Comparative response to PDT with methyl-aminolevulinate and temoporfin in cutaneous and oral squamous cell carcinoma cells.

Cutaneous and Head and Neck squamous cell carcinoma (CSCC, HNSCC) are among the most prevalent cancers. Both types of cancer can be treated with photodynamic therapy (PDT) by using the photosensitizer Temoporfin in HNSCC and the prodrug methyl-aminolevulinate (MAL) in CSCC. However, PDT is not always effective. Therefore, it is mandatory to correctly approach the therapy according to the characteristics of the tumour cells. For this reason, we have used cell lines of CSCC (A431 and SCC13) and HNSCC (HN5 and SCC9). The results obtained indicated that the better response to MAL-PDT was related to its localization in the plasma membrane (A431 and HN5 cells). However, with Temoporfin all cell lines showed lysosome localization, even the most sensitive ones (HN5). The expression of mesenchymal markers and migratory capacity was greater in HNSCC lines compared to CSCC, but no correlation with PDT response was observed. The translocation to the nucleus of ß-catenin and GSK3ß and the activation of NF-κß is related to the poor response to PDT in the HNSCC lines. Therefore, we propose that intracellular localization of GSK3ß could be a good marker of response to PDT in HNSCC. Although the molecular mechanism of response to PDT needs further elucidation, this work shows that the most MAL-resistant line of CSCC is more sensitive to Temoporfin.

Nonvenereal Infections in Spanish Dermatology Clinics: Results of the DIADERM Study. / Enfermedades infecciosas no venéreas atendidas en consultas de Dermatología en España: resultados del estudio DIADERM.

BACKGROUND AND OBJECTIVE: The burden of nonvenereal infections in Spanish dermatology practice has not yet been evaluated. The aim of this study was to analyze the overall weight of these infections in outpatient dermatology caseloads. MATERIAL AND METHODS: Observational cross-sectional study of diagnoses made by a random selection of dermatologists from the Spanish Association of Dermatology and Venereology (AEDV) working in outpatient dermatology clinics. The data were obtained through the anonymous DIADERM survey. Diagnoses of infectious diseases were selected using codes from the International Classification of Diseases, Tenth Revision. After excluding sexually transmitted infections, the diagnoses were classified into 22 groups. RESULTS: Spanish dermatologists diagnosed an estimated 16190 (95% CI, 9338-23042) nonvenereal infections on average per week, a figure that accounted for 9.33% of the dermatology caseload. The most common diagnostic groups were nonanogenital viral warts (7475 diagnoses, 46.17% of nonvenereal infections), dermatophytosis (3336, 20.61%), and other viral infections (1592, 9.84%), which included Molluscum contagiosum infections. Nonvenereal infections were more common than noninfectious dermatologic conditions in private clinics (P<.0020) and adults (P<.00001). Patients with these infections were also more likely to be discharged than those with other conditions in both public (P<.0004) and private (P<.0002) practices. CONCLUSIONS: Nonvenereal infections are frequent in dermatology. They are the third most common reason for outpatient visits, behind actinic keratosis and nonmelanoma skin cancer. By enhancing the participation of dermatologists in the management of skin infections and encouraging interactions with other specialists, we will be able to carve out a niche in an area we have scarcely ventured into to date.

Selection of Quality Indicators for the Certification of Dermato-Oncology Units: The CUDERMA Project Delphi Consensus Study. / Proyecto CUDERMA: Consenso Delphi de los indicadores de calidad para la certificación de las unidades de dermatología de atención en dermato-oncología.

Quality indicators are crucial for standardizing and guaranteeing the quality of health care practices. The Spanish Academy of Dermatology and Venereology (AEDV) launched the CUDERMA Project to define quality indicators for the certification of specialized units in dermatology; the first 2areas selected were psoriasis and dermato-oncology. The aim of this study was to achieve consensus on what should be evaluated by these indicators using a structured process comprising a literature review and selection of an initial list of indicators to be evaluated in a Delphi consensus study following review by a multidisciplinary group of experts. The selected indicators were evaluated by a panel of 28 dermatologists and classified as either «essential¼ or «of excellence¼. The panel agreed on 84 indicators, which will be standardized and used to develop the certification standard for dermato-oncology units.

Selection of Quality Indicators for the Certification of Psoriasis Units: The CUDERMA Project Delphi Consensus Study. / Proyecto CUDERMA: Consenso Delphi de los indicadores de calidad para la certificación de las unidades de dermatología de atención en psoriasis.

Defining quality indicators is a key strategy for ensuring the quality and standardization of health care. The CUDERMA project, an initiative of the Spanish Academy of Dermatology and Venerology (AEDV), was undertaken to define quality indicators for the certification of specialized units in dermatology; the first 2 areas selected were psoriasis and dermato-oncology. The aim of this study was to reach a consensus on what should be assessed by the indicators used to certify psoriasis units. The structured process used to do this comprised a literature review to identify potential indicators, the selection of an initial set of indicators to be evaluated by a multidisciplinary group of experts and, finally, a Delphi consensus study. A panel of 39 dermatologists evaluated the selected indicators and classified them as either "essential" or "of excellence". Consensus was finally reached on 67 indicators, which will be standardized and used to develop the certification standard for psoriasis units.

Dermatology Care in Spanish Public Hospitals: A Mapping Study of Health Care Resources and Medical and Surgical Activity in Dermatology Departments in 2019. / Mapa asistencial dermatológico: descripción de los recursos estructurales y de la actividad médico-quirúrgica de los servicios de dermatología de los hospitales públicos españoles en 2019.

BACKGROUND AND OBJECTIVE: No recent data on health care resources and medical and surgical activity in Spanish dermatology departments are available in the literature. The aim of this study was to compile this information for 2019. MATERIAL AND METHODS: Cross-sectional study based on an online survey sent to the heads of dermatology departments at public hospitals in Spain. RESULTS: Of the 162 department heads contacted, 59 answered the survey (participation rate, 36.4%). General findings included a shortage of staff, especially dermatologists, in hospitals of low and medium complexity. The main reason given for the shortage of dermatologists was a lack of interested applicants. Large hospital complexes had more infrastructure and equipment. Over 50% of the departments surveyed used a combination of in-person and virtual visits. Psoriasis units were the most common specialized care units. Approximately 75% of the hospitals had operating rooms with an anesthetist. More complex procedures such as sentinel lymph node biopsy and Mohs micrographic surgery were performed more often in large hospital complexes. Hospitalization and the presence of dermatology residents working call shifts were also more common in these hospitals. Teaching and research activity differed according to hospital complexity. CONCLUSIONS: We have mapped health care resource availability and medical and surgical activity in Spanish dermatology departments prior to the COVID-19 pandemic. Our findings could be useful for improving clinical management and defining future actions and areas for improvement.

Tirbanibulin: review of its novel mechanism of action and how it fits into the treatment of actinic keratosis. / Tirbanibulina: revisión de su mecanismo de acción novedoso y de cómo encaja en el tratamiento de la queratosis actínica.

Actinic keratosis (AK) is a skin condition characterized by the proliferation of mutated keratinocytes that can develop into squamous cell carcinoma. Available therapies, although effective, are associated with a high frequency of severe local skin reactions. Tirbanibulin, one of the treatments for AK currently in development, is a new synthetic chemical entity with anti-proliferative and anti-tumor effects, both in vitro and in vivo, with proved efficacy in the treatment of AK, which has been recently demonstrated in two phase III clinical trials. In the present review, the tirbanibulin mechanism of action, based on the relevant literature and the results of several unpublished preclinical studies, is shown. In addition, the current scenario regarding the available treatments and how the novel tirbanibulin mechanism of action fits into the treatment of AK is raised.

What Proportion of the Spanish Dermatology Caseload Corresponds to Primarily Sexually Transmitted Infections and Other Anogenital Dermatoses? Results From the DIADERM National Random Survey. / ¿Cuánta carga asistencial suponen las infecciones de transmisión predominantemente sexual y otras dermatosis anogenitales en las consultas de Dermatología en España? Resultados del muestreo aleatorio nacional DIADERM.

BACKGROUND AND OBJECTIVE: Predominantly sexually transmitted infections (STIs) and infestations and other anogenital dermatoses are covered in the training of specialists in dermatology and venereology in Spain. This study aimed to analyze the proportion of the dermatology caseload these diseases account for within the public and private dermatological activity of the Spanish health system. MATERIAL AND METHODS: Observational cross-sectional study of time periods describing the diagnoses made in outpatient dermatology clinics, obtained through the anonymous DIADERM survey of a representative random sample of dermatologists. Based on diagnostic codes of the International Classification of Diseases, Tenth Revision, 36 related diagnoses were selected, and classified into 12 groups. RESULTS: Only 3.16% of diagnoses corresponded to STIs and other anogenital dermatoses. The most common diagnostic group was anogenital human papillomavirus infection, followed by molluscum contagiosum, and inflammatory anogenital dermatoses. Lesions with these diagnoses were usually the main reasons for first visits in the National Health Service. In private practice, the diagnoses usually came after referrals from other physicians. CONCLUSIONS: STIs and other anogenital dermatoses account for a very small proportion of the dermatology caseload in Spain, although the inclusion of molluscum contagiosum diagnoses overestimates these conditions. The fact that no STI centers or monographic STI consultations were included in the random sample of dermatology partly explains the under-representation of these areas of the specialty. A determined effort to support and promote monographic STI centres and clinics should be made.

Cutaneous and Mucocutaneous Leishmaniasis.

Leishmaniasis is a chronic disease caused by flagellate protozoa of the genus Leishmania. It is a global disease, but most cases are seen in South America, the Mediterranean, and some areas of Asia and Africa. The 3 main types of leishmaniasis are cutaneous (the most common), mucocutaneous, and visceral (the most severe). Visceral leishmaniasis is also known as kala-azar. Leishmaniasis is diagnosed by demonstrating the presence of Leishmania amastigotes in clinical specimens using direct microscopic examination or molecular analysis. Various treatments exist, although the evidence supporting the options available for cutaneous leishmaniasis is weak. Both the classical presentation of leishmaniasis and our management of the disease have changed in recent decades because of acquired immune deficiency caused by conditions such as human immunodeficiency infection or the use of tumor necrosis factor inhibitors.

What Proportion of the Caseload at Dermatology Outpatient Clinics in Spain Do Skin Tumors Account for? Results from the DIADERM National Random Sampling Project. / ¿Cuánta carga asistencial supone la enfermedad tumoral cutánea en la actividad ambulatoria en la Dermatología española? Resultados del muestreo aleatorio nacional DIADERM.

INTRODUCTION AND OBJECTIVE: A significant part of a dermatologist's activity involves the diagnosis and management of tumors. The aim of this study was to analyze the caseload at public and private dermatology outpatient clinics in Spain to determine the proportion of tumor diagnoses. MATERIAL AND METHOD: Observational cross-sectional study of diagnoses made in dermatology outpatient clinics during 2 data-collection periods in the DIADERM study, an anonymous survey of a random, representative sample of dermatologists across Spain. Diagnoses made during the 2 periods were coded according to the CIE-10. There were 165 tumor-related codes, classified into 24 groups. For the purpose of this study, these groups were then reduced to benign melanocytic lesions, malignant melanocytic lesions, benign nonmelanocytic lesions, and malignant nonmelanocytic lesions. RESULTS: Tumors accounted for 46.2% of all diagnoses; 18.5% of the tumors were malignant (a category that included in situ forms of keratinocyte cancers). Four of the 10 most common diagnoses were of malignant tumors: in situ keratinocyte cancers, basal cell carcinoma, melanoma, and squamous cell carcinoma. Significant differences were observed between malignant and benign tumors according to type of practice (public vs. private) and geographic region. CONCLUSION: Skin cancer accounts for a significant part of the dermatologist's caseload in Spain. Differences can be observed depending on the public/private healthcare setting and other factors.

Staphylococcus lugdunensis Skin Infection: Report of 16 Cases. / Infección cutánea por Staphylococcus lugdunensis: presentación de 16 casos.

INTRODUCTION AND OBJECTIVE: Staphylococcus lugdunensis belongs to the group of coagulase-negative staphylococci. The aim of this report was to review the clinical and microbiologic features of cases of S. lugdunensis skin infections. MATERIAL AND METHODS: Observational study of all cases of skin infections in which S. lugdunensis was isolated by the microbiology department of Hospital General San Jorge in Huesca, Spain, between 2009 and 2016. RESULTS: We studied the cases of 16 patients. The most frequent site of infection was the inguinal-perineal region (n=6, 37.5%), and pustules were the most common presentation (n=5, 31.3%). Response to treatment was good in 87.6% of the patients (n=14). However, infection recurred in 3 patients, 2 of whom were on anti-TNF therapy. CONCLUSIONS: S. lugdunensis should be considered a possible cause of infection when it is isolated in both skin and subcutaneous tissues, especially in patients on biologic therapies.

Influence of the Exposome on Skin Cancer. / La influencia del exposoma en el cáncer de piel.

Skin cancer is the most frequent type of cancer in humans. While exposure to solar radiation is the most widely known and relevant causal factor, the different degrees of individual risk have not been fully elucidated. Epidemiological studies show how the risk of skin cancer is affected by other types of radiation (eg, ionizing radiation), pesticides, particulate matter in air pollution, toxins (eg, arsenic) in water and some foods. Some living entities, such as polyomavirus and human papillomavirus, can also cause specific types of cancer. Lastly, lifestyle factors such as stress, sleep, and exercise may play a role, although only a few studies shed light on these factors. The abovementioned factors make up the exposome of skin cancer, that is, the set of environmental exposures that, together with the genome and microbiome, determine the onset of disease.

Photoprotection of the future: challenges and opportunities.

The use of sunscreens is an important and essential component of photoprotection. Since their introduction during the first half of the last century, sunscreens have benefited enormously from major technological advances such as the development of novel UV filters; as a result, their efficacy in preventing UV-induced erythema is unequivocal. More recently, however, new challenges have appeared, which have prompted a robust discussion about the safety of sunscreens. These include topics directly related to photoprotection of human skin such as improved/alternative methods for standardization of assessment of the efficacy of sunscreens, but also many others such as photoprotection beyond UV, concerns about human toxicity and ecological safety, the potential of oral photoprotective measures, consequences of innovative galenic formulations. On a first glance, some of these might raise questions and doubts among dermatologists, physicians and the general public about the use sunscreens as a means of photoprotection. This situation has prompted us to critically review such challenges, but also opportunities, based on existing scientific evidence. We conclude by providing our vision about how such challenges can be met best in the future in an attempt to create the ideal sunscreen, which should provide adequate and balanced protection and be easy and safe to use.

European Dermatology Forum guidelines on topical photodynamic therapy 2019 Part 2: emerging indications - field cancerization, photorejuvenation and inflammatory/infective dermatoses.

In addition to approved indications in non-melanoma skin cancer in immunocompetent patients, topical photodynamic therapy (PDT) has also been studied for its place in the treatment of, as well as its potential to prevent, superficial skin cancers in immune-suppressed patients, although sustained clearance rates are lower than for immune-competent individuals. PDT using a nanoemulsion of ALA in a daylight or conventional PDT protocol has been approved for use in field cancerization, although evidence of the potential of the treatment to prevent new SCC remained limited. High-quality evidence supports a strong recommendation for the use of topical PDT in photorejuvenation as well as for acne, refractory warts, cutaneous leishmaniasis and in onychomycosis, although these indications currently lack approvals for use and protocols remain to be optimized, with more comparative evidence with established therapies required to establish its place in practice. Adverse events across all indications for PDT can be minimized through the use of modified and low-irradiance regimens, with a low risk of contact allergy to photosensitizer prodrugs, and no other significant documented longer-term risks with no current evidence of cumulative toxicity or photocarcinogenic risk. The literature on the pharmacoeconomics for using PDT is also reviewed, although accurate comparisons are difficult to establish in different healthcare settings, comparing hospital/office-based therapies of PDT and surgery with topical ointments, requiring inclusion of number of visits, real-world efficacy as well as considering the value to be placed on cosmetic outcome and patient preference. This guideline, published over two parts, considers all current approved and emerging indications for the use of topical photodynamic therapy in Dermatology prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence.

Systematic Review of Light-Based Treatments for Hidradenitis Suppurativa. / Revisión sistemática de las terapias con luz en el tratamiento de la hidradenitis supurativa.

Treatment options for hidradenitis suppurativa include light-based therapy. This systematic review aimed to update our understanding of the efficacy, effectiveness and safety of these treatments for hidradenitis suppurativa by evaluating the literature published since the 2015 Cochrane review on this topic. We conducted an electronic search of the following databases: MEDLINE, EMBASE, University of York Centre for Reviews and Dissemination database, Cochrane Database of Systematic Reviews, Cochrane Skin Group Specialised Skin Register, University of Nottingham's Centre of Evidence Based Dermatology database, and TESEO. The systematic review included 6 case series, 3 systematic reviews, and 2 clinical trials on the use of conventional and intralesional photodynamic therapy, intense pulsed light therapy, and Nd:YAG, carbon dioxide, and diode laser therapy for hidradenitis suppurative in 248 patients.

European Dermatology Forum guidelines on topical photodynamic therapy 2019 Part 1: treatment delivery and established indications - actinic keratoses, Bowen's disease and basal cell carcinomas.

Topical photodynamic therapy (PDT) is a widely approved therapy for actinic keratoses, Bowen's disease (squamous cell carcinoma in situ), superficial and certain thin basal cell carcinomas. Recurrence rates when standard treatment protocols are used are typically equivalent to existing therapies, although inferior to surgery for nodular basal cell carcinoma. PDT can be used both as lesional and field therapies and has the potential to delay/reduce the development of new lesions. A protocol using daylight to treat actinic keratoses is widely practised, with conventional PDT using a red light after typically a 3-h period of occlusion employed for other superficial skin cancer indications as well as for actinic keratoses when daylight therapy is not feasible. PDT is a well-tolerated therapy although discomfort associated with conventional protocol may require pain-reduction measures. PDT using daylight is associated with no or minimal pain and preferred by patient. There is an emerging literature on enhancing conventional PDT protocols or combined PDT with another treatment to increase response rates. This guideline, published over two parts, considers all current approved and emerging indications for the use of topical PDT in dermatology, prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence.

Proportion of Potentially Avoidable Referrals From Primary Care to Dermatologists for Cystic Lesions or Benign Neoplasms in Spain: Analysis of Data From the DIADERM Study. / Análisis de la proporción de derivaciones potencialmente evitables desde Atención Primaria a Dermatología por lesiones quísticas o tumorales benignas en España. Datos del estudio DIADERM.

BACKGROUND AND OBJECTIVE: Skin lesions are a common reason for consulting a primary care physician. Current legislation in Spain states that purely aesthetic skin problems that do not pose a health problem are not to be treated within the National Health Service. The aim of this study was to estimate the proportion of referrals from primary care physicians to dermatologists that were for cystic lesions or benign tumors and could potentially have been avoided. MATERIAL AND METHODS: We consulted cases registered in the DIADERM study dataset, which is representative of dermatology practice in Spain, and collected the main diagnoses given on referring patients from primary care. A referral diagnosis was classified as potentially avoidable if it corresponded to one of the primary care discharge diagnoses listed in a consensus paper of the Andalusian section of the Spanish Academy of Dermatology and Venereology (AEDV). RESULTS: We collected 2171 main reasons for first-visit referrals to dermatologists; 686 of them (31.6%) were for cystic lesions or benign tumors and classified as potentially avoidable. In 478 cases (22%) the patients were discharged on the first visit. The most frequent diagnoses in such cases were seborrheic keratosis (9.3%) and melanocytic nevus (8.6%). CONCLUSIONS: Nearly a third of referrals from primary care to a dermatologist were for cystic lesions and benign tumors and could have been avoided. A clearer understanding of our caseload can be useful for improving planning, training, and health care system management.