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The purpose of this article was to determine the safety and efficacy of adapalene gel in the treatment of actinic keratoses and solar lentigines. A prospective two-center, randomized, controlled, investigator-masked, [...]

BACKGROUND: As facial appearance can be readily quantified and skin tissue easily accessed, they could be valuable tools for determining how biological mechanisms influence tissue degeneration with age and, consequently, human health and lifespan. It is unknown, however, whether appearance reflects disease risk or lifespan independently of factors already known to associate with both health and appearance. METHODS: In a cross-sectional study, we compared the amount of skin wrinkling on a sun-protected site (upper inner arm) and the facial appearance of 261 offspring (mean age 63.2 y) of nonagenarian siblings with 253 age-matched controls (mean age 62.7 y), all with no reported disease history. We next examined whether any appearance features that significantly associated with familial longevity also associated with the Framingham cardiovascular disease (CVD) risk score. All analyses were adjusted for chronological age, smoking, photodamage, and body mass index. RESULTS: Female and male offspring had reduced upper inner arm skin wrinkling (p = .03 and p < .001, respectively), and the male offspring looked 1.4 y younger than the controls (p = .002). There were no significant associations between CVD risk and upper inner arm skin wrinkling. Women in the lowest quartile of CVD risk looked more than 2 y younger for their age than those in higher risk quartiles (p = .002). Systolic blood pressure was the most significant (p = .004) CVD risk factor that was associated with perceived age in women. CONCLUSIONS: Facial appearance and skin wrinkling at a sun-protected site reflect the propensity to reach an extreme old age, and facial appearance reflects the risk of succumbing to CVD independently of chronological age, smoking, photodamage, and BMI. [ABSTRACT FROM AUTHOR]

Siao Pei Tan,1,2 Simon B Brown,1,2 Christopher EM Griffiths,3 Richard B Weller,1,2 Neil K Gibbs3,4 1MRC Centre for Inflammation Research, 2Department of Dermatology, The University of Edinburgh, Edinburgh, 3Dermatology Centre, Division of Musculoskeletal and Dermatological Sciences, Salford Royal NHS Foundation Trust, University of Manchester, Manchester, 4Curapel, Life Sciences Hub Wales, Cardiff, UK Abstract: Atopic dermatitis (AD), also known as eczema, is one of the most common chronic skin conditions worldwide, affecting up to 16% of children and 10% of adults. It is incurable and has significant psychosocial and economic impacts on the affected individuals. AD etiology has been linked to deficiencies in the skin barrier protein, filaggrin. In mammalian skin, l-histidine is rapidly incorporated into filaggrin. Subsequent filaggrin proteolysis releases l-histidine as an important natural moisturizing factor (NMF). In vitro studies were conducted to investigate the influence of l-histidine on filaggrin processing and barrier function in human skin-equivalent models. Our further aim was to examine the effects of daily oral l-histidine supplementation on disease severity in adult AD patients. We conducted a randomized, double-blind, placebo-controlled, crossover, nutritional supplementation pilot study to explore the effects of oral l-histidine in adult AD patients (n=24). In vitro studies demonstrated that l-histidine significantly increased both filaggrin formation and skin barrier function (P0.32). The clinical effect of oral l-histidine in AD was similar to that of mid-potency topical corticosteroids and combined with its safety profile suggests that it may be a safe, nonsteroidal approach suitable for long-term use in skin conditions that are associated with filaggrin deficits such as AD. Keywords: atopic dermatitis, eczema, filaggrin, l-histidine, amino acid, skin barrier, nutritional supplement

Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribute to the development of ADA against adalimumab, thereby influencing treatment failure. In patients with psoriasis on their first course of adalimumab, in whom serum ADA had been evaluated 6-36 months after starting treatment, we observed a genome-wide association with ADA against adalimumab within the major histocompatibility complex (MHC). The association signal mapped to the presence of tryptophan at position 9 and lysine at position 71 of the HLA-DR peptide-binding groove, with both residues conferring protection against ADA. Underscoring their clinical relevance, these residues were also protective against treatment failure. Our findings highlight antigenic peptide presentation via MHC class II as a critical mechanism in the development of ADA against biologic therapies and downstream treatment response.

Background: The diagnosis of psoriasis may be missed or delayed in primary care settings., Aim: To examine trends in healthcare events before a diagnosis of psoriasis., Design and Setting: Two matched case-control studies using electronic healthcare records delineated from the Clinical Practice Research Datalink (CPRD GOLD and Aurum) in the UK., Method: Individuals aged ≥18 years with an incident diagnosis of psoriasis (case group) between 1 January 2010 and 29 December 2017 were identified and matched by age, sex, and general practice with six individuals without psoriasis (control group). Healthcare activities were examined and annual incidence rates and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for 10 years before the index date were compared between case and control groups., Results: There were 17 320 people with psoriasis and 99 320 controls included from CPRD GOLD, and 11 442 people with psoriasis and 65 840 controls extracted from CPRD Aurum. Data from CPRD GOLD showed that people with psoriasis were up to eight times more likely to be diagnosed with pityriasis rosea at 6 months (IRR 7.82, 95% CI = 4.09 to 14.95) before the index date than the control group. The case group were twice as likely to be diagnosed with eczema (IRR 1.90, 95% CI = 1.76 to 2.05) or tinea corporis (IRR 1.99, 95% CI = 1.74 to 2.27) 1 year before the index date. The case group were more likely to report dry skin, rash, skin texture changes, and itching than the control group up to 5 years before the index date. The most frequently reported clinical feature was rash with an IRR of 2.71 (95% CI = 2.53 to 2.92) at 1 year before the index date. The case group were prescribed topical corticosteroids (IRR 1.97, 95% CI = 1.88 to 2.07) or topical antifungals (IRR 1.92, 95% CI = 1.78 to 2.07) in the year before the index date twice as often as those in the control group., Conclusion: Findings suggest that the diagnosis of psoriasis may be missed or delayed in a UK primary care setting for up to 5 years for some individuals, hence leading to a potentially detrimental delay in establishing an appropriate treatment regimen., (© The Authors.)

Context: Psoriasis is an immune-mediated, inflammatory skin disease associated with comorbidities such as psoriatic arthritis, depression, obesity, and cardiovascular disease. Due to its visibility, psoriasis can induce stress and have a negative impact on a patient's quality of life. Current medical interventions are often ineffective and costly and are associated with undesirable side effects, thus emphasizing the need for innovative approaches to treatment., Objective: The study intended to explore the feasibility of an interdisciplinary approach between dermatologists and somatologists in the holistic management of psoriasis., Design: The research team performed a narrative review by searching for scientific articles in the databases Google Scholar, Scopus, PubMed, and Medline, including relevant observational studies, systematic reviews, randomized controlled trials, and meta-analyses on the diagnosis and management of psoriasis., Setting: The review took place at Durban University of Technology library, Durban, South Africa., Results: Psoriasis is a huge medical burden. It has a negative psychological impact on quality of life. Patients are not satisfied with the current treatment approach and they prefer alternative therapies. Spa therapy could be used in conjunction with medical therapy for the management of psoriasis. Through water or spa therapy, it has been shown that trace elements in mineral waters are absorbed through the skin and perhaps modulate the immune system., Conclusions: The current review has provided some practical advice on how to manage psoriasis in a holistic manner. Somatology training institutions should consider incorporating Pso Well training in their program, thereby keeping abreast of new developments associated with psoriasis management. MBCT could be added to the set of holistic interventions for patients suffering from psoriasis, particularly those who suffer from poor psychological well-being. Robust clinical tests should be performed to evaluate the effectiveness of treatments, such as integrative patient management between the two professions.

One of the major functions of human skin is to provide protection from the environment. Although we cannot entirely avoid, for example, sun exposure, it is likely that exposure to other environmental factors could affect cutaneous function. A number of studies have identified smoking as one such factor that leads to both facial wrinkle formation and a decline in skin function. In addition to the direct physical effects of tobacco smoke on skin, its inhalation has additional profound systemic effects for the smoker. The adverse effects on the respiratory and cardiovascular systems from smoking are well known. Central to the pathological changes associated with smoking is the elastic fibre, a key component of the extracellular matrices of lungs. In this study we examined the systemic effect of chronic smoking (>40 cigarettes/day; >5 years) on the histology of the cutaneous elastic fibre system, the nanostructure and mechanics of one of its key components, the fibrillin-rich microfibril, and the micromechanical stiffness of the dermis and epidermis. We show that photoprotected skin of chronic smokers exhibits significant remodelling of the elastic fibre network (both elastin and fibrillin-rich microfibrils) as compared to the skin of age- and sex-matched non-smokers. This remodelling is not associated with increased gelatinase activity (as identified by in situ zymography). Histological remodelling is accompanied by significant ultrastructural changes to extracted fibrillin-rich microfibrils. Finally, using scanning acoustic microscopy, we demonstrated that chronic smoking significantly increases the stiffness of both the dermis and the epidermis. Taken together, these data suggest an unappreciated systemic effect of chronic inhalation of tobacco smoke on the cutaneous elastic fibre network. Such changes may in part underlie the skin wrinkling and loss of skin elasticity associated with smoking. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland., (© 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.)

Competing Interests: Competing interests: None declared.

Dupilumab, a monoclonal antibody that blocks the shared receptor subunit for interleukin (IL)-4 and IL-13, is currently approved for the treatment of adults with inadequately controlled moderate-to-severe atopic dermatitis (AD). The efficacy and safety of dupilumab for AD among racial subgroups is unknown. This post hoc analysis from three phase 3 trials assessed the efficacy and safety of dupilumab vs placebo by racial subgroup (White, Asian, Black/African American). Data from LIBERTY AD SOLO 1 (NCT02277743), SOLO 2 (NCT02277769), and CHRONOS (NCT02260986) were pooled. Outcomes included mean and percent change from baseline to week 16 in the key therapeutic domains Eczema Area and Severity Index (EASI), Peak Pruritus Numerical Rating Scale (NRS), Dermatology Life Quality Index (DLQI), and Patient-Oriented Eczema Measure, as well as Investigator’s Global Assessment and pain or discomfort assessed by the European Quality of Life-5 Dimensions 3 level questionnaire. A total of 2,058 patients (White n=1,429, Asian n=501, Black/African American n=128) were included in the current analysis. Baseline demographics and disease characteristics were balanced between treatment groups and racial subgroups. In the three trials, dupilumab significantly (P<0.0001) improved all assessed outcomes compared with placebo in the White and Asian subgroups. In the smaller Black/African American subgroup, dupilumab significantly (P<0.0001) improved EASI endpoints and mean changes in Peak Pruritus NRS and DLQI vs placebo, with positive numeric trends favoring dupilumab in all other endpoints. Dupilumab was generally well tolerated, with an acceptable safety profile in all racial subgroups. Serious adverse events occurred more frequently with placebo; treatment discontinuations due to adverse events were rare in all treatment groups. Significant clinical improvement and a favorable benefit-risk profile can be achieved with dupilumab treatment in patients of White, Asian, and Black/African American racial subgroups with moderate-to-severe AD inadequately controlled with topical medications. ClinicalTrials.gov identifiers: NCT02277743, NCT02277769, NCT02260986

Background: Guttate psoriasis is a distinctive acute form of psoriasis which characteristically occurs in children and young adults. Very little specific evidence-based guidance is available in standard texts to help make rational decisions about treatment options., Objectives: To assess the effectiveness of treatments for guttate psoriasis., Search Methods: We searched the Cochrane Clinical Trials Register (Cochrane Library, Issue 3, 1999), Medline (1966- September 1999), Embase (1988-September 1999), Salford Database of Psoriasis Trials (to November 1999) and European Dermato-Epidemiology Network (EDEN) Psoriasis Trials Database (to November 1999) for terms GUTTATE and PSORIASIS. We also searched 100 unselected RCTs of psoriasis therapy and all 112 RCTs of phototherapy for psoriasis in the Salford Database of Psoriasis Trials for separate stratification for guttate psoriasis., Selection Criteria: Randomised trials in which patients with acute guttate psoriasis were randomised to different treatments, except those trials examining antistreptococcal interventions which are addressed in a separate Cochrane review., Data Collection and Analysis: Two reviewers independently assessed trial eligibility and quality., Main Results: No published report could be found to support or to challenge current commonly used methods of management.Only one trial which met the selection criteria was identified. In this small study of 21 hospitalised patients with guttate psoriasis, intravenous infusion of an n-3 fatty acid rich lipid emulsion was compared with placebo emulsion containing n-6 fatty acids. The n-3 preparation appeared to be of some benefit for patients with guttate psoriasis., Authors' Conclusions: There is currently no firm evidence on which to base treatment of acute guttate psoriasis. Studies comparing standard treatment modalities, including phototherapy and topical regimens, are required to enable informed decisions on treatment choices to be made.

Competing Interests: Competing interests: All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work. We have read and understood the BMJ policy on declaration of interests and declare that we have no competing interests.

Background: Guttate psoriasis is a distinctive acute form of psoriasis which characteristically occurs in children and young adults. It is closely associated with preceding streptococcal sore throat or tonsillitis. Some authorities have claimed that ordinary (chronic plaque) psoriasis may also be made worse by infection at distant sites. Although many dermatologists have recommended using antibiotics for guttate psoriasis in particular, it is not clear whether they influence the course of either form of psoriasis. Some dermatologists have also recommended tonsillectomy for psoriasis in patients with recurrent streptococcal sore throat., Objectives: To assess the evidence for effectiveness of antistreptococcal interventions including antibiotics and tonsillectomy in the management of acute guttate and chronic plaque psoriasis., Search Methods: We searched the Cochrane Clinical Trials Register (Cochrane Library, Issue 3, 1999), Medline (1966- September 1999), Embase (1988-September 1999), the Salford Database of Psoriasis Trials (to November 1999) and the European Dermato-Epidemiology Network (EDEN) Psoriasis Trials Database (to November 1999) for terms [STREPTOCOCC* or ANTIBIOTIC* or TONSIL*] and PSORIASIS using the Cochrane Skin Group search strategy., Selection Criteria: Randomised trials of one or more antistreptococcal interventions in patients with guttate or chronic plaque psoriasis., Data Collection and Analysis: Two reviewers independently examined each retrieved trial for eligibility and quality., Main Results: The one eligible trial we identified compared the use of two oral antibiotic schedules in 20 psoriasis patients, predominantly of guttate type, who had evidence of beta-haemolytic streptococcal colonisation. Either rifampicin or placebo was added to the end of a standard course of antistreptococcal antibiotic (phenoxymethylpenicillin or erythromycin). No patient in either arm of the study improved during the observation period.No randomised trials of tonsillectomy for psoriasis were identified., Authors' Conclusions: Although it is well known that guttate psoriasis may be precipitated by streptococcal infection, there is no firm evidence to support the use of antibiotics either in the management of established guttate psoriasis or in preventing the development of guttate psoriasis following streptococcal sore throat.Although both antibiotics and tonsillectomy have frequently been advocated for patients with recurrent guttate psoriasis or chronic plaque psoriasis, there is to date no good evidence that either intervention is beneficial.

Background: Health-related quality of life (HRQoL) measures provide patient-centred evaluations of response to treatment. In the 12-week, Phase III PSO-ABLE study, fixed-combination calcipotriol 50 μg/g as hydrate (Cal) plus betamethasone 0.5 mg/g as dipropionate (BD) aerosol foam was significantly more effective for the treatment of psoriasis than Cal/BD gel., Objective: To compare HRQoL in mild-severe psoriasis vulgaris patients (involving 2-30% body surface area) over 12 weeks of treatment with Cal/BD foam or gel., Methods: HRQoL was assessed using: Dermatology Life Quality Index (DLQI), EuroQoL-5D-5L-PSO (EQ-5D), and Psoriasis QoL (PQoL-12) questionnaires (baseline, Weeks 4, 8 and 12); DLQI score of 0/1 (range: 0-30) and weighted EQ-5D utility index score of 1 (range: 0-1) indicates there is no impact on a patient's QoL and perfect health, respectively. Itch, itch-related sleep loss, and work impairment were also assessed., Results: In total, 463 patients were randomized to the study (Cal/BD foam, n = 185; Cal/BD gel, n = 188; foam vehicle, n = 47; gel vehicle, n = 43). Significantly more Cal/BD foam patients achieved DLQI scores of 0/1 at Weeks 4 (45.7% vs 32.4%; p = 0.013) and 12 (60.5% vs 44.1%; p = 0.003) than Cal/BD gel patients. Cal/BD foam significantly improved EQ-5D utility index (0.09 vs 0.03; p<0.001) and PQoL-12 scores (-2.23 vs -2.07; p = 0.029) from baseline to Week 4 versus Cal/BD gel. Itch, itch-related sleep loss, and work impairment improved more with Cal/BD foam than gel., Conclusion: Cal/BD foam demonstrated greater HRQoL improvement in patients with psoriasis than Cal/BD gel over 12 weeks of treatment.

Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), has been shown to have significant efficacy in the treatment of moderate to severe psoriasis, psoriatic arthritis and ankylosing spondylitis. Blocking critical mediators of immunity may carry a risk of increased opportunistic infections. Here we present clinical and in vitro findings examining the effect of secukinumab on Mycobacterium tuberculosis infection. We re-assessed the effect of secukinumab on the incidence of acute tuberculosis (TB) and reactivation of latent TB infection (LTBI) in pooled safety data from five randomized, double-blind, placebo-controlled, phase 3 clinical trials in subjects with moderate to severe plaque psoriasis. No cases of TB were observed after 1 year. Importantly, in subjects with a history of pulmonary TB (but negative for interferon-γ release and receiving no anti-TB medication) or positive for latent TB (screened by interferon-γ release assay and receiving anti-TB medication), no cases of active TB were reported. Moreover, an in vitro study examined the effect of the anti-tumor necrosis factor-α (TNFα) antibody adalimumab and secukinumab on dormant M. tuberculosis H37Rv in a novel human three-dimensional microgranuloma model. Auramine-O, Nile red staining and rifampicin resistance of M. tuberculosis were measured. In vitro , anti-TNFα treatment showed increased staining for Auramine-O, decreased Nile red staining and decreased rifampicin resistance, indicative of mycobacterial reactivation. In contrast, secukinumab treatment was comparable to control indicating a lack of effect on M. tuberculosis dormancy. To date, clinical and preclinical investigations with secukinumab found no evidence of increased M. tuberculosis infections., Competing Interests: Studies and analysis were sponsored by Novartis Pharma AG. NK and PEK received a research grant from Novartis Institutes for Biomedical Research. T-FT has carried out clinical trials, provided consultancies or acted as a speaker for AbbVie, Allergan, Celgene, Eli Lilly, Galderma, Janssen-Cilag, Leo Pharma, Novartis and Pfizer. CEMG has received honoraria or research grants from AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, GSK, Janssen-Cilag, Leo, MSD, Novartis, Pfizer, Sandoz, Trident and UCB. MK, DB, SD-C, JS and TF are full-time employees of Novartis.

Background/purpose: The dermal-epidermal junction (DEJ) forms epidermal protrusions down into the dermis (rete ridges) and dermal projections up into the epidermis (dermal papillae). Usually visualized in two-dimensions (2D), our knowledge of how the DEJ changes with ageing is limited. We aimed to characterize how this structure exists in 3D and changes with age., Methods: Photoprotected and photoexposed skin were imaged using reflectance confocal microscopy (RCM) in young and aged individuals. Biopsies of the imaged areas were processed for histological sectioning and for imaging using micro-computed X-ray tomography (microCT)., Results: Images obtained from RCM and microCT were used to 3D reconstruct the DEJ. DEJ heights obtained from microCT images showed strong correlation with histology-measured heights. We proposed a novel definition of rete ridges (RR m ) and dermal papillae (DP m ), which allowed easier automated measurement of reduced DP m and RR m volumes in aged skin from microCT reconstructions. An algorithm to map DP m connectivity showed reduced lengths of DP m branches with age., Conclusion: Three-dimensional images illustrated the complex topography of the DEJ and highlighted the distinct morphology of dermal papillae compared with rete ridges, which is not evident when evaluating 2D sections. Ex vivo imaging was more successful in differentiating DEJ architecture with respect to age., (© 2016 The Authors. Skin Research and Technology Published by John Wiley & Sons Ltd.)

Background: The burden of psoriasis across many world regions is high and there is a recognized need to better understand the epidemiology of this common skin disorder., Objectives: To examine changes in the prevalence and incidence of psoriasis, and mortality rates over a 15-year period., Methods: Cohort study involving analysis of longitudinal electronic health records between 1999 and 2013 using the U.K. Clinical Practice Research Datalink (CPRD)., Results: The prevalence of psoriasis increased steadily from 2·3% (2297 cases per 100 000) in 1999 to 2·8% (2815 per 100 000) in 2013, which does not appear to be attributable to changes in incidence rates. We observed peaks in age bands characteristic of early-onset (type I) and late-onset (type II) psoriasis, and changes in incidence and prevalence rates with increasing latitude in the U.K. All-cause mortality rates for the general population and for patients with psoriasis have decreased over the last 15 years. However, the risk of all-cause mortality for patients with psoriasis remains elevated compared with people without psoriasis (hazard ratio 1·21; 95% confidence interval 1·13-1·3) and we found no significant change in this relative excess mortality gap over time., Conclusions: We found an increasing population living longer with psoriasis in the U.K., which has important implications for healthcare service delivery and for resource allocation. Importantly, early mortality in patients with psoriasis remains elevated compared with the general population and we found no evidence of change in this premature mortality gap., (© 2016 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Psoriasis is a common long-term, immune-mediated skin condition associated with behavioural factors (e.g. smoking, excess alcohol, obesity), which increase the risk of psoriasis onset, flares and comorbidities. Motivational interviewing (MI) is an evidence-based approach to health-related behaviour change that has been used successfully for patients with long-term conditions. This study assessed change in clinicians' MI skills and psoriasis knowledge following Psoriasis and Wellbeing (Pso Well ® ) training., Objectives: To investigate whether the Pso Well training intervention improves clinicians' MI skills and knowledge about psoriasis-related comorbidities and risk factors; and to explore the acceptability and feasibility of the Pso Well training content, delivery and evaluation., Methods: Clinicians attended the 1-day training programme focused on MI skills development in the context of psoriasis. MI skills were assessed pre- and post-training using the Behaviour Change Counselling Index. Knowledge about psoriasis-related comorbidity and risk factors was assessed with a novel 22-point measure developed for the study. Interviews with clinicians were analysed qualitatively to identify perceptions about the feasibility and acceptability of the training., Results: Sixty-one clinicians completed the training (35 dermatology nurses, 23 dermatologists and three primary-care clinicians). Clinicians' MI skills (P < 0·001) and knowledge (P < 0·001) increased significantly post-training. Clinicians found the training valuable and relevant to psoriasis management., Conclusions: Attendance at the Pso Well training resulted in improvements in clinicians' knowledge and skills to manage psoriasis holistically. Clinicians deemed the training itself and the assessment procedures used both feasible and acceptable. Future research should investigate how this training may influence patient outcomes., (© 2016 British Association of Dermatologists.)

Background: Medication nonadherence is known to limit the effectiveness of available therapies; however, little is known specifically about medication adherence in people with psoriasis. Medicines self-management can feel onerous to those with dermatological conditions due to the nature of therapies prescribed and many individuals with psoriasis experience additional challenges such as physical and psychological comorbidities that place significant additional demands on individuals and may undermine adherence. Viewing nonadherence to medication as an outcome of limited personal coping resources and conflicting goals may help to explain medication nonadherence., Objectives: To explore individuals' perspectives of their psoriasis, medication and its management., Methods: Twenty people with psoriasis were recruited from community samples in England and interviewed in-depth about their perceptions of their psoriasis, medication, and adherence to medication and self-management advice. Data were analysed using Framework Analysis., Results: Participants reported that adhering to recommended treatment regimens conflicted with the management of the physical and psychological demands of living with psoriasis. Medication usage was viewed as a source of unresolved emotional distress and, for some, resulted in poor self-reported adherence, which included medication overuse, underuse and rejection of prescribed therapies. Perceived lack of engagement by clinicians with participants' self-management difficulties was viewed as an additional source of stress and distress., Conclusions: Adhering to medication in psoriasis can be an additional source of considerable emotional distress. We interpreted some episodes of nonadherence to psoriasis medication as rational attempts by individuals to minimize distress and to gain control over their life., (© 2016 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Guselkumab, an interleukin-23 blocker, was superior to adalimumab in treating moderate to severe psoriasis in a phase II trial., Objectives: We sought to compare efficacy and safety of guselkumab with adalimumab and placebo in patients with psoriasis treated for 1 year., Methods: Patients were randomized to guselkumab 100 mg (weeks 0 and 4, then every 8 weeks; n = 329); placebo→guselkumab (weeks 0, 4, and 12 then guselkumab at weeks 16 and 20, then every 8 weeks; n = 174); or adalimumab (80 mg week 0, 40 mg week 1, then 40 mg every 2 weeks through week 47; n = 334). Physician-reported outcomes (Investigator Global Assessment, Psoriasis Area and Severity Index [PASI]), patient-reported outcomes (Dermatology Life Quality Index, Psoriasis Symptoms and Signs Diary), and safety were evaluated through week 48., Results: Guselkumab was superior (P < .001) to placebo at week 16 (85.1% vs 6.9% [Investigator Global Assessment score of 0/1 (cleared/minimal)] and 73.3% vs 2.9% [90% or greater improvement in PASI score from baseline (PASI 90)]). Guselkumab was also superior (P < .001) to adalimumab for Investigator Global Assessment 0/1 and PASI 90 at week 16 (85.1% vs 65.9% and 73.3% vs 49.7%), week 24 (84.2% vs 61.7% and 80.2% vs 53.0%), and week 48 (80.5% vs 55.4% and 76.3% vs 47.9%). Furthermore, guselkumab significantly improved patient-reported outcomes through week 48. Adverse event rates were comparable between treatments., Limitations: Analyses were limited to 48 weeks., Conclusions: Guselkumab demonstrated superior efficacy compared with adalimumab and was well tolerated in patients with psoriasis through 1 year., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: An estimated 50% of patients do not take their medication as prescribed, with medication adherence associated with adverse outcomes and higher costs of care. The Necessity-Concerns Framework identified individual's beliefs about their medication as playing a key role in adherence, and UK Clinical Adherence Guidelines recommend eliciting and incorporating individual's perceptions of their medication within the consultation. The Beliefs about Medicines Questionnaire (BMQ) is widely used to assess medication beliefs, however, given the condition-specific nature of some self-management regimens, it is unknown whether this tool is able to fully capture beliefs about more complex medication regimens., Methods: We examined the challenges of assessing medication beliefs using the BMQ in 20 people with a complex relapsing-remitting condition recruited from community sources. Data were collected from people with psoriasis; a patient group characterised by complex medication regimens, which include therapies that are applied topically, phototherapy/photochemotherapy, and therapies that are administered orally or via subcutaneous or intravenous injections. Semi-structured cognitive interviews were undertaken, with responses coded using established schedules and analysed using Content analysis., Results: Individual's beliefs about their condition specific therapies were not accurately captured by the BMQ. Medication beliefs as expressed during 'real-time' completion of the BMQ were underestimated, or failed to be captured, by the corresponding scores given by participants. There was mismatch between the terminology used in the scale and individuals perceptions of their condition and the complexity of its management and treatment outcomes. Currently the BMQ cannot represent beliefs about medicines underuse, even though some individuals with psoriasis viewed access to therapies as overly restrictive. Some the BMQ items were misinterpreted in part due to ambiguous item wording or due to misreading by participants., Conclusions: This is the first study to identify general and condition-specific difficulties experienced by individuals completing the BMQ in 'real time'. The main implication of this research is the need to develop condition-specific versions of the BMQ in order that this important instrument can capture the full range of medication beliefs in individuals living with a complex relapsing-remitting condition. Access to condition-specific versions could significantly increase our understanding of beliefs which facilitate or reduce medication adherence.

Background: Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. A Phase 3 withdrawal/re-treatment study (NCT01186744; OPT Retreatment) showed tofacitinib re-treatment was effective in patients with chronic plaque psoriasis., Objectives: To describe the effects of tofacitinib withdrawal/re-treatment on health-related quality of life (HRQoL) and disease symptoms measured by patient-reported outcomes (PROs)., Methods: The study was divided into initial treatment, treatment withdrawal, and re-treatment periods. Initial treatment: patients were randomized to receive tofacitinib 5 (n = 331) or 10 mg (n = 335) BID for 24 weeks. Treatment withdrawal: patients who achieved both ≥ 75% reduction in Psoriasis Area and Severity Index (PASI) score from baseline and Physician's Global Assessment of 'clear'/'almost clear' at Week (W)24 received placebo (withdrawal) or the previous dose (continuous treatment). Re-treatment: at relapse (> 50% loss of W24 PASI response) or at W40, patients received their initial tofacitinib dose. PROs included: Dermatology Life Quality Index (DLQI), Itch Severity Item (ISI), Short Form-36 (SF-36) and Patient's Global Assessment (PtGA)., Results: After initial treatment with tofacitinib 5 and 10 mg BID, substantial and significant improvements were reported for mean DLQI (baseline: 12.6 and 12.6; W24: 5.1 and 2.6) and ISI (baseline: 6.7 and 6.9; W24: 2.9 and 1.6). Patients continuously treated with tofacitinib 5 and 10 mg BID maintained those improvements through Week 56 (DLQI: 3.0 and 2.1; ISI: 2.3 and 1.4). By W40, patients withdrawn from tofacitinib 5 and 10 mg BID showed worsening in DLQI (5.0 and 6.2) and ISI (3.7 and 4.0) scores; improvements were regained upon re-treatment (W56, DLQI: 3.4 and 2.4; ISI: 2.2 and 1.6). Similar results were reported for PtGA and SF-36., Conclusion: Continuous tofacitinib treatment provided sustained improvement in HRQoL and disease symptoms. Patients randomized to treatment withdrawal lost initial improvements. Upon re-treatment, improvements were recaptured to levels comparable to those seen with continuous treatment., (© 2016 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Fixed combination calcipotriol 50 μg/g (Cal) plus betamethasone 0.5 mg/g (BD) foam has been developed as a new treatment option for patients with psoriasis., Methods: The randomized, parallel-group, investigator-blinded Phase III, 12-week PSO-ABLE study compared the efficacy and safety of Cal/BD foam with Cal/BD gel. Patients aged ≥18 years with mild-to-severe psoriasis were randomized 4:4:1:1 to once-daily Cal/BD foam, Cal/BD gel, foam vehicle or gel vehicle (NCT02132936). The primary efficacy endpoint was the proportion of patients who were clear/almost clear with a ≥ 2 grade improvement according to the physician's global assessment of disease severity (i.e. treatment success) at week 4 for Cal/BD foam vs. week 8 for Cal/BD gel. Secondary efficacy endpoints included: proportion of patients achieving at least a 75% reduction in modified psoriasis area and severity index (mPASI75), and time to treatment success (TTTS). Safety was monitored throughout., Results: A total of 463 patients were randomized: Cal/BD foam (n = 185), Cal/BD gel (n = 188), foam vehicle (n = 47), gel vehicle (n = 43); overall completion rate was 90%. Cal/BD foam achieved higher treatment success rates (38% vs. 22%; P < 0.001) and mPASI75 (52% vs. 35%; P < 0.001) by week 4 than Cal/BD gel by week 8. Median TTTS with Cal/BD foam was 6 weeks; this could not be determined for Cal/BD gel as 50% treatment success was not achieved (P < 0.001). Adverse drug reactions were reported in 14 (7.6%) Cal/BD aerosol foam patients and 7 (3.7%) Cal/BD gel patients; all were single events except for itch with Cal/BD aerosol foam (n = 5; 2.7%) and worsening psoriasis with Cal/BD gel (n = 3; 1.6%)., Conclusion: Cal/BD aerosol foam showed significantly greater efficacy after 4 weeks, than 8 weeks of treatment with Cal/BD gel, with similar tolerability., (© 2016 European Academy of Dermatology and Venereology.)

Psoriasis and atopic dermatitis are common, chronic inflammatory skin diseases. We discuss several aspects of these disorders, including: risk factors; incidence and prevalence; the complex disease burden; and the comorbidities that increase the clinical significance of each disorder. We also focus on treatment management strategies and outline why individualized, patient-centered treatment regimens should be part of the care plans for patients with either psoriasis or atopic dermatitis. Finally, we conclude that, while our theoretical knowledge of the optimum care plans for these patients is increasingly sophisticated, this understanding is, unfortunately, not always reflected in daily clinical practice.

Background: There is accumulating evidence that early-onset psoriasis (EOP; presenting at or before 40 years of age) and late-onset psoriasis (LOP; presenting after 40 years of age) are different diseases., Objectives: We aimed to identify potential clinical and immunocytochemical differences between EOP and LOP., Methods: We assessed immunocytochemistry in involved (PP) skin and uninvolved skin (n = 31) and demographics, psoriasis phenotype and psychological parameters (n = 340) in a cross-sectional study., Results: Immunocytochemistry revealed (17 EOP, 14 LOP) a greater lymphocytic infiltrate in PP skin of EOP compared with LOP (P = 0·03), with a higher epidermal CD4 + : CD8 + ratio in LOP (1·3) compared with EOP (0·5) (P = 0·002). In 340 patients with psoriasis (278 EOP, 62 LOP), we found an association with a positive first or second degree family history of psoriasis [62·0% vs. 35·6%, adjusted odds ratio (OR) 8·32, 95% confidence interval (CI) 1·90-36·52] and a higher likelihood of having parents with EOP (adjusted OR 10·34, 95% CI 1·32-81·83) in the EOP group. Patients with EOP were more likely to have received biological therapy (13·3% EOP vs. 3·5% LOP, P = 0·042), while patients with LOP had a higher likelihood of having type 2 diabetes (adjusted OR 3·43, 95% CI 1·004-11·691) and autoimmune thyroiditis (adjusted OR 5·05, 95% CI 1·62-15·7). Patients with LOP also had greater anxiety than patients with EOP (mean Hospital Anxiety and Depression Scale-A score LOP 8 ± 5, EOP 5 ± 5; P = 0·006)., Conclusions: Our findings provide further evidence for the difference between EOP and LOP., (© 2016 British Association of Dermatologists.)

Background: Unhealthy lifestyle is common in psoriasis, contributing to worsening disease and increased cardiovascular disease (CVD) risk. CVD risk communication should improve patients' understanding of risk and risk-reducing behaviours; however, the effectiveness of risk screening is debated and evaluation currently limited., Objective: To examine the process of assessing for and communicating about CVD risk in the context of psoriasis., Design: Mixed-methods study in English general practices to (i) determine proportions of CVD risk factors among patients with psoriasis at risk assessment and (ii) examine patient and practitioner experiences of risk communication to identify salient 'process' issues. Audio recordings of consultations informed in-depth interviews with patients and practitioners using tape-assisted recall, analysed with framework analysis., Participants: Patients with psoriasis (n = 287) undergoing CVD risk assessment; 29 patients and 12 practitioners interviewed., Results: A high proportion of patients had risk factor levels apparent at risk assessment above NICE recommendations: very high waist circumference (52%), obesity (35%), raised blood pressure (29%), smoking (18%) and excess alcohol consumption (18%). There was little evidence of personalized discussion about CVD risk and behaviour change support in consultations. Professionals reported a lack of training in behaviour change, while patients wanted to discuss CVD risk/risk reduction and believed practitioners to be influential in supporting lifestyle management., Conclusions: Despite high levels of risk factors identified, opportunities may be missed in consultations to support patients with psoriasis to understand CVD risk/risk reduction. Practitioners need training in behaviour change techniques to capitalize on 'teachable moments' and increase the effectiveness of risk screening., (© 2015 The Authors. Health Expectations Published by John Wiley & Sons Ltd.)

Objectives: Systemic sclerosis (SSc)-related digital ulcers (DU) cause significant pain and disability and are often a primary endpoint in clinical trials. However, their pathophysiology has been little studied. The objectives of this prospective study were to determine whether laser Doppler imaging (LDI) and thermography can identify ischaemic components in both fingertip and extensor surface DU and assess ulcer healing., Methods: Patients prospectively reported new DU over a year. Patients' DU underwent imaging until the ulcer had healed. Ischaemia was defined as lower blood flow or skin temperature (and inflammation as higher) within the ulcer, compared to a non-affected site., Results: 53 ulcers (19 fingertip, 18 extensor, 16 'other' sites) in 17 patients were imaged (53 with LDI, 52 with thermography). For LDI data 32 (60%) ulcers were ischaemic; median perfusion ulcer/unaffected area; 0.79 (range 0.11-2.9). For thermography data 35 (66%) were ischaemic; 0.98 (0.89 to 1.1). Inflammation in the surrounding area was identified for all ulcers by LDI but not thermography. In the 36 ulcers with repeat imaging, LDI showed trends (with healing) towards increased ulcer perfusion (p=0.23) and decreased hyperaemia in adjacent areas (p=0.59). Skin temperature at the ulcer site showed no significant change (p=0.13) but adjacent area showed decreased temperature (p=0.04 signifying decreased blood flow)., Conclusions: LDI and thermography are sufficiently sensitive to measure ischaemia in both fingertip and extensor ulcers. LDI was better suited to monitoring change in perfusion with healing (due to higher imaging resolution, or vascular changes occurring in more superficial skin layers).

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., (© 2016 British Association of Dermatologists.)

Senescent cells are more prevalent in aged human skin compared to young, but evidence that senescent cells are linked to other biomarkers of aging is scarce. We counted cells positive for the tumor suppressor and senescence associated protein p16INK4a in sun-protected upper-inner arm skin biopsies from 178 participants (aged 45-81 years) of the Leiden Longevity Study. Local elastic fiber morphology, facial wrinkles, and perceived facial age were compared to tertiles of p16INK4a counts, while adjusting for chronological age and other potential confounders.The numbers of epidermal and dermal p16INK4a positive cells were significantly associated with age-associated elastic fiber morphologic characteristics, such as longer and a greater number of elastic fibers. The p16INK4a positive epidermal cells (identified as primarily melanocytes) were also significantly associated with more facial wrinkles and a higher perceived age. Participants in the lowest tertile of epidermal p16INK4a counts looked 3 years younger than those in the highest tertile, independently of chronological age and elastic fiber morphology.In conclusion, p16INK4a positive cell numbers in sun-protected human arm skin are indicative of both local elastic fiber morphology and the extent of aging visible in the face., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated efficacy and safety in patients with moderate to severe plaque psoriasis., Objective: We reviewed safety data from the secukinumab psoriasis phase II/III program., Methods: Data were pooled from 10 phase II/III secukinumab psoriasis studies., Results: Analysis included 3993 subjects; 3430 received secukinumab, representing 2725 subject-years (SYs) of exposure. Over 52 weeks, for secukinumab 300 mg, 150 mg, and etanercept, respectively, exposure-adjusted incidence rates (IRs) per 100 SYs were comparable across treatments for total adverse events (AEs; 236.1, 239.9, and 243.4, respectively); infections (91.1, 85.3, and 93.7, respectively); serious AEs (7.4, 6.8, and 7.0, respectively); serious infections (1.4, 1.1, and 1.4, respectively); malignant or unspecified tumors (0.77, 0.97, and 0.68, respectively); and adjudicated major adverse cardiovascular events (0.42, 0.35, and 0.34, respectively). AEs were not dose-related except for nonserious, mild/moderate, skin/mucosal candidiasis (IRs 3.55, 1.85, and 1.37 for secukinumab 300 mg, 150 mg, and etanercept, respectively)., Limitations: There was a limited number of patients in comparator groups and the exposure to placebo was short., Conclusion: Secukinumab had a favorable safety profile, had no meaningful difference between the 300- and 150-mg doses and, in terms of safety, was comparable to etanercept over 52 weeks in patients with moderate to severe plaque psoriasis., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)