidelines and risk of incident psoriasis (P for trend 0.04). This association disappeared, when adjusting for multiple confounders (P for trend 0.50). Conclusions Although individuals with psoriasis have an unhealthier diet, diet alone does not appear to independently increase the risk of developing psoriasis. [ABSTRACT FROM AUTHOR]

Introduction • Qing Dai cream is a Chinese medicine that helps relieve the symptoms of psoriasis vulgaris. However, its mechanism hasn’t been illustrated well. Objective • To evaluate the effectiveness and comfortableness of Qing Dai cream walking jar as a nursing intervention for patients with psoriasis vulgaris. Methods • Seventy-six patients with vulgar psoriasis admitted to our hospital from February 2020 to February 2021 who met the criteria according to the including and exclusion criteria were screened as this study’s subjects. According to the randomized number and double-blind principle, all of them were separated into 2 groups, the subjects in the control group were provided with conventional care, while the subjects in the observation group were joint Qing Dai cream walking jar on this basis. The quality of life and the degree of skin lesions of the patients after the intervention were comprehensively evaluated compared and observed. Results • Compared to the control group, the psoriasis lesion area and severity index (PASI) score after the intervention was remarkably lower in the observation group (P < .05) while the symptom scores, itching degree, itching frequency, duration, lesion area, sleep condition, and self-conscious condition degrees were significantly lower in the observation group (P < .05). The observed group showed a significant effect, effective, and the overall effective rate of 57.89% (22/38), 36.84%, and 94.74% were all significantly more than those of the control group after intervention (P < .05). After the intervention, the scores of dermatological disease quality of life index (DLQI), the subjective symptoms, daily life, work and study, and interpersonal relationships in the observation group were all significantly lower than those in the control group, P < .05. In the intervention, the satisfaction, total satisfaction of 65.79% (25/38), and 97.37% were statistically significantly higher than that of the control group, P < .05. Conclusion • The Qing Dai cream walking jar is effective in improving patients’ clinical symptoms, relieving their pruritus discomfort, and promoting the repair of skin lesions, to improve their quality of life and satisfaction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Historically, patients with skin of color are underdiagnosed with psoriasis and underrepresented in clinical trials. In this study, we assess the efficacy and safety of risankizumab in patients with moderate-to-severe plaque psoriasis by race and ethnicity in the open label extension LIMMitless (NCT03047395). Methods: Patients received continuous treatment with 150 mg risankizumab through their initial trial and the open label extension. Patients self-identified their race and ethnicity. Efficacy was assessed using Psoriasis Area Severity Index (PASI) and Dermatology Life Quality Index (DLQI). Safety is reported by events/100 patient-years. Results: A total of 897 patients (race: 662 White, 196 Asian, 25 Black or African American, 14 Other; ethnicity: 98 Hispanic or Latino, 799 non-Hispanic or Latino) were included in this analysis. Compared to baseline, patients had a mean percent reduction in PASI between 94.6% (Asian) and 99.3% (Black or African American) and reported mean percent improvements in DLQI ranging from 87.1% (Asian and Black or African American) to 93.7% (Hispanic or Latino) at week 100. Conclusion: While the data presented here comprise a small retrospective descriptive analysis and cannot detect statistical differences, efficacy of risankizumab for the treatment of moderate-to-severe plaque psoriasis appears similar across the racial and ethnic groups studied and no new safety signals were detected. [ABSTRACT FROM AUTHOR]

Background: Psoriasis, a chronic, immune-mediated, inflammatory disease, affects 2‒3% of the population. Tyrosine kinase 2 (TYK2) mediates cytokine signaling involved in adaptive [interleukin (IL)-12, IL-23] and innate (type-I interferons) immune responses; IL-23–driven T-helper (Th)17 pathways play a key role in chronic inflammation in psoriasis. In a phase 2 trial, deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, reduced IL-23/Th17 and type-I interferon pathway expression in the skin of patients with moderate to severe plaque psoriasis, reductions that were accompanied by clinical improvement of psoriatic lesions. Objectives: The aim of this study was to identify biomarkers of psoriatic disease in serum from patients enrolled in the phase 2 trial and to assess the effects of deucravacitinib on those biomarkers. Methods: Serum biomarkers from Olink proteomics and other quantitative assays were evaluated for a pharmacodynamic response to deucravacitinib treatment and correlation with psoriasis disease activity measures. Results: Serum biomarkers associated with the IL-23/Th17 pathway [IL-17A, IL-17C, IL-19, IL-20, beta-defensin, and peptidase inhibitor 3 (PI3)] were upregulated in patients with psoriasis versus healthy controls. Deucravacitinib treatment reduced IL-17A (adjusted mean change from baseline at Day 85; 12 mg once daily versus placebo; −0.240 versus −0.067), IL-17C (−14.850 versus −1.664), IL-19 (−96.445 versus −8.119), IL-20 (−0.265 versus −0.064), beta-defensin (−65,025.443 versus −7553.961), and PI3 (−14.005 versus −1.360) expression. Reductions in serum biomarker expression occurred in a dose- and time-dependent manner, with significant reductions from baseline seen with deucravacitinib doses ≥ 3 mg twice daily (P ≤ 0.05). Biomarker expression correlated with disease activity measures such as Psoriasis Area and Severity Index (PASI) at baseline. Biomarker expression also correlated with PASI scores at Week 12. Conclusion: IL-23/Th17 pathway expression in the serum of patients with psoriasis is an indicator of disease activity and response to deucravacitinib treatment. Trial registration number: NCT02931838. Plain Language Summary: Plaque psoriasis is a long-term disease that causes inflammation, scaling, and itching of the skin. Compared with healthy volunteers without psoriasis, patients with psoriasis have higher amounts of certain biomarkers (molecules that indicate what is happening in the body) in their blood that are associated with inflammation. Higher amounts of these biomarkers are also associated with more severe psoriasis. In a study of patients with psoriasis, those who received the oral drug deucravacitinib had lower amounts of biomarkers after 12 weeks of treatment compared with patients who received a placebo (a lookalike pill that contains no medicine). Patients who were treated with deucravacitinib also saw an improvement in their psoriasis after 12 weeks compared with patients who received placebo. [ABSTRACT FROM AUTHOR]

Introduction: With newer biologics, the achievement of complete skin clearance has become an attainable treatment goal for patients with plaque psoriasis. We evaluate how improvements in Psoriasis Area and Severity Index (PASI) responses, particularly at incremental improvements approaching complete skin clearance (PASI 100), translate into improvements in health-related quality of life (HRQoL) and patient-perceived symptoms. Methods: Data from the BE RADIANT phase 3b trial (NCT03536884) and its open-label extension (OLE), pooled across all study visits and treatments over 16 weeks (randomised patients) and 2 years (patients entering the OLE), were analysed using mixed-effects logistic regression models. Proportions of patients achieving a Dermatology Life Quality Index (DLQI) of 0/1, DLQI item scores of 0, and Psoriasis Symptoms and Impacts Measure (P-SIM) item scores of 0 for itching, scaling, and skin pain at specific PASI improvement levels were estimated. Results: Seven hundred and forty-three patients were randomised to treatment; 654 entered the OLE. Using 16-week pooled data, there were incremental improvements in the proportions of patients estimated by our model to achieve DLQI 0/1 with PASI 100 compared with 95% (PASI = 95%) and 90% (PASI = 90%) improvements in PASI (93.0%, 89.3%, and 83.8% achieving DLQI 0/1, respectively). Estimated proportions achieving DLQI item scores of 0 had the greatest increases at higher PASI improvement levels for Items 1 (itchy, sore, painful, or stinging skin), 2 (embarrassment), and 4 (choice of clothing). Estimated proportions of patients achieving P-SIM = 0 were also higher for PASI 100 (itching: 61.7%; scaling: 82.2%; skin pain: 96.9%) than for PASI = 95% (50.8%; 72.3%; 95.7%) and PASI = 90% (39.8%; 59.5%; 94.0%). Similar benefits of incremental PASI improvements were estimated using 2-year data. Conclusions: Complete skin clearance translated into the greatest benefits to HRQoL and patient-perceived symptoms, over and above skin clearance between 90% and 100%, highlighting the importance of targeting PASI 100 as a treatment outcome for patients with psoriasis. Trial Registration Number: NCT03536884. 2APgg6-p_grKtG7KkQSkCG Complete skin clearance is associated with the greatest benefits to health-related quality of life and perceived symptoms for patients with psoriasis: KeyResults and Conclusions (MP4 72828 kb) [ABSTRACT FROM AUTHOR]

Introduction: Due to variable psoriasis symptoms, disease progression, and individual responses to therapy, patients may start, stop, or switch biologic therapies. Real-world data on the associated disease burden of patients with psoriasis who do and do not switch biologics are incomplete. Methods: This study compared disease burden among patients from the CorEvitas Psoriasis Registry (July 2017–December 2021) who switched biologics and those who did not within 4–12 months following initiation. Disease-related patient-reported outcomes (PROs) were recorded, including skin pain, itching, activity impairment, and effects on health-related quality of life (HRQoL). Disease severity was measured by body surface area (BSA) and Psoriasis Area and Severity Index (PASI). Unadjusted and adjusted regression models were used to compare study outcome measures between the two groups. Results: This study included 2145 patients, with 159 classified as switchers and 1986 as non-switchers. The most common reason for switching therapy was failure to maintain initial response (51.7%; n = 78). Moderate-to-severe disease (BSA ≥ 3) was found among 83.0% (n = 132) of switchers versus 26.1% (n = 516) of non-switchers. PASI > 5 was reported among 49.7% (n = 79) of switchers versus 8.6% (n = 171) of non-switchers. Differences in skin pain, itching, and effects on HRQoL between switchers and non-switchers were larger in magnitude for bio-experienced patients. Conclusions: Patients who switched biologic therapy experienced a greater disease burden of psoriasis across PROs than non-switchers. Patient-centered factors may be important drivers of biologic switching. Our findings suggest the association between switching and disease burden may be stronger among patients with prior biologic therapy experience. Plain Language Summary: Patients with psoriasis often need treatment over a long period of time. Common treatments include biologic medications, which help to reduce inflammation. Different patients may experience different psoriasis symptoms, and these symptoms can lead to changes in biologic over time. It is important that we understand how psoriasis severity and patients' day-to-day well-being affect switching of psoriasis biologic medications. In this study, we used information from a database of patients with psoriasis. The database includes information on patients' psoriasis-related medication history, including whether they change their medication. We looked at data from patients who switched and patients who did not switch their biologic medication, and examined differences in their skin pain, itching, tiredness, difficulty participating in normal activities, and effects on day-to-day well-being. Patterns between these two groups were also studied on the basis of whether patients had used biologic medications before or whether they had a related condition, called psoriatic arthritis, in addition to psoriasis. Overall, we found that patients who changed their biologic medication had experienced more difficult psoriasis symptoms than those who had not changed their medication, such as itching and skin pain. These symptoms had a greater impact on switching biologic medication in patients who had used a biologic medication before than for those who were using their first biologic medication. [ABSTRACT FROM AUTHOR]

This narrative literature review examined the intricate relationship between body dysmorphic disorder (BDD) and dermatological conditions, with a brief focus on those characterized by conspicuous skin irregularities such as acne vulgaris, psoriasis, and vitiligo. Highlighting the significant prevalence of BDD among individuals afflicted with dermatological issues, our analysis illuminated the profound psychological repercussions stemming from an exaggerated preoccupation with perceived skin imperfections. Through an exploration of the underlying BDD symptoms, we analyzed the complex dynamics between skin health and mental well-being, emphasizing the disorder's impact on patients' psychological and social functioning. This narrative review further investigated the consequential effects of BDD on essential aspects of dermatological treatment, including patient adherence to therapeutic regimens, overall quality of life (QOL), and the effectiveness of available treatments. In addition to presenting current therapeutic approaches, we advocate for the integration of psycho-dermatological interventions tailored to mitigate the dual burden of skin conditions and psychological distress. Future research directions proposed include longitudinal studies to assess the long-term effects of BDD on skin disease prognosis and psychosocial well-being, which aim to refine and optimize treatment modalities to contribute to a more holistic understanding of BDD within dermatological practice. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, immune-mediated, inflammatory skin disease, associated with multiple comorbidities and psychological and psychiatric disorders. The quality of life of patients with this disease is severely compromised, especially in moderate-to-severe plaque psoriasis. Secukinumab, a fully humanized monoclonal antibody, was the first anti-interleukin (IL)-17 biologic approved for treating psoriasis. Secukinumab demonstrated long-lasting efficacy and a good safety profile in individuals with plaque psoriasis, and it is associated with an improvement in health-related quality of life. While there is evidence that early treatment with systemic therapy can affect disease progression and improve long-term outcomes in other autoimmune diseases, evidence is limited in psoriasis, especially in real-world settings. This review provides an overview of studies describing the effectiveness of secukinumab in the treatment of psoriasis summarizing the literature and focusing on real-world evidence and early intervention. [ABSTRACT FROM AUTHOR]

Vitamin D plays an important role in psoriasis, but its involvement in pathogenesis remains unclear. This study aimed to evaluate vitamin D receptor (VDR) expression on peripheral blood mononuclear cells (PBMCs) in patients with psoriasis and healthy controls and to study the effects of the Etanercept treatment on VDR expression on PBMCs in patients with psoriasis. Twenty patients with moderate to severe psoriasis received treatment with Etanercept for 24 weeks. The age- and sex-matched controls did not receive any intervention. VDR expression on CD3+ lymphocytes and CD14+ monocytes, and serum levels of total and free 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxy vitamin D (1,25(OH)2D) were analyzed at baseline, after 10–12 weeks, and after 24 weeks in both groups. VDR expression was analyzed using flow cytometry. We observed higher expression of the VDR on CD14+ monocytes in psoriasis patients compared to healthy controls at baseline. This difference was no longer significant after 24 weeks of the Etanercept treatment. The patients with psoriasis improved clinically. However, VDR expression was unaltered during the Etanercept treatment, and there was no correlation between VDR expression and disease severity. [ABSTRACT FROM AUTHOR]

Psoriasis is an inflammatory skin disease with various symptoms of differing severities and with the reported prominent involvement of neutrophil extracellular traps (NETs). The excitation of neutrophils, e.g., by interleukin 8 (IL-8) or lipopolysaccharide (LPS), leads to the citrullination of histones and the release of protein–DNA complexes into the extracellular space, where they are digested by DNases. Our aim was to explore data on the levels of protein-complexed DNAs neutrophil elastase–DNA (NE-DNA) and myeloperoxidase–DNA (MPO-DNA), citrullinated histones (citH2, citH3, citH4), and NET-degrading enzyme DNase I in the serum of psoriatic patients with varying severities of clinical symptoms assessed with the Psoriasis Area Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI) scores. The levels of factors were detected in 52 patients with psoriasis and 22 healthy volunteers by the enzyme-linked immunosorbent assay (ELISA). The results showed the elevated levels of NE-DNA, MPO-DNA, citH3, and DNase I in the patients with psoriasis compared to healthy volunteers (p < 0.05). Additionally, changes were noticed in the levels of NE-DNA, citH3, and DNase I, depending on the severity of symptoms (p < 0.05). In mild psoriasis (PASI < 10, BSA < 10, DLQI < 10), the suppressing activity of the enzyme caused the impaired ability to remove the physiological level of NETs, whereas in moderate to severe psoriasis (PASI ≥ 10, BSA ≥ 10, DLQI ≥ 10), the enhanced activity of DNase I failed to remove NETs due to the observed overexpression. It may, thus, be concluded that the mechanism of action of NETs, which play an undeniable role in psoriatic diseases, seem to follow two different paths depending on the severity of disease, which may be crucial in selecting potential anti-NET treatment methods. [ABSTRACT FROM AUTHOR]

Psoriasis is one of the most frequent chronic inflammatory skin diseases and exerts a significant psychological impact, causing stigmatization, low self-esteem and depression. The pathogenesis of psoriasis is remarkably complex, involving genetic, immune and environmental factors, some of which are still incompletely explored. The cutaneous microbiome has become more and more important in the pathogenesis of inflammatory skin diseases such as acne, rosacea, atopic dermatitis and psoriasis. Dysbiosis of the skin microbiome could be linked to acute flare ups in psoriatic disease, as recent studies suggest. Given this hypothesis, we conducted a study in which we evaluated the cutaneous microbiome of psoriasis patients and healthy individuals. In our study, we collected multiple samples using swab sampling, adhesive tape and punch biopsies. Our results are similar to other studies in which the qualitative and quantitative changes found in the cutaneous microbiome of psoriasis patients are different than healthy individuals. Larger, standardized studies are needed in order to elucidate the microbiome changes in psoriasis patients, clarify their role in the pathogenesis of psoriasis, decipher the interactions between the commensal microorganisms of the same and different niches and between microbiomes and the host and identify new therapeutic strategies. [ABSTRACT FROM AUTHOR]

The gut microbiota plays a critical role in immune system function, with dysbiosis linked to systemic inflammation, contributing to conditions like psoriasis and depression. Although biological treatments for severe psoriasis are known to impact gut bacteria, less is understood about their effects on fungi. This study aims to investigate fungal gut microbiota changes in psoriasis patients transitioning from TNF-α inhibitors to brodalumab. Fecal samples from 20 patients were analyzed using Illumina MiSeq sequencing of the ITS2 region of 18S rRNA. Microbial diversity was assessed through Bray–Curtis dissimilarity and the Shannon–Wiener index. Clinical outcomes were measured using clinical scores for psoriasis and depression severity, with statistical analysis performed via Wilcoxon signed-rank tests and PERMANOVA. Results showed that Ascomycota was the dominant fungal phylum in both treatment groups, with Saccharomyces, Penicillium, Candida, and Debaryomyces as prevalent genera. No significant changes occurred at the phylum level after switching to brodalumab, though minor genome-level variations were observed. Beta diversity analysis highlighted inter-patient variability, with no significant correlation between fungal composition and clinical outcomes. Despite improved clinical scores, the fungal gut microbiota remained largely stable, suggesting that brodalumab does not significantly alter fungal communities in psoriasis patients. Further research is needed for a comprehensive understanding. [ABSTRACT FROM AUTHOR]

The aim of the study is to expound the effect of psoriasis on salivary glands by evaluating the secretion of saliva and salivary cytokine biomarkers in patients with psoriasis. This study was conducted by recruiting 120 subjects that included 60 patients diagnosed clinically with active psoriasis and 60 healthy controls who were age and gender matched to psoriatic subjects. Unstimulated whole saliva was collected from all the subjects by spitting method, and levels of tumor necrosis factor‐alpha (TNF‐α), interferon‐gamma (IFN‐γ), interleukin‐2 (IL‐2), and IL‐10 (IL‐10) were determined via enzyme‐linked immunosorbent assay (BT Lab, Shanghai, China). Secretion of saliva in psoriasis patients was considerably reduced than in healthy controls. The concentrations of pro‐inflammatory cytokines (TNF‐α, IFN‐γ, and IL‐2) were significantly increased, whereas level of anti‐inflammatory cytokine (IL‐10) was markedly decreased in the saliva of psoriasis patients with hyposalivation compared to healthy subjects. Our results demonstrated significant negative correlation of salivary flow rates with the disease severity. No significant correlations were obtained between salivary levels of tested cytokines and salivary flow rates in our study. Findings of the study reflect inflammation of salivary glands with reduced salivary flow rates in psoriasis patients. The inflammatory responses in salivary gland tissues by virtue of increased pro‐inflammatory cytokines concentrations together with lower anti‐inflammatory cytokine levels may have a role in affecting the saliva secretion in psoriasis patients. Secretion of unstimulated saliva in psoriasis patients decreases with the severity and duration of the disease. [ABSTRACT FROM AUTHOR]

Chronic recurrent multifocal osteomyelitis (CRMO) or chronic nonbacterial osteitis is a sterile autoinflammatory disease of bone in children that can mimic infectious osteomyelitis and osteosarcoma. Early diagnosis, treatment, and long-term follow-up of CRMO are essential. We describe a 10-year-old boy who presented with 15 days of left ankle bone more than joint pain, swelling, and limp. Plain radiographs and magnetic resonance imaging scans were nondiagnostic of osteomyelitis and tibial irrigation and biopsy were negative for infection and malignancy. Four years later, he again presented with similar pain in his right ankle. Repeat bone biopsy noted reactive bone changes and bone culture was sterile. Whole-body magnetic resonance imaging revealed multiple enhancing lesions in the long bones of bilateral lower extremities, spine, and sternum. He was diagnosed with CRMO, and treatment with celecoxib and subsequently pamidronate, infliximab, and methotrexate were initiated. After 6 months of treatment, the patient's gait and pain improved, and 2 years later, his CRMO was in clinical and radiologic remission. Of note, he developed palmoplantar pustular psoriasis, commonly seen in CRMO, that was not determined to be from tumor necrosis factor inhibition. [ABSTRACT FROM AUTHOR]

Objectives Rheumatic diseases may impair reproductive success and pregnancy outcomes, but systematic evaluations across diseases are lacking. We conducted a nationwide cohort study to examine the impact of rheumatic diseases on reproductive health measures, comparing the impacts with those of other immune-mediated diseases (IMDs). Methods Out of all of the 5 339 804 Finnish citizens, individuals born 1964–1984 and diagnosed with any of the 19 IMDs before age 30 (women) or 35 (men) were matched with 20 controls by birth year, sex, and education. We used data from nationwide health registers to study the impact of IMDs on reproductive health measures, such as reproductive success and, for women, ever having experienced adverse maternal and perinatal outcomes. Results Several of the rheumatic diseases, particularly SLE, JIA, and seropositive RA, were associated with higher rates of childlessness and fewer children. The risks for pre-eclampsia, newborns being small for gestational age, preterm delivery, non-elective Caesarean sections, and need of neonatal intensive care were increased in many IMDs. Particularly, SLE, SS, type 1 diabetes, and Addison's disease showed >2-fold risks for some of these outcomes. In most rheumatic diseases, moderate (1.1–1.5-fold) risk increases were observed for diverse adverse pregnancy outcomes, with similar effects in IBD, celiac disease, asthma, ITP, and psoriasis. Conclusion Rheumatic diseases have a broad impact on reproductive health, with effects comparable with that of several other IMDs. Of the rheumatic diseases, SLE and SS conferred the largest risk increases on perinatal adverse event outcomes. [ABSTRACT FROM AUTHOR]

Background: Neutrophils are key players in the innate immune system, actively migrating to sites of inflammation in the highly energetic process of chemotaxis. In this study, we focus on the role of acyl-CoA: diacylglycerol acyltransferase 1 (DGAT1), an enzyme that catalyzes the synthesis of triglycerides, the major form of stored energy, in neutrophil chemotaxis. Methods and results: Using a mouse model of psoriasis, we show that DGAT1-deficiency reduces energy-demanding neutrophil infiltration to the site of inflammation, but this inhibition is not caused by decreased glycolysis and reduced ATP production by neutrophils lacking DGAT1. Flow cytometry and immunohistochemistry analysis demonstrate that DGAT1 also does not influence lipid accumulation in lipid droplets during inflammation. Interestingly, as has been shown previously, a lack of DGAT1 leads to an increase in the concentration of retinoic acid, and here, using real-time PCR and publicly-available next-generation RNA sequencing datasets, we show the upregulation of retinoic acid-responsive genes in Dgat1KO neutrophils. Furthermore, supplementation of WT neutrophils with exogenous retinoic acid mimics DGAT1-deficiency in the inhibition of neutrophil chemotaxis in in vitro transwell assay. Conclusions: These results suggest that impaired skin infiltration by neutrophils in Dgat1KO mice is a result of the inhibitory action of an increased concentration of retinoic acid, rather than impaired lipid metabolism in DGAT1-deficient mice. [ABSTRACT FROM AUTHOR]

Background Generalized pustular psoriasis (GPP) and palmoplantar pustulosis (PPP) are chronic inflammatory skin conditions. Accumulating evidence shows that GPP and PPP have different characteristics to plaque psoriasis and are distinct clinical entities. Objectives To assess the epidemiology, comorbidities, mortality and healthcare use for patients in England with GPP and PPP versus those with plaque psoriasis. Methods We carried out a cohort study involving analyses of longitudinal electronic health record data in the Clinical Practice Research Datalink Aurum database and linked hospital and mortality data between 2008 and 2019. The primary study outcome was the incidence and prevalence rates of GPP, PPP and plaque psoriasis in England. Secondary outcomes included survival rates and healthcare resource use (HCRU) by disease type. Results We identified 373 patients with GPP, 1828 with PPP and 224 223 with plaque psoriasis. Mean (SD) age was 55.9 (18.6) years for patients with GPP, 51.5 (16.4) years for those with PPP and 48.5 (19.1) years for those with plaque psoriasis; 62.5% and 65.9% of patients with GPP and PPP, respectively, were women, vs. 49.4% of those with plaque psoriasis. About half of patients were overweight or obese at baseline (GPP 48.6%, PPP 56.0%, plaque psoriasis 45.9%). The incidence rates for GPP, PPP and plaque psoriasis were 0.25 [95% confidence interval (CI) 0.21–0.28], 2.01 (95% CI 1.92–2.11) and 103.2 (95% CI 102.5–103.9) per 100 000 person-years, respectively. From 2008 to 2019, the prevalence rates per 100 000 persons ranged from 1.61 to 3.0 for GPP, from 1.1 to 18.7 for PPP and from 1771.0 to 1903.8 for plaque psoriasis. Survival rates were lower for patients with GPP, particularly those who were > 55 years of age and those with a history of one or more comorbidities in each cohort. HCRU was lower in the cohort with plaque psoriasis and highest in the cohort with GPP, particularly among those who had more than one GPP flare. Conclusions Our results provide further evidence that, in England, GPP is a distinct disease with different epidemiology, lower survival and higher HCRU than plaque psoriasis. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic condition caused by an inflammation mediated mainly by cytokines and T cells. In COVID-19, the same type of imbalance is common, generating the Cytokine Storm and promoting a worsening in the skin conditions of patients with autoimmune disorders, such as Psoriasis. In this context, one of the main mediators of immune responses presented by SARS-CoV-2 infected patients is the Purinergic System. This immunological resource is capable of stimulating the hyperinflammatory state presented by infected individuals, mainly by the activity of the P2X7 receptor, culminating in the Cytokine Storm and consequently in the Psoriasis crisis. Currently, different drugs are used for patients with Psoriasis, such as immunosuppressants and small molecules; however, the safety of these drugs in infected patients has not been analyzed yet. In this context, studies are being developed to evaluate the possible administration of these traditional drugs to COVID-19 patients with Psoriasis crisis. Along with that, researchers must evaluate the potential of administrating P2X7 antagonists to these patients as well, improving both the systemic and the dermatological prognostics of patients, by reducing the Cytokine Storm and its general effects, but also avoiding the provocation of Psoriasis crisis. [ABSTRACT FROM AUTHOR]

Background: Cases of psoriasis associated with Tocilizumab (TCZ) are scarce. Objective: To describe a new case of TCZ-associated psoriasis and to perform a case-based review of similar cases. Methods: We searched Medline/Pubmed, Embase, Scopus, Web of Science, and Directory of Open Access Journals databases using the terms « Tocilizumab » and « Psoriasis » in the French and English literature. Results: We report a 70-year-old woman with a history of Rheumatoid Arthritis who developed Infliximab-induced plaque psoriatic eruption of the soles and palms, that resolved after Infliximab interruption, then relapsed after TCZ relay, and eventually resolved after TCZ interruption. Including our case, we identified 16 cases of TCZ-induced psoriatic eruption. Three (21%) out of 14 patients had a history of cutaneous psoriasis – data were not available for 2 patients. Eight (50%) patients had previously received TNFα antagonists. TCZ was stopped for 10 patients and continued for 4 patients. For the 2 remaining patients, the interval between two injections of TCZ was shortened. All the patients with available follow-up data had an improvement of the eruption within 4 weeks. Conclusion: To conclude, in case of TCZ-induced psoriatic eruption and in light of the published cases, we suggest using topical steroids and reassessing the patient 4 weeks later. If no healing is obtained, we suggest stopping TCZ, and treating the underlying disease with another drug. When no other drug is available, while waiting for more data regarding the value of IL-6 levels, it can be discussed to increase TCZ regimen, as it has been successful for 2 authors. Efficacy assessment of the chosen attitude should not take place before 4 weeks. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin condition associated with systemic inflammation and a higher risk of cardiovascular comorbidities. This study retrospectively evaluates coagulation parameters in psoriasis vulgaris patients treated with IL-17 inhibitors (secukinumab, ixekizumab) and IL-23 inhibitors (risankizumab, guselkumab), compared to those untreated systemically. The study reviewed records from 177 patients treated between January 2019 and March 2023. Patients were grouped into control (n = 77), secukinumab (n = 36), ixekizumab (n = 19), guselkumab (n = 24), and risankizumab (n = 21). Coagulation parameters, including PT, aPTT, PLT, MPV, INR, fibrinogen, D-dimer, and B12 levels, were analyzed. The primary endpoint was the comparison of coagulation parameters between groups. Significant differences were found in PT, with secukinumab-treated patients showing a significantly shorter PT compared to controls (p = 0.002). No significant differences were observed in other coagulation parameters across the groups. The study highlights a potential effect of secukinumab on coagulation pathways, possibly related to IL-17’s role in inflammation and endothelial function. Despite current literature suggest a risk of cerebrovascular events with risankizumab, this study did not show any significant changes in coagulation parameters with risankizumab, indicating no hypercoagulability risk associated with this IL-23 inhibitor. Our findings suggest IL-17 and IL-23 inhibitors are generally safe concerning coagulation parameters, but regular monitoring may be warranted for patients on secukinumab due to its effect on PT. Further long-term studies are needed to fully understand the cardiovascular risks associated with these therapies. [ABSTRACT FROM AUTHOR]

Background and Purpose: Psoriasis is an autoimmune inflammatory skin disease, featuring microvascular abnormalities and elevated levels of bradykinin. Contact activation of Factor XII can initiate the plasma kallikrein‐kinin cascade, producing inflammation and angioedema. The role of Factor XII in psoriasis is unknown. Experimental Approach: The effects of deficiency of Factor XII or its enzymatic substrate, prekallikrein, were examined in the imiquimod‐induced mouse model of psoriasis. Skin microcirculation was assessed using intravital confocal microscopy and laser Doppler flowmeter. A novel antibody blocking Factor XII activation was evaluated for psoriasis prevention. Key Results: Expression of Factor XII was markedly up‐regulated in human and mouse psoriatic skin. Genetic deletion of Factor XII or prekallikrein, attenuated imiquimod‐induced psoriatic lesions in mice. Psoriatic induction increased skin microvascular blood perfusion, causing vasodilation, hyperpermeability and angiogenesis. It also promoted neutrophil‐vascular interaction, inflammatory cytokine release and enhanced Factor XII / prekallikrein enzymatic activity with elevated bradykinin. Factor XII or prekallikrein deficiency ameliorated these microvascular abnormalities and abolished bradykinin increase. Antagonism of bradykinin B2 receptors reproduced the microvascular protection of Factor XII / prekallikrein deficiency, attenuated psoriatic lesions, and prevented protection by Factor XII / prekallikrein deficiency against psoriasis. Furthermore, treatment of mice with Factor XII antibody alleviated experimentally induced psoriasis and suppressed microvascular inflammation. Conclusion and Implications: Activation of Factor XII promoted psoriasis via prekallikrein‐dependent formation of bradykinin, which critically mediated psoriatic microvascular inflammation. Inhibition of contact activation represents a novel therapeutic strategy for psoriasis. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are demonstrated to be involved in psoriasis progression. CircRNAs can act as RNA-binding protein (RBP) sponges. Here, we investigated the action of circAKR1B10 in psoriasis, and explored the potential proteins interacted with circAKR1B10. Levels of genes and proteins were assayed by qRT-PCR and western blotting analyses. Keratinocytes in functional groups were treated with interleukin (IL)-22. Functional analysis were conducted using MTT, 5-ethynyl-2’-deoxyuridine (EdU), and transwell assays, respectively. Interaction analysis among circAKR1B10, Eukaryotic initiation factor 4 A-III (EIF4A3) and Aurora Kinase A (AURKA) was conducted using bioinformatics analysis, RNA pull-down assay, and RNA immunoprecipitation (RIP) assay. CircAKR1B10 was highly expressed in psoriasis patients and IL-22-induced keratinocytes. Functionally, knockdown of circAKR1B10 abolished IL-22-induced proliferation, migration and invasion in keratinocytes. AURKA expression was also higher in psoriasis patients and IL-22-induced keratinocytes, and was negatively correlated with circAKR1B10 expression. Moreover, AURKA silencing reduced the proliferative, migratory and invasive abilities of IL-22-induced keratinocytes. Mechanistically, circAKR1B10 interacted with EIF4A3 protein to stabilize and regulate AURKA expression. CircAKR1B10 contributes to IL-22-induced proliferation, migration and invasion in keratinocytes via up-regulating AURKA expression through interacting with EIF4A3 protein. [ABSTRACT FROM AUTHOR]

Objective: Two-sample Mendelian randomization (TSMR) was employed to examine the association between lipidome and five inflammatory skin diseases. Method: To evaluate the association between various molecular subtypes of lipidome and the risk of five inflammatory skin diseases, we analyzed a comprehensive GWAS dataset comprising 179 lipidome. The Two-Sample Mendelian Randomization (TSMR) method was employed to investigate causal relationships. Heterogeneity and pleiotropy were assessed using Cochran's Q test, MR-Egger intercept test, and MR-PRESSO global test. Additionally, a sensitivity analysis was conducted to evaluate the influence of individual single nucleotide polymorphisms on Mendelian Randomization study. Results: Using 179 serum lipidome as exposures and five common inflammatory skin diseases as outcomes, we investigated their associations in this large-scale study. Our findings reveal significant impacts of glycerophospholipids, glycerolipids, and sphingomyelins on inflammatory skin diseases. Glycerophospholipids were protective against pemphigus but predominantly posed risks for other inflammatory skin diseases. Specifically, phosphatidylcholine (16:0_0:0) exhibited the most significant risk association with lichen planus (OR = 1.25, 95% CI 1.11–1.40, P < 0.001). Conversely, glycerolipids showed no effect on lichen planus but were protective against pemphigus while potentially posing risks for other conditions. Triacylglycerol (46:2) showed the most substantial risk association with vitiligo (OR = 1.99, 95% CI 1.35–2.93, P < 0.001). Furthermore, sphingomyelins had no effect on atopic dermatitis but posed potential risks for other inflammatory skin diseases. Sphingomyelin (d40:1) notably emerged as a significant risk factor for pemphigus (OR = 1.91, 95% CI 1.37–2.66, P < 0.001). Conclusions: This study has elucidated the potential harmful effects of glycerophospholipids, glycerolipids, and sphingomyelins on inflammatory skin diseases, while also providing valuable insights for future research into the pathophysiology, prevention and treatment of these conditions. [ABSTRACT FROM AUTHOR]

Psoriasis (Ps) is one of the most common chronic inflammatory skin disorders with its pathogenesis correlated with dysregulated innate and adaptive system. Even though biological agents have advanced the treatment of psoriasis, however, there are huge limitations, like high adverse reactions and relapse rate. Therefore, it is of great interest in searching clinical resolutions with better safety and efficacy. In the current study, we utilized the adipose-derived mesenchymal stem cell (AD-MSCs) to treat moderate/severe cases of psoriasis in a single-arm clinical study. This AD-MSC treatment has proven to be clinically safe and effective. Interestingly, a trend of adaptome improvement, including increased diversity, elevated uCDR3s and decreased large clone after AD-MSC treatment in a short (2 weeks) and long (12 weeks) terms. In conclusion, allogenic AD-MSC treatment has shown a good safety and efficacy in treating Ps and can effectively improve the compromised adaptive immune system of Ps patients. [ABSTRACT FROM AUTHOR]