How can nanoparticle-based technologies revolutionize the topical therapy in psoriasis?

Studies show frequent usage but low adherence rates and poor satisfaction from topical therapy for psoriasis. These were attributed to low efficacy, inconvenience of application, and poor cosmetic quality for different body parts. Multicenter surveys on patients suggest a two-way holistic approach, where patients convey what bothers them most and doctors explain how products address specific concerns. New rapid response targeted topical agents, in cosmetically acceptable preparations, applied less often, are undergoing efficacy and safety studies, ideally on large populations up to 1 year or more. Until available, this review addresses gaps in knowledge on how to maximize effects of emollients, used alone, with physiologic lipids, or as base for active topical therapy. Updates—on how psoriasis skin becomes itchy, red, dry, thick, and scaly from inflammation and barrier defects—explain clinical responses to the physical, chemical, and functional properties of psoriasis topical therapies.

Background. Currently, psoriasis is the most common skin disease, its prevalence reaches 5% and this pathology often occurs together with arterial hypertension. Both arterial hypertension and psoriasis contribute to the remodeling of the cardiovascular system. As is known, myocardial remodeling is a substrate for electrical instability of the myocardium. Objective. The aim of the study was to study the parameters of the signal-averaged electrocardiogram in men with stage 2 arterial hypertension with concomitant vulgar psoriasis in the progressive stage, and to evaluate the parameters of the signal-averaged electrocardiogram against the background of psoriasis therapy. A total of 86 men with stage 2 arterial hypertension with a progressive stage of vulgar psoriasis with a severe and moderate course were examined. Signal-averaged ECG was recorded before psoriasis therapy was prescribed and after 6 months of systemic and topical psoriasis therapy. Results. A statistically significant moderate positive correlation was found between the severity of psoriasis vulgaris (according to the PASI index) and such an SU-ECG indicator as the duration of the filtered QRS complex (r = 0.32; p = 0.005), a statistically significant weak negative correlation of the PASI index with the root-mean-square amplitude of the last 40 ms of the filtered QRS complex (r = -0.27; p = 0.012). Patients with severe psoriasis had more pronounced changes in cardiac electrophysiology, in the form of more frequent recording of late ventricular potentials χ2 = 4.07; p = 0.044, a longer duration of the filtered QRS complex (p = 0.01). Systemic and topical therapy of concomitant psoriasis in patients with arterial hypertension leads to a decrease in the frequency of recording late ventricular potentials, and in patients who had severe psoriasis before the start of treatment, late potentials were recorded significantly more often after 6 months of therapy (χ2 = 3.88; p = 0.049) than in patients with initially moderate-severe psoriasis.

Psoriasis is a common, immune-mediated inflammatory skin disease characterized by red, heavily scaled plaques. The disease affects over one million people in the UK and causes significant physical, psychological and societal impact. There is limited understanding regarding the exact pathogenesis of the disease although it is believed to be a consequence of genetic predisposition and environmental triggers. Treatments vary from topical therapies, such as dithranol, for disease of limited extent (<5% body surface area) to the new immune-targeted biologic therapies for severe psoriasis. Dithranol (also known as anthralin) is a topical therapy for psoriasis believed to work by inhibiting keratinocyte proliferation. To date there have been no metabolomic-based investigations into psoriasis. The HaCaT cell line is a model system for the epidermal keratinocyte proliferation characteristic of psoriasis and was thus chosen for study. Dithranol was applied at therapeutically relevant doses to HaCaT cells. Following the optimisation of enzyme inactivation and metabolite extraction, gas chromatography-mass spectrometry was employed for metabolomics as this addresses central metabolism. Cells were challenged with 0-0.5 μg mL(-1) in 0.1 μg mL(-1) steps and this quantitative perturbation generated data that were highly amenable to correlation analysis. Thus, we used a combination of traditional principal components analysis, hierarchical cluster analysis, along with correlation networks. All methods highlighted distinct metabolite groups, which had different metabolite trajectories with respect to drug concentration and the interpretation of these data established that cellular metabolism had been altered significantly and provided further clarification of the proposed mechanism of action of the drug.

Topical treatments in psoriasis: today and tomorrow

To the Editor: Halobetasol propionate 0.01%/tazarotene 0.045% lotion (HP/TAZ) was developed as an effective, safe, and tolerable topical therapy for plaque psoriasis. It has been investigated in moderate-to-severe plaque psoriasis1-3; however, real-world data on the use of topical fixed-combination therapies for plaque psoriasis, particularly milder disease courses, are limited.

Treatment of any type of psoriasis involves the use of external therapy. Recommended topical preparations include: corticosteroids, calcipotriol in combination with corticosteroids, zinc pyrithione, keratolytics, tar. A special place in the therapy of psoriasis is occupied by a drug containing activated zinc pyrithione (Skin-cap), due to its effectiveness, safety and the availability of various forms (aerosol, cream, shampoo), which allows it to be used in both short-term and long-term therapy at different stages of the disease. Complex treatment, including the use of topical forms containing activated zinc pyrithione, is a highly effective, safe, pathogenetically substantiated method of treating various forms of psoriasis, allowing to achieve rapid regression of rashes, minimize the risk of adverse effects and achieve long-term control over the disease, which significantly improves the quality of life of patients

Journal Article Corrected proof Seeking new topical therapies in psoriasis Get access Dominika Kwiatkowska, Dominika Kwiatkowska Department of Dermatology, Institute of Medical Sciences, Medical College of Rzeszow University, Poland https://orcid.org/0000-0003-3268-012X Search for other works by this author on: Oxford Academic Google Scholar Adam Reich Adam Reich Department of Dermatology, Institute of Medical Sciences, Medical College of Rzeszow University, Poland Correspondence: Adam Reich. Email: adi_medicalis@go2.pl https://orcid.org/0000-0002-5573-1754 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad233, https://doi.org/10.1093/bjd/ljad233 Published: 07 July 2023 Article history Received: 30 June 2023 Accepted: 04 July 2023 Published: 07 July 2023 Corrected and typeset: 08 August 2023

Efficacy and safety of apremilast in patients with mild-to-moderate plaque psoriasis: Results of a phase 3, multicenter, randomized, double-blind, placebo-controlled trial

Background Crohn’s disease (CD) is characterized by a heterogeneous disease course and treatment response. There is a clinical need to identify CD patients at diagnosis who are at risk for developing a severe disease course. Patient stratification using state-of-the-art clinical, serological or genetic markers does not predict disease course sufficiently to facilitate clinical decision making. The current study aimed to investigate the additive predictive value of histopathological features at diagnosis to discriminate between patients with a long-term mild and severe disease course. Methods Diagnostic biopsies from treatment-naïve CD patients with mild or severe disease courses in the first 10 years after diagnosis (i.e. based on the number of quarterly flares) were reviewed by two senior gastrointestinal pathologists after developing a standardized form comprising 15 histopathological features related to acute and chronic inflammation. Multivariable logistic regression models were built to identify predictive features and compute receiver operating characteristics (ROC) curves. Model 1 included clinically relevant baseline characteristics (Montreal classification, smoking status and gender). Next, histopathological were added by applying two different model-building strategies (forward selection and purposeful selection algorithm)(Model 2). Prediction models were internally validated using bootstrapping to obtain optimism-corrected performance estimates. Results In total, 817 biopsies from 137 CD patients (64 mild disease course, 73 severe disease course) were included. Based on clinical baseline characteristics alone, disease course could only be moderately predicted (Model 1 Area under ROC (AUROC): 0.738 (optimism 0.018), 95%CI 0.65–0.83, sensitivity 83.6%, specificity 53.1%). When adding histopathological features, in colonic, but not ileal, biopsies a combination of (1) basal plasmacytosis, (2) severe lymphocyte and plasma cell infiltration in the lamina propria, (3) Paneth cell metaplasia and (4) absence of ulcers were identified and resulted in significantly better prediction of a severe disease course (Model 2 AUROC: 0.883 (optimism 0.033), 95%CI 0.82–0.94, sensitivity 80.4%, specificity 84.2%, model 2 vs. model 1 AUROC p = 0.001)[Figure 1]. Conclusion In this first study investigating the additive predictive value of multiple histopathological features in biopsies at CD diagnosis, we found that certain features of chronic inflammation in colonic biopsies contributed to prediction of a severe disease course, thereby presenting a novel approach to improve stratification and facilitate clinical decision making.

Aqueous solutions of mechlorethamine (Mustargen) hydrochloride (0.055 to 0.00625%) have been used in courses of seven to ten days on lesions of psoriasis in 42 patients. A significant involutionary effect was obtained with the 0.0125% to 0.05% concentrations, particularly on the trunk. The rate of contact sensitization ranged from 50% to more than 80%, and was highest with the 0.05% concentration. Occasional Koebner reactions and paradoxical results were noted. The high rate of sensitization precludes the use of this agent in the practical management of psoriasis.

A new topical formulation for psoriasis: Development of methotrexate-loaded nanostructured lipid carriers

A 38-year-old man presented with symptoms of fever and dry cough. There was a past medical history of chronic plaque psoriasis with a single active psoriatic plaque affecting the lateral...

Systemic iron chelation therapy has long been used for iron overload, providing a role in returning iron levels to proper homeostatic concentrations. Recently, topical iron chelation therapy has emerged as a potential strategy for treating skin damage. This narrative review explores the current status and future prospects of topical iron chelation therapy for treating ultraviolet (UV) and non-UV skin damage, as well as its potential application in wound healing. The review was conducted through a literature search across PubMed, Web of Science, and EMBASE databases, spanning publications from 1990 to 2023. The selection of articles was focused on primary research studies, either experimental or clinical, that explored the implications and formulations of topical iron chelators used alone or in conjunction with another therapeutic agent. The search strategy employed a combination of terms, including "topical iron chelation", "topical deferoxamine", "UV", "wound healing", "skin inflammation", "radiation-induced fibrosis", and "skin cancer". Relevant studies, including methods, intervention strategies, measured outcomes, and findings, are summarized. The review also considered the potential challenges in translating research findings into clinical practice. Results indicate that topical iron chelators, such as deferoxamine, are effective in mitigating UV-induced skin damage, reducing tumorigenesis, and decreasing oxidative damage. In addition, the use of these agents in radiation-induced fibrosis has been shown to significantly increase skin elasticity and reduce dermal fibrosis. Several studies also highlight the use of topical iron chelators in difficult-to-treat chronic wounds, such as diabetic neuropathic ulcers and sickle cell ulcers. In conclusion, topical iron chelation therapy represents a novel and promising approach for skin protection and wound healing. Its potential makes it a promising area of future research.

Several studies suggest that chronic immunosuppression in pediatric liver transplant patients may affect the severity and mortality rates of SARS-CoV-2 infection. We assessed a total of 118 pediatric liver transplant recipients for SARS-CoV-2 infection, aged 1 to 18 years, followed between March 2019 and January 2022. We compared the clinical characteristics and outcomes of SARS-CoV-2 infection in pediatric liver transplant patients to 187 non-liver transplant pediatric patients with SARSCoV-2 infection who had been diagnosed at our institution between March 15, 2020, and December 31, 2020. Demographic data, clinical features, and laboratory findings from the patients were retrospectively collected from hospital reports and telephone inquiries. A total of 20 liver transplant patients with SARS-CoV-2 infection were identified. Median age of liver transplant recipients with SARS-CoV-2 infection was higher than non-liver transplant pediatric patients with SARS-CoV-2 (14.8 [range, 7-16] vs 6.8 [range, 2-14] years; P = .016). There were no significant differences in mild and moderate disease courses of SARS-CoV-2 infection between liver transplant recipients and non-liver transplant pediatric patients (18 [90.0%] vs 133 [71.1%] patients [P = .188] and 2 [10%] vs 49 [26.2%] patients [P = .118], respectively). Fever was less frequently observed in liver transplant patients with SARS-CoV-2 infection compared with non-liver transplant patients (55.0% vs 80.2%; P = .015). We found no intergroup differences in sex (P = .342), hospitalization rate (P = .161), and overall clinical presentation. Despite the immunosuppression regimens, liver transplant patients in our series survived SARS-CoV-2 infection without serious sequelae and without graft rejection. Overall, liver transplant and non-liver transplant pediatric patients with SARSCoV-2 infection experienced a mild disease course.

Use of topical therapy for mild and moderate psoriasis continues to be a mainstay of treatment. The previous chapter introduced topical corticosteroids and vitamin D analogs as the most common therapies for psoriasis (see Tab. 1). Here the newly available topical retinoids and immunomodulators, along with the traditional therapies of tars, anthralin, and salicylic acid, will be discussed in detail.