The 50 most-cited articles in British Journal of Dermatology, 2019

BACKGROUND: Psoriasis is a chronic, systemic immune-mediated disease characterized by development of erythematous, indurated, scaly, pruritic and often painful skin plaques. Psoriasis pathogenesis is driven by proinflammatory cytokines and psoriasis is associated with increased risk for comorbidities, including, but not limited to, psoriatic arthritis, cardiovascular disease, diabetes mellitus, obesity, inflammatory bowel disease and nonalcoholic fatty liver disease compared with the general population. OBJECTIVES: To explore the pathophysiological relationship between psoriasis and its common comorbidities and discuss the need for new treatment paradigms that include strategies to reduce systemic inflammation in patients with moderate-to-severe psoriasis. METHODS: This narrative review summarizes the published evidence related to the ability of biological therapies to ameliorate the consequences of systemic inflammation in patients with psoriasis. RESULTS: Current evidence suggests that preventing damage associated with inflammation, and preventing development of future…

BACKGROUND: Dupilumab blocks the shared receptor component for interleukin (IL)-4 and IL-13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate-to-severe atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate-to-severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate-to-severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo. OBJECTIVES: To characterize further the occurrence and risk factors of conjunctivitis in dupilumab clinical trials. METHODS: We evaluated randomized placebo-controlled trials of dupilumab in AD (n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47). RESULTS: In most AD trials, dupilumab-treated patients had higher conjunctivitis incidence than placebo…

BACKGROUND: Moderate-to-severe atopic dermatitis (AD) is a chronic disease characterized by intense, persistent and debilitating itch, resulting in sleep deprivation, signs of anxiety and depression, impaired quality of life and reduced productivity. The Peak Pruritus Numerical Rating Scale (NRS) was developed and validated as a single-item, patient-reported outcome (PRO) of itch severity. OBJECTIVES: To describe the content validity and psychometric assessment (test-retest reliability, construct validity, known-groups validity, sensitivity to change) of the Peak Pruritus NRS, and to derive empirically a responder definition to identify adults with a meaningful change in itch. METHODS: Content validity was assessed through in-depth patient interviews. Psychometric assessments used data from phase IIb and phase III dupilumab clinical trials and included test-retest reliability, construct validity, known-groups validity and sensitivity to change in patients with moderate-to-severe AD. RESULTS: Interview participants indicated that the Peak Pruritus NRS was a relevant, clear and…

BACKGROUND: A transition from a subtyping to a phenotyping approach in rosacea is underway, allowing individual patient management according to presenting features instead of categorization by predefined subtypes. The ROSacea COnsensus (ROSCO) 2017 recommendations further support this transition and align with guidance from other working groups. OBJECTIVES: To update and extend previous global ROSCO recommendations in line with the latest research and continue supporting uptake of the phenotype approach in rosacea through clinical tool development. METHODS: Nineteen dermatologists and two ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and management. Voting was electronic and blinded. RESULTS: Delphi statements on which the panel achieved consensus of ≥ 75% voting 'Agree' or 'Strongly agree' are presented. The panel recommends discussing disease burden with patients during consultations, using four questions to assist conversations. The primary treatment objective should be…

BACKGROUND: There is increasing evidence of the key role that the gut microbiota plays in inflammatory diseases. OBJECTIVES: To identify differences in the faecal microbial composition of patients with psoriasis compared with healthy individuals in order to unravel the microbiota profiling in this autoimmune disease. METHODS: 16S rRNA gene sequencing and bioinformatic analyses were performed with the total DNA extracted from the faecal microbiota of 19 patients with psoriasis and 20 healthy individuals from the same geographic location. RESULTS: Gut microbiota composition of patients with psoriasis displayed a lower diversity and different relative abundance of certain bacterial taxa compared with healthy individuals. CONCLUSIONS: The gut microbiota profile of patients with psoriasis displayed a clear dysbiosis that can be targeted for microbiome-based therapeutic approaches. What's already known about this topic? Psoriasis is a chronic inflammatory immune-mediated skin disease, the aetiology of which remains unclear. The human microbiota is a complex microbial community that…

Patients with atopic dermatitis (AD) have an increased risk of bacterial skin infections, which cause significant morbidity and, if untreated, may become systemic. Staphylococcus aureus colonizes the skin of most patients with AD and is the most common organism to cause infections. Overt bacterial infection is easily recognized by the appearance of weeping lesions, honey-coloured crusts and pustules. However, the wide variability in clinical presentation of bacterial infection in AD and the inherent features of AD - cutaneous erythema and warmth, oozing associated with oedema, and regional lymphadenopathy - overlap with those of infection, making clinical diagnosis challenging. Furthermore, some features may be masked because of anatomical site- and skin-type-specific features, and the high frequency of S. aureus colonization in AD makes positive skin swab culture of suspected infection unreliable as a diagnostic tool. The host mechanisms and microbial virulence factors that underlie S. aureus colonization and infection in AD are incompletely understood. The aim of this article is…

BACKGROUND: The relationship between atopic dermatitis (AD), anxiety and depression in the U.S. adult population is not well established. OBJECTIVES: To determine the relationship of AD and its severity with symptoms and diagnosis of anxiety and depression in U.S. adults. METHODS: A cross-sectional, population-based study of 2893 adults was performed. AD was determined using modified U.K. Diagnostic Criteria. RESULTS: Adults with AD vs. those without AD had higher mean Hospital Anxiety and Depression Scale anxiety (HADS-A) (7·7 vs. 5·6) and depression (HADS-D) (6·0 vs. 4·3) scores and higher prevalences of abnormal (≥ 11) HADS-A (28·6% vs. 15·5%) and HADS-D (13·5% vs. 9·0%) scores. In multivariable linear and logistic regression models controlling for sociodemographics, AD was associated with significantly higher mean HADS-A and HADS-D scores (7·7 and 6·0) and higher odds of abnormal HADS-A [odds ratio (OR) 2·19, 95% confidence interval (CI) 1·65-2·91] and HADS-D scores (OR 1·50, 95% CI 1·04-2·17) (P ≤ 0·03 for all). Mean and abnormal HADS-A and HADS-D scores were increased in…

BACKGROUND: Global concern about vitamin D deficiency has fuelled debates on photoprotection and the importance of solar exposure to meet vitamin D requirements. OBJECTIVES: To review the published evidence to reach a consensus on the influence of photoprotection by sunscreens on vitamin D status, considering other relevant factors. METHODS: An international panel of 13 experts in endocrinology, dermatology, photobiology, epidemiology and biological anthropology reviewed the literature prior to a 1-day meeting in June 2017, during which the evidence was discussed. Methods of assessment and determining factors of vitamin D status, and public health perspectives were examined and consequences of sun exposure and the effects of photoprotection were assessed. RESULTS: 25(OH)D is a target for all individuals. Broad-spectrum sunscreens that prevent erythema are unlikely to compromise vitamin D status in healthy populations. Vitamin D screening should be restricted to those at risk of hypovitaminosis, such as patients with photosensitivity disorders, who require rigorous photoprotection.…

BACKGROUND: Basal cell carcinomas (BCCs) exhibit aberrant activation of the hedgehog pathway. Sonidegib is a hedgehog pathway inhibitor approved for the treatment of locally advanced BCC (laBCC) and metastatic BCC (mBCC) based on primary results of the BOLT study [Basal Cell Carcinoma Outcomes with LDE225 (sonidegib) Treatment]. OBJECTIVES: This is the final 42-month analysis of the BOLT study, evaluating the efficacy and safety of sonidegib. METHODS: Adults with no prior hedgehog pathway inhibitor therapy were randomized in a 1 : 2 ratio to sonidegib 200 mg or 800 mg once daily. Treatment continued for up to 42 months or until disease progression, unacceptable toxicity, death, study termination or withdrawal of consent. The primary efficacy end point was the objective response rate (ORR) by central review, assessed at baseline; weeks 5, 9 and 17; then subsequently every 8 or 12 weeks during years 1 or 2, respectively. Safety end points included adverse event monitoring and reporting. RESULTS: The study enrolled 230 patients, 79 and 151 in the 200-mg and 800-mg groups, respectively,…

Healthcare disparities are regrettably familiar: black people are 50% more likely to die from heart attacks or stroke than white people; residents of rural areas of the U.S.A. have higher prevalence of chronic obstructive pulmonary disease and Mexican‐American adults with hypertension are less likely to have controlled blood pressure.1 An especially troubling healthcare disparity for our specialty is dermatologists’ suboptimal familiarity with diagnosing skin disease in skin of colour. In one study, 47% of dermatologists felt that their training was inadequate to diagnose skin disease in skin of colour.1 One of the authors (J.C.L.), witnessed this situation leading to suboptimal care – a patient with a rash that was subsequently diagnosed as toxic epidermal necrolysis waited in the emergency room for several hours because the ‘characteristic’ redness that dermatologists seek to make the diagnosis can be subtle in skin of colour. Unfamiliarity with darker skin may have contributed to the delay in diagnosis and treatment for this patient. This example of care disparity is arresting…

BACKGROUND: Over the last few years, several articles on dermoscopy of non-neoplastic dermatoses have been published, yet there is poor consistency in the terminology among different studies. OBJECTIVES: We aimed to standardize the dermoscopic terminology and identify basic parameters to evaluate in non-neoplastic dermatoses through an expert consensus. METHODS: The modified Delphi method was followed, with two phases: (i) identification of a list of possible items based on a systematic literature review and (ii) selection of parameters by a panel of experts through a three-step iterative procedure (blinded e-mail interaction in rounds 1 and 3 and a face-to-face meeting in round 2). Initial panellists were recruited via e-mail from all over the world based on their expertise on dermoscopy of non-neoplastic dermatoses. RESULTS: Twenty-four international experts took part in all rounds of the consensus and 13 further international participants were also involved in round 2. Five standardized basic parameters were identified: (i) vessels (including morphology and distribution); (ii)…

BACKGROUND: Sebaceous glands (SGs) are appendages of mammalian skin that produce a mixture of lipids known as sebum. Acne vulgaris is an exceptionally common skin condition, characterized by elevated sebum production, altered sebum composition, and the formation of infundibular cysts, called comedones. Comedo-associated SGs are atrophic, suggesting that comedo formation involves abnormal differentiation of progenitor cells that generate the SG and infundibulum: the 'comedo switch'. Understanding the biological processes that govern SG homeostasis promises to highlight potential aetiological mechanisms underlying acne and other SG-associated skin disorders. RESULTS: In this review, we discuss the clinical data, genetic mouse models and in vitro research that have highlighted major hormones, paracrine factors, transcription factors and signalling pathways that control SG homeostasis. These include, but are not limited to androgens, progestogens and oestrogens; retinoids; receptor tyrosine kinases such as ErbB family receptors, fibroblast growth factor receptor 2 and…

BACKGROUND: Patients with psoriasis value rapid and complete skin clearance. No head-to-head studies have focused on early responses to interleukin (IL)-17 vs. IL-23 inhibitors. OBJECTIVES: To compare early and complete skin clearance by the IL-17A inhibitor ixekizumab vs. the IL-23p19 inhibitor guselkumab. METHODS: IXORA-R, a 24-week, randomized, double-blinded study, enrolled adults with moderate-to-severe plaque psoriasis [static Physician's Global Assessment of Disease (sPGA) score of ≥ 3, Psoriasis Area and Severity Index (PASI) ≥ 12, and ≥ 10% body surface area]. Patients were randomized (1 : 1) to receive the approved dose of subcutaneous ixekizumab or guselkumab. Primary end point was 100% improvement in PASI (PASI 100) at week 12. Major secondary end points included other levels of improved PASI and sPGA at different time points. Comparisons were made using the Cochran-Mantel-Haenszel test with a multiple testing strategy. Nonresponder imputation was used for missing data. After the completion of the study, the final secondary end point (PASI 100 at 24 weeks) and safety…

BACKGROUND: The 'treat to target' paradigm improves outcomes and reduces costs in chronic disease management but is not yet established in psoriasis. OBJECTIVES: To identify treatment targets in psoriasis using two common measures of disease activity: Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA). METHODS: Data from a multicentre longitudinal U.K. cohort of patients with psoriasis receiving systemic or biologic therapies (British Association of Dermatologists Biologics and Immunomodulators Register, BADBIR) were used to identify absolute PASI thresholds for 90% (PASI 90) and 75% (PASI 75) improvements in baseline disease activity, using receiver operating characteristic curves. The relationship between PGA (clear, almost clear, mild, moderate, moderate-severe, severe) and PASI (range 0-72) was described, and the concordance between absolute and relative definitions of response was determined. The same approach was used to establish treatment response and eligibility definitions based on PGA. RESULTS: Data from 13 422 patients were available (58%…

BACKGROUND: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together known as keratinocyte cancers (KCs), are the commonest cancer in white ethnic populations. Recent improvements to registry data collection in England has allowed more accurate analysis of the epidemiology of BCC and cSCC and for the first time we are able to provide an accurate (representative) tumour burden for KC in the U.K. OBJECTIVES: To estimate the incidence of BCC and cSCC in the U.K. METHODS: A cohort of patients with KCs between 2013 and 2015 were identified using linkage to diagnostic codes derived from pathology reports collected into the national cancer registry. Data from England's cancer registry were combined with data from Scotland, Northern Ireland and Wales. European age-standardized incidence rates (EASRs) of the first BCC and cSCC per patient per annum (PPPA) were calculated. RESULTS: In the U.K, the EASR of the first BCC and cSCC PPPA in 2013-15 were 285 and 77 per 100 000 person years, respectively (211 120 KCs total in 2015). The mean annual percentage increase was 5%…

Linked Comment:Uitto. Br J Dermatol 2020; 182:526–527. Plain language summary available online

BACKGROUND: Tildrakizumab is a specific anti-interleukin-23p19 monoclonal antibody approved for the treatment of plaque psoriasis. OBJECTIVES: To evaluate the long-term efficacy and safety of tildrakizumab treatment for patients with moderate-to-severe psoriasis for up to 148 weeks. METHODS: Pooled analysis from two double-blind, randomized controlled trials: reSURFACE 1 and reSURFACE 2. Efficacy was assessed for responders (≥ 75% improvement in Psoriasis Area and Severity Index; PASI 75) and partial responders (PASI 50-75) to tildrakizumab 100 mg and 200 mg at week 28 who were maintained on the same dose (administered every 12 weeks), and for partial responders or nonresponders (PASI < 50) to etanercept 50 mg at week 28 who, after a 4-week washout, were switched to tildrakizumab 200 mg (administered at weeks 32 and 36, and every 12 weeks thereafter). Safety was assessed in the all-patients-as-treated population. Three different methods of imputing missing data were used: nonresponder imputation (NRI), multiple imputation and observed cases. The Clinicaltrials.gov numbers are…

Dupilumab (monoclonal antibody inhibiting IL‐4/IL‐13 signalling) is approved for use in adolescents aged ≥ 12 years with inadequately controlled moderate‐to‐severe atopic dermatitis (AD). Dupilumab significantly improved AD signs/symptoms in a 16‐week, randomised, placebo‐controlled phase III trial in adolescents (NCT03054428). To characterize the pharmacokinetics of dupilumab, and long‐term safety and efficacy in adolescents. This was a global, multicentre, phase IIa, open‐label, ascending‐dose, sequential cohort study with a phase III open‐label extension (OLE) in adolescents with moderate‐to‐severe AD. In the phase IIa study, patients received one dupilumab dose (2 mg kg−1 or 4 mg kg−1) and 8 weeks of pharmacokinetic sampling. Thereafter, patients received the same dose weekly for 4 weeks, with 8‐week safety follow‐up. Patients then enrolled in the OLE, continuing 2 mg kg−1 or 4 mg kg−1 dupilumab weekly. Primary end points were dupilumab concentration–time profile and incidence of treatment‐emergent adverse events (TEAEs). Secondary outcomes included Eczema Area and Severity…

BACKGROUND: Dupilumab [a monoclonal antibody blocking the shared receptor subunit for interleukin (IL)-4 and IL-13] is approved for patients aged ≥ 12 years with inadequately controlled, moderate-to-severe atopic dermatitis (AD). Dupilumab trials of up to 52 weeks demonstrated efficacy and a favourable safety profile in patients with moderate-to-severe AD inadequately controlled with topical medications. OBJECTIVES: To further characterize the safety of dupilumab by evaluating clinical laboratory findings from three randomized, double-blinded, placebo-controlled phase III trials (LIBERTY AD SOLO 1 & 2 and LIBERTY AD CHRONOS). METHODS: Patients were randomized 1 : 1 : 1 (SOLO 1 & 2) or 3 : 1 : 3 (CHRONOS) for 16 and 52 weeks, respectively, to dupilumab weekly, every 2 weeks or placebo. CHRONOS patients received a standardized concomitant topical corticosteroid regimen. Laboratory outcomes were summarized descriptively in 1376 patients from SOLO 1 & 2 and 740 from CHRONOS. RESULTS: Treatment groups had similar results in baseline laboratory parameters. Platelets and neutrophils showed…

BACKGROUND: Commensal bacteria are a major factor in human health and disease pathogenesis. Interest has recently expanded beyond the gastrointestinal microbiome to include the skin microbiome and its impact on various skin diseases. OBJECTIVES: Here we present current data reviewing the role of the microbiome in dermatology, considering both the gut and skin microflora. Our objective was to evaluate whether the clinical data support the utility of oral and topical probiotics for certain dermatological diseases. METHODS: The PubMed and ClinicalTrials.gov databases were searched for basic science, translational research and clinical studies that investigated differences in the cutaneous microbiome and the impact of probiotics in patients with atopic dermatitis, acne vulgaris, psoriasis, chronic wounds, seborrhoeic dermatitis and cutaneous neoplasms. RESULTS: Few clinical trials exist that explore the utility of probiotics for the prevention and treatment of dermatological diseases, with the exception of atopic dermatitis. Most studies investigated oral probiotic interventions, and of…

BACKGROUND: ASN002 is an oral dual inhibitor of Janus kinase and spleen tyrosine kinase, which are involved in the pathogenesis of atopic dermatitis (AD) through their regulatory role on T helper (Th)1, Th2 and Th17/Th22 pathways. OBJECTIVES: The objectives of this study were to evaluate the efficacy, safety, pharmacokinetics and effects on systemic biomarkers of ASN002 in patients with moderate-to-severe AD. Methods A total of 36 patients with moderate-to-severe AD were randomized (3 : 1) to ASN002 or placebo in the phase Ib study. Three dosage cohorts were studied over a 28-day period (20 mg, 40 mg and 80 mg once daily). RESULTS: ASN002 was superior to placebo for the proportion of patients achieving Eczema Area and Severity Index (EASI) 50 (20 mg 20%, P = 0·93; 40 mg 100%, P = 0·003; 80 mg 83%, P = 0·03; placebo 22%), EASI 75 (20 mg 0%, P = 0·27; 40 mg 71%, P = 0·06; 80 mg 33%, P = 0·65; placebo 22%) and in change from baseline in pruritus (20 mg -1·3 ± 2·1, P = 0·81; 40 mg -3·1 ± 2·7, P = 0·27; 80 mg -4·7 ± 2·1, P = 0·01; placebo -1·6 ± 1·8). Adverse events were generally mild…

BACKGROUND: The role of skin microbiota in acne remains to be fully elucidated. Initial culture-based investigations were hampered by growth rate and selective media bias. Even with less biased genomic methods, sampling, lysis and methodology, the task of describing acne pathophysiology remains challenging. Acne occurs in sites dominated by Cutibacterium acnes (formerly Propionibacterium acnes) and Malassezia species, both of which can function either as commensal or pathogen. OBJECTIVES: This article aims to review the current state of the art of the microbiome and acne. METHODS: The literature regarding the microbiome and acne was reviewed. RESULTS: It remains unclear whether there is a quantitative difference in microbial community distribution, making it challenging to understand any community shift from commensal to pathogenic nature. It is plausible that acne involves (i) change in the distribution of species/strains, (ii) stable distribution with pathogenic alteration in response to internal (intermicrobe) or external stimuli (host physiology or environmental) or (iii) a…

Dupilumab is the first biologic registered for the treatment of atopic dermatitis (AD). We report on seven patients with AD presenting with a paradoxical head and neck erythema that appeared 10-39 weeks after the start of dupilumab treatment. The patients presented with a relatively sharply demarcated, patchy erythema in the head and neck area that showed no or less scaling compared with their usual eczema. Only one patient experienced symptoms of itch and burning, although this was notably different from his pre-existent facial AD. Except for a notable 'red face', eczema on other body parts had greatly improved in six of the seven patients, with a mean numerical rating scale for treatment satisfaction of 9 out of 10 at the time of biopsy. Treatment of the erythema with topical and systemic drugs was unsuccessful. Despite the presence of this erythema, none of our patients discontinued dupilumab treatment. Lesional skin biopsies showed an increased number of ectatic capillaries, and a perivascular lymphohistiocytic infiltration in all patients. In addition, epidermal hyperplasia…

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory condition that can have a large negative impact on health-related quality of life (HRQOL). A reliable and validated measure of HS-specific HRQOL in clinical studies is needed. OBJECTIVES: To develop and validate the Hidradenitis Suppurativa Quality Of Life (HiSQOL©) scale, for clinical trial measurement of HS-specific HRQOL. METHODS: In stage 1, qualitative concept elicitation interviews were conducted with patients with HS in Denmark (n = 21) and the U.S.A. (n = 21). In stage 2, cognitive debriefing interviews were performed with U.S. (n = 30) and Danish patients with HS (n = 30). In stage 3 an observational study of 222 patients with HS in the U.S.A. was conducted for item reduction, measure validation and assessment of psychometric properties. In stage 4, an observational study of 215 patients with HS in Denmark was conducted to confirm the psychometric structure derived in stage 3. In both studies the Dermatology Life Quality Index, Hospital Anxiety and Depression Scale and numerical rating scale for pain were…

BACKGROUND: Mycosis fungoides (MF) and Sézary Syndrome (SS) are the most common cutaneous T-cell lymphomas. MF/SS is accompanied by considerable morbidity from pain, itching and disfigurement. AIM: To identify factors associated with poorer health-related quality of life (HRQoL) in patients newly diagnosed with MF/SS. METHODS: Patients enrolled into Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI; an international observational study in MF/SS) had their HRQoL assessed using the Skindex-29 questionnaire. Skindex-29 scores were analysed in relation to patient- and disease-specific characteristics. RESULTS: The study population consisted of 237 patients [60·3% male; median age 60 years, (interquartile range 49-70)], of whom 179 had early MF and 58 had advanced MF/SS. In univariate analysis, HRQoL, as measured by Skindex-29, was worse in women, SS, late-stage MF, those with elevated lactate dehydrogenase, alopecia, high modified Severity Weighted Assessment Tool and confluent erythema. Linear regression models only identified female gender (β = 8·61; P = 0·003)…

Sunlight contains ultraviolet (UV)A and UVB radiation. UVB is essential for vitamin D synthesis but is the main cause of sunburn and skin cancer. Sunscreen use is advocated to reduce the sun's adverse effects but may compromise vitamin D status. To assess the ability of two intervention sunscreens to inhibit vitamin D synthesis during a week‐long sun holiday. The impact of sunscreens on vitamin D status was studied during a 1‐week sun holiday in Tenerife (28° N). Comparisons were made between two formulations, each with a sun protection factor (SPF) of 15. The UVA‐protection factor (PF) was low in one case and high in the other. Healthy Polish volunteers (n = 20 per group) were given the sunscreens and advised on the correct application. Comparisons were also made with discretionary sunscreen use (n = 22) and nonholiday groups (51·8° N, n = 17). Sunscreen use in the intervention groups was measured. Behaviour, UV radiation exposure, clothing cover and sunburn were monitored. Serum 25‐hydroxyvitamin D3 [25(OH)D3] was assessed by high‐performance liquid chromatography–tandem mass…

BACKGROUND: Sunscreen use can prevent skin cancer, but there are concerns that it may increase the risk of vitamin D deficiency. OBJECTIVES: or 25 hydroxyvitamin D [25(OH)D] concentration. METHODS: We systematically reviewed the literature following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. We identified manuscripts published in English between 1970 and 21 November 2017. Eligible studies were experimental [using an artificial ultraviolet radiation (UVR) source], field trials or observational studies. The results of each of the experimental studies and field trials are described in detail. Two authors extracted information from observational studies, and applied quality scoring criteria that were developed specifically for this question. These have been synthesized qualitatively. RESULTS: or 25(OH)D production induced by exposure to artificially generated UVR. The randomized controlled field trials found no effect of daily sunscreen application, but the sunscreens used had moderate protection [sun protection factor SPF) ~16]. The observational…

Long‐term therapy for psoriasis is impaired by gradual loss of effectiveness and treatment discontinuation. Identifying factors that affect biologic drug survival may help in treatment optimization. To identify factors that predicted biologic drug persistence or discontinuation in a real‐life setting. We identified studies of biologic persistence in psoriasis through a comprehensive, systematic literature search using predefined search criteria. Studies were screened by title and abstract then further by full‐text review. Hazard ratio (HR) data were extracted for all available predictive factors (HRs > 1 denoted biologic discontinuation, and HRs < 1 denoted biologic persistence). A meta‐analysis of HRs (random‐effects model) was used to assess any predictive factor included in at least two studies. Sixteen cohort studies were included in the review, with a total of 32 194 patients. A meta‐analysis was performed on 13 studies (n = 29 802): nine for female sex (n = 28 090), six for obesity (n = 9311) and six for psoriatic arthritis (n = 24 444). Obesity and female sex predicted…

BACKGROUND: Eczema control has been identified as an important outcome by key stakeholders in eczema research (including patients, carers, healthcare professionals and researchers) but no validated instruments for the domain have been identified. OBJECTIVES: To develop a measurement instrument to capture a patient's perspective of eczema control that is suitable for use in eczema clinical trials. METHODS: Best practice for the development of a patient-reported outcome was followed. A mixed-methods approach was used to develop and refine a conceptual framework, generate, refine and select items and to test the distribution and construct validity of the final scale. The mixed-methods approach involved expert panel meetings (including patient representatives, healthcare professionals and methodologists), and data collection using a focus group, cognitive interviews and an online survey with people with eczema and caregivers. Multivariable linear regression was used in the item selection process. RESULTS: Fourteen expert panel members co-produced the instrument, with input from people…

BACKGROUND: Management of chronic hand eczema (CHE) remains a challenge; effective topical treatment is limited to corticosteroids. OBJECTIVES: To assess the efficacy and safety of a novel, pan-Janus kinase inhibitor (delgocitinib) in patients with CHE. METHODS: or vehicle ointment for 8 weeks. The primary end point was the proportion of patients achieving treatment success ['clear'/'almost clear' skin with ≥ 2-point improvement in the Physician's Global Assessment of disease severity (PGA)] at week 8. Secondary end points included Hand Eczema Severity Index (HECSI) score changes and the proportion of patients achieving treatment success on the Patient's Global Assessment of disease severity (PaGA). RESULTS: Ninety-one patients were randomized. More patients receiving delgocitinib (46%) than vehicle (15%) [odds ratio 4·89, 95% confidence interval (CI) 1·49-16·09; P = 0·009] achieved treatment success (PGA). Adjusted mean HECSI score at week 8 was lower with delgocitinib (13·0) than with vehicle (25·8) (adjusted mean difference -12·88, 95% CI -21·47 to -4·30; P = 0·003). More…

CLINICAL QUESTION: Does weight loss reduce the severity and incidence of psoriasis or psoriatic arthritis (PsA) in obese individuals? BACKGROUND: Obesity presents a rising public health challenge and is more prevalent among individuals with psoriasis or PsA than in the general population. Longitudinal population-based studies suggest a causal role for obesity in psoriasis and PsA onset and that obesity drives greater disease severity. METHODS: We systematically reviewed evidence within the MEDLINE, Embase and CENTRAL databases and clinical trials registries examining lifestyle, pharmacological and surgical weight loss interventions in the treatment and prevention of psoriasis and PsA in obese individuals. Meta-analysis was conducted using random-effects models, followed by sensitivity analyses. RESULTS: Of 176 full-text articles reviewed, 14 met the inclusion criteria. Meta-analysis of six randomized control trials (RCTs) confirmed that weight loss following lifestyle interventions (diet or physical activity) improves psoriasis compared with control [mean change in Psoriasis Area…

BACKGROUND: Psoriatic arthritis (PsA) is a progressive and often destructive joint disease affecting approximately 20% of people with psoriasis. OBJECTIVES: To investigate associations between obesity, changes in body mass index (BMI), alcohol intake and smoking status and the development of PsA in people with psoriasis. METHODS: We undertook a cohort study involving incident cases of psoriasis identified from the U.K. Clinical Practice Research Datalink between 1998 and 2014. The associations between smoking, alcohol and BMI and development of PsA were assessed using generalized additive models. Additionally, the risks associated with a change in BMI during follow-up were investigated using distributed lag nonlinear models. RESULTS: : adjusted odds ratios (95% confidence intervals) 1·79 (1·46-2·19), 2·10 (1·67-2·63) and 2·68 (2·09-3·43), respectively. Reducing BMI over a 10-year period (linearly) was associated with a reduction in the risk of developing PsA compared with BMI remaining constant over the same period. Increased risks of developing PsA were associated with moderate…

BACKGROUND: Scabies is a frequent condition seen in infants and children. Only topical treatments have been approved in infants, but some of them are poorly tolerated. Oral ivermectin is approved for the treatment of scabies in several countries, but its use in infants and children weighing < 15 kg is off label. OBJECTIVES: To assess the safety of ivermectin in infants and young children, and to collect data on ivermectin efficacy in these age groups. METHODS: This study was performed in the dermatology and paediatric dermatology departments of 28 French centres between July 2012 and November 2015. Physicians treating an infant or child weighing < 15 kg for scabies with oral ivermectin were asked to send back a completed standardized and anonymous questionnaire, and the data were analysed. RESULTS: (P < 0·001), and a delay between those two doses of < 10 days (P = 0·025). CONCLUSIONS: and when the delay between the two doses is < 10 days. Respond to this article.

Linked Comment:Lee. Br J Dermatol 2019; 181:10–11. Plain language summary available online

Dear Editor, Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease of the apocrine gland‐rich intertriginous areas.1 HS lesions have an elevated T helper (Th)17 immune response, and it is often challenging to treat patients, with existing therapies having limited efficacy.2,3 We sought to investigate the role of secukinumab, a human monoclonal antibody that inhibits interleukin (IL)‐17A, in HS treatment. This 24‐week, open‐label pilot trial of secukinumab 300 mg administered subcutaneously weekly for 5 weeks, then every 4 weeks for 24 weeks was conducted in nine patients with moderate‐to‐severe HS (clinicaltrials.gov identifier NCT03099980). The primary outcome was to assess the proportion of participants who achieved a Hidradenitis Suppurativa Clinical Response (HiSCR) score following 24 weeks of secukinumab therapy. Secondary outcome measures included the Sartorius score and the patient‐reported Dermatology Life Quality Index (DLQI). Nine patients were enrolled and four completed the study (56% men; mean age 37 years; mean weight 102·7 kg). Participants needed to…

BACKGROUND: Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. OBJECTIVES: To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. METHODS: per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24-month efficacy and safety results were also reported. RESULTS: At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one…

The increasing prevalence of atopic dermatitis (AD) parallels a global rise in industrialization and urban living over recent decades. This shift in lifestyle is accompanied by greater cutaneous exposure to environmental pollutants during the course of daily activities. The objectives of this review are to highlight the effects of airborne pollution on epidermal barrier function, examine evidence on the relationship between pollutants and AD, synthesize a proposed mechanism for pollution-induced exacerbation of AD, and identify potential methods for the reduction and prevention of pollutant-induced skin damage. The literature review was done by searching the PubMed, Embase and Google Scholar databases. Inclusion criteria were in vitro and animal studies, clinical trials and case series. Non-English-language publications, review articles and case reports were excluded. Pollutants induce cutaneous oxidative stress and have been shown to damage skin barrier integrity by altering transepidermal water loss, inflammatory signalling, stratum corneum pH and the skin microbiome. AD…

Chronic pruritus is a distressing symptom associated with various dermatological conditions and systemic diseases. Current treatment options are often inadequate, resulting in impaired quality of life for many patients. An understanding of the underlying mechanisms of itch across pruritic conditions is important for development of effective, targeted treatments for chronic pruritus. To provide an overview of the pathogenesis of chronic pruritus, focusing on the role of substance P (SP) and neurokinin 1 receptor (NK1R) in itch signalling, and to describe data supporting NK1R antagonism as a potential strategy for the treatment of chronic pruritus. A PubMed search was conducted to determine what data were available that investigated the role of SP and NK1R in itch signalling. SP is a neuropeptide that is a mediator of itch signalling. One of the target receptors for SP is NK1R, which is expressed in the central nervous system and on multiple cell types involved in the initiation and transmission of itch. Studies demonstrating that SP and NK1R are overexpressed across multiple chronic…

BACKGROUND: The signals that induce anagen (growth) in 'quiescent' human telogen hair follicles (HFs) are as yet unknown. Their identification promises better targeted therapeutic hair growth interventions. OBJECTIVES: Recognizing the central role of Wnt signalling in hair biology, the aim was to delineate the differential expression of key agonists, antagonists and target genes of this pathway during the telogen-to-anagen transformation of human scalp HFs. METHODS: This differential expression was studied by in situ hybridization in human telogen and early-anagen scalp HF sections. RESULTS: On anagen induction, gene expression of the Wnt ligands WNT3, WNT4 and WNT10B, the Wnt ligand secretion regulator WLS, and the Wnt target genes AXIN2 and LEF1, is significantly increased within the secondary hair germ and the dermal papilla. Conversely, expression of the secreted Wnt inhibitor SFRP1 (secreted frizzled-related protein 1) is reduced. Human epithelial HF stem cells upregulate WNT4 and WNT10A expression, suggesting that these Wnt agonists are important for stem cell activation.…

BACKGROUND: Chronic exposure to ultraviolet (UV) radiation (mainly UVA) induces a sustained increase of matrix metalloproteinases (MMPs), especially MMP1, MMP2, MMP3 and MMP9 in human skin fibroblasts. MMPs can lead to the degradation of fibrous connective tissue, which is the main cause of skin photoageing. The molecular mechanisms through which fibroblasts sense UVA and trigger the cell signalling pathways involved in the upregulation of MMPs have not been well elucidated. OBJECTIVES: Here, we investigated the function and potential mechanisms of photoageing of opsin (OPN)3 in normal human dermal fibroblasts (NHDFs). METHODS: Real-time polymerase chain reaction and Western blot analysis were used to analyse the expression levels of OPN3 in NHDFs and photoageing models. Subsequently, NHDFs transfected with OPN3 inhibitors and indicators related to photoageing before and after UVA irradiation included expression levels of MMP1, MMP2, MMP3 and MMP9, and signalling pathway protein molecules were examined. RESULTS: /calmodulin-dependent protein kinase II, cyclic adenosine monophosphate…

Our understanding of the pathogenesis underlying keloid scar formation is still very limited, and the morphological distinction between hypertrophic and keloid scars remains difficult. To test whether hypertrophic and keloid scars may reflect an inability to progress from immaturity to the desired mature normotrophic scar phenotype. Using whole‐biopsy imaging and an objectively quantifiable way to analyse immunoreactivity, we have compared the immunohistopathological profiles of young immature scars with mature normotrophic scars, hypertrophic scars, and keloids with their surrounding‐normal‐skin. Abnormal scars (hypertrophic scars and keloids) maintain the immature scar phenotype, characterized by a CD34− (tumour biomarker) and α‐smooth muscle actin (α‐SMA)+ (myofibroblast) dermal region. This is in contrast to normal skin, surrounding‐normal‐skin and mature normotrophic scars that were CD34+/ α‐SMA−. Immature, hypertrophic and keloid scars showed abnormal epidermal differentiation (involucrin), but only hypertrophic scars and keloids showed increased epidermal thickness. Immature…

BACKGROUND: Dupilumab is the first biologic registered for the treatment of moderate-to-severe atopic dermatitis (AD), and efficacy was shown in phase III clinical trials (primary outcome at week 16 was reached in 38% of patients). Currently, there are limited daily practice data available for dupilumab, especially when it is combined with systemic immunosuppressants. OBJECTIVES: To evaluate dupilumab treatment in daily practice in patients with AD. METHODS: In this observational cohort study, we prospectively included all adult patients with AD who had been treated with dupilumab in two university hospitals in the Netherlands. Concomitant systemic immunosuppressive treatment was monitored. Physician-reported outcome measures and patient-reported outcome measures (PROMs) after ≥ 12 weeks of follow-up were analysed. We used a linear mixed-effects model to determine changes in scores during follow-up. RESULTS: Ninety-five patients were included. Of these, 62 patients were using systemic immunosuppressants at baseline; the use of systemic immunosuppressants was continued during…

Alopecia areata (AA) is a common autoimmune disease, causing patchy hair loss that can progress to involve the entire scalp (totalis) or body (universalis). CD8+NKG2D+ T cells dominate hair follicle pathogenesis, but the specific mechanisms driving hair loss are not fully understood. To provide a detailed insight into the systemic cytokine signature associated with AA, and to assess the association between cytokines and depression. We conducted multiplex analysis of plasma cytokines from patients with AA, patients with psoriatic arthritis (PsA) and healthy controls. We used the Hospital Anxiety and Depression Scale (HADS) to assess the occurrence of depression and anxiety in our cohort. Our analysis identified a systemic inflammatory signature associated with AA, characterized by elevated levels of interleukin (IL)‐17A, IL‐17F, IL‐21 and IL‐23 indicative of a type 17 immune response. Circulating levels of the type 2 cytokines IL‐33, IL‐31 and IL‐17E (IL‐25) were also significantly increased in AA. In comparison with PsA, AA was associated with higher levels of IL‐17F, IL‐17E and…

BACKGROUND: Atrophic acne scar, a persistent sequela from acne, is undesirably troubling to many patients due to its cosmetic and psychosocial aspects. Although there have been some reports emphasizing the role of early inflammatory responses in atrophic acne scarring, evolving perspectives on the detailed pathogenic processes are promptly needed. OBJECTIVES: Examining the histological, immunological and molecular changes in early acne lesions susceptible to atrophic scarring can provide new insights to understand the pathophysiology of atrophic acne scar. METHODS: We experimentally validated several early fundamental hallmarks accounting for the transition of early acne lesions to atrophic scars by comparing molecular profiles of skin and acne lesions between patients who were prone to scar (APS) or not (ANS). RESULTS: In APS, compared with ANS, devastating degradation of elastic fibres and collagen fibres occurred in the dermis, followed by their incomplete recovery. Abnormally excessive inflammation mediated by innate immunity with T helper 17 and T helper 1 cells was observed.…

BACKGROUND: The epidermal barrier functions to limit skin infection and inflammation by inhibiting irritant and immunogen invasion. Abundant evidence suggests that psychological stress stemming from crowding, isolation, nicotine smoking, insomnia, mental arithmetic tasks, physical pain, real-life stressors (examinations and marital strain) and lack of positive personality traits may impart both acute and chronic epidermal dysfunction. OBJECTIVES: To review the relationship between stress and epidermal barrier dysfunction. METHODS: A review of the PubMed and Embase databases was conducted to identify all English-language case-control, cross-sectional and randomized control trials that have reported the effect of stress on epidermal barrier function. The authors' conclusions are based on the available evidence from 21 studies that met the inclusion and exclusion criteria. RESULTS: Psychological stressors upregulate the hypothalamic-pituitary-adrenal axis to stimulate local and systemic stress hormone production. This ultimately leads to aberrant barrier dysfunction, characterized by…

BACKGROUND: The treatment of psoriasis has been revolutionized by the development of biologic therapies. However, the pathogenesis of psoriasis, in particular the role of the cutaneous microbiome, remains incompletely understood. Moreover, skin microbiome studies have relied heavily on 16S rRNA sequencing data in the absence of bacterial culture. OBJECTIVES: To characterize and compare the cutaneous microbiome in 20 healthy controls and 23 patients with psoriasis using metagenomic analyses and to determine changes in the microbiome during treatment. METHODS: Swabs from lesional and nonlesional skin from patients with psoriasis, and from controls matched for site and skin microenvironment, were analysed using both 16S rRNA sequencing and traditional culture combined with mass spectrometry (MALDI-TOF) in a prospective study. RESULTS: Psoriasis was associated with an increased abundance of Firmicutes and a corresponding reduction in Actinobacteria, most marked in lesional skin, and at least partially reversed during systemic treatment. Shifts in bacterial community composition in…

BACKGROUND: Transient receptor potential vanilloid subfamily, member 1 (TRPV1) may play an important role in pruritus and inflammation induction in atopic dermatitis (AD). The treatment effect of TRPV1 antagonist via topical application in patients with AD remains unknown. OBJECTIVES: To assess the clinical efficacy and safety of PAC-14028, a TRPV1 antagonist, via topical application in patients with AD. METHODS: In this 8-week, phase IIb, randomized, double-blind, multicentre, vehicle-controlled study, patients with mild-to-moderate AD were randomized to receive PAC-14028 cream 0·1%, 0·3%, 1·0% or vehicle cream twice daily. The primary efficacy end point was the Investigator's Global Assessment (IGA) success rate defined as the percentage of patients with an IGA score of 0 or 1 at week 8. The secondary efficacy end points included the severity Scoring of Atopic Dermatitis (SCORAD) index and Eczema Area and Severity Index (EASI) 75/90. RESULTS: A total of 194 patients were enrolled. IGA success rates at week 8 were 14·58% for vehicle cream, 42·55% for PAC-14028 cream 0·1% (P =…

BACKGROUND: Atopic dermatitis (AD) is associated with high disease burden, with a significant physical and social impact. However, the association between disease severity and burden of disease, with work productivity and daily activities being one aspect, has not been well characterized. OBJECTIVES: To investigate the impact of disease severity on work productivity and daily activities among adults with AD in Europe (France, Germany and the U.K.) and the U.S.A. METHODS: The survey panel participants for this cross-sectional internet-based survey on AD were sourced from the population-based National Health and Wellness Survey (Europe 2016, U.S.A. 2015 and 2016). AD severity was determined by Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD). Work productivity and work activity impairment were assessed using the Work Productivity and Activity Impairment (WPAI) - Specific Health Problem questionnaire for AD. RESULTS: The study survey was completed by 1098 respondents with moderate-to-severe AD and 134 with mild AD. Overall, the negative impact on work productivity (all WPAI…

BACKGROUND: The incidence of epidermal keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is increasing worldwide. OBJECTIVES: To study the role of the complement classical pathway components C1q, C1r and C1s in the progression of cSCC. METHODS: The mRNA levels of C1Q subunits and C1R and C1S in cSCC cell lines, normal human epidermal keratinocytes, cSCC tumours in vivo and normal skin were analysed with quantitative real-time polymerase chain reaction. The production of C1r and C1s was determined with Western blotting. The expression of C1r and C1s in tissue samples in vivo was analysed with immunohistochemistry and further investigated in human cSCC xenografts by knocking down C1r and C1s. RESULTS: Significantly elevated C1R and C1S mRNA levels and production of C1r and C1s were detected in cSCC cells, compared with normal human epidermal keratinocytes. The mRNA levels of C1R and C1S were markedly elevated in cSCC tumours in vivo compared with normal skin. Abundant expression of C1r and C1s by tumour cells was detected in invasive sporadic cSCCs and recessive dystrophic…

BACKGROUND: There is debate as to whether psoriasis and atopic dermatitis (AD) belong to the same disease spectrum. OBJECTIVES: To describe and compare disease characteristics, lifestyle factors and disease burden in adult patients with psoriasis and AD. METHODS: We linked registry data with clinical and patient-reported outcomes from the Danish Skin Cohort, containing 3348 and 3834 adults with dermatologist-verified psoriasis or AD respectively, and 2946 adults from the general population. RESULTS: The participants were predominantly women and middle-aged. Patients with psoriasis mostly reported disease onset throughout adulthood, but with a distinct early incidence peak in those with a positive family history or severe disease. AD predominantly began in childhood, with only a very discrete incidence peak in adulthood. Scalp, extremity, chest and abdomen involvement was common to both diseases. Scalp/hairline, elbows, nails, intergluteal cleft, umbilicus, knees and legs were most frequently affected in patients with psoriasis. In AD, periocular, neck, antecubital fossae, back of…