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1.
J Eur Acad Dermatol Venereol ; 37(2): 402-410, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36196047

RESUMO

BACKGROUND: Epidermolysis bullosa (EB) is a rare genetic disorder manifesting with skin and mucosal membrane blistering in different degrees of severity. OBJECTIVE: Epidemiological data from different countries have been published, but none are available from Germany. METHODS: In this population-based cross-sectional study, people living with EB in Germany were identified using the following sources: academic hospitals, diagnostic laboratories and patient organization. RESULTS: Our study indicates an overall EB incidence of 45 per million live births in Germany. With 14.23 per million live births for junctional EB, the incidence is higher than in other countries, possibly reflecting the availability of early molecular genetic diagnostics in severely affected neonates. Dystrophic EB was assessed at 15.58 cases per million live births. The relatively low incidence found for EB simplex, 14.93 per million live births, could be explained by late or missed diagnosis, but also by 33% of cases remaining not otherwise specified. Using log-linear models, we estimated a prevalence of 54 per million for all EB types, 2.44 for junctional EB, 12.16 for dystrophic EB and 28.44 per million for EB simplex. These figures are comparable to previously reported data from other countries. CONCLUSIONS: Altogether, there are at least 2000 patients with EB in the German population. These results should support national policies and pharmaceutical companies in decision-making, allow more precise planning of drug development and clinical trials, and aid patient advocacy groups in their effort to improve quality of life of people with this orphan disease.


Assuntos
Epidermólise Bolhosa Distrófica , Epidermólise Bolhosa Simples , Epidermólise Bolhosa Juncional , Epidermólise Bolhosa , Recém-Nascido , Humanos , Estudos Transversais , Qualidade de Vida , Epidermólise Bolhosa/epidemiologia , Pele , Epidermólise Bolhosa Distrófica/genética , Epidermólise Bolhosa Simples/genética
2.
Exp Dermatol ; 30(10): 1398-1408, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-32885529

RESUMO

BACKGROUND: Atopic dermatitis (AD) is driven by the interplay between a dysfunctional epidermal barrier and a skewed cutaneous immune dysregulation. As part of the complex skin barrier dysfunction, abnormalities in lipid organization and microbiome composition have been described. We set out to systematically investigate the composition of the stratum corneum lipidome, skin microbiome and skin physiology parameters at three different body sites in patients with AD and healthy volunteers. METHODS: We analysed tape strips from different body areas obtained from 10 adults with AD and 10 healthy volunteers matched for FLG mutation status for 361 skin lipid species using the Metabolon mass spectrometry platform. 16S rRNA data were available from all probands. RESULTS: Our study showed that the lipid composition differs significantly between body sites and between AD patients and healthy individuals. Ceramide species NS was significantly higher in AD patients compared to healthy volunteers and was also higher in AD patients with a FLG mutation compared to AD patients without a FLG mutation. The correlation analysis of skin lipid alterations with the microbiome showed that Staphylococcus colonization in AD is positively correlated with ceramide subspecies AS, ADS, NS and NDS. CONCLUSION: This is the first study to reveal site-specific lipid alterations and correlations with the skin microbiome in AD.


Assuntos
Ceramidas/metabolismo , Ésteres do Colesterol/metabolismo , Dermatite Atópica/microbiologia , Ácidos Graxos não Esterificados/metabolismo , Microbiota , Adulto , Feminino , Humanos , Lipidômica , Masculino , Pele/microbiologia
3.
J Allergy Clin Immunol ; 145(5): 1406-1415, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31891686

RESUMO

BACKGROUND: Although multiple studies have assessed molecular changes in chronic atopic dermatitis (AD) lesions, little is known about the transition from acute to chronic disease stages, and the factors and mechanisms that shape chronic inflammatory activity. OBJECTIVES: We sought to assess the global transcriptome changes that characterize the progression from acute to chronic stages of AD. METHODS: We analyzed transcriptome changes in paired nonlesional skin, acute and chronic AD lesions from 11 patients and 38 healthy controls by RNA-sequencing, and conducted in vivo and histological assays to evaluate findings. RESULTS: Our data demonstrate that approximately 74% of the genes dysregulated in acute lesions remain or are further dysregulated in chronic lesions, whereas only 34% of the genes dysregulated in chronic lesions are altered already in the acute stage. Nonlesional AD skin exhibited enrichment of TNF, TH1, TH2, and TH17 response genes. Acute lesions showed marked dendritic-cell signatures and a prominent enrichment of TH1, TH2, and TH17 responses, along with increased IL-36 and thymic stromal lymphopoietin expression, which were further heightened in chronic lesions. In addition, genes involved in skin barrier repair, keratinocyte proliferation, wound healing, and negative regulation of T-cell activation showed a significant dysregulation in the chronic versus acute comparison. Furthermore, our data show progressive changes in vasculature and maturation of dendritic-cell subsets with chronicity, with FOXK1 acting as immune regulator. CONCLUSIONS: Our results show that the changes accompanying the transition from nonlesional to acute to chronic inflammation in AD are quantitative rather than qualitative, with chronic AD having heightened TH2, TH1, TH17, and IL36 responses and skin barrier repair mechanisms. These findings provide novel insights and highlight underappreciated pathways in AD pathogenesis that may be amenable to therapeutic targeting.


Assuntos
Citocinas/genética , Dermatite Atópica/genética , Doença Aguda , Doença Crônica , Dermatite Atópica/imunologia , Feminino , Humanos , Masculino , Análise de Sequência de RNA , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Transcriptoma
4.
J Allergy Clin Immunol ; 141(5): 1668-1676.e16, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29421277

RESUMO

BACKGROUND: Genomic approaches have revealed characteristic site specificities of skin bacterial community structures. In addition, in children with atopic dermatitis (AD), characteristic shifts were described at creases and, in particular, during flares, which have been postulated to mirror disturbed skin barrier function, cutaneous inflammation, or both. OBJECTIVE: We sought to comprehensively analyze microbial configurations in patients with AD across body sites and to explore the effect of distinct abnormalities of epidermal barrier function. METHODS: The skin microbiome was determined by using bacterial 16S rRNA sequencing at 4 nonlesional body sites, as well as acute and chronic lesions of 10 patients with AD and 10 healthy control subjects matched for age, sex, and filaggrin (FLG) mutation status. Nonlesional sampling sites were characterized for skin physiology parameters, including chromatography-based lipid profiling. RESULTS: Epidermal lipid composition, in particular levels of long-chain unsaturated free fatty acids, strongly correlated with bacterial composition, in particular Propionibacteria and Corynebacteria abundance. AD displayed a distinct community structure, with increased abundance and altered composition of staphylococcal species across body sites, the strongest loss of diversity and increase in Staphylococcus aureus seen on chronic lesions, and a progressive shift from nonlesional skin to acute and chronic lesions. FLG-deficient skin showed a distinct microbiome composition resembling in part the AD-related pattern. CONCLUSION: Epidermal barrier integrity and function affect the skin microbiome composition. AD shows an altered microbial configuration across diverse body sites, which is most pronounced at sites of predilection and AD. Eczematous affection appears to be a more important determinant than body site.


Assuntos
Eczema/microbiologia , Eczema/patologia , Epiderme/microbiologia , Epiderme/patologia , Inflamação/microbiologia , Inflamação/patologia , Lipídeos/fisiologia , Adulto , Estudos de Casos e Controles , Dermatite Atópica/genética , Dermatite Atópica/microbiologia , Dermatite Atópica/patologia , Eczema/genética , Feminino , Proteínas Filagrinas , Humanos , Inflamação/genética , Proteínas de Filamentos Intermediários/genética , Masculino , Microbiota/fisiologia , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Fenômenos Fisiológicos da Pele/genética , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/genética , Adulto Jovem
7.
Front Cell Neurosci ; 9: 307, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26321911

RESUMO

BACKGROUND: Behavioral inhibition, which is a later-developing executive function (EF) and anatomically located in prefrontal areas, is impaired in attention-deficit and hyperactivity disorder (ADHD). While optimal EFs have been shown to depend on efficient sleep in healthy subjects, the impact of sleep problems, frequently reported in ADHD, remains elusive. Findings of macroscopic sleep changes in ADHD are inconsistent, but there is emerging evidence for distinct microscopic changes with a focus on prefrontal cortical regions and non-rapid eye movement (non-REM) slow-wave sleep. Recently, slow oscillations (SO) during non-REM sleep were found to be less functional and, as such, may be involved in sleep-dependent memory impairments in ADHD. OBJECTIVE: By augmenting slow-wave power through bilateral, slow oscillating transcranial direct current stimulation (so-tDCS, frequency = 0.75 Hz) during non-REM sleep, we aimed to improve daytime behavioral inhibition in children with ADHD. METHODS: Fourteen boys (10-14 years) diagnosed with ADHD were included. In a randomized, double-blind, cross-over design, patients received so-tDCS either in the first or in the second experimental sleep night. Inhibition control was assessed with a visuomotor go/no-go task. Intrinsic alertness was assessed with a simple stimulus response task. To control for visuomotor performance, motor memory was assessed with a finger sequence tapping task. RESULTS: SO-power was enhanced during early non-REM sleep, accompanied by slowed reaction times and decreased standard deviations of reaction times, in the go/no-go task after so-tDCS. In contrast, intrinsic alertness, and motor memory performance were not improved by so-tDCS. CONCLUSION: Since behavioral inhibition but not intrinsic alertness or motor memory was improved by so-tDCS, our results suggest that lateral prefrontal slow oscillations during sleep might play a specific role for executive functioning in ADHD.

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