Showing papers in "British Journal of Dermatology in 2012"

A systematic review of worldwide incidence of nonmelanoma skin cancer.

Abstract: Background Nonmelanoma skin cancer (NMSC) is the most common cancer affecting white-skinned individuals and the incidence is increasing worldwide. Objectives This systematic review brings together 75 studies conducted over the past half century to look at geographical variations and trends worldwide in NMSC, and specifically incidence data are compared with recent U.K. cancer registry data. Methods Following the development of a comprehensive search strategy, an assessment tool was adapted to look at the methodological quality of the eligible studies. Results Most of the studies focused on white populations in Europe, the U.S.A. and Australia; however, limited data were available for other skin types in regions such as Africa. Worldwide the incidence for NMSC varies widely with the highest rates in Australia [>1000/100, 000 person-years for basal cell carcinoma (BCC)] and the lowest rates in parts of Africa ( Conclusions NMSC is an increasing problem for health care services worldwide. This review highlights a requirement for prevention studies in this area and the issues surrounding incomplete NMSC registration. Registration standards of NMSC should be improved to the level of other invasive disease.

Successful and safe use of 2 min cold atmospheric argon plasma in chronic wounds: results of a randomized controlled trial.

Abstract: Background The development of antibiotic resistance by microorganisms is an increasing problem in medicine. In chronic wounds, bacterial colonization is associated with impaired healing. Cold atmospheric plasma is an innovative promising tool to deal with these problems. Objectives The 5-min argon plasma treatment has already demonstrated efficacy in reducing bacterial numbers in chronic infected wounds in vivo. In this study we investigated a 2-min plasma treatment with the same device and the next-generation device, to assess safety and reduction in bacterial load, regardless of the kind of bacteria and their resistance level in chronic wounds. Methods Twenty-four patients with chronic infected wounds were treated in a prospective randomized controlled phase II study with 2 min of cold atmospheric argon plasma every day: 14 with MicroPlaSter alpha device, 10 with MicroPlaSter beta device (next-generation device) in addition to standard wound care. The patient acted as his ⁄her own control. Bacterial species were detected by standard bacterial swabs and bacterial load by semiquantitative count on nitrocellulose filters. The plasma settings were the same as in the previous phase II study in which wounds were exposed for 5 min to argon plasma. Results Analysis of 70 treatments in 14 patients with the MicroPlaSter alpha device revealed a significant (40%, P <0 AE016) reduction in bacterial load in plasmatreated wounds, regardless of the species of bacteria. Analysis of 137 treatments in 10 patients with the MicroPlaSter beta device showed a highly significant reduction (23AE5%, P <0 AE008) in bacterial load. No side-effects occurred and the treatment was well tolerated. Conclusions A 2-min treatment with either of two cold atmospheric argon plasma devices is a safe, painless and effective technique to decrease the bacterial load in chronic wounds.

Fractional laser resurfacing for acne scars: a review

Abstract: This review investigates the effectiveness of ablative and nonablative fractional photothermolysis (FP) lasers for treating facial acne scars. Twenty-six studies (13 ablative FP, 13 nonablative FP) published between 2003 and January 2011 were reviewed. Quantitative and qualitative data from each article were examined and analysed. Four studies were split-face randomized controlled studies. While the data analysed were all clinically relevant and significant, there were some methodological differences between the studies. Outcomes included subjective and objective assessment of scar appearance, pre- and postoperative treatment, side-effects and pain scores. A small number of studies used three-dimensional optical imaging profiling and histology for objective assessment. Even allowing for methodological variability, ablative FP had an improvement range of 26-83% whereas nonablative FP had an improvement range of 26-50%. Patients who underwent treatment with an ablative FP laser experienced erythema for 3-14 days which resolved by 12 weeks, whereas patients who opted for the nonablative FP laser experienced erythema for between 1 and 3 days and this resolved within a week. A higher proportion of patients (up to 92·3%) who underwent ablative FP experienced postinflammatory hyperpigmentation (PIH) than those who had nonablative FP (up to 13%). The maximum duration of PIH in ablative FP was up to 6 months whereas in nonablative FP it lasted for up to 1 week. The procedure with ablative FP was relatively uncomfortable compared with nonablative FP. The pain score with ablative FP ranged from 5·90 to 8·10 (scale 1-10) and with nonablative FP from 3·90 to 5·66 (scale 1-10).

Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b randomized placebo-controlled dose-ranging study.

Abstract: Summary Background Tofacitinib is a novel, oral Janus kinase inhibitor under investigation as a potential treatment for plaque psoriasis. Objectives This Phase 2b, 12-week, dose-ranging study (A3921047, NCT00678210) aimed to characterize the exposure–response, efficacy and safety of tofacitinib vs. placebo in patients with moderate-to-severe chronic plaque psoriasis. Methods One hundred and ninety-seven patients were randomized. The primary endpoint was the proportion of patients achieving a ≥ 75% reduction in the Psoriasis Area and Severity Index (PASI 75) score at week 12. Results At week 12, PASI 75 response rates were significantly higher for all tofacitinib twice-daily groups: 25·0% (2 mg; P < 0·001), 40·8% (5 mg; P < 0·0001) and 66·7% (15 mg; P < 0·0001), compared with placebo (2·0%). Significant increases in the proportion of PASI 75 responses were seen by week 4 and were maintained at week 12. Exposure–response over the 0–15 mg tofacitinib twice-daily dose range was successfully characterized. PASI 50, PASI 90 and Physician’s Global Assessment response rates were also higher for tofacitinib vs. placebo. The most frequently reported adverse events (AEs) were infections and infestations: 22·4% (2 mg twice daily), 20·4% (5 mg twice daily), 36·7% (15 mg twice daily) and 32·0% (placebo). Discontinuations due to AEs were 6·0%, 2·0%, 4·1% and 6·1% of patients in the placebo, and 2, 5 and 15 mg twice-daily tofacitinib groups, respectively. Dose-dependent increases from baseline in mean serum high-density lipoprotein, low-density lipoprotein and total cholesterol, and decreases in haemoglobin and neutrophils were observed. Conclusion Short-term treatment with oral tofacitinib results in significant clinical improvement in patients with moderate-to-severe plaque psoriasis and is generally well tolerated.

Secukinumab induction and maintenance therapy in moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled, phase II regimen-finding study.

Abstract: Background: Interleukin-17A has major proinflammatory activity in psoriatic lesional skin. Objectives: Assess the efficacy and safety of secukinumab, a fully human IgG1κ monoclonal anti-interleukin-17A antibody, in moderate-to-severe plaque psoriasis in a phase II regimen-finding study. Methods: 404 patients were randomised to subcutaneous placebo (67 patients) or one of three secukinumab 150 mg induction regimens: Single (week 0; 66 patients), Early (weeks 0, 1, 2, 4; 133 patients), and Monthly (weeks 0, 4, 8; 138 patients). The primary outcome was ≥75% improvement from baseline Psoriasis Area and Severity Index (PASI) score at week 12. PASI 75 responders from active treatment arms at week 12 were re-randomised to either a fixed-interval (secukinumab 150 mg at weeks 12 and 24; 65 patients) or a treatment-at-start-of-relapse maintenance regimen (secukinumab 150 mg at visits at which a start of relapse was observed; 67 patients). Results: At week 12, Early and Monthly induction regimens resulted in higher PASI 75 response rates versus placebo (54·5% and 42·0% vs. 1·5%; P<0·001 for both). Among PASI 75 responders at week 12 entering the maintenance period, PASI 75 and PASI 90 achievement at least once from week 20 to week 28 was superior with the fixed-interval regimen (84·6% [n = 55] and 58·5% [n = 38], respectively) versus the start-of-relapse regimen (67·2% [n = 45], P = 0·020 and 20·9% [n = 14], respectively). Fifteen weeks after last study drug administration, <10% of patients in the fixed-interval and start-of-relapse groups experienced a start of relapse. No immunogenicity was observed, and no injection site reactions were reported. Reported cases of neutropaenia were mild-to-moderate (≤grade 2); none were associated with clinically significant adverse events or resulted in study discontinuation. Due to the brief duration of the safety assessment, no firm conclusions can be drawn regarding long-term safety. Conclusions: Secukinumab shows efficacy for induction and maintenance treatment of moderate-to-severe plaque psoriasis.

British Association of Dermatologists’ guidelines for the management of alopecia areata 2012

Abstract: The guidelines have been revised and updated in accordance with a predetermined scope, based on that used in the 2003 guidelines. Recommendations in these guidelines supersede those in the 2003 guidelines. The objectives of the guidelines are to provide up-to-date recommendations for the manage- ment of alopecia areata in adults and children and a summary of the evidence base.Rosalind.Woodworth@utas.edu.au

Accuracy of dermoscopic criteria for the diagnosis of psoriasis, dermatitis, lichen planus and pityriasis rosea.

Abstract: Summary Background Dermoscopy is useful in evaluating skin tumours, but its applicability extends also to the field of inflammatory skin disorders. Plaque psoriasis (PP), dermatitis, lichen planus (LP) and pityriasis rosea (PR) are common inflammatory skin diseases, but little is currently known about their dermoscopic features. Objectives To determine and compare the dermoscopic patterns associated with PP, dermatitis, LP and PR and to assess the validity of certain dermoscopic criteria in the diagnosis of PP. Methods Patients with PP, dermatitis, LP and PR were prospectively enrolled. The single most recently developed lesion was examined dermoscopically and histopathologically. Variables included vascular morphology, vascular arrangement, background colour, scale colour, scale distribution and presence of Wickham striae. Univariate and adjusted odds ratios were calculated. Discriminant functions were used to plot receiver-operator characteristic curves. Results Eighty-three patients with PP and 86 patients with either dermatitis, LP or PR were included in the study. Dotted vessels in a regular arrangement over a light red background and white scales were highly predictive for the diagnosis of PP, whereas dermatitis more commonly showed yellow scales and dotted vessels in a patchy arrangement. PR was characterized by yellowish background, dotted vessels and peripheral scales; whitish lines (Wickham striae) were seen exclusively in LP. Conclusions PP, LP, PR and dermatitis show specific dermoscopic patterns that may aid their clinical diagnosis. Certain combinations of dermoscopic features can reliably predict the diagnosis of PP.

Melanoma incidence and mortality in Europe: new estimates, persistent disparities

Abstract: Background Melanoma incidence and mortality in Europe are high but there are significant gaps in the epidemiological information available across the continent. Objectives With the aim of enhancing the planning of educational programmes for reducing the melanoma burden in Europe, we analysed the most recent incidence and mortality data for Europe with a new focus on the regional disparities of melanoma reporting. Methods GLOBOCAN 2008, the standard set of worldwide estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer for 2008, was used to provide the estimated age-standardized rates (world standard population) of melanoma incidence and mortality in European countries and regions. Results The estimated age-standardized incidence of melanoma (measured per 100 000 person-years) varies widely from 19·2 in Switzerland to 2·2 in Greece. The incidence rate of 4·3 of Central and Eastern Europe (CEE) is less than half of that of Western Europe. Melanoma mortality rates of 1·5 are similar in CEE and Western Europe, although rates vary with a high of 3·2 in Norway and a low of 0·9 in Greece. Over 20 000 deaths from melanoma were estimated in Europe in 2008, with CEE having the largest share (35·5%) among the four geographical European regions. Population-based data are lacking for significant parts of CEE, which must rely on estimates. Conclusions The most recent estimates of melanoma incidence and mortality in Europe reveal sharp differences between European countries, possibly related to missed opportunities for early diagnosis and incomplete reporting of melanoma in Eastern Europe. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

Efficacy of biologics in the treatment of moderate to severe psoriasis: a network meta-analysis of randomized controlled trials.

Abstract: Summary Background Ustekinumab, a novel monoclonal antibody for the treatment of moderate to severe plaque-type psoriasis, has recently received regulatory approval in Europe, bringing the total number of biologic agents licensed in this indication to five. To assist treatment selection in daily practice it is essential to understand the benefit/risk profile of these agents and in the absence of a clinical trial comparing all available biologics a number of reviews have used statistical techniques to generate estimates of the comparative effectiveness of these therapies through the available network of randomized clinical trials. These estimates have previously been published for a limited range of psoriasis biologic treatments, although, to date no review has compared all the currently available agents in Europe. Objectives To estimate the comparative effectiveness of all biologic agents indicated in the treatment of moderate to severe psoriasis currently available in Europe based on the primary trial endpoints. Methods A number of databases were searched for details of randomized controlled trials of available biologics in the treatment of plaque-type psoriasis in adults. Comparative effectiveness was estimated based on the reported Psoriasis Area and Severity Index (PASI) 50, 75 and 90 response rates. A network meta-analysis conducted on the ordered probit scale and implemented as a Bayesian hierarchical model provided estimates for the probability of response and relative risk vs. placebo, based on all observed comparisons. Results Twenty trials were included in the meta-analysis including patients with a mean disease duration of 18–22 years. Based on the indirect comparison and given a placebo PASI 50 response of 13%, infliximab had the highest predicted mean probability of response at PASI levels 50 (93%), 75 (80%) and 90 (54%), followed by ustekinumab 90 mg at 90%, 74% and 46%, respectively, and then ustekinumab 45 mg, adalimumab, etanercept and efalizumab. Conclusions The ordered probit model allowed a quantitative comparison of all currently licensed biologics, providing estimates on comparative effectiveness and a suggested ranking of treatments that is of potential use to decision-makers. However, the analysis is based on indirect comparisons of the primary endpoint reported from short-term randomized trials.

Expression of microRNAs in basal cell carcinoma.

Abstract: Summary Background Perturbations in the expression profiles of microRNAs (miRNAs) have been reported for a variety of different cancers. Differentially expressed miRNAs have not been systematically evaluated in basal cell carcinoma (BCC) of the skin. Objectives To initiate a microarray-based miRNA profiling study to identify specific miRNA candidates that are differentially expressed in BCC. Methods Patients with BCC (n = 7) were included in this study. Punch biopsies were harvested from the tumour centre (lesional, n = 7) and from adjacent nonlesional skin (intraindividual control, n = 7). Microarray-based miRNA expression profiles were obtained on an Agilent platform using miRBase 16 screening for 1205 Homo sapiens (hsa)-miRNA candidates. To validate the microarray data, the expression of seven dysregulated miRNAs was measured by TaqMan quantitative real-time reverse transcription polymerase chain reaction. Results We identified 16 significantly upregulated (hsa-miR-17, hsa-miR-18a, hsa-miR-18b, hsa-miR-19b, hsa-miR-19b-1*, hsa-miR-93, hsa-miR-106b, hsa-miR-125a-5p, hsa-miR-130a, hsa-miR-181c, hsa-miR-181c*, hsa-miR-181d, hsa-miR-182, hsa-miR-455-3p, hsa-miR-455-5p and hsa-miR-542-5p) and 10 significantly downregulated (hsa-miR-29c, hsa-miR-29c*, hsa-miR-139-5p, hsa-miR-140-3p, hsa-miR-145, hsa-miR-378, hsa-miR-572, hsa-miR-638, hsa-miR-2861 and hsa-miR-3196) miRNAs in BCC compared with nonlesional skin. Data mining revealed connections to many tumour-promoting pathways, such as the Hedgehog and the mitogen-activated protein kinase/extracellular signal-regulated kinase signalling cascades. Conclusions This study identified several miRNA candidates that may play a role in the molecular pathogenesis of BCC.

A study on the epidemiology of rosacea in the U.K.

Abstract: Rosacea is a chronic facial skin disease of unclear origin. Epidemiological data are scarce and controversial, with reported prevalences ranging from 0·09% to 22%. To our knowledge, incidence rates have not been quantified before.; In this observational study we quantified incidence rates of diagnosed rosacea in the U.K. and described demographic characteristics and the prevalence of ocular symptoms in patients with rosacea. We compared lifestyle factors such as smoking and alcohol consumption between patients with rosacea and controls.; Using the U.K.-based General Practice Research Database, we identified patients with an incident diagnosis of rosacea between 1995 and 2009 and matched them (1:1) to rosacea-free control patients. We assessed person-time of all patients at risk and assessed incidence rates of rosacea, stratified by age, sex, year of diagnosis and region.; We identified 60,042 rosacea cases and 60,042 controls (61·5% women). The overall incidence rate for diagnosed rosacea in the U.K. was 1·65 per 1000 person-years. Rosacea was diagnosed in some 80% of cases after the age of 30 years. Ocular symptoms were recorded in 20·8% of cases at the index date. We observed a significantly reduced relative risk of developing rosacea among current smokers (odds ratio 0·64, 95% confidence interval 0·62-0·67). Alcohol consumption was associated with a marginal risk increase.; We quantified incidence rates and characteristics of patients with rosacea diagnosed in clinical practice in a large epidemiological study using primary care data from the U.K. Smoking was associated with a substantially reduced risk of developing rosacea.

The Efficacy of Intravenous Immunoglobulin for the Treatment of Toxic Epidermal Necrolysis: A Systematic Review and Meta-Analysis

Abstract: Summary Background Quantitative analysis of intravenous immunoglobulin (IVIg) treatment against toxic epidermal necrolysis (TEN) is lacking. Objectives To provide a meta-analysis evidence-based examination of IVIg efficacy against TEN. Methods A systematic review and meta-analysis of literature published before 31 July 2011 was conducted. In observational controlled studies with at least eight patients with TEN receiving IVIg treatment, a pooled estimate of mortality risk was determined, comparing IVIg and supportive care. Statistical analyses were performed on raw data to compare the clinical differences between (i) high-dose and low-dose IVIg treatment in adult patients and (ii) paediatric and adult patients treated with IVIg. Results Seventeen studies met inclusion criteria. Overall mortality rate of patients with TEN treated with IVIg was 19·9%. The pooled odds ratio (OR) for mortality from six observational controlled studies comparing IVIg and supportive care was 1·00 [95% confidence interval (CI) 0·58–1·75; P = 0·99]. The pooled OR for mortality in patients treated with high-dose IVIg vs. supportive care was 0·63 (95% CI 0·27–1·44; P = 0·27). Adults treated with high-dose IVIg exhibited significantly lower mortality than those treated with low-dose IVIg (18·9% vs. 50%, respectively; P = 0·022); however, multivariate logistic regression model adjustment indicated that IVIg dose does not correlate with mortality (high vs. low dose: OR 0·494; 95% CI 0·106–2·300; P = 0·369). Paediatric patients treated with IVIg had significantly lower mortality than adults (0% vs. 21·6%; P = 0·001). Conclusions Although high-dose IVIg exhibited a trend towards improved mortality and children treated with IVIg had a good prognosis, the evidence does not support a clinical benefit of IVIg. Randomized controlled trials are necessary.

An increased incidence of Propionibacterium acnes biofilms in acne vulgaris: a case–control study

Abstract: Summary Background Acne vulgaris is a disorder of the sebaceous follicles. Propionibacterium acnes can be involved in inflammatory acne. Objectives This case-control study aimed at investigating ...

Cutaneous manifestations of dabrafenib (GSK2118436): a selective inhibitor of mutant BRAF in patients with metastatic melanoma

Abstract: Summary Background Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma carrying relevant oncogenic mutations. Cutaneous reactions are frequent and significant. We conducted a systematic prospective dermatological review of all patients enrolled at a single institution in the phase I/II clinical trial of the mutant BRAF inhibitor dabrafenib (GSK2118436). Objectives To identify the cutaneous manifestations of the BRAF inhibitor dabrafenib; to form diagnostic criteria to standardize the diagnosis of verrucal keratotic squamoproliferative lesions; and to bring awareness to the medical community of the importance of dermatological assessment of patients taking dabrafenib. Methods Patients enrolled in the phase I/II trial (n = 43) were monitored for the development of new skin lesions. Each new lesion was photographed, a clinical diagnosis recorded and, where appropriate, a biopsy taken. Human papillomavirus (HPV) and p16 immunohistochemistry analyses were performed. Results The most frequently observed lesions were verrucal keratotic squamoproliferative lesions (49%), Grover’s disease (27%) and reactive hyperkeratotic lesions on the soles, at points of friction (22%). Eighteen squamous cell carcinomas (SCCs) occurred in 20% of patients. Most SCCs appeared between weeks 6 and 24 following commencement of therapy on both sun-damaged and nonsun-damaged skin. All SCCs were well differentiated, five were of the keratoacanthoma type, and two were SCC in situ. Other lesions observed included seborrhoeic keratoses, epidermal cysts, acneiform eruptions, hair loss and changes in hair structure. HPV was negative in 15 of the 16 tissues studied and p16 expression was higher in SCCs compared with verrucal keratoses. Conclusions Administration of the mutant BRAF inhibitor dabrafenib is associated with induction of keratinocytic proliferation, which in some cases develops features of low-grade malignancy. Highly oncogenic HPV infection is unlikely to be a contributor to the formation of SCCs or verrucal keratoses.

Intensified photodynamic therapy of actinic keratoses with fractional CO2 laser: a randomized clinical trial.

Abstract: Summary Background Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is effective for thin actinic keratoses (AKs) in field-cancerized skin. Ablative fractional laser resurfacing (AFXL) creates vertical channels that facilitate MAL uptake and may improve PDT efficacy. Objectives To evaluate efficacy and safety of AFXL-assisted PDT (AFXL-PDT) compared with conventional PDT in field-directed treatment of AK. Methods Fifteen patients with a total of 212 AKs (severity grade I–III) in field-cancerized skin of the face and scalp were randomized to one treatment with PDT and one treatment with AFXL-PDT in two symmetrical areas. Following curettage of both treatment areas, AFXL was applied to one area using 10 mJ per pulse, 0·12 mm spot, 5% density, single pulse (UltraPulse®, DeepFx handpiece; Lumenis Inc., Santa Clara, CA, U.S.A.). MAL cream was then applied under occlusion for 3 h and illuminated with red light-emitting diode light at 37 J cm−2. Fluorescence photography quantified protoporphyrin IX (PpIX) before and after illumination. Results At 3-month follow-up, AFXL-PDT was significantly more effective than PDT for all AK grades. Complete lesion response of grade II–III AK was 88% after AFXL-PDT compared with 59% after PDT (P = 0·02). In grade I AK, 100% of lesions cleared after AFXL-PDT compared with 80% after PDT (P = 0·04). AFXL-PDT-treated skin responded with significantly fewer new AK lesions (AFXL-PDT n = 3, PDT n = 11; P = 0·04) and more improved photoageing (moderate vs. minor improvement, P = 0·007) than PDT-treated skin. Pain scores during illumination (6·5 vs. 5·4; P = 0·02), erythema and crusting were more intense, and long-term pigmentary changes more frequent from AFXL-PDT than PDT (P = not significant). PpIX fluorescence was higher in AFXL-pretreated skin [7528 vs. 12 816 arbitrary units (AU); P = 0·003] and photobleached to equal intensities after illumination (AFXL-PDT 595 AU, PDT 454 AU; P = 0·59). Conclusions AFXL-PDT is more effective than conventional PDT for treatment of AK in field-cancerized skin.

Long-pulsed Nd:YAG laser vs. intense pulsed light for hair removal in dark skin: a randomized controlled trial

Abstract: Summary Background Although several lasers meet the wavelength criteria for selective follicular destruction, the treatment of darker skin phototypes is particularly challenging because absorption of laser energy by the targeted hairs is compromised by an increased concentration of epidermal melanin. Objectives To compare satisfaction level, safety and effectiveness of a long-pulsed Nd:YAG laser and intense pulsed light (IPL) in axillary hair reduction in subjects with dark skin. Methods The study design was a within-patient, right-left, assessor-blinded, comparison of long-pulsed Nd:YAG laser and IPL. Fifty women (skin phototypes IV–VI) volunteered for removal of axillary hair. Five sessions at 4- to 6-week intervals were performed. Hair counts at both sides were compared at baseline and 6 months after the last session. Final overall evaluations were performed by subjects and clinician at the end of the study. Satisfaction was scored for both devices. Results Thirty-nine women completed the study. At 6 months, the decrease in hair counts on the laser side (79·4%, P < 0·001 vs. pretreatment) was significantly (P < 0·01) greater than that on the IPL side (54·4%, P < 0·01 vs. pretreatment). Only temporary adverse effects were reported at both sides. Higher pain scores and more inflammation were reported with Nd:YAG laser; however, it was preferred by 29 volunteers (74%). Volunteers reported higher satisfaction score with Nd:YAG laser (P < 0·01). Conclusions Dark skin can be treated by both systems safely and effectively; however, long-pulsed (1064 nm) Nd:YAG laser is more effective as reported by both subjects and clinician.

Alterations in leucocyte subsets and histomorphology in normal‐appearing perilesional skin and early and chronic hidradenitis suppurativa lesions

Abstract: Summary Background Current insight into the histopathological course of events during disease progression in hidradenitis suppurativa (HS) is fragmentary. Objectives To identify histological alterations and leucocyte subsets in normal-appearing perilesional skin, and early and chronic HS lesions. Methods In this observational study we examined eight perilesional skin samples, and six early and 10 chronic prototypic HS lesions, as well as skin samples from four healthy donors using in situ immunostaining. Results Perilesional skin showed mild psoriasiform hyperplasia and follicular plugging as well as a low-grade influx of tryptase-positive mast cells, CD3+ T cells, CD138+ plasma cells and factor XIIIa+ dendritic cells. In early HS lesions, neutrophilic abscess formation and influx of mainly macrophages, monocytes and dendritic cells predominated. In chronic disease, the infiltrate expanded with markedly increased frequencies of CD20+ and CD79a+ B cells and CD138+ plasma cells. As in early lesions, free keratin fibres were detected in the dermis and within giant cells. Single detached keratinocytes and strands of follicular epithelium were observed in the dermis, the latter frequently expressing Ki67, indicative of active proliferation. Conclusions Psoriasiform hyperplasia, follicular plugging and low-grade leucocytic infiltration are already present in normal-appearing perilesional skin. Keratin fibres in the dermis are associated with clinical disease. Early lesions are characterized by neutrophilic abscess formation and influx of mainly histiocytes, and chronic lesions mainly by expansion of B cells and plasma cells in ‘pseudo’ follicles. Proliferating strands of follicular epithelium may initiate fistula formation. Mast cells are increased in all stages of HS including perilesional skin.

Vitamin D status in patients with chronic plaque psoriasis.

Abstract: Summary Background Vitamin D could have important immunomodulatory effects in psoriasis. Objectives To measure 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH) and calcium serum levels in patients with psoriasis and the associations with some relevant clinical features. Methods A cross-sectional study was conducted over 1 year including 145 patients with chronic plaque psoriasis, 112 patients with rheumatoid arthritis (RA) and 141 healthy controls. 25(OH)D, PTH and calcium serum levels were measured in a centralized laboratory. Demography, comorbidities, disease severity and exposure time to sunlight (which was derived by questionnaire) were collected. Results The prevalence of vitamin D deficiency [25(OH)D levels < 20 ng mL−1] in patients with psoriasis was 57·8% vs. 37·5% in patients with RA and 29·7% in healthy controls (P < 0·001). In winter, the prevalence of vitamin D deficiency rose to 80·9% in patients with psoriasis, to 41·3% in those with RA and to 30·3% in healthy controls (P < 0·001). Patients with psoriasis or psoriatic arthritis did not differ in 25(OH)D serum levels nor in the prevalence of vitamin D deficiency. In the logistic regression analysis, vitamin D deficiency was associated with psoriasis independently of age, sex, body mass index, calcium, PTH levels and season of blood sampling. A limitation is that the study design does not allow a causal or temporal relationship between vitamin D deficiency and psoriasis to be established. Conclusions Vitamin D deficiency may be common in patients with psoriasis, especially in winter.

Once-daily topical brimonidine tartrate gel 0·5% is a novel treatment for moderate to severe facial erythema of rosacea: results of two multicentre, randomized and vehicle-controlled studies

Abstract: Rosacea is a common and chronic disorder, characterized by flushing and persistent erythema in the central facial area.1,2 The disease onset is typically between the ages of 20 and 50 years, and women are more often affected than men.3,4 Rosacea has considerable psychosocial impact and causes embarrassment, anxiety and low self-esteem.5,6 Erythema is the primary feature of rosacea and presents ubiquitously among patients. Other cutaneous signs such as telangiectasia, papules, pustules and oedema may also present.7,8 Although several medications are approved for the treatment of inflammatory lesions of rosacea, there is currently no approved medication directly targeting erythema of rosacea, making it a key unmet medical need.4 In the absence of effective treatment, patients are usually advised to avoid environmental and lifestyle triggers that can exacerbate erythema.9–11 While the exact cause of erythema of rosacea is not known, it is hypothesized that erythema results from dysregulation in the cutaneous vasomotor responses, which leads to abnormal dilation of facial blood vessels upon various stimuli.12–14 Therefore, agents with vasoconstrictive activity may have a symptomatic effect on erythema. Transcriptomic studies suggest the involvement of adrenergic receptors in the neurovascular regulation pathway.15 Brimonidine tartrate (BT) is a highly selective α2-adrenergic receptor agonist, with potent vasoconstrictive activity.16 It is currently approved for the treatment of open-angle glaucoma, with well-documented efficacy and safety.17,18 BT applied topically to the face is hypothesized to reduce erythema of rosacea. In the present two Phase II studies, we aimed to determine the optimal dose regimen of BT in the treatment of moderate to severe erythema of rosacea, and to evaluate the efficacy and safety of the treatment using two specifically developed novel scales for erythema.

Infant epidermal skin physiology: adaptation after birth.

Abstract: Summary Background Functional and structural skin adaptation is a dynamic process which starts immediately after birth in humans and in mammalian skin in general. This adjustment to the extrauterine dry environment is accomplished in the first year of postnatal life of humans. Objectives To assess the dynamic changes in vivo after birth in the molecular composition and skin physiology parameters compared with older children and adults. Methods The molecular composition of the stratum corneum (SC) and the water profile were investigated noninvasively by in vivo Raman confocal microscopy as a function of depth. Functional parameters including transepidermal water loss (characterizing epidermal permeability barrier), capacitance (as an indirect parameter for SC hydration) and skin surface pH were assessed noninvasively. The measurements were performed in 108 subjects divided into six age groups: full-term newborns (1–15 days), babies aged 5–6 weeks, babies aged 6 ± 1 months, children aged 1–2 years, children aged 4–5 years and adults aged 20–35 years. Results We showed that skin acidification is still under development during the first weeks of life. While the basal epidermal barrier is competent immediately after birth, the SC is less hydrated in the first 2 weeks of postnatal life. Similar continuous decreasing water content towards the surface for all age groups was observed, whereas this gradient was lower for the newborns. Dynamic changes in the amounts of the natural moisturizing factor constituents were revealed in the period of infancy. Conclusions We demonstrated the relation of formation of an acidic pH as well as underlying mechanisms in the induction of a fully hydrated SC over the first weeks of human life as a dynamic functional adaptation.

Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a multicentre, randomized, observer-blind phase III study in comparison with a registered methyl-5-aminolaevulinate cream and placebo

Abstract: Summary Background Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) or its methylester [methyl-5-aminolaevulinate (MAL) or 5-amino-4-oxopentanoate] was recently ranked as first-line therapy for the treatment of actinic keratosis (AK) and is an accepted therapeutic option for the treatment of neoplastic skin diseases. BF-200 ALA (Biofrontera Bioscience GmbH, Leverkusen, Germany) is a gel formulation of ALA with nanoemulsion for the treatment of AK which overcomes previous problems of ALA instability and improves skin penetration. Objectives To evaluate the efficacy and safety of PDT of AKs with BF-200 ALA in comparison with a registered MAL cream and with placebo. Methods The study was performed as a randomized, multicentre, observer-blind, placebo-controlled, interindividual trial with BF-200 ALA, a registered MAL cream and placebo in a ratio of 3 : 3 : 1. Six hundred patients, each with four to eight mild to moderate AK lesions on the face and/or the bald scalp, were enrolled in 26 study centres in Germany, Austria and Switzerland. Patients received one PDT. If residual lesions remained at 3 months after treatment, PDT was repeated. Results PDT with BF-200 ALA was superior to placebo PDT with respect to patient complete clearance rate (78·2% vs. 17·1%; P < 0·0001) and lesion complete clearance rate (90·4% vs. 37·1%) at 3 months after the last PDT. Moreover, superiority was demonstrated over the MAL cream regarding the primary endpoint patient complete clearance (78·2% vs. 64·2%; P < 0·05). Significant differences in the patient and lesion complete clearance rates and severity of treatment-related adverse events were observed for the narrow- and broad-spectrum light sources. Conclusions BF-200 ALA is a very effective, well-tolerated new formulation for AK treatment with PDT and is superior to a registered MAL medication. Efficacies and adverse events vary greatly with the different light sources used.

Overall treatment success after treatment of primary superficial basal cell carcinoma: a systematic review and meta-analysis of randomized and nonrandomized trials

Abstract: Summary Background Several noninvasive treatment modalities are available for superficial basal cell carcinoma (sBCC). Objectives This systematic review aims to determine residue, recurrence and tumour-free survival probabilities of patients with primary sBCC treated with the currently most frequently used therapies. Methods The PubMed (January 1946 to October 2010), EMBASE (January 1989 to October 2010) and Cochrane (January 1993 to October 2010) databases, and reference lists were searched without date restriction. Inclusion criteria were studies that included primary, histologically proven sBCCs, that reported on residue and/or recurrence probabilities after treatment, and had a minimum follow-up period of 12 weeks. Both randomized and nonrandomized studies were included. The primary and secondary outcomes were the probability of complete response and tumour-free survival, respectively. Two independent reviewers selected 36 studies (14 randomized and 22 nonrandomized), and extracted residue, cumulative recurrence and tumour-free survival probabilities. Results Pooled estimates of percentages of sBCC with complete response at 12 weeks post-treatment, derived from 28 studies, were 86·2% [95% confidence interval (CI) 82–90%] for imiquimod treatment, and 79·0% (95% CI 71–87%) for photodynamic therapy (PDT). With respect to tumour-free survival at 1 year, the pooled estimates derived from 23 studies were 87·3% for imiquimod (95% CI 84–91%) and 84·0% for PDT (95% CI 78–90%). Only a small number of studies reported on the results of sBCC treatment with 5-fluorouracil (one), surgical excision (one) and cryotherapy (two). Conclusions Pooled estimates from randomized and nonrandomized studies showed similar tumour-free survival at 1 year for imiquimod and PDT. The PDT tumour-free survival was higher in studies with repeated treatments. However, these results were largely derived from nonrandomized studies, and randomized studies with head-to-head comparison of imiquimod and PDT are lacking. There is a need for head-to-head comparison studies between PDT, imiquimod and other treatments with long-term follow-up to enable better recommendations for optimal sBCC treatment.

Successful treatment of moderate to severe plaque psoriasis with the PEGylated Fab′ certolizumab pegol: results of a phase II randomized, placebo-controlled trial with a re-treatment extension

Abstract: Summary Background Certolizumab pegol (CZP) is a PEGylated antitumour necrosis factor agent. Objectives To evaluate the efficacy and safety of CZP in patients with plaque psoriasis. Methods In a randomized, placebo-controlled, double-blind study, 176 patients with moderate to severe psoriasis received placebo or CZP 400 mg at week 0 followed by placebo or CZP (200 or 400 mg) every other week until week 10. Co-primary endpoints were ≥ 75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75) and a Physician’s Global Assessment (PGA) of clear-almost clear at week 12. A re-treatment extension study was conducted in 71 CZP PASI 75 responders who relapsed during a 12- to 24-week observation period without treatment. Results PASI 75 was achieved by 44/59 (75%), 48/58 (83%) and 4/59 (7%) patients in the CZP 200 mg, CZP 400 mg and placebo groups, respectively (P < 0·001 for both treatment arms vs. placebo). A PGA score of clear-almost clear was achieved by 53%, 72% and 2%, respectively (P < 0·001 for both treatment arms vs. placebo). In the re-treatment study median PASI scores were similar at week 12 in the first treatment and re-treatment periods for both CZP groups. Serious adverse events occurred in 3%, 5% and 2% of CZP 200 mg, CZP 400 mg and placebo patients, respectively. Conclusions Treatment with CZP significantly improved psoriasis at week 12. Similar efficacy was observed at week 12 in patients receiving re-treatment for loss of response after drug withdrawal.

Known and potential new risk factors for skin cancer in European populations: a multicentre case–control study

Abstract: Summary Background During recent years numerous studies have suggested that personal and environmental factors might influence cancer development Objectives To investigate environmental and personal characteristics associated with skin cancer risk Methods A multicentre hospital-based case–control study was performed in Finland, Germany, Greece, Italy, Malta, Poland, Scotland and Spain, including 409 patients with squamous cell carcinoma (SCC), 602 with basal cell carcinoma (BCC) and 360 with cutaneous malignant melanoma (CMM) and 1550 control persons Exposures were assessed by questionnaires that were partly self-administered, partly completed by dermatologists Unconditional logistic regression modelling was used to assess associations including the influence of certain drugs and food items on skin cancer risk Results The usual associations were observed for sun exposure and pigmentation characteristics, with chronic sun exposure being most strongly associated with SCC risk, and naevi and atypical naevi with CMM risk Use of ciprofloxacin was associated with a decreased risk of BCC [odds ratio (OR) 0·33] and use of thiazide diuretics was associated with an increased risk of SCC (OR 1·66) Ciprofloxacin was also associated with SCC (OR 0·34) and thiazines with BCC (OR 2·04), but these associations lost significance after correction for multiple testing Consumption of pomegranate, rich in antioxidants, was associated with decreased BCC and SCC risk, also after correcting for multiple testing Recent experience of stressful events was associated with increased risk, particularly of CMM Conclusions In this large case–control study from across Europe the expected associations were observed for known risk factors Some new potential protective factors and potential risk factors were identified for consumption of certain food items, medication use and stress, which deserve further investigation in future studies

British Association of Dermatologists’ guidelines for the management of bullous pemphigoid 2012

Abstract: British Association of Dermatologists’ guidelines for the management of bullous pemphigoid 2012 V.A. Venning, K. Taghipour, M.F. Mohd Mustapa, A.S. Highet and G. Kirtschig Department of Dermatology, Churchill Hospital, Old Road, Headington, Oxford OX3 7LJ, U.K. Department of Dermatology, Whittington Hospital, Magdala Avenue, London N19 5NF, U.K. British Association of Dermatologists, Willan House, 4 Fitzroy Square, London W1T 5HQ, U.K. York Hospital, Wigginton Road, York YO31 8HE, U.K. Vrije Universtiteit, PO Box 7057, Amsterdam NL-1007 MB, the Netherlands

Daylight‐mediated photodynamic therapy of moderate to thick actinic keratoses of the face and scalp: a randomized multicentre study

Abstract: Summary Background Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma skin cancers and actinic keratoses (AKs). Daylight-mediated PDT is a simple and tolerable treatment procedure for PDT. Methyl aminolaevulinate (MAL)-PDT is approved for the treatment of thin or nonhyperkeratotic AKs on the face and scalp. However, thick AK lesions are often treated as well when present in the field-cancerized treatment area. Objectives In a randomized multicentre study to evaluate efficacy of daylight-mediated PDT for different severity grades of AKs. Methods One hundred and forty-five patients with a total of 2768 AKs (severity grades I–III) of the face and scalp were randomized to either 1½ or 2½ h exposure groups. After application of a sunscreen (sun protection factor 20) and gentle lesion preparation, MAL was applied to the entire treatment area. Patients left the clinic immediately after application and exposed themselves to daylight according to randomization. Daylight exposure was monitored with a wrist-borne dosimeter. Results No difference in lesion response was found between the 1½ and 2½ h exposure group. The mean lesion response rate was significantly higher in grade I lesions (75·9%) than in grade II (61·2%) and grade III (49·1%) lesions (P 3·5 J cm−2. Conclusions Daylight-mediated PDT of moderate to thick AKs was less effective than daylight-mediated PDT of thin AKs especially in some centres. However, nearly all thicker lesions (grades II and III) were reduced to a lower lesion grade at 3 months after a single treatment of daylight-mediated PDT.

Psoriasis: rationale for targeting interleukin-17

Abstract: The exact pathogenesis of plaque psoriasis remains to be fully determined, but it is thought to depend on environmental and genetic factors that stimulate dysregulated innate and adaptive immune responses in the skin. The cytokine interleukin (IL)-17A plays a key role in host defence against extracellular bacteria and fungi. An increasing body of evidence suggests that IL-17A is also important in psoriasis pathogenesis. While IL-17A is a key product of Th17 cells, it is also produced by neutrophils, mast cells and Tc17 cells. Each of these cell types is found in psoriatic lesions. IL-17A acts on keratinocytes to increase expression of chemokines (e.g. CCL20, CXCL1, CXCL3, CXCL5, CXCL6 and CXCL8) involved in recruiting myeloid dendritic cells, Th17 cells and neutrophils to the lesion site. IL-17A induces production of antimicrobial peptides and proinflammatory cytokines that, in turn, may help sustain immune responses in the skin. Blocking IL-17A improved psoriasis-like pathology in experimental models, and reductions in IL-17 signalling have been associated with response to tumour necrosis factor-α blockers in patients with psoriasis. Agents that inhibit IL-17 are in development and preliminary clinical results for IL-17 inhibitors indicate the importance of IL-17A in psoriasis pathophysiology. In a proof-of-concept and two phase II trials, three agents markedly reduced disease severity in patients with moderate-to-severe plaque psoriasis. One agent downregulated cytokines, chemokines and proteins associated with inflammatory responses in lesional skin. In summary, IL-17A is an attractive therapeutic target, which may allow selective intervention to address the dysregulated immune system in plaque psoriasis.

A European multicentre photopatch test study

Abstract: Background The two most common agent groups currently responsible for photoallergic contact dermatitis (PACD) are organic ultraviolet (UV) absorbers in sunscreens and topical nonsteroidal anti‐inflammatory drugs (NSAIDs). However, availability of information on the photoallergenic potential of these agents is scarce.

Interventions for treating oral lichen planus: a systematic review

Abstract: Oral lichen planus (OLP) is a common chronic inflammatory disease associated with cell-mediated immunological dysfunction. Symptomatic OLP is painful and complete healing is rare. The aim of this review was to assess the evidence for the efficacy and safety of treatments for symptomatic OLP. The Cochrane Oral Health Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE were searched in January 2011 to identify all randomized controlled trials (RCTs) evaluating any intervention for the treatment of symptomatic OLP. A total of 28 trials were included in this Cochrane review. There was no evidence from three RCTs that topical pimecrolimus is better than placebo in reducing pain from OLP. There was weak evidence from two RCTs that topical aloe vera may be associated with a reduction in pain compared with placebo. There was weak and unreliable evidence from two small trials, at high risk of bias, that topical ciclosporin may reduce pain and clinical signs of OLP. There was no evidence (from five trials each evaluating a different steroid and/or calcineurin inhibitor) that there is a difference between treatment with topical corticosteroids (TCSs) compared with topical calcineurin inhibitors with regard to reducing pain associated with OLP or that any specific steroid therapy is more or less effective at reducing pain. Although TCSs are considered to be the first-line treatment, we did not identify any RCTs that compared TCSs with placebo in patients with symptomatic OLP. From the 28 trials included in this systematic review, the wide range of interventions compared means there is insufficient evidence to support the superior effectiveness of any specific treatment.

Dermoscopy of lentigo maligna melanoma: report of 125 cases

Abstract: Summary Background Lentigo maligna melanoma (LMM) is the most common subtype of melanoma on the face. Its presentation may be quite subtle, particularly in early stages, and delayed diagnosis is common. Few dermoscopic studies have been performed and the main dermoscopic features of LMM were defined by Stolz and coworkers in 2000. Objectives To investigate classical as well as new dermoscopic features in a large series of LMM in a white-skinned population, in order to evaluate their diagnostic value. Methods One hundred and twenty-five consecutive histopathology-proven LMMs were analysed retrospectively based on medical records, clinical and dermoscopic photographs by three independent observers for the presence of 19 predefined criteria. Results At least one of the classical Stolz criteria was present in 87% of cases (hyperpigmented follicular opening, annular-granular pattern, pigmented rhomboidal structures, obliterated hair follicles). Three original criteria were also present at a relatively high frequency: increased density of the vascular network (58%), red rhomboidal structures (40%), target-like patterns (41%). Darkening at dermoscopic examination (when compared with naked-eye examination) was observed in 25% of lesions. Classical dermoscopic features of extrafacial melanoma (atypical pigment network, irregularly distributed globules, dots, streaks and pseudopods) and vertical growth phase-associated dermoscopic criteria (ulceration, blue papular areas and black structureless areas) were rarely seen. A large number of colours, pigmented rhomboidal structures, obliterated hair follicles and red rhomboidal structures were significantly more frequent in invasive LMMs. In contrast, in situ melanomas were more often associated with one or two colours and few distinctive dermoscopic features. Conclusions We present herein, in a large series of LMM, confirmation of the diagnostic value of the classical Stolz dermoscopic criteria and describe four additional original criteria, mainly vascular. A correlation between the presence of some dermoscopic features and thicker tumoral invasion has also been demonstrated.