RESUMEN
BACKGROUND: Acne fulminans (AF) is a severe variant of inflammatory acne. It typically manifests as an explosive worsening and ulceration of skin lesions, and can be associated with systemic symptoms. However, there is a paucity of evidence-based information and no clear guidelines concerning the classification and treatment of AF. OBJECTIVE: To better define the spectrum of AF and its variants, devise optimal therapeutic approaches, and identify areas of future research. METHODS: A panel of physicians with expertise in severe acne vulgaris was convened after a comprehensive literature review of severe acne variants. Priority topics were reviewed and presented by each panelist at a 5-hour conference. Following review of the audiotape and scribed notes from the conference, surveys were utilized to address points of controversy and to clarify consensus recommendations. RESULTS: Appropriate clinical case presentations and consensus survey questions were utilized to create final recommendations based on both the literature and the expert consensus. LIMITATIONS: Limited evidenced-based data and prospective studies in the literature concerning the treatment of AF is available. CONCLUSION: These guidelines better characterize AF and provide health care practitioners approaches to the classification, treatment, and prevention of AF and its variants.
Asunto(s)
Acné Vulgar/tratamiento farmacológico , Acné Vulgar/clasificación , Medicina Basada en la Evidencia , Humanos , Guías de Práctica Clínica como AsuntoAsunto(s)
Infecciones por Coronavirus/prevención & control , Dermatología/educación , Control de Infecciones/normas , Internado y Residencia/normas , Solicitud de Empleo , Pandemias/prevención & control , Neumonía Viral/prevención & control , Betacoronavirus/patogenicidad , COVID-19 , Consenso , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Humanos , Internado y Residencia/métodos , Selección de Personal/normas , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Neumonía Viral/virología , SARS-CoV-2 , Estudiantes de MedicinaRESUMEN
Pediatric psoriasis is a chronic inflammatory skin condition. Current treatment modalities include topical medications, phototherapy, and systemic drugs, including biological agents. In cases of moderate-to-severe psoriasis recalcitrant to other therapies, biological therapies are often an attractive option given their dosing schedules, safety profiles, and need for less frequent laboratory monitoring, when compared with traditional systemic therapies. This article reviews biological treatment options approved for pediatric psoriasis and identifies others actively under investigation.
Asunto(s)
Adalimumab , Productos Biológicos , Fármacos Dermatológicos , Psoriasis , Ustekinumab , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/terapia , Niño , Adalimumab/uso terapéutico , Productos Biológicos/uso terapéutico , Ustekinumab/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Terapia Biológica , Infliximab/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Etanercept/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Rituximab/uso terapéutico , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Alefacept , Certolizumab Pegol/uso terapéuticoRESUMEN
Metastatic melanoma is a disease with a poor prognosis that currently lacks effective treatments. Critical biological features of metastasis include acquisition of migratory competence, growth factor independence, and invasive potential. In an attempt to identify genes that contribute to melanoma pathogenesis, a genome-wide search using bacterial artificial chromosome array comparative genomic hybridization and single nucleotide polymorphism arrays in a series of 64 metastatic melanoma samples and 20 melanoma cell lines identified increased copy numbers of Gab2 located on 11q14.1. Gab2 is an adaptor protein that potentiates the activation of the Ras-Erk and PI3K-Akt pathways and has recently been implicated in human cancer; however, its role in melanoma has not been explored. In this study, we found that Gab2 was either amplified (approximately 11%) and/or overexpressed (approximately 50%) in melanoma. Gab2 protein expression correlated with clinical melanoma progression, and higher levels of expression were seen in metastatic melanomas compared with primary melanoma and melanocytic nevi. We found that overexpression of Gab2 potentiates, whereas silencing of Gab2 reduces, migration and invasion of melanoma cells. Gab2 mediated the hyperactivation of Akt signaling in the absence of growth factors, whereas inhibition of the PI3K-Akt pathway decreased Gab2-mediated tumor cell migration and invasive potential. Gab2 overexpression resulted in enhanced tumor growth and metastatic potential in vivo. These studies demonstrate a previously undefined role for Gab2 in melanoma tumor progression and metastasis.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Melanoma/genética , Transducción de Señal/fisiología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Biomarcadores de Tumor/genética , Western Blotting , Movimiento Celular , Cromosomas Artificiales Bacterianos , Hibridación Genómica Comparativa , Técnica del Anticuerpo Fluorescente , Dosificación de Gen , Humanos , Hibridación Fluorescente in Situ , Melanoma/metabolismo , Melanoma/patología , Invasividad Neoplásica/genética , Metástasis de la Neoplasia/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo de Nucleótido Simple , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Matrices TisularesRESUMEN
Neurocutaneous syndromes are a heterogeneous group of congenital and hereditary disorders with manifestations in the skin and the nervous system, usually together with ocular features that represent diagnostic clues and potential sources of morbidity. Dermatologists and ophthalmologists often need to work together in identifying and managing patients with these conditions; herein, we focus on classic and under-recognized neurocutaneous syndromes. We begin with autosomal dominant genodermatoses characterized by hamartomas and tumors in the skin, eyes, and central nervous system: neurofibromatosis type 1, tuberous sclerosis complex, and PTEN hamartoma-tumor syndrome. This is followed by a discussion of two mosaic disorders, Sturge-Weber syndrome and neurocutaneous melanocytosis. In addition to providing an update on clinical presentations and evaluation of patients with these conditions, we review recent insights into their pathogenesis, drawing attention to relationships among the diseases on a molecular level and implications regarding treatment. We also highlight the major features of other neurocutaneous syndromes that have ocular findings plus pigmentary, vascular, hyperkeratotic, adnexal, connective tissue, photosensitive, and inflammatory manifestations in the skin.
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Oftalmopatías/etiología , Síndrome de Hamartoma Múltiple/complicaciones , Neurofibromatosis 1/complicaciones , Enfermedades de la Piel/etiología , Síndrome de Sturge-Weber/complicaciones , Esclerosis Tuberosa/complicaciones , Síndrome de Hamartoma Múltiple/tratamiento farmacológico , Humanos , Neurofibromatosis 1/tratamiento farmacológico , Enfermedades Cutáneas Vasculares/etiología , Esclerosis Tuberosa/tratamiento farmacológicoRESUMEN
Nail disorders comprise an important subset of dermatologic conditions and often pose both diagnostic and therapeutic challenges to the clinician. Presentation and management can differ in adults and children. Proper understanding of these differences is important in delivering optimal patient care. This contribution discusses three common nail disorders in adults and children, onychomycosis, melanonychia striata, and trachyonychia, highlighting distinct features in the adult and pediatric populations.
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Hiperpigmentación/diagnóstico , Melanoma/diagnóstico , Enfermedades de la Uña/diagnóstico , Enfermedades de la Uña/terapia , Neoplasias Cutáneas/diagnóstico , Adolescente , Adulto , Antifúngicos/uso terapéutico , Niño , Preescolar , Diagnóstico Diferencial , Humanos , Lactante , Recién Nacido , Onicomicosis/diagnóstico , Onicomicosis/tratamiento farmacológicoAsunto(s)
Control de Enfermedades Transmisibles , Infecciones por Coronavirus , Dermatología/educación , Educación de Postgrado en Medicina/organización & administración , Internado y Residencia , Pandemias , Neumonía Viral , Betacoronavirus , COVID-19 , Control de Enfermedades Transmisibles/métodos , Control de Enfermedades Transmisibles/organización & administración , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Educación de Postgrado en Medicina/tendencias , Humanos , Internado y Residencia/métodos , Internado y Residencia/organización & administración , Innovación Organizacional , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , SARS-CoV-2 , Criterios de Admisión Escolar , Facultades de MedicinaRESUMEN
IMPORTANCE: Cutaneous metastases rarely develop in patients with cancer but have important implications for prognosis and treatment. While dermoscopy is useful for many skin lesions, few data exist regarding dermoscopic findings in cutaneous metastases. OBSERVATIONS: We reviewed high-quality dermoscopic images of 20 outpatients with biopsy-proven cutaneous metastases and known diagnosis of underlying visceral malignancy and correlated these findings with clinical and histologic data. Most lesions were pink or flesh-colored, but 3 of 20 were pigmented. All 17 nonpigmented lesions demonstrated a vascular pattern on dermoscopy, with 15 of 17 (88%) having discrete vessels and 2 of 17 (12%) showing pink homogeneous structureless areas. Serpentine, or linear irregular, vessels were most common. In the 3 pigmented lesions (all metastatic breast carcinoma), various melanocytic patterns were observed. CONCLUSIONS AND RELEVANCE: Dermoscopically visible vascular structures within a cutaneous nodule in patients with a known cancer diagnosis should raise suspicion for cutaneous metastasis. Pigmentation in such lesions, in the absence of a history of melanoma, suggests a primary breast carcinoma. The high prevalence of vascular structures among cutaneous metastases may suggest a role for angiogenesis in their pathogenesis. These findings support the use of dermoscopy in the evaluation of suspected skin metastases or in the assessment of lesions of unknown origin in patients with cancer.
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Dermoscopía , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/secundario , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Neoplasias Colorrectales/patología , Neoplasias Endometriales/patología , Femenino , Humanos , Leiomiosarcoma/secundario , Neoplasias Pulmonares/patología , Masculino , Melanoma/secundario , Persona de Mediana Edad , Neoplasias Ováricas/patología , Neoplasias Peritoneales/patología , Estudios Retrospectivos , Neoplasias Cutáneas/irrigación sanguínea , Pigmentación de la Piel , Neoplasias Gástricas/patología , Neoplasias de la Tiroides/patología , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
PURPOSE: Gain-of-function mutations in BRAF, NRAS, or KIT are associated with distinct melanoma subtypes with KIT mutations and/or copy number changes frequently observed among melanomas arising from sun-protected sites, such as acral skin (palms, soles, and nail bed) and mucous membranes. GAB2 has recently been implicated in melanoma pathogenesis, and increased copy numbers are found in a subset of melanomas. We sought to determine the association of increased copy numbers of GAB2 among melanoma subtypes in the context of genetic alterations in BRAF, NRAS, and KIT. EXPERIMENTAL DESIGN: A total of 85 melanomas arising from sun-protected (n = 23) and sun-exposed sites (n = 62) were analyzed for copy number changes using array-based comparative genomic hybridization and for gain-of-function mutations in BRAF, NRAS, and KIT. RESULTS: GAB2 amplifications were found in 9% of the cases and were associated with melanomas arising from acral and mucosal sites (P = 0.005). Increased copy numbers of the KIT locus were observed in 6% of the cases. The overall mutation frequencies for BRAF and NRAS were 43.5% and 14%, respectively, and were mutually exclusive. Among the acral and mucosal melanomas studied, the genetic alteration frequency was 26% for GAB2, 13% for KIT, 30% for BRAF, and 4% for NRAS. Importantly, the majority of GAB2 amplifications occurred independent from genetic events in BRAF, NRAS, and KIT. CONCLUSIONS: GAB2 amplification is critical for melanomas arising from sun-protected sites. Genetic alterations in GAB2 will help refine the molecular classification of melanomas.