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Managing psoriasis (PsO) and its comorbidities, particularly psoriatic arthritis, often involves using interleukin (IL)-23 and IL-12/23 inhibitors. However, the comparative risk of these treatments still needs to be explored. This study evaluates the risk of developing psoriatic arthritis in patients treated with IL-23 inhibitors compared to IL-12/23 inhibitors. This retrospective cohort study utilized data from the TriNetX, including adult patients diagnosed with PsO. Patients with IL-23 or IL-12/23 inhibitors treatment were included and propensity score matched. The primary outcome was the incidence of psoriatic arthritis (PsA), analyzed using a Cox regression hazard model and Kaplan-Meier estimates. The study included matched cohorts of patients treated with IL-23 inhibitors (n = 2273) and IL-12/23 inhibitors (n = 2995). Cox regression analysis revealed no significant difference in the cumulative incidence of PsA between the IL-23i and IL-12/23i cohorts (P =.812). Kaplan-Meier estimates confirmed similar cumulative incidences of arthropathic PsO in both cohorts over the study period. Long-term follow-up studies are required to understand more of the effects of these interleukin inhibitors. No significant difference but a numerically lower risk of psoriatic arthritis in PsO patients treated with IL-23 inhibitors than with IL-12/23 inhibitors was found, underscoring their comparable efficacy in PsO management and follow-up. [ABSTRACT FROM AUTHOR]

Purinergic signaling plays a causal role in the modulation of immune inflammatory response in the course of psoriasis, but its regulatory mechanism remains unclear. As a member of purinoceptors, P2Y 6 R mainly distributed in macrophages was significantly up-expressed in skin lesions from patients with psoriasis in the present study. Here, the severity of psoriasis was alleviated in imiquimod-treated mice with macrophages conditional knockout of P2Y 6 R, while the cell-chat algorithm showed there was a correlation between macrophage P2Y 6 R and Th1 cells mediated by IL-27. Mechanistically, P2Y 6 R enhanced PLC β /p-PKC/MAPK activation to induce IL-27 release dependently, which subsequently regulated the differentiation of Th1 cells, leading to erythematous and scaly plaques of psoriasis. Interestingly, we developed a novel P2Y 6 R inhibitor FS-6, which bonds with the ARG266 side chain of P2Y 6 R, exhibited remarkable anti-psoriasis effects targeting P2Y 6 R. Our study provides insights into the role of P2Y 6 R in the pathogenesis of psoriasis and suggests its potential as a target for the development of therapeutic interventions. A novel P2Y 6 R inhibitor FS-6 could be developed as an anti-psoriasis drug candidate for the clinic. Macrophage P2Y 6 R enhances release of IL-27 to mediate Th1 cell differentiation in the pathogenesis of psoriasis via PLC β /p-PKC/MAPK signaling, which could be reversed by a novel P2Y 6 R inhibitor FS-6. [Display omitted] [ABSTRACT FROM AUTHOR]

Connective tissue, rheumatological and dermatological conditions affect a large proportion of the pregnant population and have important implications for women and their babies. Some conditions are chronic but may occur de novo in pregnancy whereas some are seen only during pregnancy. Multidisciplinary care is essential to maximise fetal and maternal outcomes, since many of these women require immunosuppressive treatment and close monitoring of their pregnancies. The development of biological therapies has revolutionised treatment of many connective tissue and arthritic diseases, allowing both more targeted treatments and an increase in treatment options. Their impact on fertility is minimal compared to older treatments and hence more women are able to conceive. With new treatments there will always be concerns about safety in pregnancy but concerns around neonatal immunosuppression have largely been unfounded and the benefits of continuing medication are significant. This article uses four cases to illustrate the challenges of management. [ABSTRACT FROM AUTHOR]

Stabilin‐1 (Stab1) and Stabilin‐2 (Stab2) are scavenger receptors expressed by liver sinusoidal endothelial cells (LSECs). The Stabilin‐mediated scavenging function is responsible for regulating the molecular composition of circulating blood in mammals. Stab1 and Stab2 have been shown to influence fibrosis in liver and kidneys and to modulate inflammation in atherosclerosis. In this context, circulating and localized TGFBi and POSTN are differentially controlled by the Stabilins as their receptors. To assess Stab1 and Stab2 functions in inflammatory and fibrotic skin disease, topical Imiquimod (IMQ) was used to induce psoriasis‐like skin lesions in mice and Bleomycin (BLM) was applied subcutaneously to induce scleroderma‐like effects in the skin. The topical treatment with IMQ, as expected, led to psoriasis‐like changes in the skin of mice, including increased epidermal thickness and significant weight loss. Clinical severity was reduced in Stab2‐deficient compared to Stab1‐deficient mice. We did not observe differential effects in the skin of Stabilin‐deficient mice after bleomycin injection. Interestingly, treatment with IMQ led to a significant increase of Stabilin ligand TGFBi plasma levels in Stab2−/− mice, treatment with BLM resulted in a significant decrease in TGFBi levels in Stab1−/− mice. Overall, Stab1 and Stab2 deficiency resulted in minor alterations of the disease phenotypes accompanied by alterations of circulating ligands in the blood in response to the disease models. Stabilin‐mediated clearance of TGFBi was altered in these disease processes. Taken together our results suggest that Stabilin deficiency‐associated plasma alterations may interfere with preclinical disease severity and treatment responses in patients. [ABSTRACT FROM AUTHOR]

Ustekinumab (UST) is a safe and effective treatment for moderate-to-severe psoriasis. To compare efficacy, safety, pharmacokinetics (PK), and immunogenicity of the proposed UST biosimilar SB17 with reference UST in subjects with moderate-to-severe plaque psoriasis. In this randomized double-blind study, subjects were randomized to receive 45 mg of SB17 or UST subcutaneously at week 0, 4, and every 12 weeks. The primary endpoint was the percent change from baseline in Psoriasis Area and Severity Index at week 12 with an equivalence margin of [−15%, 15%]. Other secondary efficacy, safety, PK, and immunogenicity endpoints were measured through week 28. Two hundred forty-nine subjects were randomized to SB17, 254 to UST. Adjusted difference of Psoriasis Area and Severity Index change from baseline at week 12 of −0.6% (95% confidence interval; −3.780, 2.579) was within the equivalence margin. Physician's Global Assessment and Dermatology Life Quality Index were also comparable. Overall treatment-emergent adverse events were comparable (SB17: 48.2%, UST: 48.8%). The overall incidence of antidrug antibodies up to Week 28 was 13.3% with SB17 and 39.4% with UST. Data were only through week 28. SB17 was clinically biosimilar to UST up to week 28. [ABSTRACT FROM AUTHOR]

The relationship between biologic treatments for psoriasis (PsO) and the development of inflammatory arthritis in patients is not fully understood. The objective of this study was to analyze the effects of biologic treatment on the development of inflammatory arthritis in patients with PsO. This retrospective study assessed patients with PsO identified in the Optum Clinformatics Data Mart database from Jan 2007 to Mar 2023 with no baseline diagnosis of inflammatory arthritis. Patients were stratified based on the class of initial biologic treatment (interleukin [IL] 23, IL-12/23, IL-17, or tumor necrosis factor [TNF] inhibitor) and followed for up to 3 years or development of inflammatory arthritis. Risk of developing inflammatory arthritis was assessed using a multivariate Cox proportional hazard model using IL-23 inhibitors as reference. Incidence rates of developing inflammatory arthritis expressed as events/100 person-years were 4.99, 7.29, 6.06, and 9.39 for IL-23, IL-17, IL-12/23, and TNF inhibitors, respectively. Adjusted hazard ratios were significantly higher for patients receiving IL-17 (1.44; P =.0294) and TNF (1.90; P <.0001) inhibitors when compared with patients receiving IL-23 inhibitors. Limitations include those associated with medical coding errors and the potential for protopathic bias. Patients receiving IL-23 inhibitors are at lower risk of developing inflammatory arthritis or psoriatic arthritis than those receiving IL-17 and TNF inhibitors. [ABSTRACT FROM AUTHOR]

Patients with psoriasis are at increased risk of liver function abnormalities. Explore rates of hepatic treatment-emergent adverse events (TEAEs) and changes in liver parameters in bimekizumab-treated patients with psoriasis. Data are reported from 5 phase 3/3b trials over 2 years. Hepatic TEAEs, laboratory elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST), and changes in clinical markers of liver fibrosis (Fibrosis-4 [FIB-4] Index and AST to Platelet Ratio Index [APRI]) are reported. TEAEs are presented using exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY). 2186 patients received ≥1 bimekizumab dose. Over 2 years, the EAIR of hepatic TEAEs was 3.5/100 PY and did not increase from first to second year. 2-year EAIRs of ALT/AST elevations >3x and >5x the upper limit of normal were 2.3 and 0.6/100 PY; rates were similar to placebo, adalimumab, secukinumab, and ustekinumab during controlled study periods. FIB-4 and APRI scores did not increase through 2 years, regardless of fibrosis risk at baseline. Obesity, diabetes, dyslipidemia, chronic alcohol consumption, and medication changes are confounding factors for hepatic dysfunction. Rates of hepatic adverse events (AEs) with bimekizumab were consistent through 2 years; incidences of transaminase elevations were similar to comparators during phase 3/3b controlled study periods. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic skin inflammation influenced by dysregulated skin microbiota, with the role of microbiota in psoriasis gaining increasing prominence. Bacterial extracellular vesicles (bEVs) serve as crucial regulators in the interaction between hosts and microbiota. However, the mechanism underlying the therapeutic potential of bEVs from commensal bacteria in psoriasis remains unclear. Here, we investigated the therapeutic role of Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs) in psoriasis treatment. To prolong the active duration of CA-EVs, we encapsulated them in gelatin methacrylate (GelMA) to fabricate hydrogel microspheres (CA-EVs@GHM) with sustained release properties. As GelMA degraded, CA-EVs were gradually released, maintaining a high concentration in mouse skin even 96 h post-treatment. In human keratinocyte cells (HaCaT), CA-EVs@GHM enhanced resistance to Staphylococcus aureus (S. aureus), promoted proliferation and migration of HaCaT cells exposed to S. aureus , and significantly reduced the expression of inflammatory genes such as interleukin (IL)-6 and C-X-C motif chemokine ligand 8 (CXCL8). In vivo , CA-EVs@GHM, more potent than CA-EVs alone, markedly attenuated proinflammatory gene expression, including tumor necrosis factor (TNF), Il6, Il17a, Il22 and Il23a in imiquimod (IMQ)-induced psoriasis-like mice, and restored skin barrier function. 16S rRNA sequencing revealed that CA-EVs@GHM might provide therapeutic effects against psoriasis by restoring microbiota diversity on the back skin of mice, reducing Staphylococcus colonization, and augmenting lipid metabolism. Furthermore, flow cytometry analysis showed that CA-EVs@GHM prevented the conversion of type 2 innate lymphoid cells (ILC2) to type 3 innate lymphoid cells (ILC3) in psoriasis-like mouse skin, reducing the pathogenic ILC3 population and suppressing the secretion of IL-17 and IL-22. In summary, our findings demonstrate that the long-term sustained release of CA-EVs alleviated psoriasis symptoms by controlling the transformation of innate lymphoid cells (ILCs) subgroups and restoring skin microbiota homeostasis, thus offering a promising therapy for psoriasis treatment. Cutibacterium acnes , which is reduced in psoriasis skin, has been reported to promote skin homeostasis by regulating immune balance. Compared to live bacteria, bacterial extracellular vesicles (bEVs) are less prone to toxicity and safety concerns. bEVs play a pivotal role in maintaining bacterial homeostasis and modulating the immune system. However,bEVs without sustained release materials are unable to function continuously in chronic diseases. Therefore, we utilized hydrogel microspheres to encapsulate Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs), enabling long term sustained release. Our findings indicate that, CA-EVs loaded gelatin methacrylate hydrogel microspheres (CA-EVs@GHM) showed superior therapeutic effects in treating psoriasis compared to CA-EVs. CA-EVs@GHM exhibited a more significant regulation of pathological type 3 innate lymphoid cells (ILC3) and skin microbiota, providing a promising approach for microbiota-derived extracellular vesicle therapy in the treatment of skin inflammation. [Display omitted] [ABSTRACT FROM AUTHOR]

Psoriasis is a persistent, inflammatory, and autoimmune condition that is difficult to treat. Estimates of the prevalence of psoriasis in people range from 0.27 % (95 % confidence interval 0.17 to 0.36) to 11.4 %, depending on factors such as age, sex, geography, ethnicity, genetics, and environmental factors. While systemic treatments are typically required for patients with moderate-to-severe instances of psoriasis, topical therapies are frequently effective for treating minor forms. In fact, phototherapy is frequently constrained by logistical considerations, and conventional systemic therapies are frequently avoided due to contraindications or the danger of adverse outcomes. In order to better serve the patient and achieve a greater level of quality of life, especially in order to sustain long-term efficacy, there is still a need for innovative therapies, which are always welcomed. Deucravacitinib is a first-in-class oral tyrosine kinase 2 (TYK2) inhibitor that is extremely selective. Through an allosteric mechanism, it stabilises an inhibitory connection between the regulatory and catalytic domains of TYK2's pseudokinase regulatory domain, which is catalytically inactive. This can be used to treat a variety of immune-mediated conditions, such as inflammatory bowel disease, lupus, psoriatic arthritis, and psoriasis. US-FDA has approved this drug on 9 September 2022 for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. This article aims to review the current knowledge on the efficacy and safety of deucravacitinib for the management of psoriasis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify the heterogeneity of atopic dermatitis and to identify key genetic factors. This can lead to new approaches and personalized treatment strategies. I conducted a literature review of three scientific publication platforms (i.e., PubMed, Cochrane Library, Scopus) for records published between July 2011 and July 2023 using key words related to the genetics of atopic dermatitis. The high heritability and genetic pleiotropia of atopic dermatitis emphasize the importance of its genetic predisposition and interaction with concomitant diseases. The study also shows the role of various genes associated with immunity and inflammatory reactions, as well as the high heritability of atopic dermatitis, particularly among twins. Genetic mutations, specifically polymorphisms of genes encoding immune factors and inflammatory responses, determine an individual's predisposition to atopic dermatitis. Research findings also point to genetic aspects associated with other skin conditions such as psoriasis and vitiligo, confirming the existence of common genetic mechanisms between these diseases. Specifically, polymorphisms of the filaggrin gene have been found to be key genetic determinants of atopic dermatitis. I analyzed the genetic basis of atopic dermatitis, emphasizing the importance of genetic determinants and their interaction with the immune system and extracellular matrix. This study contributes to the understanding of the mechanisms of atopic dermatitis and opens new perspectives for individualized treatments. [ABSTRACT FROM AUTHOR]

Scalp psoriasis is common and difficult to treat. To evaluate efficacy and safety of tildrakizumab for the treatment of scalp psoriasis. In this Phase 3b, randomized, double-blind, placebo (PBO)-controlled study (NCT03897088), patients with moderate-to-severe plaque psoriasis affecting the scalp (Investigator Global Assessment modified [IGA mod] 2011 [scalp] ≥3, Psoriasis Scalp Severity Index [PSSI] ≥12, ≥30% scalp surface area affected) received tildrakizumab 100 mg or PBO at W0 and W4. The primary endpoint was IGA mod 2011 (scalp) score of "clear" or "almost clear" with ≥2-point reduction from baseline at W16 (IGA mod 2011 [scalp] response). Key secondary endpoints were PSSI 90 response at W12 and W16 and IGA mod 2011 (scalp) response at W12. Safety was assessed from adverse events. Of patients treated with tildrakizumab (n = 89) vs PBO (n = 82), 49.4% vs 7.3% achieved IGA mod 2011 (scalp) response at W16 (primary endpoint) and 46.1% vs 4.9% at W12; 60.7% vs 4.9% achieved PSSI 90 response at W16 and 48.3% vs 2.4% at W12 (all P <.00001). No serious treatment-related adverse events occurred. Only short-term data are presented. Tildrakizumab was efficacious for the treatment of scalp psoriasis with no new safety signals. [ABSTRACT FROM AUTHOR]

Weight loss is reported with oral roflumilast, which is approved for chronic obstructive pulmonary disease (COPD). Recently, the drug has shown efficacy in psoriasis, a disease strongly linked to overweight/obesity. To describe the effects of oral roflumilast on body weight and cardio-metabolic parameters in patients with psoriasis. Posthoc analyses from the PSORRO study, where patients with moderate-to-severe plaque psoriasis were randomized 1:1 to oral roflumilast 500 μg once-daily or placebo for 12 weeks, followed by active, open-label treatment through week 24 in both groups. Changes in body weight, blood pressure, gastrointestinal symptoms, and laboratory tests were registered. No lifestyle or dietary interventions were applied. Forty-six patients were randomized. Baseline characteristics across groups were comparable; mean weight was 103.6 kg. In patients receiving roflumilast, median weight change was −2.6% and −4% at week 12 and 24, respectively. Corresponding numbers were 0.0% and 1.3% in patients initially allocated to placebo. Reduced appetite was more frequent with active therapy. No changes in blood pressure or laboratory tests were observed. Posthoc analyses and low numbers. Oral roflumilast induced weight loss and reduced appetite, which support the growing evidence of roflumilast as an attractive treatment alternative for patients with psoriasis. [ABSTRACT FROM AUTHOR]

A multitude of factors may influence fatigue in psoriasis and psoriatic arthritis (PsA); however, their individual fatigue components have not been thoroughly examined. To explore characteristics of fatigue and its potential drivers in a cohort of patients with psoriasis with or without PsA. Adults with psoriasis and a nonpsoriasis control group completed the Multidimensional Fatigue Inventory-20 questionnaire. Patients with psoriasis also reported joint pain intensity, pruritus, skin pain, and sleep problems using a numerical rating scale. Linear regression models were applied to continuous outcomes, and beta coefficients (β) for the slopes were estimated with 95% confidence intervals (CIs). Among 2741 adults with psoriasis (of which 593 also had PsA) and 3788 controls, the impact on total fatigue was greatest for PsA (β = 5.22; 95% CI, 3.55-6.90), followed by psoriasis (β = 2.10; 95% CI, 0.96-3.25), compared with the general population (P trend <.0001). Among patients with psoriasis with or without PsA, increasing joint pain intensity was associated with overall fatigue (β = 2.23 [95% CI, 2.03-2.44] for each 1-point increase in joint pain numerical rating scale score). We lacked information on the effect of pharmacotherapy. These findings highlight the importance of a symptom-based approach when treating psoriasis, rather than focusing on objective severity measures alone. [ABSTRACT FROM AUTHOR]

Cardiovascular comorbidities are believed to cause higher mortality in psoriasis patients. Conversely, systemic therapy may improve overall survival. To evaluate the impact of different comorbidities and therapy on mortality risk of psoriasis patients in the entire population of Alberta, Canada (population 4.37 million). Cohorts of psoriasis cases (n = 18,618) and controls (ambulatory patients matched 1:3 by age and sex) were retrieved from Alberta Health Services Data Repository of Reporting database within the period 2012 to 2019. Cases were stratified according to Charlson Comorbidity Index, and the type of therapy. Mortality in psoriasis cohort was significantly higher than in the controls (median age of death 72.0 years vs 74.4 years, respectively). Charlson Comorbidity Index and comorbidities were strong predictors of mortality, in particular drug induced liver injury (hazard ratio 1.8, affective bipolar disease, hazard ratio 1.6, and major cardiovascular diseases. Mortality was lower in patients treated with biologics (hazard ratio 0.54). Some factors (psoriasis type and severity, response to treatment, smoking, alcohol intake) could not be measured. Hepatic injury, psychiatric affective disorders and cardiovascular disease were major determinants of overall survival in psoriasis. Biologic therapy was associated with a reduced mortality risk. [ABSTRACT FROM AUTHOR]

The routine use of targeted systemic immunomodulatory therapies has transformed outcomes for people with severe psoriasis, with skin clearance (clinical remission) rates up to 60% at 1 year of biologic treatment. However, psoriasis may recur following drug withdrawal, and as a result, patients tend to continue receiving costly treatment indefinitely. Here, we review research into the "inflammatory memory" in resolved psoriasis skin and the potential mechanisms leading to psoriasis recurrence following drug withdrawal. Research has implicated immune cells such as tissue resident memory T cells, Langerhans cells, and dermal dendritic cells, and there is growing interest in keratinocytes and fibroblasts. A better understanding of the interactions between these cell populations, enabled by single cell technologies, will help to elucidate the events underpinning the shift from remission to recurrence. This may inform the development of personalized strategies for sustaining remission while reducing long-term drug burden. [ABSTRACT FROM AUTHOR]

Various immune cells in the skin contribute to its function as a first line of defense against infection and disease, and the skin's dense innervation by pain-sensing sensory neurons protects the host against injury or damage signals. Dendritic cells (DCs) are a heterogeneous population of cells that link the innate immune response to the adaptive response by capturing, processing, and presenting antigens to promote T-cell differentiation and activation. DCs are abundant across peripheral tissues, including the skin, where they are found in the dermis and epidermis. Langerhans cells (LCs) are a DC subset located only in the epidermis; both populations of cells can migrate to lymph nodes to contribute to broad immune responses. Dermal DCs and LCs are found in close apposition with sensory nerve fibers in the skin and express neurotransmitter receptors, allowing them to communicate directly with the peripheral nervous system. Thus, neuroimmune signaling between DCs and/or LCs and sensory neurons can modulate physiologic and pathophysiologic pathways, including immune cell regulation, host defense, allergic response, homeostasis, and wound repair. Here, we summarize the latest discoveries on DC- and LC-neuron interaction with neurons while providing an overview of gaps and areas not previously explored. Understanding the interactions between these 2 defence systems may provide key insight into developing therapeutic targets for treating diseases such as psoriasis, neuropathic pain, and lupus. [ABSTRACT FROM AUTHOR]

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that has wide-ranging roles, including regulation of inflammation and homeostasis. AhR is not a cell surface receptor; rather, it exists in a cytoplasmic complex that responds to a wide variety of structurally dissimilar endogenous, microbial, and environmental ligands. The ubiquitous expression of AhR, its ability to be activated by a wide range of ligands, and its capacity to act as a master regulator for gene expression and homeostasis make it a promising new therapeutic target. Clinical trials of tapinarof cream have now validated AhR agonism as a therapeutic approach that can deliver significant efficacy for treating inflammatory skin diseases, including psoriasis and atopic dermatitis. Tapinarof 1% cream is a first-in-class, nonsteroidal, topical, AhR agonist with a pharmacokinetic profile that results in localized exposure at sites of disease, avoiding systemic safety concerns, drug interactions, or off-target effects. Psoriasis and atopic dermatitis both involve epidermal inflammation, cellular immune responses, dysregulation of skin barrier protein expression, and oxidative stress. On the basis of the clinical effectiveness of tapinarof cream for treating inflammatory skin diseases, we review how targeting AhR may offer a significant opportunity in other conditions that share key aspects of pathogenesis, including asthma, inflammatory bowel disease, eosinophilic esophagitis, ophthalmic, and nervous system diseases. [ABSTRACT FROM AUTHOR]

Skin denervation has been shown to cause remission of psoriatic lesions in patients, which can reappear if reinnervation occurs. This effect can be induced by the activation of dendritic cells through sensory innervation. However, a direct effect of nerves on the proliferation of keratinocytes involved in the formation of psoriatic plaques has not been investigated. We developed, by tissue engineering, a model of psoriatic skin made of patient skin cells that showed increased keratinocyte proliferation and epidermal thickness compared to healthy controls. When this model was treated with CGRP, a neuropeptide released by sensory neurons, an increased keratinocyte proliferation was observed in the psoriatic skin model, but not in the control. When a sensory nerve network was incorporated in the psoriatic model and treated with capsaicin to induce neuropeptide release, an increase of keratinocyte proliferation was confirmed, which was blocked by a CGRP antagonist while no difference was noticed in the innervated healthy control. We showed that sensory neurons can participate directly to keratinocyte hyperproliferation in the formation of psoriatic lesions through the release of CGRP, independently of the immune system. Our unique tissue-engineered innervated psoriatic skin model could be a valuable tool to better understand the mechanism by which nerves may modulate psoriatic lesion formation in humans. This study shows that keratinocytes extracted from patients' psoriatic skin retain, at least in part, the disease phenotype. Indeed, when combined in a 3D model of tissue-engineered psoriatic skin, keratinocytes exhibited a higher proliferation rate, and produced a thicker epidermis than a healthy skin control. In addition, their hyperproliferation was aggravated by a treatment with CGRP, a neuropeptide released by sensory nerves. In a innervated model of tissue-engineered psoriatic skin, an increase in keratinocyte hyperproliferation was also observed after inducing neurons to release neuropeptides. This effect was prevented by concomitant treatment with an antagonist to CGRP. Thus, this study shows that sensory nerves can directly participate to affect keratinocyte hyperproliferation in psoriasis through CGRP release. [Display omitted] [ABSTRACT FROM AUTHOR]

Psoriasis, a chronic, immune-mediated disease, is a known risk factor for infectious complications following certain surgical procedures such as lower extremity arthroplasty. However, there is a paucity in the literature that observes the association of psoriasis and infectious complications following total shoulder arthroplasty (TSA). The primary research question was whether a diagnosis of psoriasis is associated with increased odds of short-term infectious complications and long-term surgical complications. A retrospective cohort analysis was performed using the PearlDiver all-payers' claims database. Patients who underwent primary TSA were identified using Current Procedural Terminology and International Classification of Diseases procedure codes. Patients were then stratified into two groups: (1) patients with psoriasis who underwent TSA, and (2) patients without psoriasis who underwent TSA. Primary outcomes included the incidence of 90-day infectious complications including periprosthetic joint infection, deep surgical site infection, and sepsis. Secondary outcomes included the incidence of 5-year surgical complications including all-cause revision, aseptic revision, and septic revision. Univariate and multivariable regression analyses were conducted to compare complications between the cohorts. In total, 89,321 patients were included in this study, with 3311 (3.71%) having psoriasis. Patients with psoriasis had significantly higher odds of 90-day infectious complications following TSA including periprosthetic joint infection (1.63; P =.014) and deep surgical site infection (1.79; P =.003), when compared to those without psoriasis. There were no significant differences in odds of 5-year all-cause revisions, septic revisions, and aseptic revisions between the two cohorts. Psoriasis is associated with significantly higher 90-day infectious complications but not long-term implant complications. Orthopedic surgeons should be aware of the increased acute infectious complications in this population, promote preoperative counseling and extensive infectious precautions, and consider the use of alternative prophylaxis against infection. These findings also have implications for risk adjustments in increasingly common bundled payments or shared risk payment models. [ABSTRACT FROM AUTHOR]

For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. Studies regarding infection rates after vaccination are lacking. Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases. [ABSTRACT FROM AUTHOR]

Approved systemic treatment options are limited for pediatric patients with moderate to severe plaque psoriasis. To assess the efficacy and safety of apremilast over 16 weeks in pediatric patients with plaque psoriasis. SPROUT (NCT03701763) was a phase 3, multicenter, randomized, double-blind, placebo-controlled study of apremilast in patients aged 6-17 years with moderate-to-severe psoriasis (Psoriasis Area and Severity Index [PASI] ≥12, body surface area ≥10%, static Physician Global Assessment [sPGA] ≥3) inadequately controlled by/inappropriate for topical therapy. Patients were stratified by age group and randomized (2:1) to apremilast (20 or 30 mg BID based on weight) or placebo for 16 weeks, followed by apremilast extension to 52 weeks. Of 245 patients randomized (apremilast: 163; placebo: 82), 221 (90%) completed the double-blind phase (apremilast: 149; placebo: 72). Significantly more patients achieved sPGA response and ≥75% reduction in PASI with apremilast than placebo, regardless of baseline age, weight, or disease severity. No new safety signals were observed. Sample size of subgroup analyses. Improvements in global disease activity and skin involvement were significantly greater in pediatric patients treated with apremilast versus placebo. Adverse events were consistent with the known apremilast safety profile. [ABSTRACT FROM AUTHOR]

Aims. The present study aimed to assess vitamin D status and serum concentrations of pro-inflammatory cytokines IL-17, Il-23, and IL-18 in patients with chronic plaque psoriasis and their association with various demographic and clinical characteristics. Methods. The study was conducted during the autumn/winter period on 48 patients with chronic plaque psoriasis and 48 controls. Total serum 25(OH)D level was determined with Roche Elecsys® 2010 Vitamin D total assay. Commercial ELISA kits were used for quantifying the serum levels of IL-17A, IL-18, and IL-23. Results. Serum 25(OH)D had a median value of 16.95 ng/mL (IQR 10.8--23.50) for patients with psoriasis and 18.80 ng/ mL (IQR 15.45--25.85) for the control group (P=0.09). A moderate negative correlation was found between PASI score and 25(OH)D levels (rs=0.34; P=0.02). The serum levels of IL-17 (P=0.001), IL-23 (P=0.01) and IL-18 (P=0.02) were significantly higher in the patient group compared to controls. IL-17 concentrations were higher in patients with moderate to severe psoriasis compared to patients with mild psoriasis (P=0.003). No significant correlations were detected between the serum concentrations of 25(H)D and IL-17, IL-23, and IL-18. Conclusion. It was confirmed that IL-17 serum level is associated with psoriasis severity. Measurement of 25(OH)D serum concentration can be useful in patients with moderate to severe psoriasis with or without comorbidities. A direct association between 25(OH)D serum concentration and the serum concentrations of IL-17, IL-23, or IL-18 was not identified in this study. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor- α (TNF- α) is a promising target for inflammatory and autoimmune diseases. Spirohypertones A (1) and B (2), two unprecedented polycyclic polyprenylated acylphloroglucinols with highly rearranged skeletons, were isolated from Hypericum patulum. The structures of 1 and 2 were confirmed through comprehensive spectroscopic analysis, single-crystal X-ray diffraction and electronic circular dichroism calculations. Importantly, 2 showed remarkable TNF- α inhibitory activity, which could protect L929 cells from death induced by co-incubation with TNF- α and actinomycin D. It also demonstrated the ability to suppress the inflammatory response in HaCaT cells stimulated with TNF- α. Notably, in an imiquimod-induced psoriasis murine model, 2 restrained symptoms of epidermal hyperplasia associated with psoriasis, presenting anti-inflammatory and antiproliferative effects. This discovery positions 2 as a potent TNF- α inhibitor, providing a promising lead compound for developing an antipsoriatic agent. Spirohypertones A and B, two new compounds with rearranged skeletons were isolated from Hypericum patulum and spirohypertone B was found to be a potential antipsoriatic via inhibit TNF- α. [Display omitted] [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory immune-related skin disease. According to literature reports, the leaves of Broussonetia papyrifera exhibit antioxidant, immune-enhancing and antibacterial effects. These leaves are not only used clinically for the treatment of superficial fungal infections and hepatitis, but also used in the development of health food. However, the treatment of psoriasis with the leaves of B. papyrifera has not been reported yet. The in vitro antioxidant activity of B. papyrifera leaf extract was investigated by DPPH, OH and ABTS assays. Furthermore, IMQ was used to induce a mouse psoriasis-like model and HE staining, enzyme-linked immunosorbent assay and biochemical kits were used to measure relevant pathological indexes. The results showed that the B. papyrifera leaf extract has certain antioxidant capacity in vitro, which was positively correlated with its concentration. In addition, the extract can not only improve IMQ-induced skin damage on the back of mice, inhibit TNF-α and IL-6 factor secretion, but also regulate activity of SOD and the serum levels of MDA. Its mechanism of action related to inhibiting the secretion of inflammatory factors and the regulation of oxidative stress in vivo. [ABSTRACT FROM AUTHOR]

Mast cell degranulation plays a pivotal role in urticaria and is also an early histologic characteristic of psoriasis. However, whether the activation of mast cells contributes to psoriasis recurrence after discontinuation of interleukin (IL)-17A blockers remains unclear. To investigate the role of mast cells in ixekizumab treatment-associated urticaria (ITAUR) and assess the effect of urticaria eruption on psoriasis relapse. A retrospective analysis was performed on biopsies of patients who experienced psoriasis relapse after discontinuation of ixekizumab. Transcriptomic and histopathologic features were assessed. Patterns were compared between patients with ITAUR and nonurticaria (NUR) as well as psoriasis-like mice with mast cell activation or inactivation. Patients with ITAUR experienced early relapse compared with NUR group after treatment withdrawal. Transcriptomic and histopathologic analyses revealed that patients with ITAUR had an elevated proportion of mast cells in resolved skin. Especially, the proportion of IL-17A+ mast cells was inversely correlated with the duration of remission. The mechanism of mast cell activation in ITAUR has not been precisely elucidated. Ixekizumab treatment increases IL-17A+ mast cells in lesions of ITAUR, which is associated with early psoriasis relapse after ixekizumab withdrawal. [ABSTRACT FROM AUTHOR]

Scalp involvement in plaque psoriasis is challenging to treat. To evaluate the efficacy and safety of deucravacitinib (DEUC) in scalp psoriasis. POETYK PSO-1 and PSO-2 were global phase 3, 52-week, double-blinded trials in adults with moderate to severe psoriasis. Patients were randomized 1:2:1 to oral placebo, DEUC 6 mg once daily, or apremilast 30 mg twice daily. This pooled secondary analysis evaluated scalp-specific Physician Global Assessment score of 0 or 1 (0/1), ≥90% improvement from baseline in Psoriasis Scalp Severity Index, and change from baseline in Psoriasis Scalp Severity Index. Adverse events were evaluated through week 16. Overall, 1084 patients with moderate to severe scalp psoriasis at baseline were included. At week 16, response rates were greater with DEUC versus placebo or apremilast for scalp-specific Physician Global Assessment 0/1 (64.0% vs 17.3% vs 37.7%; P <.0001), ≥90% improvement from baseline in Psoriasis Scalp Severity Index (50.6% vs 10.5% vs 26.1%; P <.0001), and change from baseline in Psoriasis Scalp Severity Index. Responses were maintained through 52 weeks with continuous DEUC. Safety was consistent with the entire study population. Lack of data in milder scalp psoriasis. DEUC was significantly more efficacious than placebo or apremilast in improving moderate to severe scalp psoriasis and was well tolerated. [ABSTRACT FROM AUTHOR]

Evolution has created complex mechanisms to sense environmental danger and protect tissues, with the nervous and immune systems playing pivotal roles. These systems work together, coordinating local and systemic reflexes to restore homeostasis in response to tissue injury and infection. By sharing receptors and ligands, they influence the pathogenesis of various diseases. Recently, a less-explored aspect of neuroimmune communication has emerged: the release of neuropeptides from immune cells and cytokines/chemokines from sensory neurons. This article reviews evidence of this unique neuroimmune interplay and its impact on the development of allergy, inflammation, itch, and pain. We highlight the effects of this neuroimmune signaling on vital processes such as host defense, tissue repair, and inflammation resolution, providing avenues for exploration of the underlying mechanisms and therapeutic potential of this signaling. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin disorder, and current treatments include topical therapies, phototherapy, systemic immune modulators, and biologics, aiming to alleviate symptoms and improve quality of life. The prevalence of psoriasis varies globally, affecting around 2% of the population. However, challenges persist, such as adverse effects, treatment resistance, high costs, and variability in response among individuals Phototherapy using PUVA or UVB is another option for moderate to severe cases.The future of psoriasis treatment shows promising emerging trends. New biologic agents targeting novel pathways, such as interleukin 23 inhibitors like mirikizumab, offer enhanced efficacy. Small molecule inhibitors like RORγt inhibitors and ROCK2 inhibitors provide additional treatment options. Combination therapies, including biologics with methotrexate, may improve treatment response. Advancements in topical treatments utilizing microneedles and nanoparticle-based carriers can enhance drug delivery and improve therapeutic outcomes. Biomarkers and multi-omics technologies hold potential for personalized treatment approaches, thus aiding in diagnosis, predicting treatment response, and guiding therapeutic decisions. Collaboration among researchers, clinicians, and industry stakeholders is crucial to translating these scientific break throughs into clinical practice. By addressing current challenges and exploring these promising trends, we can optimize psoriasis management and improve the lives of those affected by this chronic condition. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether women with psoriasis who receive adequate management or achieve better control of their psoriasis before and during pregnancy could eliminate the negative effects. Objectives: The objective of this study was to investigate the association between physician visits for psoriasis and adverse pregnancy outcomes. Methods: This study used the National Health Insurance database and Birth Certificate Application in Taiwan. This research further categorized the study subjects into mothers with mild/severe psoriasis who visited physicians for psoriasis before delivery, mothers with mild/severe psoriasis who did not visit a physician for psoriasis before delivery, and mothers without psoriasis. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the occurrence of adverse pregnancy outcomes, including maternal and neonatal outcomes. Results: 3,339 mothers with severe psoriasis, 41,296 mothers with mild psoriasis, and 2,017,271 mothers without psoriasis were included in this study. The mothers with mild/severe psoriasis demonstrated a significantly higher risk of labor complications and maternal risk factors. After adjusting for confounders, mothers with severe psoriasis who did not visit a physician for psoriasis demonstrated significantly higher odds of labor complications (OR: 1.217), maternal risk factors (OR: 1.507), having low‑birth weight infants (OR: 1.236), etc., than mothers without psoriasis. Conclusion: This study demonstrated that mothers with psoriasis had a higher risk of adverse pregnancy outcomes. In addition, seeking medical care for psoriasis, particularly for women with severe psoriasis, appeared to exert a protective effect against adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background: Biological treatments are effective in the management of psoriasis. However, results in the real‑world setting may differ from clinical trials. Objectives: We aimed to evaluate the effectiveness of biological drugs among patients with psoriasis in Malaysia. Methods: This was a retrospective review of adult patients on biologics who were notified to the Malaysian Psoriasis Registry between 2011 and 2019. Univariate and multivariate logistic regression was performed to identify factors associated with response to treatment in terms of the Psoriasis Area and Severity Index (PASI) 75, PASI 90, and Dermatology Life Quality Index (DLQI) 0/1. Results: Of 130 patients, the most prescribed drug was ustekinumab (40.8%), followed by adalimumab (29.2%) and secukinumab (24.6%). Overall, the differences in the median PASI scores from baseline were −23.9 at 3–6 months, −25.8 at 12 months, and −27.8 at 3 years, while the difference in the median DLQI scores was −13.0 at 3–6 months. At 3–6 months, 57.6% achieved PASI‑75, 32.9% achieved PASI‑90, and 4.7% achieved PASI‑100. These responses were sustained at 12 months and 3 years. Adalimumab was the most effective treatment with 88.9% achieving PASI‑75, 77.8% PASI‑90, and 22.2% PASI‑100 at 3 years. However, secukinumab was more effective at achieving a PASI‑100 response at 3–6 months (9.1%). Chinese or Indian ethnicity, concurrent use of systemic therapy or phototherapy, comorbidities, and a longer duration of psoriasis were associated with poorer response. Conclusion: Biological treatments, particularly adalimumab and secukinumab, are effective in reducing disease severity and improving the quality of life of patients with psoriasis in Malaysia. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Psoriasis and psoriatic arthritis (PsA) are closely linked to cancer, as supported by the literature. Systemic treatments for psoriasis and PsA, namely non-biological disease-modifying anti-rheumatic drugs (DMARDs), have been associated with increased cancer risk in both conditions. New, more effective biological DMARDs (bDMARDs) do not seem to be associated with higher overall cancer risk compared to those not receiving bDMARDs, opening up possibilities for treating patients with previous or ongoing oncological disease alongside psoriasis and PsA. However, limited literature exists on treating PsA patients with cancer with bDMARDs. This study aims to assess the safety of secukinumab, a bDMARD, in patients with PsA and concurrent cancer. Here, we describe a case series of four patients with PsA treated with bDMARD secukinumab and review the literature on the subject. CASE SERIES: We assessed the laboratory parameters and clinical characteristics of 4 patients with PsA treated with the bDMARD secukinumab and followed up until 30 months. Three patients had oncological disease in remission, while one had active neoplasia. No cancer progression was observed during the treatment of these patients with secukinumab. CONCLUSIONS: In conclusion, our case series, consisting of four PsA patients with concurrent neoplasia treated with secukinumab, showed no evidence of cancer progression and represents the first case of PsA described in the literature treated during active oncological disease, lending support to the safety of secukinumab for the treatment of patients with PsA and concomitant neoplasia. [ABSTRACT FROM AUTHOR]

Inflammatory diseases of the nail, including nail psoriasis and nail lichen planus, are associated with significant disease burden and have a negative impact on quality of life. Diagnosis is often delayed, especially when patients present without cutaneous findings. Therefore, recognizing clinical signs and symptoms of inflammatory nail diseases, and initiating timely and appropriate treatment, is of utmost importance. We review recent studies on diagnostic techniques, discuss severity grading and scoring systems, and describe consensus treatment recommendations for nail psoriasis and nail lichen planus. An updated literature review was performed using the PubMed database on studies assessing diagnostic techniques or treatment modalities for nail psoriasis and nail lichen planus. Recent studies on diagnostic techniques for inflammatory nail disease have focused on use of dermoscopy, capillaroscopy, and ultrasound modalities. Treatment of these conditions is dichotomized into involvement of few (≤3) or many (>3) nails. Recent psoriatic therapeutics studied for nail outcomes include brodalumab, tildrakizumab, risankizumab, deucravacitinib, and bimekizumab, while emerging treatments for nail lichen planus include JAK inhibitors and intralesional platelet rich plasma injections. We emphasize the need for increased awareness and expanded management strategies for inflammatory nail diseases to improve patient outcomes. [ABSTRACT FROM AUTHOR]