Showing papers in "British Journal of Dermatology in 2016"

A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis†

Abstract: SummaryBackground The interleukin-17 cytokine family plays a central role in psoriasis pathogenesis. Objectives To evaluate the efficacy and safety of brodalumab, a human anti-interleukin-17 receptor antibody, in treating patients with moderate-to-severe plaque psoriasis. Methods In this phase III, double-blind, placebo-controlled study (NCT01708590; AMAGINE-1), adult patients in the U.S.A., Canada and Europe were randomized to brodalumab (140 or 210 mg) or placebo every 2 weeks (Q2W), with an additional dose at week 1, for a 12-week induction phase. At week 12, patients receiving brodalumab who achieved static Physician's Global Assessment 0 or 1 (sPGA success) were rerandomized to the placebo or induction dose. After week 16, patients with sPGA ≥ 3 were re-treated with the induction dose. After ≥ 12 weeks of retreatment, patients with sPGA 2 for ≥ 4 weeks or sPGA ≥ 3 were rescued with brodalumab 210 mg Q2W. At week 12, patients randomized to brodalumab with sPGA ≥ 2 or placebo received brodalumab 210 mg Q2W. Coprimary end points were the percentage of patients with ≥ 75% improvement in Psoriasis Area and Severity Index score (PASI 75) and sPGA success at week 12. Results There were 661 patients randomized: 220 placebo, 219 brodalumab 140 mg and 222 brodalumab 210 mg. At week 12, 60% (140 mg) and 83% (210 mg) vs. 3% (placebo) achieved PASI 75, and 54% (140 mg) and 76% (210 mg) vs. 1% (placebo) achieved sPGA success. The safety profile was considered acceptable. Conclusions Brodalumab therapy resulted in significant clinical benefit and an acceptable safety profile in patients with moderate-to-severe plaque psoriasis.

Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial.

Abstract: SummaryBackground Despite unmet need, 15 years have passed since a topical therapy with a new mechanism of action for atopic dermatitis (AD) has been approved. Janus kinase (JAK) inhibitor treatment effect via topical application in patients with AD is unknown. Objectives Tofacitinib, a small-molecule JAK inhibitor, was investigated for the topical treatment of AD. Methods In this 4-week, phase IIa, randomized, double-blind, vehicle-controlled study (NCT02001181), 69 adults with mild-to-moderate AD were randomized 1:1 to 2% tofacitinib or vehicle ointment twice daily. Percentage change from baseline (CFB) in Eczema Area and Severity Index (EASI) score at week 4 was the primary end point. Secondary efficacy end points included percentage CFB in body surface area (BSA), CFB in EASI Clinical Signs Severity Sum Score, proportion of patients with Physician's Global Assessment (PGA) response and CFB in patient-reported pruritus. Safety, local tolerability and pharmacokinetics were monitored. Results The mean percentage CFB at week 4 in EASI score was significantly greater (P < 0·001) for tofacitinib (−81·7%) vs. vehicle (−29·9%). Patients treated with tofacitinib showed significant (P < 0·001) improvements vs. vehicle across all prespecified efficacy end points and for pruritus at week 4. Significant improvements in EASI, PGA and BSA were observed by week 1 and improvements in pruritus were observed by day 2. Safety/local tolerability were generally similar for both treatments, although more adverse events were observed for vehicle vs. tofacitinib. Conclusions Tofacitinib ointment showed significantly greater efficacy vs. vehicle across end points, with early onset of effect and comparable safety/local tolerability to vehicle. JAK inhibition through topical delivery is potentially a promising therapeutic target for AD.

Prevalence and odds of Staphylococcus aureus carriage in atopic dermatitis: a systematic review and meta-analysis.

Abstract: SummaryBackground Staphylococcus aureus is increasingly implicated as a possible causal factor in the pathogenesis of atopic dermatitis (AD). However, the reported prevalence rates of skin and nasal colonization in the literature vary widely. Objectives This study evaluates the prevalence and odds of skin and nasal colonization with S. aureus in patients with AD. Methods A systematic literature search was conducted. Odds ratios (ORs) for colonization in patients vs. controls and the prevalence of colonization in patients were pooled using the random-effects model. Results Overall, 95 observational studies were included, of which 30 had a control group. The Newcastle–Ottawa Scale was used to assess study quality, with the majority of studies being of fair to poor quality. Patients with AD were more likely to be colonized with S. aureus than healthy controls [OR 19·74, 95% confidence interval (CI) 10·88–35·81]. Differences were smaller in nonlesional skin (OR 7·77, 95% CI 3·82–15·82) and in the nose (OR 4·50, 95% CI 3·00–6·75). The pooled prevalence of S. aureus colonization among patients was 70% for lesional skin, 39% for nonlesional skin and 62% for the nose. In lesional skin, meta-regression showed that the prevalence of colonization increased with disease severity. Study heterogeneity should be taken into consideration when interpreting the results. Conclusions These results demonstrate the importance of colonization with S. aureus in AD. Further evaluation of the mechanisms by which S. aureus influences inflammation is required in addition to the development of targeted strategies to decrease skin and nasal S. aureus load.

Prevalence of contact allergy in the general population in different European regions.

Abstract: Background Population/based studies about contact allergy are scarce. Objectives To obtain reliable estimates of the prevalence of contact allergy in the general population in Europe. Methods A cross-sectional study of a random sample from the general population, aged 18-74 years, in five different European countries (Sweden, the Netherlands, Germany, Italy and Portugal). In total, 12 377 subjects were interviewed and a random sample (n = 3119) patch tested to TRUE Test panels 1-3 and Fragrance Mix (FM) II, hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) and sesquiterpene lactone mix. A positive patch test reaction is considered as contact allergy. Results In total, 27.0% [95% confidence interval (CI) 25.5-28.5] had at least one positive reaction to an allergen of the European baseline series, with a significantly higher prevalence in women than in men. The highest age-standardized prevalences (>= 1%) were found for nickel (14.5%, 95% CI 13.2-15.8), thiomersal (5.0%, 95% CI 4.2-5.8), cobalt (2.2%, 95% CI 1.7-2.7), FM II (1.9%, 95% CI 1.5-2.5), FM I (1.8%, 95% CI 1.4-2.3), HICC (1.4%, 95% CI 1.0-1.9), p-tert-butylphenol formaldehyde resin (1.3%, 95% CI 0.9-1.7) and para-phenylenediamine (1.0%, 95% CI 0.6-1.3). Only nickel and thiomersal showed a statistically significantly different prevalence for contact allergy among the different European populations. Subjects reporting contact dermatitis in their lifetime (age-standardized prevalence 15.1%, 95% CI 13.8-16.3) had an increased risk for contact allergy (odds ratio 1.9, 95% CI 1.5-2.5). The risk of having a contact allergy was not increased in those with atopic dermatitis (prevalence 7.6%, 95% CI 6.7-8.6; odds ratio 1.0, 95% CI 0.7-1.4). Conclusions Contact allergy to at least one allergen of the European baseline series was diagnosed in more than one-quarter of the general European population. Therefore measures to improve the primary prevention of contact allergy have to be enforced.

A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis.

Abstract: SummaryBackground Plaque psoriasis is a chronic and often debilitating skin disorder and proinflammatory cytokines are known to play a key role in the disease process. Objectives To evaluate the safety and efficacy of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis in a randomized, double-blind, placebo-controlled, dose-ranging phase 2b study. Methods Patients were randomized (n = 271) to receive placebo or oral baricitinib at 2, 4, 8 or 10 mg once daily for 12 weeks (Part A). Dose adjustment for 12 additional weeks was based on percentage improvement in the Psoriasis Area and Severity Index (PASI) score. The primary end point was Psoriasis Area and Severity Index (PASI) 75% (PASI-75) at 12 weeks for North American patients (n = 238); secondary end points were safety and efficacy measures in the entire population. Results At week 12, more North American patients in the 8-mg (43%) and 10-mg (54%) baricitinib groups than in placebo group (17%; P < 0·05) achieved PASI-75. All baricitinib-treated groups had greater mean changes from baseline in their PASI scores (P < 0·05) at 12 weeks and (except 2 mg) had higher rates of PASI-50 than the placebo group; statistically significant PASI-90 responses were achieved in the 8-mg and 10-mg groups at 8 and 12 weeks. More than 81% of PASI-75 responders maintained their scores through 24 weeks. During Part A, study discontinuations due to adverse events (AEs) were 0%, 0%, 2·8%, 6·3% and 5·8% and treatment-emergent AE rates were 44%, 50%, 47%, 58% and 64% for placebo and 2-, 4-, 8- and 10-mg baricitinib groups, respectively. No opportunistic infections were observed in any treatment group. Dose-dependent changes in laboratory values were observed. Conclusions Patients with moderate-to-severe psoriasis treated with baricitinib for 12 weeks achieved significant improvements in PASI-75.

U.K. guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016

Abstract: U.K. guidelines for the management of Stevens–Johnson syndrome/toxic epidermal necrolysis in adults 2016 D. Creamer, S.A. Walsh, P. Dziewulski, L.S. Exton, H.Y. Lee, J.K.G. Dart, J. Setterfield, C.B. Bunker, M.R. Ardern-Jones, K.M.T. Watson, G.A.E. Wong, M. Philippidou, A. Vercueil, R.V. Martin, G. Williams, M. Shah, D. Brown, P. Williams, M.F. Mohd Mustapa and C.H. Smith Department of Dermatology, King’s College Hospital NHS Foundation Trust, London SE5 9RS, U.K. St Andrews Centre for Plastic Surgery and Burns, Mid Essex Hospital Services NHS Trust, Chelmsford CM1 7ET, U.K. British Association of Dermatologists, Willan House, 4 Fitzroy Square, London W1T 5HQ, U.K. Dermatology Unit, Singapore General Hospital, Singapore Moorfields Eye Hospital, 162 City Road, London EC1V 2PD, U.K. Mucosa and Salivary Biology, Dental Institute, King’s College London, Guy’s Campus, Great Maze Pond, London SE1 9RT, U.K. University College Hospital, London NW1 2BU, U.K. Clinical Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, U.K. Department of Dermatology, Orpington Hospital, Orpington, Kent BR6 9JU, U.K. Department of Dermatology, University Hospital of South Manchester NHS Foundation Trust, Manchester M23 9LT, U.K. Department of Histopathology and Intensive Care Medicine, King’s College Hospital NHS Foundation Trust, London SE5 9RS, U.K. Late of the Burns Centre, Chelsea and Westminster NHS Foundation Trust, London SW10 9NH, U.K. Department of Burns and Plastic Surgery, University Hospitals of South Manchester, Southmoor Road, Wythenshawe, Manchester M23 9LT, U.K. St John’s Institute of Dermatology, Guy’s and St Thomas NHS Foundation Trust, London SE1 9RT, U.K.

Keratinocytes and neutrophils are important sources of proinflammatory molecules in hidradenitis suppurativa.

Abstract: SummaryBackground The pathogenesis of the chronic inflammatory skin disease hidradenitis suppurativa (HS, also known as acne inversa) involves epidermal alterations such as psoriasiform epidermal hyperplasia and keratin plugging. Keratinocytes are an important source of proinflammatory molecules in inflammatory skin diseases and can be stimulated by interleukin (IL)-17+ cells. Objectives To explore the possible role of the epithelium in the pathogenesis of HS. Methods We performed immunohistochemical stainings and Western blot experiments to investigate the localization and expression of inflammation-associated molecules, including the cytokine IL-17, components of the inflammasome including caspase-1, and the endogenous danger-associated molecular pattern molecules S100A8 and S100A9 (calprotectin). To examine a possible effect of upregulated proinflammatory cytokines on the inflammatory infiltrate, differences in the cellular composition of perifollicular and deep dermal infiltrates were analysed. Results The number of IL-17+ cells is increased in lesional and perilesional HS skin. The epidermis produces proinflammatory molecules and shows an upregulated expression of components of the NLRP3 inflammasome, activated caspase-1 and expression of S100A8/S100A9. Additionally, the course of the inflammatory process in HS involves influx of innate immune cells, particularly IL-17-expressing neutrophils. Conclusions IL-17-producing cells are present in lesional and perilesional HS skin and may contribute to the initiation of inflammatory processes. Furthermore, the epidermis is a source of proinflammatory cytokines, shows inflammasome activation and expresses S100A8/S100A9, thereby possibly contributing to the propagation of inflammation. A massive influx of IL-17-expressing neutrophils is observed in the deep infiltrate.

Ustekinumab in hidradenitis suppurativa: clinical results and a search for potential biomarkers in serum.

Abstract: BACKGROUND: Treatment of hidradenitis suppurativa (HS) is difficult and the search for effective therapies continues. OBJECTIVES: 1.To evaluate the efficacy of ustekinumab. 2.To discover a potential biomarker. METHODS: Seventeen patients were included in this open label study and treated with 45 to 90 mg ustekinumab at weeks 0, 4, 16 and 28. Proteomic technology and enzyme-linked assay analysis (ELISA) was applied on serum. RESULTS: Twelve patients completed the protocol. Moderate to marked improvement of the modified Sartorius Score was achieved in 82% of patients at week 40 and the hidradenitis suppurativa clinical response (HiSCR-50) in 47%. At baseline, a significant difference was observed in the expression of 54 serum proteins between patients and healthy controls. Involved pathways were related to inflammation, immune cell signaling, and tissue morphology/development. Good responders had milder disease and lower expression of leukotriene A4-hydrolase (LTA4H). IL-2R, TNF-α, IL17A and IL-17F were not elevated and did not change during treatment. CONCLUSIONS: The majority of patients improved with ustekinumab. Although no biomarker was discovered, low LTA4H concentrations with mild disease severity may be predictive for the effectiveness of ustekinumab. This article is protected by copyright. All rights reserved.

The first trial of CIM331, a humanized antihuman interleukin‐31 receptor A antibody, in healthy volunteers and patients with atopic dermatitis to evaluate safety, tolerability and pharmacokinetics of a single dose in a randomized, double‐blind, placebo‐controlled study

Abstract: SummaryBackground The cytokine interleukin-31 (IL-31) is considered to be responsible for the development of pruritus in humans. At present, no available evidence has been provided on the safety and efficacy of blocking the IL-31 signal in humans for the amelioration of pruritus in atopic dermatitis (AD). CIM331 is a humanized antihuman IL-31 receptor A (IL-31RA) monoclonal antibody, which binds to IL-31RA to inhibit subsequent IL-31 signalling. Objectives To assess the tolerability, safety, pharmacokinetics and preliminary efficacy of CIM331 in healthy Japanese and white volunteers, and Japanese patients with AD. Methods In this randomized, double-blind, placebo-controlled phase I/Ib study, CIM331 was administered in a single subcutaneous dose. The primary outcomes were safety and tolerability; the exploratory analysis was efficacy. Results No deaths, serious adverse events (AEs) or discontinuations due to AEs were reported in any part of the study. No dose-dependent increase in the incidence of AEs occurred in any part of the study. In healthy volunteers, all AEs occurred once in the placebo groups, and increased creatine phosphokinase was more common in the CIM331 groups. In patients with AD, CIM331 reduced pruritus visual analogue scale score to about −50% at week 4 with CIM331 compared with −20% with placebo. CIM331 increased sleep efficiency and decreased the use of hydrocortisone butyrate. Conclusions A single subcutaneous administration of CIM331 was well tolerated in healthy volunteers and patients with AD. It decreased pruritus, sleep disturbance and topical use of hydrocortisone. CIM331 may become a novel therapeutic option for AD by inhibiting IL-31.

Updosing nonsedating antihistamines in patients with chronic spontaneous urticaria: a systematic review and meta-analysis

Abstract: There is a lack of large, randomized, double-blind studies that address antihistamine updosing for chronic spontaneous urticaria (CSU). The objective of this systematic review is to explore and analyse available data to provide clinical evidence for the efficacy of antihistamine updosing. We searched the literature in Medline, Scopus, Google Scholar, Embase, Web of Science and Cochrane databases using the keywords 'chronic, urticaria, antihistamines' to identify studies published between January 1990 and November 2014. We assessed quality using the Jadad score that evaluates quality of randomization, double-blinding and losses to follow-up. We identified 1042 articles and 15 articles were included in the final evaluation. We performed two meta-analyses, one that included studies that analysed treatment response among groups receiving different antihistamine dosages vs. placebo, and another that analysed antihistamine updosing in those patients who did not respond to standard dosages. Only five articles obtained a high quality level score. We did not find significant differences in response rates or number of weals in those patients who received a standard dosage vs. a high dosage. We found a significant improvement only in the pruritus variable of the Urticaria Activity Score scale. The estimated relative risk for improvement by increasing the antihistamine dosage was 2·27 [95% confidence interval (CI) 1·68-3·06]; however, there was significant heterogeneity. The proportion of nonrespondent patients with CSU who responded to antihistamine updosing was 63·2% (95% CI 57-69·6). We found that updosing antihistamines significantly improved control of pruritus but not weal number. However, the relative weakness of the studies and the significant heterogeneity among them made it difficult to reach a final conclusion.

Bullous pemphigoid and dipeptidyl peptidase IV inhibitors: a case–noncase study in the French Pharmacovigilance Database

Abstract: SummaryBackground Inhibitors of dipeptidyl peptidase (DPP)-IV have been suspected in the onset of bullous pemphigoid for several years now. However, comparative studies assessing the link between DPP-IV inhibitor exposure and bullous pemphigoid have not yet been performed. Objectives To detect, from the French Pharmacovigilance Database (FPVD), a signal of risk of bullous pemphigoid during DPP-IV inhibitor exposure by comparative study. Methods All spontaneous reports of DPP-IV inhibitor-related bullous pemphigoid recorded in the FPVD between April 2008 and August 2014 were described. We conducted disproportionality analyses (case–noncase method) to assess the link between DPP-IV inhibitors and bullous pemphigoid, calculating reporting odds ratios (RORs). We also compared DPP-IV inhibitor-induced bullous pemphigoid reports rated per million defined daily doses dispensed during the study period. Results Among 217 331 spontaneous adverse drug reaction reports registered in the FPVD, 1297 involved DPP-IV inhibitors. Among these observations, 42 were bullous pemphigoid (vildagliptin, n = 31; sitagliptin, n = 10; saxagliptin, n = 1). The ROR for pooled DPP-IV inhibitors was 67·5 [95% confidence interval (CI) 47·1–96·9]. Disproportionality was also observed for each DPP-IV inhibitor: vildagliptin (ROR 225·3, 95% CI 148·9–340·9), sitagliptin (ROR 17·0, 95% CI 8·9–32·5) and saxagliptin (ROR 16·5, 95% CI 2·3–119·1). Analyses adjusted on dispensing data led to similar results. Conclusions These data confirm a strong signal for an increased risk of bullous pemphigoid during DPP-IV inhibitor exposure. This adverse drug reaction is observed for each DPP-IV inhibitor, suggesting a class effect. The signal was higher with vildagliptin than with the other DPP-IV inhibitors.

Alopecia areata and health‐related quality of life: a systematic review and meta‐analysis

Abstract: SummaryBackground No systematic review has yet evaluated the available evidence on health-related quality of life (HRQOL) in alopecia areata (AA). Objectives To conduct a systematic review and meta-analysis of HRQOL studies among patients diagnosed with AA. Methods A systematic search was performed for papers published between 1946 and 15 December 2014 in Medline, Embase, Web of Science, CINAHL, PsycINFO and the Cochrane Library. Random-effects meta-analyses were conducted to pool data. Results Twenty-one studies were included, representing a total of 2530 adult patients with AA. Of the 14 different HRQOL measures used in the studies, Dermatology Life Quality Index (DLQI; n = 8) and SF-36 (n = 7) were the most common. Three AA-specific HRQOL instruments were identified: Alopecia Areata Quality of Life Index, Alopecia Areata Quality of Life and Alopecia Areata Symptom Impact Scale. The mean pooled DLQI score of patients with AA was 6·3 (95% confidence interval 5·6–7·1). Comparing age- and sex-matched controls, the meta-analysis of SF-36 studies revealed significantly reduced HRQOL across the role-emotional, mental health and vitality domains (P < 0·001). Wearing a wig had a positive impact, while scalp involvement, anxiety and depression had a negative impact on HRQOL. Conflicting results were found regarding the association between HRQOL and age, sex, marital status and disease duration. Conclusions Patients with AA experience significant impairment in HRQOL, especially in the area of mental health. Several generic and dermatology-specific HRQOL instruments have been used, but no validation studies have confirmed their applicability in AA. The newly developed AA-specific measures seem very promising; however, a more extensive assessment of validity and reliability is needed.

Oxidative stress and ageing

Abstract: Summary Oxidative stress is the resultant damage due to redox imbalances (increase in destructive free radicals [reactive oxygen species (ROS)] and reduction in antioxidant protection/pathways) and is linked to ageing in many tissues including skin. In ageing skin there are bioenergetic differences between keratinocytes and fibroblasts which provide a potential ageing biomarker. The differences in skin bioenergy are part of the mitochondrial theory of ageing which remains one of the most widely accepted ageing theories describing subsequent increasing free radical generation. Mitochondria are the major source of cellular oxidative stress and form part of the vicious cycle theory of ageing. External and internal sources of oxidative stress include UVR/IR, pollution (environment), lifestyle (exercise and diet), alcohol and smoking all of which may potentially impact on skin although many exogenous actives and endogenous antioxidant defence systems have been described to help abrogate the increased stress. This also links to differences in skin cell types in terms of the UVR action spectrum for nuclear and mitochondrial DNA damage (the latter a previously described UVR biomarker in skin). Recent work associates bioenergy production and oxidative stress with pigment production thereby providing another additional potential avenue for targeted anti-ageing intervention in skin. This new data supporting the detrimental effects of the numerous wavelengths of UVR may aid in the development of cosmetic/sunscreen design to reduce the effects of photoageing. Recently, complex II of the mitochondrial electron transport chain appears to be more important than previously thought in the generation of free radicals (suggested predominantly by non-human studies). We investigated the relationship between complex II and ageing using human skin as a model tissue. The rate of complex II activity per unit of mitochondria was determined in fibroblasts and keratinocytes cultured from skin covering a wide age range. Complex II activity significantly decreased with age in fibroblasts (P = 0·015), but not in keratinocytes. This was associated with a significant decline in transcript expression (P = 0·008 and P = 0·001) and protein levels (P = 0·0006 and P = 0·005) of the SDHA and SDHB catalytic subunits of complex II respectively. In addition there was a significant decrease in complex II activity with age (P = 0·029) that was specific to senescent skin cells, our study being the first to investigate these differences with senescence and skin age. There was no decrease in complex IV activity with increasing age, suggesting possible locality to complex II. Our study provides a future potential biomarker for monitoring the progression of skin ageing.

Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)

Abstract: This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12–14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long-term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole-group and small-group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small-group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole-group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long-term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long-term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon.

High neutrophil to lymphocyte ratio measured before starting ipilimumab treatment is associated with reduced overall survival in patients with melanoma.

Abstract: Summary Background There is an unmet need to identify markers predictive of response to ipilimumab in patients with melanoma because the number of responders to ipilimumab is low and its cost is very high. An increase in absolute lymphocyte count (ALC) or low neutrophil/lymphocyte ratio (NLR) just before the third infusion has been reported to be associated with better overall survival (OS). Objectives Our aim was to determine whether NLR measured before the first infusion was associated with OS. Patients and methods Data were collected on a consecutive series of 58 patients treated with ipilimumab in four hospitals, including 51 at stage M1c and four at stage M1b. The influences of the NLR and other factors such as lactate dehydrogenase (LDH), performance status, ALC, absolute neutrophil count (ANC) and corticosteroids on survival were studied. We also assessed this association with NLR categorized as a binary variable. The cut-off value for the NLR was determined with time-dependent receiver operating characteristic (ROC) analysis. Univariate and multivariate analyses were performed using Cox regression models. Results High NLR (≥) 4, high ANC LDH levels (>2), performance status ≥2, symptomatic brain metastases, and corticosteroids before week 1 were associated with poorer survival on univariate analysis. Using multivariate analysis, a significant association between high NLR (continuous variable) and poorer survival was demonstrated and remained significant after adjustment on potential confounders [hazard ratio (HR) = 1·21, 95% confidence interval (CI) 1·07–1·36]. NLR ≥4 was an independent prognostic factor (HR = 2·2, 95% CI 1·01–4·78). Intake of corticosteroids before week 1 was not an independent prognostic factor (HR = 1·28, 95% CI 0·54–3·06). Conclusions High NLR (≥4) before initiating ipilimumab treatment in patients with metastatic melanoma is an independent prognostic indicator of poor survival.

Association between atopic dermatitis and attention deficit hyperactivity disorder in U.S. children and adults.

Abstract: SummaryBackground Atopic dermatitis (AD) is associated with chronic itch, allergic disease and sleep disturbance, all of which might increase the risk of attention deficit (hyperactivity) disorder (ADD/ADHD). Previous analyses have found a consistent association between AD and ADD/ADHD, although the underlying factors contributing to such an association remain underexplored. Additionally, the relationship has been underexplored in adults. Objectives To determine if childhood and adult AD and AD severity are associated with ADD/ADHD and to delineate the factors contributing to such an association. Methods We analysed data on 354 416 children aged 2–17 years and 34 613 adults age 18+ years from 19 U.S. population-based surveys, including the National Health Interview Survey 1997–2013 and the National Survey of Children's Health 2003/4 and 2007/8. Results In multivariate models adjusting for age, sex, sociodemographics, allergic disease and healthcare utilization, AD was associated with ADD/ADHD in both children [adjusted odds ratio (95% confidence interval), 1·14 (1·03–1·26)] and adults [1·61 (1·25–2·06)]. Children with both severe AD and only 0–3 nights of adequate sleep per week had much higher odds of ADD/ADHD [16·83 (7·02–40·33)] than those with 0–3 nights of adequate sleep per week [1·83 (1·47–2·26)] or mild–moderate AD alone [1·56 (1·22–1·99)]. AD was most strongly associated with severe ADHD. AD unaccompanied by other allergic disease was also associated with increased risk of ADD/ADHD in children. Among children with AD, history of anaemia, headaches and obesity were associated with even higher odds of ADD/ADHD. Asthma, insomnia and headaches increased the odds of ADHD in adults with AD, although underweight body mass index was protective. Conclusions Atopic dermatitis is associated with increased odds of ADD/ADHD in adults and children. Several factors increase the risk of ADHD in adults and children with AD.

Pyoderma gangrenosum and its syndromic forms: evidence for a link with autoinflammation.

Abstract: Pyoderma gangrenosum is a rare inflammatory neutrophilic dermatosis manifesting as painful ulcers with violaceous, undermined borders on the lower extremities. It may occur in the context of classic syndromes like PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis), as well as in a recently described entity named PASH (pyoderma gangrenosum, acne and suppurative hidradenitis). Pyoderma gangrenosum has recently been included within the spectrum of autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T cells. In PAPA syndrome, different mutations involving the PSTPIP1 gene, via an increased binding affinity to pyrin, induce the assembly of inflammasomes. These are molecular platforms involved in the activation of caspase 1, a protease that cleaves inactive prointerleukin (pro-IL)-1β to its active isoform IL-1β. The overproduction of IL-1β triggers the release of a number of proinflammatory cytokines and chemokines, which are responsible for the recruitment and activation of neutrophils, leading to neutrophil-mediated inflammation. In SAPHO syndrome, the activation of the PSTPIP2 inflammasome has been suggested to play a role in inducing the dysfunction of the innate immune system. Patients with PASH have recently been reported to present alterations of genes involved in well-known autoinflammatory diseases, such as PSTPIP1, MEFV, NOD2 and NLRP3. Pyoderma gangrenosum and its syndromic forms can be regarded as a single clinicopathological spectrum in the context of autoinflammation.

Increased expression of CXCR3 and its ligands in patients with vitiligo and CXCL10 as a potential clinical marker for vitiligo.

Abstract: Background Vitiligo is a skin disorder characterized by loss of melanocytes from the epidermis. A recent study reported that CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo, but there is very limited clinical data regarding this issue and little is known about the dynamic changes or correlations with disease severity of these chemokines throughout the disease course. Objectives To present clinical data that supports and identifies the pathway of CXCR3 and its ligands in T-lymphocytic cell recruitment in vitiligo. Methods Cytometric bead array, flow cytometry, quantitative real-time polymerase chain reaction and immunohistology were used to examine their systemic and local expression in 80 patients with vitiligo and 40 controls. Results We showed that serum CXCL9 and CXCL10 were significantly elevated in patients with vitiligo and were higher in patients in progressive stages than in stable stages. The relative expression of CXCR3 mRNA in peripheral blood mononuclear cells was higher in vitiligo. There were higher percentages of both circulating CXCR3(+) CD4(+) and CXCR3(+) CD8(+) T cells in patients with progressive vitiligo compared with controls, while only the expression of CXCR3(+) CD8(+) T cells increased in patients with stable vitiligo. Histological findings also demonstrated an abundance of CXCR3(+) cells within vitiligo lesions. Furthermore, serum CXCL10 levels were associated with Vitiligo Area Scoring Index scores of patients with progressive vitiligo and were reduced after successful treatment. Conclusions The CXCL10/CXCR3 axis mediates T-cell recruitment into the skin in progressive vitiligo. Blocking this chemotactic mechanism may present a new form of therapy. Serum CXCL10 may be a novel biomarker in monitoring disease activity and guiding treatment of progressive vitiligo.

Frontal fibrosing alopecia: possible association with leave-on facial skin care products and sunscreens; a questionnaire study.

Abstract: SummaryBackground Since its first description in 1994, frontal fibrosing alopecia (FFA) has become increasingly common, suggesting that environmental factors are involved in the aetiology. Objectives To identify possible causative environmental factors in FFA. Methods A questionnaire enquiring about exposure to a wide range of lifestyle, social and medical factors was completed by 105 women with FFA and 100 age- and sex-matched control subjects. A subcohort of women with FFA was patch tested to an extended British standard series of allergens. Results The use of sunscreens was significantly greater in the FFA group compared with controls. Subjects with FFA also showed a trend towards more frequent use of facial moisturizers and foundations but, compared with controls, the difference in frequencies just failed to reach statistical significance. The frequency of hair shampooing, oral contraceptive use, hair colouring and facial hair removal were significantly lower in the FFA group than in controls. Thyroid disease was more common in subjects with FFA than controls and there was a high frequency of positive patch tests in women with FFA, mainly to fragrances. Conclusions Our findings suggest an association between FFA and the use of facial skin care products. The high frequency of sunscreen use in patients with FFA, and the fact that many facial skin care products now contain sunscreens, raises the possibility of a causative role for sunscreen chemicals. The high frequency of positive patch tests in women with FFA and the association with thyroid disease may indicate a predisposition to immune-mediated disease.

Rescue therapy with anti-programmed cell death protein 1 inhibitors of advanced cutaneous squamous cell carcinoma and basosquamous carcinoma: preliminary experience in five cases.

Abstract: DEAR EDITOR, Cutaneous squamous cell carcinomas (CSCC) represent the second most frequent cancer. While most are cured with primary resection, some CSCC are associated with significant morbidity and death. Current approaches to locally advanced inoperable or metastatic disease include radiotherapy and/or chemotherapy. However, response rates are modest. Immune checkpoint antibodies that block the programmed cell death protein 1 (PD-1)/PD-ligand 1 (PD-L1) pathway mediate regression of tumours with pre-existing immunity. Response correlates with a local inflammatory signature that appears enhanced in highly mutated tumours. CSCC have a very high degree of genomic alterations and appear more often in patients with defective immune response. There are almost no data regarding PD-1 blockade for CSCC. We report our experience utilizing anti-PD-1 antibodies in five patients with locally advanced and/or metastatic CSCC or basosquamous carcinoma in whom all reasonable therapies had been exhausted. Five consecutive heavily pretreated patients with advanced unresectable or metastatic CSCC and basosquamous carcinoma were included. Patient characteristics with location and tumour type are summarized in Table 1. Common terminology criteria for adverse events were applied. The index case is a 79-year-old man who presented with CSCC on the forehead and scalp in 2012 (Fig. 1). The patient had multiple surgical resections and adjuvant radiotherapy. Progression was observed following several lines of systemic treatment including capecitabine, cetuximab and paclitaxel combined with carboplatin followed by progression and doselimiting neuropathy. Biopsy confirmed a moderately to poorly differentiated CSCC with a mild inflammatory infiltrate. The tumour-infiltrating lymphocytes as well as the tumour cells showed no anti-PD-1 staining. Next-generation sequencingbased assay (Foundation ONE, Cambridge, MA, U.S.A.) demonstrated numerous genomic alterations (Table S1). The tumour involved the scalp and left occipitotemporal region with two ulcerated areas of 20 5 9 6 and 9 9 4 5 cm (Fig. 2). Staging computed tomography (CT) scans showed a new cystic brain lesion, soft tissue involvement of the scalp, a level 2 B adenopathy of 0 8 9 0 6 cm in size and erosions of the inner table of the left frontal bone. In August 2015, the patient received pembrolizumab 2 mg kg 1 every 3 weeks along with stereotactic radiation to the brain lesion. The patient experienced mild fatigue (grade 1). In November 2015, examination revealed a reduction in size of the vertex and occipitotemporal ulcerations, which measured 13 2 9 8 and 5 9 3 5 cm, respectively. CT imaging demonstrated a near resolution of the soft tissue nodules of the scalp including the nonirradiated area (Fig. 2) and decrease in right level 2 B adenopathy to 0 5 9 0 4 cm. In January 2016 magnetic resonance imaging of the brain showed a size reduction of the central lobe mass. The patient continues on therapy with partial response greater than 7 months. Case 2 is a 65-year-old patient who presented with CSCC on the scalp and face. Despite repeated surgeries and courses of cetuximab, radiotherapy and chemotherapies, his tumours progressed. In September 2015 there were two ulcerated lesions on the right hemiface and left frontotemporal region measuring 15 9 15 and 5 5 9 5 cm in diameter, respectively (Fig. 3). The baseline CT scan showed cranial and facial bone involvement, a right level 1 B adenopathy of 2 2 9 1 1 cm and a right parotid lymph node measuring 1 3 9 0 7 cm. Immunohistochemistry studies of the CSCC showed positive PD-1 staining of the tumour-infiltrating cells, while PD-L1 staining was negative. Nivolumab, 3 mg kg 1 every 2 weeks was started. Four months later, after a total of five infusions, the CSCC on the right hemiface and on the left frontal scalp showed a significant reduction passing to 9 9 8 and 4 5 9 2 cm in diameter, respectively (Fig. S1). The CT scan of the soft tissue of the neck performed 1 month later showed a significant size reduction of the right level 1 B adenopathy and of the parotid lymph node to 0 8 9 0 6 and 0 7 9 0 5 cm, respectively. The patient continues on therapy with partial response longer than 7 months. Case 3 is a 61-year-old patient who presented with basal cell carcinomas treated by surgery and radiotherapy. To control recurrences, vismodegib was started, which was later stopped due to intolerable side-effects. The patient developed an infiltrating lesion in the left axilla. The patient was given paclitaxel with carboplatin and subsequent left upper extremity amputation. Pathology of the tumour samples resected from the axilla found an invasive basosquamous

Epidemiology of chronic spontaneous urticaria: results from a nationwide, population-based study in Italy.

Abstract: SummaryBackground Chronic spontaneous urticaria (CSU) is a common skin disease, but there is a paucity of precise epidemiological data on this disease. Objectives To obtain information on the epidemiology of CSU in Italy. Methods The data source was the Health Search IMS Health Longitudinal Patient Database. The study population was formed by patients aged ≥ 15 years, registered with a total of 700 general practitioners, homogeneously distributed across Italy. An algorithm based on the International Classification of Diseases, ninth revision, Clinical Modification was used for the identification of patients with CSU. The annual prevalence and incidence rates of CSU over a 12-year period (2002–2013) were estimated, along with demographic and clinical determinants. Results The annual prevalence of CSU ranged from 0·02% in 2002 to 0·38% in 2013. The incidence was 0·10–1·50 per 1000 person-years. For both prevalence and incidence rates, female patients outnumbered male. The risk of CSU was statistically significantly higher in the presence of the following variables: obesity; anxiety, dissociative and somatoform disorders; malignancies; use of immunosuppressive drugs; and chronic use of systemic corticosteroids. History of autoimmune thyroiditis showed a trend towards an increased risk of CSU, though it was not statistically significant. Smoking was associated with a significantly reduced risk of CSU. Conclusions Our findings on CSU prevalence are consistent with those obtained in previous studies. Furthermore, this large population-based study provides important information regarding the association of CSU with demographic and clinical determinants, which have been examined in the primary-care setting.

Association between psoriasis and inflammatory bowel disease: a Danish nationwide cohort study

Abstract: SummaryBackground Psoriasis, Crohn disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders with overlapping genetic architecture. However, data on the frequency and risk of CD and UC in psoriasis are scarce and poorly understood. Objectives To investigate the association between CD and UC in patients with psoriasis. Methods All Danish individuals aged ≥ 18 years between 1 January 1997 and 31 December 2012 were linked in nationwide registers. Psoriasis severity was defined in two models: hospital visits and medication. Incidence rates per 10 000 person-years were calculated, and incidence rate ratios (IRRs) were estimated by Poisson regression. Results In the total cohort (n = 5 554 100) there were 75 209 incident cases of psoriasis, 11 309 incident cases of CD and 30 310 incident cases of UC, during follow-up. The adjusted IRRs (95% confidence intervals) of CD were 1·28 (1·03–1·59), 2·56 (1·87–3·50), 2·85 (1·72–4·73) and 3·42 (2·36–4·95) in patients with mild psoriasis, severe psoriasis (hospital), severe psoriasis (medication) and psoriatic arthritis, respectively. Similarly, the adjusted IRRs of UC were 1·49 (1·32–1·68), 1·56 (1·22–2·00), 1·96 (1·36–2·83) and 2·43 (1·86–3·17), respectively. The 10-year incidence of CD was 2–5 per 1000 patients and of UC 7–11 per 1000 patients, depending on psoriasis severity and the presence of psoriatic arthritis. Additionally, an increased risk of incident psoriasis was found following CD or UC. Conclusions We observed a psoriasis-associated increased risk of CD and UC, which was higher in severe psoriasis, and an increased risk of psoriasis in patients with inflammatory bowel disease. Increased focus on gastrointestinal symptoms in patients with psoriasis may be warranted.

Skin expression of mammalian target of rapamycin and forkhead box transcription factor O1, and serum insulin‐like growth factor‐1 in patients with acne vulgaris and their relationship with diet

Abstract: Background Acne vulgaris is a multifactorial disorder of the pilosebaceous units. Several studies have reported that insulin-like growth factor (IGF)-1, forkhead box transcription factor (Fox)O1 and mammalian target of rapamycin (mTOR) interactions may be the key to understanding the links between genetic and environmental factors in acne vulgaris. Objectives To evaluate the immunohistochemical detection of mTOR and FoxO1 in the skin, and the serum level of IGF-1 in patients with acne vulgaris. Methods This study was carried out on 60 participants, including 40 patients with acne and 20 controls. A diet questionnaire was administered to the patients and controls. Serum levels of IGF-1 were measured using enzyme-linked immunosorbent assay, and skin biopsies were taken from lesions on the backs of the patients and controls. FoxO1 and mTOR expression was detected using immunohistochemistry. Results A significantly higher serum IGF-1 level was found in the patients with acne than in the controls. The cytoplasmic expression of FoxO1 was found to be significantly greater in the acne group, whereas in the control subjects this expression was likely to be nuclear. Both the cytoplasmic expression and the nuclear expression of mTOR were significantly more intense in the patients with acne than in the controls. Excess consumption of a high-glycaemic-load diet was significantly associated with higher serum levels of IGF-1 and cytoplasmic expression of FoxO1 and mTOR. Conclusions These results suggest that FoxO1, mTOR, serum IGF-1 and a high-glycaemic-load diet may play a role in acne pathogenesis.

Management of cutaneous squamous cell carcinoma in patients with epidermolysis bullosa: best clinical practice guidelines.

Abstract: This article summarizes recommendations reached following a systematic literature review and expert consensus on the diagnosis and management of cutaneous squamous cell carcinomas in people with epidermolysis bullosa. The guidelines are intended to help inform decision making by clinicians dealing with this complex complication of a devastating disease.

Sentinel lymph node biopsy in Merkel cell carcinoma: a 15-year institutional experience and statistical analysis of 721 reported cases.

Abstract: Merkel cell carcinoma (MCC) is a rare aggressive cutaneous neuroendocrine malignancy that frequently metastasizes to the regional lymphatic basin. Pathological assessment of regional lymph nodes with sentinel lymph node biopsy (SLNB) in patients without clinical involvement has permitted more accurate staging and more appropriate management. Nonetheless, concerns have been raised regarding the accuracy of this technique and its prognostic implications. We conducted a review of previously published data analysing the positive and false negative rates of SLNB in MCC. A search of the Medline and Embase databases to April 2015 identified 36 published studies between 1997 and 2015 comprising 692 patients. With the addition of 29 patients treated at our own institution, we conducted an analysis of 721 patients. Among this cumulative cohort, SLNBs were performed from 736 regional sites with 29·6% recorded as positive. Regional metastasis occurred in 45 cases following a negative SLNB, for a false negative rate of 17·1%. Adjuvant regional radiotherapy in the setting of a negative SLNB did not affect regional recurrence (P = 0·31), providing credence to emerging evidence that regional therapy can be safely omitted in the setting of a negative SLNB. Distant relapse was noted far more frequently following a positive rather than negative SLNB (17·6% vs. 7·3%, P < 0·001).

A phase II randomized controlled trial of nicotinamide for skin cancer chemoprevention in renal transplant recipients

Abstract: DEAR EDITOR, Immunosuppressed organ transplant recipients have an 80-fold increased risk of squamous cell carcinoma (SCC) and a 16-fold increased risk of basal cell carcinoma (BCC); SCCs are more aggressive and more likely to metastasize in these patients. While mammalian target of rapamycin (mTOR) inhibitors may help reduce the incidence of SCC, the current mainstay of nonmelanoma skin cancer (NMSC) chemoprevention post-transplant is oral retinoids, which have side-effects, including liver and lipid abnormalities, mucocutaneous dryness and teratogenicity. Nicotinamide (vitamin B3) enhances repair of photodamaged DNA and prevents the inhibitory effects of ultraviolet radiation on the immune system without altering baseline immune reponses. In 386 immunocompetent participants at high risk of having skin cancer, nicotinamide 500 mg twice daily reduced new NMSCs by 23% (P = 0 02), with 20% fewer BCCs and 30% fewer SCCs compared with placebo. Actinic keratoses (AKs) were also significantly reduced by nicotinamide in the same phase III randomized controlled trial. However, it is unknown whether nicotinamide prevents NMSCs and is safe in immunosuppressed renal transplant recipients. Eligible adult immunosuppressed participants included those who had received a renal transplant ≥ 12 months ago, had stable renal function and a history of ≥ 2 NMSCs in the previous 12 months. Participants were ineligible if they commenced retinoids or mTOR inhibitors within 6 months, or used nicotinamide supplements or AK field treatments within the 4 weeks prior to enrolment. This double-blind study was conducted at the Royal Prince Alfred Hospital (Sydney, Australia; Australian New Zealand Clinical Trials Registry ACTRN12612000628842) after ethical approval was received. All participants provided written informed consent. Participants were enrolled (by A.C.C. and R.A.D.) and randomized 1:1 to receive either nicotinamide 500 mg twice daily or matched placebo (Insolar; Blackmores, Warriewood, Australia) by centralized randomization (permuted blocks; National Health and Medical Research Council Clinical Trials Centre) stratified by lifetime NMSC history (< 6 or ≥ 6 NMSCs), oral retinoid use and mTOR inhibitor use. Compliance was monitored by tablet counts at each visit (A.C.C). Skin cancer checks were performed at baseline and twice monthly up to 6 months by dermatologists blinded to treatment allocation (D.L.D., P.M.L.). AKs on the face, scalp, forearms and hands were counted at baseline and twice monthly up to 6 months by a dermatology Fellow blinded to allocation (A.C.C). All squamous lesions were reviewed by a single (blinded) histopathologist (C.A.M.) to ensure consistent reporting of SCC differentiation. Blood and urine samples were taken at baseline, 2 and 4 weeks, and 2, 4 and 6 months for full blood count, electrolytes, renal and liver function tests, drug levels and urine microalbumin/creatinine ratio. Blood pressure and weight were measured at baseline and twice monthly for 6 months. The primary end point was the number of new NMSCs (BCC + SCC, including invasive and in situ SCC) up to 6 months. Secondary end points included new BCCs, new SCCs, AK counts up to 6 months and safety. The planned sample size was 80 participants, in order to provide 80% power to detect a 50% reduction in the 6-month NMSC rate at the 5% level of significance, assuming that NMSC counts followed a Poisson distribution with a mean of 1 5 for the placebo group, allowing for ≤ 10% noncompliance. However, owing to slow recruitment because of an overestimation of the eligible participant population at our site, the study was stopped early; 22 participants were recruited over 1 5 years. Analyses were by intention to treat. As per the provision specified in the statistical analysis plan, a negative binomial model was used to analyse NMSC, SCC and BCC data, owing to overdispersion that rendered the Poisson model inappropriate. Models included an offset term to account for variation in follow-up duration. The 2-monthly postbaseline AK data were analysed using a mixed model for repeated measures, including treatment group, baseline value, time point and a time-by-treatment group interaction as covariates. From August 2012 to March 2014, 25 participants were assessed for eligibility and 22 were randomized [11 in each group; Figure S1 (see Supporting Information)]. The groups had similar baseline characteristics (Table 1). Follow-up was from August 2012 to August 2014. Median compliance was 93% and 98% for the placebo and nicotinamide groups, respectively. The 6-month NMSC rate was not significantly lower for the nicotinamide group [mean 2 7, 95% confidence interval (CI) 1 4–5 3; total 30 cancers] compared with placebo (mean 4 2, 95% CI 2 2–7 8; total 45 cancers); however, the numeric trend was dominated by one patient in the placebo group

Effectiveness and safety of omalizumab in chronic spontaneous or inducible urticaria: evaluation of 154 patients.

Abstract: DEAR EDITOR, Out-of-trial data on long-term safety and predictors of effectiveness of omalizumab (anti-IgE) in chronic urticaria are lacking. We evaluated the outcome of treatment with omalizumab in a large cohort of patients with chronic spontaneous or chronic inducible urticaria (CSU and CINDU, respectively). Data were retrieved via retrospective review of patient records from a tertiary dermatological referral centre (Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark). Complete ascertainment of patient records was possible as the department keeps track of all administered biological therapy. A consultant dermatologist (S.F.T.) verified the urticaria diagnosis and assessed response to treatment. Two authors (M.N.G. and S.F.T.) extracted the data and, in cases of disagreement, consensus was obtained by discussion with all the authors. According to Danish law, scientific ethics approval is not needed for retrospective chart reviews. Approval for the study was obtained from the National Board of Health (to examine patient records) and from the Data Protection Agency (to save patient data on file). All patients diagnosed with CSU or CINDU who had received at least one injection of omalizumab from 30 June 2010 to 31 December 2014 were included in the study. Response to omalizumab treatment was graded according to the degree of relief of symptoms reported by the patient and according to the physician’s assessment. It was possible to score the clinical response to treatment with omalizumab for each patient as a ‘complete or almost complete response’, ‘partial response’ and ‘no/limited response’ after 3–6 months of treatment. This grading is in accordance with the modified physician global assessment used in other dermatological diseases, where a complete or almost complete response corresponds to ≥ 90% reduction of symptoms; partial response is reduction in symptoms of between 30% and 89%; and no response or a limited response is a reduction in symptoms of < 30%. In total, 154 patients were identified; 110 (71 4%) women and 44 (28 6%) men (Table 1). The majority of the patients were diagnosed with CSU (89 0%). Of these, 30 7% had concomitant angioedema, 34 3% had a positive histamine release (HR) test and 22 6% had significant comorbidities, the most common being asthma, diabetes, hypertension and hypothyroidism. The 17 patients with CINDU had delayed-pressure urticaria (n = 5), cold urticaria (n = 5), cholinergic urticaria (n = 4), symptomatic dermographism (n = 2) and solar urticaria (n = 1). The average age at disease onset was significantly

British Association of Dermatologists and British Photodermatology Group guidelines for the safe and effective use of psoralen-ultraviolet A therapy 2015.

Abstract: British Association of Dermatologists and British Photodermatology Group guidelines for the safe and effective use of psoralen–ultraviolet A therapy 2015 T.C. Ling, T.H. Clayton, J. Crawley, L.S. Exton, V. Goulden, S. Ibbotson, K. McKenna, M.F. Mohd Mustapa, L.E. Rhodes, R. Sarkany and R.S. Dawe Dermatology Centre and Dermatology Research Centre, Faculty of Medical and Human Sciences, Salford Royal NHS Foundation Trust, Salford, Manchester M6 8HD, U.K. Department of Dermatology, University College Hospital, 235 Euston Road, London NW1 2BU, U.K. British Association of Dermatologists, Willan House, 4 Fitzroy Square, London W1T 5HQ, U.K. Department of Dermatology, Leeds Teaching Hospitals NHS Trust, Leeds LS7 4SA, U.K. Department of Dermatology, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, U.K. Department of Dermatology, Belfast City Hospital, Belfast BT9 7AB, U.K.

The epidemiology of childhood psoriasis: a scoping review

Abstract: Psoriasis is an inflammatory noncommunicable skin disease that affects both adults and children. At present, the epidemiology and natural history of psoriasis are not widely understood. This scoping review aimed to map the existing literature on the epidemiology of childhood psoriasis, identify research gaps for future studies and provide a comprehensive, clinically useful review. Search strategies were developed for Ovid Medline, Ovid Embase, Google Scholar and hand searching. In total, 131 articles met the inclusion criteria and were mapped; 107 articles were included for data extraction. Over the last 25 years there has been a dramatic increase in the volume of published observational epidemiological studies on childhood psoriasis. The majority were case series or cross-sectional studies, concentrated in Europe, Asia and North America. The prevalence of childhood psoriasis was found to be higher in European countries, older children and girls. Up to 48·8% of children had a family history of psoriasis in a first-degree relative. The most frequent subtype was plaque psoriasis and the most common initial sites of presentation were the scalp, limbs and trunk. Specific genetic differences have been found between child-onset and adult-onset populations. Case–control and cohort studies investigating risk factors for psoriasis onset, comorbidities and long-term health outcomes were extremely limited. The choice of study design and heterogeneity in methodology limit the validity and generalizability of the information, consistency of the results, and comparability of the studies. Well-designed epidemiological studies are needed to provide precise and consistent information about the frequency and clinical presentation, risk factors, associated diseases and long-term outcomes in childhood psoriasis.

British Association of Dermatologists’ guidelines for the safe and effective prescribing of methotrexate for skin disease 2016

Abstract: British Association of Dermatologists’ guidelines for the safe and effective prescribing of methotrexate for skin disease 2016 R.B. Warren, S.C. Weatherhead, C.H. Smith, L.S. Exton, M.F. Mohd Mustapa, B. Kirby and P.D. Yesudian The Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, Manchester M6 8HD, U.K. Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, U.K. St John’s Institute of Dermatology, Guy’s and St Thomas NHS Foundation Trust, London SE1 9RT, U.K. British Association of Dermatologists, Willan House, 4 Fitzroy Square, London W1T 5HQ, U.K. St Vincent’s University Hospital, Elm Park, Dublin, Ireland Glan Clwyd Hospital, Sarn Lane, Rhyl LL18 5UJ, U.K.