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ABSTRACT Psoriasis is a chronic inflammatory skin disease characterised by inflammatory cell infiltration, keratinocyte hyperproliferation and increased neovascularization. Despite extensive research, the precise mechanisms underlying psoriasis pathology and treatment strategies remain unclear because of a complex aetiology and disease progression. Hence, in this study, we aimed to identify potential therapeutic targets for psoriasis and explore their effects on disease progression. We observed that G protein‐coupled receptor LGR4 attenuates psoriasis progression. Bioinformatics analysis of publicly available clinical data revealed lower LGR4 expression in the skin lesions of patients with psoriasis than in their non‐lesioned skin. Both in vitro (HaCaT cell) and in vivo (mouse) models confirmed this phenomenon. The Lgr4‐knockout mouse model further confirmed that LGR4 plays a positive role in psoriasis progression. Specifically, Lgr4 knockout promoted the secretion of inflammatory factors, accumulation of local immunocyte infiltration in skin lesions, and keratinocyte proliferation. In conclusion, we demonstrated that LGR4 is critical to limiting psoriasis progression, suggesting that it is a viable target for the clinical management of this skin condition. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic inflammatory disease often associated with serious cardiovascular comorbidities. The aim of this study was to investigate the systemic inflammatory burden in psoriasis by examining various inflammatory markers and to assess the relationship between these markers and the severity of the disease. Methods: This retrospective study was conducted on medical records of patients who visited the dermatology outpatient clinic between 1 January 2016 and 31 December 2022. The study included patients with psoriasis vulgaris and healthy volunteers. Demographic data, Psoriasis Area and Severity Index score, C‐reactive protein, monocyte‐high‐density lipoprotein cholesterol ratio, neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, monocyte‐to‐lymphocyte ratio, systemic immune‐inflammation index, and Systemic Inflammation Response Index were analysed and compared. Results: A total of 278 psoriasis patients and 90 healthy volunteers were analysed. Compared to the control group, psoriasis patients showed significantly higher systemic immune‐inflammation index, Systemic Inflammation Response Index, neutrophil‐to‐lymphocyte ratio, monocyte‐high‐density lipoprotein cholesterol ratio, serum C‐reactive protein levels, neutrophil count, monocyte count, body mass index, and waist circumference (p < 0.001, p = 0.001, p < 0.001, p = 0.014, p < 0.001, p < 0.001, p = 0.046, p < 0.001, and p = 0.011, respectively). Among patients with severe psoriasis (Psoriasis Area and Severity Index >10), systemic immune‐inflammation index, neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, and serum C‐reactive protein levels were significantly higher compared to patients with mild/moderate psoriasis (Psoriasis Area and Severity Index ≤10). In the ROC curve analysis, the optimal cut‐off (AUC, sensitivity, specificity) values for neutrophil‐to‐lymphocyte ratio, systemic immune‐inflammation index, and platelet‐to‐lymphocyte ratio were found to be 2.11 (0.592, 62%, 57%), 552.9 (0.579, 61%, 58%), and 111.9 (0.578, 64%, 46%), respectively. The inflammatory parameters that showed correlation with Psoriasis Area and Severity Index were systemic immune‐inflammation index, Systemic Inflammation Response Index, neutrophil‐to‐lymphocyte ratio, monocyte‐high‐density lipoprotein cholesterol ratio, monocyte‐to‐lymphocyte ratio, and C‐reactive protein. Conclusion: The findings of this study suggest that systemic immune‐inflammation index, Systemic Inflammation Response Index, neutrophil‐to‐lymphocyte ratio, monocyte‐high‐density lipoprotein cholesterol ratio, and C‐reactive protein values have the potential to serve as simple and cost‐effective markers for assessing the inflammatory burden in individuals with psoriasis. [ABSTRACT FROM AUTHOR]

Vitiligo is a chronic depigmenting disorder that significantly impacts the quality of life of patients. Though there have been significant advancements in targeted therapies in skin diseases such as psoriasis or eczema, the progress in the treatment of vitiligo has been slow, with minimal studies assessing the effect of biologics, though there has been recent evidence of the effectiveness of JAK inhibition. This paper reviews the published case reports and studies for the use of systemic targeted therapies including biologics and JAK inhibitors in vitiligo. [ABSTRACT FROM AUTHOR]

Background: The advent of novel biologics has led to an increase in biologic‐switching as patients and clinicians pursue improved clinical outcomes. However, guidance on treatment sequencing in an Australian setting is sparse. This study examines the patterns of care across two tertiary centres in Australia and characterizes the factors contributing to biologic‐switching. Methods: A retrospective study of patients who attended the outpatient Dermatology biologic clinics across two tertiary hospitals was conducted. Data on treatment sequencing and patients' PASI at every visit from April 2006 to December 2020 were collected. Patterns of biologic‐switching were examined. The speed of treatment response for each biologic was determined by the time to achieve PASI‐90 and ‐100 for each treatment course. Results: A total of 440 treatment courses were analysed. Ustekinumab and adalimumab were the most frequently prescribed first‐line biologics. The highest proportion of biologic‐switching was observed among patients on TNF‐α inhibitors (63.8%). After 2015, more patients were prescribed IL‐12/23 and IL‐17 inhibitors in favour of TNF‐α inhibitors. IL‐17 inhibitors demonstrated the most rapid treatment response and low PASI scores relative to other biologics. Patients who did not switch biologics had lower rates of psoriatic arthritis and lower BMI, compared to patients who switched biologics. The median PASI on discontinuation generally exceeded 3.0, while on continuation, it was less than 1.2, reflecting patients' and clinicians' thresholds for biologic‐switching. Conclusions: This study demonstrates an increased uptake of more novel biologics as they become available, due to improved safety profiles and clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: In comparison with TNF‐α inhibitors, anti‐IL‐17A agents are considered to have a lower risk of active tuberculosis (TB) or latent TB infection (LTBI) reactivation. Methods: In this study, we aimed to evaluate the TB infection status and serial QuantiFERON‐TB‐Gold in tube test (QFT) results of psoriasis patients using IL‐17 inhibitors (secukinumab [SEC] and ixekizumab [IXE]) in a real‐world setting from a tuberculosis‐endemic country. Patients who used an anti‐IL‐17 agent for at least 3 months in our follow‐up were included in the study. Patients' clinical and demographic features, baseline QFT results and latest QFT results (if any), and TB infection status were noted from the past medical records. Results: A total of 717 patients, of whom 333 (46.4%) were female, were included in the study. The cumulative exposure time to an anti‐IL‐17 agent was 14,147 patient‐months, 9743 patient‐months for SEC and 4404 patient‐months for IXE. Also, 459 (SEC = 305/IXE = 154) patients used an anti‐IL‐17 agent for ≥ 12 months. Of these, 125 had positive baseline QFT results. In all, 334 had negative baseline QFT results. The latest QFT result of 309 was also negative (persistent seronegative group). During follow‐up, the QFT results of 10 patients changed from negative to positive (positive seroconversion group). Seven of them were using SEC and three were using IXE, respectively. No case of active TB infection was detected. Conclusion: In our study, the positive seroconversion rate of 10/334 seems high, but this did not translate to active disease. However, closer monitoring may be required, especially in patients with advanced age, the presence of PsA, long disease duration and long anti‐IL‐17 treatment duration. [ABSTRACT FROM AUTHOR]

Objective: Inhibitors of the interleukin 13 (IL‐13) pathway, such as dupilumab, are licensed for atopic dermatitis and asthma. Adverse events resembling psoriatic disease after dupilumab initiation have been reported, but evidence is limited to case reports with uncertain causality. We aimed to investigate whether genetically mimicked IL‐13 inhibition (IL‐13i) is associated with risk of psoriatic arthritis (PsA) and psoriasis. Methods: We instrumented IL‐13i using a protein‐coding variant in the IL13 gene, rs20541, that is associated with circulating eosinophil count (biomarker of IL‐13i) at genome‐wide significance in a study of 563,946 individuals. Outcome genetic data were taken from studies of PsA, psoriasis, and related spondyloarthritis traits in up to 10,588 cases and 209,287 controls. Colocalization analysis was performed to examine genetic confounding. We additionally used circulating IgE as a biomarker to test whether associations were replicated, both in the test and in an independent genetic dataset. We also replicated analyses using individual‐level data from the UK Biobank. Results: Genetically proxied IL‐13i was associated with increased risk of PsA (odds ratio [OR] 37.39; 95% confidence interval [95% CI] 11.52–121.34; P = 1.64 × 10−9) and psoriasis (OR 20.08; 95% CI 4.38–92.01; P = 1.12 × 10−4). No consistent associations were found for Crohn disease, ulcerative colitis, ankylosing spondylitis, or iritis. Colocalization showed no strong evidence of genetic confounding for psoriatic disease. Results were replicated using circulating IgE for the exposure, using independent outcome data and using individual‐level data. Conclusion: We provide supportive genetic evidence that IL‐13i is linked to increased risk of PsA and psoriasis. Physicians prescribing IL‐13 inhibitors should be vigilant for these adverse events. [ABSTRACT FROM AUTHOR]

Background: Brodalumab, a fully human monoclonal immunoglobulin IgG2 antibody that binds the human interleukin 17 receptor subunit A, is available for the treatment of moderate‐to‐severe plaque psoriasis in Europe since September 2017, but so far there are only a few studies on its use in real‐world conditions. Objectives: To assess the management of moderate‐to‐severe psoriasis with brodalumab 210 mg in daily practice after 12 and 52 weeks (W). In addition, patient profiles and treatment pathways are described. Methods: LIBERO is a prospective, multicenter, non‐interventional study including adult patients with plaque psoriasis treated with brodalumab 210 mg. Results: In total, 638 patients (65% male, mean age: 49.3 ± 14.4 years) from 148 sites in Germany were enrolled. The majority suffered from severe (51.1%) or very severe (13.1%) psoriasis according to physician global assessment (PGA0‐5). When starting with brodalumab, 58.5% were biologic naïve and 41.5% were previously treated with another biologic, mainly adalimumab (18.5%) and secukinumab (17.9%). About 74.0% of patients met the primary endpoint of an absolute PASI ≤3 at ~W12 (n = 618, LOCF). The mean PASI was reduced significantly as of ~W2 from 17.2 (±11.7) to 9.7 (±8.8) and improved further to 3.3 (±6.3) at ~W12 (p < 0.001). At ~W52 85.5% of patients reached a PGA0/1‐response (primary endpoint) and 54.1% patients were assessed as completely clear (PGA0) (both n = 399, as observed). Effectiveness of brodalumab was confirmed in relevant subgroup analysis by previous treatment regimen. Most frequently reported adverse events were nasopharyngitis (4.6%), psoriasis (4.6%) and arthralgia (4.1%), new safety signals were not detected. Conclusions: This representative, non‐interventional study confirms the short‐ and long‐term effectiveness and safety profile of brodalumab in the management of psoriasis in daily practice as well as in relevant treatment pathways. [ABSTRACT FROM AUTHOR]

Background: Evidence describing the types and annual costs of biological treatments for psoriasis in Latin America is scarce. This study aimed to estimate the frequency of use and costs of biologic therapy for psoriasis in Colombia in 2019. Methods: This secondary data analysis uses the International Classification of Diseases terms associated with psoriasis, excluding those related to psoriatic arthritis, based on data from the registry of the Colombian Ministry of Health. We estimated the prevalence of psoriasis per 100,000 inhabitants; then, we retrieved the frequency of use of biologic therapy in patients with psoriasis and estimated the cost per year of each and overall therapies in 2019 in US dollars (USD). Results: There were 100,823 patients with psoriasis in Colombia in 2019, which amounts to a prevalence of 0.2% in the general population. Of those patients, 4.9% received biologic therapy, most frequently males (60%). The most commonly used biological therapies for psoriasis in Colombia in 2019 were ustekinumab (35.2%), with an annual cost per patient of $12,880 USD; adalimumab (26%), with a yearly cost per patient of $7130 USD; and secukinumab (19.8%), with an annual cost per patient of $6825 USD. Conclusion: This is the first study to describe the use and cost of biological therapy for psoriasis in Colombia. It provides valuable cost‐awareness information for the Colombian health system. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is an immune‐mediated inflammatory skin disorder with a multifaceted pathogenesis. Immune dysregulation and immune cell dysfunction are among the mechanisms involved. TEA domain family member 4 (TEAD4) is suggested to play a role in psoriasis development. TEAD4 expression in keratinocytes may have a chemotactic effect and could disturb the function of FOXP3‐positive T lymphocytes. This study aimed to evaluate the expressions of TEAD4 and FOXP3 in lesional, nonlesional psoriatic, and healthy skin and assess the clinical impact of their expression. Methods: This case–control study included 32 cases with psoriasis vulgaris and 32 control groups. Hematoxylin and eosin‐stained slides were examined to evaluate the histopathological findings. Moreover, other sections were immunohistochemically stained with FOXP3 and TEAD4. Results: FOXP3 was expressed in inflammatory cells in 56.5, 37.5, and 12.5% of lesional, nonlesional, and healthy skin, whereas it was entirely negative in the keratinocytes. TEAD4 was expressed in keratinocytes in 93.7 and 46.9% of lesional and nonlesional skin, while negative in healthy skin. Significant differences were observed between their lesional, nonlesional, and healthy skin expressions. Furthermore, FOXP3 expression in lesional skin was significantly associated with early onset (P = 0.016), low PASI score (P = 0.002), mild psoriasis (P = 0.007), and axial affection (P = 0.022), while TEAD4 expression was associated with progressive course (P = 0.032), high PASI score (P = 0.002), severe psoriasis (P = 0.001), severe inflammation (P = 0.001), and progressive course (P = 0.017). Conclusion: TEAD4 expression was higher in lesional than nonlesional skin and absent in healthy skin, suggesting a role in psoriasis development. TEAD4 expression was also associated with severe and progressive psoriasis. This may be mediated by the downregulation of FOXP3 and dysfunction of Treg cells. TEAD4 could serve as a promising therapeutic target in psoriasis. [ABSTRACT FROM AUTHOR]

Background: Generalized pustular psoriasis (GPP) is a rare, potentially life‐threatening skin disease often requiring long‐term therapy. We aimed to evaluate the use of Interleukin (IL)‐17A inhibitors (secukinumab and ixekizumab) in GPP patients over 96 weeks. Methods: We retrospectively analyzed a case series of 18 patients with GPP who received secukinumab (n = 13) and ixekizumab (n = 5) therapy with a 96‐week follow‐up period. The primary effectiveness analysis included determining the percentage of patients who achieved ≥90% or 100% improvement in the Generalized Pustular Psoriasis Area and Severity Index (GPPASI) score. Adherence was captured using the medication possession ratio (MPR). Results: Using the as‐observed (AO) method, 87% and 67% of patients treated with secukinumab or ixekizumab achieved GPPASI 90 and 100 responses, respectively. At Week 96, the mean GPPASI improvements from baseline GPPASI were 96.3% (95% CI: 0.91–1.01) using the AO method. After Week 48, 14 patients tapered (n = 8) or terminated (n = 6) the treatment. High‐adherence therapy (MPR ≥ 80%) was significantly superior to the low‐adherence group in the rate of patients achieving a GPPASI 100 response (AO, 100% vs. 38%, P < 0.05). By Week 96, 5 (27.8%) patients had new GPP flares, and 4 (80%) were in the low‐adherence group. No new safety signals occurred. Conclusion: IL‐17A inhibitors led to effective and sustained improvement in GPP patients, and high‐adherence therapy had long‐term positive effects on skin clearance. Given its relapsing nature, improving compliance is beneficial for long‐term clinical management. [ABSTRACT FROM AUTHOR]

Psoriasis is a skin disease that is inflammatory and persistent, causing a high rate of recurrence, poor quality of life, and significant socioeconomic burden. Its main pathological manifestations are abnormal activation and infiltration of T cells and excessive proliferation of keratinocytes (KCs). The great majority of patients with psoriasis will relapse after remission. It usually lasts a lifetime and necessitates long‐term treatment strategies. During periods of activity and remission, one of the main cell types in psoriasis is memory T cells, which include tissue‐resident memory T (TRM) cells, central memory T (TCM) cells, and effector memory T (TEM) cells. They work by releasing inflammatory factors, cytotoxic particles, or altering cell subpopulations, leading to increased inflammation or recurrence. This review summarizes the role of memory T cells in the pathology and treatment of psoriasis, with a view to potential novel therapies and therapeutic targets. [ABSTRACT FROM AUTHOR]

Purpose: Biological treatment has been a game changer in the management of moderate‐to‐severe psoriasis. In Denmark, biological treatment for psoriasis is registered in two data sources. We aimed to describe the utilization of biologics for psoriasis in Denmark using data from both data sources separately. Methods: We used data from two different nationwide Danish data sources: The healthcare registries and the clinical quality database, Dermbio. Utilization patterns were described by three different parameters: (1) distribution of drugs used in the first treatment episodes, (2) treatment cascade on a population level, and (3) drug survival using Kaplan Meier (KM) analysis and the proportion of patients covered (PPC) method. Results: From January 1, 2011, to December 31, 2018, we found 1878 users of biologics in the healthcare registries and 2264 in Dermbio. Adalimumab, ustekinumab, and secukinumab were the most common first‐choice treatments throughout the study period. According to the healthcare registries, it was most common to have more than one treatment episode with the same drug. In Dermbio, most were registered to have only one observable treatment episode overall in the study period. Ustekinumab showed the longest drug survival in both databases. Drug survival was longer for all biologics in Dermbio than in the healthcare registries. Conclusion: Adalimumab, ustekinumab, and secukinumab were the most common first‐choice treatments in Denmark. Overall, ustekinumab showed the longest drug survival. We observed important differences in treatment cascades and drug survival between Dermbio and the healthcare registries, which should be considered when using these data sources to perform drug utilization studies on biologics. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Background and Objective: Erosions of the skin and mucous membranes with epidermal dysmaturation are a known side effect of cytostatic chemotherapy regimens and can also be observed during low‐dose methotrexate (MTX) therapy. The study aimed to delineate the clinical and histopathological alterations. Patients and Methods: A database search of the archive for dermatopathology was conducted, identifying 22 patients who developed epidermal dysmaturation on low‐dose MTX. Clinical and laboratory changes, along with an array of histologic parameters were analyzed and statistically evaluated using SPSS. Results: Patients were predominantly female with a mean age of 69.1 years. The main indications were psoriasis vulgaris and rheumatoid arthritis. Clinically, patients mostly presented erosive plaques at the injection site, on mucosal surfaces, and disseminated lesions. Most patients showed normal laboratory values. Histopathologically, key findings included enlarged keratinocytes with pale cytoplasm and enlarged nuclei with prominent nucleoli, along with the degeneration of the basal layer. Consistent observations in the dermal compartment included infiltration of neutrophilic granulocytes, lymphocytes, and histiocytes. Conclusions: This study proposes clinicopathological criteria for the diagnosis of MTX‐associated skin toxicity, aiming to increase awareness among clinicians and pathologists for early diagnosis. Early recognition can prevent potentially life‐threatening progression. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Background and Objectives: Up to 30% of psoriasis (PsO) is clinically associated with psoriatic arthritis (PsA). A large proportion of new onset of PsA is diagnosed at a later stage, despite the necessity of early effective treatment to prevent structural damage. This study aimed to identify the routine screening practices used for PsA in patients with PsO. Patients and Methods: This non‐interventional, prospective, epidemiological, cross‐sectional study conducted in Germany focuses on screening activity and treatment selection of dermatological practices in suspected PsA. Descriptive statistics and patient characteristics were analyzed for different center types. Results: One hundred ninety‐five patients from 34 office‐based physicians, five non‐university hospitals, and nine university hospitals were included. Questionnaires or imaging techniques were not routinely used (< 45%). Especially, ultrasounds (≤ 5%) and MRIs (< 6.3%) were rarely performed. Between 30% and 75% of suspected PsA could be confirmed. Referral to rheumatologists and/or appropriate therapy initiation were the most frequent consequences. Conclusions: Results of this study reflect the status of PsA screening activity by dermatologists. Imaging techniques, particularly ultrasound or MRIs to detect early forms of PsA, were inadequately used, which may have contributed to continued underdiagnoses. Collaboration between dermatologists and rheumatologists should be reviewed with a view to improving effective PsA screening. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is a chronic, inflammatory articular disease regarded as a specific subtype of psoriasis. Long‐term assessment for PsA using ultrasonography has not yet been investigated. The present study was conducted to delineate the changes in articular lesions after the initiation of biologics using ultrasonography, and to provide the evidence of the utility of ultrasonography in long‐term follow‐up of PsA patients. We retrospectively recruited 17 Japanese PsA patients treated with biologics who met the classification criteria for psoriatic arthritis. Ultrasonographic images were recorded using a high‐frequency linear 18 MHz probe through Doppler‐ and B‐modes. Before the treatment with biologics, all examined patients (100%) had enthesitis and extensor tendinitis, while only six patients (35.3%) had loss of the fibrillar pattern of the tendon (LFP). There were significant changes over time in the numerical rating scale score for pain, and in the degree of ultrasonographic findings, including enthesitis, extensor tendinitis, and LFP. Also, there were significant changes over time between these ultrasonographic findings. The study identified the improvement course for a specific PsA lesion after the initiation of biologics. The improvement courses in enthesitis, extensor tendinitis, and LFP were found to differ from each other. These results may contribute to deeper understanding of the pathogenesis of PsA. [ABSTRACT FROM AUTHOR]

Objectives Design Methods Results Conclusions Psoriasis is a chronic skin condition that can develop at any age. Childhood psoriasis can lead to stigmatization and reduced quality of life in children and parents. This study aimed to gather a detailed family‐level understanding of the experience of childhood psoriasis during the time of transition to adolescence.A multi‐perspectival interpretative phenomenological analysis (IPA) was used.Sixteen semi‐structured interviews with eight parent–child dyads were conducted and analysed in accordance with IPA principles.Three superordinate themes and three sub‐themes were identified: 1. ‘Transition and transaction’ including: 1.1 ‘Shifting responsibilities and self‐efficacy’; 2. ‘Stigma and social impact’; and 3. ‘The treatment journey’ including: 3.1 ‘Finding an effective treatment’, 3.2 ‘Coping with on‐going management’. Uncertainties surrounding treatment options were an initial focus of difficulty for families. In adolescence, the difficulty shifted to be more identity focussed as the responsibility for disease management and the increased awareness on body image posed added challenges. Both parents and children described visibility and stigma as the most distressing aspects of living with psoriasis and experienced negative emotions that resurfaced during adolescence.This study suggests that childhood psoriasis can have a significant impact on children, particularly as they begin to transition to adolescence. Findings also highlight the burden of psoriasis for parents. As such, psychological interventions (such as adapted forms of mindfulness‐based Cognitive‐Behavioural‐Therapy) are needed to target and reduce stress. Such interventions are likely to require a systemic focus and support validation of the real impact and fear of stigmatization. [ABSTRACT FROM AUTHOR]

ABSTRACT Line‐field confocal optical coherence tomography (LC‐OCT) is a novel imaging technique for in vivo examination of the skin that has recently been introduced in the dermatologic armamentarium of non‐invasive diagnostic tools. Its usefulness in the diagnosis and treatment monitoring of some neoplastic, inflammatory, and infectious skin conditions has been demonstrated. The aim of this study was to evaluate the LC‐OCT features of psoriasis in a large number of psoriatic plaques along with their histopathologic correlation. In this retrospective study, the LC‐OCT and the corresponding histopathologic images of 100 psoriatic plaques of the trunk, upper and lower arms from 60 patients that underwent both procedures were evaluated and correlated. The following microscopic findings, typical of plaque psoriasis, were observed at both LC‐OCT and histopathology: hyperkeratosis, parakeratosis, acanthosis, papillomatosis and vascular changes, Munro microabscesses, and pustules of Kogoj. The LC‐OCT findings perfectly matched with histopathology. Our study confirms the usefulness of this new imaging technique in the non‐invasive visualization of the common diagnostic clues of psoriasis. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic skin disease characterized by abnormal proliferation and inflammation of epidermal keratinocytes. Fibroblast growth factor 12 (FGF12) is implicated in the regulation of diverse cellular signals; however, its precise mechanism in psoriasis requires further investigation. In this study, high expression of FGF12 is observed in the epidermis of skin lesion in psoriasis patients and imiquimod (IMQ)‐induced psoriasis like‐dermatitis. Moreover, specific loss of FGF12 in keratinocytes in IMQ‐induced psoriasis model alleviates psoriasis‐like symptoms and reduces proliferation. In vitro RNA sequencing demonstrates that knockdown of FGF12 effectively arrests the cell cycle, inhibits cell proliferation, and predominantly regulates the p53 signaling pathway. Mechanistically, FGF12 is selectively bound to the RING domain of MDM2, thus partially inhibiting the binding of β‐Trcp to MDM2. This interaction inhibits β‐Trcp‐induced‐K48 ubiquitination degradation of MDM2, thereby suppressing the activity of the p53 signaling pathway, which results in excessive cell proliferation. Last, the alleviatory effect of FGF12 deficiency on psoriasis progression is reversed by p53 knockdown. In summary, these findings provide valuable insights into the mechanisms by which FGF12 suppresses p53 signaling in keratinocytes, exacerbating the development of psoriasis. This positive regulatory loop highlights the potential of FGF12 as a therapeutic target to manage psoriasis. [ABSTRACT FROM AUTHOR]

Psoriasis, a common chronic inflammatory skin disorder, encompasses various subtypes, including guttate, pustular, erythrodermic, and the most common type, plaque psoriasis. Irrespective of the subtype, psoriasis can manifest with multisystemic presentations, including psoriatic arthritis, metabolic disorders, cardiovascular disease, malignancies, chronic kidney disease (CKD), psychiatric illness, and inflammatory bowel disease (IBD). Many comorbidities and concomitant conditions must be considered when selecting the most appropriate therapy for a patient (Kaushik et al., 2019 and Monks et al., 2021) . Ongoing clinical trials and the development of new therapeutic targets contribute to the continuous improvement of available treatment options. Given the dynamic landscape of therapies, particularly when managing complex patients with multiple comorbidities, dermatologists are constantly challenged with the task of adeptly tailoring treatments to each psoriasis patient. This article systematically reviews the current evidence, presenting it as an updated Psoriasis Decision Tree to assist physicians in selecting tailored treatment options. [ABSTRACT FROM AUTHOR]

Targeted biologic drugs and small molecules have transformed the psoriasis treatment landscape in recent years. The Belgian healthcare system, in common with many others across Europe, must balance the burgeoning use of these transformative, yet expensive, drugs with the sustainable use of limited resources. Drawing on recent updates to the EuroGuiDerm and the German S2 psoriasis guidelines, eight Belgian dermatologists experienced in treating patients with psoriasis undertook a quasi‐Delphi initiative to provide perspectives on the current opportunities and challenges in psoriasis. This update focuses on responsible ways to rationalize the use of innovative treatments (e.g. biologics and small molecules). Inherently, this required viewpoints on the International Psoriasis Council's new definition of severe psoriasis, defining psoriasis severity and the concept of treating to target. It discusses the appropriateness of using older biologics classes, biosimilars and personalized dosing and lastly, how teledermatology may play a role in providing sustainable, patient‐centric psoriasis care. In addition, this manuscript includes the updated Belgian evidence‐based treatment advice in psoriasis (BETA‐PSO) to reflect recent data and drug approvals. The recommendations reflect the best practices for clinicians when using systemic and biologic therapies to treat patients with psoriasis and offer guidance on how they may prescribe these drugs sustainably and efficiently. [ABSTRACT FROM AUTHOR]

Persistent inflammation, characterized by the intense interplay of inflammatory chemokine secretion and immune cell infiltration, is a hallmark of many skin disorders including diabetic wounds and psoriasis with inadequate therapeutic interventions. Monocyte chemotactic protein‐1 (MCP‐1) is an inflammatory chemokine that plays a key role in recruiting and polarizing monocytes into pro‐inflammatory macrophages to establish a vicious cycle that worsens the inflamed tissue microenvironment. Here, the sponge‐like microneedles (HPMN) technology is described to alleviate inflammatory skin disorders. Heparin/4‐arm PEG‐NH2 network crosslinked onto microneedle surface spatially attracted and sequestered multiple inflammatory chemokines including MCP‐1. Enrichment of MCP‐1 on microneedles recruits and traps inflammatory monocytes within the porous structure of microneedles. Subsequent removal of microneedles not only depletes inflammatory chemokine, MCP‐1, but also its cellular source. As a result, HPMN treatment facilitates 47.1% smaller open wound area in mice and 27.2% shorter wound length in pigs. To demonstrate the versatility of the HPMN technology, it is also shown that combining the method with standard‐of‐care immunosuppressants reduces 45.1% epidermis thickening and attenuated immune cell influx in a mouse psoriasis model. Overall, the HPMN technology is a novel demonstration of employing inflammatory chemokine and cell extraction to treat a broad range of inflammatory skin disorders. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions 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.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.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.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. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions 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.Retrospective immunohistochemical and chart review pilot study.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).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. [ABSTRACT FROM AUTHOR]

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]

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]

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]

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]

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]

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]

Nail psoriasis is a chronic condition characterized by nail dystrophy affecting the nail matrix and bed. The severity of nail psoriasis is commonly assessed using the Nail Psoriasis Severity Index (NAPSI), which evaluates the characteristics and extent of nail involvement. Although the NAPSI is numeric, reproducible, and simple, the assessment process is time‐consuming and often challenging to use in real‐world clinical settings. To overcome the time‐consuming nature of NAPSI assessment, we aimed to develop a deep learning algorithm that can rapidly and reliably evaluate NAPSI, thereby providing numerous clinical and research advantages. We developed a dataset consisting of 7054 single fingernail images cropped from images of the dorsum of the hands of 634 patients with psoriasis. We annotated the eight features of the NAPSI in a single nail using bounding boxes and trained the YOLOv7‐based deep learning algorithm using this annotation. The performance of the deep learning algorithm (DLA) was evaluated by comparing the NAPSI estimated using the DLA with the ground truth of the test dataset. The NAPSI evaluated using the DLA differed by 2 points from the ground truth in 98.6% of the images. The accuracy and mean absolute error of the model were 67.6% and 0.449, respectively. The intraclass correlation coefficient was 0.876, indicating good agreement. Our results showed that the DLA can rapidly and accurately evaluate the NAPSI. The rapid and accurate NAPSI assessment by the DLA is not only applicable in clinical settings, but also provides research advantages by enabling rapid NAPSI evaluations of previously collected nail images. [ABSTRACT FROM AUTHOR]

Langerhans cells (LCs) are the key antigen‐presenting cells in the epidermis in normal conditions and respond differentially to environmental and/or endogenous stimuli, exerting either proinflammatory or anti‐inflammatory effects. Current knowledge about LCs mainly originates from studies utilizing mouse models, whereas with the development of single‐cell techniques, there has been significant progress for human LCs, which has updated our understanding of the phenotype, ontogeny, differentiation regulation, and function of LCs. In this review, we delineated the progress of human LCs and summarized LCs' function in inflammatory skin diseases, providing new ideas for precise regulation of LC function in the prevention and treatment of skin diseases. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and Objective Methods Results Conclusions As the population and life expectancy of people with Down syndrome increases, identifying common skin conditions throughout the lifespan will help inform clinical care and research. We sought to evaluate dermatologic conditions diagnosed in pediatric and adult patients with Down syndrome.This multicenter retrospective study analyzed demographic and outpatient visit International Classification of Diseases codes of patients with Down syndrome evaluated at outpatient dermatology clinics in the United States or Canada between 2011 and 2021.A total of 1529 patients with Down syndrome were identified from eight academic medical centers: 50.8% were children (0–12 years), 25.2% were adolescents (13–17 years), and 24% were adults (18 years and older). Eczematous dermatitis was the most common diagnosis overall (26%), followed by folliculitis (19.3%) and seborrheic dermatitis (15.6%). Other notable diagnoses included dermatophyte infections (13%), alopecia areata (11.6%), and psoriasis (6.7%). About 4.3% of visits included a code for high‐risk medication use. Eczematous dermatitis, alopecia areata, and folliculitis were the most common diagnoses observed in children; folliculitis, hidradenitis suppurativa, and eczematous dermatitis in adolescents; and seborrheic dermatitis, eczematous dermatitis, and folliculitis in adults.Dermatologic conditions in patients with Down syndrome vary by age, but are most often eczematous, adnexal, and cutaneous autoimmune disorders. This multicenter retrospective review identifies skin diseases that should be prioritized for clinical care guideline development and research in the Down syndrome community. [ABSTRACT FROM AUTHOR]

In the RUSTIC trial, pharmacokinetic (PK) similarity between the proposed ustekinumab biosimilar FYB202 and EU‐approved (EU‐Ref) and US‐licensed ustekinumab (US‐Ref) as well as between both reference drugs was assessed after a single 45‐mg subcutaneous injection. Safety analyses comprised immunogenicity (antidrug antibodies, neutralizing antibodies), adverse events, and local tolerability. Overall, 491 healthy adults were randomized 1:1:1 and observed for up to 112 days; 486 completed the trial, and 478 were included in the PK analysis. All 3 comparisons showed PK similarity, since the 90% confidence intervals of the respective geometric mean ratios for area under the concentration‐time curve from time 0 to infinity and maximum serum concentration were contained within the acceptance interval of 80%‐125%. No clinically meaningful differences regarding overall safety, immunogenicity, and local tolerability were observed. Notably, after FYB202 administration, in fewer subjects at least 1 positive antidrug antibody result was observed compared to the reference groups (FYB202, 20%; EU‐Ref, 42%; US‐Ref, 51%). In conclusion, the RUSTIC trial demonstrated equivalent PK characteristics for FYB202 when compared to both EU‐Ref and US‐Ref ustekinumab and between both reference drugs. It provides the basis for the marketing authorization of FYB202, together with an extensive analytical characterization and the results of a confirmatory efficacy and safety trial in patients with moderate to severe plaque psoriasis. [ABSTRACT FROM AUTHOR]

Psoriasis is a common immune‐related polygenic inflammatory skin disease. Salidroside (SAL) exerts anti‐inflammatory and antioxidant effects and is used to treat skin diseases. However, the specific effects of SAL on psoriasis remain unclear. In this study, we aimed to investigate the efficacy of SAL for psoriasis treatment. Mice were treated with imiquimod (IMQ) to establish an in vivo psoriasis model. Histological analysis was conducted via hematoxylin and eosin staining. Cytokine release was determined via enzyme‐linked immunosorbent assay. Additionally, mRNA levels were determined via reverse transcription‐quantitative polymerase chain reaction. Protein expression was assessed via Western blotting. Gasdermin D (GSDMD) and Ki‐67 expression levels were determined via immunohistochemistry. Caspase 1 and GSDMD expression levels were determined via immunofluorescence assay. Furthermore, macrophage function and keratinocyte pyroptosis were also analyzed via flow cytometry. Cell proliferation was determined using 5‐ethynyl‐2ʹdeoxyuridine assay. SAL alleviated IMQ‐induced psoriasis. IMQ‐mediated GSDMD‐driven pyroptosis and keratinocyte hyperproliferation promoted M1 macrophage polarization. However, SAL treatment suppressed GSDMD expression, thereby inhibiting keratinocyte proliferation and pyroptosis and promoting M2 macrophage polarization. GSDMD deficiency further promoted the effects of SAL and suppressed psoriasis progression. Overall, our findings suggest that SAL exerts protective effects against psoriasis. Specifically, it exerts anti‐inflammatory effects by regulating M2 macrophage polarization and inhibiting keratinocyte pyroptosis‐driven proliferation induced by the immune microenvironment in psoriasis. [ABSTRACT FROM AUTHOR]

The objective of this article is to evaluate the salivary levels of tumor necrosis factor‐alpha (TNF‐α), interferon‐gamma (IFN‐γ), interleukin‐2 (IL‐2), and IL‐10 in patients with active psoriasis and compare them with those in healthy control subjects. This study included 60 subjects who were clinically diagnosed cases with active psoriasis (categorized further into 33 mild to moderate and 27 severe cases based on the Psoriasis Area Severity Index score) and 60 age‐ and gender‐matched healthy control subjects. Levels of TNF‐α, IFN‐γ, IL‐2, and IL‐10 in the unstimulated saliva of subjects were determined via enzyme‐linked immunosorbent assay (BT Lab). The salivary levels of TNF‐α, IFN‐γ, and IL‐2 were significantly higher, whereas IL‐10 concentration was significantly reduced in psoriatic patients in comparison to controls, and the difference increased with the progressing severity of the disease. Assessment of cytokine profiles in psoriasis patients is significant for diagnostic validation and monitoring the disease severity. Saliva offers an alternate, noninvasive, and readily available biological sample for evaluating cytokine levels. Extensive research in this field has been recommended for better scientifically proven conclusions. [ABSTRACT FROM AUTHOR]

Reconstructed epidermal equivalents (REEs) consist of two distinct cell layers – the stratum corneum (SC) and the keratinocyte layer (KL). The interplay of these layers is particularly crucial in pruritic inflammatory disorders, like psoriasis, where a defective SC barrier is associated with immune dysregulation. However, independent evaluation of the skin barrier function of the SC and KL in REEs is highly challenging because of the lack of quantitative methodologies that do not disrupt the counter layer. Here, a non‐invasive impedance spectroscopy technique is introduced for dissecting the distinct contributions of the SC and KL to overall skin barrier function without disrupting the structure. These findings, inferred from the impedance spectra, highlight the individual barrier resistances and maturation levels of each layer. Using an equivalent circuit model, a correlation between impedance parameters and specific skin layers, offering insights beyond traditional impedance methods that address full‐thickness skin only is established. This approach successfully detects subtle changes, such as increased paracellular permeability due to mild irritants and the characterization of an immature SC in psoriatic models. This research has significant implications, paving the way for detailed mechanistic investigations and fostering the development of therapies for skin irritation and inflammatory disorders. [ABSTRACT FROM AUTHOR]

Xeligekimab, a recombinant fully human IgG4 monoclonal antibody, has been strategically developed to target IL‐17A and is presently in the developmental phase for treating moderate to severe plaque psoriasis. This study aims to investigate the pharmacokinetic profile of Xeligekimab, utilizing data derived from clinical trials specifically conducted in Chinese patients. The study conducted a population pharmacokinetic (PopPK) analysis involving 614 patients with plaque psoriasis. Examined covariates encompassed demographics, baseline laboratory tests, anti‐drug antibodies (ADA), injection site, and disease‐related baseline characteristics. Model evaluation utilized goodness‐of‐fit, prediction‐corrected visual prediction check, and bootstrap methods. The clinical significance of covariates statistically associated with Xeligekimab was assessed through simulation analysis. The PopPK model of Xeligekimab demonstrated characteristics of a two‐compartment model with first‐order absorption and linear elimination. Inter‐individual variability (IIV) was estimated for clearance and volume of distribution. For a typical plaque psoriasis patient, the estimated values for absorption rate constant (Ka), apparent clearance (CL/F), central compartment volume (Vc/F), peripheral compartment volume (Vp/F), and inter‐compartmental clearance (Q/F) was 0.225 per day, 2.223 L/day, 4.02 L, 4.13 L, and 1.11 L/day, respectively. The estimated IIV for CL/F and Vc/F was 25.8% and 49.8%, respectively. The elimination half‐life (t1/2) was approximately 28.5 days. CL/F was significantly influenced by factors such as body weight, age, gender, and baseline total protein. Vc/F was significantly influenced by body weight, age, gender, and baseline albumin. However, the clinical relevance of these covariate effects on exposure parameters was determined to be limited. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a rare, chronic skin disease, characterized by widespread pustules and erythema, often accompanied with systemic signs and symptoms. GPP flares occur episodically but may be protracted. Left untreated, GPP can be life‐threatening. Despite being first reported over 100 years ago, definitions and diagnostic criteria for GPP have been inconsistent and varied due, in part, to its rarity and a limited understanding of its pathogenesis. As such, many patients with GPP face delays in diagnosis and subsequent treatment. This manuscript aims to increase the recognition of GPP and provide foundational considerations to aid in the definition and diagnosis of this disease. [ABSTRACT FROM AUTHOR]