The effect of age on the acquisition and selection of cancer driver mutations in sun-exposed normal skin.

BACKGROUND: The accumulation of somatic mutations contributes to ageing and cancer. Sunlight is the principal aetiological factor associated with skin cancer development. However, genetic and phenotypic factors also contribute to skin cancer risk. This study aimed at exploring the role of photoaging, as well as other well-known epidemiological risk factors, in the accumulation of somatic mutations in cancer-free human epidermis. MATERIAL AND METHODS: We deeply sequenced 46 genes in normal skin biopsies from 123 healthy donors, from which phenotypic data (including age, pigmentation-related genotype and phenotype) and sun exposure habits were collected. We determined the somatic mutational burden, mutational signatures, clonal selection and frequency of driver mutations in all samples. RESULTS: Our results reveal an exponential accumulation of UV-related somatic mutations with age, matching skin cancer incidence. The increase of mutational burden is in turn modified by an individual's skin phototype. Somatic mutations preferentially accumulated in cutaneous squamous cell carcinoma cancer genes and clonally expanded with age, with distinct mutational processes underpinning different age groups. Our results suggest a loss of fidelity in transcription-coupled repair later in life. CONCLUSION: Our findings reveal that ageing is not only associated with an exponential increase in the number of somatic mutations accumulated in normal epidermis, but also with selection and expansion of cancer-associated mutations. Aged, sun-exposed normal skin is thus an extended mosaic of multiple clones with driver mutations, poised for the acquisition of transforming events.

Psoriasis y enfermedad arterial coronaria isquémica / Psoriasis and Ischemic Coronary Artery Disease

INTRODUCCIÓN: La psoriasis es una enfermedad inflamatoria crónica que se ha asociado a un aumento de riesgo de enfermedad arterial coronaria isquémica (EACI) en algunas poblaciones. El objetivo de nuestro estudio fue determinar la asociación entre psoriasis y EACI en nuestro medio. MATERIAL Y MÉTODO: Se realizó un estudio transversal en la provincia de Castellón con datos procedentes del sistema de información asistencial Abucasis (Datamart) desde el año 2005 hasta el 2012. Se seleccionó a los pacientes con psoriasis y como grupo control a los pacientes con nevus melanocítico. Se estudió la prevalencia de EACI en ambos grupos estratificando por los principales factores de riesgo cardiovascular. RESULTADOS: Se estudiaron 9.181 pacientes con psoriasis y 21.925 con nevus melanocítico. En el análisis de regresión logística univariante la EACI se asoció significativamente a las variables psoriasis, edad (en años), sexo, hipertensión, diabetes mellitus, dislipidemia y obesidad (p < 0,05). En el análisis de regresión logística multivariante, tras ajustar por edad, sexo y el resto de los factores de riesgo cardiovascular, se establece una relación independiente entre la presencia de EACI y psoriasis (p < 0,029). CONCLUSIÓN: Nuestros resultados apoyan la existencia de mayor riesgo de EACI en pacientes con psoriasis en una población amplia del área mediterránea

INTRODUCTION: Psoriasis is a chronic inflammatory disease associated with an increased risk of ischemic coronary artery disease (CAD) in some populations. We aimed to determine the association between these 2 diseases in our geographic area. MATERIAL AND METHOD: We performed a cross-sectional study of patient records between 2005 and 2012 in the database (Abucacis, Datamart) that contains all medical case histories in the province of Castellón, Spain. Patients diagnosed with psoriasis were compared with a control group of patients diagnosed with melanocytic nevus. The prevalence of CAD and the presence or absence of the main cardiovascular risk factors were analyzed in each group. RESULTS: A total of 9181 patients with psoriasis and 21925 with melanocytic nevus were studied. Univariate logistic regression analysis showed that CAD was significantly associated with psoriasis, age (in years), sex, hypertension, diabetes mellitus, dyslipidemia, and obesity (P < .05). On adjustment for age, sex, and the other cardiovascular risk factors, multivariate regression analysis established that psoriasis was independently associated with CAD (P < .029). CONCLUSION: Our findings in a large sample of patients in a Mediterranean area support the hypothesis that patients in this population have an increased risk of ischemic CAD

Psoriasis and ischemic coronary artery disease.

INTRODUCTION: Psoriasis is a chronic inflammatory disease associated with an increased risk of ischemic coronary artery disease (CAD) in some populations. We aimed to determine the association between these 2 diseases in our geographic area. MATERIAL AND METHOD: We performed a cross-sectional study of patient records between 2005 and 2012 in the database (Abucacis, Datamart) that contains all medical case histories in the province of Castellón, Spain. Patients diagnosed with psoriasis were compared with a control group of patients diagnosed with melanocytic nevus. The prevalence of CAD and the presence or absence of the main cardiovascular risk factors were analyzed in each group. RESULTS: A total of 9181 patients with psoriasis and 21925 with melanocytic nevus were studied. Univariate logistic regression analysis showed that CAD was significantly associated with psoriasis, age (in years), sex, hypertension, diabetes mellitus, dyslipidemia, and obesity (P<.05). On adjustment for age, sex, and the other cardiovascular risk factors, multivariate regression analysis established that psoriasis was independently associated with CAD (P<.029). CONCLUSION: Our findings in a large sample of patients in a Mediterranean area support the hypothesis that patients in this population have an increased risk of ischemic CAD.

Plan estratégico de la Academia Española de Dermatología y Venereología (AEDV). FuturAEDV 2013-2017 / Strategic Plan for the Spanish Academy of Dermatology and Venerology (AEDV): FuturAEDV 2013-2017

ANTECEDENTES: La Academia Española de Dermatología y Venereología (AEDV) ha planteado la necesidad de definir un plan estratégico para adaptarse y anticiparse al nuevo escenario. OBJETIVOS: 1) Posicionar a la AEDV como una sociedad con capacidad de influencia en todo lo relacionado con la dermatología; 2) contribuir al desarrollo de la especialidad reforzando el prestigio de la misma y de sus profesionales; y 3) introducir en el seno de la Academia un modelo de funcionamiento y de pensamiento estratégico que permita anticiparse a los retos del futuro y que se transmita a las sucesivas juntas directivas. MÉTODOS: Análisis de las tendencias del sistema sanitario, diagnóstico de la situación actual de la AEDV y de la dermatología mediante un análisis interno a través de encuestas y entrevistas a los académicos, análisis de los puntos fuertes y débiles, así como las amenazas y oportunidades, declaración de la misión, y finalmente, la identificación, el desarrollo y la realización de un mapa estratégico con la priorización de las líneas de acción estratégicas. RESULTADOS: Se definió un mapa estratégico con 16 objetivos generales agrupados en 4 ejes (alcanzar la visión, clientes internos y externos, procesos internos e innovación), encuadrados en un plan de acción con 19 iniciativas y acciones concretas para cada una de ellas. La monitorización de su desarrollo la realizará el comité de seguimiento del plan estratégico, formado por la junta permanente y los responsables de los 9 comités técnicos encargados de llevar a cabo cada una de las iniciativas. Comentario: El plan funcional debe guiar la gestión de la AEDV hasta 2017 y su implantación le permitirá posicionarse como referente en cuanto a su modelo funcional y contribuir al desarrollo y prestigio de la especialidad

BACKGROUND: The Spanish Academy of Dermatology and Venereology (AEDV) has decided that a Strategic Plan is needed to help the association adapt to new circumstances and anticipate future developments. OBJECTIVES: 1) To position the AEDV as a medical association that can exert an influence in everything related to dermatology. 2) To contribute to the development of the specialty, strengthening the prestige and reputation of dermatology and dermatologists. 3) To establish a model for operating and strategic thinking that can be handed on to successive Boards of Directors and will enable the Academy to identify future challenges. METHODS: The approach used to develop the Strategic Plan was as follows: analysis of trends in the health care system; assessment of the current situation of AEDV and of dermatology in general through an internal analysis based on surveys and interviews with academics; analysis of strengths, weaknesses, opportunities, and threats; preparation of a mission statement; and identification, development, and implementation of a strategy map prioritizing strategic lines of action. RESULTS: The strategy map set out 16 general goals grouped into 4 main topics (achieving the vision, internal and external customers, internal processes, and innovation) and detailed in an action plan with 19 initiatives, each with specific actions. The plan will be monitored by the Strategic Plan Monitoring Committee, which is made up of the members of the Standing Committee and the chairs of the 9 Technical Committees responsible for implementing the initiatives. Comment: The Functional Plan should guide the management of AEDV until 2017, and its implementation will enable the association to contribute to the development and prestige of the specialty and position itself as a reference in terms of its functional model

Actualización del consentimiento informado en dermatología / Informed Consent in Dermatology: An Update

La legislación de nuestro país reconoce que el paciente tiene derecho a ser informado sobre los distintos aspectos de su enfermedad y a su autonomía en la toma de decisiones relativas al diagnóstico y tratamiento de la misma. Como dermatólogos tenemos la obligación de conocer, respetar y ejecutar dicha normativa en nuestra labor asistencial

Spanish legislation recognizes patients' right to be informed about various aspects of their illness and to make autonomous decisions regarding diagnosis and treatment. As dermatologists, we need to become familiar with this legislation, heed its stipulations, and implement them in our practice

Strategic Plan for the Spanish Academy of Dermatology and Venerology (AEDV): FuturAEDV 2013-2017.

BACKGROUND: The Spanish Academy of Dermatology and Venereology (AEDV) has decided that a Strategic Plan is needed to help the association adapt to new circumstances and anticipate future developments. OBJECTIVES: 1) To position the AEDV as a medical association that can exert an influence in everything related to dermatology. 2) To contribute to the development of the specialty, strengthening the prestige and reputation of dermatology and dermatologists. 3) To establish a model for operating and strategic thinking that can be handed on to successive Boards of Directors and will enable the Academy to identify future challenges. METHODS: The approach used to develop the Strategic Plan was as follows: analysis of trends in the health care system; assessment of the current situation of AEDV and of dermatology in general through an internal analysis based on surveys and interviews with academics; analysis of strengths, weaknesses, opportunities, and threats; preparation of a mission statement; and identification, development, and implementation of a strategy map prioritizing strategic lines of action. RESULTS: The strategy map set out 16 general goals grouped into 4 main topics (achieving the vision, internal and external customers, internal processes, and innovation) and detailed in an action plan with 19 initiatives, each with specific actions. The plan will be monitored by the Strategic Plan Monitoring Committee, which is made up of the members of the Standing Committee and the chairs of the 9 Technical Committees responsible for implementing the initiatives. COMMENT: The Functional Plan should guide the management of AEDV until 2017, and its implementation will enable the association to contribute to the development and prestige of the specialty and position itself as a reference in terms of its functional model.

Informed consent in dermatology: an update.

Spanish legislation recognizes patients' right to be informed about various aspects of their illness and to make autonomous decisions regarding diagnosis and treatment. As dermatologists, we need to become familiar with this legislation, heed its stipulations, and implement them in our practice.

Metástasis placentarias de melanomamaligno materno / Placental metastasis of maternal malignant melanoma

La aparición de metástasis placentarias o fetales secundarias a un cáncer materno es un hecho infrecuente, siendo el melanoma maligno el que conmayor frecuencia metastatiza a este nivel. Presentamos el caso de una paciente gestante que a los tres años del diagnóstico y tratamiento de un melanomamaligno, desarrolló metástasis cutáneas y viscerales que afectaron a la placenta aunque no al feto. El melanoma maligno no es el tumor más frecuenteen mujeres embarazadas, pero sí el que tiene mayor capacidad de afectar a la placenta o al feto (AU)

Placental or fetal metastasis due to a maternal cancer are rare, but malignant melanoma is the most common tumor to metastasize at this level. Wereport the case of a pregnant woman who developed visceral and cutaneous metastasis 3 years after the diagnosis and treatment of a malignantmelanoma. Metastasis affected the placenta but not the fetus. Malignant melanoma is not the most frequent malignant tumor during pregnancy, butis the most common type of cancer to metastasize to the placenta and the fetus (AU)

Úlcera labial secundaria a leishmaniasisvisceral en un paciente VIH-positivo / Lip ulceration due to visceral leishmaniasis in a HIV-positive patient

La Leishmaniasis es una infección intracelular poducida por el protozoo Leishmania.En países mediterráneos, L infantum puede causar leishmaniasis cutánea (LC) y visceral (LV).En pacientes VIH-positivos con LV, las lesiones cutáneas son en ocasiones el primer signo de afectación visceral. Presentamos el caso de un pacienteVIH-positivo con una ulceración de labio. Este hallazgo representó el primer síntoma de una LV oculta (AU)

Leishmaniasis is an intracellular infection caused by the protozoa Leishmania.L. infantum may cause both cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) in Mediterranean countries.In HIV-positive patients with VL, cutaneous lesions are sometimes the first sign of visceral involvement. We report the case of a HIV-positive patient,with a lip ulceration as a first symptom of an occult LV (AU)

Lymphangioma circumscriptum: an example of Whimster's hypothesis.

Lymphangioma circumscriptum is an uncommon hamartomatous malformation that is not only localized to an area of skin, but also spreads to subcutaneous tissue and muscle (Whimster's hypothesis). We describe a 7-year-old boy with a bluish plaque on the left side of the back and abdomen with clusters of translucent vesicles (frog spawn). Magnetic resonance imaging showed the lymphangioma had spread to muscles and even fat adjacent to the left kidney. We decided against radical surgery as it would have been too aggressive, and limited excision can produce new surface lymphangiomas.

Langerhans' cells and lymphocytic infiltrate in AIDS-associated Kaposi's sarcoma. An immunohistochemical study.

The epidermal Langerhans' cells are dendritic cells of the skin capable of triggering cutaneous immune responses. They possess the membrane antigens required to this effect: class II histocompatibility antigen, CD1a and CD4; the latter acts as receptor for the human immunodeficiency virus. The skin is the organ primarily affected by Kaposi's sarcoma (KS). In epidemic KS, the local immunologic conditions of the skin are little known. We therefore studied 12 patients with AIDS-associated KS, evaluating the density and phenotypic expression in KS-affected and unaffected skin of the following antigens: CD1a, HLA-DR, CD4 in dendritic epidermal cells and dermis, and CD3, CD4 and CD8 in cells of the inflammatory infiltrate, using monoclonal antibodies applied to frozen sections with the avidin-biotin-peroxidase technique. Langerhans' cells in the AIDS-KS skin lesions were found to be decreased in number. This decrease was even more pronounced in the case of cells expressing HLA-DR antigen. A number of them were also revealed with CD4. The tumour lymphocytic infiltrate was almost exclusively composed of CD3+ CD8+ phenotype lymphocytes. The dermis also revealed CD4+ dendritic cells. The basal keratinocytes focally expressed HLA-DR. These phenotypical alterations of the Langerhans' cells and the local immunological imbalance observed may contribute to the growth and continuity of the KS lesions.

Interleukin-6 in normal skin and psoriasis.

Interleukin-6 (IL-6 or BSF-2/IFN beta 2) is a component of normal human skin. IL-6 was immunologically detected in basal keratinocytes, endothelial cells and in a number of mononucleated cells and fibroblasts in normal skin and sudoriparous ducts. In psoriasis, intense labelling of the cytoplasm in the vicinity of keratinocyte membranes was detected in all epidermal layers and other skin appendages. The fact that this interleukin acts synergistically with respect to IL-1 and Tumour Necrosis Factor (TNF) strengthens the hypothesis whereby IL-6 may contribute via its receptor action to EGF function in modulating cell hyper-proliferation in psoriasis.

[Kaposi's sarcoma associated with human immunodeficiency virus infection: a clinical, histological, immunohistochemical, serological and development review]. / Sarcoma de Kaposi asociado a infección por el virus de la inmunodeficiencia humana: revisión clínica, histológica, inmunohistoquímica, serológica y evolutiva.

BACKGROUND: A clinical, histologic, immunohistochemical, serological and evolutive review was carried out in 12 cases of Kaposi's sarcoma, representing 5.5% (12/217) of the HIV positive patients consecutively seen during an 18 month period. METHODS: The patients were clinically examined and staging was assessed. Skin biopsy was performed in all cases, and of healthy perilesional skin in eight, with HE and Perls stains. Immunohistochemical study of the skin lesions was carried out with monoclonal anti-collagen, anti-laminin, anti-HLA-DR, OKM5 and UEA-I antibodies. Statistical analysis was carried out with chi-square and Student's tests. RESULTS: There were 11 homosexual males and a prostitute parenteral drugs addicted female. The clinical presentation spectrum ranged from a single longitudinal lesion to multiple disseminated lesions in the whole skin and mucosae. Visceral or lymph node involvement was shown in three cases. Histological study also showed a spectrum of lesions from initial endothelial proliferation in perilesional healthy skin areas to mixed fusocellular and endothelial proliferation in nodular lesions. The immunohistochemical study with the appropriate monoclonal antibodies demonstrated the endothelial origin of cellular components. Some laboratory parameters (beta-2-microglobulin, total lymphocytes/mm3, total CD4 cells/mm3) were useful for prognostic evaluation at the time of diagnosis. CONCLUSIONS: KS associated with HIV infection is a vascular hyperplasia of endothelial origin virtually exclusive of homosexual males. Although the diagnose of KS does not determine by itself the vital prognosis of these patients, some laboratory parameters at the time of diagnosis are useful for the prognosis of HIV infection.

[Ultrastructural study of a case of argyria]. / Estudio ultraestructural de un caso de argiria.

The authors studied by transmission electron microscopy a case of cutaneous argyria. Found round and oval forms into which there are a silver granules forming rings. Those images sequencied permit hypothesized that the winning of the solved silver by phagocytes into which are precipitate and eliminate out of the cell.

[Expression of HLA-Dr and CD1+ cells in malignant and benign pigmentary tumors]. / Expresión del HLA-Dr y células CD1+ en tumores pigmentarios malignos y benignos.

The authors studied the expression of CD1 and HLA-Dr antigen in benign and malignant melanic tumors to known if were the melanoma's cells or Langerhans cells, presents on the tumor, which exhibited the HLA-Dr antigens, and if the HLA-Dr expression was related to volume, depth and metastatic characteristics. These antigens were studied with the monoclonal antibodies labelled to avidin-biotin-peroxidase system. The results shows than the proportion between the number of Langerhans cells and HLA-Dr positive cells is inverse. No differences were found between the expression of the HLA-Dr antigens and number of Langerhans cells and volume, depth or metastatic characteristics.

[Palmoplantar and disseminated porokeratosis: immunohistochemical study]. / Poroqueratosis palmoplantar y diseminada: estudio inmunohistoquímico.

We present a new case of porokeratosis plantaris palmaris et disseminata (PPPD), observe in it a histological picture of cornoid lamella in palms, soles, arms, legs and trunk. In this dermatosis, mediant lectins and involucrin to establish keratinocytes alteration. The immunohistochemical studies have reveals not normal formation in the envelope cornea, and fundamentally D-galactose show a marked diminution in the cell membrane.

A study of local immunity in psoriasis.

We have studied biopsies of lesional skin with monoclonal and polyclonal antibodies to determine the nature of the infiltrate in different forms of psoriasis. In guttate psoriasis the number of Langerhans cells (LC) was not increased and CD8+ cells predominated, however, most CD4+ cells were activated. In erythrodermal psoriasis some CDI+ cells were found in the dermis although CD8+ cells predominated and were activated. In palmo-plantar psoriasis LC were found in the epidermis and superficial dermis and CD4+ cells were more numerous than CD8+ cells, some in turn expressing HLA-DR. In flexural psoriasis the LC formed clusters in the epidermis, and activated CD4+ cells predominated. In psoriasis vulgaris CD4+ cells predominated over CD8+ although the latter were activated. Our observations tend to support Valdimarsson's hypothesis on the immune basis of psoriasis, but we believe that two cycles coexist in psoriasis--one inflammatory and the other immunological--and that interaction between these leads to epidermal hyperproliferation.