The 50 most-cited articles in British Journal of Dermatology, 2022

BACKGROUND: Since May 2022, a new outbreak of monkeypox has been reported in several countries, including Spain. The clinical and epidemiological characteristics of the cases in this outbreak may differ from those in earlier reports. OBJECTIVES: To document the clinical and epidemiological characteristics of cases of monkeypox in the current outbreak. METHODS: We conducted a prospective cross-sectional study in multiple medical facilities in Spain to describe the cases of monkeypox in the 2022 outbreak. RESULTS: In total, 185 patients were included. Most cases started with primarily localized homogeneous papules, not pustules, in the probable area of inoculation, which could be cutaneous or mucous, including single lesions. Generalized small pustules appeared later in some of them. Heterogeneous lesions occurred during this generalized phase. All patients had systemic symptoms. Less common lesions included mucosal ulcers (including pharyngeal ulcers and proctitis) and monkeypox whitlows. Four patients were hospitalized, none died. Smallpox vaccination and well-controlled HIV disease…

Human epithelia are constantly exposed to microorganisms present in the environment or residing as part of commensal flora. Despite this exposure, infections involving the skin and subcutaneous tissue in healthy individuals are, fortunately, quite rare. Many of the wounds that afflict the human body occur in individuals of ill health and/or where the mechanism of wounding is impeded by host immunological, physiological or regenerative dysfunction. The interplay between microorganisms and host immunity is complex and remains ill defined; however, the interpretation of downstream manifestations of the host response to invading microorganisms is still based largely on the clinical signs and symptoms of an active infectious process. In this review article we will provide a brief overview of the current challenges clinicians face in diagnosing wound infections, how chronic infections caused by biofilms are a major challenge, and how there have been minimal advancements in developing new diagnostics or therapeutics in the identification and management of wound infections.

BACKGROUND: CONCORD-3 highlighted wide disparities in population-based 5-year net survival for cutaneous melanoma during 2000-2014. Clinical evidence suggests marked international differences in the proportion of lethal acral and nodular subtypes of cutaneous melanoma. OBJECTIVES: We aimed to assess whether the differences in morphology may explain global variation in survival. METHODS: Patients with melanoma were grouped into the following seven morphological categories: malignant melanoma, not otherwise specified (International Classification of Diseases for Oncology, third revision morphology code 8720), superficial spreading melanoma (8743), lentigo maligna melanoma (8742), nodular melanoma (8721), acral lentiginous melanoma (8744), desmoplastic melanoma (8745) and other morphologies (8722-8723, 8726-8727, 8730, 8740-8741, 8746, 8761, 8770-8774, 8780). We estimated net survival using the nonparametric Pohar Perme estimator, correcting for background mortality by single year of age, sex and calendar year in each country or region. All-ages survival estimates were standardized…

Summary Background Various treatments for acne vulgaris exist, but little is known about their comparative effectiveness in relation to acne severity. Objectives To identify best treatments for mild-to-moderate and moderate-to-severe acne, as determined by clinician-assessed morphological features. Methods We undertook a systematic review and network meta-analysis of randomized controlled trials (RCTs) assessing topical pharmacological, oral pharmacological, physical and combined treatments for mild-to-moderate and moderate-to-severe acne, published up to May 2020. Outcomes included percentage change in total lesion count from baseline, treatment discontinuation for any reason, and discontinuation owing to side-effects. Risk of bias was assessed using the Cochrane risk-of-bias tool and bias adjustment models. Effects for treatments with ≥ 50 observations each compared with placebo are reported below. Results We included 179 RCTs with approximately 35 000 observations across 49 treatment classes. For mild-to-moderate acne, the most effective options for each treatment type were as…

BACKGROUND: Janus kinase (JAK)-mediated cytokine signalling contributes to local and systemic inflammation in hidradenitis suppurativa (HS). OBJECTIVES: To describe the safety and efficacy results from two multicentre phase II trials of the JAK1 inhibitor INCB054707 in patients with moderate-to-severe HS. METHODS: Patients received open-label INCB054707 15 mg once daily (QD; Study 1) or were randomized to INCB054707 30, 60 or 90 mg QD or placebo (3 : 1 within each cohort; Study 2) for 8 weeks. Eligible patients were aged 18-75 years and had moderate-to-severe HS (Hurley stage II/III disease), lesions present in at least two anatomical locations, and a total abscess and inflammatory nodule count ≥ 3. The primary endpoint for both studies was safety and tolerability. Secondary endpoints included HS Clinical Response (HiSCR) and other efficacy measures. RESULTS: Ten patients were enrolled in Study 1 (15 mg INCB054707) and 35 in Study 2 (INCB054707: 30 mg, n = 9; 60 mg, n = 9; 90 mg, n = 8; placebo, n = 9). Overall, 70% of patients in Study 1 and 81% of patients receiving INCB054707 in…

Background Chronic hand eczema (CHE) is a burdensome disease, and new well-documented, safe and efficacious treatments are warranted. In a recent CHE phase IIa trial, the pan-Janus kinase (JAK) inhibitor delgocitinib in an ointment formulation was found to be efficacious and well tolerated. Objectives This trial assessed the dose response, efficacy and safety of delgocitinib cream in CHE. Methods In this double-blind, phase IIb dose-ranging trial, adults with CHE and a recent history of inadequate response or contraindication to topical corticosteroids were randomized to delgocitinib cream 1, 3, 8, 20 mg g–1 or vehicle treatment twice daily for 16 weeks. The primary endpoint was the Investigator’s Global Assessment for CHE (IGA-CHE) treatment success [0 (clear) or 1 (almost clear) with a ≥ two-point improvement from baseline to week 16]. Secondary endpoints were the time to IGA-CHE treatment success and changes in Hand Eczema Severity Index (HECSI); other endpoints were itch and pain numerical rating scale (NRS) scores, and Patient’s Global Assessment (PaGA) at week 16. Results…

BACKGROUND: Alopecia areata (AA) is a common cause of nonscarring hair loss that can have a profound psychological impact. OBJECTIVES: To assess the co-occurrence of depression and anxiety in adults with AA compared with the general population, and to evaluate the mental health treatment burden and impact on time off work and unemployment. METHODS: In total, 5435 people with newly diagnosed AA in UK primary care were identified from the Oxford Royal College of General Practitioners Research and Surveillance Centre network database, and matched to 21 740 controls. In cases and controls, we compared the prevalence and incidence of depressive episodes, recurrent depressive disorder and anxiety disorder, rates of time off work and unemployment, and, in those with pre-existing mental health conditions, rates of mental health-related prescribing and referral rates. This observational was registered with ClinicalTrials.gov (NCT04239521). RESULTS: Depression and anxiety were more prevalent in people diagnosed with AA than in controls (P < 0·001). People with AA were also more likely to…

BACKGROUND: Body dysmorphic disorder (BDD) is a common psychiatric disorder associated with high costs for healthcare systems as patients may repeatedly ask for different, often not effective, interventions. BDD symptoms are more prevalent in patients with dermatological conditions than in the general population, but there are no large sample studies comparing the prevalence of BDD symptoms between patients with dermatological conditions and healthy skin controls. OBJECTIVES: To compare the prevalence of BDD symptoms between patients with different dermatological conditions and healthy skin controls and to describe sociodemographic, physical and psychological factors associated with BDD symptoms to identify patients who may have a particularly high chance of having this condition. METHODS: This observational, cross-sectional, comparative multicentre study included 8295 participants: 5487 consecutive patients with different skin diseases (56% female) recruited among dermatological outpatients at 22 clinics in 17 European countries, and 2808 healthy skin controls (66% female). BDD…

BACKGROUND: Cutaneous melanomas are common cancers in white-skinned populations, and early detection is promoted as a means of reducing morbidity and mortality. There is concern that increased skin screening is leading to overdiagnosis of indolent melanomas with low risk of lethality. The extent of melanoma overdiagnosis associated with screening is unknown. OBJECTIVES: To estimate possible overdiagnosis by comparing subsequent melanoma incidence and biopsy rates among people subjected to skin screening those who were not. METHODS: We recruited 43 762 residents of Queensland, Australia, aged 40-69 years, with no prior history of melanoma, selected at random from a population register in 2010. At baseline, participants completed a comprehensive melanoma risk factor survey and were asked if their skin had been examined by a doctor in the 3 years prior to baseline. We calculated incidence and relative risk of histologically confirmed melanoma (invasive and in situ) in years 2-7 of follow-up, obtained through linkage to the cancer registry. In secondary analyses, we measured biopsy…

BACKGROUND: Tralokinumab is a fully human monoclonal antibody that neutralizes the activity of interleukin-13, a key pathogenic driver of atopic dermatitis (AD). Clinical trials including adults with moderate-to-severe AD, of up to 52 weeks' duration, showed tralokinumab was efficacious and well tolerated. OBJECTIVES: To characterize the safety profile of tralokinumab for the treatment of moderate-to-severe AD. METHODS: Safety and laboratory measures were assessed in pooled analyses of phase II and III placebo-controlled clinical trials of tralokinumab in moderate-to-severe AD (NCT02347176, NCT03562377, NCT03131648, NCT03160885, NCT03363854). RESULTS: In total, 2285 patients were randomized in the initial treatment periods up to 16 weeks (1605 tralokinumab, 680 placebo). The frequencies of any adverse event (AE) were 65·7% for tralokinumab and 67·2% for placebo. The respective rates were 640 and 678 events per 100 patient-years of exposure (ep100PYE); rate ratio 1·0, 95% confidence interval (CI) 0·9-1·1. Serious AEs occurred in 2·1% of patients with tralokinumab and 2·8% with…

BACKGROUND: Baricitinib, an oral selective Janus kinase (JAK)1 and JAK 2 inhibitor, was shown to improve the signs and symptoms of moderate-to-severe atopic dermatitis (AD). OBJECTIVES: To evaluate the efficacy and safety of baricitinib with background topical corticosteroids (TCS) in patients with moderate-to-severe AD and inadequate response, intolerance or contraindication to ciclosporin A (CA). METHODS: In this double-blind, randomized, placebo-controlled, phase III study, patients were randomized 1: 1: 2: 1 to placebo (N = 93), baricitinib 1 mg (N = 93), 2 mg (N = 185) or 4 mg (N = 92) with background TCS. The primary endpoint was the proportion of patients receiving baricitinib 4 mg or 2 mg (+ TCS) vs. placebo + TCS who achieved ≥ 75% improvement from baseline in the Eczema Area and Severity Index (EASI 75) at week 16. RESULTS: Baricitinib 4 mg + TCS was superior to placebo + TCS for EASI 75 (4 mg: 32%, placebo: 17%, P = 0·031) at week 16 and for improvements in itch, skin pain and number of night-time awakenings owing to itch. Improvements were maintained through 52 weeks of…

Abstract Background Alcohol consumption and smoking have been reported to be associated with psoriasis risk. However, a conclusion with high-quality evidence of causality could not be easily drawn from regular observational studies. Objectives This study aims to assess the causal associations of alcohol consumption and smoking with psoriasis. Methods Genome-wide association study (GWAS) summary-level data for alcohol consumption (N = 941 280), smoking initiation (N = 1 232 091), cigarettes per day (N = 337 334) and smoking cessation (N = 547 219) was obtained from the GSCAN consortium (Sequencing Consortium of Alcohol and Nicotine use). The GWAS results for lifetime smoking (N = 462 690) were obtained from the UK Biobank samples. Summary statistics for psoriasis were obtained from a recent GWAS meta-analysis of eight cohorts comprising 19 032 cases and 286 769 controls and the FinnGen consortium, comprising 4510 cases and 212 242 controls. Linkage disequilibrium score regression was applied to compute the genetic correlation. Bidirectional Mendelian randomization (MR) analyses were…

BACKGROUND: Epidermolysis bullosa (EB) is a heterogeneous group of rare, difficult-to-treat, inherited multisystem diseases affecting epithelial integrity. Patients with EB are affected by mechanical fragility of epithelial surfaces including the skin and, as a result, extensive recurrent blistering is a characteristic of the condition. Chronic wounds predispose patients with EB to the development of squamous cell carcinoma, which is a major cause of premature death. OBJECTIVES: EASE was a double-blind, randomized, vehicle-controlled, phase III study to determine the efficacy and safety of the topical gel Oleogel-S10 (birch triterpenes) in EB. EASE was funded by Amryt Research Limited. METHODS: Patients with dystrophic EB, junctional EB or Kindler EB and a target partial-thickness wound lasting ≥ 21 days and < 9 months that was 10-50 cm2, were enrolled and randomized via computer-generated allocation tables 1 : 1 to Oleogel-S10 or control gel - both with standard-of-care dressings. Study gel was applied to all wounds at least every 4 days. The primary endpoint was the proportion of…

BACKGROUND: Identification of those at risk of more severe psoriasis and/or associated morbidities offers opportunity for early intervention, reduced disease burden and more cost-effective healthcare. Prognostic biomarkers of disease progression have thus been the focus of intense research, but none are part of routine practice. OBJECTIVES: To identify and catalogue candidate biomarkers of disease progression in psoriasis for the translational research community. METHODS: A systematic search of CENTRAL, Embase, LILACS and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving patients with psoriasis (any age, n ≥ 50) reporting biomarkers associated with disease progression. The main outcomes were any measure of skin severity or any prespecified psoriasis comorbidity. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (longitudinal design and/or use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by…

BACKGROUND: Atopic dermatitis (AD) is a prevalent inflammatory, pruritic skin disease. The Janus kinase (JAK) pathway is a treatment target. OBJECTIVES: To assess the efficacy, safety and pharmacokinetics of topical cream brepocitinib, a small-molecule tyrosine kinase 2 (TYK2)/JAK1 inhibitor, in participants with mild-to-moderate AD. METHODS: In this phase IIb, double-blind, dose-ranging study, participants were randomized to receive one of eight treatments for 6 weeks: brepocitinib 0·1% once daily (QD), 0·3% QD or twice daily (BID), 1·0% QD or BID, 3·0% QD, or vehicle QD or BID. The primary endpoint was the percentage change from baseline in the Eczema Area and Severity Index (EASI) total score at week 6. Adverse events (AEs) were monitored. RESULTS: Overall, 292 participants were enrolled and randomized. The brepocitinib 1% QD and 1% BID groups achieved statistically significantly greater (with multiplicity-adjusted P < 0·05 due to Hochberg's step-up method) percentage reductions from baseline in EASI total score at week 6 [least squares mean (90% confidence interval, CI): QD:…

BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating inflammatory skin disease characterized by painful nodules, drainage and scarring in skin folds. Injectable adalimumab is the only drug approved by the US Food and Drug Administration for the treatment of HS. Although systemic Janus kinase (JAK) inhibitors show promise, serious side-effects have been reported. There are no highly effective topical treatments for HS; furthermore, the contribution of epidermal keratinocytes to the intense inflammation has largely been unexplored. OBJECTIVES: We investigated the role of keratinocytes and epidermal immune cells in HS inflammation at all Hurley stages of disease severity. We aimed to determine whether ruxolitinib can mitigate inflammation from keratinocytes and to develop a better understanding of how topical therapeutics might benefit patients with HS. METHODS: We used skin samples from 87 patients with HS (Hurley stages I-III) and 39 healthy controls to compare keratinocyte- and immune cell-driven epidermal inflammation, in addition to the response of lesional HS keratinocytes…

The interleukin (IL)-1 family of cytokines is a central regulator of a myriad of immunological responses. It comprises several cytokines, including those belonging to the IL-1, IL-36 and IL-18 subfamilies, as well as IL-33. The IL-1 family primarily plays a role in orchestrating innate immune responses, but is also involved in adaptive immunity. Increased interest in the IL-1 family occurred following the discovery that dysregulation of IL-1 signalling underlies the pathogenesis of several monogenic autoinflammatory diseases, characterized by sterile inflammation involving the skin and other organs. This also provided increased understanding of the role of innate immunity and the IL-1 family in polygenic autoinflammatory skin conditions, such as neutrophilic dermatoses, as well as in some of the most common chronic inflammatory skin diseases, such as psoriasis and hidradenitis suppurativa. Several therapeutic agents have been developed to inhibit the IL-1 family members and their signalling pathways. These have shown therapeutic efficacy in several chronic inflammatory skin…

BACKGROUND: At present there is no standard nomenclature for describing the diversity of human constitutive skin colour. OBJECTIVES: To develop a standard nomenclature to describe human constitutive skin colour. METHODS: Monthly focus group discussions were carried out among a multidisciplinary group of specialists over a 7-month period. Topics covered were (i) limitations and unmet needs of current nomenclature(s) pertaining to human cutaneous diversity, (ii) practical considerations about the function and role of any proposed nomenclature pertaining to human cutaneous diversity, (iii) review of the cellular basis and current molecular genetic understanding of variation in human skin pigmentation and (iv) in vivo methods to evaluate human skin pigmentation. In addition, a preliminary review of the published literature was undertaken to collate data on published skin reflectance measurements, notably melanin index values for well-referenced human populations. RESULTS: We developed a five-point scale to describe the full spectrum of human constitutive skin colour, termed the…

BACKGROUND: Baricitinib, an oral, selective, reversible Janus kinase (JAK)1/JAK2 inhibitor, is an approved treatment for adults with severe alopecia areata (AA) in the USA, European Union and Japan. OBJECTIVES: To report safety data for baricitinib in patients with severe AA from two clinical trials including long-term extension periods. METHODS: This analysis includes pooled patient-level safety data from two trials, an adaptive phase II/III trial (BRAVE-AA1) and a phase III trial (BRAVE-AA2) (ClinicalTrials.gov, NCT03570749 and NCT03899259). Data are reported in three datasets: (i) the placebo-controlled dataset (up to week 36): baricitinib 2 mg and 4 mg vs. placebo; (ii) the extended dataset (up to the data cutoff): patients remaining on continuous treatment with baricitinib 2 mg or 4 mg from baseline; and (iii) the all-baricitinib dataset (all-BARI, up to the data cutoff): all patients receiving any dose of baricitinib at any time during the trials. Safety outcomes include treatment-emergent adverse events (TEAEs), adverse events of special interest and abnormal laboratory…

BACKGROUND: Programmed cell death receptor-1 (PD-1) monotherapy is a standard treatment for advanced cutaneous melanoma, but its efficacy and toxicity are defined in white populations and remain poorly characterized in other ethnic groups, such as East Asian, Hispanic and African. OBJECTIVES: To determine the efficacy and toxicity of PD-1 monotherapy in different ethnic groups. METHODS: Clinical data for patients with unresectable or advanced melanoma treated with anti-PD-1 monotherapy between 2009 and 2019 were collected retrospectively from five independent institutions in the USA, Australia and China. Tumour response, survival and immune-related adverse events (irAEs) were compared by ethnicity (white vs. East Asian/Hispanic/African) across different melanoma subtypes: nonacral cutaneous (NAC)/unknown primary (UP) and acral/mucosal/uveal. RESULTS: In total, 1135 patients were included. White patients had significantly higher objective response rate (ORR) [54%, 95% confidence interval (CI) 50-57% vs. 20%, 95% CI 13-28%; adjusted P < 0·001] and longer progression-free survival…

BACKGROUND: The validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD™) is a standardized severity assessment for use in clinical trials and registries for atopic dermatitis (AD). OBJECTIVES: To investigate the reliability, validity, responsiveness and within-patient meaningful change of the vIGA-AD. METHODS: Data were analysed from adult patients with moderate-to-severe AD in the BREEZE-AD1 (N = 624 patients; NCT03334396), BREEZE-AD2 (N = 615; NCT03334422) and BREEZE-AD5 (N = 440; NCT03435081) phase III baricitinib clinical studies. RESULTS: Across studies, test-retest reliability for stable patients showed moderate-to-good agreement [range of Kappa values for Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD), 0·516-0·639; for Eczema Area and Severity Index (EASI), 0·658-0·778]. Moderate-to-large correlations between vIGA-AD and EASI or body surface area (range at baseline, 0·497-0·736; Week 16, 0·716-0·893) supported convergent validity. Known-groups validity was demonstrated vs. EASI and PGI-S-AD (vIGA-AD for severe vs. moderate EASI categories…

BACKGROUND: The key pathophysiological changes in androgenetic alopecia (AGA) are limited to hair follicles (HFs) in frontal and vertex regions, sparing the occipital region. OBJECTIVES: To identify biological differences among HF subpopulations. METHODS: Paired vertex and occipital HFs from 10 male donors with AGA were collected for RNA sequencing assay. Furthermore, HF and cell experiments were conducted on the identified key genes to reveal their roles in AGA. RESULTS: Transcriptome profiles revealed that 506 mRNAs, 55 microRNAs and 127 long noncoding RNAs were differentially expressed in the AGA vertex HFs. Pathway analysis of mRNAs and microRNAs revealed involvement of the hypoxia-inducible factor (HIF)-1, Wnt/β-catenin, and focal adhesion pathways. Differential expression of HIF-1 prolyl hydroxylase enzymes (EGLN1, EGLN3) and Wnt/β-catenin pathway inhibitors (SERPINF1, SFRP2) was experimentally validated. In vitro studies revealed that reduction of EGLN1, EGLN3, SERPINF1 and SFRP2 stimulated proliferation of dermal papilla cells. Ex vivo HF studies showed that downregulation…

BACKGROUND: Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness; however, the factors associated with mental illness are unclear. OBJECTIVES: To synthesize and evaluate all available evidence on factors associated with depression, anxiety and severe mental illness (SMI) among adults with AE or psoriasis. METHODS: We searched electronic databases, grey literature databases and clinical trial registries from inception to February 2022 for studies of adults with AE or psoriasis. Eligible studies included randomized controlled trials (RCTs), cohort, cross-sectional or case-control studies where effect estimates of factors associated with depression, anxiety or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesized results narratively, and if at least two studies were sufficiently homogeneous, we pooled effect estimates in a random effects meta-analysis. RESULTS: We included 21 studies (11 observational, 10 RCTs). No observational studies in AE…

BACKGROUND: In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis. OBJECTIVES: To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis. METHODS: Responders with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials - ERASURE and FIXTURE - were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150 mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300 mg continuing on their dose, while those on secukinumab 150 mg or placebo received secukinumab…

BACKGROUND: Generalized pustular psoriasis (GPP) is a severe form of pustular psoriasis with generalized eruption of sterile pustules, often along with systemic symptoms. There is a scarcity of population-based estimates of GPP prevalence and incidence. OBJECTIVES: To estimate (i) the prevalence and incidence of GPP in the Swedish general population and (ii) the prevalence of psoriasis vulgaris within the GPP population. METHODS: We identified cases (2004-2015) with one ICD-10 diagnostic code (base case) for GPP within the Swedish National Patient Register, which covers inpatient and outpatient secondary care. Cases were linked to the Swedish Total Population Register, and point prevalence was estimated as on 31 December 2015. In two alternative analyses we changed case definitions to: (i) requiring two visits (strict case 1) and (ii) requiring two visits of which one was within dermatology/internal medicine (strict case 2). RESULTS: The base case point prevalence of GPP was estimated at 9.1 per 100 000 (women, 11.2; men, 7.0) and the annual prevalence in 2015 was estimated at 1.53…

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that affects intertriginous skin. OBJECTIVES: To determine the extent of work ability and productivity impairment as a result of HS in Germany. METHODS: A prospective, multicentre, epidemiological, noninterventional study of patients with HS was conducted. Medical history, medical examination performed by dermatologists and patient-reported outcomes [Work Ability Index (WAI) and Work Productivity and Activity Impairment (WPAI)] were collected. RESULTS: Of the 481 patients with HS included in the study, 99% were below the current statutory retirement age. In total, 53·3% of patients were working full time, 16·8% part time and 7·3% had retired. The unemployment rate was 12·6%, two times higher than in the general German population. Medical leave because of HS, within the last 6 months, was reported in 41·4% [95% confidence interval (CI) 36·9-46·0], with a duration of 39·3 days on average (95% CI 32·4-46·1). The mean HS-related WPAI absenteeism was 13.3% (95% CI 9·7-16·8), and the loss in productivity because…

BACKGROUND: Checkpoint inhibitor (CPI) therapy has significantly improved overall survival in several cancers including metastatic melanoma (MM) and in the adjuvant setting. Cutaneous immune-related adverse events (irAEs) secondary to CPIs are commonly observed; however, autoimmune blistering disorders such as bullous pemphigoid (BP) are rare. OBJECTIVES: To review the prevalence, incidence risk, clinicopathological features and management of toxicity in bullous cutaneous irAEs associated with CPI therapy. METHODS: A multicentre, retrospective, observational study of CPI-associated bullous irAEs in adults with all cancers across four UK specialist centres between 2006 and 2019. RESULTS: In total, 7391 patients were identified. CPI-associated bullous irAEs including BP (n = 16) occurred in 0·3% (n = 22). The median age of onset was 76 years, and there was a male predominance. Most patients had cutaneous melanoma (73%, n = 16), of which 81% (13 of 16) were BRAF wildtype. Grade 1, 2, 3 and 4 skin toxicity occurred in 9%, 45%, 41% and 5%, respectively. The mucosae were involved in 27%,…

Background Hidradenitis suppurativa (HS) is an inflammatory skin disease with dysregulation of the interleukin (IL)-17 axis. Recently, we reported the clinical benefit of brodalumab, a human anti-IL-17 receptor A (IL-17RA) monoclonal antibody, in moderate-to-severe HS. Objectives To characterize the molecular response to brodalumab in HS skin and serum, and to identify biomarkers of treatment response. Methods Ten participants, who received brodalumab 210 mg /1·5 mL subcutaneously at weeks 0, 1, 2, 4 and every 2 weeks thereafter, were included in this molecular profiling study (NCT03960268). RNA sequencing and immunohistochemistry of nonlesional, perilesional and lesional HS skin biopsies, and Olink high-throughput proteomics of serum at baseline, weeks 4 and 12 were assessed. Results At week 12, brodalumab led to a decrease of overall inflammation, and improvement of psoriasis-, keratinocyte- and neutrophil-related pathways. Despite perilesional and lesional skin exhibiting no differentially expressed genes at baseline, treatment response was best assessed in perilesional skin. In…

The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the management of squamous cell carcinoma in situ (SCC in situ). The document aims to: offer an appraisal of all relevant literature up to 13th August 2021, focusing on any key developments; address important, practical clinical questions relating to the primary guideline objective; provide guideline recommendations and if appropriate research recommendations.

BACKGROUND: Keratinocyte cancers (KCs) are the most common type of cancer in the White population worldwide, with associated high healthcare costs. Understanding the epidemiological trends for KCs, namely basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs), is required to assess burden of disease, project future trends and identify strategies for addressing this pressing global health issue. OBJECTIVES: To report trends in BCC and SCC incidence, and SCC mortality and disability-adjusted life-years (DALYs). METHODS: An observational study of the Global Burden of Disease (GBD) database between 1990 and 2017 was performed. European Union countries and other selected high-income countries, including the UK and the USA, classified as having high-quality mortality data, were included. Annual age-standardized incidence rates (ASIRs), age-standardized death rates (ASDRs) and DALYs for each country were obtained from the GBD database. Trends were described using joinpoint regression analysis. RESULTS: Overall, 33 countries were included. For both BCC and SCC in…

BACKGROUND: Obesity is a common comorbidity of psoriasis and can attenuate response to biologic treatment. OBJECTIVES: To investigate the efficacy, safety and tolerability of secukinumab 300 mg every 2 weeks (Q2W) vs. secukinumab 300 mg every 4 weeks (Q4W) in patients with a higher bodyweight. METHODS: In this multicentre, double-blind, parallel-group trial, 331 patients with moderate-to-severe chronic plaque psoriasis weighing ≥ 90 kg were randomized to receive secukinumab 300 mg Q2W or secukinumab 300 mg Q4W. Patients who did not achieve Psoriasis Area and Severity Index (PASI) 90 at week 16 on the Q4W regimen were reallocated to remain on the Q4W regimen or uptitrate to Q2W. RESULTS: At week 16, Q2W dosing (n = 165) led to significantly higher PASI 90 responses vs. Q4W [n = 166; 73.2% vs. 55.5%, one-sided P-value = 0.0003, odds ratio estimate (95% confidence intervals): 2.3 (1.4-3.8)]. At week 52, higher efficacy responses were maintained in the Q2W arm (n = 165) vs. Q4W (n = 83); PASI 75: 88.9% vs. 74.8%; PASI 90: 76.4% vs. 52.4%; PASI 100: 46.7% vs. 27.3%; Investigator's Global…

BACKGROUND: Interleukin-23 inhibitors are effective and safe for treating moderate-to-severe plaque psoriasis. OBJECTIVES: To evaluate the efficacy and safety of mirikizumab in adult patients with moderate-to-severe plaque psoriasis through 52 weeks in a phase III randomized controlled trial. METHODS: OASIS-1 (NCT03482011) was a double-blind, placebo-controlled, randomized withdrawal, phase III trial. Patients (n = 530, randomized 4 : 1) received subcutaneous mirikizumab 250 mg or placebo every 4 weeks (Q4W) through week 16. Coprimary endpoints were superiority of mirikizumab vs. placebo on static Physician's Global Assessment (sPGA; score of 0 or 1 with ≥ 2-point improvement) and ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90, responders) at week 16. Mirikizumab responders were rerandomized (1 : 1 : 1) to mirikizumab 250 mg every 8 weeks (Q8W), mirikizumab 125 mg Q8W, or placebo Q8W through week 52. Secondary endpoints were evaluated at weeks 16 and 52. Safety was monitored in all patients. RESULTS: All primary and key secondary endpoints were met. At week 16,…

BACKGROUND: Evidence linking prenatal maternal vitamin D supplementation with the offspring's risk of atopic eczema is inconsistent, with most data coming from observational studies. OBJECTIVES: To examine the influence of maternal cholecalciferol supplementation during pregnancy on the risk of atopic eczema in the offspring at ages 12, 24 and 48 months. METHODS: Within the UK Maternal Vitamin D Osteoporosis Study (MAVIDOS) double-blind, randomized placebo-controlled trial, we examined the relationship of maternal vitamin D supplementation during pregnancy with offspring atopic eczema at ages 12, 24 and 48 months. In MAVIDOS, pregnant women were allocated to either cholecalciferol 1000 IU per day or matched placebo, taken from around 14 weeks' gestation until delivery, with the primary outcome of neonatal whole-body bone mineral content. The prevalence of atopic eczema in the offspring was ascertained at ages 12 (n = 635), 24 (n = 610) and 48 (n = 449) months, based on the UK Working Party criteria for the definition of atopic dermatitis. The trial was registered with ISRCTN…

BACKGROUND: Pain is rated by patients with hidradenitis suppurativa (HS) as the disease's most impactful symptom. HS therapies are often insufficient to control inflammatory disease activity and pain. A better understanding of patient experiences with pain may improve patient-provider relationships and help identify strategies for addressing HS pain. OBJECTIVES: This qualitative study sought to characterize lived pain experiences of those with HS. METHODS: English-speaking patients ≥ 18 years old with a dermatologist-confirmed diagnosis of HS and an average numerical rating scale pain score of ≥ 1 over the preceding week were recruited from a single academic medical centre in Atlanta, Georgia, USA. Semistructured interviews were conducted from November 2019 to March 2020 to explore participants' HS pain experiences and the subsequent impact on their lives. Thematic saturation was reached after interviewing 21 participants. Interviews were audio recorded, transcribed, and analysed using thematic analysis. RESULTS: Among 21 study participants, the median 7-day average pain score was 6…

BACKGROUND: The pathogenesis of pityriasis rubra pilaris (PRP) is not completely understood, but interleukin (IL)-17 has been shown to play a critical role. There are no reliable immunomodulatory agents to treat PRP. We conducted an open-label, single-arm clinical trial of secukinumab, a monoclonal antibody that inhibits IL-17A, for the treatment of PRP. OBJECTIVES: To evaluate the clinical efficacy of secukinumab and define the transcriptomic landscape of PRP and its response to IL-17A blockade. METHODS: Twelve patients with PRP were recruited for an open-label trial of secukinumab. Patients received a 24-week course of secukinumab. The primary endpoint was a ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75) from baseline to week 28. Secondary endpoints included PASI 90, change in Physician's Global Assessment (PGA), and change in Dermatology Life Quality Index (DLQI). RNA sequencing was performed on lesional and nonlesional skin biopsies obtained at baseline and week 2. Sample groups were compared to identify differential gene expression and pathway enrichment. This…

Chronic prurigo is a distinct disease defined by the presence of chronic pruritus for at least 6 weeks, a history and/or signs of repeated scratching, and multiple localized or generalized pruritic skin lesions (whitish or pinkish papules, nodules and/or plaques). Although chronic prurigo is frequently named prurigo nodularis, the nodular type of chronic prurigo is only the main clinical aspect of chronic prurigo. Chronic prurigo occurs due to neural sensitization to pruritus and the development of a vicious pruritus-scratching cycle. Chronic prurigo can be of allergological, dermatological, systemic, neurological, psychiatric/psychosomatic, mixed or undetermined origin. The prevalence is still debated. The burden is high. Current treatments often remained disappointing. Fortunately, recent research results on the pathophysiology of pruritus evidenced neuroimmune interactions and allow new therapeutic perspectives. Among them, antagonists of T-helper 2 cytokines, κ-opioids and Janus kinase inhibitors may be promising. What is already known about this topic? Chronic prurigo or…

BACKGROUND: Responses to the systemic treatments commonly used to treat psoriasis vary. Biomarkers that accurately predict effectiveness and safety would enable targeted treatment selection, improved patient outcomes and more cost-effective healthcare. OBJECTIVES: To perform a scoping review to identify and catalogue candidate biomarkers of systemic treatment response in psoriasis for the translational research community. METHODS: A systematic search of CENTRAL, Embase, LILACS and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving patients with psoriasis (any age, n ≥ 50) reporting biomarkers associated with systemic treatment response. The main outcomes were any measure of systemic treatment efficacy or safety. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multistakeholder group using a majority voting consensus exercise and…

Hidradenitis suppurativa (HS) is a chronic, recurrent, debilitating disorder of the pilosebaceous unit. Although its pathophysiology is not fully explained, inflammation seems to play an essential role in the development of HS. A link between obesity - often considered a state of chronic inflammation - and a higher prevalence of HS has been described. Nevertheless, the exact association is not well understood. Adipose tissue is a highly active endocrine organ that produces and secretes a variety of metabolically and immunologically active molecules called adipokines. The imbalances in concentrations of several adipokines in patients with HS have already been described. A shift towards the overproduction of proinflammatory adipokines (including leptin, resistin and visfatin) with the suppression of anti-inflammatory ones (adiponectin) has been noted. We conducted a review of the available data on adipokines in HS, concentrating on the described imbalances in adipokine concentrations, as well as possible implications in HS pathogenesis. Moreover, new, unstudied adipokines with…

BACKGROUND: Cutaneous immune-related adverse events (irAEs) represent the most frequent toxicities induced by immune checkpoint inhibitors (ICIs). OBJECTIVES: To investigate clinical associations of cutaneous toxicities induced by different ICI therapies. METHODS: This was a multicentre retrospective international cohort study of patients with cancer who developed cutaneous irAEs under ICI therapy. Analysis was performed of the rates and basic characteristics of all cutaneous toxicities, and identification of any associations was performed using univariate and multivariate models. RESULTS: In total, 762 patients were included, who developed 993 cutaneous toxicities. Forty different types of skin toxicities were identified. Psoriasis (175 patients, 23·0%) and pruritus (171 patients, 22·4%) were the most common toxicities, followed by macular rash (161 patients, 21·1%) and eczematous-type reactions (150 patients, 19·7%). Multivariate analysis showed that among patients with macular rash, vitiligo or multiple toxicities, patients received ICIs more frequently for melanoma than for…

BACKGROUND: The ichthyoses are rare genetic keratinizing disorders that share the characteristics of an impaired epidermal barrier and increased risk of microbial infections. Although ichthyotic diseases share a T helper (Th) 17 cell immune signature, including increased expression of antimicrobial peptides, the skin microbiota of ichthyoses is virtually unexplored. OBJECTIVES: To analyse the metagenome profile of skin microbiome for major congenital ichthyosis subtypes. METHODS: Body site-matched skin surface samples were collected from the scalp, upper arm and upper buttocks of 16 healthy control participants and 22 adult patients with congenital forms of ichthyosis for whole metagenomics sequencing analysis. RESULTS: Taxonomic profiling showed significant shifts in bacteria and fungi abundance and sporadic viral increases across ichthyosis subtypes. Cutibacterium acnes and Malassezia were significantly reduced across body sites, consistent with skin barrier disruption and depletion of lipids. Microbial richness was reduced, with specific increases in Staphylococcus and…

Skin of colour or pigmented skin has unique characteristics: it has a higher eumelanin-to-pheomelanin ratio, more mature melanosomes, an increased amount of melanin distributed in the upper layers of the epidermis, and more efficient DNA repair compared with lighter skin. However, individuals with skin of colour are at a significant risk of skin damage caused by ultraviolet radiation, including the development of photodermatoses and photoageing changes such as uneven skin tone, and are predisposed to pigmentary disorders. In fact, one of the most common conditions leading to dermatology consultations by patients with skin of colour is photoexacerbated pigmentary disorders. Unfortunately, individuals with skin of colour may be less prone to engage in photoprotective measures, including the use of sunscreens. Physicians are also less likely to prescribe sunscreens for them. There is thus a clear need for better education on photodamage and for more efficient and suitable photoprotection in populations with skin of colour. However, this need has thus far only partially been met, and…

Dear Editor, The recent monkeypox (MP) outbreak is an increasingly alarming public health concern, as multiple clusters are being identified throughout Europe, especially in men who have sex with men (MSM).1–3 This emerging zoonotic disease is transmitted through intimate contact and air droplets, with the possibility of spread via sexual fluids still under investigation.2,4,5 A 44‐year‐old Ukrainian individual, identifying himself as an MSM, presented to the sexually transmitted diseases outpatient service of our dermatology unit in Milan for an asymptomatic cutaneous eruption that had appeared 5 days before on his external genitalia and the third finger of his right hand. Prior to the appearance of skin lesions, he had reported low‐grade fever, headache and malaise for a week. His medical history was positive for past nodal tuberculosis and untreated chronic hepatitis C virus infection. Moreover, he was HIV‐1 positive and currently under combination antiretroviral therapy (CD4 count 0·935 × 109 cells L−1; HIV viral load < 200 copies mL−1). Recently, he had also been treated for…

Abstract Background Several studies have linked various chronic inflammatory skin diseases (CISDs) with inflammatory bowel disease (IBD) in a range of data sources with mixed conclusions. Objectives We compared the incidence of IBD – ulcerative colitis (UC) and Crohn disease (CD) – in patients with a CISD vs. similar persons without a CISD. Methods In this cohort study using nationwide, longitudinal, commercial insurance claims data from the USA, we identified adults and children who were seen by a dermatologist between 2004 and 2020, and diagnosed with either psoriasis, atopic dermatitis, alopecia areata, vitiligo or hidradenitis suppurativa. Comparator patients were identified through risk-set sampling; they were eligible if they were seen by a dermatologist at least twice and not diagnosed with a CISD. Patient follow-up lasted until either IBD diagnosis, death, disenrolment or end of data stream, whichever came first. IBD events, UC or CD, were identified via validated algorithms: hospitalization or diagnosis with endoscopic confirmation. Incidence rates were computed before and…

Inflammatory wounds of the skin can be caused by many different diseases. Of particular importance here are the very heterogeneous groups of vasculitides and vasculopathies. These are usually interdisciplinary relevant diseases that require extensive diagnostics in specialized centres. Clinically, these inflammatory wounds present as very painful ulcers that develop from necrosis and are surrounded by erythematous livid borders. The healing process is often difficult and protracted. Moreover, it considerably impairs the quality of life of the affected patients. In addition to clinical evaluation, histopathological examination of biopsies taken as early as possible is particularly important in diagnosis. Numerous differential diagnoses must be ruled out. Therapeutically, in addition to the often necessary systemic therapies, which include immunosuppressants (immunomodulating drugs and/or rheologics), appropriate topical wound treatment, usually in combination with compression therapy, should always be considered. Whenever possible, the causative factors should be diagnosed early and…

BACKGROUND: Accumulating evidence supports the findings of an altered gut microbiota in patients with autoimmune disease. However, existing studies on the role of the gut microbiota in patients with psoriasis have demonstrated conflicting results and have mainly been based on 16s rRNA gene sequencing analysis. OBJECTIVES: To examine whether the gut microbiota of patients with psoriasis was altered in composition and functional potentials compared with healthy controls, and as a second approach compared with healthy cohabitant partners. A further aim was to investigate relationships to disease severity, and seasonal impact on the gut microbiota. METHODS: In a case-control study, 126 faecal samples were collected from a sample of 53 systemically untreated patients with plaque psoriasis; 52 healthy controls matched for age, sex and body mass index; and 21 cohabitant partners. A subpopulation of 18 patients with psoriasis and 19 healthy controls continued in a longitudinal study, where four to six faecal samples were collected over 9-12 months. The gut microbiota was characterized using…

BACKGROUND: Prurigo nodularis is a debilitating skin condition that is classified as rare by the Genetic and Rare Diseases Information Center (GARD) and the National Organization for Rare Diseases (NORD). There are currently no estimates of the prevalence of prurigo nodularis in England. OBJECTIVES: We aimed to address this data gap by describing the epidemiology of prurigo nodularis in a representative dataset derived from the English National Health Service. METHODS: The study utilized data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics inpatient data. Patients with a diagnosis of prurigo nodularis were selected by clinical code in the primary care or inpatient datasets. Case definition was based on a minimum of two distinct diagnoses to maximize specificity. Point prevalence was calculated for the midpoint of 2018 and incidence rates from 2008 to 2018 were presented. For those classified as incident cases, demographic and clinical characteristics were reported. In sensitivity analyses the case definition was modified to relax the multiple…

Summary Background Primary cutaneous peripheral T-cell lymphomas with a T-follicular helper phenotype (pcTFH-PTCL) are poorly characterized, and often compared to, but not corresponding with, mycosis fungoides (MF), Sézary syndrome, primary cutaneous CD4+ lymphoproliferative disorder, and skin manifestations of angioimmunoblastic T-cell lymphomas (AITL). Objectives We describe the clinicopathological features of pcTFH-PTCL in this original series of 23 patients, and also characterize these cases molecularly. Methods Clinical and histopathological data of the selected patients were reviewed. Patient biopsy samples were also analysed by targeted next-generation sequencing. Results All patients (15 men, eight women; median age 66 years) presented with skin lesions, without systemic disease. Most were stage T3b, with nodular (n = 16), papular (n = 6) or plaque (atypical for MF, n = 1) lesions. Three (13%) developed systemic disease and died of lymphoma. Nine (39%) patients received more than one line of chemotherapy. Histologically, the lymphomas were CD4+ T-cell proliferations, usually…

Dear Editor, Dupilumab‐associated head and neck dermatitis (DAHND) refers to the de novo development or exacerbation of head and neck dermatitis (HND) in the setting of dupilumab therapy.1, 2 It has been observed in 10% of atopic patients,3, 4 with the causative mechanisms incompletely understood. Proposed hypotheses have included site‐specific treatment failure of dupilumab as well as localized inflammatory reaction to facial Malassezia species.5, 6, 7 This prospective cohort study aimed to assess whether baseline (pretreatment) Malassezia‐specific IgE levels were associated with the development of DAHND in individuals commencing dupilumab therapy for moderate‐to‐severe atopic dermatitis. Over a 6‐month period from 1 March 2021 to 1 September 2021, 171 consecutive patients were included. Age, sex, Eczema Area and Severity Index (EASI) score, total serum IgE and Malassezia‐specific serum IgE as measured by ImmunoCAP solid phase sandwich immunoassay (Thermo Fisher Scientific, Waltham, MA, USA) were recorded. DAHND was defined as de novo or worsening (defined as a 50% worsening in…

Mycosis fungoides (MF) and Sézary syndrome (SS) are the best-studied subtypes of cutaneous T-cell lymphoma, a rare non-Hodgkin lymphoma that primarily presents in the skin but can also involve blood, lymph nodes and viscera. The role of blood involvement in the assessment and staging of MF and SS has evolved in recent years from being classed as simply 'present' or 'absent', with no impact on staging, to full analysis of abnormal peripheral blood T cells using flow cytometry (FC) to detect and quantify aberrant T-cell phenotypes and polymerase chain reaction (PCR) to characterize T-cell receptor gene rearrangements. These sensitive peripheral blood assessments are replacing manual Sézary cell counts and have become an important part of clinical workup in MF and SS, providing the potential for more accurate prognosis and appropriate management. However, although international recommendations now include guidelines for FC analysis of peripheral blood markers for staging purposes, many clinics only perform these analyses in patients with advanced-stage lymphoma, if at all, and there is…

BACKGROUND: Psoriasis can be provoked by both external and internal factors. The effects of environmental factors on psoriasis remain unclear. OBJECTIVES: To investigate the effects of air pollution on outpatient visits for psoriasis. METHODS: A distributed lag nonlinear model following quasi-Poisson regression was used to evaluate the lag effects of air pollutants on psoriasis outpatient visits, adjusting for potential confounders. Stratified analyses were performed to identify potential effect modifications by sex, age and season. RESULTS: In total, 13 536 outpatient visits for psoriasis were recorded in Wuhan, China from 1 January 2015 to 31 December 2019. In the single-pollutant model, exposures to particulate matter (PM) smaller than 2.5 μm (PM2.5), PM smaller than 10 μm (PM10), NO2 and SO2 were found to be significantly associated with increased daily psoriasis outpatient visits. For the largest effects, a 10-μg m-3 increase in concentrations of PM2.5 (lag1), PM10 (lag1), NO2 (lag0) and SO2 (lag3) corresponded to 0.32% [95% confidence interval (CI) 0.01-0.63], 0.26% (95% CI…