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The management of actinic keratoses and the field of cancerization constitutes a true therapeutic challenge. Tirbanibulin 1% ointment is a promising new drug for use in special locations or patients who are refractory or reluctant to other more aggressive treatments.

Background: Large prospective studies on the safety of Mohs micrographic (MMS) surgery are scarce, and most focus on a single type of surgical adverse event. Mid-term scar alterations and functional loss have not been described. Objectives: To describe the risk of MMS complications and the risk factors for them. Methods: A nationwide prospective cohort collected all adverse events on consecutive patients in 22 specialised centres. We used multilevel mixed-effects logistic regression to find out factors associated with adverse events. Results: 5,017 patients were included, with 14,421 patient-years of follow-up. 7.0% had some perioperative morbidity and 6.5% had mid-term and scar-related complications. The overall risk of complications was mainly associated with use of antiaggregant/anticoagulant and larger tumours, affecting deeper structures, not reaching a tumour-free border, and requiring complex repair. Age and outpatient setting were not linked to the incidence of adverse events. Risk factors for haemorrhage (0.9%) were therapy with antiaggregant/anticoagulants, tumour size, duration of surgery, and unfinished surgery. Wound necrosis (1.9%) and dehiscence (1.0%) were associated with larger defects and complex closures. Immunosuppression was only associated with an increased risk of necrosis. Surgeries reaching deeper structures, larger tumours and previous surgical treatments were associated with wound infection (0.9%). Aesthetic scar alterations (5.4%) were more common in younger patients, with larger tumours, in H-area, and in flap and complex closures. Risk factors for functional scar alterations (1.7%) were the need for general anaesthesia, larger tumours that had received previous surgery, and flaps or complex closures. Conclusions: MMS shows a low risk of complications. Most of the risk factors for complications were related to tumour size and depth, and the resulting need for complex surgery. Antiaggregant/anticoagulant intake was associated with a small increase in the risk of haemorrhage, that probably does not justify withdrawal. Age and outpatient setting were not linked to the risk of adverse events.

[EN] Three-dimensional (3D) wound measurement lacks a gold standard to test accuracy. It is useful to develop procedures to scan wounds and reconstruct their 3D model with low-cost techniques. We present a new procedure (Structure from Motion [SfM]-3DULC) that uses photographs for measuring nine wound variables. We also propose a new variant of ImageJ in which an orthophoto is used to measure the projected area (Ortho-ImageJ). In addition, we compare the wound measurements made by dermatologists and non-experts. A group of five experts in dermatology and five non-specialists measured 33 leg wounds five times per procedure. Intra-rater and inter-rater reliability scores of SfM-3DULC were evaluated with the intraclass correlation coefficient (ICC 2,1). The accuracy of the two new procedures (SfM-3DULC and Ortho-ImageJ) in the measurement of projected area was assessed by comparing their values with those obtained using ImageJ, with the Wilcoxon matched-pairs signed rank test (alpha = 0.05). This test was also used to analyse the differences between the measurements made by dermatologists and non-experts. All the variables measured by dermatologists using SfM-3DULC showed excellent scores of intra-rater reliability (ICC > 0.99) and inter-rater reliability (ICC > 0.98). No significant differences between the three procedures were found when comparing their projected area values. Significant differences between the measurements of dermatologists and non-experts were found in most of the variables: circularity coefficient, perimeter, projected area, surface area, and reference surface area. The wound measurement procedure SfM-3DULC has an excellent reliability, is accurate for the measurement of projected area, and can be used by dermatologists for wound monitoring in everyday clinical practice., The authors thank Mr. Ramon Dura Mora and the Unidad de Enfermeria, ulceras y Heridas complejas La Fe. This work is part of the Ph.D. research of D.S-J., which is supported by a grant from Generalitat Valenciana-Conselleria de Educacion, Investigacion, Cultura y Deporte, and the European Social Fund (ACIF/2018/160).

Resumen: Sonidegib es un inhibidor del receptor transmembrana Smoothened (SMO), de la vía de señalización de Hedgehog, indicado para el tratamiento del carcinoma basocelular localmente avanzado (CBCla), no susceptible a cirugía curativa ni a radioterapia. Sonidegib ha demostrado su eficacia y seguridad en pacientes con CBCla en el ensayo de fase II (BOLT), donde el 61% (IC 95%: 48; 72) de los pacientes tratados con 200 mg de sonidegib tuvo una respuesta objetiva al tratamiento, con un tiempo medio hasta la respuesta de cuatro meses. La mediana de duración de respuesta fue de 26,1 meses y la mediana de supervivencia libre de progresión fue de 22,1 meses. Los eventos adversos más frecuentes fueron los espasmos musculares (54,4%), alopecia (49,4%) y disgeusia (44,3%), siendo principalmente de grado 1 y 2. Esta revisión proporciona un resumen sobre la eficacia, seguridad y tolerabilidad de sonidegib, así como consideraciones sobre su uso en el manejo de pacientes con CBCla. Abstract: Sonidegib is an antagonist of the transmembrane protein Smoothened in the Hedgehog signaling pathway. It is indicated for the treatment of locally advanced basal cell carcinoma (BCC) that is not amenable to curative surgery or radiotherapy. Sonidegib's efficacy and safety were demonstrated in the phase 2 BOLT trial, where 61% (95% CI, 48-72%) of patients with locally advanced BCC treated with sonidegib 200 mg achieved an objective response to treatment with a mean time to response of 4 months. The median duration of response was 26.1 months and the median progression-free survival was 22.1 months. The most common adverse events were muscle spasms (54.4%), hair loss (49.4%), and loss of taste (44.3%); most events were grade 1 or 2. In this review, we summarize the main findings on the efficacy, safety, and tolerability of sonidegib and discuss the management of locally advanced BCC with this drug.

Sonidegib is an antagonist of the transmembrane protein Smoothened in the Hedgehog signaling pathway. It is indicated for the treatment of locally advanced basal cell carcinoma (BCC) that is not amenable to curative surgery or radiotherapy. Sonidegib's efficacy and safety were demonstrated in the phase 2 BOLT trial, where 61% (95% CI, 48-72%) of patients with locally advanced BCC treated with sonidegib 200 mg achieved an objective response to treatment with a mean time to response of 4 months. The median duration of response was 26.1 months and the median progression-free survival was 22.1 months. The most common adverse events were muscle spasms (54.4%), hair loss (49.4%), and loss of taste (44.3%); most events were grade 1 or 2. In this review, we summarize the main findings on the efficacy, safety, and tolerability of sonidegib and discuss the management of locally advanced BCC with this drug.

Resumen: El diagnóstico y tratamiento del melanoma en atención especializada es un campo en el que se han producido numerosos cambios. El objetivo de esta guía es ofrecer a los dermatólogos españoles una referencia para resolver las dudas clínicas más frecuentes basándose en la evidencia actual. Para la realización de esta guía se escogió a miembros del Grupo Español de Dermato-Oncología y Cirugía con experiencia en el tratamiento de estos tumores y con interés en participar en la elaboración de la guía. Se hizo una adaptación de las guías de práctica clínica existentes mediante el método ADAPTE: inicialmente se resumió el proceso de atención y se elaboraron las preguntas clínicas relevantes. Se seleccionaron las guías mejor puntuadas mediante el instrumento AGREE II, realizando la búsqueda de las respuestas en dichas guías y elaborando las recomendaciones. Finalmente se sometió la guía a revisión externa. La guía se estructuró a partir de 21 preguntas clínicas que fueron seleccionadas por su relevancia, dado que se centran en aspectos que pueden plantear decisiones difíciles en el manejo del melanoma, y se han respondido empleando la evidencia obtenida de las mejores guías existentes. Entre las limitaciones de esta guía merece reseñarse que la evidencia es escasa para responder a algunas preguntas. En algunos aspectos el cambio es rápido y exige una actualización frecuente de la guía. Esta guía responde a preguntas habituales sobre el manejo del melanoma en la práctica clínica diaria, sirviendo a los dermatólogos como referencia en la toma de decisiones, siempre teniendo presente los recursos y preferencias del paciente. Abstract: Specialist approaches to the diagnosis and treatment of melanoma have undergone many changes. This guideline aims to provide Spanish dermatologists with evidence-based information for resolving the most common doubts that arise in clinical practice. Members of the Spanish Oncologic Dermatology and Surgery Group (GEDOC) with experience treating melanoma were invited to participate in drafting the guideline. The group developed a new guideline on the basis of existing ones, using the ADAPTE collaboration process, first summarizing the care process and posing relevant clinical questions, then selecting guidelines with the best scores according to the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. Finally, the group searched the selected guidelines for answers to the clinical questions, drafted recommendations, and sent them for external review. The guideline is structured around 21 clinical questions chosen for their relevance to issues that make clinical decisions about the management of melanoma difficult. Evidence from existing guidelines was used to answer the questions. A limitation of this guide derives from the scarce evidence available for answering some questions. Moreover, some areas are changing rapidly, so recommendations must be updated often. The present guideline offers answers to clinical questions about the routine management of melanoma in clinical practice and provides dermatologists with a reference to guide decisions, taking into consideration the resources available and patient preferences.

Several studies have focused on identifying microRNAs involved in the pathogenesis of melanoma. However, its association with clinicopathological features has been scarcely addressed. The aim of this study is to identify microRNAs expression profiles related to aggressive clinicopathological and molecular features, and to analyze the association with melanoma survival. A retrospective and observational study was performed in a series of 179 formalin-fixed paraffin embedded primary cutaneous melanomas. First, a screening analysis on a discovery set (n = 22) using miRNA gene chip array (Affymetrix, Santa Clara, California, USA) was performed. Differentially expressed microRNAs were detected employing the software Partek Genomic Suite. Validation of four microRNAs was subsequently performed in the entire series (n = 179) by quantitative real time PCR (qRT-PCR). MicroRNAs expression screening analysis identified 101 microRNAs differentially expressed according to Breslow thickness (=1 mm vs. >1 mm), 79 according to the presence or absence of ulceration, 78 according to mitosis/mm2 (

Severe cutaneous adverse reactions (SCARs) [Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic syndrome (DRESS), acute generalized exanthematous pustulosis (AGEP), and generalized bullous fixed eruption (GBFE)] are severe drug reactions that often require hospitalization and could be fatal. BRAF and MEK inhibitors (BRAF/MEKi) are a standard of care in patients with BRAF-mutated metastatic melanomas. These agents are administered until disease progression or unacceptable toxicity occurs. This review has focus on BRAF/MEKi-induced SCARs. A systematic search of the following terms: 'vemurafenib', 'cobimetinib', 'dabrafenib', 'trametinib', 'encorafenib', 'binimetinib', 'Acute Generalized Exanthematous Pustulosis', 'Stevens Johnson syndrome', 'Toxic Epidermal Necrolysis', 'Generalized Bullous Fixed Eruption' 'Drug Hypersensitivity Syndrome', and 'DRESS' in simple combination (every drug with each disease) and all in combination, was performed on MEDLINE, EMBASE, Web of Knowledge and The Cochrane Library repositories, with no restriction on language, for original studies. One hundred sixty-eight original articles were found, 26 (retrospective series, case reports and conference abstracts) were selected, and 21 were included in the qualitative synthesis. A total of 31 SCAR cases (23 DRESS and 8 SJS/TEN - 1 SJS and 7 TEN -) were identified. Vemurafenib was the culprit drug in all but one case, which was dabrafenib-induced. Mean time to SCAR onset from drug intake was 15.5 and 11.4 days, for SJS/TEN and DRESS, respectively. For the DRESS cases, hepatic involvement occurred in 96% and renal alterations in 87% of patients. Overall, BRAF/MEKi-induced SCARs are rare. Among them, vemurafenib is the drug that requires more close monitoring for SCARs. Prior immunotherapy can favour SCARs. Vemurafenib DRESS is likely to occur within the first fifteen days of treatment accompanied by hepatic and renal involvement. Following vemurafenib-induced SCAR resolution, switching to dabrafenib seems to be a safe alternative for these patients' treatment.

Epidermal necrolysis (EN) compromises a spectrum of life-threatening dermatoses (Stevens-Johnson Syndrome [SJS], overlap syndrome and toxic epidermal necrolysis [TEN]). Currently, no active therapeutic regimen with unequivocal benefit exists for SJS/TEN. SCORTEN is the widely-used prognostic scale specific for SJS/TEN. Nevertheless, a new prognostic scale, the ABCD-10, has been recently proposed. In this context, acute renal failure (ARF) seems to be an important comorbidity that could influence prognosis in SJS/TEN patients more than it is assumed by these two scales. Our objectives were to compare the accuracy of the SCORTEN and ABCD-10 scales in predicting the mortality in SJS/TEN, and to investigate the influence of renal failure on prognosis. The prognostic results of 18 patients with EN treated in two referral centers between 2013 and 2018 are presented. SCORTEN, ABCD-10 and renal function values were retrospectively collected for all patients. Out of the 18 patients who were analyzed, nine (50%) received only supportive therapy, four were treated with etanercept 50 mg in a single dose (22.2%) and five with corticosteroids (27.8%). Five patients developed ARF. Predicted mortality was 3.48 for SCORTEN and 2.33 for ABCD-10. Eventually, four patients died (22.2%), all had ARF and none of them received active treatment. Despite study limitations and in the absence of active treatment of choice, SCORTEN behaved as a reliable predictor of mortality in patients with EN, outperforming the newer ABCD-10. ARF was an early event associated with a poor prognosis, which could represent a prognostic marker to consider in the future.

Treatment with hyaluronic acid (HA) fillers as a strategy for rejuvenation has experienced a significant growth in recent years, accompanied by a parallel increase in its complications, the treatment of which, such as hyaluronidase, we must be aware of.14 patients (28 eyes) had indication for upper blepharoplasty surgery in the Hospital Universitario y Politécnico La Fe. After surgery, periocular skin of one eye of each patient was infiltrated with 300 U of hyaluronidase (14 cases) while the skin of the fellow eye was preserved untreated (14 controls). All samples were studied by the Pathology department, and finally, 6 variables (skin structure alteration, degeneration of elastic fibers, deposits, collagen fibers destructuring, inflammation, and other findings) were analyzed.No differences in skin structure, elastic fibers, and collagen dermal fibers were found between hyaluronidase-treated skin and controls. A significant association between ex vivo application of hyaluronidase in periocular skin and the presence of amorphous extracellular deposits within the dermis was found.Hyaluronidase applied ex vivo to periocular skin led to presence of deposits within the extracellular matrix compared to control eyelid skin but elastin and collagen dermis structure remained unaltered.

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Background/Objectives Primary cutaneous lymphomas are rare in pediatric patients. The clinical and histopathological manifestations may differ from those in adults. Due to their low frequency and the insidious clinical picture, the diagnosis is usually delayed. The Spanish Primary Cutaneous Lymphoma Registry was initiated in 2016 as a multicenter registry that would allow better insight into the epidemiological, clinical, histopathological, and treatment response characteristics of patients with primary cutaneous lymphomas. Methods We conducted a prospective observational cohort study of primary cutaneous lymphomas in pediatric patients participating in the Spanish Academy of Dermatology and Venereology (AEDV) Primary Cutaneous Lymphoma Registry. Results At the time of the analysis, 10 patients under 18 years of age out of 799 all-age cases (1.25%) had been included in the registry (7 males, 3 females). The mean age at diagnosis was 9.7 years (SD: 4.8). Seven (70%) had mycosis fungoides, 2 of them had the folliculotropic variant; and 3 (30%) had primary cutaneous marginal zone B-cell lymphoma. Conclusions Primary cutaneous lymphomas are extremely rare in pediatric patients and usually have a good prognosis. Therefore, a high level of suspicion is necessary for the diagnosis. We suggest management by experienced physicians and follow-up into adulthood.

BACKGROUND The SCORTEN score is a specific predictor of the probability of death for patients diagnosed with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). OBJECTIVES To evaluate the overall accuracy of SCORTEN and the influence of several moderators such as age, sex, geographical region and age of the study. METHODS A systematic search was performed on MEDLINE, The Cochrane Library, EMBASE, SCOPUS and Web of Knowledge, with no restriction on language (last update 5 February 2019 for all databases). Original studies on the use of SCORTEN were eligible. The standardized mortality ratio (SMR), defined as the quotient between the number of deaths observed and the number expected following SCORTEN, was taken as the measurement of analysis. RESULTS Sixty-four papers were part of the main meta-analysis carried out in the study. A pooled log(SMR) of -0.0889 (95% CI: -0.2023 to 0.0245) was obtained, suggesting a reasonable behaviour of SCORTEN as a predictor of mortality. The possible influence of several factors in the accuracy of SCORTEN was studied by means of meta-regression models. Multivariate meta-regression allowed finding that the mean age of the patients and the ending year of the study are the only factors that significantly influence SCORTEN predictions. The mean age of the group of patients was associated with a significant increase in the observed/expected ratio, whereas a progressive reduction in the observed/expected ratio can be appreciated over the years. Finally, an underestimation of mortality was found for SCORTEN values of 3 or less and the opposite for those above 3 (SCORTEN range: 0-7). CONCLUSIONS The rarity of the disease and the heterogeneity of the studies included are major limitations. Despite the overall remarkable accuracy displayed by SCORTEN, the influence of several factors, as comorbidities (e.g. renal impairment), involved body surface area and patient's age, seem of enough relevance to consider a redefinition of the scale.

Characterization of patients, surgery procedures and the risk factors for dermatofibrosarcoma protuberans (DFSP) recurrences is poorly defined. In this study, we aimed to describe the demographics, tumor characteristics and interventions of DFSP treated with Mohs micrographic surgery (MSS) to determine the rate and risk factors for recurrence. Data were collected from REGESMOHS, a nationwide prospective cohort study of patients treated with MMS in Spain. From July 2013 to February 2020, 163 patients with DFSP who underwent MMS were included. DFSP was mostly located on trunk and extremities. Recurrent tumors had deeper tumor invasion and required higher number of MMS stages. Paraffin MMS was the most frequently used technique. Overall recurrence rate was 0.97 cases/100 person-years (95% IC = 0.36-2.57). No differences were found in epidemiological, tumor, surgery characteristics or surgical technique (frozen or paraffin MMS [p = 0.6641]) in terms of recurrence. Median follow-up time was 28.6 months with 414 patient-years of follow-up. In conclusion, we found an overall low recurrence rate of DFSP treated with MMS. None of the studied risk factors, including MMS techniques, was associated with higher risk for recurrence.

Biological drugs targeting tumour necrosis factor are effective for psoriasis. However, 30–50% of patients do not respond to these drugs and may even develop paradoxical psoriasiform reactions. This study search-ed for DNA copy number variations that could predict anti-tumour necrotic factor drug response or the ap-pearance of anti-tumour necrotic factor induced pso-riasiform reactions. Peripheral blood samples were collected from 70 patients with anti-tumour necrotic factor drug-treated moderate-to-severe plaque pso-riasis. Samples were analysed with an Illumina 450K methylation microarray. Copy number variations were obtained from raw methylation data using conumee and Chip Analysis Methylation Pipeline (ChAMP) R packa-ges. One copy number variation was found, harbouring one gene (CPM) that was significantly associated with adalimumab response (Bonferroni-adjusted p-value < 0.05). Moreover, one copy number variation was identified harbouring 3 genes (ARNT2, LOC101929586 and MIR5572) related to the development of paradoxical psoriasiform reactions. In conclusion, this study has identified DNA copy number variations that could be good candidate markers to predict response to ada-limumab and the development of anti-tumour necrotic factor paradoxical psoriasiform reactions., This study was supported by Instituto de Salud Carlos III PI 13/01598 and the Ministry of Science and Innovation and the European Regional Development’s funds (FEDER).

While some papers report an increased risk of COVID-19 and worse outcomes1 in oncological patients, others have found no differences2 . We are not aware of studies assessing risk for COVID-19 and clinical outcomes of patients with Primary Cutaneous Lymphomas (PCL).

Importance A novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been identified as the cause of a pandemic called coronavirus disease 2019 (COVID-19). In this context, some associated skin diseases have been described. Cutaneous lesions referred to as acute acro-ischemia have been reported as a possible sign of COVID-19 in adolescents and children. Objective To evaluate the pathogenesis of these newly described acute acral lesions. Design, Setting, and Participants This prospective case series was conducted at La Fe University Hospital, a tertiary referral hospital in Valencia, Spain, between April 9 and April 15, 2020. Among 32 referred patients, 20 children and adolescents with new-onset inflammatory lesions did not have a diagnosis. Exposures Patients were not exposed to any drug or other intervention. Main Outcomes and Measures We performed reverse transcriptase-polymerase chain reaction for SARS-CoV-2 and a range of blood tests for possible origins of the lesions. Skin biopsies were performed in 6 patients. Results Of the 20 patients enrolled, 7 were female and 13 were male, with an age range of 1 to 18 years. Clinical findings fit into the following patterns: acral erythema (6 patients), dactylitis (4 patients), purpuric maculopapules (7 patients), and a mixed pattern (3 patients). None of the patients had remarkable hematologic or serologic abnormalities, including negative antibodies to SARS-CoV-2. Biopsies performed in 6 patients showed histologic findings characteristic of perniosis. Conclusions and Relevance The clinical, histologic, and laboratory test results were compatible with a diagnosis of perniosis, and no evidence was found to support the implication of SARS-CoV-2 infection. This case series describes 20 children and adolescents who presented with new-onset acral inflammatory lesions during the COVID-19 pandemic. Question What is the association between acute acral lesions and coronavirus disease 2019 (COVID-19) in children and adolescents? Findings In this case series of 20 patients aged 1 to 18 years with new-onset acral inflammatory lesions, all lacked systemic manifestations of COVID-19. Both reverse transcriptase-polymerase chain reaction and serologic test results were negative for severe acute respiratory syndrome coronavirus 2. Meaning An association between acral skin disease and COVID-19 has yet to be proved.

We read with interest the article by Recalcati et al. about the report of cutaneous manifestations in COVID‐19 patients. We would like to highlight that some potentially severe manifestations in these patients are not directly related to the coronavirus but to the medications administered.

Recent publication of the results of clinical trials in which lymph node dissection was not associated with any survival benefit in patients with sentinel node metastasis makes it necessary to reconsider the treatment of patients with melanoma. This article provides an update on the available evidence on the diverse factors (routes of metastatic spread, predictors, adjuvant therapy, etc.) that must be considered when treating patients with sentinel node-positive melanoma. The authors propose a decision-making algorithm for use in this clinical setting. The current evidence no longer supports lymph node dissection in patients with low-risk sentinel node metastasis (sentinel node tumor load ≤ 1 mm).

Background The SCORTEN score is a specific predictor of mortality for patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). There is little evidence in support of the common immunomodulating therapies for SJS/TEN. Objectives To systematically assess the effectiveness of several therapies for SJS/TEN through the SCORTEN score. Methods Databases were searched for original studies on the use of SCORTEN. Six meta-analyses were carried out on patients with SJS/TEN who received supportive care only or in combination with immunomodulating drugs: corticosteroids, cyclosporine, etanercept, immunoglobulins or a combination of corticosteroids with immunoglobulins. A multivariate meta-regression and a network meta-analysis were also performed. Results Of 3893 studies identified, fifty-two involving 2466 patients with SJS/TEN were preselected. Data from thirty-eight of these studies (1827 patients) were finally pooled, and results [log(SMR)] from meta-analyses were as follows: -0.13 (95% CI, -0.42,0.16) for corticosteroids, -0.39 (95% CI, -0.87,0.09) for immunoglobulins, 0.13 (95% CI, -0.15,0.40) for supportive treatment, -0.88 (95% CI, -1.47, -0.29) for cyclosporine, -0.95 (95% CI, -1.82, -0.07) for etanercept and - 0.56 (95% CI, -0.94, -0.19) for immunoglobulins plus corticosteroids. The meta-regression analysis confirmed that cyclosporine and immunoglobulins plus corticosteroids were associated with less deaths than predicted by SCORTEN. In the network meta-analysis, no treatment achieved a significant reduction in the SMR. Limitations Heterogeneity and quality of the included studies. Conclusions Some treatments for SJS/TEN show a better performance, but there is not sufficient evidence to recommend its widespread use in all patients.