The 50 most-cited articles in British Journal of Dermatology, 2018

BACKGROUND: The exact prevalence and incidence of rosacea remain unknown, although it is a common condition associated with severe noncutaneous diseases. OBJECTIVES: To perform a systematic review of the published literature to examine the global incidence and prevalence of rosacea. METHODS: A systematic review of population-based and dermatological outpatient studies reporting the incidence and/or prevalence of rosacea was performed using three electronic medical databases: PubMed, Embase and Web of Science. Data were extracted and a proportion meta-analysis was performed to obtain pooled proportions. RESULTS: In total 32 studies were included examining a total of 41 populations with 26 519 836 individuals. Twenty-two populations were from Europe, three from Africa, four from Asia, nine from North America and three from South America. The pooled proportion of individuals with rosacea was 5·46% [95% confidence interval (CI) 4·91-6·04] in the general population and 2·39% (95% CI 1·56-3·39) among dermatological outpatients. Self-reported rosacea gave higher prevalence estimates than…

Abstract Linked Comment: Akel and Fuller. Br J Dermatol 2018; 178:823–824. Plain language summary available online

BACKGROUND: Application of deep-learning technology to skin cancer classification can potentially improve the sensitivity and specificity of skin cancer screening, but the number of training images required for such a system is thought to be extremely large. OBJECTIVES: To determine whether deep-learning technology could be used to develop an efficient skin cancer classification system with a relatively small dataset of clinical images. METHODS: A deep convolutional neural network (DCNN) was trained using a dataset of 4867 clinical images obtained from 1842 patients diagnosed with skin tumours at the University of Tsukuba Hospital from 2003 to 2016. The images consisted of 14 diagnoses, including both malignant and benign conditions. Its performance was tested against 13 board-certified dermatologists and nine dermatology trainees. RESULTS: The overall classification accuracy of the trained DCNN was 76·5%. The DCNN achieved 96·3% sensitivity (correctly classified malignant as malignant) and 89·5% specificity (correctly classified benign as benign). Although the accuracy of malignant…

BACKGROUND: Alopecia areata is a disorder that results in nonscarring hair loss. The psychological impact can be significant, leading to feelings of depression and social isolation. Objectives In this article, we seek to review the pathophysiological mechanisms proposed in recent years in a narrative fashion. METHODS: We searched MEDLINE and Scopus for articles related to alopecia areata, with a particular emphasis on its pathogenesis. RESULTS: The main theory of alopecia areata pathogenesis is that it is an autoimmune phenomenon resulting from a disruption in hair follicle immune privilege. What causes this breakdown is an issue of debate. Some believe that a stressed hair follicle environment triggers antigen presentation, while others blame a dysregulation in the central immune system entangling the follicles. Evidence for the latter theory is provided by animal studies, as well investigations around the AIRE gene. Different immune-cell lines including plasmacytoid dendritic cells, natural killer cells and T cells, along with key molecules such as interferon-γ, interleukin-15,…

BACKGROUND: Atopic dermatitis is the most common chronic inflammatory skin disorder, affecting up to 20% of children and 10% of adults in industrialized countries. This highly debilitating condition poses a considerable burden to both the individual and society at large. The pathophysiology of atopic dermatitis is complex, encompassing both genetic and environmental risk factors. METHODS: This is a narrative review based on a systematic literature search. CONCLUSIONS: Dysregulation of innate and adaptive immunity plays a key role; however, recent epidemiological, genetic and molecular research has focused interest on skin barrier dysfunction as a common precursor and pathological feature. Current understanding of the aetiology of atopic dermatitis highlights disruption of the epidermal barrier leading to increased permeability of the epidermis, pathological inflammation in the skin, and percutaneous sensitization to allergens. Thus, most novel treatment strategies seek to target specific aspects of the skin barrier or cutaneous inflammation. Several studies have also shown promise…

BACKGROUND: Survival in mycosis fungoides (MF) is varied and may be poor. The PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study is a web-based data collection system for early-stage MF with legal data-sharing agreements permitting international collaboration in a rare cancer with complex pathology. Clinicopathological data must be 100% complete and in-built intelligence in the database system ensures accurate staging. OBJECTIVES: To develop a prognostic index for MF. METHODS: Predefined datasets for clinical, haematological, radiological, immunohistochemical, genotypic, treatment and quality of life are collected at first diagnosis of MF and annually to test against survival. Biobanked tissue samples are recorded within a Federated Biobank for translational studies. RESULTS: In total, 430 patients were enrolled from 29 centres in 15 countries spanning five continents. Altogether, 348 were confirmed as having early-stage MF at central review. The majority had classical MF (81·6%) with a CD4 phenotype (88·2%). Folliculotropic MF was diagnosed in 17·8%.…

BACKGROUND: The lack of objective diagnostic criteria renders pyoderma gangrenosum (PG) a diagnosis of exclusion. The diagnostic approaches proposed to date have not been systematically evaluated. Thus, PG remains a challenging and frequently misdiagnosed disorder. OBJECTIVES: To develop and assess a comprehensive, yet clinically practicable, sensitive diagnostic scoring system for PG. METHODS: Clinical history and images of a total of 60 participants with previously confirmed PG located on the lower extremity and a control cohort of 50 patients with venous leg ulcers were retrospectively evaluated by expert teams at two tertiary dermatological centres specializing in wound care using a newly developed diagnostic scoring system composed of 10 criteria. RESULTS: The three major diagnostic criteria are rapidly progressing disease, assessment of relevant differential diagnoses and a reddish-violaceous wound border (prevalent in 98% of patients with PG). Minor criteria (evident in 61-95% of patients with PG) include amelioration by immunosuppressant drugs, characteristically irregular…

BACKGROUND: Transepidermal water loss (TEWL) is one of the most important skin barrier characteristics. Higher TEWL is usually associated with skin barrier impairments, and lower TEWL with healthy skin. OBJECTIVES: To update an existing systematic review and meta-analysis to provide TEWL reference values for healthy skin in adults. METHODS: The databases MEDLINE and Embase and other sources were searched. This update includes studies identified by two combined searches that cover the period from 1947 to 13 April 2017. Primary empirical observational and interventional studies in healthy adults providing quantitative estimates of TEWL measurements including measures of spread, such as SDs, with clear reporting of skin areas and age were included. Data were extracted per skin area and statistically pooled. RESULTS: (95% confidence interval 39·8-48·2) for the axilla. Sample sizes ranged from four (forehead middle left middle) to 4013 (mid volar right forearm). The clinical relevance of the difference between TEWL estimates for different measurement devices seems to be minimal. TEWL in…

BACKGROUND: There is no consensus on core outcome domains for hidradenitis suppurativa (HS). Heterogeneous outcome measure instruments in clinical trials likely leads to outcome-reporting bias and limits the ability to synthesize evidence. OBJECTIVES: To achieve global multistakeholder consensus on a core outcome set (COS) of domains regarding what to measure in clinical trials for HS. METHODS: Six stakeholder groups participated in a Delphi process that included five anonymous e-Delphi rounds and four face-to-face consensus meetings to reach consensus on the final COS. The aim was for a 1 : 1 ratio of patients to healthcare professionals (HCPs). RESULTS: A total of 41 patients and 52 HCPs from 19 countries in four continents participated in the consensus process, which yielded a final COS that included five domains: pain, physical signs, HS-specific quality of life, global assessment and progression of course. A sixth domain, symptoms, was highly supported by patients and not by HCPs but is recommended for the core domain set. CONCLUSIONS: Routine adoption of the COS in future HS…

Linked Comment:Jemec. Br J Dermatol 2019; 180:975. Plain language summary available online

Linked Editorial:Wang and Bagot. Br J Dermatol 2019; 180:443–444.

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…

Dear Editor, Higher rates of conjunctivitis have been reported in patients with atopic dermatitis (AD) treated with dupilumab, an anti‐interleukin (IL)‐4Rα antibody inhibiting IL‐4 and IL‐13, vs. patients treated with placebo.1 However, the exact pathomechanism has not been clarified. Given the necessity for optimal treatment and risk management, the aim of this study was to describe the histopathological characteristics of conjunctivitis during dupilumab treatment in patients with AD. Participants, selected from the BioDay registry, consisted of 74 patients with moderate‐to‐severe AD treated with dupilumab for at least 16 weeks. Of these, 23% developed ophthalmologist‐confirmed conjunctivitis requiring anti‐inflammatory treatment. We sequentially included six patients [three male; median age 39 years, interquartile range (IQR) 29–54] in whom a diagnostic conjunctival biopsy of the inferior fornix was performed before initiation of ocular anti‐inflammatory treatment. Biopsies were fixed, paraffin‐embedded and stained with haematoxylin and eosin for histological assessment, and…

Hidradenitis suppurativa (HS) influences patients' lives in many ways. The most troublesome symptom of HS is chronic pain, of mild-to-moderate intensity, which is reported by almost all patients. With reference to psychosocial evaluation, HS appears to be a highly debilitating disease. The major factors influencing patients' well-being are disease severity, the number of flares or affected skin areas, and the lesion location. The mean Dermatology Life Quality Index scores of 8·3-12·7 points obtained among patients with HS are typical for severe dermatoses, which have a large impact on patients' quality of life (QoL). HS not only affects skin-related QoL issues, but also has a profound impact on general QoL measures - it causes substantial deterioration of both physical and mental health. Considering the impaired QoL due to HS and HS-associated, nonpsychiatric comorbidities, it is not surprising that patients with HS experience psychological disturbances. In both observational and registry studies, depression and anxiety were significantly related to HS. The prevalences were…

BACKGROUND: Adalimumab is used to treat several inflammatory diseases, including plaque psoriasis. GP2017 is a proposed adalimumab biosimilar. OBJECTIVES: To assess the impact of multiple switches between GP2017 and reference adalimumab (ref-ADMB) following the demonstration of equivalent efficacy and similar safety and immunogenicity, in adult patients with active, clinically stable, moderate-to-severe plaque psoriasis. METHODS: This 51-week double-blinded, phase III study randomly assigned patients to GP2017 (n = 231) or ref-ADMB (n = 234) 80 mg subcutaneously at week 0, then 40 mg biweekly from week 1. At week 17, patients were rerandomized to switch (n = 126) or continue (n = 253) treatment. The primary end point was patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 16, with equivalence confirmed if the 95% confidence interval (CI) for the difference in PASI 75 between treatments was ± 18%. The key secondary end point was the change from baseline to week 16 in continuous PASI. Other end points were PASI over time; PASI 50, 75, 90 and100;…

BACKGROUND: Bakuchiol is a phytochemical that has demonstrated cutaneous antiageing effects when applied topically. Early studies have suggested that bakuchiol is a functional analogue of topical retinoids, as both compounds have been shown to induce similar gene expression in the skin and lead to improvement of cutaneous photodamage. No in vivo studies have compared the two compounds for efficacy and side-effects. OBJECTIVES: To compare the clinical efficacy and side-effect profiles of bakuchiol and retinol in improving common signs of cutaneous facial ageing. METHODS: This was a randomized, double-blind, 12-week study in which 44 patients were asked to apply either bakuchiol 0·5% cream twice daily or retinol 0·5% cream daily. A facial photograph and analytical system was used to obtain and analyse high-resolution photographs of patients at 0, 4, 8 and 12 weeks. Patients also completed tolerability assessment questions to review side-effects. During study visits, a board-certified dermatologist, blinded to study group assignments, graded pigmentation and redness. RESULTS: Bakuchiol…

BACKGROUND: Rosacea is a common chronic facial dermatosis. Classification of rosacea has evolved from subtyping to phenotyping. OBJECTIVES: To update our systematic review on interventions for rosacea. METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index and ongoing trials registers (March 2018) for randomized controlled trials. Study selection, data extraction, risk-of-bias assessment and analyses were carried out independently by two authors. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess certainty of evidence. RESULTS: We included 152 studies (46 were new), comprising 20 944 participants. Topical interventions included brimonidine, oxymetazoline, metronidazole, azelaic acid, ivermectin and other topical treatments. Systemic interventions included oral antibiotics, combinations with topical treatments or other systemic treatments. Several studies evaluated laser or light-based treatment. We present the most current evidence for rosacea management based on a phenotype-led approach. CONCLUSIONS: For reducing…

BACKGROUND: Atopic dermatitis is a systemic disorder characterized by abnormal barrier function across multiple organ sites. Causes of epidermal barrier breakdown are complex and driven by a combination of structural, genetic, environmental and immunological factors. In addition, alteration in microflora diversity can influence disease severity, duration, and response to treatment. Clinically, atopic dermatitis can progress from skin disease to food allergy, allergic rhinitis, and later asthma, a phenomenon commonly known as the atopic march. The mechanism by which atopic dermatitis progresses towards gastrointestinal or airway disease remains to be elucidated. OBJECTIVES: This review addresses how epithelial dysfunction linking microbiome alteration and immune dysregulation can predispose to the development of the atopic march. METHODS: A literature search was conducted using the PubMed database for relevant articles with the keywords 'atopic dermatitis', 'epithelial barrier', 'skin', 'gut', 'lung', 'microbiome' and 'immune dysregulation'. RESULTS: Initial disruption in the skin…

BACKGROUND: Genital psoriasis (GenPs) is a common, debilitating and difficult-to-treat manifestation of plaque psoriasis. However, few controlled, interventional studies of GenPs exist. OBJECTIVES: To determine the efficacy of ixekizumab vs. placebo in patients with moderate-to-severe GenPs with ≥ 1% involved body surface area (BSA). METHODS: Patients with moderate-to-severe GenPs, defined as a baseline static Physician's Global Assessment of Genitalia (sPGA-G) score of ≥ 3, with BSA ≥ 1% were randomized 1 : 1 to receive placebo (n = 74) or the recommended dosing of ixekizumab (n = 75). Major outcomes included the percentage of patients achieving 0 or 1 scores on the sPGA-G (primary end point), overall sPGA, GenPs Sexual Frequency Questionnaire (GenPs-SFQ) item 2, and ≥ 3-point improvement from baseline on the GenPs itch numerical rating scale. RESULTS: At week 12, ixekizumab was superior to placebo for sPGA-G 0/1 (73% vs. 8%, P < 0·001), overall sPGA 0/1 (73% vs. 3%, P < 0·001), GenPs-SFQ item 2 score of 0 or 1 (78% vs. 21%, P < 0·001) and genital itch (60% vs. 8%, P < 0·001). No…

These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016, and a consensus on the discussions. These guidelines summarize evidence and expert-based recommendations and intend to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part two, covering the management of complications and the particularities of some forms of congenital ichthyosis.

BACKGROUND: Biologic therapies have revolutionized the treatment of moderate-to-severe psoriasis. However, for reasons largely unknown, many patients do not respond or lose response to these drugs. OBJECTIVES: To evaluate demographic, social and clinical factors that could be used to predict effectiveness and stratify response to biologic therapies in psoriasis. METHODS: Using a multicentre, observational, prospective pharmacovigilance study (BADBIR), we identified biologic-naive patients starting biologics with outcome data at 6 (n = 3079) and 12 (n = 3110) months. Associations between 31 putative predictors and outcomes were investigated in univariate and multivariable regression analyses. Potential stratifiers of treatment response were investigated with statistical interactions. RESULTS: Eight factors associated with reduced odds of achieving ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) at 6 months were identified (described as odds ratio and 95% confidence interval): demographic (female sex, 0·78, 0·66-0·93); social (unemployment, 0·67, 0·45-0·99);…

BACKGROUND: Few studies have reported the clinical features, complications and predictors of Kasabach-Merritt phenomenon (KMP) associated with Kaposiform haemangioendothelioma (KHE). OBJECTIVES: To determine the clinical characteristics present at diagnosis and to identify features that may aid clinicians in managing KHE. METHODS: We conducted a cohort study of 146 patients diagnosed with KHE. RESULTS: KHE precursors or lesions were present at birth in 52·1% of patients. In 91·8% of patients, lesions developed within the first year of life. The median age at diagnosis of KHE was 2·3 months (interquartile range 1·0-6·0). The extremities were the dominant location, representing 50·7% of all KHEs. Among KHEs in the cohort, 63·0% were mixed lesions (cutaneous lesions with deep infiltration). Approximately 70% of patients showed KMP. A KHE diagnosis was delayed by ≥ 1 month in 65·7% of patients with KMP. Patients with KMP were more likely to have major complications than patients without KMP (P = 0·023). Young age (< 6 months), trunk location, large lesion size (> 5·0 cm) and mixed…

BACKGROUND: Recurrent cutaneous squamous cell carcinoma (cSCC) has been associated with an increased risk of local functional and aesthetic comorbidity, metastasis and mortality. OBJECTIVES: To compare the risk of recurrence between Mohs micrographic surgery (MMS) and standard excision for cSCC of the head and neck. METHODS: This was a retrospective cohort study of all patients with a cSCC treated with MMS or standard excision at the departments of dermatology of a secondary or tertiary care hospital in the Netherlands between 2003 and 2012. To detect all recurrences, patients were linked to the Dutch pathology registry. To compare the risk of recurrence between MMS and standard excision, hazard ratios (HRs) were used adjusted for clinical tumour size > 2 cm and deep tumour invasion. RESULTS: A total of 579 patients with 672 cSCCs were included: 380 cSCCs were treated with MMS and 292 with standard excision. The risk of recurrence was 8% (22 of 292) after standard excision during a median follow-up of 5·7 years [interquartile range (IQR) 3·5-7·8], which was higher than the 3% (12 of…

These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016 and a consensus on the discussions. They summarize evidence and expert‐based recommendations and are intended to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part one, covering topical therapies, systemic therapies, psychosocial management, communicating the diagnosis and genetic counselling.

BACKGROUND: Living with alopecia areata (AA) totalis and universalis (collectively referred to here as AA) involves unpredictable, sometimes rapid hair loss. There is currently no effective treatment and patients describe feelings of shock, loss, trauma and disrupted identity. Cultural meanings attached to hair and hair loss, including associations between hair and femininity, and hair loss and cancer may exacerbate distress. Consequently, wigs and make-up are frequently used as camouflage, but this can produce feelings of inauthenticity, shame and anxiety. OBJECTIVES: This article explores how meanings associated with hair and hair loss influence experiences of living with AA. We also aim to identify how this understanding might inform practice by healthcare professionals to best support patients to cope with the condition. METHODS: A total of 95 participants with AA completed an online qualitative survey about their experiences of living with the condition. Data were subjected to thematic analysis within a critical realist theoretical framework. RESULTS: The following four themes…

BACKGROUND: Biomarkers of atopic dermatitis (AD) are largely lacking, especially in infant AD. Those that have been examined to date have focused mostly on serum cytokines, with few on noninvasive biomarkers in the skin. OBJECTIVES: We aimed to explore biomarkers obtainable from noninvasive sampling of infant skin. We compared these with plasma biomarkers and structural and functional measures of the skin barrier. METHODS: We recruited 100 infants at first presentation with AD, who were treatment naive to topical or systemic anti-inflammatory therapies, and 20 healthy children. We sampled clinically unaffected skin by tape stripping the stratum corneum (SC). Multiple cytokines and chemokines and natural moisturizing factor were measured in the SC and plasma. We recorded disease severity and skin barrier function. RESULTS: Nineteen SC and 12 plasma biomarkers showed significant differences between healthy and AD skin. Some biomarkers were common to both the SC and plasma, and others were compartment specific. Identified biomarkers of AD severity included T helper 2-skewed markers…

Dear Editor, Psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are chronic inflammatory conditions. Effective long‐term treatment may be necessary in women of childbearing age, but data concerning current treatments and pregnancy remain incomplete. Due to immunological changes, psoriasis and, to a lesser extent, PsA generally improve during pregnancy;1,2 however, many pregnant patients still require treatment. AS tends to have an adverse effect on health‐related quality of life during pregnancy.3 There is growing evidence to suggest that biological treatments for inflammatory conditions are not detrimental during pregnancy.1 Secukinumab is a fully human monoclonal antibody that selectively targets ilnterleukin‐17A, and shows sustained efficacy in the treatment of moderate‐to‐severe psoriasis, PsA and AS, with a favourable safety profile.4,5 As an IgG1 molecule, secukinumab could theoretically cross the placenta, but most antibody transfer occurs in the third trimester.6 Animal studies do not indicate harmful effects of secukinumab with respect to pregnancy,…

BACKGROUND: Disintegration of the infundibula of terminal hair follicles (HFs) in intertriginous skin areas exhibits the histological hallmark of hidradenitis suppurativa (HS)/acne inversa, featuring a dissecting terminal hair folliculitis. Elevated serum levels of interleukin (IL)-17 and local increase in the ratio of proinflammatory T helper (Th)17 cells and anti-inflammatory regulatory T cells (Tregs) have been reported. Perifollicular Tregs play a key role in HF stem cell homeostasis and infundibular integrity. OBJECTIVES: In this review, we evaluate the Th17/Treg ratio in HS, its aggravating conditions and associated comorbidities. Furthermore, we intended to clarify whether drugs with reported beneficial effects in the treatment of HS readjust the deviated Th17/Treg axis. METHODS: PubMed-listed, peer-reviewed original research articles characterizing Th17/Treg regulation in HS/acne inversa and associated comorbidities were selected for this review. RESULTS: This review presents HS as a disease that exhibits an increased Th17/Treg ratio. Perifollicular deficiencies in Treg…

BACKGROUND: Hidradenitis suppurativa (HS), a chronic cutaneous disease, can negatively affect work life. OBJECTIVES: This retrospective cohort study evaluates the indirect burden among employed patients with HS in the U.S.A. METHODS: Newly diagnosed and general patients with HS, who were employees (age 18-64 years) from a large claims database (Q1 1999 to Q1 2015), were matched 1 : 5 to controls. Income growth and risk of leaving the workforce were assessed among the newly diagnosed HS and control cohorts in the 5-year study period. Income, work loss days and indirect costs (absenteeism and disability) were assessed among the general HS and control cohorts in the 1-year study period. RESULTS: Newly diagnosed (n = 1003, mean age 39·5 years, 66·3% female) and general patients with HS (n = 1204, mean age 39·9 years, 69·1% female) were matched to 5015 and 6020 controls, respectively. Newly diagnosed patients with HS had significantly slower income growth ($324 per year) and higher risk of leaving the workforce (adjusted hazard ratio 1·65, 95% confidence interval 1·45-1·88) compared with…

BACKGROUND: Nail psoriasis is associated with functional impairment, pain and reduced quality of life. OBJECTIVES: To demonstrate the superiority of secukinumab over placebo in clearing nail psoriasis as assessed by the Nail Psoriasis Severity Index (NAPSI) at week 16 and over time up to week 132. Presented here is the week 32 interim analysis. Impact on quality of life was assessed by Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) patient questionnaires. METHODS: TRANSFIGURE is a double-blind, randomized, placebo-controlled study in patients with moderate-to-severe plaque and nail psoriasis. RESULTS: The primary objective of this study was met: both doses of secukinumab were superior to placebo at week 16 (NAPSI improvements of -45·3%, -37·9% and -10·8% for secukinumab 300 mg and 150 mg and placebo, respectively, P < 0·001). Significant improvements were seen in patients' quality of life: the NAPPA-Quality of Life total score median decreases at week 16 were 60·9%, 49·9% and 15·8% for secukinumab 300 mg and 150 mg and placebo, respectively (P < 0·001). Improvement in…

BACKGROUND: Topical photodynamic therapy (PDT) is widely used to treat superficial nonmelanoma skin cancer and dysplasia, and is generally well tolerated. However, as with all treatments, adverse effects may occur and awareness may facilitate approaches to prevention and management. OBJECTIVES: To review the available evidence relating to the adverse effects of topical PDT, to help inform recommendations in updated clinical guidelines produced by the British Association of Dermatologists and British Photodermatology Group, and the efficacy of preventative and therapeutic approaches. METHODS: This review summarizes the published evidence related to the adverse effects of topical PDT and attempts to interpret this evidence in the context of patient risk and management. RESULTS: Pain and discomfort during PDT are acute adverse effects, which can be minimized through the use of modified and low-irradiance PDT regimens and do not therefore usually limit successful treatment delivery. Other adverse effects include the risk of contact allergy to photosensitizer prodrugs, although this is…

BACKGROUND: Adherence to topical psoriasis treatments is low, which leads to unsatisfactory treatment results. Smartphone applications (apps) for patient support exist but their potential to improve adherence has not been systematically evaluated. OBJECTIVES: To evaluate whether a study-specific app improves adherence and reduces psoriasis symptoms compared with standard treatment. METHODS: We conducted a randomized controlled trial (RCT, clinicaltrials.gov registration: NCT02858713). Patients received once-daily medication [calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam] and were randomized to no app (n = 66) or app intervention (n = 68) groups. In total, 122 patients (91%) completed the 22-week follow-up. The primary outcome was adherence, which was defined as medication applied ≥ 80% of days during the treatment period and assessed by a chip integrated into the medication dispenser. Secondary outcomes were psoriasis severity measured by the Lattice System Physician's Global Assessment (LS-PGA) and quality of life, measured using the Dermatology Life Quality Index…

Interleukin (IL)‐31 is implicated in pruritus associated with pruritic skin diseases like atopic dermatitis. Although pruritus is a prominent feature in dermatomyositis (DM), few studies have evaluated the pathogenesis of DM‐associated itch. To establish the prevalence of itch in DM, and to investigate the role of IL‐31 in DM‐related itch. Pruritus and disease activity of DM were evaluated by a visual analogue scale (VAS) and the Cutaneous Disease and Activity Severity Index (CDASI), respectively. Expression of IL‐31 and IL‐31 receptor alpha (IL‐31RA) in lesional DM, nonlesional DM and healthy control skin was evaluated by quantitative reverse‐transcriptase polymerase chain reaction and immunofluorescence. Flow cytometry was performed on skin cells isolated from lesional DM skin to identify cellular sources of IL‐31 in DM. Among 191 patients with DM, 50·8% had moderate‐to‐severe itch, and itch was correlated with increased cutaneous severity (r = 0·34). In patients with itchy DM, gene expression of IL31 and IL31RA in lesional skin was upregulated compared with nonlesional skin and…

BACKGROUND: Incontinence-associated dermatitis (IAD) is a specific type of irritant contact dermatitis with different severity levels. An internationally accepted instrument to assess the severity of IAD in adults, with established diagnostic accuracy, agreement and reliability, is needed to support clinical practice and research. OBJECTIVES: To design the Ghent Global IAD Categorization Tool (GLOBIAD) and evaluate its psychometric properties. METHODS: The design was based on expert consultation using a three-round Delphi procedure with 34 experts from 13 countries. The instrument was tested using IAD photographs, which reflected different severity levels, in a sample of 823 healthcare professionals from 30 countries. Measures for diagnostic accuracy (sensitivity and specificity), agreement, interrater reliability (multirater Fleiss kappa) and intrarater reliability (Cohen's kappa) were assessed. RESULTS: The GLOBIAD consists of two categories based on the presence of persistent redness (category 1) and skin loss (category 2), both of which are subdivided based on the presence of…

BACKGROUND: The patient's perspective of their facial scar after skin cancer surgery influences perception of care and quality of life (QoL). Appearance satisfaction after surgery is also an important but often overlooked treatment outcome. OBJECTIVES: To report the psychometric validation of the FACE-Q Skin Cancer Module consisting of five scales, measuring appearance satisfaction (Satisfaction with Facial Appearance, Appraisal of Scars), QoL (Cancer Worry, Appearance-related Psychosocial Distress) and the patient experience (Satisfaction with Information: Appearance). METHODS: Participants underwent Mohs surgery for facial basal or squamous cell carcinoma or excision of early facial melanoma. Cohort 1 received a set of scales before and after surgery. Cohort 2 received the scales on two occasions in the postoperative period for test-retest reliability. Rasch measurement theory was used to select (item-reduce) the most clinically meaningful items for the scales. Reliability, validity, floor and ceiling effects and responsiveness were also analysed. RESULTS: Of 334 patients, 209…

BACKGROUND: Psoriasis is a chronic, immune-mediated disease, characterized by symptoms that include itching and skin pain and is often associated with comorbidities. Patients have a substantial detriment to quality of life (QoL) and work productivity with associated cost burden. OBJECTIVES: To investigate the incremental burden of comorbidities, itch and affected body areas among systemic eligible patients with psoriasis, using a multinational survey of dermatologists and their patients with psoriasis. METHODS: Multinational data from the Growth from Knowledge (GfK) Disease Atlas Global Real-World Evidence program were used. Eligible patients were identified as those who were currently having or had ever had moderate-to-severe psoriasis, and must have been receiving prescription treatments at the time of the survey. Multivariable regression analyses were conducted to assess the incremental burden among psoriasis patients with physical and psychological comorbidities, itch and affected visible and sensitive body areas vs. psoriasis patients without these conditions, respectively.…

Limitations of the guidelinesThis document has been prepared on behalf of the BAD and is based on the best data available when the document was prepared.It is recognized that under certain conditions it may be necessary to deviate from the guidelines and that the results of future studies may require some of the recommendations herein to be changed.Failure to adhere to these guidelines should not necessarily be considered negligent, nor should adherence to these recommendations constitute a defence against a claim of negligence.Limiting the review to Englishlanguage references was a pragmatic decision but the authors recognize this may exclude some important information published in other languages.For example, certain papers cited in the European guidelines on chronic pruritus, published in 2012, are not written in English.5 Plans for guideline revisionThe proposed revision for this set of recommendations is scheduled for 2023; where necessary, important interim changes will be updated on the BAD website.

BACKGROUND: Acne is a complex and multifactorial skin disorder. Alterations in skin surface lipid (SSL) are believed to be an important factor in the pathogenesis of acne and SSL plays a key role in the initiation of acne lesions. OBJECTIVES: To analyse the lipidome profiles of SSL in patients with acne and in healthy controls in order to understand SSL abnormity in acne in young men. METHODS: Ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and multivariate data analysis were used to investigate the SSL variations in main lipid classes, subclasses and individual species. RESULTS: Results showed that there were significant differences in the lipidome between the two groups. Significantly increased levels of three main classes of glycerophospholipids, fatty acyls and sterol lipids and significantly decreased levels of two main classes of prenol lipids and saccharolipids were observed in patients with acne. Subsequent analysis showed that there were 18 subclasses, which varied significantly and shared the same changing trends of the…

BACKGROUND: Automated classification of medical images through neural networks can reach high accuracy rates but lacks interpretability. OBJECTIVES: To compare the diagnostic accuracy obtained by using content-based image retrieval (CBIR) to retrieve visually similar dermatoscopic images with corresponding disease labels against predictions made by a neural network. METHODS: A neural network was trained to predict disease classes on dermatoscopic images from three retrospectively collected image datasets containing 888, 2750 and 16 691 images, respectively. Diagnosis predictions were made based on the most commonly occurring diagnosis in visually similar images, or based on the top-1 class prediction of the softmax output from the network. Outcome measures were area under the receiver operating characteristic curve (AUC) for predicting a malignant lesion, multiclass-accuracy and mean average precision (mAP), measured on unseen test images of the corresponding dataset. RESULTS: In all three datasets the skin cancer predictions from CBIR (evaluating the 16 most similar images) showed…

Anti‐melanoma differentiation‐associated gene 5 (MDA5) dermatomyositis (DM) is a distinctive subtype of DM that carries a significant risk of interstitial lung disease (ILD). The mechanisms remain elusive. To explore the role of the type I interferon (IFN) system in the pathogenesis of anti‐MDA5 DM. Twenty patients with anti‐MDA5 DM were studied and compared with patients with anti‐aminoacyl‐tRNA synthetase (ARS) DM (n = 10) and autoantibody‐negative patients with DM (n = 20). The levels of inflammatory cytokines, B‐cell‐activating factor (BAFF) and Krebs von den Lungen (KL)‐6 in blood were tested by enzyme‐linked immunosorbent assay and multiplex assays. Expressions of transcripts for IFN‐associated sensors and type I IFN‐inducible genes in peripheral blood mononuclear cells (PBMCs) were detected by real‐time polymerase chain reaction. Expressions of the signal transducer and activator of transcription (STAT)1, interferon‐stimulated gene (ISG)15 and MxA proteins in skin lesions were analysed by immunohistochemistry. Plasma IFN‐α levels were significantly increased in patients with…

Peripheral eosinophilia has been reported in 50–60% of patients with bullous pemphigoid (BP) and correlated positively with disease severity. To establish an association of peripheral eosinophilia with the different morphological characteristics of BP. The study was designed as a case–control study. Diagnosis of BP was grounded on well‐established immunopathological criteria. Five age‐, sex‐ and ethnicity‐matched controls were randomly selected for each patient with BP. Overall, 225 patients with BP and 1125 control participants were enrolled. A total of 113 (50·2%) patients with BP and 49 (4·4%) controls had pathological peripheral eosinophilia (P < 0·001). An independent association between eosinophil count and the diagnosis of BP was observed [odds ratio 59·9 (per 1000 eosinophil μL−1 increase); P < 0·001]. Patients with BP with eosinophilia were significantly older at presentation (P = 0·003) and had increased palmoplantar involvement (P = 0·005), whereas patients with normal eosinophil counts had greater involvement of mucosal surfaces (P = 0·002) and the head and neck (P =…

Dear Editor, Cutaneous melanoma is the most common malignant skin cancer and its incidence and mortality rates have been increasing over the last few decades.1 The standard treatment method for cutaneous melanoma is surgical excision with a certain margin from the visible boundary of the tumour region.2 It is extremely important to choose an appropriate excision margin to reduce the surgical operation time, cost and patients' discomfort. However, complete excision of the tumour, particularly lentigo maligna or other forms of lentiginous superficial spreading melanomas, is difficult due to invisible invasion of melanoma into the surrounding tissue. The selection of the excision margin is typically decided by the colour of the skin and the surgeons' experience. Thus, additional noninvasive imaging methods that can provide information outlining the melanoma and its surrounding tissue are essential for surgeons to determine the optimal excision margin. Here we report our initial pilot study to demonstrate photoacoustic (PA) imaging as an imaging method to provide additional information…

BACKGROUND: Genital psoriasis is often under-recognized. OBJECTIVES: To assess the instantaneous prevalence of genital psoriasis and describe its clinical features, association with a particular subtype of psoriasis and its impact on general and sexual quality of life (QoL). METHODS: GENIPSO is a prospective study conducted by private and hospital-based dermatologists. This study featured the consecutive inclusion of patients consulting for extragenital psoriasis. The clinical features of psoriasis and genital psoriasis were recorded and QoL and sexual health questionnaires were distributed to patients. RESULTS: Overall, 335 of 776 patients (43·2%) included in the study had genital involvement. All were aware that they had genital lesions but only 135 patients (40%) declared that they had been previously examined. Genital lesions were associated with male sex, severity of psoriasis, age of onset > 20 years, inverse psoriasis and involvement of scalp, nail and external auditory canal, but were not associated with obesity, psoriatic arthritis and active sex life. Itching was the main…

BACKGROUND: Atopic dermatitis (AD) affects children of all skin types. Most research has focused on light skin types. Studies investigating biomarkers in people with AD with dark skin types are lacking. OBJECTIVES: To explore skin barrier and immune response biomarkers in stratum corneum (SC) tape strips from children with AD with different skin types. METHODS: Tape strips were collected from lesional and nonlesional forearm skin of 53 children with AD and 50 controls. We analysed 28 immunomodulatory mediators, and natural moisturizing factors (NMF) and corneocyte morphology. RESULTS: Interleukin (IL)-1β, IL-18, C-X-C motif chemokine (CXCL) 8 (CXCL8), C-C motif chemokine ligand (CCL) 22 (CCL22), CCL17, CXCL10 and CCL2 were significantly higher (P < 0·05) in lesional AD skin compared with nonlesional AD skin; the opposite trend was seen for IL-1α. CXCL8, CCL2 and CCL17 showed an association with objective SCORing Atopic Dermatitis score. NMF levels showed a gradual decrease from healthy skin to nonlesional and lesional AD skin. This gradual decreasing pattern was observed in skin…

The overall objective of the guideline is to provide up‐to‐date, evidence‐based recommendations for the use of topical photodynamic therapy (PDT). The document aims to: offer an appraisal of all relevant literature up to April 2018, focusing on any key developments address important, practical clinical questions relating to the primary guideline objective and provide guideline recommendations and if appropriate research recommendations. The guideline is presented as a detailed review with highlighted recommendations for practical use in primary care and in the clinic, in addition to an updated patient information leaflet [available on the British Association of Dermatologists (BAD) website, www.bad.org.uk/leaflets]. The guideline does not cover systemically administered PDT or PDT as a treatment option for genital warts and anal intraepithelial neoplasia, as these are out of the remit of dermatology for this guideline This set of guidelines has been developed using the BAD's recommended methodology1 (see Appendix K in the Supporting Information) with reference to the Appraisal of…

BACKGROUND: Infantile haemangiomas (IH) are the most common vascular tumours of infancy. Despite their frequency and potential complications, there are currently no unified U.K. guidelines for the treatment of IH with propranolol. There are still uncertainties and diverse opinions regarding indications, pretreatment investigations, its use in PHACES (posterior fossa malformations-haemangiomas-arterial anomalies-cardiac defects-eye abnormalities-sternal cleft and supraumbilical raphe) syndrome and cessation of treatment. OBJECTIVES: To provide unified guidelines for the treatment of IH with propranolol. METHODS: This study used a modified Delphi technique, which involved an international treatment survey, a systematic evidence review of the literature, a face-to-face multidisciplinary panel meeting and anonymous voting. RESULTS: The expert panel achieved consensus on 47 statements in eight categories, including indications and contraindications for starting propranolol, pretreatment investigations, starting and target dose, monitoring of adverse effects, the use of propranolol in…

BACKGROUND: Sleep is essential for daytime functioning and health. Given the physical symptoms of psoriasis, a higher prevalence of sleep disorders can be expected. So far, the studies examining sleep disturbance in psoriasis have been of less-than-optimal methodological quality and with mixed results. OBJECTIVES: To examine the prevalence of sleep disturbance in patients with plaque psoriasis compared with a control group, to evaluate associations with health-related quality of life (HRQoL) and examine possible disease-related predictors of disturbed sleep. METHODS: We used a cross-sectional, case-controlled design. Participants included 179 consecutively recruited patients with plaque psoriasis and 105 controls. Measures included psoriasis severity (Psoriasis Area and Severity Index); HRQoL (Dermatology Life Quality Index); insomnia severity [Insomnia Severity Index (ISI)]; sleep quality [Pittsburgh Sleep Quality Index (PSQI)]; stress (Perceived Stress Scale); itch (Itch Severity Scale); and depressive symptoms (Beck Depression Inventory). Analyses included group comparisons and…

BACKGROUND: Despite the heavy purulence observed in hidradenitis suppurativa (HS), the kinetics of complement anaphylatoxins acting to prime chemotaxis of neutrophils has not been studied. OBJECTIVES: To explore complement activation in HS. METHODS: Circulating concentrations of complement factor C5a, as well as of membrane attack complex C5b-9, were determined in the plasma of 54 treatment-naïve patients and of 14 healthy controls, as well as in the pus of seven patients. Results were correlated with Hurley stage and International Hidradenitis Suppurativa Severity Score. Peripheral blood mononuclear cells (PBMCs) were isolated from seven patients with Hurley stage III HS and seven healthy volunteers and stimulated in the presence of 25% of plasma for the production of tumour necrosis factor-α (TNF-α). RESULTS: were associated with a specificity > 90% with the occurrence of HS. Circulating levels of C5a and C5b-9 were greater in patients with more severe HS. PBMCs of patients produced high concentrations of TNF-α only when growth medium was enriched with patient plasma; this was…

Patients with pustular psoriasis or related pustular diseases may have genetic abnormalities impairing the function of key players of the innate skin immune system. Recently, identification of these abnormalities has changed the paradigm of several of these diseases. These include generalized pustular psoriasis, palmoplantar pustular psoriasis and acrodermatitis continua of Hallopeau, and also drug-induced acute exanthematous generalized pustular eruption. Identified mutations in IL36RN, CARD14 and AP1S3 in different groups of patients lead to enhanced inflammatory cascade in several cellular subtypes including keratinocytes, and to the recruitment and activation of neutrophils and macrophages. These insights have unveiled pathophysiological features that shift the existing paradigms and emphasize the autoinflammatory nature of skin pustular disorders. They also highlight the crucial role of the innate immune system across entities belonging to the psoriasis disease spectrum, allowing identification of new appealing therapeutic targets.

BACKGROUND: First- and third-generation retinoids are the main treatment for acne. Even though efficacious, they lack full selectivity for retinoic acid receptor (RAR) γ, expressed in the epidermis and infundibulum. OBJECTIVES: To characterize the in vitro metabolism and the pharmacology of the novel retinoid trifarotene. MATERIALS AND METHODS: In vitro assays determined efficacy, potency and selectivity on RARs, as well as the activity on the expression of retinoid target genes in human keratinocytes and ex vivo cultured skin. In vivo studies investigated topical comedolytic, anti-inflammatory and depigmenting properties. The trifarotene-induced gene expression profile was investigated in nonlesional skin of patients with acne and compared with ex vivo and in vivo models. Finally, the metabolic stability in human keratinocytes and hepatic microsomes was established. RESULTS: Trifarotene is a selective RARγ agonist with > 20-fold selectivity over RARα and RARβ. Trifarotene is active and stable in keratinocytes but rapidly metabolized by human hepatic microsomes, predicting improved…