La dermatite atopique est une dermatose inflammatoire apparaissant préférentiellement avant l’âge de cinq ans, et évoluant naturellement vers la guérison après l’adolescence dans plus de 90% des cas. L’origine de cette amélioration spontanée n’est pas clairement établie dans cette dermatose multifactorielle dont l’étiopathogénie reste encore à déterminer (maturation du système immunitaire ?). Les liens de cette pathologie avec le psychisme sont certains : retentissement psychologique important avec altération de la qualité de vie, aggravation voire déclenchement des poussées par le stress, amélioration des lésions par psychothérapie. L’observation de la nature de la structure d’attachement est importante dans le domaine de la psychopathologie. Elle est encore peu réalisée dans le domaine da la pathologie organique. Nous avons étudié la structure d’attachement de 80 adultes ayant présenté dans l’enfance une dermatite atopique, 40 d’entre eux ayant une guérison de celle-ci depuis l’adolescence, 40 autres présentant une pérennisation des crises d’eczéma. L’évaluation de l’attachement a été réalisée avec un autoquestionnaire (CAMIR de PIERREHUMBERT) et la cotation de l’entretien d’attachement avec la méthode Q-SORT selon KOBAK. Nous avons également mesuré les symptômes psychopathologiques associés avec l’échelle SCL90-R, le niveau d’anxiété avec l’inventaire trait-état de SPIELBERGER (STAIY) et le coping avec le WCC-R de VITALIANO. Les IgE totales ont été dosées. Les sujets avec dermatite atopique ayant débutée avant trois ans ne sont pas plus insécures que ceux avec un début plus tardif de leur dermatose. Ceci fait évoquer la possibilité d’une absence de retentissement sur la structure d’attachement d’une dermatite atopique apparaissant dans les premiéres années de vie, contrairement à ce qui est noté dans toute pathologie chronique d’apparition précoce. Il est alors supposé un effet positif des soins cutanés sur la nature de la relation de la dyade mère-enfant. Par contre, le retentissement ultérieur de la dermatite atopique chez l’adulte est important, avec augmentation d’une insécurité préoccupée en termes de représentations d’attachement, une augmentation des scores de toutes les dimensions psychopathologiques mesurées et une recherche anxieuse de soutien à l’extérieur. Ce retentissement est d’autant plus important que les IgE sont élevées, ceci n’étant pas uniquement le reflet de la gravité de la maladie. Les adultes présentant une dermatite atopique pérennisée sont structurellement plus insécures que ceux qui ont guéris : si nous considèrons l’aspect stable dans le temps de la structure d’attachement, ces résultats positionneraient celle ci en tant que possible facteur dispositionnel prédictif dans l’évolution de la dermatite atopique. Le score de sécurité des patients guéris est d’autant plus élevé que les IgE sont normales. Un phénomène d’interaction entre le système d’attachement et le système adaptatif au stress, à dépendance développementale commune sur certains aspects, est évoqué. Le rôle des IgE reste à déterminer. En termes de psychologie de la santé, la structure d’attachement pourrait être considérée comme un facteur dispositionnel susceptible d’influer l’évolution de la dermatite atopique. / Atopic dermatitis is an inflammatory skin disorder which usually appears before the age of five, and heals naturally little by little after adolescence in over 90% of cases. Why this spontaneous improvement occurs is not clearly established for this multi-factor skin disorder, for which the etiopathology has yet to be determined (immune system maturity?).There is a clear relationship between this pathology and the psyche: major psychological repercussions affecting the quality of life, aggravation or triggering of skin reactions due to stress, alleviation of lesions using psychotherapy. Observation of patterns of attachment is important in the field of psychopathology, but is not often undertaken in the domain of organic pathology. We studied the patterns of attachment for 80 adults having suffered from atopic dermatitis during childhood, 40 of them had been cured since adolescence, the other 40 continued to suffer from outbreaks of eczema. Attachment was evaluated using a self-completion questionnaire (CAMIR by PIERRE HUMBERT) and the attachment interview was graded using the Q-SORT method, by KOBAK. We also measured the associated psychopathological symptoms using the SCL90-R scale, level of anxiety using SPIELBERGER’s state-trait-anxiety inventory (STAIY), and coping measurement using the WCC-R scale devised by VITALIANO. Total IgE was measured. Patients suffering from atopic dermatitis that began before the age of 3 years are not more insecure than patients whose skin disorder started later in life. This meant that there were possibly no repercussions on the pattern of attachment for cases of atopic dermatitis that had appeared in the first years of life, contrary to all reports regarding a chronic pathology appearing early in life. This implies that caring for the skin has a positive effect on the mother-child relationship. On the other hand, adults suffer from major repercussions of atopic dermatitis later on in life: increased sense of preoccupied insecurity in terms of representations of attachment, increased scores in all the psychopathological dimensions measured, and an anxious need for outside support. These repercussions are even more serious when IgE is high, but this is not solely connected with the gravity of the illness. Adults suffering from persistent atopic dermatitis are basically more insecure than those who are cured: if long-term stability in the pattern of attachment is considered, this study could place pattern of attachment as a possible predictive disposition factor in the evolution of atopic dermatitis. The security score of cured patients is all the greater when IgE is normal. The existence of an interaction between the attachment pattern and the system for adapting to stress has been suggested, since they are both dependent on development. The role played by IgE remains to be determined. In terms of health psychology, the pattern of attachment could be considered as a disposition factor likely to influence the evolution of a skin disorder.

Atopic dermatitis (AD) is a common, chronic relapsing inflammatory skin disease associated with cutaneous hyper-reactivity to environmental triggers that are innocuous to normal nonatopic individuals. AD affects 10% to 15% of children and 2% to 10% of adults in industrialized countries. There has been increasing interest in this disease triggered by its increasing prevalence in western societies and its contribution to the increasing health care costs. Yet, the underlying pathophysiologic and genetic mechanisms leading to the manifestation of AD are not clear. AD results from a complex interplay between environmental triggers, susceptibility genes including mutations in the keratinocyte protein filaggrin and altered immune responses resulting in allergic CD4+ T cell (Th2) immunity to epidermally encountered antigens. Regulatory T cells (Tregs) play an important role in controlling responsiveness to self-antigens and preventing autoimmune diseases, as well as in limiting inflammatory responses during inflammation and infection. Currently, studies investigating the number and function of Tregs in patients with AD have shown controversial results. It has been long established that symptoms of AD improve on exposure to sunlight. Narrowband UVB (NB-UVB) phototherapy is a common treatment modality for a variety of skin diseases. Considering the adverse effects for systemic treatment for severe adult AD, phototherapy, especially NB-UVB phototherapy may be a more practical long-term treatment. However, approximately 50% of patients over an 8-week treatment course do not improve after NB-UVB phototherapy. Therefore, it is important to identify characteristics of AD patients to determine whether they will respond to phototherapy and to avoid adverse effects for unresponsive patients. UVB exposure has also been associated with induction of Tregs in mice and increasing their numbers and/or functional capacity may offer benefit to patients with chronic AD. Active vitamin D (1,25(OH)2D3), one of the factors induced by UV-B radiation induces Tregs and is suggested to contribute to the suppressive effect of NB-UVB phototherapy. However, UV radiation could also have beneficial effects through other pathways known to affect immunoregulation. UVB exposure upregulates production of nitric oxide (NO) in the skin which also affects immune cell function. The protein filaggrin is broken down in differentiating keratinocytes to form the natural moisturizer of the skin. The gene encoding filaggrin (FLG) has been shown to be a major predisposing factor for AD. A key breakdown product is urocanic acid (UCA) which also acts as a natural sunscreen and undergoes trans-cis isomerisation on exposure to UV-B. Cis-UCA is known to modulate immune responses, however, the mechanisms of its action remain elusive. The production of all three compounds, vitamin D, cis-UCA and NO might all increase in the circulation of patients undergoing UVB phototherapy. While the immunomodulatory effect of Vitamin D is well described, cis-UCA and NO may also affect the behaviour of T lymphocytes systemically. Therefore, I investigated the effect of NO and cis-UCA on the phenotype and function of CD4+T cells and monocyte-derived dendritic cells (Mo-DCs) derived from peripheral blood mononuclear cells (PBMCs) from healthy volunteers. I also investigated the correlation between plasma concentration of 25(OH) vitamin D and nitrate, FLG genotype, circulating Tregs and clinical efficacy of NB-UVB phototherapy. My results showed that NO did not affect the phenotype of human mo-DCs and directly affected peripheral CD4+ T cells by inducing functional CD25+Foxp3+CD127-Tregs from CD4+CD25lo/- effector T cells. Moreover, NO increased expression of the of skin homing marker CLA on these Tregs, suggesting an increased ability of NO-induced Tregs to migrate to the skin. These NO-induced CD25+Foxp3+CD127-Tregs had immunosuppressive functions and inhibited autologous CD4+ T cell proliferation. Cytokines, at least IL-10, secreted by NO-treated CD4+ T cells were not sufficient for the suppressive function of NOinduced Foxp3+Tregs. The immune regulatory function of NO-induced Fopx3+Tregs required cell-cell contact and was mediated by membrane bound TGFβ and PD-1/PD-L1 but not CTLA-4. Results also showed that cis-UCA might have both pro- and anti-inflammatory effects. Cis- UCA significantly decreased the proportion of CD25hi Foxp3+ cells from activated CD4+ T cells. It also decreased the expression of vitamin D receptor in CD4+ T cells which may interfere with the immune regulatory function of vitamin D. These results suggested that there might be a fine balance between UV-induced anti-inflammatory molecules’ effect on CD4+ T cells. However, Cis-UCA also modulated CD4+ T cell directly by decreasing CD4+ T cell proliferation, decreasing phosphorylation of ERK after TCR activation, enhancing immune suppressive cytokines secretion, and inhibiting the percentage of CLA+CD4+T cells suggesting a decreased ability to migrate to the skin, . Cis-UCA also affected the phenotype and function of antigen presenting cells by decreasing the expression of HLA-DR, CD86 and CD40 on immature mo-DCs, which led to increased proportion of CD25+Foxp3+CD127- T cells when co-cultured with allogenic CD4+ T cells. Results generated from the clinical study in which all 29 patients got better after phototherapy suggested although circulating 25 (OH) vitamin D concentration was significantly increased after NB-UVB phototherapy, the change of circulating 25 (OH) vitamin D concentration did not correlate with disease improvement. This suggests that vitamin D is not the only pathway involved and that other molecules contribute to UVB-induced immune-regulation. The data also show that of the levels of circulating nitrate and the FLG genotype did not correlate with improvement / change with phototherapy. However, the expression of CD69 and CLA on circulating CD4+ T cells was decreased after treatment suggesting that UVB affected T cell activation and migration to the skin, and their importance in determining clinical responses requires further investigation. Taken together, the results from my study provide evidence that vitamin D is not the only molecule responsible for the beneficial effect of NB-UVB phototherapy. NO and cis-UCA may down-regulate immune responses by affecting human peripheral CD4+ T cells and mo- DCs phenotype and function. A further understanding of the effect of NO and cis-UCA on skin resident immune cells will provide more insights for narrowing NB-UVB phototherapy which will help to select patients that most likely to benefit from a mechanism-based treatment.

La marche atopique désigne la progression séquentielle des maladies atopiques, en particulier l’apparition d’asthme chez les enfants précédée par celle d’une dermatite atopique (DA) sévère chez les nourrissons. De plus, l’asthme est influencé par le degré de sévérité de la DA, qui pourrait ainsi être considérée comme la porte d’entrée pour le développement ultérieur d’une inflammation allergique des voies aériennes.Mon travail de thèse a consisté à déterminer l’implication de la cytokine TSLP produite par les kératinocytes pendant la marche atopique et implication de la cytokine TSLP pendant le développement de la DA. Pour atteindre ces objectifs, j’ai utilisé des modèles murins de maladies atopiques, en combinaison avec plusieurs lignées de souris génétiquement modifiées.Dans la première partie de mon travail de thèse, nous avons montré que la production de la cytokine TSLP dans les kératinocytes est un facteur nécessaire, non seulement pour l’inflammation cutanée, mais aussi pour générer une réponse immunitaire systémique à l’allergène.Dans la deuxième partie de mon travail de thèse, nous avons montré que la cytokine TSLP induise un recrutement de basophiles d’une façon innée, suite d’une augmentation de ce recrutement induit par l'immunité adaptative. De plus, nous avons montré que la réponse de type “Th2” induit par la cytokine TSLP ce le résultat de une coopération coordonnée de cellules dendritiques, de cellules T CD4+ et de basophiles. Des études cliniques sont nécessaires pour déterminer si l’inhibition de l’expression de la cytokine TSLP et/ou son activité pendant une DA peut réduire l’inflammation cutanée et prévenir la sensibilisation aux allergènes. / Atopic march refers to the natural history of allergic diseases, which is characterized by a typical sequence of sensitization and manifestation of symptoms in different tissues. Commonly, the clinical manifestation of atopic dermatitis (AD) appears in the early life and precedes the development of airway allergic diseases. AD has been proposed as an entry point for subsequent atopic diseases.The objective of my thesis was to better understand the role of TSLP in the atopic march and the cascade events initiated by TSLP in vivo in the development of AD. To reach my thesis objectives we used mouse models of atopic diseases in combination with various deficient-mouse lines.In the first part of this work, using a atopic march mouse model developed during my PhD work, we demonstrated that keratinocytic TSLP is essentially required not only for the development of allergic skin inflammation, but also for the generation of the allergen-specific immune response. In the second part of this work, using a cytokine TSLP-induced AD mouse model (topical MC903 treatment), we demonstrated that skin TSLP induces an early innate recruitment of basophils in the skin, followed by a late recruitment involving adaptive immunity. In addition, we demonstrate that TSLP-induced Th2 response requires an orchestrated cooperation of dendritic cells, CD4+ T cells and basophils.This work provide new knowledge in the cellular and molecular mechanisms implicated in atopic diseases involving TSLP and should provide new insight for the development of therapeutic options of these diseases.

Mon travail, lors de ma thèse, avait pour but d’étudier la différentiation des lymphocytes Tfh, ainsi que leur fonction et leur régulation dans la pathogenèse de la DA. Pour cela, j’ai utilisé un modèle murin précédemment établi au sein de notre laboratoire consistant en l’application topique de MC903 (un analogue de la vitamine D3) induisant la production de TSLP par les kératinocytes et, par conséquence, la réponse immunitaire Th2 et la pathogenèse de la DA. mon travail doctoral s’est porté sur la différentiation des lymphocytes Tfh, leur production cytokinique ainsi que la formation des centres germinatifs dans le contexte d’un modèle murin de DA induite par le MC903. Mes études ont démontré un rôle critique joué par TSLP dans la réponse Tfh et ont exploré le rôle potentiellement joué par les cellules dendritiques langerine+ et la signalisation OX40L dans le développement des réponses Tfh et de type 2. Ceci nous a permis d’approfondir nos connaissances concernant les mécanismes sous-tendant la réponse immunitaire de type 2 dans la pathogenèse de la DA. Dans la deuxième partie de ma thèse, nous avons examiné le rôle de MC903 dans la régulation de l’inflammation due au psoriasis, en utilisant un modèle de psoriasis induit par l’Aldara. Nous avons montré que MC903 inhibe l’axe 23/IL-17/IL-22 chez les souris souffrant de psoriasis. De plus, cette inhibition semblait être dose-dépendante. Nous avons en outre exploré le rôle de TSLP et VDR dans la médiation de cet effet dû au MC903. / My thesis aimed at studying the Tfh cell differentiation, function and regulation in AD pathogenesis. To this aim, I employed our previously established AD mouse model in which MC903 (a vitamin D analog) topical treatment on the skin induces TSLP production bykeratinocytes, promotes Th2 cell response and drives the pathogenesis of AD. my thesis work investigated Tfh cell differentiation, its cytokine expression and germinal center formation using MC903-induced AD mouse model. By exploring the role of TSLP,Langerin+ DCs and OX40L signaling in Tfh cell differentiation and regulation, my study provides novel insights into the mechanisms underlying the type 2 immune response in AD pathogenesis. In the second part of my study, we examined the role of MC903 in regulating the psoriatic inflammation using Aldara-induced psoriasis model. We showed that MC903 inhibited IL-23/IL-17/IL-22 axis in mouse psoriasis. Moreover, this inhibition exhibited a dose-dependent manner. We further explored the role of TSLP and VDR in mediating such effect of MC903.

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: 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

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

Abstract The purpose of the study was to get knowledge of everyday life of children (aged 0–10 years) with atopic dermatitis and their families. An ethnographic approach was used. Different data sets were collected by interviewing, observing and presenting questionnaires. The interviews (n = 24) and observations (n = 24) of the families (n = 7) took place at their homes. Children aged 5–10 years (n = 80), assisted by their parents, filled in a quality of life questionnaire. In the case of children younger than 5 years (n = 174) and families (n = 254), the quality of life questionnaire was filled in by the parents. The severity of atopic dermatitis of each participating child (n = 254) was evaluated by a physician. The professional perspective was introduced into the study in the form of discussions between dermatological nurses and dermatologists (n = 4). Triangulation of data, methods and analyses was performed. The quantitative data were analyzed by means of SPSS 11.5 for Windows. Categorical and ordinal variable were presented as frequency and percentage distributions, and medians, quartiles and arithmetic means were quoted. The interrelations between variables were presented as cross-tabulations, and Khi square test was used. The interviews were analyzed by methods of data-based content analysis. The more severe the child's atopic dermatitis was, the more the quality of life of the child and the family was impaired. The quality of life of the children was better than the quality of life of the families. The impact of the atopic dermatitis to the quality of life of the children was moderate and of the family severe. The children's quality of life was impaired most by itching and scratching. The need to participate in the treatment of the children's skin problems was the most important single factor that impaired the families' quality of life. The child's severe, long-term dermatitis and its treatment on a day-to-day basis were described as a desperate process. The knowledge that eczema is alleviated as the child grows older gave the families hope and helped them to cope. The avoidance of various foods and allergens and the opportunities to try different treatments raised hopes about the alleviation of eczema. On the other hand, however, these trials easily turned into desperate efforts to try any available alternative, which often wore out the mother or the whole family. Families did not receive adequate counselling or support when their quality of life was seriously compromised. The results of the study can be used when developing the public health care services to better meet the needs of families. / Tiivistelmä Tutkimuksen tarkoituksena on saada tietoa ihoatoopikkolasten (0–10 vuotta) ja heidän perheidensä arjesta. Tutkimuksen lähestymistapa on etnografinen. Erilaisia aineistoja kerättiin haastattelemalla, havainnoimalla ja kyselylomakkeilla. Perheiden (n = 7) haastattelut (n = 24) ja havainnoinnit (n = 24) tehtiin heidän kodeissaan. Perheiden arki heijastui haastattelutilanteisiin siten, että niissä ei aina ollut läsnä koko perhe, ja haastatteluun osallistujien toiveiden mukaan tapaamisia oli myös esimerkiksi ihotautien vuodeosastolla ja poliklinikalla. 5–10-vuotiaat lapset (n = 80) täyttivät itse tai vanhempiensa avustamana omaa elämänlaatuaan koskevan kyselylomakkeen. Alle 5-vuotiaiden lasten (n = 174) ja perheiden (n = 254) elämänlaatukyselyyn vastasivat vanhemmat. Lääkäri arvioi jokaisen tutkimukseen osallistuneen lapsen (n = 254) atooppisen ihottuman vaikeuden. Ammattilaisten näkökulman tutkimukseen toivat ihotautisairaanhoitajien ja -lääkäreiden kanssa käydyt keskustelut (n = 4). Tutkimuksessa käytetään aineisto-, menetelmä- ja analyysitriangulaatiota. Kvantitatiivinen aineisto analysoidaan SPSS 11.5 for Windows -ohjelmalla. Luokittelu- ja järjestysasteikollisia muuttujia kuvataan frekvenssi- ja %-jakaumilla, ja sijaintilukuina ovat mediaanit, kvartiilit ja aritmeettinen keskiarvo. Muuttujien yhteyksiä tarkastellaan ristiintaulukoimalla ja parametrittomana testinä on chi2-testi. Haastattelu- ja havainnointiaineisto analysoidaan aineistolähtöisellä sisällönanalyysillä. Mitä vaikeampi lapsen ihottuma oli, sitä enemmän se heikensi perheen ja lapsen elämänlaatua. Lasten elämänlaatu oli parempi kuin perheiden elämänlaatu. Atooppisen ihottuman vaikutus lasten elämänlaatuun oli kohtalainen ja perheiden elämänlaatuun huomattava. Lasten elämänlaatua heikensivät eniten kutina ja raapiminen. Lapsen hoidossa auttaminen oli tärkein perheen elämänlaatua heikentävä tekijä. Lapsen vaikeaa, pitkäaikaista ihottumaa ja sen päivästä toiseen jatkuvaa hoitamista kuvattiin ajoittain epätoivoiseksi. Toisaalta tieto, että ihottuma lievittyy lapsen kasvaessa, antoi toivoa ja auttoi perhettä jaksamaan. Perheet hankkivat ja saivat paljon ja monenlaista tietoa lapsen atooppisesta ihottumasta ja sen hoitamisesta, joten vanhemmat joutuivat suodattamaan ja puntaroimaan saamaansa tietoa oman lapsen tilanteeseen sopivaksi. Yhtäältä erilaisten ruokien tai ärsyttävien tekijöiden välttämiseen ja hoitovaihtoehtojen kokeilemiseen liittyi toivoa lapsen ihottuman lievittymisestä. Toisaalta kokeileminen saattoi kääntyä epätoivoiseksi tarttumiseksi jokaiseen tarjolla olevaan oljenkorteen, mikä puolestaan johti äidin tai koko perheen väsymiseen. Perheiden ohjauksessa ja tukemisessa oli puutteita, kun perheen elämänlaatu oli huomattavasti heikentynyt. Perheet käyttivät monipuolisesti terveydenhuollon palveluja, mutta ajoittain hoito koettiin pirstaleiseksi, ja hoitovastuu jäi perheen itsensä kannettavaksi. Tutkimustuloksia voidaan käyttää kehitettäessä terveydenhuoltopalveluja paremmin perheiden tarpeita vastaaviksi. Keskeistä on tunnistaa ne perheet, joiden elämänlaatu on huomattavasti heikentynyt lapsen atooppisen ihottuman vuoksi. Ihoatoopikkolapsen hoitaminen on moniammatillista yhteistyötä, jonka tekemistä yli ammattikunta- tai sektorirajojen on entisestään syytä tehostaa.

Background: Birch pollen is an important outdoor allergen able to aggravate symptoms in atopic dermatitis (AD). Specific immunotherapy (SIT), an established procedure for allergic airway diseases, might also represent an attractive therapeutic option for the causal treatment of allergen-triggered cutaneous symptoms in these patients. Studies with house dust mite SIT have already shown beneficial effects in AD patients, whereas the safety and efficacy of SIT with birch pollen extract in AD patients have not been studied so far. The aim of this study was to evaluate for the first time the safety and efficacy of SIT with a depigmented polymerized birch pollen extract in AD patients. Methods: Fifty-five adult patients with moderate-to-severe AD and clinically relevant sensitization to birch pollen received SIT for 12 weeks. SIT was continued during birch pollen season. The assessment of safety, the total SCORAD value, and the Dermatology Life Quality Index (DLQI) were evaluated. Results: The median total SCORAD value was reduced by 34% (p < 0.001) during the course of treatment and the mean DLQI improved by 49% (p < 0.001) despite strong simultaneous birch pollen exposure. Eight patients (14.5%) developed systemic reactions and 19 patients (34.5%) developed local reactions which were of mild intensity in most cases. No patient discontinued the study prematurely due to adverse drug reactions. Coseasonal treatment was well tolerated. Conclusion: SIT with a depigmented polymerized birch pollen extract leads to significant improvement of the SCORAD value and the DLQI in patients suffering from moderate-to-severe AD sensitized to birch pollen. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

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