The 50 most-cited articles in British Journal of Dermatology, 2020

BACKGROUND: The cutaneous manifestations of COVID-19 disease are poorly characterized. OBJECTIVES: To describe the cutaneous manifestations of COVID-19 disease and to relate them to other clinical findings. METHODS: We carried out a nationwide case collection survey of images and clinical data. Using a consensus we described five clinical patterns. We later described the association of these patterns with patient demographics, the timing in relation to symptoms of the disease, the severity and the prognosis. RESULTS: The lesions may be classified as acral areas of erythema with vesicles or pustules (pseudo-chilblain) (19%), other vesicular eruptions (9%), urticarial lesions (19%), maculopapular eruptions (47%) and livedo or necrosis (6%). Vesicular eruptions appear early in the course of the disease (15% before other symptoms). The pseudo-chilblain pattern frequently appears late in the evolution of the COVID-19 disease (59% after other symptoms), while the rest tend to appear with other symptoms of COVID-19. The severity of COVID-19 shows a gradient from less severe disease in…

BACKGROUND: Several new genes and clinical subtypes have been identified since the publication in 2014 of the report of the last International Consensus Meeting on Epidermolysis Bullosa (EB). OBJECTIVES: We sought to reclassify disorders with skin fragility, with a focus on EB, based on new clinical and molecular data. METHODS: This was a consensus expert review. RESULTS: In this latest consensus report, we introduce the concept of genetic disorders with skin fragility, of which classical EB represents the prototype. Other disorders with skin fragility, where blisters are a minor part of the clinical picture or are not seen because skin cleavage is very superficial, are classified as separate categories. These include peeling skin disorders, erosive disorders, hyperkeratotic disorders, and connective tissue disorders with skin fragility. Because of the common manifestation of skin fragility, these 'EB-related' disorders should be considered under the EB umbrella in terms of medical and socioeconomic provision of care. CONCLUSIONS: The proposed classification scheme should be of…

BACKGROUND: Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin-13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms. OBJECTIVES: To evaluate the efficacy and safety of tralokinumab monotherapy in adults with moderate-to-severe AD who had an inadequate response to topical treatments. METHODS: In two 52-week, randomized, double-blind, placebo-controlled, phase III trials, ECZTRA 1 and ECZTRA 2, adults with moderate-to-severe AD were randomized (3 : 1) to subcutaneous tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Primary endpoints were Investigator's Global Assessment (IGA) score of 0 or 1 at week 16 and ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. Patients achieving an IGA score of 0 or 1 and/or EASI 75 with tralokinumab at week 16 were rerandomized to tralokinumab Q2W or every 4 weeks or placebo, for 36 weeks. The trials were registered with…

BACKGROUND: The Global Burden of Disease (GBD) Study provides an annually updated resource to study disease-related morbidity and mortality worldwide. OBJECTIVES: Here we present the burden estimates for atopic dermatitis (AD), including data from inception of the GBD project in 1990 until 2017. METHODS: Data on the burden of AD were obtained from the GBD Study. RESULTS: Atopic dermatitis (AD) ranks 15th among all nonfatal diseases and has the highest disease burden among skin diseases as measured by disability-adjusted life-years (DALYs). Overall, the global DALY rate for AD in 1990 was 121 [95% uncertainty interval (UI) 65·4-201] and remained similar in 2017 at 123 (95% UI 66·8-205). The three countries with the highest DALY rates of AD were Sweden (327, 95% UI 178-547), the UK (284, 95% UI 155-478) and Iceland (277, 95% UI 149-465), whereas Uzbekistan (85·1, 95% UI 45·2-144), Armenia (85·1, 95% UI 45·8-143) and Tajikistan (85·1, 95% UI 46·1-143) ranked lowest. CONCLUSIONS: The global prevalence rate of AD has remained stable from 1990 to 2017. However, the distribution of AD by…

BACKGROUND: Chilblains ('COVID toes') are being seen with increasing frequency in children and young adults during the COVID-19 pandemic. Detailed histopathological descriptions of COVID-19 chilblains have not been reported, and causality of SARS-CoV-2 has not yet been established. OBJECTIVES: To describe the histopathological features of COVID-19 chilblains and to explore the presence of SARS-CoV-2 in the tissue. METHODS: We examined skin biopsies from seven paediatric patients presenting with chilblains during the COVID-19 pandemic. Immunohistochemistry for SARS-CoV-2 was performed in all cases and electron microscopy in one. RESULTS: Histopathology showed variable degrees of lymphocytic vasculitis ranging from endothelial swelling and endotheliitis to fibrinoid necrosis and thrombosis. Purpura, superficial and deep perivascular lymphocytic inflammation with perieccrine accentuation, oedema, and mild vacuolar interface damage were also seen. SARS-CoV-2 immunohistochemistry was positive in endothelial cells and epithelial cells of eccrine glands. Coronavirus particles were found in…

BACKGROUND: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced atopic dermatitis (AD) severity in a phase II study with concomitant topical corticosteroids. OBJECTIVES: To evaluate the efficacy and safety of baricitinib in patients with moderate-to-severe AD who had an inadequate response to topical therapies. METHODS: In two independent, multicentre, double-blind, phase III monotherapy trials, BREEZE-AD1 and BREEZE-AD2, adults with moderate-to-severe AD were randomized 2 : 1 : 1 : 1 to once-daily placebo, baricitinib 1 mg, 2 mg, or 4 mg for 16 weeks. RESULTS: At week 16, more patients achieved the primary end point of Validated Investigator's Global Assessment of AD (0, 1) on baricitinib 4 mg and 2 mg compared with placebo in BREEZE-AD1 [N = 624; baricitinib 4 mg 16·8% (P < 0·001), 2 mg 11·4% (P < 0·05), 1 mg 11·8% (P < 0·05), placebo 4·8%], and BREEZE-AD2 [N = 615; baricitinib 4 mg 13·8% (P = 0·001), 2 mg 10·6% (P < 0·05), 1 mg 8·8% (P = 0·085), placebo 4·5%]. Improvement in itch was achieved as early as week 1 for 4 mg and week 2 for 2 mg.…

Chronic urticaria (CU) affects about 1% of the world population of all ages, mostly young and middle‐aged women. It usually lasts for several years (> 1 year in 25–75% of patients) and often takes > 1 year before effective management is implemented. It presents as chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU) or both in the same person. More than 25% of cases are resistant to H1‐antihistamines, even at higher doses, and third‐ and fourth‐line therapies (omalizumab and ciclosporin) control the disease only in two‐thirds of H1‐antihistamine‐resistant patients. Here we review the impact of CU on different aspects of patients’ quality of life and the burden of this chronic disease for the patient and society. CU may have a strong impact on health‐related quality of life (HRQoL), particularly when CSU is associated with angio‐oedema and/or CIndU (Dermatology Life Quality Index > 10 in 30% of patients). Comorbidities, such as anxiety and depression, which are present in more than 30% of patients with CSU, compound HRQoL impairment. Severe pruritus and the…

In the past, the skills required to make an accurate dermatological diagnosis have required exposure to thousands of patients over many years. However, in recent years, artificial intelligence (AI) has made enormous advances, particularly in the area of image classification. This has led computer scientists to apply these techniques to develop algorithms that are able to recognize skin lesions, particularly melanoma. Since 2017, there have been numerous studies assessing the accuracy of algorithms, with some reporting that the accuracy matches or surpasses that of a dermatologist. While the principles underlying these methods are relatively straightforward, it can be challenging for the practising dermatologist to make sense of a plethora of unfamiliar terms in this domain. Here we explain the concepts of AI, machine learning, neural networks and deep learning, and explore the principles of how these tasks are accomplished. We critically evaluate the studies that have assessed the efficacy of these methods and discuss limitations and potential ethical issues. The burden of skin…

BACKGROUND: Scabies is a common parasitic skin condition that causes considerable morbidity globally. Clinical and epidemiological research for scabies has been limited by a lack of standardization of diagnostic methods. OBJECTIVES: To develop consensus criteria for the diagnosis of common scabies that could be implemented in a variety of settings. METHODS: Consensus diagnostic criteria were developed through a Delphi study with international experts. Detailed recommendations were collected from the expert panel to define the criteria features and guide their implementation. These comments were then combined with a comprehensive review of the available literature and the opinion of an expanded group of international experts to develop detailed, evidence-based definitions and diagnostic methods. RESULTS: The 2020 International Alliance for the Control of Scabies (IACS) Consensus Criteria for the Diagnosis of Scabies include three levels of diagnostic certainty and eight subcategories. Confirmed scabies (level A) requires direct visualization of the mite or its products. Clinical…

BACKGROUND: Tralokinumab is a fully human monoclonal antibody that specifically neutralizes interleukin-13, a key driver of atopic dermatitis (AD). OBJECTIVES: To evaluate the efficacy and safety of tralokinumab in combination with topical corticosteroids (TCS) in patients with moderate-to-severe AD who were candidates for systemic therapy. METHODS: This was a double-blind, placebo plus TCS controlled phase III trial. Patients were randomized 2 : 1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks (Q2W) with TCS as needed over 16 weeks. Patients who achieved an Investigator's Global Assessment (IGA) score of 0/1 and/or 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16 with tralokinumab were rerandomized 1 : 1 to tralokinumab Q2W or every 4 weeks (Q4W), with TCS as needed, for another 16 weeks. RESULTS: At week 16, more patients treated with tralokinumab than with placebo achieved IGA 0/1: 38·9% vs. 26·2% [difference (95% confidence interval): 12·4% (2·9-21·9); P = 0·015] and EASI 75: 56·0% vs. 35·7% [20·2% (9·8-30·6); P < 0·001]. Of the patients who…

Psoriasis is a chronic inflammatory disease with a strong genetic component that can be triggered by environmental factors. Disease pathogenesis is mainly driven by type 1 and type 17 cytokine-producing cells which, in healthy individuals, are modulated by regulatory T cells (Tregs). Tregs play a fundamental role in immune homeostasis and contribute to the prevention of autoimmune disease by suppressing immune responses. In psoriasis, Tregs are impaired in their suppressive function leading to an altered T-helper 17/Treg balance. Although Treg dysfunction in patients with psoriasis is associated with disease exacerbation, it is unknown how they are functionally regulated. In this review, we discuss recent insights into Tregs in the setting of psoriasis with an emphasis on the effect of current treatments on Tregs and how already available therapeutics that modulate Treg frequency or functionality could be exploited for treatment of psoriasis.

Linked Comment:Ormerod. Br J Dermatol 2020; 183:604. Plain language summary available online

BACKGROUND: The infection caused by the recently identified SARS-CoV-2, called coronavirus disease-19 (COVID-19), has rapidly spread throughout the world. With the exponential increase of patients worldwide, the clinical spectrum of COVID-19 is being better defined and new symptoms are emerging. Numerous reports are documenting the occurrence of different cutaneous manifestations in patients with COVID-19. OBJECTIVES: To provide a brief overview of cutaneous lesions associated with COVID-19. METHODS: A literature search was performed in the PubMed, Scopus and Web of Science databases up to 30 April 2020. This narrative review summarizes the available data regarding the clinical and histological features of COVID-19-associated skin manifestations. RESULTS: The literature reports showed a great heterogeneity in COVID-19-associated cutaneous manifestations, as well as in their latency periods and associated extracutaneous symptoms. Pathogenic mechanisms are unknown, although the roles of a hyperactive immune response, complement activation and microvascular injury have been…

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease defined clinically by multiple, painful inflammatory lesions occurring predominantly in flexural sites. Onset is typically soon after puberty; however, it remains unknown whether the menopause induces remission. In North American and European patients with HS the female-to-male ratio is approximately 3 : 1 but the ratio is 1 : 2 in South Korean patients. It may be that some elements of HS epidemiology cannot be generalized across all populations. Elements of HS epidemiology in the USA and Europe are well established, including strong associations with obesity and smoking, which may increase disease severity. There are associations between HS and other cardiovascular disease (CVD) risk factors, including type 2 diabetes and metabolic syndrome. People with HS have double the risk of death from CVD compared with those without HS and 1·5 times the risk compared with patients with psoriasis. Depression and anxiety are associated with HS and completed suicide rates in those with HS are more than double the rates in…

BACKGROUND: Patients with plaque psoriasis treated with biologic therapies need more efficacious, safe and convenient treatments to improve quality of life. Risankizumab and secukinumab inhibit interleukin-23 and interleukin-17A, respectively, and are effective in adult patients with moderate-to-severe plaque psoriasis but have different dosing regimens. OBJECTIVES: To compare directly the efficacy and safety of risankizumab vs. secukinumab over 52 weeks. METHODS: IMMerge was an international, phase III, multicentre, open-label, efficacy-assessor-blinded, active-comparator study, in which adult patients with chronic, moderate-to-severe plaque psoriasis were randomized in a 1 : 1 ratio to treatment with risankizumab 150 mg or secukinumab 300 mg. Primary efficacy endpoints were the proportions of patients achieving ≥ 90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90) at week 16 (noninferiority comparison with margin of 12%) and week 52 (superiority comparison). RESULTS: In total 327 patients from nine countries were treated with risankizumab (n = 164) or…

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder. Patients develop inflamed nodules and abscesses and, at later stages of disease, epithelialized tunnels and scars in skinfolds of axillary, inguinal, gluteal and perianal areas. Quality of life is affected due to severe pain, purulent secretion, restricted mobility and systemic involvement. Genetics and lifestyle factors including smoking and obesity contribute to the development of HS. These factors lead to microbiome alteration, subclinical inflammation around the terminal hair follicles, and infundibular hyperkeratosis, resulting in plugging and rupture of the follicles. Cell-damage-associated molecules and propagating bacteria trigger inflammation and lead to massive immune cell infiltration that clinically manifests as inflamed nodules and abscesses. The immune system plays a key role also in the progression and chronification of skin alterations. Innate proinflammatory cytokines (e.g. interleukin-1β and tumour necrosis factor-α), mediators of activated T helper (Th)1 and Th17 cells (e.g. interleukin-17 and…

Dear Editor, During the outbreak of coronavirus disease 2019 (COVID‐19), healthcare workers (HCWs) caring for patients with COVID‐19 have to wear personal protective equipment (PPE) and are therefore susceptible to PPE‐related adverse skin reactions. However, little is known about the prevalence and characteristics of these adverse skin reactions and their associated risk factors. To address this, we conducted a cross‐sectional questionnaire survey during 6–11 February 2020 in Wuhan and its surrounding regions. Five university hospitals in Wuhan and five regional hospitals around Wuhan were included. The study respondents included doctors and nurses caring for patients with COVID‐19. Demographic information was recorded, in addition to data on self‐perceived adverse skin reactions, types (dryness or scales, papules or erythema, maceration, erosion or fissure) and sites of eruptions. Univariate and multivariate analyses were performed to assess associations between adverse skin reactions and the following variables: age, sex, hospital size and area, epidemic level, working place,…

BACKGROUND: There is a lack of any overview of changes over time and variation in the epidemiology of psoriasis with age and between genders. OBJECTIVES: To perform a systematic review of published population-based studies on variations in psoriasis incidence and prevalence with age and between genders, and to explore trends in psoriasis epidemiology over time. METHODS: Eleven electronic and regional databases were searched from their inception dates to October 2019. No language restrictions were applied. Studies were eligible if they reported on changes in psoriasis incidence and/or prevalence over time and/or by age group and gender. RESULTS: In total 308 papers were critically appraised, from which 90 studies from 22 countries were included. Incidence data confirmed a clear bimodal age pattern in psoriasis onset, with the first and second peaks at around 30-39 and 60-69 years of age, respectively, and evidence suggesting that it presents slightly earlier in women than in men. Prevalence data showed an increasing trend with age until around 60 or 70 years, after which it…

BACKGROUND: The anti-tumour necrosis factor (TNF)-α adalimumab is the only licenced biologic for moderate-to-severe hidradenitis suppurativa (HS). No predictors of response have been identified so far. OBJECTIVES: To identify clinical parameters predicting response to adalimumab and confirm its efficacy/safety. METHODS: The data of 389 patients with HS treated with adalimumab in 21 Italian centres were reviewed. Sex, age at onset/diagnosis/baseline, body mass index, smoking, phenotype, previous treatments, concomitant antibiotics and 'therapeutic delay', defined as the time from HS onset to adalimumab initiation, were assessed. Response to adalimumab and its impact on quality of life (QoL) were evaluated using the Hidradenitis Suppurativa Clinical Response (HiSCR) and the Dermatology Life Quality Index (DLQI) or the Visual Analogue Scale for pain (VAS pain), respectively. Logistic regression analysis was performed. RESULTS: The therapeutic delay correlated to lack of response to adalimumab at week 16 [odds ratio (OR) 1·92 for therapeutic delay > 10 years; 95% confidence interval…

Acne (also known as acne vulgaris) remains the most common inflammatory dermatosis treated worldwide, as estimated by global skin disease prevalence studies. Latest reports suggest that the prevalence may be increasing in adolescents and adults, particularly female adults. The concept of 'burden of skin disease' is multidimensional and can be difficult to quantify in light of different healthcare systems across the globe. In acne, the resulting burden may vary according to patient demographics, access to treatments and duration of the disease. The visible nature of acne, symptoms and sequelae all contribute physically and psychosocially to the overall burden of disease, as do the costs required for management. Acne typically presents in adolescence at a time of significant transition. Profound effects on functional status have been demonstrated, along with a strong impact on interpersonal relationships, social functioning and mental health. The high prevalence of acne also presents an economic burden for society. The widespread and prolonged use of antibiotics introduces a potential…

The body is host to a vast range of microorganisms and this diversity of microorganisms is known as the microbiome. The human microbiome is collectively composed of resident bacteria, fungi, viruses, and small arthropods that live in and on our bodies. This microbiome is important to human health and disease, including in dermatology. Research has shown that probiotics, or live microorganisms, can help restore a healthy microbiome and may give us health benefits. This review evaluates the role of the microbiome in dermatology, and presents the clinical data supporting the use of probiotics for skin diseases, including oral probiotics that are ingested and topical probiotics that are directly applied to the skin. Different types of studies were included, such as basic science, translational research and clinical studies, which investigated the differences in the skin microbiome and the impact of probiotics in patients with eczema, acne, psoriasis, chronic wounds, dandruff, and certain types of skin cancer. The authors found that only a few clinical trials explored the usefulness of…

Optical coherence tomography (OCT) is a noninvasive optical imaging method that can generate high-resolution en face and cross-sectional images of the skin in vivo to a maximum depth of 2 mm. While OCT holds considerable potential for noninvasive diagnosis and disease monitoring, it is poorly understood by many dermatologists. Here we aim to equip the practising dermatologist with an understanding of the principles of skin OCT and the potential clinical indications. We begin with an introduction to the technology and discuss the different modalities of OCT including angiographic (dynamic) OCT, which can image cutaneous blood vessels at high resolution. Next we review clinical applications. OCT has been most extensively investigated in the diagnosis of keratinocyte carcinomas, particularly basal cell carcinoma. To date, OCT has not proven sufficiently accurate for the robust diagnosis of malignant melanoma; however, the evaluation of abnormal vasculature with angiographic OCT is an area of active investigation. OCT, and in particular angiographic OCT, also shows promise in monitoring…

Human hair follicles (HFs) carry complex microbial communities that differ from the skin surface microbiota. This likely reflects that the HF epithelium differs from the epidermal barrier in that it provides a moist, less acidic, and relatively ultraviolet light-protected environment, part of which is immune-privileged, thus facilitating microbial survival. Here we review the current understanding of the human HF microbiome and its potential physiological and pathological functions, including in folliculitis, acne vulgaris, hidradenitis suppurativa, alopecia areata and cicatricial alopecias. While reviewing the main human HF bacteria (such as Propionibacteria, Corynebacteria, Staphylococci and Streptococci), viruses, fungi and parasites as human HF microbiome constituents, we advocate a broad view of the HF as an integral part of the human holobiont. Specifically, we explore how the human HF may manage its microbiome via the regulated production of antimicrobial peptides (such as cathelicidin, psoriasin, RNAse7 and dermcidin) by HF keratinocytes, how the microbiome may impact on…

Significantly more patients with moderate‐to‐severe plaque psoriasis treated with the interleukin (IL)‐17A inhibitor ixekizumab vs. the IL‐23p19 inhibitor guselkumab in the IXORA‐R head‐to‐head trial achieved 100% improvement in Psoriasis Area and Severity Index (PASI 100) at week 12. To compare skin and nail clearance and patient‐reported outcomes for ixekizumab vs. guselkumab, up to week 24. IXORA‐R enrolled adults with moderate‐to‐severe plaque psoriasis, defined as static Physician’s Global Assessment ≥ 3, PASI ≥ 12 and involved body surface area ≥ 10%. Statistical comparisons were performed using the Cochran–Mantel–Haenszel test stratified by pooled site. Time‐to‐first‐event comparisons were performed using Kaplan–Meier analysis, and P‐values were generated using adjusted log‐rank tests stratified by treatment group. Cumulative days at clinical and patient‐reported responses were compared by ancova. The trial was registered with ClinicalTrials.gov (NCT03573323). Of the 1027 patients randomly assigned, 90% completed the trial (465 of 520 ixekizumab and 459 of 507 guselkumab). As…

BACKGROUND: Content-valid and clinically meaningful instruments are required to evaluate outcomes of therapeutic interventions in alopecia areata (AA). OBJECTIVES: To develop an Investigator's Global Assessment (IGA) to interpret treatment response in AA treatment studies. METHODS: Qualitative interviews were conducted in the USA with expert dermatologists and with patients with AA who had experienced ≥ 50% scalp-hair loss. Thematic data analysis identified critical outcomes and evaluated the content validity of the new IGA. RESULTS: Expert clinicians (n = 10) judged AA treatment success by the amount of scalp-hair growth (median 80% scalp hair). Adult (n = 25) and adolescent (n = 5) patients participated. Scalp-hair loss was the most bothersome AA sign/symptom for most patients. Perceived treatment success - short of 100% scalp hair - was the presence of ~ 70-90% scalp hair (median 80%). Using additional clinician and patient insights, the Alopecia Areata Investigator Global Assessment (AA-IGA™) was developed. This clinician-reported outcome assessment is an ordinal, static measure…

Dear Editor, Severe acute respiratory syndrome coronavirus 2 has spread across the globe, causing respiratory manifestations of coronavirus disease (COVID)‐19 and satisfying the epidemiological criteria for a pandemic.1 As of 1 April 2020, more than one million cases testing positive for COVID‐19 have been identified and more than 54 000 deaths have occurred worldwide (https://systems.jhu.edu). In Italy, 110 574 positive cases, 49 285 hospitalized patients and 13 155 deaths from a population of 60 359 546 inhabitants were reported.2 The highest number of deaths occurred in the northern Italian regions, i.e. Lombardy, Emilia‐Romagna, Veneto and Piedmont.3 There is uncertainty concerning the outcome of COVID‐19 infection in patients with chronic plaque psoriasis receiving biological systemic therapies.3 Indeed, it is largely debated whether biologics for psoriasis should be interrupted for preventing severe complications of the COVID‐19 infection, such as interstitial pneumonia.4,5,6 We performed a retrospective multicentre observational study, which included patients with chronic…

BACKGROUND: Plaque psoriasis affects children and adults, but treatment options for paediatric psoriasis are limited. OBJECTIVES: To evaluate the efficacy and safety of ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, for moderate-to-severe paediatric psoriasis. METHODS: In a randomized, double-blind, placebo-controlled, phase III study (IXORA-PEDS), patients aged 6 to < 18 years with moderate-to-severe plaque psoriasis were randomized 2 : 1 to weight-based dosing of IXE every 4 weeks (IXE Q4W, n = 115) or placebo (n = 56) through week 12, followed by open-label IXE Q4W. Coprimary endpoints were the proportions of patients at week 12 achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and those achieving a static Physician's Global Assessment score of 0 or 1 (sPGA 0,1). RESULTS: IXE was superior (P < 0·001) to placebo for both coprimary endpoints of PASI 75 (IXE Q4W, 89%; placebo, 25%) and sPGA (0,1) (IXE Q4W, 81%; placebo, 11%). IXE was also superior for all gated secondary endpoints, including PASI 75 and sPGA…

BACKGROUND: Real-world biologic drug survival is an important proxy measure for effectiveness. Predictors of drug survival may help patients with psoriasis choose between biologic therapies. OBJECTIVES: (i) To assess the relative drug survival of adalimumab, ustekinumab and secukinumab in patients with psoriasis. (ii) To investigate predictors of biologic drug survival. METHODS: A prospective cohort study was performed in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) between November 2007 and August 2019. We performed survival analysis and fitted a flexible parametric survival model for biologic discontinuation due to ineffectiveness. RESULTS: In total 9652 patients were included: 5543 starting on adalimumab (57·4%), 991 on secukinumab (10·3%) and 3118 on ustekinumab (32·3%). The overall drug survivals of adalimumab, secukinumab and ustekinumab in year 1 were 0·78 [95% confidence interval (CI) 0·77-0·79], 0·88 (95% CI 0·86-0·91) and 0·88 (95% CI 0·87-0·89), respectively. The adjusted hazard ratios (adjHRs) for discontinuation of…

BACKGROUND: There are two distinctive acral manifestations of COVID-19 embodying disparate clinical phenotypes. One is perniosis occurring in mildly symptomatic patients, typically children and young adults; the second is the thrombotic retiform purpura of critically ill adults with COVID-19. OBJECTIVES: To compare the clinical and pathological profiles of these two different cutaneous manifestations of COVID-19. METHODS: We compared the light microscopic, phenotypic, cytokine and SARS-CoV-2 protein and RNA profiles of COVID-19-associated perniosis with that of thrombotic retiform purpura in critical patients with COVID-19. RESULTS: dendritic cell infiltrates. Both COVID-associated and idiopathic perniosis showed striking expression of the type I interferon-inducible myxovirus resistance protein A (MXA), an established marker for type I interferon signalling in tissue. SARS-CoV-2 RNA, interleukin-6 and caspase 3 were minimally expressed and confined to mononuclear inflammatory cells. The biopsies from livedo/retiform purpura showed pauci-inflammatory vascular thrombosis without any…

Dear Editor, There are now over 1 million confirmed cases of COVID‐19 globally, with more than 270 000 recorded deaths to date.1 COVID‐19 has been shown to impact people of colour disproportionately, both in the UK and in the USA, where black people make up 13·4% of the population but 30% of cases of COVID‐19.2 3 Mounting evidence shows that COVID‐19 impacts several organ systems, including the skin.4 Knowledge of cutaneous manifestations of COVID‐19 and the ability to identify them in patients of all skin types is important for dermatologists and other healthcare providers who may be evaluating patients who are otherwise asymptomatic. In order to provide optimal care to all patients, it is therefore important that we are able to identify cutaneous manifestations of COVID‐19 in patients with darker skin. We completed a systematic literature review, using the PRISMA guidelines, of all articles describing cases of cutaneous manifestations associated with COVID‐19. We included English‐language articles published between 31 December 2019 and 3 May 2020. We extracted patient case…

BACKGROUND: A rising incidence and high mortality were found for bullous pemphigoid (BP) over a decade ago in the UK. Updated estimates of its epidemiology are required to understand the healthcare needs of an ageing population. OBJECTIVES: To determine the incidence, prevalence and mortality rates of BP in England from 1998 to 2017. METHODS: We conducted a cohort study of longitudinal electronic health records using the Clinical Practice Research Datalink and linked Hospital Episode Statistics. Incidence was calculated per 100 000 person-years and annual point prevalence per 100 000 people. Multivariate analysis was used to determine incidence rate ratios by sociodemographic factors. Mortality was examined in an age-, sex- and practice-matched cohort, using linked Office of National Statistics death records. Hazard ratios (HRs) were stratified by matched set. RESULTS: The incidence was 7·63 [95% confidence interval (CI) 7·35-7·93] per 100 000 person-years and rose with increasing age, particularly for elderly men. The annual increase in incidence was 0·9% (95% CI 0·2-1·7). The…

Dear Editor, Coronavirus disease 2019 (COVID‐19) has been associated with several cutaneous manifestations.1–3 A temporary field hospital was implemented during the pandemic peak in Madrid, Spain, to attend patients with COVID‐19 who had mild‐to‐moderate pneumonia. A team of dermatologists working as medical volunteers performed a cross‐sectional study between 10 and 25 April 2020 to evaluate cutaneous findings of such patients. A total of 666 patients with COVID‐19 fulfilled the inclusion criteria: either positive real‐time reverse‐transcription polymerase chain reaction (RT‐PCR) testing for SARS‐CoV‐2, or bilateral pneumonia. Mean age was 55·7 years; with a slight female predominance (58%). Notably, 47·1% were from Latin America. Overall, 304 (45·7%) of our patients presented with one or more mucocutaneous manifestations. Oral cavity findings were seen in 78 cases (25·7%), including transient lingual papillitis (11·5%), glossitis with lateral indentations (6·6%) (Figure 1a), aphthous stomatitis (6·9%), glossitis with patchy depapillation (3·9%) (Figure 1b) and mucositis (3·9%).…

Dear Editor, Coronavirus disease 2019 (COVID‐19) is already well known globally.1 Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection causes a spectrum of severe clinical manifestations, which lead to a high rate of intensive care unit admissions and mortality. We report a first case of COVID‐19 with reactivation of the human herpesvirus (HHV) alpha subfamily – herpes simplex virus (HSV)‐1 and varicella zoster virus (VZV). Due to the immunosuppressive state associated with COVID‐19, infection with the HHV alpha subfamily could be potentially life‐threatening. A 73‐year‐old man, with respiratory symptoms and positive nucleic acid test of throat swab specimens, was diagnosed with SARS‐CoV‐2 infection on 2 February 2020. As the respiratory symptoms deteriorated, he was admitted to intensive care. Due to the rapid aggravation of respiratory distress, onset of septic shock, and progression of chest imaging, the application of venovenous extracorporeal membrane oxygenation for respiratory support was performed on 15 February. After comprehensive treatment and assisted…

BACKGROUND: Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T-cell (CTCL) and B-cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in Europe and about potential changes over time. OBJECTIVES: The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients. METHODS: Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included. RESULTS: The calculated incidence was unprecedently high at 1·06 per 100 000 person-years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal-zone CBCL increased over time. CONCLUSIONS: Changes in PCL…

BACKGROUND: The rapid expansion of psoriasis biologics has led to an urgent need to understand their relative efficacy and tolerability to inform treatment decisions better and, specifically, to inform guideline development. OBJECTIVES: To update a 2017 meta-analysis on the comparative efficacy and tolerability of biologic treatments for psoriasis. METHODS: We searched the MEDLINE, PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs), published up to 7 September 2018, of 11 licensed, NICE-approved biologics targeting tumour necrosis factor (adalimumab, etanercept, infliximab, certolizumab pegol), interleukin (IL)-12/IL-23p40 (ustekinumab), IL-17A (secukinumab, ixekizumab), IL-17RA (brodalumab) and IL-23p19 (guselkumab, tildrakizumab, risankizumab). A frequentist network meta-analysis ascertained direct or indirect evidence comparing biologics with one another, methotrexate or placebo. This was combined with hierarchical cluster analyses to consider efficacy (≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) or Physician's Global Assessment 0…

Dear Editor, Artificial intelligence (AI) has emerged as a hot topic within dermatology, and during recent years several studies have demonstrated its benefits in a research setting. While this development is unravelling rapidly and has also been made available to consumers, little is known about the attitudes towards AI among dermatologists. To increase our understanding of dermatologists’ attitudes towards AI within dermatology we prepared an anonymous and voluntary online survey including 29 questions. The survey was distributed to dermatologists through several online channels, including mailing lists, to members of the International Dermoscopy Society. The survey was set up using SurveyMonkey® (SurveyMonkey, San Mateo, CA, U.S.A.) and was open from January to June 2019. The complete survey text and aggregated survey responses are available online.1,2 Linear regression models were used to correlate answers to sex and age group using a score for the answers. All tests were two sided and P‐values < 0·05 were considered statistically significant. In total, 1271 surveys were…

Children aged ≥ 6 to < 12 years with severe atopic dermatitis (AD) have limited treatment options. In a 16‐week, randomized, placebo‐controlled, phase III trial in children, dupilumab, a monoclonal antibody inhibiting interleukin (IL)‐4/IL‐13 signalling, significantly improved signs and symptoms with acceptable safety; longer‐term safety and efficacy data are lacking. To report the pharmacokinetic profile and long‐term safety and efficacy of dupilumab in children (aged ≥ 6 to < 12 years) with severe AD. Children (aged ≥ 6 to < 12 years) with severe AD were enrolled in a global, multicentre, phase IIa, open‐label, ascending‐dose, sequential cohort study and subsequent open‐label extension (OLE) study. Patients received single‐dose dupilumab 2 or 4 mg kg−1 followed by 8‐week pharmacokinetic sampling, then 2 or 4 mg kg−1 weekly for 4 weeks (phase IIa), followed by the same weekly regimen (OLE). Primary endpoints were dupilumab concentration–time profile and treatment‐emergent adverse events (TEAEs); secondary assessments included Eczema Area and Severity Index (EASI) and Peak Pruritus…

BACKGROUND: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF). OBJECTIVES: To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB) staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures. METHODS: In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review. RESULTS: The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smaller percentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA-IB vs. IIA, P < 0·001), presence of…

Dear Editor, A previously healthy 57‐year‐old woman presented with fever (39 °C) lasting for 4 days, and dry cough and rash appeared 2 days before. Diffuse fixed erythematous blanching maculopapular lesions were present, asymptomatic over the limbs and trunk, with burning sensation over the palms (a, b). She denied any drug intake, excepting paracetamol for fever. Thorax computed tomography scan was typical of COVID‐19; nasopharyngeal swab polymerase chain reaction (PCR) confirmed SARS‐CoV‐2. Infectious enquiry was otherwise negative. Skin biopsy specimen showed slight spongiosis, basal cell vacuolation and mild perivascular lymphocytic infiltrate (c). PCR on whole‐skin biopsy specimen was negative for SARS‐CoV‐2. Fever and rash resolved within 9 days, dry cough within 2 weeks. Urticarial and chilblain‐like lesions have been reported in patients with COVID‐19, but other phenotypes could be observed.1,2 In our patient an immune reaction to the virus is possible. Funding sources: none. Conflicts of interest: the authors declare they have no conflicts of interest.

BACKGROUND: Limited options are available for treatment of paediatric psoriasis. OBJECTIVES: To evaluate the efficacy and safety of ustekinumab in paediatric patients with psoriasis (≥ 6 to < 12 years of age). METHODS: ; ≥ 60 to ≤ 100 kg: 45 mg; > 100 kg: 90 mg) administered by subcutaneous injection at weeks 0 and 4, then every 12 weeks through week 40. Study endpoints (all at week 12) included the proportions of patients achieving a Physician's Global Assessment score of cleared/minimal (PGA 0/1) and ≥ 75%/90% improvement in Psoriasis Area and Severity Index (PASI 75/90), and change in Children's Dermatology Life Quality Index (CDLQI). Serum ustekinumab concentrations, antidrug antibodies and cytokine levels were measured through week 52. Safety was evaluated through week 56. RESULTS: In total, 44 patients (median age 9·5 years) received at least one dose of ustekinumab. Three patients discontinued the study agent through week 40. At week 12, 77% of patients achieved PGA 0/1, 84% achieved PASI 75 and 64% achieved PASI 90 response. The mean change in CDLQI was -6·3. Trough serum…

Tape strips have been used widely in dermatology research as a minimally invasive method to sample the epidermis, avoiding the need for skin biopsies. Most research has focused on epidermal pathology, such as atopic eczema, but there is increasing research into the use of tape strips in other dermatoses, such as skin cancer, and the microbiome. This review summarizes the technique of tape stripping, and discusses which dermatoses have been studied by tape stripping and alternative minimally invasive sampling methods. We review the number of tape strips needed from each patient and the components of the epidermis that can be obtained by tape stripping. With a focus on protein and RNA extraction, we address the techniques used to process tape strips. There is no optimal protocol to extract protein, as this depends on the abundance of the protein studied, its level of expression in the epidermis and its solubility. Many variables can alter the amount of protein obtained from tape strips, which must be standardized to ensure consistency between samples. No study has compared different…

BACKGROUND: Acral lesions, mainly chilblains, are the most frequently reported cutaneous lesions associated with COVID-19. In more than 80% of patients tested, nasopharyngeal swabs were negative on reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 when performed, and serology was generally not performed. METHODS: A national survey was launched on 30 March 2020 by the French Society of Dermatology asking physicians to report cases of skin manifestations in patients with suspected or confirmed COVID-19 by using a standardized questionnaire. We report the results for acral manifestations. RESULTS: We collected 311 cases of acral manifestations [58.5% women, median age 25.7 years (range 18-39)]. The most frequent clinical presentation (65%) was typical chilblains. In total, 93 cases (30%) showed clinical suspicion of COVID-19, 67 (22%) had only less specific infectious symptoms and 151 (49%) had no clinical signs preceding or during the course of acral lesions. Histology of skin biopsies was consistent with chilblains. Overall, 12 patients showed significant…

BACKGROUND: The number of qualitative studies on eczema has increased rapidly in recent years. Systematically reviewing these can provide greater understandings of people's perceptions of eczema and eczema treatments. OBJECTIVES: We sought to systematically review and thematically synthesize qualitative studies exploring views and experiences of people with eczema and parents/carers of children with eczema. METHODS: We searched MEDLINE, EMBASE, PsycINFO and CINAHL from the earliest date available to February 2019. We selected papers focusing on views and experiences of eczema and eczema treatments, and barriers/facilitators to eczema self-management. We excluded papers focusing on health service provision models or health professionals' views. RESULTS: We synthesized 39 papers (reporting 32 studies) from 13 countries. We developed four analytical themes: (1) Eczema not viewed as a long-term condition; (2) Significant psychosocial impact not acknowledged by others; (3) Hesitancy (patient/carer uncertainty) about eczema treatments; and (4) Insufficient information and advice. Our…

BACKGROUND: Dermatophytic infections have undergone unprecedented changes in India in the recent past. Clinical trials to find out the effectiveness of the four main oral antifungal drugs are lacking. OBJECTIVES: We tested the effectiveness of oral fluconazole, griseofulvin, itraconazole and terbinafine in chronic and chronic relapsing tinea corporis, tinea cruris and tinea faciei in an investigator-initiated, randomized, pragmatic trial. METHODS: per day. Allocation was performed by concealed block randomization and the patients were treated for 8 weeks or until cure. Effectiveness was calculated based on intention-to-treat analysis. The trial was registered with the Clinical Trials Registry India (CTRI/2017/04/008281). RESULTS: At 4 weeks, all drugs were similarly ineffective, with cure rates being 8% or less (P = 0·42). At 8 weeks, the numbers of patients cured were as follows: fluconazole 21 (42%), griseofulvin seven (14%), itraconazole 33 (66%) and terbinafine 14 (28%) (P < 0·001). Itraconazole was superior to fluconazole, griseofulvin and terbinafine (adjusted P ≤ 0·048).…

Individual studies have suggested that the association between occupational exposure to solar ultraviolet radiation (UVR) and the development of keratinocyte cancers (KCs) may only be valid in populations of European ancestry living in certain geographical regions. Comparative global data are scarce and so this review aimed to summarize current evidence on the association between occupational exposure to solar UVR and the development of KCs, with a specific focus on geographical location and skin colour. Ovid MEDLINE, PubMed, Embase and Web of Science were searched for potentially relevant records. Extracted data were summarized by study, country and region. We included one prospective cohort study and 18 case-control studies (n = 15 233) from 12 countries in regions where the majority of the population is white skinned (Americas, Europe and Oceania). Eighteen of the 19 studies reported effect estimates suggesting an increased risk of basal cell carcinoma (BCC) and/or squamous cell carcinoma (SCC) among outdoor workers. Only 11 studies found a significantly increased risk and many…

Epidermolysis bullosa (EB) is a highly diverse group of inherited skin disorders, resulting from mutations in genes encoding proteins of the dermoepidermal junction. Itch (pruritus) is one of the most common symptoms across all EB subtypes. It occurs in blistered or wounded sites, or manifests as a generalized phenomenon, thereby affecting both intact skin and healing wounds. The mechanism of pruritus in EB is unclear. It is likely that skin inflammation secondary to barrier disruption, wound healing cascades and dysregulated activation of epidermal sensory nerve endings are all involved in its pathophysiology on the molecular and cellular level. Understanding these mechanisms in depth is crucial in developing optimized treatments for people with EB and improving quality of life. This review summarizes current evidence on the prevalence, mechanisms and management of itch in EB.

BACKGROUND: Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A, a cornerstone cytokine in psoriasis, has shown long-lasting efficacy and safety in the complete spectrum of psoriasis manifestations. OBJECTIVES: To report the long-term (2·5-year) efficacy and safety of secukinumab in nail psoriasis. METHODS: TRANSFIGURE, a double-blind, randomized, placebo-controlled, parallel-group, multicentre phase IIIb study in 198 patients, investigated secukinumab 150 mg and 300 mg in patients with moderate-to-severe nail psoriasis. RESULTS: At week 16, the primary endpoint Nail Psoriasis Severity Index (NAPSI) was met, demonstrating superiority of secukinumab to placebo. The effect was sustained over 2·5 years with a large benefit for nail clearance, with mean NAPSI improvement of -73·3% and -63·6% with secukinumab 300 mg and 150 mg, respectively. At 2·5 years, secukinumab demonstrated sustained clinically significant reductions in total mean Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) quality-of-life (QoL) scores of -52·4% and -18·1%,…

BACKGROUND: Frontal fibrosing alopecia (FFA) is a scarring alopecia with unclear pathogenesis and a progressive course. The disease has a major impact on patients' quality of life and there is a lack of effective treatment to halt disease progression. METHODS: We profiled lesional and nonlesional scalp biopsies collected in 2017 from patients with FFA (n = 12) compared with scalp biopsies from patients with alopecia areata (AA) (n = 8) and controls (n = 8) to evaluate gene and protein expression, including the primary outcome (CXCL9). We determined significant differences between biomarkers using a two-sided Student's t-test adjusting P-values by false discovery rate. RESULTS: Significant increases were seen in CD8+ cytotoxic T cells, CD11c+ dendritic cells, CD103+ and CD69+ tissue-resident memory T cells in FFA and AA vs. control scalp (P < 0·05), with corresponding significantly upregulated granzyme B mRNA, particularly in FFA (P < 0·01). In AA, cellular infiltrates were primarily concentrated at the bulb, while in FFA these were mainly localized at the bulge. FFA demonstrated…