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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. [ABSTRACT FROM AUTHOR]

Extensive morphoea causes major morbidity, disability and disfigurement; pathophysiology is poorly understood. The aim of this study was to investigate, with non-invasive imaging, the relationship between localised abnormalities of skin structure and perfusion, which characterise morphoea. Thirty-two patients with morphoea underwent imaging at affected and unaffected sites. Skin thickness was imaged with optical coherence tomography (OCT) and high-frequency ultrasound (HFUS). Perfusion was imaged with dual-wavelength laser Doppler imaging (LDI) and thermography. Epidermal thickness showed a small increase from affected to unaffected site (OCT, active and inactive plaques [p = 0.005 and p = 0.004], HFUS active plaques only [p = 0.03]). Deeper perfusion was higher within affected than unaffected sites (LDI p < 0.001, thermography p < 0.0001, active and inactive plaques). Epidermal thickness was inversely related to superficial (but not deeper) perfusion. This novel study of OCT, HFUS, LDI and thermography confirms loss of epidermal thickness and increased deeper perfusion in morphoea plaques. [ABSTRACT FROM AUTHOR]

The article discusses the background and objectives of the development of the academic-industrial stratified medicine consortium in psoriasis, Psoriasis Stratification to Optimize Relevant Therapy (PSORT). The consortium is funded by the government agency Medical Research Council in Great Britain, and its main objective is to use clinical, pharmacological, genetic, and immune biomarkers to predict psoriasis response to therapies. Other topics discussed include PSORT's focus and the partners.

Background Ixekizumab is a humanised monoclonal antibody against the proinflammatory cytokine interleukin 17A. We report two studies of ixekizumab compared with placebo or etanercept to assess the safety and efficacy of specifically targeting interleukin 17A in patients with widespread moderate-to-severe psoriasis. Methods In two prospective, double-blind, multicentre, phase 3 studies (UNCOVER-2 and UNCOVER-3), eligible patients were aged 18 years or older, had a confirmed diagnosis of chronic plaque psoriasis at least 6 months before baseline (randomisation), 10% or greater body-surface area involvement at both screening and baseline visits, at least a moderate clinical severity as measured by a static physician global assessment (sPGA) score of 3 or more, and a psoriasis area and severity index (PASI) score of 12. Participants were randomly assigned (1:2:2:2) by computer-generated random sequence with an interactive voice response system to receive subcutaneous placebo, etanercept (50 mg twice weekly), or one injection of 80 mg ixekizumab every 2 weeks, or every 4 weeks after a 160 mg starting dose. Blinding was maintained with a double-dummy design. Coprimary efficacy endpoints were proportions of patients achieving sPGA score 0 or 1 and 75% or greater improvement in PASI at week 12. Analysis was by intention to treat. These trials are registered with ClinicalTrials.gov, numbers NCT01597245 and NCT01646177. Findings Between May 30, 2012, and Dec 30, 2013, 1224 patients in UNCOVER-2 were randomly assigned to receive subcutaneous placebo (n=168), etanercept (n=358), or ixekizumab every 2 weeks (n=351) or every 4 weeks (n=347); between Aug 11, 2012, and Feb 27, 2014, 1346 patients in UNCOVER-3 were randomly assigned to receive placebo (n=193), etanercept (n=382), ixekizumab every 2 weeks (n=385), or ixekizumab every 4 weeks (n=386). At week 12, both primary endpoints were met in both studies. For UNCOVER-2 and UNCOVER-3 respectively, in the ixekizumab every 2 weeks group, PASI 75 was achieved by 315 (response rate 89·7%; [effect size 87·4% (97·5% CI 82·9–91·8) vs placebo; 48·1% (41·2–55·0) vs etanercept]) and 336 (87·3%; [80·0% (74·4–85·7) vs placebo; 33·9% (27·0–40·7) vs etanercept]) patients; in the ixekizumab every 4 weeks group, by 269 (77·5%; [75·1% (69·5–80·8) vs placebo; 35·9% (28·2–43·6) vs etanercept]) and 325 (84·2%; [76·9% (71·0–82·8) vs placebo; 30·8% (23·7–37·9) vs etanercept]) patients; in the placebo group, by four (2·4%) and 14 (7·3%) patients; and in the etanercept group by 149 (41·6%) and 204 (53·4%) patients (all p<0·0001 vs placebo or etanercept). In the ixekizumab every 2 weeks group, sPGA 0/1 was achieved by 292 (response rate 83·2%; [effect size 80·8% (97·5% CI 75·6–86·0) vs placebo; 47·2% (39·9–54·4) vs etanercept]) and 310 (80·5%; [73·8% (67·7–79·9) vs placebo; 38·9% (31·7–46·1) vs etanercept]) patients; in the ixekizumab every 4 weeks group by 253 (72·9%; [70·5% (64·6–76·5) vs placebo; 36·9% (29·1–44·7) vs etanercept]) and 291 (75·4%; [68·7% (62·3–75·0) vs placebo; 33·8% (26·3–41·3) vs etanercept]) patients; in the placebo group by four (2·4%) and 13 (6·7%) patients; and in the etanercept group by 129 (36·0%) and 159 (41·6%) patients (all p<0·0001 vs placebo or etanercept). In combined studies, serious adverse events were reported in 14 (1·9%) of 734 patients given ixekizumab every 2 weeks, 14 (1·9%) of 729 given ixekizumab every 4 weeks, seven (1·9%) of 360 given placebo, and 14 (1·9%) of 739 given etanercept; no deaths were noted. Interpretation Both ixekizumab dose regimens had greater efficacy than placebo and etanercept over 12 weeks in two independent studies. These studies show that selectively neutralising interleukin 17A with a high affinity antibody potentially gives patients with psoriasis a new and effective biological therapy option. INSET: Panel: Research in context.. [ABSTRACT FROM AUTHOR]

Objective To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions. Methods A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated. Results Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody-positive patients received lower median dosages of methotrexate compared with antidrug antibody-negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels. Conclusion Pharmacologic testing in anti-tumor necrosis factor-treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months. [ABSTRACT FROM AUTHOR]

Circulatory levels of insulin-like growth factor (IGF-1), glucose, and cortisol have been previously associated with facial aging. However, as these serum measures are related, it is unclear whether their associations with skin aging occur independently from each other. We aimed to investigate whether the associations between serum IGF-1, glucose, and cortisol levels and perceived age/wrinkle grade occur independently of each other and whether these are mediated via skin wrinkling or via other skin aging features. Perceived age and skin wrinkling grade were assessed in a random sample from the Leiden Longevity Study with non-fasted (N = 579) and fasted blood sampling (N = 219). In our study population, a higher non-fasted IGF-1 level was associated with a lower skin wrinkling grade (p value = 0.014) and tended to associate with a lower perceived age (p value = 0.067), which was mediated for approximately 100 % by skin wrinkling. A higher non-fasted glucose level was associated with a higher perceived age (p value = 0.017), which was mediated for 51 % by skin wrinkling grade (p value = 0.112). A higher fasted cortisol level tended to associate with a higher perceived age (p value = 0.116), which was mediated for 29 % by skin wrinkling. Results remained similar when the serum measures were statistically adjusted for each other. Thus, the previously reported serum measures associate independently from each other with skin aging. IGF-1 is predominantly associated with perceived age by skin wrinkling, whereas cortisol and glucose also by other skin aging features. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Sodium cromoglicate (SCG) is a chromone with anti-inflammatory, anti-itch and anti-allergic activity. This trial is a 12-week comparison (RCT) of a 4% SCG cutaneous emulsion with its vehicle in AD. Materials and methods: 208 children aged 2-12 years participated, 104 in each group. The primary endpoint was change in SCORAD score. Secondary endpoints included SASSAD score, topical steroid usage and global assessments. Results: SCORAD was reduced by 28% (SCG group) and by 19% (vehicle): difference was statistically significant ( p = 0.03) after 8 weeks and nearly significant ( p = 0.09) after 12. A similar result occurred in SASSAD ( p = 0.001 at 8 weeks). In subjects without major protocol deviations (SCG-64, vehicle-63), difference in SCORAD remained significant at 12 weeks ( p = 0.04). Weight of topical steroids reduced in both groups: −0.60 ± 1.3 g/day (35%), SCG and −0.05 ± 1.1 g/day vehicle ( p = 0.04). Treatment success, defined as investigator global opinion graded very or moderately effective, was significantly more frequent in SCG group ( p = 0.025). Application site discomfort reported by 12.5% of subjects in SCG group and 16.5% in vehicle group. Conclusions: SCG 4% cutaneous emulsion provides an effective, well-tolerated, steroid-sparing treatment for AD in children. [ABSTRACT FROM AUTHOR]

Background: The influence of environmental factors in shaping behaviour is becoming increasingly prominent in public health policy, but whether health promotion strategies use this knowledge is unknown. Health promotion is important in the management of psoriasis, a long-term inflammatory skin condition, and health centre waiting areas are ideal places to promote health information to such patients. We systematically examined patient information materials containing either general, or specific, health messages for patients with psoriasis. Methods: An observation schedule was used to record the frequency and quality of leaflets and posters addressing lifestyle behaviour change in health centre waiting areas. Content analysis was used to analyse: frequency, characteristics and standard of the materials. Results: Across 24 health centres 262 sources of lifestyle information were recorded (median per site = 10; range = 0-40). These were mainly: generic posters/displays of lifestyle support (n =113); and generic materials in waiting areas (n = 98). Information quality was poor and poorly displayed, with no high quality psoriasis-specific patient materials evident. Conclusions: There is little attempt to promote healthy lifestyle as an important aspect of psoriasis management in the clinic environment. Evidence about using environmental cues/techniques to prompt behaviour change in people with psoriasis does not currently inform the design and display of such information in standard health centre settings, which are prime locations for communicating messages about healthy lifestyle. Future research should test the efficacy and impact of theory-informed, high quality health promotion messages on health outcomes for patients with psoriasis. [ABSTRACT FROM AUTHOR]

Objective. Cutaneous telangiectases are a characteristic and psychologically distressing feature of SSc. Our aim was to assess the efficacy of two light-based treatments: pulsed dye laser (PDL) and intense pulsed light (IPL).Methods. Nineteen patients with facial or upper limb telangiectases underwent three treatments with PDL and IPL (randomly assigned to left- and right-sided lesions). Outcome measures were clinical photography (assessed by two clinicians), dermoscopy (assessed by two observers), laser Doppler imaging (LDI) and observer and patient opinion, including patient self-assessment psychological questionnaires [Hospital Anxiety and Depression Scale (HADS), Adapted Satisfaction with Appearance Scale (ASWAP)].Results. Comparison between 16-week follow-up and baseline photography scores (from −2 to +2 on a Likert scale, with >0 being improvement) were a mean score for PDL of 1.7 (95% CI 1.4, 2.0) and for IPL 1.4 (0.9, 1.8), with a mean difference between PDL and IPL of −0.3 (−0.5, −0.1) (P = 0.01). Dermoscopy scores also improved with both therapies: PDL 1.3 (1.1, 1.5) and IPL 0.8 (0.5, 1.1), again greater with PDL (P = 0.01). LDI showed decreases in blood flow at 16 weeks, indicating a response to both therapies. All patients reported benefit from treatment (more preferred PDL at 16 weeks). Psychological questionnaires also indicated improvement after therapy with mean change in ASWAP of −13.9 (95% CI −20.5, −7.4). No side effects were reported for IPL; PDL caused transient bruising in most cases.Conclusion. Both PDL and IPL are effective treatments for SSc-related telangiectases. Outcome measures indicate that PDL has better outcomes in terms of appearance, although IPL had fewer side effects. [ABSTRACT FROM PUBLISHER]

The Simplified Psoriasis Index (SPI) is a summary measure of psoriasis with separate components for current severity (weighted for functionally or psychosocially important sites), psychosocial impact, and past behavior. The current severity components of the professionally assessed SPI (proSPI-s) and self-assessed SPI (saSPI-s) have each been shown to be valid and reliable. Their responsiveness to change and equivalence to the current standard (Psoriasis Area and Severity Index, PASI) were investigated. Responsiveness and minimum clinically important differences (MCIDs) were derived from PASI changes from baseline at weeks 4 (n=100) and 10 (n=65) in patients commencing therapy for psoriasis. Receiver operating characteristic (ROC) analysis confirmed that both measures detected responsiveness well (area under the curve (AUC)=0.72-0.96). On ROC and PASI-based anchor analysis, MCIDs equated to mean absolute and percentage changes of 5 and 60% (proSPI-s), and 7 and 70% (saSPI-s). Satisfactory response as defined by 75% reduction in PASI equated to 85 and 95% reductions in proSPI-s and saSPI-s, respectively. PASI-equivalent cutoff scores for mild (PASI<10) and severe (PASI>20) psoriasis were <9 and >18 for proSPI-s (n=300) and <10 and >20 for saSPI-s (n=200; AUC=0.86-0.96). These studies further support the validity of SPI for use in routine clinical practice. [ABSTRACT FROM AUTHOR]

The Simplified Psoriasis Index (SPI) is a summary measure of psoriasis with separate components for current severity (SPI-s), psychosocial impact (SPI-p), and past history and interventions (SPI-i). It derives from the Salford Psoriasis Index but replaces Psoriasis Area and Severity Index (PASI) with a composite weighted severity score designed to reflect the impact of psoriasis affecting functionally or psychosocially important body sites. Two complementary versions are available, differing only in that current severity (SPI-s) is either professionally (proSPI-s) or patient self-assessed (saSPI-s). This study examined the criterion and construct validity and response distribution of proSPI-s, saSPI-s, and SPI-p in 100 patients with plaque psoriasis. A further 50 patients were assessed for test-retest reliability of these three components. Interrater reliability of proSPI-s was assessed in 12 patients, each assessed by 12 assessors (144 assessments). There was close correlation between PASI and proSPI-s (r=0.91); SPI-p was closely correlated with the Dermatology Life Quality Index (r=0.89). Strong intrarater (proSPI-s, saSPI-s, SPI-p, and SPI-i) and interrater (proSPI-s) reliability was demonstrated (all intraclass correlation coefficients >0.75). There were wide response distributions for all three components. We believe that both professional (proSPI) and self-assessed (saSPI) versions can readily be introduced into routine clinical practice. [ABSTRACT FROM AUTHOR]

Immunomodulatory biologics, which render their therapeutic effects by modulating or harnessing immune responses, have proven their therapeutic utility in several complex conditions including cancer and autoimmune diseases. However, unwanted adverse reactions - including serious infections, malignancy, cytokine release syndrome, anaphylaxis and hypersensitivity as well as immunogenicity - pose a challenge to the development of new (and safer) immunomodulatory biologics. In this article, we assess the safety issues associated with immunomodulatory biologics and discuss the current approaches for predicting and mitigating adverse reactions associated with their use. We also outline how these approaches can inform the development of safer immunomodulatory biologics. [ABSTRACT FROM AUTHOR]

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 PUBLISHER]

The article describes the extensive use of biologic therapies, particularly for anti-cytokines in dermatology that manages of severe skin diseases. It also states that Tumor necrosis Factor (TNF) antagonists which offers high efficacy for psoriasis and several skin condition. Topics include biologic therapy targeting interleukin-12 along with interleukin-23 cytokines, biologic therapy targeting B-cells, and miscellaneous biologic therapies.

Background Psoriasis is a chronic, inflammatory skin disease affecting approximately 2% of the UK population and is currently incurable. It produces profound effects on psychological wellbeing and social functioning and has significant associated co-morbidities. The majority of patients with psoriasis are managed in primary care, however in-depth patient and GP perspectives about psoriasis management in this setting are absent from the literature. This article reports an in-depth study which compares and contrasts the perspectives of people with psoriasis and of GPs on the challenges of managing psoriasis in primary care. Methods In-depth, qualitative semi-structured interviews were conducted with a diverse sample of 29 people with psoriasis and 14 GPs. Interviews were coded using principles of Framework Analysis to enable a comparison of patient and practitioner perspectives on key issues and concepts arising from the data. Results Patients perceived GPs to be lacking in confidence in the assessment and management of psoriasis and both groups felt lacking in knowledge and understanding about the condition. While practitioners recognised that psoriasis has physical, emotional and social impact, they assumed patients had expertise in the condition and may not address these issues in consultations. This resulted in patient dissatisfaction and sub-optimal assessment of severity and impact of psoriasis by GPs. Patients and GPs recognised that psoriasis was not being managed as a complex long-term condition, however this appeared less problematic for GPs than for patients who desired a shared management with their GP incorporating appropriate monitoring and timely reviews. Conclusions The research suggests that current routine practice for psoriasis management in primary care is mismatched with the expressed needs of patients. To address these needs, psoriasis must be recognised as a complex long-term condition involving exacting physical, psychological and social demands, co-morbidity and the development of new treatments. General practitioners need to improve both their knowledge and skills in the assessment and management of psoriasis. This in turn will facilitate management of the condition in partnership with patients. Commissioning multi-disciplinary services, which focus on long-term impacts on wellbeing and quality of life, might address current deficits in care. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a rare auto‐inflammatory skin disease characterised by acute episodes of sterile pustule formation. Diagnosis and treatment of the disease have historically been complicated by a lack of awareness, and no consistent global definition or clinical coding standards. Now acknowledged as a distinct clinical entity with a recognised genetic component, GPP can take a serious and life‐threatening course due to systemic inflammatory complications and its association with various comorbidities. As with other rare diseases, there are significant challenges to understanding the epidemiology of GPP, notably a small patient population, non‐standardised study methodologies and ethnic differences in its presentation. A clearer understanding of GPP is therefore required for clinicians to better manage patients with this rare condition. In this review article, we present an overview of the available data on GPP prevalence estimates in key demographics and report the frequency of genetic mutations associated with the disease. We detail the incidence of known comorbidities and summarise the data on mortality and assigned causes of death. Lastly, we discuss the various factors that impact the collection, interpretation and comparison of these data. [ABSTRACT FROM AUTHOR]