Treatment of extramammary Paget's disease with imiquimod in a real-life setting: a multicenter retrospective analysis in Spain.

BACKGROUND: Topical imiquimod has shown to be an effective treatment for EMPD, although available evidence supporting its use is based on case reports and small series of patients. OBJECTIVES: To investigate the therapeutic outcomes and analyze potential clinico-pathological factors associated with imiquimod response in a large cohort of EMPD patients. METHODS: Retrospective chart review of 125 EMPD patients treated with imiquimod at 20 Spanish tertiary-care hospitals. RESULTS: During the study period, patients received 134 treatment regimens with imiquimod, with 70 (52.2%) cases achieving complete response (CR), 41 (30.6%) partial response and 23 (17.2%) no response. The cumulative CR rates at 24 and 48 weeks of treatment were 46.3% and 71.8%, respectively, without significant differences between first-time and previously treated EMPD. Larger lesions (≥6 cm; p = 0.038) and EMPD affecting >1 anatomical site (p = 0.002) were significantly associated with a worse treatment response. However, the CR rate did not differ significantly by the number of treatment applications (≤4 vs. > 4 times/week; p = 0.112). Among patients who achieved CR, 30 (42.9%) developed local recurrences during a mean follow-up period of 36 months, with an estimated 3 and 5-year recurrence free-survival of 55.7% and 36.4%, respectively. CONCLUSIONS: Imiquimod appears as an effective therapeutic alternative for both first-line and previously treated EMPD lesions. However, a less favorable therapeutic response could be expected in larger lesions and those affecting >1 anatomical site. Based on our results, a 3-4 times weekly regimen of imiquimod with a treatment duration of at least 6 months could be considered an appropriate therapeutic strategy for EMPD patients.

Therapeutic outcomes and survival analysis of Extramammary Paget's disease: A multicentre retrospective study of 249 patients.

BACKGROUND: Evidence regarding long-term therapeutic outcomes and disease-specific survival (DSS) in Extramammary Paget's disease (EMPD) is limited. OBJECTIVES: To assess the DSS and outcomes of surgical and nonsurgical therapeutic modalities in a large cohort of EMPD patients. METHODS: Retrospective chart review of EMPD patients from 20 Spanish tertiary care hospitals. RESULTS: Data on 249 patients with a median follow-up of 60 months were analyzed. The estimated 5-, 10-, and 15-year DSS was 95.9%, 92.9%, and 88.5%, respectively. A significantly lower DSS was observed in patients showing deep dermal invasion (≥1 mm) or metastatic disease (P < .05). A ≥50% reduction in EMPD lesion size was achieved in 100% and 75.3% of patients treated with surgery and topical therapies, respectively. Tumor-free resection margins were obtained in 42.4% of the patients after wide local excision (WLE). The 5-year recurrence-free survival after Mohs micrographic surgery (MMS), WLE with tumor-free margins, WLE with positive margins, radiotherapy, and topical treatments was 63.0%, 51.4%, 20.4%, 30.1%, and 20.8%, respectively. LIMITATIONS: Retrospective design. CONCLUSIONS: EMPD is usually a chronic condition with favorable prognosis. MMS represents the therapeutic alternative with the greatest efficacy for the disease. Recurrence rates in patients with positive margins after WLE are similar to the ones observed in patients treated with topical agents.

Increasing incidence of lentigo maligna and lentigo maligna melanoma in Catalonia.

BACKGROUND: Recent epidemiological studies suggest that past data where superficial spreading melanoma was by far the most common subtype of melanoma may not reflect current patterns of sun exposure or other risk factors more involved in other subtypes of melanoma as lentigo maligna (LM) or lentigo maligna melanoma (LMM). METHODS: In order to measure the current situation in our country, all cases of LM and LMM diagnosed in 23 hospitals in Catalonia, from 2000 to 2007, were recorded. RESULTS: Although for the global period LM/LMM represented only 8.4% of cases, an increasing trend in this percentage was observed throughout the study period (from 6.9% [27 cases] in 2000 to 13.1% [94 cases] in 2007). Also, an increasing incidence of LM/LMM was observed, especially in chronically sun-exposed areas (85.5% involving the head and neck region). During the 8 years of the registry, the mean Breslow thickness of LMM remained stable. However, the increase in the number of LM (in situ) cases was significantly higher than the increase of the invasive ones. CONCLUSIONS: An important observation from this data is that aging of population and current sun exposure patterns could keep increasing the incidence of LM/LMM, which may become an important public healthcare problem, over the other histological subtypes. In order to establish primary or secondary preventive measures to the LM/LMM risk-population, it is imperative to highlight the importance of chronic sun damage as a melanoma risk factor, and not only sunburn, most commonly addressed in melanoma prevention campaigns.

Melanoma incidence increases in the elderly of Catalonia but not in the younger population: effect of prevention or consequence of immigration?

All cases of MM diagnosed in 23 hospitals in Catalonia, from 2000 to 2007 were recorded and melanoma incidence calculated and adjusted for the European standard population via the direct method. The age standardised rate/100,000 inhabitants varied from 6.74 in 2000 to 8.64 in 2007 for all melanomas and from 4.79 to 5.80 for invasive MMs; the Breslow thickness was stable during the period. The increase in invasive melanoma incidence in the elderly was remarkable, the crude rate/100,000 inhabitants increasing from 11.04 (2000) to 15.49 (2007) in the 60-64 year population, while remaining more stable in the 30-34 year range, from 3.97 in 2000 to 4.55 in 2007, and with a tendency to decrease from 5.1 in 2000 to 2.5 in 2007 for the age range of 25-29 years. These lower age ranges are much more affected by immigration. Despite the large immigrant population (nearly one million immigrants arrived in Catalonia during the study period from countries with a low melanoma incidence), melanoma incidence in our region has risen considerably and this trend is likely to persist in the near future.

Mutations in SNRPE, which encodes a core protein of the spliceosome, cause autosomal-dominant hypotrichosis simplex.

Hypotrichosis simplex (HS) comprises a group of hereditary isolated alopecias that are characterized by a diffuse and progressive loss of hair starting in childhood and shows a wide phenotypic variability. We mapped an autosomal-dominant form of HS to chromosome 1q31.3-1q41 in a Spanish family. By direct sequencing, we identified the heterozygous mutation c.1A>G (p.Met1?) in SNRPE that results in loss of the start codon of the transcript. We identified the same mutation in a simplex HS case from the UK and an additional mutation (c.133G>A [p.Gly45Ser]) in a simplex HS case originating from Tunisia. SNRPE encodes a core protein of U snRNPs, the key factors of the pre-mRNA processing spliceosome. The missense mutation c.133G>A leads to a glycine to serine substitution and is predicted to disrupt the structure of SNRPE. Western blot analyses of HEK293T cells expressing SNRPE c.1A>G revealed an N-terminally truncated protein, and therefore the mutation might result in use of an alternative in-frame downstream start codon. Subcellular localization of mutant SNRPE by immunofluorescence analyses as well as incorporation of mutant SNRPE proteins into U snRNPs was found to be normal, suggesting that the function of U snRNPs in splicing, rather than their biogenesis, is affected. In this report we link a core component of the spliceosome to hair loss, thus adding another specific factor in the complexity of hair growth. Furthermore, our findings extend the range of human phenotypes that are linked to the splicing machinery.

Bebé colodión transitorio / Self-healing collodion baby

Introducción. El bebé colodión neonatal es una forma clínica de presentación de la ictiosis congénita. En el estudio colaborativo español de malformaciones congénitas (ECEMC) la frecuencia es inferior a un caso cada 100.000 recién nacidos. Caso clínico. Presentamos el caso clínico de un recién nacido afectado de esta patología que, a pesar de la espectacularidad de la exploración clínica en el periodo neonatal, presentó una buena evolución posterior. Comentarios. Se plantea el diagnóstico diferencial de las posibles entidades que pueden debutar en el periodo neonatal en forma de bebé colodión y se comenta la posibilidad de efectuar estudios genéticos moleculares(AU)

Introduction. Congenital ichthyosis, which presents as collodion baby, is a very rare disorder. In our national collaborative study of congenital malformations (ECEMC) only one out of more than 100.000 newborns is diagnosed as having congenital ichthyosis. Case report. We describe the case of a trasient collodion baby who, despite the prominent clinical findings at birth, had a bening course. Bebè col·lodió transitori M. Mar Garcia González 1, Mar Calvo 1, Pilar Villalobos 1, Stephan Schneider 1, Elena Riera 1, M. Jesús Muntané 2, Miquel Just 3, Vicente Villa 4 1 Servei de Pediatria 2 Servei d’Anatomia Patològica; 3 Servei de Dermatologia; Fundació Salut Empordà. Figueres (Girona). 4 Servei de Dermatologia. Hospital Sant Joan de Déu. Barcelona Comments. The differential diagnosis of possible clinical disorders that can manifest as collodion baby in the perinatal period is discussed. Molecular genetic studies are also reviewed(AU)

Relationships between lung function, smoking and morphology of dermal elastic fibres.

OBJECTIVE: To investigate the relationship between lung function and dermal elastic fibres in non-smokers and smokers with and without chronic obstructive pulmonary disease (COPD). METHOD: A cross-sectional study was performed with lung function as the outcome [forced expiratory volume in the first second (FEV1)%, FEV1/forced vital capacity (FVC)% and residual volume (RV)/total lung capacity (TLC)%] and smoking (pack-years) and morphology of dermal elastic fibres (fibres/mm(2) and percentage histologic field filled with them) as independent variables, with assessment of the associations between these variables by univariate and multivariate testing. RESULTS: Sixty outpatients reporting chronic cough and/or phle\gm were enrolled (16 non-smokers/44 smokers; COPD: 26, 43.3%). Both lung function and elastic fibres in the reticular dermis (fibres/mm(2)r(s) = 0.36, percentage of the histologic field filled by elastic fibres r(s) = 0.48, P < or = 0.01) correlated with cumulative smoking (Spearman's rank correlation coefficient). Lung function parameters correlated with percentage of the histologic field filled by elastic fibres (FEV1%: r = -0.43; FEV1/FVC%: r = -0.36 and RV/TLC%: r = 0.43; P < or = 0.01, Pearson correlation coefficient), and COPD was significantly related to this morphologic parameter (odds ratio 1.26, 95% confidence interval 1.06-1.48; P = 0.006), associations that depended mainly on cumulative smoking. CONCLUSION: Lung function impairment with an obstructive pattern is associated with morphologic abnormalities in the reticular dermis appearing in the histologic section as an increase in the percentage of the field filled by elastic fibres. This relationship depends on cumulative smoking and suggests a common effect of smoking on the elastic fibres in both lung and skin.

Alteraciones de las fibras elásticas de la piel en pacientes fumadores y su relación con el deterioro de la función pulmonar / Alterations in the elastic fibers of the skin in smokers and their relation to the deterioration of pulmonary function

Objetivo: Investigar los efectos del consumo de tabaco sobre las fibras elásticas de la dermis, así como la relación entre estas fibras elásticas de la dermis y la función pulmonar, tanto en no fumadores como en fumadores. Método: Estudio transversal con los parámetros de función pulmonar (volumen espiratorio forzado en el primer segundo, FEV1/capacidad vital forzada, FVC) como variables dependientes y el consumo de tabaco y la morfología de las fibras elásticas de la dermis, analizada mediante morfometría estática (número y densidad de las fibras elásticas de la dermis en piel no fotoexpuesta), como variables independientes. La asociación entre las variables se analizó mediante tests bivariados y multivariados. Resultados: Se incluyeron 60 pacientes en el estudio (media 58,1; desviación estándar [DE] 6,9 años/16 no fumadores, 26 ex fumadores y 18 fumadores activos). La morfometría de la dermis reticular mostró un aumento del número y de la densidad de las fibras elásticas en fumadores (666,6 DE 208,7 fibras/mm2 y 145,4 DE 3,8%) respecto a los no fumadores (506,5 DE 156,1 fibras/mm2 y 11,3 DE 1,7%) (p < 0,01, test t). Los parámetros de función pulmonar mostraron una correlación con la densidad de las fibras elásticas (FEV1: r = -0,43; FVC: r = -0,31; coeficiente de correlación de Pearson). La asociación entre la densidad de las fibras elásticas y FEV1 (coeficiente de correlación parcial = -0,27; p = 0,04) se mantuvo estadísticamente significativa después de ajustar por el consumo de tabaco. Conclusión: Los pacientes fumadores presentan un aumento significativo de la densidad de las fibras elásticas de la piel respecto a los no fumadores. Asimismo, este aumento de la densidad de las fibras elásticas de la dermis muestra una correlación con el deterioro de la función pulmonar. Esta relación depende sólo parcialmente del consumo de tabaco, hallazgo que sugiere la existencia de factores genéticos que afectarían de forma similar a las fibras elásticas del pulmón y a las de la piel (AU)

Dermatitis exfoliativa generalizada por eritropoyetina / Generalized exfoliative dermatitis due to erythropoietin

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