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2.
Clin Dermatol ; 38(4): 399-407, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32972599

RESUMO

Genodermatoses are heritable skin diseases that can cause significant morbidity and mortality. Most of them show characteristic cutaneous findings. Genodermatoses can be associated with extracutaneous system abnormalities. Diagnosing hereditary skin disorders is still a challenging task due to their rarity and diversity, due to diseases evolving over many years, and the initial manifestations not always being diagnostic; therefore, ongoing evaluation and surveillance is often required to make the accurate diagnosis. The algorithm for the diagnosis depends on a combination of thorough clinical and family history clinical examination, laboratory findings, consultation of multiple medical specialists, and molecular analysis. Diagnostic testing targeted at differentiation of similar genodermatoses may be required. Recognition is crucial for the initiation of the treatment for skin manifestations and detection of other extracutaneous abnormalities, including malignancy. Diagnostic accuracy and molecular diagnosis may help in providing a template for ongoing management, testing, and education and prognostication for families of children with genodermatoses.


Assuntos
Técnicas e Procedimentos Diagnósticos , Doenças Raras , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/patologia , Pele/patologia , Algoritmos , Diagnóstico Precoce , Feminino , Testes Genéticos , Humanos , Masculino , Síndrome
3.
Clin Dermatol ; 38(4): 408-420, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32972600

RESUMO

Genodermatoses are inherited disorders presenting with cutaneous manifestations with or without the involvement of other systems. The majority of these disorders, particularly in cases that present with a cutaneous patterning, may be explained in the context of genetic mosaicism. Despite the barriers to the genetic analysis of mosaic disorders, next-generation sequencing has led to a substantial progress in understanding their pathogenesis, which has significant implications for the clinical management and genetic counseling. Advances in paired and deep sequencing technologies in particular have made the study of mosaic disorders more feasible. In this review, we provide an overview of genetic mosaicism as well as mosaic cutaneous disorders and the techniques required to study them.


Assuntos
Mosaicismo , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/genética , Feminino , Aconselhamento Genético , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Fenótipo , Dermatopatias Genéticas/etiologia , Dermatopatias Genéticas/patologia
4.
Clin Dermatol ; 38(4): 421-431, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32972601

RESUMO

Café au lait spots are common birthmarks seen sporadically and in association with several genetic syndromes. Dermatologists are often asked to evaluate these birthmarks both by other physicians and by parents. In some cases, it is challenging to know when and how to pursue further evaluation. Diagnostic challenges may come in the form of the appearance of the individual lesions, areas and patterns of cutaneous involvement, and associated features (or lack thereof). In this review, we aim to clarify when and how to evaluate the child with multiple or patterned café au lait spots and to explain some emerging concepts in our understanding of the genetics of these lesions.


Assuntos
Manchas Café com Leite/congênito , Manchas Café com Leite/diagnóstico , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/genética , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/genética , Pele/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Manchas Café com Leite/genética , Manchas Café com Leite/patologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Deleção de Genes , Estudos de Associação Genética , Mutação em Linhagem Germinativa , Humanos , Lactente , Recém-Nascido , Masculino , Neurofibromatose 1/patologia , Neurofibromina 1/genética , Dermatopatias Genéticas/patologia , Síndrome
5.
Clin Dermatol ; 38(4): 432-454, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32972602

RESUMO

The hereditary nature of some forms of cancer was recognized long ago. Over time, recognition of associated findings led to the delineation of numerous hereditary cancer syndromes. Many of these syndromes also have cutaneous manifestations, the recognition of which can lead to their early identification. Recognition of these syndromes allows vigilant surveillance and preemptive treatment, which can dramatically impact the risks of morbidity and mortality for affected patients. The rise of rapid and accurate genetic testing now allows the early identification of asymptomatic at risk family members so that monitoring can be initiated as early as possible. The dermatologist plays a critical role in early identification of these syndromes and, in many cases, their treatment. This review summarizes many known hereditary cancer syndromes with cutaneous findings, their etiology, identification, evaluation, and management. Importantly, this is an ever evolving topic and new findings and syndromes will continue to be recognized. The dermatologist must be always alert to ensure they are detected.


Assuntos
Síndromes Neoplásicas Hereditárias , Dermatopatias Genéticas , Síndrome do Nevo Basocelular , Síndrome de Birt-Hogg-Dubé , Complexo de Carney , Neoplasias Colorretais Hereditárias sem Polipose , Diagnóstico Precoce , Feminino , Síndrome de Gardner , Testes Genéticos , Síndrome do Hamartoma Múltiplo , Humanos , Masculino , Neoplasia Endócrina Múltipla , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/patologia , Síndromes Neoplásicas Hereditárias/terapia , Neurofibromatoses , Pele/patologia , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/genética , Dermatopatias Genéticas/patologia , Dermatopatias Genéticas/terapia
6.
An Bras Dermatol ; 95(3): 351-354, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32265056

RESUMO

Secondary osteoma cutis is a phenomenon that may occur in several conditions. When it occurs in a melanocytic nevus it is named osteonevus of Nanta, an event considered uncommon and characterized by the presence of bone formation adjacent or interposed with melanocytic cells. There are reports of its occurrence in various melanocytic lesions, being more frequently associated with intradermal nevus. We report a case of osteonevus of Nanta in combined nevus, possibly the first description of this association.


Assuntos
Doenças Ósseas Metabólicas/patologia , Nevo Intradérmico/patologia , Nevo Pigmentado/patologia , Ossificação Heterotópica/patologia , Dermatoses do Couro Cabeludo/patologia , Dermatopatias Genéticas/patologia , Neoplasias Cutâneas/patologia , Adulto , Doenças Ósseas Metabólicas/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Melanócitos/patologia , Nevo Intradérmico/cirurgia , Nevo Pigmentado/cirurgia , Ossificação Heterotópica/cirurgia , Dermatoses do Couro Cabeludo/cirurgia , Dermatopatias Genéticas/cirurgia , Neoplasias Cutâneas/cirurgia
9.
Invest Ophthalmol Vis Sci ; 61(3): 16, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32176264

RESUMO

Purpose: In this experimental study, we quantify retinal microvasculature morphological features with depth, region, and age in immature and mature ovine eyes. These data identify morphological vulnerabilities in young eyes to inform the mechanics of retinal hemorrhage in children. Methods: Retinal specimens from the equator and posterior pole of preterm (n = 4) and adult (n = 9) sheep were imaged using confocal microscopy. Vessel segment length, diameter, angular asymmetry, tortuosity, and branch points were quantified using a custom image segmentation code. Significant differences were identified through two-way ANOVAs and correlation analyses. Results: Vessel segment lengths were significantly shorter in immature eyes compared to adults (P < 0.003) and were significantly shorter at increasing depths in the immature retina (P < 0.04). Tortuosity significantly increased with depth, regardless of age (P < 0.05). These data suggest a potential vulnerability of vasculature in the deeper retinal layers, particularly in immature eyes. Preterm retina had significantly more branch points than adult retina in both the posterior pole and equator, and the number increased significantly with depth (P < 0.001). Conclusions: The increased branch points and decreased segment lengths in immature microvasculature suggest that infants will experience greater stress and strain during traumatic loading compared to adults. The increased morphological vulnerability of the immature microvasculature in the deeper layers of the retina suggest that intraretinal hemorrhages have a greater likelihood of occurring from trauma compared to preretinal hemorrhages. The morphological features captured in this study lay the foundation to explore the mechanics of retinal hemorrhage in infants and identify vulnerabilities that explain patterns of retinal hemorrhage in infants.


Assuntos
Hemorragia Retiniana/patologia , Vasos Retinianos/anatomia & histologia , Envelhecimento/patologia , Envelhecimento/fisiologia , Animais , Animais Recém-Nascidos , Artérias/anormalidades , Artérias/patologia , Artérias/fisiopatologia , Fenômenos Biomecânicos , Feminino , Humanos , Instabilidade Articular/patologia , Instabilidade Articular/fisiopatologia , Microscopia Confocal , Microvasos/anatomia & histologia , Microvasos/fisiologia , Variações Dependentes do Observador , Hemorragia Retiniana/etiologia , Vasos Retinianos/fisiologia , Ovinos , Dermatopatias Genéticas/patologia , Dermatopatias Genéticas/fisiopatologia , Malformações Vasculares/patologia , Malformações Vasculares/fisiopatologia
10.
J Dermatol Sci ; 97(2): 94-100, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31928837

RESUMO

Revertant mosaicism refers to a condition in which a pathogenic germline mutation is spontaneously corrected in somatic cells, resulting in the presence of two or more cell populations with different genotypes in an organism arising from a single fertilized egg. If the revertant cells are clonally expanded due to a survival advantage over the surrounding mutant cells, patients benefit from this self-healing phenomenon which leads to the development of milder-than-expected clinical phenotypes; in genetic skin diseases, patients with revertant mosaicism present with small islands of healthy skin. To date, revertant mosaicism has been reported in ∼50 genetic diseases involving the skin, blood, liver, muscle, and brain. In this review, I briefly summarize current knowledge on revertant mosaicism in two particular skin diseases, ichthyosis with confetti (IWC) and loricrin keratoderma (LK), both of which develop numerous revertant skin patches. Notably, homologous recombination (HR) is the only mechanism underlying the reversion of pathogenic mutations in IWC and LK, and this was identified following the analysis of ∼50 revertant epidermis samples. All the samples showed long-tract loss of heterozygosity (LOH) that originated at regions centromeric to pathogenic mutations and extended to the telomere of the mutation-harboring chromosomes. Elucidating the molecular mechanisms underlying revertant mosaicism in IWC and LK-especially how mutant proteins induce long-tract LOH-would potentially expand the possibility of manipulating HR to induce the reversion of disease-causing mutations and help devising novel therapies not only for IWC and LK but also for other intractable genetic diseases.


Assuntos
Recombinação Homóloga , Eritrodermia Ictiosiforme Congênita/genética , Proteínas de Membrana/genética , Mosaicismo , Dermatopatias Genéticas/genética , Epiderme/patologia , Humanos , Eritrodermia Ictiosiforme Congênita/patologia , Perda de Heterozigosidade , Dermatopatias Genéticas/patologia
11.
J Immunol ; 204(1): 137-146, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31801815

RESUMO

Dysregulation of monocyte and macrophage responses are often observed in children with systemic juvenile idiopathic arthritis (sJIA) and cytokine storm syndrome (CSS), a potentially fatal complication of chronic rheumatic diseases. Both conditions are associated with activation of TLR signaling in monocyte and macrophage lineage cells, leading to overwhelming inflammatory responses. Despite the importance of TLR engagement in activating proinflammatory macrophages, relatively little is known about activation of intrinsic negative regulatory pathways to attenuate excessive inflammatory responses. In this study, we demonstrate that loss of diacylglycerol (DAG) kinase (Dgk) ζ, an enzyme which converts DAG into phosphatidic acid, limits inflammatory cytokine production in an arthritic mouse model dependent on TLR2 signaling and in a CSS mouse model dependent on TLR9 signaling. In vitro, Dgkζ deficiency results in reduced production of TNF-α, IL-6, and IL-1ß and in limited M1 macrophage polarization. Mechanistically, Dgkζ deficiency decreases STAT1 and STAT3 phosphorylation. Moreover, Dgkζ levels are increased in macrophages derived from mice with CSS or exposed to plasma from sJIA patients with active disease. Our data suggest that Dgkζ induction in arthritic conditions perpetuates systemic inflammatory responses mediated by macrophages and highlight a potential role of Dgkζ-DAG/phosphatidic acid axis as a modulator of inflammatory cytokine production in sJIA and CSS.


Assuntos
Artrite Juvenil/metabolismo , Calcinose/metabolismo , Citocinas/metabolismo , Diacilglicerol Quinase/metabolismo , Modelos Animais de Doenças , Doenças das Valvas Cardíacas/metabolismo , Hipotricose/metabolismo , Macrófagos/metabolismo , Dermatopatias Genéticas/metabolismo , Animais , Artrite Juvenil/imunologia , Artrite Juvenil/patologia , Calcinose/imunologia , Calcinose/patologia , Parede Celular/imunologia , Parede Celular/metabolismo , Células Cultivadas , Citocinas/imunologia , Diacilglicerol Quinase/deficiência , Diacilglicerol Quinase/imunologia , Doenças das Valvas Cardíacas/imunologia , Doenças das Valvas Cardíacas/patologia , Hipotricose/imunologia , Hipotricose/patologia , Macrófagos/imunologia , Macrófagos/patologia , Camundongos , Camundongos Knockout , Dermatopatias Genéticas/imunologia , Dermatopatias Genéticas/patologia
13.
Photodermatol Photoimmunol Photomed ; 36(2): 105-110, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31541482

RESUMO

BACKGROUND: Actinic prurigo is a chronic photodermatosis of unclear pathogenesis. Epidermal Langerhans cell resistance to migration after ultraviolet radiation exposure has been proposed as a possible mechanism, as occurs in polymorphic light eruption patients. The purpose of this study was to evaluate the effect of solar-simulated radiation (SSR) on epidermal Langerhans cells in the uninvolved skin of actinic prurigo patients. PATIENTS AND METHODS: Fifteen patients with actinic prurigo participated in the study. A biopsy from the uninvolved and unirradiated skin of the left buttock was performed, and another from the uninvolved skin of the right buttock, 72 hours after exposure to two MEDs of SSR. Immunohistochemistry staining was used to identify Langerhans cells (CD1a) in all samples. RESULTS: In actinic prurigo patients with normal MED, there was a significant decrease in the number of epidermal Langerhans cells on the buttock skin exposed to two MED of SSR compared with the unirradiated buttock skin (P = .02 and .035 respectively). On the contrary, in patients with low MED there were no significant differences in the number of epidermal Langerhans cells between irradiated and unirradiated skin (P = .39). CONCLUSION: Epidermal Langerhans cells migration after ultraviolet radiation exposure is decreased in actinic prurigo patients with low MED as has been reported in PLE patients, especially, those with low MED or positive UVB provocation tests. Langerhans cells resistance could be part of a common pathogenic mechanism in these two photodermatoses.


Assuntos
Epiderme/metabolismo , Células de Langerhans/metabolismo , Transtornos de Fotossensibilidade/radioterapia , Dermatopatias Genéticas/radioterapia , Luz Solar , Adulto , Epiderme/patologia , Eritema/metabolismo , Eritema/patologia , Feminino , Humanos , Células de Langerhans/patologia , Masculino , Pessoa de Meia-Idade , Transtornos de Fotossensibilidade/metabolismo , Transtornos de Fotossensibilidade/patologia , Dermatopatias Genéticas/metabolismo , Dermatopatias Genéticas/patologia
17.
An Bras Dermatol ; 94(5): 608-611, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777364

RESUMO

Dissecting cellulitis is an inflammatory, chronic, and recurrent disease of the hair follicles that mainly affects young Afro-descendent men. Trichoscopy is a method of great diagnostic value for disorders of the scalp. Clinical and trichoscopic findings of dissecting cellulitis are heterogeneous and may present features common to non-cicatricial and scarring alopecia. This article presents the trichoscopic findings of dissecting cellulitis that help in the diagnosis and consequent institution of the appropriate therapy and better prognosis of the disease.


Assuntos
Celulite (Flegmão)/diagnóstico por imagem , Celulite (Flegmão)/patologia , Dermoscopia/métodos , Folículo Piloso/diagnóstico por imagem , Folículo Piloso/patologia , Dermatoses do Couro Cabeludo/diagnóstico por imagem , Dermatoses do Couro Cabeludo/patologia , Dermatopatias Genéticas/diagnóstico por imagem , Dermatopatias Genéticas/patologia , Eritema/diagnóstico por imagem , Eritema/patologia , Cabelo/diagnóstico por imagem , Cabelo/patologia , Humanos
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