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.

O objetivo deste trabalho e o desenvolvimento de roupas utilizando malha de linho para uso como primeira camada em contato direto com o corpo em usuários com dermatite atópica. Roupas disponíveis para essas pessoas com pele sensível, incluindo algumas com algodão, muitas vezes provocam irritação na pele e uma malha de linho pode ser uma boa opção de uso, com base em suas reconhecidas propriedades de contato saudável ao corpo humano, principalmente em climas quentes. Protótipos de malhas consideradas pelo autor como clássicas ou oclusivas e outras como não oclusivas foram produzidas com algodão, fibras descontinuas de poliéster e linho em estrutura jérsei de malharia circular. As malhas foram confeccionadas em roupas para um teste de uso experimental em 4 crianças entre 5-8 anos de idade, sendo 2 delas saudáveis e duas com dermatite atópica, previamente avaliadas por um dermatologista. O resultado final demonstrou um bom grau de tolerância por todos os usuários quanto ao uso da malha com linho em contato direto com a pele. As malhas não oclusivas foram as que apresentaram os melhores índice de permeabilidade ao ar,atributo que pode evitar o bloqueio da transpiração insensível durante rotinas diárias, minimizando o abafamento, desconforto térmico e potencial gatilho de irritação da pele. Câmera infravermelha foi utilizada como uma ferramenta adicional na Avaliação térmica durante o uso. Os resultados sugerem que a malha com linho não oclusiva e uma opção viavel de uso pelos portadores de dermatite atópica em clima subtropical como o da cidade de São Paulo. O controle da estabilidade dimensional da malha com linho e amaciantes naturais amigáveis a pele para a lavagem domestica das roupas são desafios que devem ser equacionados em futuros desenvolvimentos / Linen (Linum usitatissimum L.) in single jersey of circular knitting machine for wearer with atopic dermatitis in subtropical climate The purpose of this work is the development of first layer linen knitted structure aiming wearers with Atopic Dermatitis (AD). Available clothing for these sensitive skin people, including some cotton garments, very often presents skin irritation and linen is an option based upon it recognized friendly contact to human body and comfortable wear during hot climates. Classic or occlusive and non-occlusive garments prototypes knitted in single jersey of circular knitting machines with cotton, polyester staple and linen fibers were designed to accomplish an experimental wear test with 4 children with 5-8 years old, 2 with AD and 2 health kids. Voluntaries showed good wear tolerance to knitted linen that presented highest air permeability index that can help to avoid blocking of insensible perspiration during daily routine, minimizing buffering effect and potential trigger of skin irritation. Infrared camera was used as an additional tool for thermal evaluation during use. Results suggest that non-occlusive knitted linen is a possible option for AD wears at subtropical climate like the city of Sao Paulo. Dimensional stability control of nonhocclusive knitted linen and natural home laundry softeners are challenges to be overcome in future developments

Introdução: Eczemas são manifestações inflamatórias da pele. Na infância se destacam a dermatite atópica (DA) e a dermatite de contato (DC). Os testes de contato correspondem a um método auxiliar para diferenciar a dermatite de contato por irritante primário (DCIP) da dermatite de contato alérgica (DCA) e definir a etiologia da DCA. Nos pacientes com DA, têm a faculdade de também auxiliar na identificação de substâncias que possam estar contribuindo para a piora do quadro. Objetivos: verificar a frequência de testes de contato positivos em crianças com hipóteses diagnósticas de DC e de DA associada ou não à DC; obter os principais sensibilizantes nessa faixa etária e comparar os dados obtidos entre os grupos de pacientes com DC e DA. Métodos: Durante o período entre julho de 2007 e agosto de 2009, 62 crianças com idades entre 2 e 12 anos foram submetidas aos testes de contato com a bateria padrão e/ou bateria de cosméticos de testes de contato padronizadas pelo Grupo Brasileiro de Estudos em Dermatite de Contato. As leituras foram realizadas em 48 e 96 horas. Resultados: Entre os 62 pacientes submetidos aos testes de contato, 38 pacientes apresentaram pelo menos um teste de contato positivo e 24, todos negativos. Entre os 44 pacientes com hipótese diagnóstica inicial de DA, 19 tinham DA associada à DCA. Entre os 18 pacientes com hipótese diagnóstica inicial de DC, 12 apresentavam DCA. No total, foram encontrados 76 testes positivos, sendo 53 (70%) relevantes, e 23 (30%) não relevantes com a história clínica do paciente. Os pacientes com DA apresentaram mais testes positivos não relevantes do que os pacientes com hipótese diagnóstica apenas de DC, e essa diferença foi estatisticamente significativa.( 2 = 6,55 e p = 0,01 ). Considerando os testes relevantes com a história clínica, o sulfato de níquel foi o principal sensibilizante com 14 (22,6%) testes positivos, a neomicina foi o segundo sensibilizante mais comum com sete testes positivos (11,3%), e a terceira substância mais comum foi o cloreto de cobalto com quatro (6,4%) testes positivos. Testes não relevantes foram encontrados em 30% do total de substâncias com testes positivos. O timerosol foi positivo em 11 casos, porém em oito pacientes com DA não foram relevantes com a história clínica. Conclusões: Pacientes na faixa etária entre 2 e 12 anos com DA e DC apresentaram testes de contato positivos, e não houve diferenças quanto à frequência dos testes positivos entre esses dois grupos. Os principais sensibilizantes relevantes com a história clínica foram o sulfato de níquel, a neomicina e o cloreto de cobalto, o que está de acordo com vários estudos na literatura. Pacientes com DA apresentaram mais testes falso-positivos que os pacientes com DC, possivelmente por um defeito da barreira cutânea dos pacientes com DA, e maior exposição precoce aos medicamentos tópicos ou emolientes para o controle da DA. Teste de contato em crianças pode ser considerado importante ferramenta para auxiliar no diagnóstico dos eczemas, identificando o agente causador da DC ou de piora nos casos de DA, e deve ser levado em conta em todos esses pacientes / Eczema is a cutaneous inflammatory manifestation in some dermatosis. In children, we highlight atopic dermatitis (AD) and contact dermatitis (CD). Patch tests help to differentiate irritative contact dermatitis (ICD) from allergic contact dermatitis (ACD), and define the etiology of allergic contact dermatitis. In patients with AD, it may also help to identify substances that may contribute to the worsening of this dermatosis. Objectives: To determine the frequency of positive patch tests in children with diagnosis of CD and AD with or without CD; to detect the main sensitizers in this group and compare the results between the groups of patients with CD and AD. Methods: From July 2007 to August 2009, 62 children aged between 2 to 12 years old were patch tested with the Brazilian standard battery of patch tests and cosmetic series. The readings were taken at 48 and 96 hours. Results: Thirty-eight patients had at least one positive patch test reactions and 24, all negative. Among the 44 patients with initial diagnosis of AD, 19 were associated with ACD. Among the 18 patients with initial diagnosis of CD, 12 had ACD. In total, there were 76 positive tests, 53 (70%) relevant, and 23 (30%) not relevant to the patient\'s clinical history. Patients with AD showed more positive tests not relevant than patients with diagnosis of CD only, and this difference was statistically significant. (2 = 6.55 and p = 0.01). Considering the relevant tests, nickel sulphate was the main allergen with 14 (22.6%) positive tests, neomycin was the second with seven positive tests (11.3%), and the third substance was cobalt chloride with four (6.4%) positive tests. Tests not relevant were found in 30% of the total of the positive tests. Thimerosol was positive in 11 cases, but in eight patients with AD were not relevant to the clinical history. Conclusions Patients aged between 2 to 12 years old with AD and CD had positive tests, and there were no differences in the frequency of positive tests between these two groups. The main sensitizers, relevant to the clinical history were nickel sulfate, neomycin and cobalt chloride. This result is consistent with several studies in the literature. Patients with AD showed more false-positive tests than patients with CD, possibly due to a defective skin barrier of AD patients, and earlier exposure to topical emollients and treatments for the control of AD. Patch test in children can be considered an important tool for the diagnosis of eczema, identifying the causative agent of CD or worsening cases of AD, and should be performed in all these patients. The correct interpretation of the patch tests is essential to evaluate the association of ACD in patients with AD and to identify the causative agent of the ACD

<p>Mast cell (MC) accumulation around tumours is an old observation gaining new relevance due to the multifaceted nature of MCs and their many roles in immunity, beyond allergy. Knowledge about tumour specific recruitment of, and interactions with, MCs is needed to unravel the function of their presence.</p><p>This study investigates the participation of mast cells in the tumourigenesis of Hodgkin lymphoma (HL), a tumour with many inflammatory features. We report that MC recruitment into HL lymphomatous tissue is possibly due to the production of CCL5/RANTES by malignant Hodgkin and Reed-Sternberg (HRS) cells. In addition, increased levels of IL-9, a cytokine implicated in mast cell heterogeneity and as an autocrine growth factor for HRS cells, were found in HL patient sera and correlate with negative prognostic factors. The ubiquitous expression of CD30 by HRS cells has been implicated in HL tumour development. In HL tissue MCs were found to be the predominant CD30 ligand (CD30L) expressing cells, and through CD30L/CD30 engagement they induced a proliferative response in HRS cells. This interaction proved to be bi-directional as it induced a degranulation-independent <i>de novo</i> synthesis of a specific set of chemokines in MCs, including IL-8. This novel trigger of MC activation is suggested to be of importance also in atopic dermatitis (AD) and psoriasis since increased numbers of CD30L and IL-8 positive MCs were detected along with increased expression of CD30.</p><p>Data presented in this study supports a specific recruitment of MCs into HL tumours and co-operative interactions between HRS cells and MCs. Our identification of reversed signalling via CD30L as a novel MC trigger provides a mechanism behind leukocyte infiltration and chronic development in diseases associated with CD30 and MCs, such as HL, AD and psoriasis.</p>

Mast cell (MC) accumulation around tumours is an old observation gaining new relevance due to the multifaceted nature of MCs and their many roles in immunity, beyond allergy. Knowledge about tumour specific recruitment of, and interactions with, MCs is needed to unravel the function of their presence. This study investigates the participation of mast cells in the tumourigenesis of Hodgkin lymphoma (HL), a tumour with many inflammatory features. We report that MC recruitment into HL lymphomatous tissue is possibly due to the production of CCL5/RANTES by malignant Hodgkin and Reed-Sternberg (HRS) cells. In addition, increased levels of IL-9, a cytokine implicated in mast cell heterogeneity and as an autocrine growth factor for HRS cells, were found in HL patient sera and correlate with negative prognostic factors. The ubiquitous expression of CD30 by HRS cells has been implicated in HL tumour development. In HL tissue MCs were found to be the predominant CD30 ligand (CD30L) expressing cells, and through CD30L/CD30 engagement they induced a proliferative response in HRS cells. This interaction proved to be bi-directional as it induced a degranulation-independent de novo synthesis of a specific set of chemokines in MCs, including IL-8. This novel trigger of MC activation is suggested to be of importance also in atopic dermatitis (AD) and psoriasis since increased numbers of CD30L and IL-8 positive MCs were detected along with increased expression of CD30. Data presented in this study supports a specific recruitment of MCs into HL tumours and co-operative interactions between HRS cells and MCs. Our identification of reversed signalling via CD30L as a novel MC trigger provides a mechanism behind leukocyte infiltration and chronic development in diseases associated with CD30 and MCs, such as HL, AD and psoriasis.

Atopic dermatitis (AD), ichthyosis vulgaris (IV), and X-linked recessive ichthyosis (XLRI) are characterized by dry skin and impaired skin barrier. AD and IV are related to loss-of-function mutations in FLG (encoding filaggrin), whereas XLRI is caused by deletions or inactivating mutations in the steroid sulphatase gene (STS). Patients regularly use moisturizing creams, but little is known about the creams’ effects on the skin barrier. The present work combines objective scorings, non-invasive techniques, and molecular analyses of skin biopsies to characterize the skin in 57 patients with AD, IV, or XLRI, and in 14 healthy controls. Patients were classified according to their FLG and STS mutation status: AD with FLG+/+ (n = 14), AD with FLG+/– (n = 14), AD/IV with FLG–/– (n = 15), and XLRI with STS– (n = 14), as well as one man with a novel point mutation. Assessments were conducted at baseline and after four weeks of treatment with three different moisturizers applied to volar forearm skin. At baseline, dryness scoring and non-invasive assessments verified impaired skin barrier function in all patients. In patients with AD/IV, microarray analysis identified 300–3000 up- or downregulated mRNA transcripts involved in signalling pathways important for inflammation and barrier repair. The skin phenotype and number of altered transcripts were correlated with the FLG mutation status, with FLG–/– patients displaying the highest transepidermal water loss (TEWL) and the most altered transcript levels. In contrast, despite an equally dysfunctional skin barrier, only limited changes in mRNA transcripts occurred in XLRI patients. Treatment with moisturizers improved skin dryness similarly in all groups, but TEWL behaved differently: it decreased slightly in the AD/IV group and increased in the XLRI group, especially after urea treatment. Only minute effects on skin pH and mRNA expression were observed. In conclusion, FLG mutations elicit pro-inflammatory mechanisms probably aimed at restoring barrier competence. This does not occur in patients with XLRI, presumably because STS deficiency automatically increases the barrier thickness. Moisturizing treatment improves skin dryness in patients with AD, IV, or XLRI, but does not seem to normalize the altered epidermal gene expression profile in AD/IV patients.

published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Medical Sciences

Isolation and identification of all yeast species found on skin affected by atopic dermatitis, evaluation of their influence to the synthesis of IgE antibodies, and assessment of the possible cross-reactivity between different yeast species was performed. It was shown that in 36.9 % of the cases of atopic dermatitis, the affected skin was colonized with yeast belonging to three genera: Candida, Malassezia and Rhodotorula. Systematic and phylogenetic analysis of sequences from atypical Malassezia restricta strain M8 indicated that this isolate could be a member of a new yeast species. Three atypical Malassezia isolates M47, M54 and M235 were identified as non-lipid-dependent variants of Malassezia furfur. It was shown that in atopic dermatitis, cutaneous colonization with yeast is two-fold higher in adults than in children. The sera of atopic dermatitis patients have specific IgE antibodies to cross-reactive intracellular yeast antigens. Candida pelliculosa and house dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae might share some allergenic epitopes. The results of this study suggest that attention should be given to a cutaneous colonization by saprophytic yeast since the immune response to the allergens could further exacerbate allergic inflammation due to cross-reactive epitopes. / Išskirtos ir identifikuotos atopinio dermatito pažeistą odą kolonizuojančios mielių rūšys, įvertinta jų įtaka specifinių IgE antikūnų sintezei bei kryžminių reakcijų tarp skirtingų mielių rūšių galimybė. Nustatyta, kad 36,9 % atvejų atopinio dermatito pažeista oda yra kolonizuojama Candida, Malassezia ir Rhodotorula genties mielėmis. Išskirtas netipinėmis fiziologinėmis savybėmis pasižymintis Malassezia restricta kamienas M8 gali būti naujos rūšies atstovas. Išskirti netipinėmis fiziologinėmis savybėmis pasižymintys Malassezia genties kamienai M47, M54 ir M235 identifikuoti kaip nuo išorinio lipidų šaltinio nepriklausantys Malassezia furfur. Įrodyta, kad mielės suaugusių asmenų atopinio dermatito pažeistą odą kolonizuoja du kartus dažniau negu vaikų. Įrodyta, kad atopiniu dermatitu sergančių asmenų kraujo serume aptinkama prieš kryžmiškai reaguojančius mielių viduląstelinius antigenus nukreiptų specifinių IgE antikūnų. Taip pat nustatyta, kad Candida pelliculosa ir namų dulkių erkių Dermatophagoides pteronyssinus ir Dermatophagoides farinae alergenai gali turėti panašius epitopus. Darbo rezultatai patikimai rodo, kad atopinio dermatito pažeistą odą kolonizuojančios komensalinės mielės gali pasunkinti atopinio dermatito eigą dėl kryžmiškai reaguojančių epitopų tarp skirtingų biologinių rūšių antigenų.

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Mémoire (M.Med.Exp.)--Université du Québec à Chicoutimi, 2000. / Document électronique également accessible en format PDF. CaQCU