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BackgroundVascular dysfunction is a significant contributor to the pathophysiology of psoriasis. Some individuals have variation within the gene for vascular endothelial growth factor-A (VEGF-A), which confers an increased risk of developing psoriasis and having a severe disease phenotype, and may determine responsiveness to treatment.AimTo determine whether patients with psoriasis have alterations in cutaneous microvascular anatomy and physiology due to expression of VEGF and whether laser Doppler imaging has utility in the assessment of this.MethodsTwelve adult volunteers with Type 1 chronic plaque psoriasis underwent laser Doppler imaging of plaque and uninvolved skin. Skin biopsies were taken from the areas imaged for immunohistochemistry, including blood and lymphatic vessel markers, and VEGF-A isotype analysis (VEGF-A121, VEGF-A165 and VEGF-D). Venous blood was collected for DNA extraction, VEGF-A genotyping and peripheral blood mononuclear cell culture.ResultsMean blood vessel area (P < 0·01), number of blood vessels (P < 0·001), number of lymphatic vessels (P < 0·001) and blood flow (P < 0·001) was significantly increased in psoriasis plaques, as was expression of VEGF-A121 (P < 0·01), VEGF-A165 (P < 0·04) and VEGF-D (P < 0·01). Blood flow within psoriasis plaques was independent of their increased vascularity (P < 0·01) and may be associated with baseline productivity of VEGF. The number of blood vessels within uninvolved skin in patients with psoriasis was associated with the VEGF-A (rs833061) genotype (P = 0·01), in a relationship suggesting an allele dosing effect.ConclusionNoninvasive imaging of blood flow may help determine the cutaneous vascular signature for individual patients. This may be a useful prognostic indicator of psoriasis susceptibility and severity, and thus support selection of treatments.

The physiology and pathology of the skin are influenced by daily oscillations driven by a master clock located in the brain, and peripheral clocks in individual cells. The pathogenesis of psoriasis is circadian-rhythmic, with flares of disease and symptoms such as itch typically being worse in the evening/night-time. Patients with psoriasis have changes in circadian oscillations of blood pressure and heart rate, supporting wider circadian disruption. In addition, shift work, a circadian misalignment challenge, is associated with psoriasis. These features may be due to underlying circadian control of key effector elements known to be relevant in psoriasis such as cell cycle, proliferation, apoptosis and inflammation. Indeed, peripheral clock pathology may lead to hyperproliferation of keratinocytes in the basal layers, insufficient apoptosis of differentiating keratinocytes in psoriatic epidermis, dysregulation of skin-resident and migratory immune cells and modulation of angiogenesis through circadian oscillation of vascular endothelial growth factor A (VEGF-A) in epidermal keratinocytes. Chronotherapeutic effects of topical steroids and topical vitamin D analogues have been reported, suggesting that knowledge of circadian phase may improve the efficacy, and therapeutic index of treatments for psoriasis. In this viewpoint essay, we review the current literature on circadian disruption in psoriasis. We explore the hypothesis that psoriasis is circadian-driven. We also suggest that investigation of the circadian components specific to psoriasis and that the in vitro investigation of circadian regulation of psoriasis will contribute to the development of a novel chronotherapeutic treatment strategy for personalised psoriasis management. We also propose that circadian oscillations of VEGF-A offer an opportunity to enhance the efficacy and tolerability of a novel anti-VEGF-A therapeutic approach, through the timed delivery of anti-VEGF-A drugs.

Background: Junior doctors are required to make career decisions at an early stage in their postgraduate training. Trainees also feel inadequately prepared for the transition to consultant roles. Aim: To explore the key factors influencing the choice of dermatology as a postgraduate medical career and to identify the training needs required for transition from trainee to consultant. Methods: An online questionnaire was designed to identify (i) why trainees chose a postgraduate medical career in dermatology, and (ii) the training required for transition from trainee to consultant. Results: In total, 46 responses were received from trainees in their first to final years (ST3–6), of whom 89% had undertaken an undergraduate dermatology placement, with a median duration of 2 weeks. Dermatology was considered as a career during medical school by 61% of trainees, and 41% confirmed their decision to pursue a career in dermatology during foundation training. The most influential factors involved in speciality selection were first, enjoyment of the work, second, postgraduate experience and equal third, the variety of the speciality and the regularity of working hours (P

Background: As biosimilars have become available in various parts of the world, the International Psoriasis Council has reviewed aspects of their use. Objective: To provide consensus statements from the Biosimilar Working Group about the use of biosimilars in patients with psoriasis. Methods: A semiqualitative structured process was employed to approve the consensus statements on biosimilars using the nominal group technique. The final statements were validated by a survey of the paricipants. The approval of the consensus statements was predefined as >80% positive opinions. Results: A consensus was reached in 36/38 statements regarding regulatory considerations, extrapolation of indication, interchangeability, substitution at the pharmacy level, pharmacovigilance, traceability, naming, biosimilar policy, education, and cost of biosimilars. Example statements include “Switching a stable patient from a reference product to a biosimilar product is appropriate if the patient and physician agree to do so” and “Patients and patients' organisations should be involved in all decision making and policy development about the use of biosimilars.” Conclusion: The International Psoriasis Council Biosimilar Working Group provides consensus statements for the use of biosimilars in the treatment of patients with psoriasis. We suggest that these statements provide global guidance to clinicians, healthcare organizations, pharmaceutical companies, regulators, and patients regarding the development and use of biosimilars in patients with psoriasis.

Background/Aims: Vascular endothelial growth factor (VEGF), a key mediator of angiogenesis, plays a key role in physiological processes and is a major contributor to several diseases including cancer and psoriasis. Anti-VEGF therapies are widely used as cancer and ophthalmological treatments. There is some evidence that VEGF blockade may have utility in the management of psoriasis, although their potential has been largely unexplored. We hypothesized that a human skin organ culture could provide a stable ex vivo model in which the cutaneous microvascular network could be studied and experimentally manipulated. Methods: Punch biopsies (3 mm) of skin, donated by healthy individuals (39–72 years old, n = 5), were incubated with monoclonal antibody (mAb) to human VEGF (bevacizumab) at doses based on data from animal and clinical studies. After 3-day culture, cell death and proliferation as well as vascular endothelial cell changes were assessed using quantitative immunohistomorphometry. Results: Anti-VEGF mAb at 0.8 mg/mL induced a significant increase in cleaved caspase-3 expression in CD31+ cells (p < 0.05). None of the doses tested increased TUNEL or decreased Ki-67 expression in the basal layer of the epidermis, confirming the model’s viability. In addition, the lactate dehydrogenase (LDH) assay showed no increase in LDH activity in treated samples compared to untreated control. The highest anti-VEGF mAb dose (0.8 mg/mL) induced an increase in TUNEL expression in the upper epidermis, which did not correlate with caspase-3 immunoreactivity. Further investigation revealed that anti-VEGF mAb did not change the expression of markers of terminal differentiation such as keratin 10, filaggrin, and involucrin, suggesting that VEGF depletion does not affect keratinocyte terminal differentiation. In contrast to the control group, levels of VEGF protein were undetectable in the culture supernatant of samples treated with 0.8 mg/mL of anti-VEGF mAb, suggesting sufficient dose. Conclusion: Our pilot study provides the first evidence that anti-VEGF therapy promotes endothelial cell apoptosis in human skin ex vivo. Our pragmatic human skin organ culture assay offers a valuable tool for future preclinical endothelial cell and translational microvascular network/anti-angiogenesis research in human skin.

Background: Patients with psoriasis have a level of physical activity below that recommended for cardiovascular health, which is significantly limited by severity of disease and other psoriasis-specific barriers.Objectives: We hypothesised that physical activity is important for cardiovascular health in patients with psoriasis and that its objective measurement could have clinical utility. The purpose of this study was to explore whether physical activity influences the risk of cardiovascular disease in patients with psoriasis. Methods: 242 patients with chronic plaque psoriasis were recruited. History, examination and physical activity were assessed and arteriography, the non-invasive measurement of arterial function, was performed for each participant.Results: We observed a significant relationship between volume of physical activity and the likelihood of future cardiovascular disease (CVD) as measured by pulse wave velocity (PWV; p=0.017). We identified a significant relationship between health-promoting levels of physical activity (pConclusion: Our study describes a significant relationship between exercise, cardiorespiratory fitness and PWV, a preclinical indicator of future CVD risk, in patients with psoriasis. The DRA offers a non-invasive, objective, measurement of exercise adherence which could have clinical utility in the future.

Summary Background Expression of vascular endothelial growth factor A (VEGFA) is increased in chronic inflammatory skin diseases, including psoriasis, and loci for two VEGFA single nucleotide polymorphisms are associated with early‐onset psoriasis (presenting before the age of 40 years). Studies have suggested that expression of placenta growth factor (PGF) is also upregulated in cutaneous inflammation and that VEGFA‐mediated angiogenesis may be dependent on the simultaneous presence of PGF within the skin. Aim To elucidate the biological importance of PGF in psoriasis. Methods We investigated whether two commonly occurring PGF polymorphisms were associated with early‐onset psoriasis and the genetic interaction between VEGFA and PGF in psoriasis. Results We observed a significant (P = 0.04) association between rs2268614 TT and rs2268615 AA genotypes of PGF and early‐onset psoriasis. In addition, genetic complement, comprising the PGF rs2268615 AA genotype and the VEGFA −460 (rs833061) T allele, was significantly associated with the development of early‐onset psoriasis (P

Purpose of Review: Over the last several years, major changes have occurred in Europe regarding the use of biosimilars. Some countries such as Norway, Denmark, and the United Kingdom (UK) have a relatively high market penetration of biosimilars, whereas in other European countries, biosimilar uptake is low. The objectives of this review are to describe the use of biosimilars in selected European countries, using “real-life” information from members of the International Psoriasis Council (IPC) who are key opinion leaders in dermatology. The use of biosimilars for patients with psoriasis is continuously discussed and reviewed by the IPC, through in-person meetings by members of the Biosimilar Working Group (BSWG). Recent Findings: In preparation for this paper, we surveyed the use of biosimilars for patients with psoriasis through European BSWG members, who were asked to describe the situation in their countries. The survey collected information from each IPC councilor regarding the use of biosimilars currently on the market, guidelines for interchangeability, traceability, and naming of these agents. In addition, information regarding pricing, access, and physician/patient education was obtained. The status of biosimilars was discussed at an IPC biosimilar working group roundtable event which was held in Stockholm on June 28th, 2018. Summary: With increased use of biosimilars likely in the future, the IPC will continue to provide leadership, education, and guidance for dermatologists to maximize the challenges presented by the adoption of biosimilars into clinical practice and improve the choice of biologic treatment for patients with moderate-severe psoriasis.

Background: Psoriasis impacts the health and psychosocial functioning of patients, conferring a significant economic burden on healthcare systems. There remain unmet needs in psoriasis care, which if addressed by research, could improve clinical outcomes. Aim: To research priorities and identify a health service delivery model from the UK Psoriasis Priority Setting Partnership (PsPSP). Methods: Between July 2017 and November 2018, we invited people with lived experience of psoriasis and healthcare professionals to (i) identify unmet needs, and (ii) prioritize the order in which these should be addressed by research. We collaborated with the Psoriasis Association and used methodology established by the James Lind Alliance, which pioneers the joint setting of research priorities by patients and clinicians worldwide. Results: In our initial harvesting survey (Survey 1), 2133 questions were submitted by 805 individuals. Submissions that had not been answered by research (true uncertainties) were supplemented with evidence gaps from systematic reviews/guidelines published in the previous 5 years and refined to produce 55 indicative questions. Voting in Survey 2, by 1154 individuals, enabled a shortlist of questions, which were prioritized during the final workshop to produce a top 20 list of research questions. Submissions on health service delivery (5.8% of the total submissions), which were analysed separately, described a blueprint for psoriasis care. Conclusions: The PsPSP will inform the translational research agenda, ensuring that future research is relevant for the needs of people with psoriasis and those who manage the disease. Submissions on health service delivery describe a model of holistic, patient-focused care providing high-quality, effective management for patients with psoriasis.

Psoriasis is an immune-mediated skin disorder associated with severe systemic co-morbidities. While IL-36 is a key disease driver, the pathogenic role of this cytokine has mainly been investigated in skin. Thus, its effects on systemic immunity and extra-cutaneous disease manifestations remain poorly understood. To address this issue, we investigated the consequences of excessive IL-36 activity in circulating immune cells. We initially focused our attention on generalised pustular psoriasis (GPP), a clinical variant associated with pervasive up-regulation of IL-36 signalling. By undertaking blood and neutrophil RNA-sequencing, we demonstrated that affected individuals display a prominent Type-I IFN signature, which correlates with abnormal IL-36 activity. We then validated the association between IL-36 de-regulation and Type-I IFN over-expression in patients with severe psoriasis vulgaris (PsV). We also found that the activation of Type-I IFN genes was associated with extra-cutaneous morbidity, in both GPP and PsV. Finally, we undertook mechanistic experiments, demonstrating that IL-36 acts directly on plasmacytoid dendritic cells (pDCs), where it potentiates Toll-like Receptor (TLR)-9 activation and IFN-α production. This effect was mediated by the up-regulation of PLSCR1, a phospholipid scramblase mediating endosomal TLR-9 translocation. These findings identify an IL-36/Type-I IFN axis contributing to extra-cutaneous inflammation in psoriasis.

Summary Background Psoriasis is associated with an increased risk of cardiovascular disease. Despite recommendation that exercise is important for cardiorespiratory fitness, patients with psoriasis avoid participation in physical activities for reasons that are, as yet, unclear. Objectives This study investigated the relationship between psoriasis‐specific experiences and self‐reported patterns of exercise, hypothesizing that individuals with psoriasis are less likely to engage in physical activity for reasons that are related to their psoriasis. Methods In total 404 patients with chronic plaque psoriasis were recruited. History, examination and physical activity were assessed for each participant. Results Overall, 52·8% (n = 188) of patients with psoriasis aged 18–65 years and 66% (n = 37) of those aged > 65 years engaged in less than the recommended amount of physical activity for cardiorespiratory fitness. As the severity and psychosocial impact of psoriasis increased, the participation in exercise (of all intensities) decreased. There was a significant negative correlation between Psoriasis Area and Severity Index and total activity in women aged 18–65 years (r = −0·19, 95% confidence interval −0·36 to 0; P = 0·04) and a significant negative correlation between physical activity and Dermatology Life Quality Index (DLQI) in all participants (r = −0·11, 95% confidence interval −0·21 to 0; P = 0·04). Individual components of the DLQI identified barriers to physical activity including skin sensitivity and reluctance to participate in leisure activities. Conclusions Psoriasis‐specific factors – severity, skin sensitivity, clothing choice, participation in social/leisure activities, and treatments – contribute to exercise avoidance and may augment the increased risk of cardiovascular disease in patients with psoriasis., What is already known about this topic? Psoriasis is associated with an increased prevalence of risk factors for cardiovascular disease.Despite recommendation that exercise is important for cardiorespiratory fitness, patients with moderate‐to-severe psoriasis participate in very little physical exercise for reasons that are, as yet, unclear. What does this study add? This study quantifies the significant lack of engagement with exercise in the population of people with psoriasis.Physical activity in those with psoriasis is significantly influenced by psoriasis severity, quality of life and a number of previously unrecognized psoriasis‐specific barriers. What is the translational message? Supporting patients with psoriasis to undertake regular physical activity could directly benefit weight management, cardiovascular disease and risk of metabolic syndrome, and increase wellbeing and psychosocial functioning. Linked Comment: Jarrett.Br J Dermatol 2020; 183:988–989. Plain language summary available online

Engaging global key opinion leaders, the International Psoriasis Council (IPC) held a day-long roundtable discussion with the primary purpose to discuss the treatment goals of psoriasis patients and worldwide barriers to optimal care. Setting clear expectations might ultimately encourage undertreated psoriasis patients to seek care in an era in which great gains in therapeutic efficacy have been achieved. Here, we discuss the option for early treatment of all categories of psoriasis to alleviate disease impact while emphasizing the need for more focused attention for psoriasis patients with mild and moderate forms of this autoimmune disease. In addition, we encourage policy changes to keep pace with the innovative therapies and clinical science and highlight the demand for greater understanding of treatment barriers in resource-poor countries.

The introduction of biological drugs for the treatment of patients with psoriasis has revolutionized treatment paradigms and enabled numerous patients to achieve disease control with an acceptable safety profile. However, the high cost of biologics limits access to these medications for the majority of patients worldwide. In recent years, the introduction of biosimilars for inflammatory diseases has become a fast evolving field. The future use of biosimilars offers the potential for decreased cost and increased access to biologics for patients with psoriasis. For approval of biosimilars, different regulatory agencies use highly variable methods for definition, production, approval, marketing and postmarketing surveillance. Due to potential interchangeability between biologics and biosimilars, traceability and pharmacovigilance are required to collect accurate data about adverse events in patients with psoriasis; spontaneous reporting, registries and use of 'big data' should facilitate this process on a global basis. The current article describes biosimilar regulatory guidelines and examples of biosimilar uptake in clinical practice in several countries around the world. As it is apparent that biological therapy treatment decisions may become more physician independent, the International Psoriasis Council recommends that dermatologists should take an active role in the development of biosimilar prescribing policies with their respective healthcare settings and government agencies.

Summary Background Studies assessing cardiovascular disease (CVD) risk factors in patients with psoriasis have been limited by selection bias, inappropriate controls or a reliance on data collected for clinical reasons. Objectives To investigate whether screening for CVD risk factors in patients with psoriasis in primary care augments the known prevalence of CVD risk factors in a cross‐sectional study. Methods Patients listed as having psoriasis in primary care were recruited, screened and risk assessed by QRISK2. Results In total, 287 patients attended (mean age 53 years, 57% women, 94% white British, 22% severe disease, 33% self‐reported psoriatic arthritis). The proportion with known and screen‐detected (previously unknown) risk factors was as follows: hypertension 35% known and 13% screen‐detected; hypercholesterolaemia 32% and 37%; diabetes 6·6% and 3·1% and chronic kidney disease 1·1% and 4·5%. At least one screen‐detected risk factor was found in 48% and two or more risk factors were found in 21% of patients. One in three patients (37%) not previously known to be at high risk were found to have a high (> 10%) 10‐year CVD risk. Among the participants receiving treatment for known CVD risk factors, nearly half had suboptimal levels for blood pressure (46%) and cholesterol (46%). Conclusions Cardiovascular risk factor screening of primary care‐based adults with psoriasis identified a high proportion of patients (i) at high CVD risk, (ii) with screen‐detected risk factors and (iii) with suboptimally managed known risk factors. These findings need to be considered alongside reports that detected limited responses of clinicians to identified risk factors before universal CVD screening can be recommended., What's already known about this topic? Several studies have suggested that patients with psoriasis have a greater number of risk factors for cardiovascular disease (CVD) and a higher risk for vascular events compared with the general population.However, the prevalence data used to support systematic CVD risk factor screening in psoriasis have been limited by selection bias, inappropriate choice of control groups or reliance on risk factors measured for other clinical reasons. What does this study add? Cardiovascular risk factor screening of primary care‐based adults with psoriasis identified a high proportion of patients (i) at high CVD risk, (ii) with screen‐detected risk factors and (iii) with suboptimally managed known risk factors.These findings need to be considered alongside reports that detected limited responses of clinicians to identified risk factors before universal CVD screening can be recommended. Plain language summary available online

Psoriasis is an immune-mediated skin disorder associated with severe systemic co-morbidities. Both chronic and acute forms of the disease are characterised by abnormal interleukin (IL)-36 signalling. While the mechanisms whereby IL-36 promotes cutaneous inflammation are well established, its systemic effects have not been investigated. To address this issue, we initially measured leukocyte gene expression in generalised pustular psoriasis, an acute disease variant caused by mutations of the IL-36 receptor antagonist. By undertaking whole-blood and neutrophil RNA-sequencing in affected individuals, we identified a Type-I IFN signature, which correlated with IL-36 signalling up-regulation. We then validated these observations in patients with chronic plaque psoriasis. Finally, we demonstrated that IL-36 acts directly on plasmacytoid dendritic cells, where it potentiates Toll-like Receptor (TLR)-9 activation and IFN-alpha production. This effect was mediated by the induction of PLSCR1, an endosomal TLR-9 transporter. These results define an IL-36/TLR-9/Type-I IFN axis that could be targeted for the treatment of psoriasis co-morbidities.

As a long-term condition, psoriasis demands significant personal and professional input for optimal self-management. Low levels of well-being and high levels of psychological distress in patients with psoriasis are associated with reduced resources for self-care. Patient-reported outcome (PRO) measures can be used to assess physical, social and psychological functioning in order to guide treatment. In this article, we systematically reviewed the development and validation of existing PRO measures. PubMed (Medline), PsycINFO and CINAHL were searched systematically using predefined search terms. The search was limited to articles in the English language relating to human subjects. Articles were selected for full review through explicit inclusion/exclusion criteria. PRO measures were critically reviewed in accordance with the published guidelines and theory on the development and validation of PROs. The search identified 967 abstracts; 71 of these articles met the criteria for full review. In these 71 articles, 45 PRO measures were found: 16 were specific to psoriasis, 21 assessed other dermatological conditions and eight were developed for generic nondermatological health conditions. The review revealed several limitations of the existing measures, including: (i) a composite structure assessing multiple, poorly-defined concepts; (ii) a lack of evidence for face and content validity; (iii) a failure to include both patient and clinician perspectives and requirements and (iv) a lack of evidence regarding the feasibility and acceptability for patients and physicians. No single PRO measure with adequate evidence of validity, reliability and sensitivity to change captures patient well-being in psoriasis. A valid, sensitive, specific and acceptable PRO that assesses the full impact of psoriasis on well-being is needed for the comprehensive clinical management of psoriasis.

BACKGROUND: Psoriasis affects over two million people in the UK. It confers a significant psychological and social impact on individuals and an associated high economic cost to the National Health Service. There are many unanswered questions about psoriasis.OBJECTIVES: 1. To develop a protocol in order to work with patients, families, carers and healthcare professionals to identify psoriasis uncertainties. 2. To agree by consensus a top ten list of psoriasis uncertainties. 3. To disseminate prioritised unanswered questions to researchers and funders to promote work focused on answering the uncertainties considered most important by stakeholders.METHODS: A Psoriasis Priority Setting Partnership has been established to gather psoriasis uncertainties following the transparent methodology advocated by the James Lind Alliance. A Steering Group composed of stakeholders will disseminate a survey to patients, families, carers and healthcare professionals to collect information on important psoriasis questions. After removing duplications, uncertainties will be collated and checked against existing evidence to determine whether any have already been resolved. 'True uncertainties' will be circulated to stakeholders in a second survey where they will be ranked by importance. At a final workshop, information will be distilled to generate a top ten list of uncertainties.RESULTS: By following the protocol outlined in this paper a prioritised list of uncertainties will be identified which will be inform the psoriasis research agenda.CONCLUSIONS: Research, targeted to address priorities identified by a range of stakeholders is imperative. This project will inform policymakers and research funding bodies of what really matters to these groups. This article is protected by copyright. All rights reserved.

Summary Background Psoriasis is an inflammatory long‐term condition involving comorbidities, unhealthy lifestyle and significant life impact. Patients’ understanding of psoriasis is limited and support lacking. The Common‐Sense Model of Self‐Regulation of Health and Illness emphasizes the role of illness and treatment beliefs on coping and self‐management. New ‘Pso Well®’ patient materials informed by the model, addressed psoriasis as a long‐term condition, medication management and lifestyle behaviours. Objectives To investigate whether Pso Well® materials (i) broaden understanding of psoriasis without increasing anxiety; (ii) are acceptable; and (iii) comprise features that appear to effect change. Methods The Revised Illness Perceptions Questionnaire (IPQ‐R modified) and the Hospital Anxiety and Depression Scale (HADS) were administered in patients before and after intervention. Numerical rating scales assessed perceptions of change in understanding and anxiety resulting from engagement with the materials. Qualitative interviews explored acceptability and perceived ‘active ingredients’. Results Fifty‐five patients completed pre‐ and postintervention questionnaires (56% female; median age 59 years). Postintervention, a large effect size was indicated in two IPQ‐R domains – illness coherence [t(55) = −3·48, P = 0·001 (two‐tailed), η2 = 0·19] and personal control [t(55) = −2·98, P = 0·004 (two‐tailed), η2 = 0·14] – and a medium effect in one, treatment control [t(55) = −2·08, P = 0·042 (two‐tailed), η2 = 0·08]. HADS scores did not change. For numerical rating scales, 80% of participants reported increased understanding of psoriasis and none reported increased anxiety. Interviews with 19 patients indicated the materials were acceptable and usable. Factors reported to broaden understanding and promote engagement with self‐management included linking of related disease aspects, personally relevant content and high‐quality design. Conclusions High‐quality, theory‐based psoriasis materials are acceptable to patients and can improve understanding and sense of control without increasing anxiety., What's already known about this topic? Psoriasis is associated with comorbidities, unhealthy lifestyle and significant life impact.Patients’ understanding of psoriasis is limited, self‐management support is lacking and disengagement from healthcare services is common. What does this study add? The new, theory‐informed Pso Well® patient materials address psoriasis as a long‐term condition; medications management and lifestyle behaviour.The Pso Well® patient materials can increase understanding of psoriasis, promote feelings of self‐worth and encourage a desire to engage in self‐management and behaviour change, without increasing anxiety or depression. What are the clinical implications of this work? The Pso Well® patient materials could support clinical consultations by helping patients recognize the remitting–relapsing nature of psoriasis.This will help to improve understanding of the disease, as well as providing a clearer rationale for treatment adherence and lifestyle behaviour change. Linked Comment: Prinsen. Br J Dermatol 2017; 177:616–617

Psoriasis, a common disease affecting 2%-3% of the UK population, produces significant impairment of quality of life and is an immense burden on sufferers and their families. Psoriasis is associated with significant cardiovascular comorbidity and the metabolic syndrome. Angiogenesis, a relatively under-researched component of psoriasis, is a key factor in pathogenesis of psoriasis and also contributes to the development of atherosclerosis. Vascular endothelial growth factor (VEGF) is a well-established mediator of pathological angiogenesis which is upregulated in psoriasis. It is possible that, in patients with psoriasis, cutaneous angiogenesis may be both a marker for systemic vascular pathology and a novel therapeutic target. In this viewpoint study, the role of VEGF-mediated angiogenesis as a cause for cardiovascular events in patients with psoriasis is explored.

Introduction: Pimecrolimus is a calcineurin inhibitor which has a role in the treatment of psoriasis. However, it remains an off-license treatment, despite its potential use in patients with treatment-resistant psoriasis or in those who have had multiple adverse effects to other therapies. Areas covered: This review covers the efficacy and role of both topical and oral Pimecrolimus in the management of psoriasis and compares them to other available treatments. The paper provides a comprehensive review of the literature on topical and oral Pimecrolimus and its utility in the treatment of patients with psoriasis following literature searches via PubMed and Embase. Expert opinion: Topical Pimecrolimus is an effective, off-license treatment option particularly for facial and intertriginous psoriasis. Oral Pimecrolimus shows great promise as an alternative systemic treatment option, but Phase III trials are required before further recommendations can be made.

Psoriasis affects 1%-3% of the population in the United Kingdom and can convey significant detriment to the physical and mental health of sufferers. Plaques of psoriasis typically affect the extensor skin surfaces and scalp. Less frequently inverse psoriasis can affect more sensitive skin such as the face, genitals, and intertriginous areas. Psoriasis is incurable, but there are a range of treatment modalities that can be used to manage the condition. Treatment options include topical preparations, phototherapy, systemic therapy, and biological agents. Tacrolimus is a macrolide calcineurin inhibitor licensed for immunosuppression in transplant patients and topical administration in atopic dermatitis. Tacrolimus administered orally and in topical form has been shown to produce successful outcomes in patients with psoriasis. Topical tacrolimus is particularly effective for inverse psoriasis, which is likely to be due to the reduced level of induration seen in these psoriatic lesions, which allows greater skin penetrance, compared with hyperkeratotic plaques of psoriasis on the body. It is also notable that the areas affected by inverse psoriasis are more susceptible to adverse effects of topical corticosteroid therapy, and thus a topical preparation without the risk of skin atrophy, telangiectasia, and striae could be a valuable addition to current topical treatment options. Oral tacrolimus has shown efficacy in the treatment of severe, refractory psoriasis. Compared to ciclosporin, systemic tacrolimus may be more suited to a patient population with increased cardiovascular risk. This review will draw together the current literature on topical and oral tacrolimus for the treatment of psoriasis. Efficacy and safety have been evaluated by case reports and randomized controlled trials and comparisons have been made between tacrolimus therapy and standard treatment.

First described by John Debes(1) in 1968, visual literacy (VL) refers to the ability of an observer to derive meaning from images.(2) In addition to understanding the image itself, the wider meaning is considered and deeper critical thinking encouraged.(1,3) In contrast with other medical specialties, the interpretation of visual signs and gross pathology remains key to dermatological practice.(4) Diagnostic accuracy may be increased by careful observation without preconceptions.(4) Thus, description of lesions in dermatological practice may be considered as "the expression of pathological art".(5) On this basis we believe dermatologists should have fluent VL skills, which could be developed throughout their training. This article is protected by copyright. All rights reserved.

Psoriasis is a common chronic inflammatory disease of the skin that has a significant impact on quality of life. A small number of systemic therapies are well established in psoriasis management. These have immunosuppressive and/or anti-proliferative effects on the skin and immune system. As understanding of the pathogenesis of psoriasis has advanced over the last 2 decades, there has been clearer appreciation of the genetic, cellular and immunological components of disease expression, which has provided new insight into potential therapeutic targets, including the development of biological therapies. Biologics offer a unique opportunity to block or inhibit specific key components of psoriasis pathogenesis. The introduction of tumour necrosis factor (TNF).α and interleukin (IL)-12/-23 inhibitors has resulted in remarkable clinical responses in patients with severe psoriasis and has led to the development of a range of other cytokine modulators currently undergoing investigation. More recently, research in keratinocyte biology and immune cell function, particularly intracellular signalling, has afforded additional opportunities to develop a range of small-molecule oral preparations that may prove effective in disease control. This paper reviews current and emerging systemic treatments in the management of psoriasis.

Vascular endothelial growth factor (VEGF) mediates angiogenesis consequent to binding to VEGF receptors (VEGFRs) and is upregulated in patients with psoriasis. VEGF is also upregulated in other diseases characterised by angiogenesis including proliferative retinopathy and cancer. Several VEGF antagonists have been approved for the treatment of these conditions and may also have the potential to treat psoriasis.A PubMed literature search was performed to identify preclinical and clinical research regarding investigational VEGF antagonists for the treatment of psoriasis. Various agents have been reviewed including monoclonal antibodies against VEGF and VEGFRs, decoy anti-VEGF receptors and tyrosine kinase inhibitors that block the effects of VEGF/VEGFR binding.Several investigational drugs have demonstrated potential to treat psoriasis. Clinical observations of psoriasis remission following administration of bevacizumab, sunitinib and sorafenib in cancer patients are encouraging. Of particular interest is a novel anti-VEGF/anti-TNF-α decoy receptor (Valpha), whose dual action could be beneficial given the numerous pathogenetic pathways in psoriasis. A topical tyrosine kinase inhibitor also has potential given the cost and safety advantages conferred by this mode of administration. More research is warranted both in the prototypical drugs and in those already marketed for other indications.

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.

Philip M Laws, Helen S YoungThe University of Manchester, Manchester Bioscience and Academic Health Sciences Centre, Department of Dermatology, Salford Royal Hospital (Hope), Manchester, UKAbstract: Psoriasis is a common, chronic inflammatory skin disease which is associated with a number of significant co-morbidities including: impairment of quality of life; cardiovascular disease; and a seronegative arthritis known as psoriatic arthritis. Our understanding of the pathogenesis of psoriasis has developed at a remarkable rate in recent years. These new insights have significantly changed our perception of the condition and have led to the development of several new treatment strategies. Biological agents have proved a major step forward in therapeutic options for psoriasis. The ability to clear, or almost clear, cutaneous disease has changed the outcomes and expectations of many patients with this disease. The impact on both physical and psychological health may be great. This review covers the clinical features and management of psoriasis with specific reference to new therapeutic options.Keywords: psoriasis, management, biological therapy, treatment

Objective Recent reports have confirmed association of single-nucleotide polymorphisms (SNPs) mapping to the interleukin-23 receptor (IL-23R) and IL-12β genes with psoriasis susceptibility. The aim of this study was to determine whether these variants are also associated with susceptibility to psoriatic arthritis (PsA). Methods Two IL23R SNPs (rs7530511 and rs11209026) and 2 IL12B SNPs (rs3212227 and rs6887695) were genotyped in DNA samples from 520 white patients with PsA and 2,260 control subjects, all of whom resided in the UK. For SNP rs3212227, data on a larger group of controls (n = 4,681) were publicly available; this information was used in the analysis. Genotype counts were compared between patients with PsA and population controls, using the trend test. Results A haplotype comprising carriage of the common variants of both IL23R SNPs was associated with PsA susceptibility (adjusted P = 0.013 [1,000 permutations]). Both IL12B SNPs were independently associated with PsA susceptibility, and this association was strongest under a dominant model, with homozygosity for the common allele being more frequent in patients with PsA than in control subjects: for rs3212227, the odds ratio (OR) for carriage of AA versus other genotypes was 1.43 (95% confidence interval [95% CI] 1.17–1.76); for rs6887695, the OR for carriage of GG versus other genotypes was 1.43 (95% CI 1.18–1.74). Conclusion Variation within IL23R and IL12B is associated with susceptibility to both psoriasis and PsA. The effect sizes observed in patients with PsA appear to be smaller than those previously reported in patients with psoriasis, suggesting that both loci are primarily associated with psoriasis susceptibility. However, this does support the idea that the genetic etiology of the psoriasis present in patients with PsA has susceptibility loci in common with those observed in patients with uncomplicated psoriasis.

Substantial evidence indicates that psoriasis is a T-lymphocyte-mediated autoimmune disease. However, longstanding data also indicate IgG and complement deposition in upper epidermis of psoriasis plaques. This led us to propose that autoantigen–autoantibody interactions in the skin may also be of pathogenic importance. Here, we have confirmed the presence of IgG in upper lesional epidermis and used high-resolution two-dimensional immunoblotting of extracts from this tissue, and laser desorption mass spectrometry of tryptic peptides, to define a series of epidermal proteins that bind IgG from psoriatic serum. The most prominent of these autoantigens are homologues of the serpin, squamous cell carcinoma antigen (SCCA), the other autoantigens identified including arginase 1, enolase 1, and keratin 10. Blood levels of IgG autoantibodies that bind to SCCA proteins were significantly higher in psoriasis than healthy controls ( P =0.005), but were not detectable in sera from patients with active atopic dermatitis. To our knowledge, SCCA proteins have not previously been described as autoantigenic in animals or humans and form complexes with IgG that are associated with complement deposition. These findings expose potentially pathogenic humoral immunologic events and thus possible therapeutic targets in psoriasis.

Psoriasis is an immune-mediated skin disorder that is inherited as a multifactorial trait. Linkage studies have clearly identified a primary disease susceptibility locus lying within the major histocompatibility complex (MHC), but have generated conflicting results for other genomic regions. To overcome this difficulty, we have carried out a genome-wide association scan, where we analyzed more than 408,000 SNPs in an initial sample of 318 cases and 288 controls. Outside of the MHC, we observed a single cluster of disease-associated markers, spanning 47 kb on chromosome 20q13. The analysis of two replication data sets confirmed this association, with SNP rs495337 yielding a combined P-value of 1.4 x 10(-8) in an overall sample of 2679 cases and 2215 controls. Rs495337 maps to the SPATA2 transcript and is in absolute linkage disequilibrium with five SNPs lying in the adjacent ZNF313 gene (also known as RNF114). Real-time PCR experiments showed that, unlike SPATA2, ZNF313 is abundantly expressed in skin, T-lymphocytes and dendritic cells. Furthermore, an analysis of the expression data available from the Genevar database indicated that rs495337 is associated with increased ZNF313 transcripts levels (P = 0.003), suggesting that the disease susceptibility allele may be a ZNF313 regulatory variant tagged by rs495337. Homology searches indicated that ZNF313 is a paralogue of TRAC-1, an ubiquitin ligase regulating T-cell activation. We performed cell-free assays and confirmed that like TRAC-1, ZNF313 binds ubiquitin via an ubiquitin-interaction motif (UIM). These findings collectively identify a novel psoriasis susceptibility gene, with a putative role in the regulation of immune responses.

Objective: Psoriasis of early onset (type I; age of onset ⩽40 years) is associated with HLA-Cw*06 while the shared epitope (SE) is associated with rheumatoid arthritis susceptibility. Our aim was to investigate the role of HLA-Cw*06 and HLA-DRB1 genes (including SE) with psoriatic arthritis (PsA) susceptibility. Methods: In a case–control association study, HLA-Cw*06 phenotype frequencies were compared between patients with PsA (n = 480), psoriasis alone (n = 611) and healthy controls (n = 166). Similarly, at the HLA-DRB1 locus, phenotype and SE frequencies were compared in patients with PsA (n = 480), early undifferentiated inflammatory arthritis alone (n = 1621) and healthy controls (n = 537). Results: The HLA-Cw*06 phenotype was associated with type I psoriasis (OR 6.9, 95% CI 4.4, 11.1, p = 2.2×10 −21 ) and with patients with PsA having type I psoriasis (OR 5.0, 95% CI 3.2, 7.9, p = 4.39×10 −13 ), but not with patients with PsA having type II psoriasis (age of onset >40 years). HLA-DRB1*07 , in linkage disequilibrium with HLA-Cw*06 , was also associated with patients with PsA having type I psoriasis (OR 2.7, 95% CI 2.1, 3.7, p HLA-DRB1*04 alleles and the SE were associated with undifferentiated inflammatory arthritis but not with PsA. Conclusions: The SE is not a PsA susceptibility locus. HLA-Cw*06 and HLA-DRB1*07 are associated with patients with PsA having type I psoriasis, suggesting that the primary association is with age of onset of psoriasis. Patients with PsA having type I psoriasis, therefore, have a genetic background different to those with type II psoriasis, and adjustment for this is necessary in future studies that investigate the genetic susceptibility of PsA.

We read with interest the report describing a series of patients with posterior scleritis.1 We noted that one patient was identified as having concomitant necrobiotic xanthogranuloma (NXG) and late...

OBJECTIVES\ud \ud A draft patient-reported outcome measure for psoriasis treatment (PROMPT) was developed through patient interviews and comprised 91 items across seven core domains. This study aimed to evaluate the scaling properties and construct validity of the draft measure using the Rasch measurement model.\ud \ud METHODS\ud \ud Patients with chronic plaque psoriasis were identified and recruited according to pre-defined inclusion and exclusion criteria through psoriasis-specific secondary care clinics in the United Kingdom and two national patient organizations. Patients completed the draft measure at two time points, 14 days apart. Respondents with ≥40% of missing data were removed from the final analyses. Data from each sub-scale were analyzed separately using RUMM2030 software to explore Rasch model fit, item difficulty, local dependence, item category thresholds, and differential item functioning (DIF) by age and gender. Where necessary, items were removed individually and the scale iteratively reassessed for fit and unidimensionality.\ud \ud RESULTS\ud \ud A sample of n=209 patients with chronic plaque psoriasis completed the draft measure. Initial fit to the model was poor; disordered category thresholds were identified for items in all scales. Post-hocre-scoring from a 5-point Likert scale to a 3-point Likert scale improved model fit. Items which showed local dependence were removed in context of qualitative findings. Following removal of 11 items, all 7 scales demonstrated acceptable fit with the Rasch model (Chi Sq = 0.09 to 0.2) There was no evidence of DIF by age and gender.\ud \ud CONCLUSIONS\ud \ud The new measure, PROMPT, comprised 80 items in 6 independent, unidimensional scales, free from age or gender bias, with acceptable fit to the Rasch model. As such, the measure is considered to show initial promise for use with patients with chronic plaque psoriasis in a clinical setting. The psychometric properties and scoring of the measure should be explored further and confirmed in future studies.

Vascular endothelial growth factor (VEGF) promotes angiogenesis, and elevated levels are found in plaques of psoriasis. Two VEGF polymorphisms, +405 and -460, are associated with early-onset psoriasis and are close to the functional activator protein-1 site (+419) through which retinoids, an established systemic therapy for psoriasis, can block production of VEGF. We report that peripheral blood mononuclear cells (PBMCs) and epidermal keratinocytes (KC) from patients with psoriasis demonstrate differential, genotype-dependent, regulation of VEGF. For PBMCs, VEGF genotype distinguishes two groups of patients with psoriasis - "high and low VEGF producers" (P < 0.001). In contrast, KC production of VEGF is not genotype dependent. However, the effects of all-trans retinoic acid (RA) on cellular expression of VEGF are determined by both cell type and genotype. RA inhibits KC production of VEGF in a genotype-dependent manner (P < 0.005) whereas RA stimulates PBMCs production irrespective of VEGF genotype (P < 0.001). We also report that the -460 VEGF polymorphism appears to have a clinical pharmacogenetic role in predicting response or non-response of psoriasis to acitretin (P = 0.01). In future, determination of VEGF gene polymorphisms and thus individual patient VEGF "signatures" may be used as a prognostic factor for psoriasis susceptibility/severity and as a means for optimizing treatment response.

We have examined whether psoriasis is associated with systemic effects on epidermal Langerhans cell (LC) function and, specifically, the migration of LCs from the skin. Compared with normal skin, the frequency and morphology of epidermal LCs in uninvolved skin from patients with psoriasis was normal. However, mobilization of these cells in response to stimuli that normally induce migration (chemical allergen, tumor necrosis factor alpha [TNF-alpha], and interleukin-1beta [IL-1beta]) was largely absent, despite the fact that treatment with TNF-alpha and IL-1beta was associated with comparable inflammatory reactions in patients and controls. The failure of LC migration from uninvolved skin was not attributable to altered expression of receptors for IL-1beta or TNF-alpha that are required for mobilization, nor was there an association with induced cutaneous cytokine expression. Although a role for altered dynamics of LC migration/turnover has not been formally excluded, these data reveal a very consistent decrement of LC function in psoriasis that may play a decisive role in disease pathogenesis.

Summary Background Psoriasis is associated with abnormal plasma lipid metabolism and a high frequency of cardiovascular events. Increased lipid levels are also seen in patients with psoriasis treated with acitretin. Apolipoprotein E (ApoE) variants have been linked to hypertriglyceridaemia and hypercholesterolaemia in normal individuals. Two coding single nucleotide polymorphisms at +3937 and +4075 define the three common ApoE alleles e2, e3 and e4. Objectives To test the hypothesis that particular ApoE polymorphism(s) are associated with psoriasis and that specific ApoE allelic variant(s) may be a marker for predicting disease response to acitretin. Methods DNA was genotyped for ApoE polymorphisms using a radioactive hybridization technique in cohorts of patients with psoriasis, including patients with chronic plaque psoriasis (CPP, n = 212), guttate psoriasis (GP, n = 94), palmoplantar pustulosis (PPP, n = 101), controls (n = 137), acitretin responders (n =106) and acitretin nonresponders (n = 84). Results The frequency of the e4 allele (+3937C/+4075C) was significantly higher in patients with CPP and GP than in controls (P = 0·008 and P = 0·02, respectively). There was no significant difference in allele frequencies between patients with PPP and controls. Allelic distribution was similar in acitretin responders and nonresponders. Conclusions These data demonstrate an association between the Apo e4 allele and CPP and GP, suggesting a possible pathogenic role for ApoE in psoriasis. Our results do not support a link between disease response to acitretin and the e2, e3 or e4 allelic variants of ApoE.