The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is pivotal in the immune defense against infections and cancer. However, aberrant activation of this pathway can trigger autoimmune and inflammatory diseases by inducing excessive production of type I interferon (IFN) and pro-inflammatory cytokines. Inhibition of the aberrant activation of the cGAS-STING signaling pathway by targeting STING represents a novel therapeutic strategy for these autoimmune and inflammatory disorders. In this study, we discovered three novel STING antagonists based on surface plasmon resonance (SPR), differential scanning fluorimetry (DSF), and ISRE (interferon stimulated response element)-luciferase assays. The efficacy and pharmacological mechanisms of the three STING antagonists for treating imiquimod (IMQ)-induced psoriasis-like dermatitis by western blotting (WB), flow fluorescence, and immunostaining. The three STING antagonists exhibited pan-inhibitory activities on the activation of both the human and mouse cGAS-STING signaling pathway. Intravenous and topical administration of the three antagonists alleviated the inflammation and skin lesions associated with IMQ-induced psoriasis-like dermatitis via suppression of the inflammatory cascade mediated by the IMQ-TLR-7-NF-κB/cGAS-STING-NF-κB/IL-1β-IL-1R-NF-κB/TNFα-TNF-R-NF-κB signaling axis. In conclusion, we identified three novel STING antagonists with pan-inhibitory activities against human and mouse STING, providing lead compounds for the future development of both STING antagonists and immune agents for therapeutically manipulating STING-driven diseases, such as psoriasis. Our findings offer another new therapeutic strategy for managing STING-driven autoimmune and inflammatory diseases, while also reemphasizing the critical role of the cGAS-STING signaling pathway in such conditions.

The use of the current available therapies for psoriasis management may sometimes be limited by reduced patients' compliance, safety issues for patients' comorbidities, primary lack of efficacy, loss of effectiveness, development of side effects. In this context, several clinical trials investigating the use of both topical and systemic therapies are ongoing, and other new drugs will be approved soon.

The aim of this manuscript is to review current literature and to provide an overview of the current and future trends in psoriasis treatment. A comprehensive review of the English-language medical literature was performed using Pubmed and clinicaltrials.gov databases.

Although several therapies are currently available for psoriasis' treatment, unmet needs still exist for patients with moderate and severe psoriasis and hence expanding the therapeutic armamentarium is desirable for a more personalized approach. The ongoing development of innovative therapies could provide effective and safe therapies in the future enhancing the therapeutic management of moderate-severe unresponsive psoriasis.

Psoriasis is a common inflammatory skin disease involving interactions between keratinocytes and immune cells that significantly affects the quality of life. It is characterized by hyperproliferation and abnormal differentiation of keratinocytes and excessive infiltration of immune cells in the dermis and epidermis. The immune mechanism underlying this disease has been elucidated in the past few years. Research shows that psoriasis is regulated by the complex interactions among immune cells, such as keratinocytes, dendritic cells, T lymphocytes, neutrophils, macrophages, natural killer cells, mast cells, and other immune cells. An increasing number of signaling pathways have been found to be involved in the pathogenesis of psoriasis, which has prompted the search for new treatment targets. In the past decades, studies on the pathogenesis of psoriasis have focused on the development of targeted and highly effective therapies. In this review, we have discussed the relationship between various types of immune cells and psoriasis and summarized the major signaling pathways involved in the pathogenesis of psoriasis, including the PI3K/AKT/mTOR, JAK-STAT, JNK, and WNT pathways. In addition, we have discussed the results of the latest omics research on psoriasis and the epigenetics of the disease, which provide insights regarding its pathogenesis and therapeutic prospects; we have also summarized its treatment strategies and observations of clinical trials. In this paper, the various aspects of psoriasis are described in detail, and the limitations of the current treatment methods are emphasized. It is necessary to improve and innovate treatment methods from the molecular level of pathogenesis, and further provide new ideas for the treatment and research of psoriasis.

The main objective is to evaluate clinical efficacy and safety of using calcipotriol-betamethasone compounding agent for psoriasis treatment through a systematic review and meta-analysis. We searched MEDLINE, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), and WanFang Data from inception till July 31, 2020. Efficacy was evaluated based on primary outcome indicators including skin lesion improvement and overall adverse reaction rate. Secondary outcome indicators included degree of life quality improvement, clinical effectiveness rate, and specific adverse reaction rates. RevMan5.3 was used to perform the meta-analysis. 22 studies finally met our inclusion criteria for the meta-analysis. The results indicated that for short-term treatment, a sequential therapy that uses calcipotriol betamethasone compounding agent and calcipotriol improves PASI score (MD = -0.94, 95% CI - 1.38 ~ - 0.49, P < 0.0001, I² = 49%), comparing with using only calcipotriol. From a drug safety perspective, the difference in overall adverse reaction rate is not significant between the calcipotriol group and the sequential treatment group (RR = 0.50, 95% CI 0.22 ~ 1.14, P = 0.10, I² = 33%). Calcipotriol betamethasone compounding agent may be more effective in plaque psoriasis treatment compared to use only calcipotriol, with no significant difference in adverse reaction rate between the two groups. Although the data were collected from 13 comparison groups, each group may not have sufficient data for a thorough and comprehensive analysis. Further research may be necessary for a more detailed evaluation of effectiveness of using calcipotriol betamethasone compounding agent for plaque psoriasis treatment.

The dry and scaly skin of psoriatic patients decreases the efficacy of ultraviolet B (UVB) phototherapy. Different agents are used to facilitate the transmission of light, but most of these preparations are cosmetically unfavorable. We have tested a novel preparation containing sodium hyaluronate and nicotinic acid (UV Fotogel®; Pernix Ltd.) with the double aim to improve the efficacy of UVB phototherapy and assess the cosmetic acceptability of the preparation.

Ninety patients with plaque psoriasis were enrolled in the study, of whom 44 received narrow-band UVB (NB-UVB) phototherapy. Prior to phototherapy, one side of the patient's body was treated with UV Fotogel while the other side served as a control. The other 46 patients used the preparation at their homes before regular sunbathing. The Local Psoriasis Severity Index (L-PSI), cosmetic acceptability and tolerability were recorded. The median values with the 25th and 75th percentiles (25p and 75p, respectively) were determined for the UV Fotogel-treated and control sites and then compared.

The sides of the body to which UV Fotogel was applied prior to NB-UVB phototherapy had a significantly lower median L-PSI score than the non-treated control sides at the end of the treatment (1.0 [25p-75p: 0.0-2.0] vs. 2.0 [1.0-3.0], respectively). The application of UV Fotogel prior to sunbathing also led to a significant decrease in L-PSI score. There was a significant reduction in the median L-PSI score of patients at the final visit compared to baseline (2.5 [25p-75p: 1.5-3.5] vs. 6.0 [6.0-7.0], respectively). Use of the preparation was not accompanied by considerable adverse effects, and the patients found it cosmetically acceptable. Application of UV Fotogel prior to sunbathing was well tolerated by the patients, and the cosmetic acceptability was also good.

UV Fotogel is potentially a useful device for enhancement of the efficacy of phototherapy in patients with psoriasis.

Hydrogels are playing an increasingly important role in medicine and pharmacy. Due to their favorable physicochemical properties, biocompatibility, and designed interaction with living surroundings, they seem to be one of the most promising groups of biomaterials. Hydrogel formulations from natural, semi, or synthetic polymeric materials have gained great attention in recent years for treating various dermatology maladies and for cosmetology procedures. The purpose of this review is to present a brief review on the basic concept of hydrogels, synthesis methods, relevant mechanisms, and applications in dermatology or cosmetology. This review discusses transdermal therapies and the recent advances that have occurred in the field.

Many international guidelines for management of psoriasis exist and most have variations in grading evidence quality, strength of recommendations, and dosing. The objective of our review is to compare international guidelines published in the United Kingdom, Canada, Europe, and the United States for the management of moderate-to-severe plaque psoriasis.

We conducted a literature review on systemic therapies and phototherapy for moderate-to-severe plaque psoriasis in adult patients. The British, Canadian, European, and American guidelines served as the key comparators in our review. To identify relevant supporting clinical trials not referenced in the guidelines, we conducted literature searches in PubMed and EMBASE. Two authors independently extracted data on indications, dosing, efficacy, evidence grade, and strength of clinical recommendation for each therapy.

Monoclonal antibodies directed toward tumour necrosis factor and interleukin (IL)-12/23 received the strongest recommendations for treatment of moderate-to-severe plaque psoriasis, supported by robust, high-quality randomized controlled trials (RCTs). Newer agents such as IL-17 and IL-23 inhibitors are not referenced in most guidelines. There are fewer RCTs for conventional therapies and few head-to-head comparisons with biologics, making it difficult to draw direct comparisons. Among older agents, methotrexate is most strongly recommended for long-term maintenance and cyclosporine is recommended for short-term control of flares.

Physicians should individualize psoriasis-management strategies based on medication tolerance, efficacy, safety, patient comorbidities, availability of the medication, and patient preference.

Psoriasis is one of the most common chronic autoinflammatory skin disease, associated with hyperproliferation and abnormal differentiation of keratinocytes, inflammation, and angiogenesis. The available treatments for psoriasis are not curative and may have numerous side effects, and topical administration is preferred over systemic therapy due to the reduced systemic burden of the drug. Thus, novel and more efficacious formulations of anti-inflammatory and/or differentiating compounds for topical application could be very useful for the disease management and for improving the quality of life of the patients. Here we evaluated the potential as anti-psoriatic of an equimolar mixture of two compounds, 2,4-Monofurfurylidene-tetra-O-methylsorbitol (Compound A) and 4,6-dimethyl-2-(3,4,5-trimethoxyphenylamino)pyrimidine (Compound B), that, used individually, are known to possess immunomodulating properties (Compound A) and keratolitic and anti-inflammatory activity (Compound B). Human immortalized keratinocyte cell line (HaCaT cells) and primary human keratinocyte cells from adult donor (HEKa) were used as in vitro experimental models. We show that the mix A + B exhibits antiproliferative activity and induces terminal differentiation more efficiently than compounds A and B used individually. We confirm that the compound B is the active ingredient of the mixture and the mainly responsible for anti-psoriatic activity, but the mix A + B is more effective and possesses lower cytotoxicity than the compound B alone. This could be ascribable to the association with compound A, that is known to possess, in addition to the immunomodulating ability, antioxidant and antiradical action. Our results indicate that mix A + B could be a suitable candidate for a new cosmeceutical formulation for topical treatment of psoriasis.

Hypertrophic scars are a consequence of wound healing.

The objective of the present study is to evaluate vitamin D and inflammatory biomarker plasma levels during wound healing.

A prospective study was performed in patients (n = 63) submitted to body contouring surgery. Blood samples were collected before (t ₀) and 5 days after surgery (t ₅). Blood cell count, protein inflammatory biomarkers, and circulating plasma levels of 25(OH)D, vitamin A and vitamin E were quantified. Six months after surgery, scars were evaluated and classified as normal or hypertrophic.

At the end of the study, 73% of the patients developed a normal scar (control group, n = 46) and 27% of the patients presented hypertrophic scars (HT group, n = 17). The patients in the HT group presented higher eosinophil (0.145 × 10⁹ /L vs. 0.104 × 10⁹ /L, p = 0.028) and basophil count (0.031 × 10⁹ /L vs. 0.22 × 10⁹ /L, p = 0.049) and C-reactive protein levels (6.12 mg/L vs. 2.30 mg/L, p = 0.015) in t ₀ than the patients in the control group. At t ₅, the patients in the HT group showed a decrease in neutrophil (3.144 × 10^9/L vs. 4.03 × 10⁹/L, p = 0.031) and an increase in basophil (0.024 × 10⁹/L vs. 0.015 × 10⁹/L, p = 0.005) and lymphocyte count (1.836 × 10⁹ /L vs. 1.557 × 10⁹/L; p = 0.028). Before surgery, vitamin D plasma levels were found to be decreased by almost 50% (23.52 ng/mL vs. 15.46 ng/mL, p = 0.031) in the patients who developed hypertrophic scars. Thirty-one percent of the patients submitted to bariatric surgery had more hypertrophic scars, versus 24% of the patients with no previous bariatric surgery.

There is a different systemic inflammatory profile response in the patients during the formation of hypertrophic scars. Vitamin D plasma levels are marked reduced in these patients. Considering the powerful anti-inflammatory effect of vitamin D, these findings could be related.

To provide primary care clinicians with an up-to-date and practical overview of the diagnosis and management of psoriasis.

PubMed, MEDLINE, EMBASE, and Cochrane databases were searched for relevant meta-analyses, randomized controlled trials, systematic reviews, and observational studies about the diagnosis and management of psoriasis.

Psoriasis is a chronic, multisystem inflammatory disease with predominantly skin and joint involvement. Beyond the physical dimensions of disease, psoriasis has an extensive emotional and psychosocial effect on patients, affecting social functioning and interpersonal relationships. As a disease of systemic inflammation, psoriasis is associated with multiple comorbidities, including cardiovascular disease and malignancy. The diagnosis is primarily clinical and a skin biopsy is seldom required. Depending on the severity of disease, appropriate treatment can be initiated. For mild to moderate disease, first-line treatment involves topical therapies including corticosteroids, vitamin D3 analogues, and combination products. These topical treatments are efficacious and can be safely initiated and prescribed by primary care physicians. Patients with more severe and refractory symptoms might require further evaluation by a dermatologist for systemic therapy.

Many patients with psoriasis seek initial evaluation and treatment from their primary care providers. Recognition of psoriasis, as well as its associated medical and psychiatric comorbidities, would facilitate timely diagnosis and appropriate management with effective and safe topical therapies and other medical and psychological interventions, as needed. More severe and refractory cases might warrant referral to a dermatologist for further evaluation and possible systemic therapy.

Current work reports the development and optimization of clobitasol propionate (CP) and calcipotriol (CT) loaded nanoemulsion based gel for topical treatment of psoriasis. Components of nanoemulsion viz., oil and surfactant/co-surfactant were selected depending upon solubility and emulsification potential respectively. The optimized ratio of 5:3:2 of Capmul MCM C8 EP, Cremophor RH 40 and Labrafil 1944 CS was selected. Carbopol 980 was used as gelling agent to achieve final drug concentration of 0.05% w/w and 0.005% w/w respectively for CP and CT. HaCaT cell lines showed higher uptake of drug from nanoemulsion in correlation with the enhancement in penetration of both drugs in stratum corneum (SC) and viable layer from nanoemulsion and gel as compared to free drugs. Imiquimod induced psoriatic BALB/c mice revealed significantly higher anti-psoriatic activity of nanoemulsion gel as compared to free drugs and marketed formulation. The developed formulation showed negligible skin irritation despite increased penetration into the skin.

Topical vitamin D is approved by the US Food and Drug Administration for the treatment of psoriasis but is also used off-label in the treatment of a variety of cutaneous diseases despite a lack of evidence-based guidelines.

The objective of this study was to provide evidence-based clinical guidelines for the off-label use of topical vitamin D in the treatment of dermatologic disease.

A systematic literature review was conducted via the MEDLINE, Embase, and CENTRAL databases for off-label uses of topical vitamin D analogues in the treatment of dermatologic disease other than psoriasis. The data were synthesized, and evidence-based recommendations were rendered according to the highest level of evidence available.

A total of 165 articles met the inclusion criteria. A moderate to strong recommendation was given for the use of topical vitamin D in combination with corticosteroids and phototherapy in vitiligo and as monotherapy for various ichthyoses, morphea, pityriasis alba, prurigo nodularis, and polymorphous light eruption. There is evidence showing that topical vitamin D is ineffective in the treatment of actinic keratosis, seborrheic keratosis, lichen planus, seborrheic dermatitis, alopecia areata, chemotherapy-induced alopecia, and hypertrophic scars.

Topical vitamin D analogues have an important role in the off-label treatment of dermatologic disease, but higher quality studies are still required.

Chronic plaque psoriasis is the most common type of psoriasis, and it is characterised by redness, thickness, and scaling. First-line management of chronic plaque psoriasis is with topical treatments, including vitamin D analogues, topical corticosteroids, tar-based preparations, dithranol, salicylic acid, and topical retinoids.

To compare the effectiveness, tolerability, and safety of topical treatments for chronic plaque psoriasis, relative to placebo, and to similarly compare vitamin D analogues (used alone or in combination) with other topical treatments.

We updated our searches of the following databases to February 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2011, Issue 2), MEDLINE (from 1948), EMBASE (from 1980), Science Citation Index (from 2008), Conference Proceedings Citation Index - Science (from 2008), BIOSIS (from 1993), Dissertation Abstracts via DialogClassic (all publication years), and Inside Conferences (all publication years).We identified ongoing and unpublished studies from the UK Clinical Research Network Study Portfolio and the metaRegister of Controlled Trials. We checked the bibliographies of published studies and reviews for further references to relevant trials, and we contacted trialists and companies for information about newly published studies.A separate search for adverse effects was undertaken in February 2011 using MEDLINE and EMBASE (from 2005).Final update searches for both RCTs and adverse effects were undertaken in August 2012. Although it has not been possible to incorporate RCTs and adverse effects studies identified through these final searches within this review, we will incorporate these into the next update.

Randomised trials comparing active topical treatments against placebo or against vitamin D analogues (used alone or in combination) in people with chronic plaque psoriasis.

One author extracted study data and assessed study quality. A second author checked these data. We routinely contacted trialists and companies for missing data. We also extracted data on withdrawals and on local and systemic adverse events. We defined long-term trials as those with a duration of at least 24 weeks.

This update added 48 trials and provided evidence on 7 new active treatments. In total, the review included 177 randomised controlled trials, with 34,808 participants, including 26 trials of scalp psoriasis and 6 trials of inverse psoriasis, facial psoriasis, or both. The number of included studies counted by Review Manager (RevMan) is higher than these figures (190) because we entered each study reporting a placebo and an active comparison into the 'Characteristics of included studies' table as 2 studies.When used on the body, most vitamin D analogues were significantly more effective than placebo, with the standardised mean difference (SMD) ranging from -0.67 (95% CI -1.04 to -0.30; 1 study, 119 participants) for twice-daily becocalcidiol to SMD -1.66 (95% CI -2.66 to -0.67; 1 study, 11 participants) for once-daily paricalcitol. On a 6-point global improvement scale, these effects translate into 0.8 and 1.9 points, respectively. Most corticosteroids also performed better than placebo; potent corticosteroids (SMD -0.89; 95% CI -1.06 to -0.72; I² statistic = 65.1%; 14 studies, 2011 participants) had smaller benefits than very potent corticosteroids (SMD -1.56; 95% CI -1.87 to -1.26); I² statistic = 81.7%; 10 studies, 1264 participants). On a 6-point improvement scale, these benefits equate to 1.0 and 1.8 points, respectively. Dithranol, combined treatment with vitamin D/corticosteroid, and tazarotene all performed significantly better than placebo.Head-to-head comparisons of vitamin D for psoriasis of the body against potent or very potent corticosteroids had mixed findings. For both body and scalp psoriasis, combined treatment with vitamin D and corticosteroid performed significantly better than vitamin D alone or corticosteroid alone. Vitamin D generally performed better than coal tar, but findings relative to dithranol were mixed. When applied to psoriasis of the scalp, vitamin D was significantly less effective than both potent corticosteroids and very potent corticosteroids. Indirect evidence from placebo-controlled trials supported these findings.For both body and scalp psoriasis, potent corticosteroids were less likely than vitamin D to cause local adverse events, such as burning or irritation. Combined treatment with vitamin D/corticosteroid on either the body or the scalp was tolerated as well as potent corticosteroids, and significantly better than vitamin D alone. Only 25 trials assessed clinical cutaneous dermal atrophy; few cases were detected, but trials reported insufficient information to determine whether assessment methods were robust. Clinical measurements of dermal atrophy are insensitive and detect only the most severe cases. No comparison of topical agents found a significant difference in systemic adverse effects.

Corticosteroids perform at least as well as vitamin D analogues, and they are associated with a lower incidence of local adverse events. However, for people with chronic plaque psoriasis receiving long-term treatment with corticosteroids, there remains a lack of evidence about the risk of skin dermal atrophy. Further research is required to inform long-term maintenance treatment and provide appropriate safety data.

Medicines reclassification from prescription to nonprescription (switch) has slowed in some countries, including the United States. New thinking may be necessary to drive this area, including third-party reclassification and better use of the pharmacist, collaborative care, or innovative technologies.

The goal of this study was to describe a recent, successful, third-party reclassification of topical calcipotriol, a treatment for psoriasis, including the process, challenges, and solutions.

This case study used multiple sources of information, including an application to the Medicines Classification Committee (MCC) in New Zealand, the response letter from the MCC, published minutes of the relevant MCC meeting, and interview data. A heuristic qualitative approach was used that embraces the involvement and experiences of the lead researcher.

The third-party reclassification of topical calcipotriol generated challenges, mainly due to initial manufacturer opposition. The greatest hurdle was an inability to change the label. However, requiring mandatory pharmacist consultation, with supply under specified conditions, overcame the barriers. Such conditions included supply only to adults with mild to moderate psoriasis, limits on weekly usage and pack size supplied, and the use of a collaborative care approach requiring previous physician diagnosis and advising the physician of usage. An algorithm for supply was developed. The flexibility of the MCC, an advisory committee, and the medicines regulator, both in considering a third-party approach and in allowing an exemption to prescription supply under specific conditions, was vital to the success of the reclassification.

Third-party reclassification may be possible in some countries, particularly where supply can be limited to pharmacists only. A flexible approach may be needed from the committee and regulator to assist such reclassification. Given the multiple beneficiaries of reclassification, removing reliance on the pharmaceutical companies to drive reclassification and/or using new models of supply may provide impetus to the reclassification arena.

New clinical treatment guidelines for plaque psoriasis, written by a panel of 16 Canadian dermatologists, were recently published online. These Canadian Guidelines for the Management of Plaque Psoriasis are evidence based and free of any influence from corporate sponsors and have been endorsed by the Canadian Dermatology Association (CDA). The Guidelines offer treatment recommendations for mild and moderate to severe body psoriasis, as well as for psoriasis affecting specific areas of the skin, such as the facial, flexural, and genital areas; nails; scalp; and palms and soles. The present overview describes the genesis and contents of the Guidelines, which are available in full through the CDA at <http://www.dermatology.ca/guidelines/cdnpsoriasisguidelines.pdf> (English) or <http://www.dermatology.ca/french/psoriasisguidelines.html> (French).

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In the first 5 parts of the American Academy of Dermatology Psoriasis Guidelines of Care, we have presented evidence supporting the use of topical treatments, phototherapy, traditional systemic agents, and biological therapies for patients with psoriasis and psoriatic arthritis. In this sixth and final section of the Psoriasis Guidelines of Care, we will present cases to illustrate how to practically use these guidelines in specific clinical scenarios. We will describe the approach to treating patients with psoriasis across the entire spectrum of this fascinating disease from mild to moderate to severe, with and without psoriatic arthritis, based on the 5 prior published guidelines. Although specific therapeutic recommendations are given for each of the cases presented, it is important that treatment be tailored to meet individual patients' needs. In addition, we will update the prior 5 guidelines and address gaps in research and care that currently exist, while making suggestions for further studies that could be performed to help address these limitations in our knowledge base.

Psoriasis is a common chronic inflammatory skin disease and many patients require lifelong treatment. Characteristic scaly, itchy, unsightly psoriatic lesions affect many body areas and most patients commonly experience scalp involvement. The cosmetic embarrassment of visible body lesions, inaccessibility of scalp skin to application of therapies and proximity of sensitive facial skin add to the challenges of most patients managing their psoriasis long term. Psoriasis can severely impact patients' quality of life. This can impact significantly on the patient. In economic terms patients may incur increased out-of-pocket expenditure or extended time away from work as a direct consequence of psoriasis, particularly in severe cases; In many countries, specialist review of patients provides pressures on hard-pressed services and the costs of psoriasis care are substantial, particularly in patients with severe recalcitrant psoriasis which may require lengthy inpatient admission. Around 80% of patients with psoriasis have mild to moderately severe disease and the majority are treated with topical medicines by their physician in primary care. Despite the availability of a wide range of treatment options, regimens have been unsatisfactory, associated with patient dissatisfaction, poor compliance and often safety concerns with long-term use. Evidence-based clinical guidelines aim to improve healthcare of patients and while there are such guidelines for psoriasis, to date the challenges of (and recommendations for) managing scalp psoriasis are often limited or missing from these treatment guidelines. In the following in-journal supplement, a connected suite of five papers focus on the use of topical therapies for the treatment of the person afflicted with psoriasis. This work harnesses robust evidence from randomised clinical trials (RCTs) of topical therapies commonly used in psoriasis patients and translates this into recommendations for the most appropriate treatment of patients with body or scalp psoriasis, from an efficacy, safety and cost-effectiveness perspective. Based upon systematic review and harnessing 'state of the art' evidence assessment methodologies, the modelling work suggests that the use of a two-compound formulation (TCF) product of calcipotriol and betamethasone dipropionate is the most appropriate treatment option for both body and scalp psoriasis. This Editorial acknowledges the results of any modelling exercise have limitations; indeed such limitations are acknowledged in each modelling contribution in this issue. With these caveats in mind, this introductory paper considers the implications of this research and distillation of the evidence. This work should guide cost-effective treatment choices for body and scalp psoriasis, assist in recommendations for management of scalp psoriasis in future iterations of psoriasis clinical guidelines and help primary care physicians striving to attain best outcomes in the care of the person with psoriasis.

The efficacy of the two-compound formulation (TCF) product containing calcipotriol and betamethasone dipropionate applied once daily in psoriasis has been demonstrated in phase III trials but no randomised clinical trial comparing all commonly used topical treatments exists. The aim of the study was to compare the efficacy of once-daily use of the TCF product relative to other commonly used topical agents in plaque psoriasis.

Data on change in Psoriasis Area and Severity Index (PASI) score from baseline and PASI 75 (percentage of patients achieving a 75% reduction in PASI score), after 4 weeks of treatment were obtained by means of a systematic literature review of randomised controlled trials and synthesised with a Bayesian mixed treatment comparison meta-analysis.

Relative to all active interventions, except for the unlicensed twice-daily application of the TCF product, the TCF once daily showed a greater efficacy based on PASI 75 response (relative risk ranging from 1.22 to 3.18) and improvement in PASI score from baseline (difference in % CFB PASI between TCF once daily and other active interventions ranged from 4.01 to 49.68).

Among topical therapies evaluated, TCF once daily can be considered the most efficacious treatment for plaque psoriasis.

The majority of patients with psoriasis can be safely and effectively treated with topical therapy alone, either under the supervision of a family physician or dermatologist. For those requiring systemic agents, topical therapies can provide additional benefit. Optimal use of topical therapy requires an awareness of the range and efficacy of all products.

The review covers the efficacy and role of topical therapies including emollients, corticosteroids, vitamin D analogs, calcineurin inhibitors, dithranol, coal tar, retinoids, keratolyics and combination therapy. The report was prepared following a PubMed and Embase literature search up to April 2010.

The paper provides a broad review of the relevant topical therapeutic options available in routine clinical practice for the management of psoriasis and a recommendation for selection of treatment.

Topical therapies used appropriately provide a safe and effective option for the management of psoriasis. An awareness of the available products and their efficacy is key to treatment selection and patient satisfaction.

Treating psoriasis in patients with concomitant hepatitis C virus (HCV) infection presents a special challenge. Not only is psoriasis exacerbated by interferon therapy, the standard of care for HCV, but many psoriasis therapies are potentially hepatotoxic, immunosuppressive, or both, which has been generally thought to be a contraindication in chronic infections such as HCV.

Our aim was to arrive at a consensus on treating psoriasis in patients with concomitant HCV infection.

Reports in the literature were reviewed regarding common psoriasis therapies and liver toxicity.

Topical therapies are first-line therapy for patients with limited psoriasis and HCV. Ultraviolet B phototherapy may be considered as a second-line treatment when needed. Ultraviolet B phototherapies in combination with topical therapies are first line for patients with moderate to severe psoriasis, and are considered safe in those patients with concomitant HCV infection. Other systemic therapies, such as acitretin, etanercept, and, possibly, other tumor necrosis factor inhibitors, are considered second line. Psoralen plus ultraviolet A should also be considered a second-line therapy.

There are few evidence-based studies on treating psoriasis with systemic therapy in patients with pre-existing liver disease.

There are no large double-blind clinical trials addressing the treatment of psoriasis in patients with HCV infection and more studies are needed.

Psoriasis is an inflammatory and immunological cutaneous disease. The high morbidity in patients with psoriasis results from severe clinical manifestations and/or adverse effects of treatment. The Undersea and Hyperbaric Medical Society and Federal Medicare and Medicaid Services have approved the use of hyperbaric oxygen (HBO(2)) for more than 15 indications, including wound healing, infections and late effects of radiation, which are largely unresponsive to conventional treatments. Accumulated data show that HBO(2) has anti-inflammatory effects and other positive influences on the immune system, making it a rational treatment in the management of psoriasis plaques and arthritis.

We present the cases of two patients with long histories of psoriasis vulgarus who exhibited marked improvement with use of HBO(2.) The first patient was 40 years old and had pustular psoriasis and psoriatic arthritis. He was treated with six sessions of HBO(2) (at 2.8 atmospheres of pressure for 60 minutes), which successfully controlled his symptoms. At the 18-month post-treatment follow up, the patient exhibited complete remission of psoriasis and marked improvement in psoriatic arthritis without medication. The second patient was 55 years old with extensive psoriatic lesions, and exhibited marked improvement within 15 sessions of HBO(2). No adverse effects of HBO(2) were identified.

HBO(2) may possess potential therapeutic efficacy in the management of psoriasis. We outline the pathogenesis of psoriasis and the selective anti-inflammatory and immunosuppressive effects of HBO(2). We hope that this will provide a basis for elucidating the mechanisms of action and consequently pave the way for further controlled studies.

Psoriasis is a relatively common, chronic and disabling skin disease, due to a disturbed proliferation and differentiation of keratinocytes, accompanied by vascular alterations and infiltration of inflammatory cells with a local T(H)1-type cytokine immune response. There is no cure, but several treatment options are available.

The treatment of psoriasis is far from being satisfactory, due to the impractical modalities of topical treatment and the suboptimal safety profile of the systemic treatments available. In the last few years, parallel to an improved understanding of the disease pathogenesis, there has been a boosting of research in new agents for the treatment of psoriasis. These new agents are the focus of this paper.

After a short review of the treatment options already available (mainly based on the available systematic reviews), we focused on agents that are still in clinical development (Phase I - III) and have not yet entered the market. For the purpose of this study, we systematically searched the main registries of ongoing trials up to August 2008.

The field is very dynamic, with both immunopharmacology of recombinant DNA techniques and more traditional small-molecule pharmacology actively delivering new agents. With the increasing number of new options, there is a need for research systems that enable to effectively collect long-term safety data on treated patients.

Chronic plaque psoriasis is the most common type of psoriasis and is characterised by redness, thickness and scaling. First line management of chronic plaque psoriasis is with topical treatments, including vitamin D analogues, topical corticosteroids, tar-based preparations, dithranol, salicylic acid and topical retinoids.

To compare the effectiveness, tolerability and safety of topical treatments for chronic plaque psoriasis with placebo; to compare vitamin D analogues with other topical treatments.

The Cochrane Skin Group's Trials Register was searched (2004/12). To update an unpublished 2002 review we also searched CENTRAL in The Cochrane Library (Issue 1,2005); MEDLINE (to 2005/02); EMBASE (to 2005/08); Science Citation Index (to 2005); Biosis (to 2005); Dissertation Abstracts (all publication years); Inside Conferences (all publication years); SIGLE (to 2005); National Research Register (all projects with a start date of 2001 to 2005); metaRegister of Current Controlled Trials.

Randomised trials comparing treatments against placebo or against vitamin D analogues in people with chronic plaque psoriasis.

One author extracted study data and assessed study quality. A second author checked these data. We routinely contacted triallists and companies for missing data. We extracted data on withdrawals and adverse events.

The review included 131 RCTs with 21,448 participants. Vitamin D was significantly more effective than placebo, although there was a wide variation in effect size with the standardised mean difference (SMD) ranging from -0.82 (95% CI -1.34 to -0.29) to -1.90 (95% CI -2.09 to -1.71). With one exception, all corticosteroids performed better than placebo, with potent corticosteroids (SMD: -0.95 (95% CI: -1.11 to -0.80; I(2): 61.1%; 17 studies; 2386 participants)) having smaller benefits than very potent corticosteroids (SMD: -1.29 (95% CI: -1.45 to -1.13; I(2): 53.2%; 11 studies; 1571 participants)). Dithranol and tazarotene performed better than placebo. Head-to-head comparisons of vitamin D against potent or very potent corticosteroids found no significant differences. However, combined treatment with vitamin D /corticosteroid performed significantly better than either vitamin D alone or corticosteroid alone. Vitamin D performed better than coal tar, but findings relative to dithranol were mixed. Potent corticosteroids were less likely than vitamin D to cause local adverse events. No comparison of topical agents found a significant difference in systemic adverse effects.

Corticosteroids perform as well as vitamin D analogues and are associated with a lower incidence of local adverse events. Further research is required to inform long-term maintenance treatment.

Psoriasis affects 1-3% of the population, in some people causing changes to the nails and joints in addition to skin lesions.

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of systemic drug treatments, topical drug treatments, and non-drug treatments (other than ultraviolet light) for chronic plaque psoriasis? What are the effects of ultraviolet light treatments for chronic plaque psoriasis? What are the effects of combined treatment with drugs plus ultraviolet light on chronic plaque psoriasis? What are the effects of combined systemic plus topical drug treatments for chronic plaque psoriasis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

We found 122 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, adding calcipotriol (topical) to psoralen plus ultraviolet light A or ultraviolet light B, adding oral retinoids to psoralen plus ultraviolet A (PUVA), alefacept, balneotherapy, ciclosporin, dithranol, T cell-targeted therapies, cytokine blocking agents, emollients (alone or plus ultraviolet light B), etanercept, fish oil supplementation, fumaric acid derivatives, Goeckerman treatment, heliotherapy, infliximab, Ingram regimen, keratolytics (salicylic acid, urea), leflunomide, methotrexate, oral pimecrolimus, phototherapy plus balneotherapy, psoralen plus ultraviolet A, psychotherapy, oral retinoids (alone or with ultraviolet light B), systemic drug treatments plus topical vitamin D derivatives, tars, tazarotene, topical corticosteroids (alone or plus oral retinoids), topical Vitamin D derivatives, ultraviolet light A, and ultraviolet light B.

Vitamin D insufficiency during winter is common in the Nordic countries. Heliotherapy (HT) may heal atopic dermatitis (AD) but its effect on vitamin D balance has not been examined.

To study the effect of HT on serum calcidiol (25-hydroxyvitamin D) concentration and on healing of AD.

Twenty-three adult patients with AD received a 2-week course of HT in the Canary Islands in either January or March 2005. Daily solar ultraviolet (UV) radiation was measured and personal UV exposure calculated as standard erythema doses (SED). Blood samples were taken during HT and during a 1-2 month follow-up. Serum calcidiol concentration was measured by radioimmunoassay. Healing of AD was examined by SCORAD index.

Before HT 17 (74%) AD patients had vitamin D insufficiency (calcidiol < 50 nmol L(-1)) and four patients high (> 80 nmol L(-1)) serum calcidiol values. The median personal UV dose during the 2-week HT course was 60 SED in the January group and 109 SED in the March group. Serum calcidiol concentration increased significantly in both groups, by 13.4 and 24.0 nmol/L(-1), respectively, and after HT only four (17%) patients had vitamin D insufficiency. SCORAD improved from 34 to 9 in the January HT group and from 30 to 9 in the March group.

A 2-week course of HT significantly improved vitamin D balance by increasing serum calcidiol concentration, and caused a marked healing of AD. These parallel positive responses should be taken into account when the benefits of HT are considered.

Management of psoriasis begins with identification of the extent of cutaneous disease. However, a holistic, contractual approach to treatment is encouraged, with particular reference to psychosocial disability and quality-of-life issues. The presence of psoriasis on palms, soles, body folds, genitals, face, or nails, and concomitant joint disease, are also important when considering treatment options. An evidence-based approach is essential in delineating differences between the many available treatments. However, archaic approaches, especially combinational ones, are routinely used by some clinicians, with inadequate prospective or comparative evidence. Treatments currently available are: topical agents used predominantly for mild disease and for recalcitrant lesions in more severe disease; phototherapy for moderate disease; and systemic agents including photochemotherapy, oral agents, and newer injectable biological agents, which have revolutionised the management of severe psoriasis. Other innovative treatments are undergoing clinical studies, with the aim of maintaining safe, long-term control of the condition.

Becocalcidiol is a vitamin D(3) analogue which has not caused hypercalcaemia or significant irritation in preclinical trials.

To evaluate the efficacy and safety of two dosing regimens of becocalcidiol ointment (low dose = 75 microg g(-1) once daily for 8 weeks; high dose = 75 microg g(-1) twice daily for 8 weeks) in the treatment of plaque-type psoriasis.

One hundred and eighty-five subjects with chronic plaque-type psoriasis affecting 2-10% of their body surface area took part in a multicentre, double-blind, parallel-group, vehicle-controlled, randomized controlled trial comparing topical application of placebo, becocalcidiol 75 microg g(-1) once daily (low dose) or becocalcidiol twice daily (high dose) for 8 weeks. Main outcomes included Physician's Static Global Assessment of Overall Lesion Severity (PGA) score; Psoriasis Symptom Severity (PSS) score; adverse events; and laboratory assessment.

In the intent-to-treat population at week 8, high-dose becocalcidiol was statistically superior to vehicle [P = 0.002; 95% confidence interval (CI) 6.7-32.2], with 16 of 61 (26%) subjects achieving a PGA score of clear or almost clear. Greater improvement in PSS score was seen with high-dose becocalcidiol than with vehicle, but this result did not quite achieve statistical significance (P = 0.052; 95% CI -16.2 to 0.1). In all groups, therapy was safe and well tolerated, with fewer subjects experiencing irritation than is reported in studies using calcipotriol.

Treatment with high-dose topical becocalcidiol for 8 weeks led to almost or complete clearing of moderate plaque-type psoriasis in over a quarter of patients. Therapy was safe and well tolerated.

We have previously reported that 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) can selectively suppress key functions of interferon-gamma (IFN-gamma) activated macrophages. To further explore this mechanism for its relevance in vivo, we investigated an infection model that crucially depends on the function of IFN-gamma activated macrophages, the infection with the intracellular protozoan Leishmania major. 1Alpha,25(OH)2D3 treatment of L. major infected macrophages demonstrated a vitamin D receptor (Vdr) dependent inhibition of macrophage killing activity. Further analysis showed that this was a result of decreased production of nitric oxide by 1alpha,25(OH)2D3-treated macrophages due to Vdr-dependent up-regulation of arginase 1 expression, which overrides NO production by Nos2. When analyzing the course of infection in vivo, we found that Vdr-knockout (Vdr-KO) mice were more resistant to L. major infection than their wild-type littermates. This result is in agreement with an inhibitory influence of 1alpha,25(OH)2D3 on the macrophage mediated host defense. Further investigation showed that Vdr-KO mice developed an unaltered T helper cell type 1 (Th1) response on infection as indicated by normal production of IFN-gamma by CD4+ and CD8+ T cells. Therefore, we propose that the absence of 1alpha,25(OH)2D3-mediated inhibition of macrophage microbicidal activity in Vdr-KO mice results in increased resistance to Leishmania infection.

Calcitriol and calcipotriol are widely used in the topical treatment of psoriasis. However, studies comparing both treatment modalities are scarce. Especially, there are almost no studies comparing the effects on epidermal cell populations in a quantitative manner.

The aim of this study was to quantitatively compare the effects of topical calcitriol and topical calcipotriol on clinical scores and epidermal subpopulations.

From five patients with stable plaque psoriasis, skin biopsies were taken from two symmetrical regions on the trunk or extremities before and after treatment with either calcitriol or calcipotriol. Frozen sections were labelled immunofluorescently using direct immunofluorescence for beta-1 integrin and the Zenon labelling technique for keratin (K) 6, K10 and K15. The digital photographs of the stained sections were quantitatively analysed and the results of both treatments were compared.

The clinical SUM-score improved significantly for both the calcitriol- and the calcipotriol-treated lesions. In the calcipotriol-treated group the expression of K10 and K15 increased and the expression of K6 decreased significantly. No changes were seen for the marker beta-1 integrin. In the calcitriol-treated group none of the markers changed significantly. A tendency towards significance was seen for the changes in the expression of K6 and K15 in favour of calcipotriol.

Both calcitriol and calcipotriol gave a significant improvement in clinical scores. However, treatment with calcipotriol resulted in a normalization of K6, K10 and K15, whereas treatment with calcitriol did not. Comparison of both treatments showed a tendency towards significance for the above-mentioned markers for calcipotriol only.

The vitamin D receptor (VDR) is a member of the large family of nuclear receptor transcription factors and specifically binds the micronutrient-derived hormone 1alpha,25(OH)2D3. A central endocrine role for this receptor in bone health was established at the beginning of the 20th century. Over the last 25 years, additional roles, perhaps through autocrine and paracrine mechanisms, have been established for VDR to regulate cell proliferation and differentiation, and more recently to exert immunomodulatory and antimicrobial functions. These findings, from in vitro and in vivo experiments, have generated considerable interest in targeting the VDR in multiple therapeutic settings. As with many potential therapeutics, it has also become clear that cells and tissues may also display de novo and acquired mechanisms of resistance to these actions. Consequently, a range of experimental and clinical options are being developed to bring about more targeted actions, overcome resistance and enhance efficacy of VDR-centred therapeutics.

The choice of drug treatment for an individual patient is a complex matter. In the case of psoriasis there is a range of treatments available, with varying degrees of efficacy and risk of adverse events.

To examine the extent to which the attributes of a treatment affect dermatologists' choice of drug therapy and explore the magnitude and nature of the trade-offs between the risks and benefits of treatment.

A postal questionnaire was sent to members of the British Association of Dermatologists (BAD). The questionnaire used a discrete choice experiment (DCE) to elicit dermatologists' preferences for the treatment of psoriasis. In all, 227 dermatologists completed the questionnaire. The results indicated that time to moderate improvement, time to relapse, risk of hypertension, liver damage, skin cancer and skin irritation were all important factors affecting dermatologists' choice of treatment. Comparing the coefficients for the different side-effects indicated that the dermatologists considered the risk of liver damage to be the most important side-effect, followed by the risk of skin cancer. The time to achieve a moderate (50%) improvement in psoriasis was prioritized over the time to relapse.

This study has provided novel insight into the trade-offs that dermatologists face when selecting treatment for psoriasis patients. Future research should explore the extent to which dermatologists' preferences for treatment match those of psoriasis sufferers.

The two-compound product calcipotriol/betamethasone dipropionate is arising as a first-line treatment for mild-to-moderate plaque psoriasis. Its beneficial action is attributed to the synergistic effect of its components on keratinocyte proliferation and differentiation, and on inflammation. The good tolerability of the two-compound product is thought to be due to the anti-inflammatory effect of betamethasone. Evidence from short-term (4-12 weeks) and long-term use (> 1 year) has shown a good safety profile. Areas such as the face or skin folds, which are sensitive to the components of the combination, should be avoided. Finally, it is unsuitable for use in unstable psoriasis, in which potent steroids may lead to an increased inflammatory response.

The effect of the established antipsoriatic treatment with topical calcipotriol (with a maximum of 100 g per week) in addition to systemic treatment with alefacept, a new biological agent for psoriasis, on epidermal cell populations in the psoriatic lesion was investigated using a combination of the Zenon labelling technique and microscopic image analysis. Epidermal cell populations were measured quantitatively with this sensitive method.

Frozen sections of non-treated psoriatic epidermis and psoriatic epidermis treated with either alefacept intramuscular or alefacept intramuscular in combination with topical calcipotriol for 12 weeks were compared immunohistochemically. Antibodies against keratin 6, 10 and 15 were labelled with the Zenon technique, whereas antibodies against the Ki-67 antigen and beta-1 integrin were covalently Fluorescein Isothiocyanate (FITC)-labelled. Using image analysis, these markers were measured in the epidermis in a standardized manner.

Treatment of psoriasis with alefacept resulted in a good clinical response in several patients and in a normalization of epidermal expression of the immunohistochemical parameters for differentiation and proliferation. The addition of topical calcipotriol resulted in a faster clinical improvement with a similar overall clinical response and a similar response of epidermal cell populations as compared to treatment with alefacept monotherapy after 12 weeks of treatment. This study also suggests that the appearance of keratin 15 has a predictive value for the duration of remission. It can be concluded that the addition of a low-dose calcipotriol treatment does not contribute to the clinical efficacy of alefacept, both at the clinical level and with respect to markers for epidermal proliferation and differentiation.

Daivobet is a once-daily treatment of psoriasis vulgaris containing betamethasone dipropionate and calcipotriol in a new ointment vehicle.

To assess the cost-effectiveness of once-daily treatment with Daivobet (4 weeks) followed by calcipotriol (4 weeks) compared to tacalcitol (8 weeks).

Resource utilization was assessed within a double-blind 8-week clinical trial (all treatments for psoriasis, adverse events and concomitant dermatological medication), estimated from the French societal perspective.

Total direct medical costs for psoriasis were comparable (Daivobet: EUR 107.53 and tacalcitol EUR 113.50) despite a higher acquisition cost for Daivobet. The probability of > or =75% reduction in the Psoriasis Area and Severity Index (effectiveness criterion) was 46.6% with Daivobet and 13.9% with tacalcitol at 4 weeks, and 44.6 and 23.8%, respectively, at 8 weeks (both: p < 0.001). Over 8 weeks, Daivobet was almost twice as cost-effective as tacalcitol (EUR 241.22 per successful treatment vs. EUR 476.70); this result was robust to sensitivity assumptions.

Daivobet is more effective and less costly than tacalcitol for treating psoriasis.