RESUMO
Ichthyoses are a group of rare genetic skin disorders that pose numerous clinical challenges, in particular with respect to the correct diagnosis and appropriate management. The present update of the German ichthyosis guidelines addresses recent diagnostic advances that have resulted in the Sorèze consensus classification. In this context, we provide an updated diagnostic algorithm, taking into account clinical features as well as the molecular genetic basis of these disorders. Moreover, we highlight current therapeutic approaches such as psychosocial support, balneotherapy, mechanical scale removal, topical therapy, and systemic retinoid therapy. General aspects such as the indication for physical therapy, ergotherapy, or genetic counseling are also discussed. The present update was consented by an interdisciplinary consensus conference that included dermatologists, pediatricians, human geneticists, and natural scientists as well as representatives of the German patient support organization Selbsthilfe Ichthyose e. V.
Assuntos
Fidelidade a Diretrizes , Ictiose/diagnóstico , Ictiose/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Predisposição Genética para Doença/genética , Alemanha , Humanos , Ictiose/classificação , Ictiose/genética , Lactente , Recém-Nascido , Masculino , Gravidez , Prognóstico , Adulto JovemRESUMO
Chronic obstructive pulmonary disease (COPD) is a frequent diagnosis in older individuals and contributor to global morbidity and mortality. Given the link between lung disease and aging, we need to understand how molecular indicators of aging relate to lung function and disease. Using data from the population-based KORA (Cooperative Health Research in the Region of Augsburg) surveys, we associated baseline epigenetic (DNA methylation) age acceleration with incident COPD and lung function. Models were adjusted for age, sex, smoking, height, weight, and baseline lung disease as appropriate. Associations were replicated in the Normative Aging Study. Of 770 KORA participants, 131 developed incident COPD over 7 years. Baseline accelerated epigenetic aging was significantly associated with incident COPD. The change in age acceleration (follow-up - baseline) was more strongly associated with COPD than baseline aging alone. The association between the change in age acceleration between baseline and follow-up and incident COPD replicated in the Normative Aging Study. Associations with spirometric lung function parameters were weaker than those with COPD, but a meta-analysis of both cohorts provide suggestive evidence of associations. Accelerated epigenetic aging, both baseline measures and changes over time, may be a risk factor for COPD and reduced lung function.
Assuntos
Envelhecimento/genética , Metilação de DNA , Epigênese Genética , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/genética , Adulto , Fatores Etários , Feminino , Predisposição Genética para Doença , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Medição de Risco , Fatores de Risco , EspirometriaRESUMO
Most genetic diseases are complex, i.e. associated to combinations of SNPs rather than individual SNPs. In the last few years, this topic has often been addressed in terms of SNP-SNP interaction patterns given as expressions linked by logical operators. Methods for multiple testing in high-dimensional settings can be applied when many SNPs are considered simultaneously. However, another less well-known multiple testing problem arises within a fixed subset of SNPs when the logic expression is chosen optimally. In this article, we propose a general asymptotic approach for deriving the distribution of the maximally selected chi-square statistic in various situations. We show how this result can be used for testing logic expressions - in particular SNP-SNP interaction patterns - while controlling for multiple comparisons. Simulations show that our method provides multiple testing adjustments when the logic expression is chosen such as to maximize the statistic. Its benefit is demonstrated through an application to a real dataset from a large population-based study considering allergy and asthma in KORA. An implementation of our method is available from the Comprehensive R Archive Network (CRAN) as R package 'SNPmaxsel'.
Assuntos
Simulação por Computador , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Distribuição de Qui-Quadrado , Humanos , Desequilíbrio de LigaçãoRESUMO
BACKGROUND: Regulatory T cells (T-reg cells) have been described as an important cell population in the UV treatment of inflammatory skin diseases. METHODS: We have treated five patients with generalized atopic eczema (AE) using medium-dose (15 cycles of 50 J/cm(2), total dose of 750 J/cm(2)) UVA1 therapy and have analyzed the skin-infiltrating T-cellular subsets before and after therapy. Skin biopsies were split for immunohistochemistry and Real-time PCR and analyzed for CD4, Fox-P3, GATA-3, and IL-10 transcription as well as for CD3, CD4, CD152, Fox-P3, and GITR staining. RESULTS: In all the investigated patients, we observed a good clinical response to UVA1. As described previously, the number of epidermal T cells slightly declined after irradiation. However, we did not observe a general decrease in T cell numbers. Within the population of T cells, no specific difference in the kinetics of Fox-P3-positive cells and Fox-P3-specific mRNA was noted as compared with GATA-3 positive T cells. These results were paralleled by RT-PCR for IL-10 and staining for CD152, a surface molecule that has been described for T-reg cells. CONCLUSION: In our hands, the clinical benefit of UVA1 treatment in AE patients does not seem to be due to a preferential survival/proliferation of T-reg cells.
Assuntos
Dermatite Atópica/imunologia , Dermatite Atópica/radioterapia , Fatores de Transcrição Forkhead/biossíntese , Linfócitos T/efeitos da radiação , Raios Ultravioleta , Adulto , Idoso , Antígenos CD4/biossíntese , Dermatite Atópica/patologia , Feminino , Fatores de Transcrição Forkhead/genética , Fator de Transcrição GATA3/biossíntese , Humanos , Imunoquímica , Interleucina-10/biossíntese , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/análise , Doses de Radiação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/imunologia , Pele/patologia , Pele/efeitos da radiação , Linfócitos T/imunologia , Terapia UltravioletaRESUMO
There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.