Treatment Of Psoriasis Research Articles

Safety and Efficacy of Combination Therapy of Upadacitinib and Biologic Agents for Treatment-Resistant Psoriasis and Psoriatic Arthritis

Importance: Although there are many available treatments for psoriasis and psoriatic arthritis (PsA), there are patients resistant to standard conventional therapy. For these patients, combination therapy of biologic agents and upadacitinib may be a viable alternative option; however, there is limited data on concomitant usage. Objective: To evaluate the safety and efficacy of combination therapy of upadacitinib and biologic agents for the treatment of refractory psoriasis and psoriatic arthritis. Design: We report the results of a retrospective chart review of 3 patients in a single practice treated with a combination of upadacitinib and biologics for psoriasis and PsA. The risks, benefits, and safety warnings of combination therapy of upadacitinib and biologic agents were discussed before initiation. After shared decision-making with the provider, patients were placed on a trial of combination therapy. Results: All three patients, previously refractory to monotherapy, experienced significant improvement of their symptoms while on combination therapy. No adverse reactions (malignancy, cardiovascular events, venous thromboembolism) occurred during treatment. However, one patient experienced a shingles outbreak and diverticulitis while on combination treatment. Further studies are needed to determine long-term efficacy with a larger sample size.

Health-related quality of life in patients with generalized pustular psoriasis – a Swedish register study

Background Real-world data on health-related quality of life (HRQoL) in generalized pustular psoriasis (GPP) are scarce and studies have been restricted in terms of instruments used for assessments. Objective To assess generic and dermatology-specific HRQoL of patients with GPP compared with patients with plaque psoriasis using real-world data from the Swedish National Register for Systemic Treatment of Psoriasis. Methods Cross-sectional data from 2006 to 2021 including 7041 individuals with plaque psoriasis without GPP and 80 patients with GPP, of which 19% also had plaque psoriasis. Total scores for the EuroQol-5 Dimensions (EQ-5D) and Dermatology Life Quality Index (DLQI), as well as degree of severity within the instruments’ dimensions/questions, were compared between patient groups. Results EQ-5D scores were significantly (p < .01) lower (worse) in patients with GPP (mean [standard deviation (SD)] 0.613 [0.346]) vs. patients with plaque psoriasis (mean [SD] 0.715 [0.274]), indicating lower generic HRQoL of patients with GPP. Significantly (p < .01) higher (worse) total DLQI scores were observed for patients with GPP (mean [SD] 10.6 [8.9]) compared with patients with plaque psoriasis (mean [SD] 7.7 [7.1]), with proportionally more patients with GPP having severe (20% vs. 16%) and very severe (17% vs. 8%) problems. The worsened scores for GPP vs. plaque psoriasis were consistent across EQ-5D dimensions and DLQI questions. Conclusions Individuals with GPP have a considerable impairment in both generic and dermatology-specific HRQoL. The HRQoL was significantly worse in individuals with GPP compared to individuals with plaque psoriasis. The significant HRQoL impairment of GPP shows the potential value of better healthcare interventions for this multisystem disease.

Reactive oxygen species-responsive supramolecular deucravacitinib self-assembly polymer micelles alleviate psoriatic skin inflammation by reducing mitochondrial oxidative stress

IntroductionThe new topical formula is urgent needed to meet clinical needs for majority mild patients with psoriasis. Deucravacitinib exerts outstanding anti-psoriatic capacity as an oral TYK2 inhibitor; however, single therapy is insufficient to target the complicated psoriatic skin, including excessive reactive oxygen species (ROS) and persistent inflammation. To address this need, engineered smart nano-therapeutics hold potential for the topical delivery of deucravacitinib.Methodshydrophobic Deucravacitinib was loaded into polyethylene glycol block-polypropylene sulphide (PEG-b-PPS) for transdermal delivery in the treatment of psoriasis. The oxidative stress model of HaCaT psoriasis was established by TNF-α and IL-17A in vitro. JC-1 assay, DCFH-DA staining and mtDNA copy number were utilized to assess mitochondrial function. 0.75% Carbopol®934 was incorporated into SPMs to produce hydrogels and Rhb was labeled to monitor penetration by Immunofluorescence. In vivo, we established IMQ-induced psoriatic model to evaluate therapeutic effect of Car@Deu@PEPS.ResultsDeu@PEPS exerted anti-psoriatic effects by restoring mitochondrial DNA copy number and mitochondrial membrane potential in HaCaT. In vivo, Car@Deu@PEPS supramolecular micelle hydrogels had longer retention time in the dermis in the IMQ-induced ROS microenvironment. Topical application of Car@Deu@PEPS significantly restored the normal epidermal architecture of psoriatic skin with abrogation of splenomegaly in the IMQ-induced psoriatic dermatitis model. Car@Deu@PEPS inhibited STAT3 signaling cascade with a corresponding decrease in the levels of the differentiation and proliferative markers Keratin 17 and Cyclin D1, respectively. Meanwhile, Car@Deu@PEPS alleviated IMQ-induced ROS generation and subsequent NLRP3 inflammasome-mediated pyroptosis.ConclusionDeu@PEPS exerts prominent anti-inflammatory and anti-oxidative effects, which may offers a more patient-acceptable therapy with fewer adverse effects compared with oral deucravacitinib.

The impact of serum uric acid on psoriasis: NHANES 2005–2014 and Mendelian randomization

Background:Psoriasis is a chronic systemic inflammatory disease, and hyperuricemia is a common comorbidity in patients with psoriasis. However, the exact relationship between uric acid levels and psoriasis remains unclear. This study aimed to explore the association between uric acid levels and psoriasis.Methods:Observational study participant data (≥16 years, n = 23,489) from NHANES 2003–2014. We conducted analyses using a weighted multiple logistic regression model. Genetic data sets for uric acid levels and psoriasis were obtained from the IEU database. We selected genetically independent loci closely associated with serum uric acid levels as instrumental variables and performed Mendelian randomization analyses using five complementary methods: inverse variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode.Results:After adjusting for other covariates, the results revealed no significant association between serum uric acid levels and psoriasis (b = 0.999, 95% CI: 0.998, 1.001, p = 0.275). Subgroup analyses stratified by gender and ethnicity showed no significant association between sUA and psoriasis in any of the subgroups. Furthermore, the MR analysis involved the selection of 227 SNPs that were associated with both sUA and psoriasis. IVW results demonstrated no causal relationship between sUA and psoriasis (OR = 0.282, 95% CI: -0.094–0.657, p = 0.142).Conclusion:Our study suggests that uric acid levels are not significantly causally related to psoriasis. This finding provides valuable insights for the treatment and prevention of psoriasis, indicating that merely reducing uric acid levels may not be an effective strategy to reduce the risk of psoriasis onset.

A comparative study between nanostructured lipid carriers and invasomes for the topical delivery of luteolin: Design, optimization and pre-clinical investigations for psoriasis treatment

Psoriasis is an inflammatory skin condition manifested by hyper-proliferation and reactive aberrant epidermal differentiation, in which genetic and environmental factors have a significant role. The current context is focused on designing novel nanovesicular systems (invasomes) incorporating terpenes with reported anti-inflammatory potential and loaded with a nutraceutical compound (luteolin/Lut) for treatment of psoriasis. Additionally, their topical efficacy in psoriasis treatment compared to lipid-based nanocarriers (nanostructured lipid carriers) was investigated. Invasomes were assessed regarding their particle size (PS), zeta potential (ζ-potential), drug entrapment (EE%), storage stability, in-vitro drug release profile and release kinetics. The optimized vesicles were investigated for their ex-vivo skin deposition and in-vitro anti-inflammatory potential in comparison with nanostructured lipid carriers (NLCs). The optimized formulation was selected to carry out the in-vivo study using rat model of imiquimod-induced psoriasis. Luteolin-invasomes were found to have spherical shape and promising colloidal properties. They possessed PS ranging from 277.80 to 812.91 nm, negative ζ-potential (−35.22–38.55 mV), and high EE% values, which ranged from 89.38 to 99.75 %. Furthermore, they exhibited good stability properties and significant sustainment of drug release in comparison to NLCs. In addition, they were able to enhance Lut deposition by 2.1-fold in the stratum corneum (SC) and 5.5-fold in epidermis and dermis compared to control suspension of Lut. Moreover, invasomes showed more potential to retain Lut into deep skin layers 1.5-fold higher than NLCs. They also displayed higher in-vitro anti-inflammatory activity compared to plain invasomes and control suspension, and comparable activity compared to NLCs. In the in-vivo animal study, the ability of Lut to alleviate psoriatic symptoms was significantly enhanced after its encapsulation in invasomal dispersions, where Lut-invasomes possessed a great inhibitory potential compared to the control Lut suspension, and even to Lut-NLCs. This suggests their efficiency in treating psoriasis, delineating them promising for further use in treating other inflammatory skin conditions.

Whole-Genome Shotgun Metagenomic Sequencing Reveals Shifts in the Skin Microbiome and Bacteriophages of Psoriasis: An Extended Analysis of Published Data

Background Psoriasis is an immune-mediated cutaneous disease that may have shifts in the skin microbiome. Prior research on the skin microbiome in psoriasis has been limited to rRNA based approaches that lack resolution of taxonomic and functional level assessment. Objective To further illuminate strain and sub-strain level analysis of psoriatic lesions using the CosmosID-HUB Microbiome pipeline. Methods A previous study completed by Tett et al recruited patients with psoriasis who had skin microbiome samples taken from psoriatic plaques on the ear and the elbow as well as sites on the skin unaffected by psoriasis. They performed whole genome shotgun sequencing and made their dataset publicly available. We analyzed the dataset using the CosmosID-HUB Microbiome pipeline to evaluate the strain and sub-strain taxonomic analysis as well as functional gene profiling. Results When analyzed with the CosmosID pipeline, both ear and elbow sites in affected areas had decreased alpha diversity compared to unaffected areas. There was an increased relative abundance of Staphylococcus and Corynebacteria at affected sites. We identified distinguishing species and strains of the yeast Malassezia, including M. restricta. that were significantly enriched in healthy elbow samples. Vitamin B12 production genes were not present in psoriatic skin whereas it was present in healthy samples, supporting the notion of relative vitamin B12 deficiency in psoriatic plaques. Phage analysis revealed a greater diversity of Staphylococcus-related phages in unaffected elbow samples. Conclusion A greater diversity of microbial strains and their functional roles identified in this study may help to tailor treatment for psoriasis.

Patients’ Preferences Regarding Modes of Systemic Psoriasis Treatment – A Qualitative Study

Background Treatment with pathogenesis-directed biologics and oral systemic drugs have made complete clearance of psoriasis a realistic expectation for many patients with psoriasis. Patients’ preferences among these treatments varies. Objective To understand factors impacting psoriasis patients’preferences for injection vs oral medication. Methods Psoriasis patients who receive systemic psoriasis treatment were asked to participate in a semi-structured interview. Sample size was based on achieving saturation with equal number of patients preferring oral vs injectable medications to ensure equal representation of both groups. Qualitative analysis was performed to interpret the results. Results Twenty-two patients participated in the study, 12 males and 10 females. Ten patients were receiving oral medication (apremilast or methotrexate) and 12 patients were receiving injectables (guselkumab, adalimumab, risankizumab, secukinumab, ixekizumab, or tildrakizumab) due to self-reported preference. Five themes resulted from the analysis: patients receiving injectables more frequently discussed the positive impact of the medication on quality of life compared to patients on oral medication; fear of side effects, particularly fear of immunosuppression, is associated with injection medications; avoidance of needles drives patients away from injection medication and towards oral systemic medication; patients prioritize convenience when selecting systemic therapy, though the definition of convenience is subject to perception; and patients value the medication recommendation of the physician, regardless of the route of administration. Conclusion Improving medication adherence and disease outcomes through individualized treatment plans, with an emphasis on patients’ preferences using a shared decision-making approach, may be helpful.

The discovery of a novel pyrrolo[2,3-b]pyridine as a selective CDK8 inhibitor offers a new approach against psoriasis

Currently, the drugs used in clinical to treat psoriasis mainly broadly suppress cellular immunity. However, these drugs can only provide temporary and partial symptom relief, they do not cure the condition and may lead to recurrence or even serious toxic side effects. In this study, we describe the discovery of a novel potent CDK8 inhibitor as a treatment for psoriasis. Through structure-based design, compound 46 was identified as the most promising candidate, exhibiting a strong inhibitory effect on CDK8 (IC50 value of 57 nM) along with favourable inhibition against NF-κB. Additionally, it demonstrated a positive effect in an in vitro psoriasis model induced by TNF-α. Furthermore, this compound enhanced the thermal stability of CDK8 and exerted evident effects on the biological function of CDK8, and it had favourable selectivity across the CDK family and tyrosine kinase. This compound showed no obvious inhibitory effect on CYP450 enzyme. Further studies confirmed that compound 46 exhibited therapeutic effect on IMQ-induced psoriasis, alleviated the inflammatory response in mice, and enhanced the expression of Foxp3 and IL-10 in the dorsal skin in vivo. This discovery provides a new strategy for developing selective CDK8 inhibitors with anti-inflammatory activity for the treatment of psoriasis.

The Potential Anti-psoriatic Effects of Andrographolide: A Comparative Study to Topical Corticosteroids.

Andrographolide (AP), a bioactive anti-inflammatory compound of Sambiloto, inhibits NF-κB, TNF-α, and interleukin IL-6. Nowadays, molecular docking simulation between AP and dexamethasone against NF-κB receptor presented the energy AP higher than dexamethasone. This becomes a potential treatment for psoriasis. This manuscript reported the effectiveness of AP from Sambiloto in treating psoriasis compared to topical steroids. This study conducted TLC analysis of AP content and its metabolite impurities, emulgel formulation, molecular docking, in-silico skin toxicity study, and in-vivo anti-psoriatic activity. This was a combination study of an in-silico study and an in-vivo study. This in-silico study was analyzed through multivariate statistical analysis (PCA) to elucidate the data constellation relationship of andrographolide derivatives with several target proteins. The intervention was performed in seven days. The PASI score, molecular parameters (IL-6, IL-17, VEGF, and TNF-a levels), and histopathological findings were assessed. Molecular docking results revealed andrographolide to exhibit a relatively high binding affinity towards IL-6, NF-kB, and TNF-α which is comparable to the corticosteroids, andrographolide also shares similar residue interaction profile with each of the respective protein's native ligand. In the in-vivo study, we found several parameters statistically significantly different regarding the intervention, including final PASI score (p = 0.017), redness (p = 0.017), scale (p = 0.040), thickness (p = 0.023), total histopathology of psoriasis score (p = 0.037), keratin layer score (p = 0.018). Emulgel AP 0.1% could lower the anti-inflammatory agent, which is vital to psoriasis progression.

Management of Psoriasis Patients with Serious Infectious Diseases.

The management of patients affected by moderate-to-severe psoriasis may be challenging, in particular in patients with serious infectious diseases [tuberculosis (TB), hepatitis B and C, HIV, COVID-19]. Indeed, these infections should be ruled out before starting and during systemic treatment for psoriasis. Currently, four conventional systemic drugs (methotrexate, dimethyl fumarate, acitretin, cyclosporine), four classes of biologics (anti-tumour necrosis factor alpha, anti-interleukin (IL)12/23, anti-IL-17s, and anti-IL-23], and two oral small molecules (apremilast, deucravacitinib) have been licensed for the treatment of moderate-to-severe psoriasis. Each of these drugs is characterized by a unique safety profile which should be considered before starting therapy. Indeed, some comorbidities or risk factors may limit their use. In this context, the aim of this manuscript was to evaluate the management of patients affected by moderate-to-severe psoriasis with serious infectious diseases.

The impact of temperature on vascular function in connection with vascular laser treatment

Pulsed dye lasers are used effectively in the treatment of psoriasis with long remission time and limited side effects. It is, however, not completely understood which biological processes underlie its favorable outcome. Pulsed dye laser treatment at 585-595 nm targets hemoglobin in the blood, inducing local hyperthermia in surrounding blood vessels and adjacent tissues. While the impact of destructive temperatures on blood vessels has been well studied, the effects of lower temperatures on the function of several cell types within the blood vessel wall and its periphery are not known. The aim of our study is to assess the functionality of isolated blood vessels after exposure to moderate hyperthermia (45 to 60°C) by evaluating the function of endothelial cells, smooth muscle cells, and vascular nerves. We measured blood vessel functionality of rat mesenteric arteries (n=19) by measuring vascular contraction and relaxation before and after heating vessels in a wire myograph. To this end, we elicited vascular contraction by addition of either high potassium solution or the thromboxane analogue U46619 to stimulate smooth muscle cells, and electrical field stimulation (EFS) to stimulate nerves. For measurement of endothelium-dependent relaxation, we used methacholine. Each vessel was exposed to one temperature in the range of 45-60°C for 30 seconds and a relative change in functional response after hyperthermia was determined by comparison with the response per stimulus before heating. Non-linear regression was used to fit our dataset to obtain the temperature needed to reduce blood vessel function by 50% (Half maximal effective temperature, ET50). Our findings demonstrate a substantial decrease in relative functional response for all three cell types following exposure to 55°C-60°C. There was no significant difference between the ET50 values of the different cell types, which was between 55.9°C and 56.9°C (P>0.05). Our data show that blood vessel functionality decreases significantly when exposed to temperatures between 55°C-60°C for 30 seconds. The results show functionality of endothelial cells, smooth muscle cells, and vascular nerves is similarly impaired. These results help to understand the biological effects of hyperthermia and may aid in tailoring laser and light strategies for selective photothermolysis that contribute to disease modification of psoriasis after pulsed dye laser treatment.

Functional Genomics and Insights into the Pathogenesis and Treatment of Psoriasis

Psoriasis is a lifelong, systemic, immune mediated inflammatory skin condition, affecting 1–3% of the world’s population, with an impact on quality of life similar to diseases like cancer or diabetes. Genetics are the single largest risk factor in psoriasis, with Genome-Wide Association (GWAS) studies showing that many psoriasis risk genes lie along the IL-23/Th17 axis. Potential psoriasis risk genes determined through GWAS can be annotated and characterised using functional genomics, allowing the identification of novel drug targets and the repurposing of existing drugs. This review is focused on the IL-23/Th17 axis, providing an insight into key cell types, cytokines, and intracellular signaling pathways involved. This includes examination of currently available biological treatments, time to relapse post drug withdrawal, and rates of primary/secondary drug failure, showing the need for greater understanding of the underlying genetic mechanisms of psoriasis and how they can impact treatment. This could allow for patient stratification towards the treatment most likely to reduce the burden of disease for the longest period possible.

Activity of hydrogel-vitamin D3 /bacterioruberin nanoparticles on imiquimod-induced fibroblasts-keratinocytes spheroids

Topical administration of vitamin D3 (VD3) analogs and corticosteroids is the mainstay treatment for mild localized psoriasis. VD3 however is an unstable class II drug (insoluble and permeable), classically formulated as unattractive viscous and oil-based ointments or creams. In this work, nanostructured archaeolipid carriers (NAC) with a core loaded with VD3 and the C50 dipolar carotenoid from halophilic archaea bacterioruberin (BR): NAC-VD3, were formulated into a carbopol hydrogel: gNAC-VD3. After its rheological characterization, its anti-inflammatory and antioxidant activity was assessed on bi-cellular spheroids, consisting of a core of fibroblasts surrounded by a ring of keratinocytes activated with imiquimod (IMQ) as a psoriasis model. gNAC-VD3 (0.8 mg VD3/135 μg BR/gram gel) conserved the antioxidant activity, showed pseudoplastic non-Newtonian behaviour, stability over time, good occlusion capacity and spreadability, all suitable properties for topical application in patients with psoriasis. gNAC-VD3 did not decrease the viability of spheroids but significantly reduced the release of proinflammatory cytokines (IL-8, IL-6, TNF-α), oxidative stress (ROS), and matrix metalloproteinases from IMQ-induced spheroids to levels similar to the uninduced spheroids. Results suggest that gNAC-VD3 may constitute a potential anti-inflammatory agent for the topical treatment of mild psoriasis and deserves further in vivo exploration.

Evaluation of the efficacy and safety of cold laser (Diode 808 nm) therapy in the treatment of localized plaque psoriasis: clinical, dermoscopic and ultrastructural study

Background Psoriasis is a chronic, recurring, and immune-mediated inflammatory skin disease. Throughout the period of the last few decades, phototherapy has become widely used in treating stable psoriatic lesions. For the treatment of psoriasis, several light/laser therapies with distinct modes of action have been developed. Cold laser therapy might be an effective therapeutic choice for localized plaque psoriasis. Objective To assess the safety and efficacy of cold laser therapy clinically and microscopically in localized plaque psoriasis treatment. Patients and methods 40 patients with localized mild plaque psoriasis were selected from the Dermatology and Venereology outpatient clinic–Tanta University Hospitals and enrolled in the clinical trial. They were treated by cold laser 808 nm wavelength (Endolaser 422, Enraf–nonious B.V. Rotterdam, Netherlands) one session for 10 min on each plaque twice weekly separated by 2 days until clinical cure or for a maximum of 8 weeks. Evaluation was done immediately after the last session by taking the average of three blinded dermatologists of the photos, the modified Psoriasis Area and Severity Index [mPASI], dermoscopic examination, patients’ satisfaction scale and histopathological and electron microscopic examination of punch biopsy specimens taken before and after the end of treatment from psoriatic lesions in four patients only. Results There was a statistically significant clinical improvement after the end of treatment compared with before treatment as 16 patients (40%) showed excellent improvement, 8 patients (20%) showed good improvement, 9 patients (22.5%) showed mild improvement, and 7 patients (17.5%) showed poor improvement. As regard mPASI, a statistically significant decrease in mPASI was found after the end of treatment (P&lt;0.001). Regarding dermoscopic examination, a statistically significant reduction in the percentage of patients showing dermoscopic red dots and white scales after the end of treatment (P&lt;0.01). As regard the patients’ satisfaction scale, 82.5% of patients were satisfied from the results. Histopathological and ultrastructural evaluation revealed normalization of the psoriatic microscopic changes with cold laser. Conclusion The use of cold laser therapy for the management of localized mild plaque psoriasis is safe, tolerable, effective, and can be used as an alternative therapy for psoriasis.

Cardiovascular Considerations and Implications for Treatment in Psoriasis: An Updated Review.

Psoriasis, a prevalent chronic inflammatory skin disorder affecting 2-3% of the global population, has transcended its dermatological confines, revealing a profound association with cardiovascular diseases (CVD). This comprehensive review explores the intricate interplay between psoriasis and cardiovascular system, delving into genetic links, immune pathways, and adipose tissue dysfunction beyond conventional CVD risk factors. The pathophysiological connections unveil unique signatures, distinct from other inflammatory skin conditions, in particular psoriasis-specific genetic polymorphisms in IL-23 and TNF-α have consistently been linked to CVD. The review navigates the complex landscape of psoriasis treatments, addressing challenges and future directions in particular relevance to CVDs in psoriasis. Therapeutic interventions, including TNF inhibitors (TNFi), present promise in reducing cardiovascular risks, and methotrexate could constitute a favourable choice. Conversely, the relationship between IL-12/23 inhibitors and cardiovascular risk remains uncertain, while recent evidence indicates that Janus kinase inhibitors may not carry CVD risks. Emerging evidence supports the safety and efficacy of IL-17 and IL-23 inhibitors in patients with CVDs, hinting at evolving therapeutic paradigms. Lifestyle modifications, statins, and emerging therapies offer preventive strategies. Dedicated screening guidelines for CVD risk assessment in psoriasis are however lacking. Further, the impact of different disease phenotypes and treatment hierarchies in cardiovascular outcomes remains elusive, demanding ongoing research at the intersection of dermatology, rheumatology, and cardiology. In conclusion, unraveling the intricate connections between psoriasis and CVD provides a foundation for a holistic approach to patient care. Collaboration between specialties, advancements in screening methodologies, and a nuanced understanding of treatment impacts are essential for comprehensive cardiovascular risk management in individuals with psoriasis.

Italian S3-Guideline on the treatment of Atopic Eczema - Part 1: Systemic therapy, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Environmental Dermatology (SIDAPA).

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for pediatric, adolescent, pregnant and breastfeeding patients.

Italian S3-Guideline on the treatment of atopic eczema Part 2: non-systemic treatments and treatment recommendations for special AE patient populations, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Occupational Dermatology (SIDAPA).

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for pediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.

Challenges in Immunomodulation for Psoriasis: Recent Advancements and Need of Therapies

Abstract: Psoriasis is a chronic immune-mediated skin disorder affecting millions worldwide. The pathogenesis of psoriasis involves dysregulated immune responses characterized by aberrant activation of T cells and proinflammatory cytokines. Immunomodulation has emerged as a promising therapeutic approach for managing psoriasis, aiming to restore immune homeostasis. However, despite significant advancements, challenges persist in developing effective immunomodulatory therapies. This abstract reviews recent developments in psoriasis immunomodulation, encompassing novel targets and therapeutic modalities. Advances in biologics targeting interleukins (IL) and their receptors, such as IL-17, IL-23, and IL-12/23, have demonstrated substantial clinical efficacy. Additionally, small molecules that inhibit Janus kinases (JAK) and phosphodiesterase 4 (PDE4) have shown promise in regulating immune responses. Despite these advancements, certain limitations hinder the success of immunomodulatory therapies. Treatment resistance, safety concerns, and high costs remain critical challenges. Furthermore, a deeper understanding of the complex immunopathogenesis of psoriasis is essential for developing targeted and personalized therapies. In conclusion, immunomodulation has revolutionized the management of psoriasis, offering remarkable improvements in patient outcomes. Continued research and innovative therapeutic strategies are needed to overcome current challenges and pave the way for more efficient, safe, and accessible treatments for psoriasis.

Research hotspots and trends in Biological Agents for Psoriasis: Visualization and Bibliometric Analysis

Psoriasis is a global health concern, and biological therapies have proven to be highly effective in treating psoriatic patients in many countries. We performed a bibliometric analysis of current research on biological agents for the treatments of psoriasis, investigating research patterns and public interest in this area. We conducted a thorough review of articles on biological agents for psoriasis in the Web of Science Core Collection spanning from 2000 to 2022. Our study involved examining the distribution of these articles based on publication year, affiliations, countries, authors, and journals. To visualize this data effectively, we employed bibliometric tools like CiteSpace and the R package bibliometrix. Our analysis encompassed 8,047 publications. The number of papers published sharply increased from 2009, either reaching its peak in 2022 or not yet reaching it. The United States (n = 2,292), Kristian Reich (n = 166), and British Journal of Dermatology (n = 368) emerged as the top countries, author, and journal, respectively, in terms of publication productivity. The burst references predominantly focused on evaluating the safety and efficacy of biological treatments. The keyword citation network identified 11 clusters, with research themes revolving around “double blind”, “efficacy”, “therapy”, “safety”, and “psoriatic arthritis” were the research focuses. Additionally, potential future research areas such as "multicenter," "drug survival," and "severity" were emphasized.This study sheds light on the evolving research landscape and public interest in biological agents for psoriasis. The results suggest rapid expansion in this field, with the United States at the forefront. Enhanced international collaboration is recommended, and forthcoming research endeavors may concentrate on predicting treatment outcomes and adverse effects. Researching new biological agents, broadening the indications for biological agent treatment, and creating personalized treatment plans may pave the way for further research.

Wearable dual-drug controlled release patch for psoriasis treatment

Wearable drug delivery systems (DDS) have made significant advancements in the field of precision medicine, offering precise regulation of drug dosage, location, and timing. The performance qualities that wearable DDS has always strived for are simplicity, efficiency, and intelligence. This paper proposes a wearable dual-drug synergistic release patch. The patch is powered by a built-in magnesium battery and utilizes a hydrogel containing viologen-based hyperbranched polyamidoamine as both a cathode material and an integrated drug reservoir. This design allows for the simultaneous release of both dexamethasone and tannic acid, overcoming the limitations of monotherapy and ensuring effective synergy for on-demand therapy. In a mouse model with praziquimod-induced psoriasis, the patch demonstrated therapeutic efficacy at a low voltage. The inflammatory skin returned to normal after 5days with the on-demand release of dual drugs. This work provides a promising treatment option considering its straightforward construction and the therapeutic advantages of dual-drug synergy.