Search

Background: Psoriasis can present different phenotypes and could affect diverse body areas. In contrast to the high effectiveness of biological drugs in the treatment of trunk and extremities plaque psoriasis, in palmoplantar phenotypes and in plaque scalp psoriasis, these same drugs usually have reduced efficacy. Anti-TNF drugs could induce the appearance of palmoplantar pustulosis (PPP) in patients with other inflammatory diseases. The objective of this study is to identify if there are DNA Copy Number Variations (CNVs) associated with these different clinical phenotypes, which could justify the differences found in clinical practice. Moreover, we intend to elucidate if anti-TNF-induced PPP has a similar genetic background to idiopathic PPP. Methods: Skin samples were collected from 39 patients with different patterns of psoriasis and six patients with anti-TNF-induced PPP. The CNVs were obtained from methylation array data (Illumina Infinium Human Methylation) using the conumee R package. Results: No significant CNVs were found between the different phenotypes and the locations of psoriasis compared. Nevertheless, we found two significant bins harboring five different genes associated with anti-TNF-induced PPP in patients with a different background other than psoriasis. Conclusions: Our results may help to predict which patients could develop anti-TNF-induced PPP.

Background Reduced minimal erythema dose (MED) is an abnormal erythematous reaction to light according to the skin phototype, which is determined by phototest. MED is reduced or abnormal in some photodermatoses. However, we have not found information about reduced MED in patients with solar urticarial (SU), a condition which causes hives after sun exposure. Objective To determine MED in a series of patients with SU. Methods We conducted a prospective study of SU cases diagnosed in our department between January 2007 and December 2017, either by anamnesis, provocation with natural sunlight or provocation with artificial light sources. In all patients, a phototest with reading at 24 h was performed according to the protocol of the Spanish Group of Photobiology. Variables related to the patient (age, sex, phototype), disease (time of evolution, action spectrum) and others related to possible reduced MED (autoantibodies, phototoxic medication) were collected. Results Twenty-five patients were studied. Six patients (24%) had abnormal MED. Eighty-three percent of patients with abnormal MED were men, and 50% had action spectrum in UVB. Conclusion Abnormal MED can be seen in up to a fourth of the patients with SU. This could have implications in the selection of patients and protocols for treatment with phototherapy.

Resumen: Antecedentes: La dosis eritematosa mínima (DEM) reducida es una reacción anormal a la luz según el fototipo de piel y que se determina mediante fototest. La DEM es reducida o anormal en algunas fotodermatosis. Sin embargo, no hemos encontrado información sobre la DEM reducida en pacientes con urticaria solar (US), enfermedad que cursa con urticaria tras la exposición al sol. Objetivo: Determinar la DEM en una serie de pacientes con US. Métodos: Llevamos a cabo un estudio prospectivo de casos de US diagnosticados en nuestro departamento entre enero de 2007 y diciembre de 2017, a través de anamnesis o por provocación mediante exposición a la luz solar natural o a fuentes de luz artificial. De acuerdo con el protocolo del Grupo Español de Fotobiología, a las 24 horas se llevó a cabo la lectura del fototest en todos los pacientes. Se recopilaron las variables relativas al paciente (edad, sexo, fototipo), enfermedad (tiempo de evolución, espectro de activación) y otras relacionadas con la posible DEM reducida (autoanticuerpos, medicación fototóxica). Resultados: Se estudiaron 25 pacientes, de los cuales, seis (24%) presentaron una DEM anormal, el 83% de ellos eran hombres, y el 50% mostraba el espectro de acción en el rango de la radiación UVB. Conclusión: Hasta en una cuarta parte de los pacientes con US se puede observar la DEM anormal. Esta circunstancia podría tener implicaciones en la selección de los pacientes y en los protocolos para el tratamiento con fototerapia. Abstract: Background: Reduced minimal erythema dose (MED) is an abnormal erythematous reaction to light according to the skin phototype, which is determined by phototest. MED is reduced or abnormal in some photodermatoses. However, we have not found information about reduced MED in patients with solar urticarial (SU), a condition which causes hives after sun exposure. Objective: To determine MED in a series of patients with SU. Methods: We conducted a prospective study of SU cases diagnosed in our department between January 2007 and December 2017, either by anamnesis, provocation with natural sunlight or provocation with artificial light sources. In all patients, a phototest with reading at 24 h was performed according to the protocol of the Spanish Group of Photobiology. Variables related to the patient (age, sex, phototype), disease (time of evolution, action spectrum) and others related to possible reduced MED (autoantibodies, phototoxic medication) were collected. Results: Twenty-five patients were studied. Six patients (24%) had abnormal MED. Eighty-three percent of patients with abnormal MED were men, and 50% had action spectrum in UVB. Conclusion: Abnormal MED can be seen in up to a fourth of the patients with SU. This could have implications in the selection of patients and protocols for treatment with phototherapy.

Epigenetics is the study of the mechanisms that regulate gene expression without modifying DNA sequences. Knowledge of and evidence about how epigenetics plays a causative role in the pathogenesis of many skin diseases is increasing. Since the epigenetic changes present in tumor diseases have been thoroughly reviewed, we believe that knowledge of the new epigenetic findings in non-tumor immune-mediated dermatological diseases should be of interest to the general dermatologist. Hence, the purpose of this review is to summarize the recent literature on epigenetics in most non-tumor dermatological pathologies, focusing on psoriasis. Hyper- and hypomethylation of DNA methyltransferases and methyl-DNA binding domain proteins are the most common and studied methylation mechanisms. The acetylation and methylation of histones H3 and H4 are the most frequent and well-characterized histone modifications and may be associated with disease severity parameters and serve as therapeutic response markers. Many specific microRNAs dysregulated in non-tumor dermatological disease have been reviewed. Deepening the study of how epigenetic mechanisms influence non-tumor immune-mediated dermatological diseases might help us better understand the role of interactions between the environment and the genome in the physiopathogenesis of these diseases.

Attempts have been made to establish discriminative criteria between classic calciphylaxis (CPX) and those cases in which cutaneous vascular calcification (CVC) represents an incidental finding (epiphenomenon).Retrospective, observational cohort study of patients with CVC to distinguish clinicopathological features between CVC as classic CPX (CVC in cutaneous lesions with erythematous-violaceous plaques with or without ulceration) or as an epiphenomenon (CVC in cutaneous lesions with known diagnosis). Different clinicopathological parameters and the presence of perieccrine calcification and pseudoxanthoma elasticum (PXE)-like changes were evaluated.Sixty-six patients were studied. The CPX group showed a significantly higher percentage of renal failure, hypertension, altered laboratory parameters, painful lesions, and mortality rate. Histopathologically, the CPX group was associated with more than one vessel per field involved with subintimal concentric calcification and perieccrine calcification (observed exclusively in the CPX group), while PXE-like changes, although more frequent in the CPX group, were also observed in the epiphenomenon group.Perieccrine calcification and the presence of more than one vessel per field involved by concentric pattern calcification could be used as a diagnostic marker of CPX. Although PXE-like changes are not an exclusive marker, they could suggest CPX diagnosis.

Background Bullous pemphigoid (BP) has been associated with dipeptidyl peptidase-4 inhibitors (DPP4i). Clinical features, outcomes, and risk of BP for new DPP4i (linagliptin, saxagliptin, and alopgliptin) are not well established. Comparison of risk of BP appearance for DPP4i and other oral antidiabetic drugs (OADs) such as sodium glucose cotransporter 2 inhibitors has not been studied to date. Objectives To describe the prevalence, sociodemographic, clinical, and histopathological characteristics, and outcome after drug withdrawal in DPP-4i-associated BP cases from our hospital. To review all Spanish spontaneous notifications of BP where DPP4i or OADs were included as suspected drugs and calculate the reporting odds ratios (RORs). Methods A retrospective observational study was performed examining the association between DDP4i and BP. Clinical features and RORs were analyzed. Data from the Spanish Pharmacovigilance System (SEFV) are included. Results In our center, 28 of 89 patients with BP (31.5%) were under DPP4i treatment; 53.6% were male, and mean age was 80.8 years. BP debuted the first year after DPP4i in 57.2%. BP control was achieved within 3.7 months after drug withdrawal. Regarding SEFV, 22 of 972 spontaneous notifications were related to BP and DPP4i. RORs were superior for DPP4i compared to other OADs. Vildagliptin had the highest ROR. Conclusions We present the largest DPP4i-induced BP case series in a single center, with a detailed study of the sociodemographic, clinical, and histopathological characteristics of each patient, and their treatment and outcome. Vildagliptin had the highest risk. DPP4i-associated BP does not seem to have specific clinical characteristics.

The body of literature supporting the use of Mohs micrographic surgery (MMS) in tumors outside the main indications (basal cell carcinoma, squamous cell carcinoma, dermatofibrosacroma protuberans, lentigo maligna) is constantly growing, but it is still based on case reports, case series, or at best institutional case series that focus on a single malignancy. Our aim in this review was to assess use of MMS in an array of rare tumors outside the usual indications. A review was performed using the MEDLINE database and the search engine ClinicalKey®. We reviewed the use of MMS on atypical fibroxanthoma (AFX)/malignant fibrous histiocytoma, microcystic adnexal carcinoma, extramammary Paget's disease, Merkel cell carcinoma, pocrine/eccrine carcinoma/porocarcinoma, trichilemmal carcinoma, leiomyosarcoma, and angiosarcoma. Mohs micrographic surgery appears to be scarcely used in these tumors due to their low incidence. It is mainly performed for tumors in the H-zone of the face, and can be performed safely. The overall recurrence rate is lower compared with simple or wide local excision. MMS should be used in a more generalized fashion for these tumors.

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).

Epigenetics is the study of the mechanisms that regulate gene expression without modifying DNA sequences. Knowledge of and evidence about how epigenetics plays a causative role in the pathogenesis of many skin diseases is increasing. Since the epigenetic changes present in tumor diseases have been thoroughly reviewed, we believe that knowledge of the new epigenetic findings in non-tumor immune-mediated dermatological diseases should be of interest to the general dermatologist. Hence, the purpose of this review is to summarize the recent literature on epigenetics in most non-tumor dermatological pathologies, focusing on psoriasis. Hyper- and hypomethylation of DNA methyltransferases and methyl-DNA binding domain proteins are the most common and studied methylation mechanisms. The acetylation and methylation of histones H3 and H4 are the most frequent and well-characterized histone modifications and may be associated with disease severity parameters and serve as therapeutic response markers. Many specific microRNAs dysregulated in non-tumor dermatological disease have been reviewed. Deepening the study of how epigenetic mechanisms influence non-tumor immune-mediated dermatological diseases might help us better understand the role of interactions between the environment and the genome in the physiopathogenesis of these diseases.

Background and objectives: Psoriasis is a chronic immune-mediated skin disease caused by several complex factors, both environmental and genetic, many of which are still not fully understood. Nowadays, several groups of biological drugs are being used for psoriasis treatment. Although these therapies are very effective, they show significant variability in efficacy among individuals. Therefore, there is a need for biomarkers to predict treatment outcomes in order to guide personalized therapeutic decisions. Pharmacogenetics is the study of variations in DNA sequences related to drug response. Materials and Methods: In this article, we review pharmacogenetics studies on the treatment of moderate-to-severe psoriasis focusing on anti-interleukin (IL) 12/23 (ustekinumab) and anti-IL17 drugs (secukinumab and ixekizumab), as well as recent studies concerning anti-TNF drugs. Results: Several polymorphisms have been studied over the years in reference to anti-TNF drugs; some of the most recent studies included the performance of a genome-wide association study (GWAS) and pharmacogenetics studies focused on the optimization of a treatment regimen. Various polymorphisms in different genes have been related to ustekinumab response; among them, the most commonly studied is the HLA-C*06:02 allele. Conclusions: Although not confirmed in some studies, most studies have shown that patients carrying this allele present a significantly higher response rate to ustekinumab. Some polymorphisms have been studied in patients treated with anti-IL17 drugs, mostly related to secukinumab; however, up to now, no association has been found between any of these polymorphisms and response. Nevertheless, further studies involving larger cohorts are needed in order to confirm these results before the implementation of this biomarker in clinical practice.

While anti-TNF therapies are effective against psoriasis, 30%-50% of patients do not show an adequate response to these drugs. Different candidate-gene pharmacogenetics studies have identified single nucleotide polymorphisms that may predict anti-TNF drugs response in psoriasis. Nevertheless, only one paper has undertaken a pharmacogenomic approach failing to find significant biomarkers of biological drug response along the whole genome. Furthermore, most of the pharmacogenetic candidate biomarkers identified previously have not been confirmed in a different cohort of patients. The objective of this study was to find biomarkers that could predict anti-TNF drugs response along the whole genome and validate biomarkers identified previously. A genome-wide association study (GWAS) was performed using the Human Omni Express-8 v1.2 Beadchips in 243 psoriasis patients treated with anti-TNF drugs. This study was multicentric and did not interfere with clinical practice. Associations between single nucleotide polymorphisms (SNP) and PASI75 (a 75% reduction with respect to baseline PASI) at 3 months were evaluated. Imputation was performed using SNPs with R2 > 0.7. There were two SNPs located in NPFFR2 that were close to the significant threshold of 5 × 10-8 . These data suggest that NPFFR2 might be associated with anti-TNF drug response. However, further studies involving a larger cohort of patients are needed in order to confirm these results.

Background The use of Mohs micrographic surgery (MMS) for rare cutaneous tumors is poorly defined. We aim to describe the demographics, tumor presentation and topography, surgery characteristics and complications of MMS for rare cutaneous tumors in a national registry. Methods Prospective cohort study of patients treated with MMS in Spain between July 2013 and June 2018. The inclusion criteria were patients with cutaneous tumors with final diagnosis different from basal cell carcinoma, squamous cell carcinoma, dermatofibrosarcoma protuberans, or any kind of melanoma. Results Five thousand and ninety patients were recorded in the registry, from which only 73 tumors (1.4%) fulfilled the inclusion criteria: atypical fibroxanthoma (18), microcystic adnexal carcinoma (10), extramammary Paget's disease (7), Merkel cell carcinoma (5), dermatofibroma (4), trichilemmal carcinoma (4), desmoplastic trichoepithelioma (4), sebaceous carcinoma (3), leiomyosarcoma (2), porocarcinoma (2), angiosarcoma (2), trichoblastoma (1), superficial acral fibromyxoma (1), and others (10). No intra-surgery morbidity was registered. Postsurgery complications appeared in six patients (9%) and were considered mild. Median follow-up time was 0.9 years during which three Merkel cell carcinomas, one angiosarcoma, one microcystic adnexal carcinoma, and four others recurred (12.3%). Conclusion This national registry shows that rare cutaneous tumors represent a negligible part of the total MMS performed in our country with a low complication rate.

[Introduction] Epigenetic factors play an important role in psoriasis onset and development. Biological drugs are used to treat moderate-to-severe psoriasis patients resistant to conventional systemic drugs. Although they are safe and effective, some patients do not respond to them. Therefore, it is necessary to find biomarkers that could predict response to these therapies., [Objective] To find epigenetic biomarkers that could predict response to biological drugs (ustekinumab, secukinumab, adalimumab, ixekizumab)., [Materials and methods] Peripheral blood mononuclear cells (PBMCs) were isolated from 39 psoriasis patients treated with biological therapies before and after drug administration and from 42 healthy subjects. Afterwards, histones were extracted from PBMCs. Four histone modifications (H3 and H4 acetylation, H3K4 and H3K27 methylation) were determined by ELISA. Data were analysed by IBM-SPSS v.23., [Results and conclusions] Psoriasis patients presented reduced levels of acetylated H3 and H4 and increased levels of methylated H3K4 compared to controls. Nonsignificant changes were observed after treatment administration in any of the histone modifications analysed. Nevertheless, significant changes in methylated H3K27 were found between responders and non-responders to biological drugs at 3 months. As 28% of these patients also presented psoriatic arthritis (PsA), the former analysis was repeated in the subsets of patients with or without PsA. In patients without PsA, significant changes in methylated H3K4 were found between responders and nonresponders to biological drugs at 3 and 6 months. Although further studies should confirm these results, these findings suggest that H3K27 and H3K4 methylation may contribute to patients’ response to biological drugs in psoriasis., This study was supported by Instituto de Salud Carlos III PI 13/01598, PI 14/01751, PI 17/01972, Fundación Teófilo Hernando, the Ministry of Science and Innovation and the European Regional Development’s funds (FEDER)

Pharmacogenetics is the study of variations in DNA sequence related to drug response. Moreover, the evolution of biotechnology and the sequencing of human DNA have allowed the creation of pharmacogenomics, a branch of genetics that analyzes human genes, the RNAs and proteins encoded by them, and the inter-and intra-individual variations in expression and function in relation to drug response. Pharmacogenetics and pharmacogenomics are being used to search for biomarkers that can predict response to systemic treatments, including those for moderate-to-severe psoriasis. Psoriasis is a chronic inflammatory disease with an autoimmune contribution. Although its etiology remains unknown, genetic, epigenetic, and environmental factors play a role in its development. Diverse systemic and biologic therapies are used to treat moderate-to-severe psoriasis. However, these treatments are not curative, and patients exhibit a wide range of responses to them. Moderate-to-severe psoriasis is usually treated with systemic immunomodulators such as acitretin, ciclosporin, and methotrexate. Anti-tumor necrosis factor (TNF) drugs (adalimumab, etanercept, or infliximab) are the first-line treatment for patients resistant to conventional systemic therapies. Although these therapies are very efficient, around 30-50% of patients have inadequate response. Ustekinumab is a monoclonal antibody that targets interleukin (IL)-12 and IL-23 and is used for moderate-to-severe psoriasis. New drugs (apremilast, brodalumab, guselkumab, ixekizumab, and secukinumab) have recently been approved for psoriasis. However, response rates to systemic treatments for moderate-to-severe psoriasis range from 35 to 80%, so it is necessary to identify non-invasive biomarkers that could help predict treatment outcomes of these therapies and individualize care for patients with psoriasis. These biomarkers could improve patient quality of life and reduce health costs and potential side effects. Pharmacogenetic studies have identified potential biomarkers for response to biologic treatments for moderate-to-severe psoriasis. These biomarkers need to be validated in clinical trials involving large cohorts of patients before they can be translated to the clinic. We review pharmacogenetics and pharmacogenomics studies for the treatment of moderate-to-severe plaque psoriasis.

It has recently been discovered that epigenetic modifications, specially DNA methylation, participates in the pathology of psoriasis. DNA methylation is a covalent modification dynamic and heritable that takes place in Cytosine-Phosphate-Guanine (CpG) sites and may exert transcriptional effects. Although anti-tumour necrosis factor α (TNF) therapies (adalimumab, etanercept and infliximab) are efficient drugs for moderate-to-severe psoriasis, around 30–50% of psoriasis patients present an inadequate response. This article is protected by copyright. All rights reserved.

espanolIntroduccion. La informacion sobre la situacion laboral de los especialistas MIR tras su periodo formativo deberia ser un requisito indispensable para una adecuada planifi cacion de la oferta en formacion especializada. De igual forma, seria conveniente disponer de la opinion de los egresados sobre su periodo formativo para identifi car areas de mejora. El objetivo de este estudio es el analisis de ambos aspectos entre los especialistas formados en el Hospital Universitario San Juan de Alicante y su Departamento de Salud tras 20 anos de experiencia docente (1993-2012). Sujetos y metodos. Entre junio de 2013 y abril de 2014 se llevo a cabo un estudio observacional descriptivo mediante encuesta de opinion que incluia preguntas en dos bloques, laboral y formativo, y que se distribuyo entre los MIR formados en el centro en el periodo 1993-2012. El numero de especialidades analizadas fue 16. Resultados. De los 272 especialistas, respondio a la encuesta un 71%, el 93% en las especialidades hospitalarias. Al responderla, ninguno se encontraba en paro. Un 74% tenia trabajo estable y el 75% trabajaba en la provincia de Alicante. En nueve de las 16 especialidades, mas del 80% de los especialistas encontro trabajo en el mes tras finalizar el periodo MIR. Casi el 70% volveria a elegir la plaza en la que se formo. El 93% de los encuestados manifesto sentirse solvente al realizar su trabajo. Conclusiones. Aunque un 7% de los especialistas tardo mas de seis meses en encontrar trabajo y en dos especialidades (medicina nuclear y medicina interna) el trabajo inestable supero al estable, la situacion laboral y formativa de los MIR egresados en nuestro departamento hasta el ano 2012 puede considerarse satisfactoria, con pleno empleo y niveles altos de percepcion de solvencia en su trabajo como especialistas. EnglishIntroduction. Information about medical employment after the specialist’s training period should be an essential requirement for planning of future teaching needs. In the same way, it would be convenient to consider the trainee’s opinion about their training period in order to identify diff erent areas to be improved. The aim of this study was to analyse the opinion of doctors trained in the University Hospital of San Juan de Alicante about their working conditions and teaching program. Subjects and methods. In the period between June/2013 and April/2014, an observational descriptive study through a questionnaire survey was performed, including two groups of questions that were answered by the specialists trained in the Health Department of Alicante-San Juan after 20 years (1993-2012). Sixteen medical specialities were analysed. Results. The questionnaire was answered by 71% of 272 trained specialists, 93% of hospital specialties (not including primary care). When the questionnaire was answered, any of the specialists was on unemployment. Seventy four percent had a stable job, and 75% were working in the province of Alicante. In 9 of the 16 specialties, more than 80% of the specialists were already working in the fi rst month after fi nishing their training period. Almost 70% would choose the same specialty again. Ninety three percent expressed to feel solvent in their job as a specialist. Conclusions. Seven percent of the specialists remained in unemployment more than 6 months and, in nuclear and internal medicine, the number of unstable jobs exceeded the stable jobs. However, up to 2012, the working and educational situation of medical specialists trained in the University Hospital of San Juan de Alicante can be considered satisfactory, with full employment and a very good self-perception of solvency.