Biogeographical origin and timing of the founder ichthyosis TGM1 c.1187G > A mutation in an isolated Ecuadorian population.

An unusually high frequency of the lamellar ichthyosis TGM1 mutation, c.1187G > A, has been observed in the Ecuadorian province of Manabí. Recently, the same mutation has been detected in a Galician patient (Northwest of Spain). By analyzing patterns of genetic variation around this mutation in Ecuadorian patients and population matched controls, we were able to estimate the age of c.1187G > A and the time to their most recent common ancestor (TMRCA) of c.1187G > A Ecuadorian carriers. While the estimated mutation age is 41 generations ago (~1,025 years ago [ya]), the TMRCA of Ecuadorian c.1187G > A carrier haplotypes dates to just 17 generations (~425 ya). Probabilistic-based inferences of local ancestry allowed us to infer a most likely European origin of a few (16% to 30%) Ecuadorian haplotypes carrying this mutation. In addition, inferences on demographic historical changes based on c.1187G > A Ecuadorian carrier haplotypes estimated an exponential population growth starting ~20 generations, compatible with a recent founder effect occurring in Manabí. Two main hypotheses can be considered for the origin of c.1187G > A: (i) the mutation could have arisen in Spain >1,000 ya (being Galicia the possible homeland) and then carried to Ecuador by Spaniards in colonial times ~400 ya, and (ii) two independent mutational events originated this mutation in Ecuador and Galicia. The geographic and cultural characteristics of Manabí could have favored a founder effect that explains the high prevalence of TGM1 c.1187G > A in this region.

Systemic Treatment of Moderate to Severe Psoriasis in Pediatric Patients in Galicia, Spain: A Descriptive Study. / Tratamiento sistémico de la psoriasis moderada-grave en edad pediátrica en Galicia: estudio descriptivo.

BACKGROUND AND OBJECTIVE: Studies on the use of systemic therapy for psoriasis in pediatric patients are scarce. The main aim of this study was to describe the systemic treatments used for moderate to severe psoriasis in pediatric clinical settings. The second aim was to describe the effectiveness and safety of these treatments. MATERIAL AND METHODS: Descriptive, cross-sectional, multicenter study of patients under 18 years of age with moderate to severe psoriasis who were being treated or had been treated with a systemic drug (conventional or biologic) or phototherapy. We recorded demographic and clinical information, treatments received, tolerance, adverse effects, and response to treatment. RESULTS: Data were collected for 40 patients (60% female; mean age, 13 years) who had received 63 treatments in total. The most common first treatment (n=40) was phototherapy (administered to 68% of patients), followed by acitretin (15%). The most common treatments overall (n=63) were phototherapy (57%) and methotrexate (16%). At week 12 (evaluation of systemic treatment and phototherapy), 66% of the patients were classified as good responders and 22% as partial responders. The respective rates for week 24 (evaluation of systemic treatment only) were 36% and 32%. The treatments were well tolerated (97%) and adverse effects were reported in just 11% of cases. There were no treatment discontinuations because of adverse effects. CONCLUSIONS: Phototherapy, followed by methotrexate, was the most common treatment for moderate to severe psoriasis in this series of patients under 18 years. The treatments showed a favorable safety profile and were associated with a good response rate of 66% at week 12 (systemic treatment and phototherapy) and 36% at week 24 (systemic treatment only).

Tratamiento sistémico de la psoriasis moderada-grave en edad pediátrica en Galicia: estudio descriptivo / Systemic Treatment of Moderate to Severe Psoriasis in Pediatric Patients in Galicia, Spain: A Descriptive Study

ANTECEDENTES Y OBJETIVO: Los trabajos sobre el tratamiento sistémico de la psoriasis en edad pediátrica son escasos. El objetivo principal de este trabajo consistió en describir qué tratamientos sistémicos se emplean en práctica clínica en psoriasis moderada-grave en edad pediátrica. Secundariamente se describió la efectividad y perfil de seguridad de dichos tratamientos. MATERIALES Y MÉTODOS: Estudio descriptivo transversal multicéntrico, de los pacientes con psoriasis moderada-grave, que siendo menores de 18 años estuviesen recibiendo o hubieran recibido tratamiento sistémico (clásico o biológico) o fototerapia. Se recogieron datos clínico-demográficos, tipo de tratamiento recibido, y tolerancia, efectos indeseables y respuesta al mismo. RESULTADOS: Se obtuvieron datos de 40 pacientes (60% sexo femenino, edad media 13 años), que realizaron 63 ciclos de tratamiento. Teniendo en cuenta el primer tratamiento (n = 40), la fototerapia fue la opción más frecuente (68%), seguida de acitretino (15%). Considerando el total de ciclos de tratamiento (n = 63), el tratamiento más frecuentemente empleado fue la fototerapia (57%), seguida de metotrexato (16%). En la semana 12 (incluye evaluación de fototerapia), el 66% y el 22% fueron buenos respondedores o respondedores parciales, respectivamente. En la semana 24 (datos exclusivos sobre fármacos sistémicos), el 36% y el 32% continuaron con respuestas buenas y parciales. Los tratamientos fueron bien tolerados (97%) y los efectos indeseables escasos (11%), sin que en ningún caso motivasen la suspensión del fármaco. CONCLUSIONES: En la población menor de 18 años con psoriasis moderada-grave evaluada la fototerapia fue el tratamiento más utilizado, seguida de metotrexato. Los tratamientos consiguieron porcentajes de buenos respondedores del 66% en la semana 12 (incluida fototerapia), y del 36% en la semana 24 (fármacos sistémicos sin fototerapia), presentando un buen perfil de seguridad

BACKGROUND AND OBJECTIVE: Studies on the use of systemic therapy for psoriasis in pediatric patients are scarce. The main aim of this study was to describe the systemic treatments used for moderate to severe psoriasis in pediatric clinical settings. The second aim was to describe the effectiveness and safety of these treatments. MATERIAL AND METHODS: Descriptive, cross-sectional, multicenter study of patients under 18 years of age with moderate to severe psoriasis who were being treated or had been treated with a systemic drug (conventional or biologic) or phototherapy. We recorded demographic and clinical information, treatments received, tolerance, adverse effects, and response to treatment. RESULTS: Data were collected for 40 patients (60% female; mean age, 13 years) who had received 63 treatments in total. The most common first treatment (n = 40) was phototherapy (administered to 68% of patients), followed by acitretin (15%). The most common treatments overall (n =63) were phototherapy (57%) and methotrexate (16%). At week 12 (evaluation of systemic treatment and phototherapy), 66% of the patients were classified as good responders and 22% as partial responders. The respective rates for week 24 (evaluation of systemic treatment only) were 36% and 32%. The treatments were well tolerated (97%) and adverse effects were reported in just 11% of cases. There were no treatment discontinuations because of adverse effects. CONCLUSIONS: Phototherapy, followed by methotrexate, was the most common treatment for moderate to severe psoriasis in this series of patients under 18 years. The treatments showed a favorable safety profile and were associated with a good response rate of 66% at week 12 (systemic treatment and phototherapy) and 36% at week 24 (systemic treatment only)

Incidencia y mortalidad del cáncer cutáneo en España: revisión sistemática y metaanálisis / Skin Cancer Incidence and Mortality in Spain: A Systematic Review and Meta-Analysis

INTRODUCCIÓN Y OBJETIVOS: El objetivo de la revisión sistemática es describir la incidencia y mortalidad en España del carcinoma basocelular, carcinoma espinocelular, melanoma y carcinoma de células de Merkel. MATERIAL Y MÉTODOS: Se realizó una búsqueda en Medline, Embase y revisión de artículos de la Red Española de Registros de Cáncer (REDECAN) y la Agencia Internacional de Investigación sobre el Cáncer (IARC). Se evaluó la calidad metodológica de los estudios. La heterogeneidad estadística se midió usando el estadístico I2. Para el metaanálisis de los datos se empleó un modelo de efectos aleatorios debido a la heterogeneidad de los resultados. RESULTADOS: Se incluyeron un total de 32 trabajos en la revisión sistemática. La tasa de incidencia del carcinoma basocelular global cruda fue 113,05 (IC 95%: 89,03-137,08)/100.000 personas-año para los estudios que emplean la metodología de los registros de cáncer (contando un solo tumor por persona y diagnóstico histológico). La tasa de incidencia mediante criterios clínicos e histológicos, y contando tumores en lugar de personas, fue de 253,23 (IC 95%: 273,01-269,45)/100.000 personas-año. La incidencia de carcinoma espinocelular fue de 38,16 (IC 95%: 31,72-39,97)/100.000 personas-año, de 8,76 (IC 95%: 7,50-10,02)/100.000 personas-año para el melanoma y 0,28 (IC 95%: 0,15-0,40)/100.000 personas-año para el carcinoma de células de Merkel. CONCLUSIONES: La tasa de incidencia del carcinoma basocelular y espinocelular en España está probablemente infraestimada al utilizar el método habitual de los registros. La tasa de incidencia del melanoma cutáneo es baja en comparación con otros países europeos, al igual que la tasa de incidencia del carcinoma de células de Merkel

INTRODUCTION AND OBJECTIVES: The aim of this systematic review was to describe the incidence and mortality of basal cell carcinoma, squamous cell carcinoma, melanoma, and Merkel cell carcinoma in Spain. MATERIAL AND METHODS: We performed a search of the MEDLINE and Embase databases and reviewed articles from the Spanish Network of Cancer Registries (REDECAN) and the International Agency for Research on Cancer (IARC). The methodological quality of the studies was evaluated and statistical heterogeneity was measured using the I2 index. A random-effects model was used to perform the meta-analysis because of the heterogeneity of the data. RESULTS: Thirty-two papers were included in the systematic review. The crude incidence rate for basal cell carcinoma was 113.05 (95% CI, 89.03-137.08) cases per 100 000 person-years for the studies based on the registration methodology normally used by registries (in which only 1 tumor with histological confirmation is counted per person). However, the same incidence rate calculated on the basis of clinical and histologic criteria and counting tumors rather than individual patients was 253.23 (95% CI, 273.01-269.45) cases per 100 000 person-years. The incidence was 38.16 (95% CI, 31.72-39.97) cases per 100 000 person-years for squamous cell carcinoma, 8.76 (95% CI, 7.50-10.02) cases per 100 000 person-years for melanoma, and 0.28 (95% CI, 0.15-0.40) cases per 100 000 person-years for Merkel cell carcinoma. CONCLUSIONS: The registration methodology normally used by cancer registries probably underestimates the incidence rates of basal cell and squamous cell carcinoma in Spain. The incidence rates of cutaneous melanoma and Merkel cell carcinoma are lower in Spain than in other European countries

Skin Cancer Incidence and Mortality in Spain: A Systematic Review and Meta-Analysis. / Incidencia y mortalidad del cáncer cutáneo en España: revisión sistemática y metaanálisis.

INTRODUCTION AND OBJECTIVES: The aim of this systematic review was to describe the incidence and mortality of basal cell carcinoma, squamous cell carcinoma, melanoma, and Merkel cell carcinoma in Spain. MATERIAL AND METHODS: We performed a search of the MEDLINE and Embase databases and reviewed articles from the Spanish Network of Cancer Registries (REDECAN) and the International Agency for Research on Cancer (IARC). The methodological quality of the studies was evaluated and statistical heterogeneity was measured using the I(2) index. A random-effects model was used to perform the meta-analysis because of the heterogeneity of the data. RESULTS: Thirty-two papers were included in the systematic review. The crude incidence rate for basal cell carcinoma was 113.05 (95% CI, 89.03-137.08) cases per 100 000 person-years for the studies based on the registration methodology normally used by registries (in which only 1 tumor with histological confirmation is counted per person). However, the same incidence rate calculated on the basis of clinical and histologic criteria and counting tumors rather than individual patients was 253.23 (95% CI, 273.01-269.45) cases per 100 000 person-years. The incidence was 38.16 (95% CI, 31.72-39.97) cases per 100 000 person-years for squamous cell carcinoma, 8.76 (95% CI, 7.50-10.02) cases per 100 000 person-years for melanoma, and 0.28 (95% CI, 0.15-0.40) cases per 100 000 person-years for Merkel cell carcinoma. CONCLUSIONS: The registration methodology normally used by cancer registries probably underestimates the incidence rates of basal cell and squamous cell carcinoma in Spain. The incidence rates of cutaneous melanoma and Merkel cell carcinoma are lower in Spain than in other European countries.

Alopecia triangular temporal / Temporal triangular alopecia

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Fotosensibilidad por tiazidas / Photosensitivity Due to Thiazides

Las tiazidas son diuréticos que se comenzaron a usar en la década de 1950 y su uso está muy extendido en la actualidad. Poco después de su introducción se describieron las primeras reacciones de fotosensibilidad, aunque han sido descritas solo de forma infrecuente con posterioridad. Revisamos los casos de fotosensibilidad por tiazidas publicados hasta diciembre de 2011. Encontramos 62 casos, de los cuales 33 eran mujeres y 29 varones. La forma de presentación más común fue con lesiones eccematosas fotodistribuidas. La hidroclorotiazida fue el agente causal más frecuente. Solo algunos casos publicados recogen el resultado del estudio fotobiológico. En la mayoría el fototest mostró un respuesta alterada a ultravioleta A (UVA) sola y a UVA + ultravioleta B (UVB). En algunos casos el fototest fue normal y solo el fotoparche estaba alterado. El diagnóstico de fotosensibilidad por tiazidas requiere un alto índice de sospecha. De forma ideal debería confirmarse mediante estudio fotobiológico

Thiazides are widely used diuretics that first became available in the 1950s. The first reports of photosensitivity reactions to thiazides were published shortly after the introduction of these drugs, but few cases have been described since. We review all the cases of photosensitivity due to thiazides published up to December 2011. We found 62 cases, 33 in women and 29 in men. The most common presentation was eczematous lesions in a photodistributed pattern, and the most common causative agent was hydrochlorothiazide. The results of photobiological studies were published in only some of the cases reviewed. In most cases, phototesting revealed an abnormal response to UV-A alone or to both UV-A and UV-B. In some cases, the results of phototesting were normal and only photopatch testing yielded abnormal results. Diagnosis of photosensitivity due to thiazides requires a high degree of suspicion. Ideally, diagnosis should be confirmed by a photobiological study

Photosensitivity due to thiazides.

Thiazides are widely used diuretics that first became available in the 1950s. The first reports of photosensitivity reactions to thiazides were published shortly after the introduction of these drugs, but few cases have been described since. We review all the cases of photosensitivity due to thiazides published up to December 2011. We found 62 cases, 33 in women and 29 in men. The most common presentation was eczematous lesions in a photodistributed pattern, and the most common causative agent was hydrochlorothiazide. The results of photobiological studies were published in only some of the cases reviewed. In most cases, phototesting revealed an abnormal response to UV-A alone or to both UV-A and UV-B. In some cases, the results of phototesting were normal and only photopatch testing yielded abnormal results. Diagnosis of photosensitivity due to thiazides requires a high degree of suspicion. Ideally, diagnosis should be confirmed by a photobiological study.

Eritema multiforme fotodistribuido / Photodistributed Erythema Multiforme

A pesar de que la fotodistribución del eritema multiforme se conoce desde hace muchos años, pocos casos de eritema multiforme fotodistribuido (EMF) han sido descritos hasta la fecha. El EMF es una dermatosis infrecuente, y probablemente infradiagnosticada, que puede afectar a sujetos de ambos sexos y de todas las edades. Se ha relacionado con fármacos, reactivaciones del virus herpes simple y erupción polimorfa lumínica. Su diagnóstico se basa en la anamnesis, la exploración física, la histopatología y el estudio fotobiológico. Su curso es benigno y autolimitado, pero pueden aparecer brotes durante varios años si no se suprime el agente causal. Se trata de forma sintomática, evitando los desencadenantes y adoptando medidas de fotoprotección (AU)

Although the existence of photodistributed erythema multiforme has been recognized for years, few cases have been described to date. It is an uncommon, and probably underdiagnosed, skin disorder that can affect individuals of both sexes and all ages. It has been associated with drugs, reactivation of herpes simplex virus infection, and polymorphous light eruption. A diagnosis is made on the basis of history, physical examination, histology, and phototesting. The condition runs a benign, self-limiting course but patients may experience outbreaks for several years if the causative agent is not eliminated. It is treated symptomatically and patients are advised to avoid triggers and excessive sun exposure (AU)

Photodistributed erythema multiforme.

Although the existence of photodistributed erythema multiforme has been recognized for years, few cases have been described to date. It is an uncommon, and probably underdiagnosed, skin disorder that can affect individuals of both sexes and all ages. It has been associated with drugs, reactivation of herpes simplex virus infection, and polymorphous light eruption. A diagnosis is made on the basis of history, physical examination, histology, and phototesting. The condition runs a benign, self-limiting course but patients may experience outbreaks for several years if the causative agent is not eliminated. It is treated symptomatically and patients are advised to avoid triggers and excessive sun exposure.

Ictiosis congénitas autosómicas recesivas / Autosomal Recessive Congenital Ichthyosis

Las ictiosis congénitas autosómicas recesivas (ICAR) son trastornos infrecuentes de la queratinización que se engloban en las formas no sindrómicas de ictiosis. Clásicamente se distinguían en este grupo la ictiosis laminar (IL) y la eritrodermia ictiosiforme congénita (EIC). Actualmente se incluyen también la ictiosis arlequín, el bebé colodión autorresolutivo, el bebé colodión autorresolutivo acral y la ictiosis en traje de baño. Se ha estimado una prevalencia conjunta para IL y EIC de 1:138.000-1:300.000. En algunos países o regiones, como Noruega y la costa gallega, la prevalencia podría ser mayor debido a la existencia de efectos fundadores. Desde el punto de vista genético son muy heterogéneas. Seis genes se han asociado a estas entidades: TGM1, ALOXE3, ALOX12B, NIPAL4, CYP4F22 y ABCA12. En este trabajo se pretenden revisar los conocimientos actuales en el campo de las ICAR, incluyendo aspectos clínicos, histológicos, ultraestructurales, genético-moleculares y de tratamiento (AU)

The term autosomal recessive congenital ichthyosis (ARCI) refers to a group of raredisorders of keratinization classified as non syndromic forms of ichthyosis. This group was traditionally divided into lamellar ichthyosis (LI) and congenital ichthyosi form erythroderma (CIE)but today it also includes harlequin ichthyosis, self-healing collodion baby, acral self-healing collodion baby, and bathing suit ichthyosis.The combined prevalence of LI and CIE has been estimated at 1 case per 138 000 to 300 000population. In some countries or regions, such as Norway and the coast of Galicia, the prevalence may be higher due to founder effects. ARCI is genetically highly heterogeneous and has been associated with 6 genes to date: TGM1, ALOXE3, ALOX12B, NIPAL4, CYP4F22, and ABCA12. In this article, we review the current knowledge on ARCI, with a focus on clinical, histological, ultrastructural, genetic, molecular, and treatment-related aspects (AU)

Autosomal recessive congenital ichthyosis.

The term autosomal recessive congenital ichthyosis (ARCI) refers to a group of rare disorders of keratinization classified as nonsyndromic forms of ichthyosis. This group was traditionally divided into lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE) but today it also includes harlequin ichthyosis, self-healing collodion baby, acral self-healing collodion baby, and bathing suit ichthyosis. The combined prevalence of LI and CIE has been estimated at 1 case per 138 000 to 300 000 population. In some countries or regions, such as Norway and the coast of Galicia, the prevalence may be higher due to founder effects. ARCI is genetically highly heterogeneous and has been associated with 6 genes to date: TGM1, ALOXE3, ALOX12B, NIPAL4, CYP4F22, and ABCA12. In this article, we review the current knowledge on ARCI, with a focus on clinical, histological, ultrastructural, genetic, molecular, and treatment-related aspects.

Analysis of TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 in autosomal recessive congenital ichthyosis from Galicia (NW Spain): evidence of founder effects.

BACKGROUND: Mutations in six genes have been identified in autosomal recessive congenital ichthyosis (ARCI). To date, few studies have analysed the spectrum of these mutations in specific populations. OBJECTIVES: We have studied the characteristics of patients with ARCI in Galicia (NW Spain). Methods We recruited patients by contacting all dermatology departments of Galicia and the Spanish patient organization for ichthyosis. TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 were analysed in the patients and their relatives. RESULTS: We identified 23 patients with ARCI and estimated a prevalence of 1 : 122 000. Twenty of the patients were studied. Seventeen of them were clinically categorized as having lamellar ichthyosis (LI) and three as having congenital ichthyosiform erythroderma (CIE). TGM1 and ALOXE3 mutations were identified in 12/16 (75%) probands whereas no ALOX12B, NIPAL4 and CYP4F22 mutations were found. TGM1 mutations were found in 11/13 (85%) of LI probands. ALOXE3 mutations were identified in a single patient with CIE. Remarkably, mutations p.Arg760X, p.Asp408ValfsX21 and c.984+1G>A of TGM1 were present in six, four and two families, accounting for 41%, 23% and 14% of all TGM1 mutant alleles, respectively. CONCLUSIONS: The high percentage of patients with the same TGM1 mutations, together with the high number of homozygous probands (64%), indicates the existence of a strong founder effect in our population.