Pharmacogenetic biomarkers for secukinumab response in psoriasis patients in real-life clinical practice.

BACKGROUND: Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation. OBJECTIVE: To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting. METHODS: We studied 180 SNPs in patients with moderate-to-severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed. RESULTS: A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR-146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83-0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes. CONCLUSION: We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non-response to this drug in patients with plaque psoriasis.

Estudio de la dosis eritematosa mínima en una serie de urticaria solar / Study of Minimal Erythema Dose in a Series of Solar Urticaria

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 (AU)

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 (AU)

Epigenetics in Non-tumor Immune-Mediated Skin Diseases.

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.

Enseñanza de la ecografía clínica en el pregrado: los estudiantes como mentores / Teaching of clinical ultrasonography to undergraduates: students as mentors

Introducción: La ecografía es una técnica diagnóstica por imagen muy útil que complementa la exploración física tradicional. Objetivo: Demostrar que estudiantes previamente formados en ecografía clínica son capaces de instruir a otros estudiantes de forma similar en un corto periodo de tiempo («mentoría paritaria»). Metodología: Cinco estudiantes de medicina de 5.° curso formados en ecografía abdominal y cardiaca por médicos con experiencia instruyeron con el mismo procedimiento a otros 24 estudiantes. La formación constaba de un curso teórico online y de prácticas de unas 12 horas de duración en las que cada uno de los estudiantes debía realizar 6 planos abdominales y 4 planos cardiacos básicos a 20 voluntarios sanos. Posteriormente, los estudiantes fueron sometidos a una evaluación objetiva sobre modelos sanos realizada por facultativos expertos en ecografía clínica. Resultados: Los alumnos consiguieron identificar correctamente el 90,2% de los planos básicos abdominales, a excepción de los planos coronal izquierdo (bazo y riñón izquierdo) y subcostal (vesícula biliar), con unos porcentajes de éxito ligeramente inferiores, del 82,5 y del 80%, respectivamente. Debido a la mayor dificultad de obtención de los planos cardiacos, el porcentaje de aciertos fue menor: 70,3%, en los planos subxifoideo, paraesternal corto y cuatro cámaras. El plano cardiaco con menor error de identificación fue el paraesternal largo (90% de aciertos). No observamos diferencias estadísticamente significativas entre los resultados (capacidad docente) de los distintos mentores. Conclusión: Los estudiantes de medicina son capaces de instruir a otros compañeros (mentoría paritaria) en aspectos básicos de ecografía abdominal y cardiaca tras un periodo de formación relativamente corto (AU)

Background: Ultrasonography is a highly useful diagnostic technique that supplements traditional physical examinations. Objective: To demonstrate that students previously trained in clinical ultrasonography are capable of instructing other students in a similar manner in a short period of time (“peer mentoring”). Methodology: Five medical students in their 5th year, trained in abdominal and cardiac ultrasonography by physicians with experience, instructed 24 other students in the same procedure. The training consisted of an online theoretical course and practical training lasting about 12hours, in which each student had to perform 6 basic abdominal planes and 4 basic cardiac planes on 20 healthy volunteers. Subsequently, the students underwent an objective assessment test on healthy models performed by expert physicians in clinical ultrasonography. Results: The students managed to correctly identify 90.2% of the basic abdominal planes, except for the left coronal (spleen and left kidney) and subcostal (gallbladder) planes, with slightly lower success rates of 82.5% and 80%, respectively. Due to the greater difficulty of obtaining cardiac planes, the success rate was lower: 70.3%, in the subxiphoid, short parasternal and four chamber planes. The cardiac plane with the fewest errors in identification was the parasternal long plane (90% success). We observed no statistically significant differences between the results (teaching capacity) of the various mentors. Conclusion: Medical students are capable of instructing other colleagues (peer mentoring) on the basic aspects of abdominal and cardiac ultrasonography after a relatively short training period (AU)

Teaching of clinical ultrasonography to undergraduates: students as mentors. / Enseñanza de la ecografía clínica en el pregrado: los estudiantes como mentores.

BACKGROUND: Ultrasonography is a highly useful diagnostic technique that supplements traditional physical examinations. OBJECTIVE: To demonstrate that students previously trained in clinical ultrasonography are capable of instructing other students in a similar manner in a short period of time ("peer mentoring"). METHODOLOGY: Five medical students in their 5th year, trained in abdominal and cardiac ultrasonography by physicians with experience, instructed 24 other students in the same procedure. The training consisted of an online theoretical course and practical training lasting about 12hours, in which each student had to perform 6 basic abdominal planes and 4 basic cardiac planes on 20 healthy volunteers. Subsequently, the students underwent an objective assessment test on healthy models performed by expert physicians in clinical ultrasonography. RESULTS: The students managed to correctly identify 90.2% of the basic abdominal planes, except for the left coronal (spleen and left kidney) and subcostal (gallbladder) planes, with slightly lower success rates of 82.5% and 80%, respectively. Due to the greater difficulty of obtaining cardiac planes, the success rate was lower: 70.3%, in the subxiphoid, short parasternal and four chamber planes. The cardiac plane with the fewest errors in identification was the parasternal long plane (90% success). We observed no statistically significant differences between the results (teaching capacity) of the various mentors. CONCLUSION: Medical students are capable of instructing other colleagues (peer mentoring) on the basic aspects of abdominal and cardiac ultrasonography after a relatively short training period.