京都大学 / 新制・論文博士 / 博士(社会健康医学) / 乙第13613号 / 論社医博第19号 / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 森田 智視, 教授 椛島 健治, 教授 村井 俊哉 / 学位規則第4条第2項該当 / Doctor of Public Health / Kyoto University / DFAM

Introdução: Dermatite atópica (DA) é uma doença cutânea crônica, predominante na infância, cujo sintoma principal é o prurido de intensidade variável, e os sinais são classicamente as lesões de padrão eczematoso. Há anormalidades na formação e função da barreira cutânea, que estão presentes não somente nas lesões cutâneas como na pele clinicamente não afetada. Objetivo: Analisar a correlação entre as medidas biofísicas da função de barreira cutânea e os critérios clínicos e intensidade da dermatite, de acordo com os critérios de Rajka e Langeland. Métodos: 231 doentes do Departamento de Dermatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, com diagnóstico clínico de dermatite atópica segundo os critérios diagnósticos de Rajka e Langeland foram avaliados por exame físico, anamese, medidas biofísicas de grau de hidratação de camada córnea pelo método de capacitância (corneometria) e pelo método de perda de água transepidérmica (TEWL); a medida sérica de IgE também foi solicitada no ato do exame. Resultados: Houve uma relação significativa entre as medidas de corneometria, TEWL e gravidade clínica da dermatite atópica. Os dados demonstraram uma correlação inversamente proporcional entre a corneometria e o TEWL, e houve uma diferença estatisticamente significativa (p<0,001) entre as médias de corneometria e TEWL e grau de DA (leve, moderada ou intensa). Com relação aos níveis séricos de IgE, as medidas de corneometria apresentaram uma correlação negativa significativa; para TEWL, a correlação positiva foi estatisticamente significativa (p<0,001). Conclusão: As medidas biofísicas de barreira cutânea na DA, mesmo em pele aparentemente não lesada, podem funcionar como fator de avaliação do grau clínico da DA e da intensidade do prurido. / Background: Atopic dermatitis (AD) is a chronic dermatosis, predominant in childhood, characterized by pruritus and eczematous type lesions with xerosis as the proeminent clinical sign. Objectives: To analyze the correlation between biophysical measurements of skin barrier function and other assessment criteria of clinical severity according to Rajka and Langelands criteria. Methods: Biophysical measurements (Transepidermal water loss and corneometry) were obtained from 231 patients from the department of dermatology, Hospital das Clinicas FMUSP with the diagnsosis of atopical dermatitis. Serum levels of IgE were also evaluated. Results: A significant correlation between corneometry, TEWL and clinical severity of atopic dermatitis were found. Data showed an inverse correlation between corneometry, TEWL, and AD severity, and a significant difference (p<0,001) between means of corneometry and TEWL and AD severity (mild, moderate and severe). As for IgE levels, corneometry had significant negative correlation, in contrast with TEWL, wich showed a significant positive correlation (p<0,001). Conclusion: Biophysical measurements of skin barrier in non lesional skin of atopic dermatitis may work as an evaluation factor for AD severity and pruritus.

Ching, Ka Wai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves [69-80]). / Abstract also in Chinese. / Abstract (in English) --- p.ii / Abstract (in Chinese) --- p.v / Acknowledgement --- p.viii / Table of Contents --- p.ix / List of Tables --- p.xii / List of Figures --- p.xiii / Glossary of Terms and Abbreviations --- p.xv / Chapter Chapter 1: --- Introduction --- p.1 / Chapter 1.1 --- Introduction of Atopic Eczema (AE) --- p.1 / Chapter 1.1.1 --- Definition and classification of AE --- p.1 / Chapter 1.1.2 --- Epidemiology --- p.3 / Chapter 1.1.2.1 --- The hygiene hypothesis --- p.5 / Chapter 1.2 --- Pathogenesis and Etiology --- p.6 / Chapter 1.2.1 --- Biphasic type-1/type-2 T-helper lymphocyte (Thl/Th2) immunological responses --- p.6 / Chapter 1.2.2 --- Nature and involvements of immunoglobin E (IgE) --- p.8 / Chapter 1.2.3 --- Microbial colonization --- p.9 / Chapter 1.2.4 --- Cytokines involvement --- p.10 / Chapter 1.2.5 --- Pruritus inducing neurotrophic factors --- p.11 / Chapter 1.2.6 --- "Food allergens, aeroallergens" --- p.12 / Chapter 1.2.7 --- Dysregulation of innate immune system --- p.13 / Chapter 1.2.7.1 --- Dysregulation of antimicrobial peptides --- p.14 / Chapter 1.2.7.2 --- Skin barrier impairment --- p.14 / Chapter 1.2.8 --- Genetic predisposition --- p.15 / Chapter 1.3 --- Assessments of Atopic Eczema (AE) --- p.17 / Chapter 1.3.1 --- AE severity assessment --- p.17 / Chapter 1.3.1.1 --- Scoring of atopic dermatitis (SCORAD) system --- p.17 / Chapter 1.3.1.2 --- Nottingham eczema severity score (NESS) --- p.20 / Chapter 1.3.2 --- Dermatological parameter - skin hydration (SH) and transepidermal water loss (TEWL) --- p.22 / Chapter 1.4 --- Chitinase (CHIA) --- p.22 / Chapter 1.4.1 --- Chitin and CHIA --- p.22 / Chapter 1.4.2 --- Association of acid mammalian chitinase (AMCase) with asthma --- p.23 / Chapter 1.4.3 --- Hygiene hypothesis implies: AMCase and allergy relationship --- p.24 / Chapter Chapter 2: --- Hypothesis and Objectives --- p.25 / Chapter 2.1 --- Hypothesis - based on CHIA involvements in canine AE --- p.25 / Chapter 2.2 --- Hypothesis --- p.25 / Chapter 2.3 --- Objective 226}0ؤ based on AMCase single nucleotide polymorphism (SNPs) in asthma susceptibility --- p.25 / Chapter 2.4 --- Objectives --- p.27 / Chapter Chapter 3: --- Methodology --- p.28 / Chapter 3.1 --- Recruitment of cases and controls --- p.28 / Chapter 3.2 --- Assessment of clinical parameters --- p.29 / Chapter 3.2.1 --- Scoring of atopic dermatitis (SCORAD) system --- p.29 / Chapter 3.2.2 --- Nottingham eczema severity score (NESS) --- p.29 / Chapter 3.2.3 --- Dermatologic parameters --- p.29 / Chapter 3.2.3.1 --- Cutaneous bacterial colonization --- p.29 / Chapter 3.2.3.2 --- Skin hydration (SH) and transepidermal water loss (TEWL) --- p.30 / Chapter 3.3 --- Peripheral blood collection and genomic deoxyribonucleic acid (DNA) extraction --- p.30 / Chapter 3.4 --- Acid mammalian chitinase (AMCase) polymorphism genotyping --- p.31 / Chapter 3.4.1 --- Polymerase chain reactions (PCR) amplification of AMCase gene --- p.31 / Chapter 3.4.1.1 --- List of PCR reagents --- p.32 / Chapter 3.4.1.2 --- Electrophoresis reagents --- p.33 / Chapter 3.4.2 --- Restriction fragment length polymorphism (RFLP) analysis of AMCase and confirmation with direct sequencing --- p.33 / Chapter 3.5 --- Statistical analysis --- p.34 / Chapter Chapter 4: --- Results and Data Analysis --- p.36 / Chapter 4.1 --- Results --- p.36 / Chapter 4.1.1 --- Demographic data of cases and controls --- p.36 / Chapter 4.1.2 --- PCR amplification and RFLP analysis of AMCase gene --- p.37 / Chapter 4.1.3 --- PCR cycle sequencing of the PCR fragments --- p.40 / Chapter 4.2 --- Data analysis --- p.41 / Chapter 4.2.1 --- Data overview --- p.41 / Chapter 4.2.2 --- Genotypes distribution of AMCase polymorphisms --- p.43 / Chapter 4.2.2.1 --- Allele frequency comparison of AMCase single nucleotide polymorphism (SNPs) by chi-square --- p.43 / Chapter 4.2.2.2 --- Allele frequency comparison of AMCase SNPs by logistic regression analysis --- p.44 / Chapter 4.2.3 --- Haplotype frequency estimation via maximum likelihood algorithm --- p.45 / Chapter 4.2.4 --- Association of AMCase polymorphism with Atopic Eczema (AE) clinical parameters --- p.47 / Chapter 4.2.4.1 --- Peripheral blood eosinophil counts --- p.48 / Chapter 4.2.4.2 --- Serum immunoglobin E (IgE) level --- p.49 / Chapter 4.2.4.3 --- Dermatologic factors --- p.49 / Chapter 4.2.4.3.1 --- Cutaneous Staphylococcus aureus colonization --- p.49 / Chapter 4.2.4.3.2 --- Skin hydration (SH) and transepidermal water loss (TEWL) --- p.50 / Chapter Chapter 5: --- Discussion --- p.52 / Chapter 5.1 --- Data overview --- p.52 / Chapter 5.2 --- AMCase rs3806448 polymorphism was significantly different among AE cases and controls --- p.53 / Chapter 5.2.1 --- Allele frequency comparison of AMCase SNPs polymorphisms by chi-square --- p.53 / Chapter 5.2.2 --- Allele frequency comparison of AMCase SNPs polymorphisms by logistic regression analysis --- p.54 / Chapter 5.2.3 --- The possible genetic modification by rs3806448 homozygous recessive genotype --- p.55 / Chapter 5.3 --- "Significant difference of haplotype frequency, 2212 among case-control comparison" --- p.56 / Chapter 5.4 --- Strong associations between AMCase SNPs polymorphisms and clinical parameters of AE --- p.57 / Chapter 5.4.1 --- Peripheral blood eosinophil counts --- p.57 / Chapter 5.4.2 --- Dermatologic factors --- p.58 / Chapter 5.4.2.1 --- Cutaneous Staphylococcus aureus colonization --- p.58 / Chapter 5.4.2.2 --- Skin hydration (SH) and transepidermal water loss (TEWL) --- p.59 / Chapter 5.5 --- Limitation of the present study --- p.59 / Chapter Chapter 6: --- Conclusion and Future Prospect --- p.62 / Chapter 6.1 --- Conclusion --- p.62 / Chapter 6.2 --- Future prospect --- p.62 / Chapter Chapter 7: --- Appendices --- p.64 / Chapter Chapter 8: --- References --- p.69

Background: Evidence-based treatment algorithms, successfully established for asthma, are missing for atopic eczema (AE). Objectives: To investigate whether treatment according to an evidence-based algorithm is an effective and applicable concept for the management of AE. Methods: Based on a systematic literature review, we developed an evidence-based severity-score-oriented treatment algorithm for AE and compared its effectiveness to that of an individualised symptom-oriented treatment (individual therapy) in a randomised controlled trial. Sixty-three participants were randomised to algorithm (n = 32) or individual therapy (n = 31) and treated accordingly for 12 months. Study end points included difference between baseline SCORAD and mean SCORAD under treatment (primary end point), quality of life and treatment utilisation. Analysis was by intention to treat (registration: ClinicalTrials.gov:NCT00148746). Results: No statistically significant differences in clinical or subjective response were observed between groups. Treatment following the algorithm and individual treatment both effectively controlled AE. Mean SCORAD reductions were 47% (95% confidence interval, CI = 38–55; algorithm) and 42% (95% CI = 29–54; individual). Clinical response was paralleled by improved quality of life in both groups. Physicians adhered to the algorithm option in 93% of their treatment decisions. Conclusion: Treatment following an evidence-based algorithm is an effective and applicable concept for the management of AE but does not show clear advantages compared to individualised treatment in a dermatological setting. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Introdução: Dermatite atópica (DA) é uma doença cutânea crônica, predominante na infância, cujo sintoma principal é o prurido de intensidade variável, e os sinais são classicamente as lesões de padrão eczematoso. Há anormalidades na formação e função da barreira cutânea, que estão presentes não somente nas lesões cutâneas como na pele clinicamente não afetada. Objetivo: Analisar a correlação entre as medidas biofísicas da função de barreira cutânea e os critérios clínicos e intensidade da dermatite, de acordo com os critérios de Rajka e Langeland. Métodos: 231 doentes do Departamento de Dermatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, com diagnóstico clínico de dermatite atópica segundo os critérios diagnósticos de Rajka e Langeland foram avaliados por exame físico, anamese, medidas biofísicas de grau de hidratação de camada córnea pelo método de capacitância (corneometria) e pelo método de perda de água transepidérmica (TEWL); a medida sérica de IgE também foi solicitada no ato do exame. Resultados: Houve uma relação significativa entre as medidas de corneometria, TEWL e gravidade clínica da dermatite atópica. Os dados demonstraram uma correlação inversamente proporcional entre a corneometria e o TEWL, e houve uma diferença estatisticamente significativa (p<0,001) entre as médias de corneometria e TEWL e grau de DA (leve, moderada ou intensa). Com relação aos níveis séricos de IgE, as medidas de corneometria apresentaram uma correlação negativa significativa; para TEWL, a correlação positiva foi estatisticamente significativa (p<0,001). Conclusão: As medidas biofísicas de barreira cutânea na DA, mesmo em pele aparentemente não lesada, podem funcionar como fator de avaliação do grau clínico da DA e da intensidade do prurido. / Background: Atopic dermatitis (AD) is a chronic dermatosis, predominant in childhood, characterized by pruritus and eczematous type lesions with xerosis as the proeminent clinical sign. Objectives: To analyze the correlation between biophysical measurements of skin barrier function and other assessment criteria of clinical severity according to Rajka and Langelands criteria. Methods: Biophysical measurements (Transepidermal water loss and corneometry) were obtained from 231 patients from the department of dermatology, Hospital das Clinicas FMUSP with the diagnsosis of atopical dermatitis. Serum levels of IgE were also evaluated. Results: A significant correlation between corneometry, TEWL and clinical severity of atopic dermatitis were found. Data showed an inverse correlation between corneometry, TEWL, and AD severity, and a significant difference (p<0,001) between means of corneometry and TEWL and AD severity (mild, moderate and severe). As for IgE levels, corneometry had significant negative correlation, in contrast with TEWL, wich showed a significant positive correlation (p<0,001). Conclusion: Biophysical measurements of skin barrier in non lesional skin of atopic dermatitis may work as an evaluation factor for AD severity and pruritus.

Background: Evidence-based treatment algorithms, successfully established for asthma, are missing for atopic eczema (AE). Objectives: To investigate whether treatment according to an evidence-based algorithm is an effective and applicable concept for the management of AE. Methods: Based on a systematic literature review, we developed an evidence-based severity-score-oriented treatment algorithm for AE and compared its effectiveness to that of an individualised symptom-oriented treatment (individual therapy) in a randomised controlled trial. Sixty-three participants were randomised to algorithm (n = 32) or individual therapy (n = 31) and treated accordingly for 12 months. Study end points included difference between baseline SCORAD and mean SCORAD under treatment (primary end point), quality of life and treatment utilisation. Analysis was by intention to treat (registration: ClinicalTrials.gov:NCT00148746). Results: No statistically significant differences in clinical or subjective response were observed between groups. Treatment following the algorithm and individual treatment both effectively controlled AE. Mean SCORAD reductions were 47% (95% confidence interval, CI = 38–55; algorithm) and 42% (95% CI = 29–54; individual). Clinical response was paralleled by improved quality of life in both groups. Physicians adhered to the algorithm option in 93% of their treatment decisions. Conclusion: Treatment following an evidence-based algorithm is an effective and applicable concept for the management of AE but does not show clear advantages compared to individualised treatment in a dermatological setting. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

INTRODUÇÃO: O aumento da prevalência das doenças alérgicas tem sido associado a vários fatores de risco e a detecção destes e a avaliação da prevalência em diferentes regiões é fundamental. O protocolo padronizado ISAAC (International Study of Asthma and Allergies in Childhood), possibilitou a comparação destes dados epidemiológicos. Os OBJETIVOS deste estudo foram: avaliar a prevalência da asma, rinite e eczema alérgicos e sintomas relacionados, entre escolares de 13 a 14 anos, da região oeste da cidade de São Paulo, utilizando-se o questionário escrito ISAAC e identificar possíveis fatores de risco associados à presença de asma ou à positividade ao teste cutâneo de hipersensibilidade imediata (TCHI). MÉTODOS: Entre fevereiro de 2002 e outubro de 2003 foi aplicado questionário escrito ISAAC em 3181 alunos. Após amostragem sistemática, 528 alunos foram submetidos ao TCHI para o diagnóstico de atopia e responderam a um questionário complementar sobre antecedentes familiares e condições ambientais. Foram constituídos grupos de alunos com ou sem asma, considerando-se a presença de sintomas de asma nos últimos 12 meses, e com ou sem TCHI positivo a pelo menos um aeroalérgeno. A análise dos fatores de risco foi realizada pelo teste do qui-quadrado ou teste exato de Fisher e por regressão binária logística (Backward Stepwise). RESULTADOS: As prevalências encontradas foram: asma de 21,9%, diagnóstico médico de asma 8,9%, rinite de 30,1%, rinoconjuntivite de 19,8% , diagnóstico médico de rinite 18,9%, eczema atópico de 9,7% e o diagnóstico médico de eczema 8,6%. Houve associação entre asma, rinite e eczema atópico em 2,3% dos adolescentes. O sexo feminino foi prevalente em todas as questões sobre asma, rinite e eczema atópico. Houve associação entre TCHI e a presença de asma (OR = 2,6) e de rinite (OR = 1,9). Em relação à asma, os fatores de risco foram: sintomas de rinite no último ano (ORajustado = 3,2); positividade ao TCHI (ORajustado = 2,8); parto prematuro (ORajustado = 3,8); nunca consumir vegetais cozidos (ORajustado = 2,6); presença de eczema em locais característicos (ORajustado = 2,9) e mãe alérgica (ORajustado = 2,0). Em relação à positividade do TCHI, os fatores de risco foram: presença de asma (ORajustado = 2,3); sintomas de rinite no último ano (ORajustado = 1,9); pai alérgico (ORajustado = 2,2) e parto cesáreo (ORajustado = 1,7). CONCLUSÕES: A prevalência de asma neste estudo mostrou valores elevados em comparação ao diagnóstico médico de asma. A prevalência da rinoconjuntivite foi comparável ao diagnóstico médico de rinite, que foram menores que a prevalência de rinite no último ano. A prevalência de eczema atópico foi maior que aquela avaliada pelo critério combinado. Houve predomínio do sexo feminino nas respostas positivas para todas as doenças atópicas. Houve associação entre TCHI e presença de rinite ou asma. Os fatores de risco associados à asma foram: mãe alérgica, rinite, parto prematuro, eczema em locais característicos, dieta sem vegetais cozidos e TCHI positivos e os relacionados à positividade do TCHI: pai alérgico, cesárea, asma e rinite no último ano. / INTRODUCTION: The increase of allergic diseases has been associated to several risk factors, the detection of them and prevalences evaluations from different areas are essential. The written questionnaire standardized by "International Study of Asthma and Allergies in Childhood" - ISAAC, made possible the comparison of epidemiologic data. The aims of the present study were: to evaluate the prevalence of asthma, rhinitis and allergic eczema and related symptoms, among students from 13 to 14 years in the west area of São Paulo city, through the written questionnaire from the ISAAC study and to identify possible risk factors associated to asthma or positive skin prick test in this population. METHODS: In the period from February/2002 to October/2003 written questionnaire was applied to 3181 students. After selection by systematic samples, 528 students were submitted to skin prick test regarding the atopic diagnose and they answered a complementary questionnaire about family history and environmental conditions. The students' groups were constituted with or without asthma according the positive answer to asthma symptoms in the last 12 months, and with or without positive skin prick test at least one aeroallergen. The risk factors analysis was accomplished by univariated (qui-square or Fisher’ exact test) and multivariated analysis by binary logistic regression (Backward Stepwise). RESULTS: The prevalence found were: asthma 21,9%, medical diagnosis of asthma 8,9%, rhinitis 30,1%, rhinoconjunctivitis 19,8%, medical diagnosis of rhinitis 18,9%, atopic eczema 9,7% and the medical diagnosis of eczema 8,6%. There was association among asthma, rhinitis and atopic eczema in 2,3% of the adolescents. Female sex was prevalent in all of the subjects on asthma, rhinitis and atopic eczema. There was association between skin prick test and asthma (OR = 2,6) and rhinitis (OR = 1,9). In relation to asthma, the risk factors were: rhinitis symptoms in the last year (ORadjusted = 3,2); positive skin prick test (ORadjusted = 2,8); premature delivery (ORadjusted = 3,8); never to consume cooked vegetables (ORadjusted = 2,6); eczema presence in characteristic areas (ORadjusted = 2,9) and allergic mother (ORadjusted = 2,0). In relation to positive skin prick test, the risk factors were: asthma (ORadjusted = 2,3); rhinitis symptoms in the last year (ORadjusted = 1,9); allergic father (ORadjusted = 2,2) and cesarean section (ORadjusted = 1,7). CONCLUSIONS: This study showed high prevalence of asthma when compared with medical diagnosis of asthma. The prevalence of rhinoconjunctivitis was similar to medical diagnostic of rhinitis that was lower than the rhinitis prevalence in the last year. The prevalence of atopic eczema was higher than combined criteria. The female gender predominates in all positive responses regarding allergic diseases. There was association between skin prick test and asthma or rhinitis. The risk factors associated with asthma were allergic mother, rhinitis, premature delivery, eczema at characteristic areas, diet without cooked vegetables and positive skin prick test. The risk factors associated with positive skin prick test were: allergic father, cesarean section, asthma and rhinitis in the last year.

A dermatite atópica é uma doença de pele de caráter inflamatório crônico que normalmente precisa de tratamento com glicocorticóide tópico. O objetivo deste estudo foi avaliar o impacto da Dermatite atópica no consumo de nutrientes, no estado nutricional e no metabolismo ósseo de crianças com dermatite atópica moderada e grave comparadas à crianças saudáveis. Foram incluídas neste estudo 60 crianças de 4 a 12 anos com AD moderada/grave e 54 controles. O consumo alimentar foi avaliado por três recordatórios de 24 horas. O estado nutricional foi determinado pelo z-escore de altura para idade, peso por idade e do índice de massa corporal. Os marcadores ósseos séricos foram 25OH vitamina D, fosfatase alcalina óssea, cálcio sérico, fósforo, PTH, osteocalcina, CTX e cortisol. Os pacientes e familiares foram questionados quanto à fraturas, exposição solar e escore de atividade física. Por meio de densitometria dupla de Raio-X avaliou-se o conteúdo mineral ósseo (CMO), a densidade mineral óssea (DMO) e o z-score da coluna lombar, do fêmur total e do corpo inteiro. As crianças com dermatite atópica usavam glicocorticóide tópico em média por 3,9 ±1,81 anos. O tempo de exposição solar foi menor nas crianças com dermatite atópica. O consumo alimentar evidenciou um alto consumo de proteínas em ambos os grupos, e a ingestão de gordura foi mais baixo na crianças com DA. A média consumida de cálcio e vitamina D foi abaixo da recomendação nutricional em ambos os grupos. As crianças com DA apresentaram mais casos de rinite, asma e alergia alimentar do que o grupo controle. Segundo o zscore de altura para idade as crianças com DA foi significativamente mais baixas quando comparadas com o grupo controle. O CTX sérico foi menor no grupo DA. O CMO da coluna lombar foi mais baixo nas crianças com DA, e o CMO, a DMO e o z-score do fêmur total também foram significativamente menores no grupo DA do que no grupo controle. Neste grupo de crianças com DA, estudado o uso do glicocorticóide tópico pode ter diminuído a altura para idade, e a massa óssea. / Atopic dermatitis is an inflammatory allergic skin disease that often requires glicocorticosteroids therapy. The aim of this study was to determine the atopic dermatitis impact on food ingestion, nutritional status and bone mass in children with moderate to severe AD compared with a control group. Food ingestion was evaluated with 3 days 24-hour food recordathory. Nutritional status was determined with height to age z-score, weight for age z-score and BMI z-score. Bone markers measured in serum were 25OH vitamin D, bone phosphatase alkaline, CTX, serum calcium, phosphorus, osteocalcin, PTH and cortisol. Information on lifestyle parameters, bone fractures, sun exposure and physical activity were collected by use of a standardized questionnaire. Lumbar spine, total femur and whole body, bone mineral content (BMC), bone mineral density (BMD) and z-score was measured by dual-energy X-ray absorptiometry in 60 children (age 4-12years) with moderate to severe AD and 54 health controls, with the same age. In children, low BMD was defined as a Z-score less than -2. The AD children used topic glicocorticosteroids for a mean of 3,9 ±1,81 years. The sun exposure was lower in the AD group. Food ingestion showed high protein ingestion levels in both groups, and the fat consumption was lower in the AD children. The calcium and vitamin ingestion were bellow the recommendations in the two groups. Children with AD had more riniths, asthma and food allergy then control group. The CTX was lower in the AD group. The children with AD were significantly smaller according to the height for age zscore. There was significant smaller BMC on lumbar spine, and in the BMC, BMD and z-score in the total femur on the AD children. Low BMD occured more frequently in this population of children with moderate to severe AD compared with the control group. Use of topical glicocorticosteroids in the previous could be 5 years associated with the decrease in BMD.

INTRODUÇÃO: A dermatite atópica (DA) é considerada a principal e mais freqüente manifestação cutânea da atopia, podendo acometer até 20% da população pediátrica mundial. Trata-se de uma doença multifatorial onde agentes infecciosos como S.aureus são relevantes no desencadeamento das crises. OBJETIVOS: (1) Avaliar a taxa de colonização do S.aureus na pele e vestíbulo nasal de pacientes com DA e o seu perfil de sensibilidade a antibióticos (2) Comparar os resultados com a taxa de colonização do vestíbulo nasal dos cuidadores primários (3) Avaliar a associação entre colonização por S.aureus gravidade da doença e hábitos de higiene. MÉTODOS: Foi realizado estudo prospectivo entre dezembro de 2016 a fevereiro de 2017. Foram avaliados aspectos clínicos, epidemiológicos e laboratoriais de crianças com DA em seguimento na unidade de alergia e imunologia do Instituto da Criança da Faculdade de Medicina da Universidade de São Paulo (ICr HCFMUSP). Foram incluídos pacientes que apresentaram DA moderada ou grave, classificados de acordo com o escore de gravidade SCORAD (scoring atopic dermatitis). Foram excluídos pacientes que haviam utilizado antibioticoterapia há menos de 30 dias da inclusão, que apresentavam infecções cutâneas ou utilizavam imunossupressores por via sistêmica. A pesquisa de S.aureus em pacientes foi realizada por meio de coleta de swab em vestíbulo nasal, lesão aguda e crônica dos pacientes com DA e nos cuidadores primários foi realizado swab de vestibulo nasal. RESULTADOS: Foram avaliados 27 pacientes (14M), 18 com DA moderada e 9, grave. O início da doença ocorreu entre 2 e 60 meses de idade (mediana de 12m) e a coleta de swab ocorreu ao 9 anos (mediana, com variação entre 2 e 15 anos). Todos os pacientes apresentaram colonização por S.aureus em pelo menos um local de coleta, sendo a lesão aguda o mais frequente (24/27), seguido do nariz (23/27) e lesão crónica (20/27). Dezenove cuidadores apresentaram S.aureus em vestíbulo nasal. A presença de S.aureus meticilino resistente (MRSA) foi detectada em 9/23 pacientes no vestíbulo nasal, 8/24 na lesão aguda e 6/20 na lesão crônica. Entre os cuidadores 6/19 apresentaram S.aureus MRSA em vestíbulo nasal. Pacientes e cuidadores primários apresentaram semelhança no perfil de sensibilidade a antibióticos (kappa 0,75). A gravidade da doença (SCORAD), não se correlacionou de maneira significante com a taxa de colonização, mas pacientes com escores de prurido mais elevados apresentaram estafilococos MRSA com maior freqüência de maneira estatisticamente significante (p= 0,29). Houve uma elevada taxa de compartilhamento de produtos com destaque: produtos pessoais (17/27) cama (11/27) e toalha (3/27) CONCLUSÃO: S.aureus permanece como uma bactéria bastante presente na pele de quem apresenta dermatite atópica, independentemente do tipo de lesão. A presença de elevadas taxas de S.aureus MRSA é um sinal de alerta para o cuidadoso manejo de pacientes com DA e estratégias que envolvam a orientação com relação as medidas de higiene e cuidado pessoal devem fazer parte do tratamento da dermatite atópica / Atopic dermatitis (AD) is considered the main and most common cutaneous manifestation of atopy, affecting up to 20% of the world pediatric population. It is a multifactorial disease where infectious agents such as S. aureus are relevant in the onset of crises. OBJECTIVES: (1) To evaluate the rate of colonization of S.aureus in the skin and nasal vestibule of patients with AD and its antibiotic susceptibility profile. (2) To compare the results with the nasal vestibular colonization rate of primary caregivers (3 ) Evaluate the association between S.aureus colonization, disease severity and hygiene habits. METHODS: A prospective study was carried out between December 2016 and February 2017. Clinical, epidemiological and laboratory aspects of children with AD were evaluated at the unit of allergy and immunology of the Children\'s Institute of the School of Medicine of the University of São Paulo (ICr HCFMUSP). Patients with moderate or severe AD, classified according to SCORAD (scoring atopic dermatitis) severity score were included. Patients who used antibiotic therapy less than 30 days before inclusion, who had cutaneous infections or who used systemic immunosuppressants were excluded. The study of S.aureus in patients was performed through nasal vestibule swab collection, acute and chronic lesion of patients with AD, and nasal vestibule swabs were performed in primary caregivers. RESULTS: Twenty-seven patients (14M), 18 patients with moderate AD and 9 patients, were diagnosed. The onset of the disease occurred between 2 and 60 months of age (median of 12 m) and swab collection occurred at 9 years (median, Between 2 and 15 years). All patients presented colonization by S.aureus in at least one collection site, with acute lesion being the most frequent (24/27), followed by the nose (23/27) and chronic lesion (20/27). Nineteen caregivers presented S .aureus in the nasal vestibule. The presence of methicillin-resistant S.aureus (MRSA) was detected in 9/23 patients in the nasal vestibule, 8/24 in the acute lesion and 6/20 in the chronic lesion. Carriers 6/19 presented S.aureus MRSA in the nasal vestibule. Patients and primary caregivers presented similarity in the sensitivity profile to antibiotics (kappa 0.75). The severity of the disease (SCORAD) did not correlate significantly with the rate of colonization, but patients with higher pruritus scores had statistically more significant MRSA staphylococci (p = 0.29). There was a high rate of product sharing with emphasis on: personal products (17/27) bed (11/27) and towel (3/27) CONCLUSION: S.aureus remains a very present bacterium in the skin of those with atopic dermatitis , Regardless of the type of injury. The presence of high rates of S.aureus MRSA are a warning sign for the careful management of patients with AD and strategies that involve guidance regarding hygiene measures and personal care should be part of the treatment of atopic dermatitis

Introdução: A asma é uma doença inflamatória crônica com alta morbi-mortalidade na adolescência. Objetivos: O objetivo geral foi estudar a prevalência da asma em adolescentes na cidade de Taubaté (SP). Os específicos foram determinar a prevalência da asma, rinite e eczema, utilizando os questionários ISAAC (International Study of Asthma and Allergies in Childhood) Fase I em escolares de 13 a 14 anos residentes na cidade de Taubaté e estabelecer uma correlação entre os sintomas de asma ativa (\"sibilos nos últimos 12 meses\") e os fatores de risco: tabagismo (ativo e passivo) e a presença de animais e/ou insetos no domicílio. Métodos: No estudo transversal de uma amostra casual probabilística por conglomerados, foram aplicados questionários a 920 adolescentes de 13 a 14 anos sorteados ao acaso, matriculados entre as 7a e 8a séries de escolas públicas e privadas na cidade de Taubaté no período de agosto de 2004 à janeiro de 2005. Os questionários foram auto-aplicáveis sendo a primeira parte composta por 8 questões referentes à asma, 6 referentes à rinite e uma ao eczema(ISAAC), e a segunda parte composta por 8 questões referentes ao tabagismo e 4 referentes à presença de animais de estimação e/ou insetos no domicílio (questionário complementar). Resultados: Nos 809 adolescentes que completaram os questionários, a prevalência de \"sibilos alguma vez\" foi de 44,6%; \"sibilos nos últimos 12 meses\" 15,3%; \"uma ou mais crises de sibilos nos últimos 12 meses\" 15,4%; \"sono perturbado por crises de sibilos\" 10,6%; \"fala prejudicada por crises de sibilos\" 1,7%; \"asma alguma vez\" 6,8%, \"sibilos aos exercícios físicos\" 13,5%; \"tosse seca noturna sem estar resfriado ou gripado\" 33,1%;\"rinite alguma vez\" 37,6%, \"eczema alguma vez\" 16,2%, sem diferenças estatisticamente significativas em relação aos sexos. Houve diferença estatística entre os sexos para os adolescentes que relataram o \"problema nasal nos últimos 12 meses acompanhado de lacrimejamento ou coceira nos olhos\" com predomínio no sexo feminino (p=0,03). Houve associação significativa em ambos os sexos para \"asma e rinite alguma vez\" (p=0,02). Entretanto, os adolescentes de ambos os sexos que negaram ter \"asma alguma vez\" tiveram associação significativa entre \"rinite e eczema alguma vez\"( p=0,04), e também entre \"chiado após exercício físico e tosse seca noturna sem estar resfriado ou gripado\" (p=0,001) sugerindo o sub-diagnóstico de asma.Os fatores de risco foram relacionados apenas aos sintomas de asma ativa por fornecerem informação mais segura como recordatório. A prevalência de adolescentes fumantes no estudo foi de 0,7%. Com relação ao tabagismo passivo a prevalência foi de 41% e destes 35% correspondia às mães fumantes. A presença de animais de estimação foi verificada em 55,6% e em 34% intradomiciliar. A presença de insetos foi relatada por 55,1% da população estudada. Quando os fatores de risco foram correlacionados aos sintomas de asma ativa, não houve associação estatisticamente significativa. Conclusões: A prevalência da asma no estudo foi de 6,8%. As prevalências de rinite e eczema foram respectivamente 37,6% e 16,2%. Os fatores de risco não tiveram associação com asma ativa. / Introduction: Asthma is a chronic inflamatory disease with high morbi-mortality in adolescence. Objectives: The general goal was to study the prevalence of asthma in adolescents in the city of Taubaté (SP). The specific goals were to determine the prevalence of asthma, rhinitis and eczema using the ISAAC questionnaire (International Study of Asthma and Allergies in Childhood), Phase I, for schoolchildren aged 13 to 14, residents in the city of Taubaté and to establish a relation between the symptoms of active asthma (\"wheezing in the last 12 months\") and the risk factors of smoking (active and passive) and the presence of pets and/or insects at home. Methods: In Cross sectional study of probabilistic sample, questionnaires were applied to 920 adolescents aged 13 to 14 enrolled in 7th and 8th grades, chosen at random, from the public and private schools in Taubaté, from August 2004 to January 2005. The questionnaires were self-applied with the first part consisting of 8 questions related to asthma; 6 related to rhinitis and one related to eczema (ISAAC), and the second part consisting of 8 questions related to smoking and 4 related to the presence of pets and/or insects at home (additional questionnaire). Results: In 809 adolescents who completed the questionnaires, the prevalence of \"wheezing ever\" was 44.6%; \"wheezing in the last 12 months\" 15.3%; \"one or more crisis of wheezing in the last 12 months\" 15.4%; \"sleeping disturbed by wheezing\" 10.6%; \"speech disturbed by wheezing\" 1.7%; \"asthma ever\" 6.8%; \"wheezing following exercise\" 13.5%; \"nocturnal dry coughing without respiratory infection\" 33.1%; \"rhinitis ever\" 37.6% and \"eczema ever\" 16.2% with no statistically significant difference between girls and boys. There was a significant difference between adolescent girls and boys who related \" nose symptoms in the last 12 months with watery and itchy eyes\", predominant in girls (p=0.03). There was a significant association in all adolescents between \"asthma and rhinitis ever\"(p=0.02). However, the adolescents( boys and girls) who denied having \"asthma ever\", had significant association between \"rhinitis and eczema ever\" and also between \"wheezing following exercise and/or nocturnal dry coughing without respiratory infection\"(p=0.001), which suggests the subdiagnosis of asthma. The risk factors studied were related only to the symptoms of active asthma in order to favor recall. The prevalence of adolescent smokers in the study was 0.7%. In relation to passive smoking, the prevalence was 41% of which 35% corresponded to the mothers who smoked. The presence of pets was noted in 55.6% of the answers and of these, 34.9% were house pets. The presence of insects at home was related to 55.1% of the sample studied. When the risk factors were related to the symptoms of active asthma, there wasn\'t a statistically significant association. Conclusions: The prevalence of asthma in the study was 6.8%. The prevalence of rhinitis and eczema was respectively 37.6% and 16.2%. The risk factors didn\'t have association with active asthma.