No description available.

A psoríase é uma doença de pele inflamatória crônica, que afeta cerca de 2-4% da população mundial. Se desenvolve ao longo do tempo, principalmente no final da adolescência ou início da idade adulta e depende de uma complexa interação entre fatores genéticos e ambientais. Dados experimentais demostram que a dermatite induzida por imiquimode (IMQ) em camundongos assemelha-se estreitamente às lesões de psoríase humana, tanto nas características fenotípicas e histológicas como no desenvolvimento das lesões na epiderme. O estudo avaliou os efeitos anti-inflamatórios do óleo de semente de maracujá (Passiflora edulis) no tratamento da psoríase, utilizando a análise histológica e imunológica da epiderme. O experimento foi realizado com 36 camundongos Balb/c, os quais foram submetidos à indução da psoríase por imiquimode, por 10 dias consecutivos. O tratamento foi realizado com óleo de semente de maracujá in natura 100%, pomada LECIGEL® 2%, pomada associação de óleo de semente de maracujá 20% e LECIGEL® 2%, por 15 dias. Tanto o óleo da semente do maracujá quanto a associação do mesmo ao LECIGEL® diminuíram o quadro inflamatório induzido por imiquimode nas orelhas tratadas. Através das análises imuno-histoquímicas realizadas na epiderme (PCNA, IL-6, VEGF, CD34), observou-se um aumento na formação de corpos apoptóticos, diminuição a hiperplasia epitelial e redução do infiltrado inflamatório. Os resultados deste experimento demonstraram que o óleo da semente do maracujá desempenha um efeito anti-inflamatório no tratamento da psoríase induzida por imiquimode. / Psoriasis is a chronic inflammatory skin disease that affects about 2-4% of the world\'s population. It develops over time, especially in late adolescence or early adulthood and depends on a complex interaction between genetic and environmental factors. Experimental data show that imiquimode-induced dermatitis (IMQ) in mice closely resembles human psoriasis lesions, both in phenotypic and histological characteristics and in the development of lesions in the epidermis. The study evaluated the anti-inflammatory effects of passion fruit (Passiflora edulis) oil in the treatment of psoriasis, using the histological and immunological analysis of the epidermis. The experiment was performed with 36 Balb / c mice, which were submitted to psoriasis induction by imiquimode, for 10 consecutive days. The treatment was carried out with 100% fresh passion fruit seed oil, LECIGEL ® 2% ointment, 20% passion fruit seed oil ointment and LECIGEL ® 2% for 15 days. Both passionflower seed oil and its association with LECIGEL ® decreased the imiquimod-induced inflammation in the treated ears. Through the immunohistochemical analyzes performed on the epidermis (PCNA, IL-6, VEGF, CD34), an increase in the formation of apoptotic bodies, decrease in epithelial hyperplasia and reduction of inflammatory infiltrate was observed. The results of this experiment suggest that passion fruit seed oil has an anti-inflammatory effect in the treatment of imiquimode-induced psoriasis.

Introdução: A terapêutica da psoríase foi modificada pela introdução dos imunobiológicos, que permitem melhor controle da doença e melhor qualidade de vida aos pacientes, mas promovem aumento do risco de tuberculose latente, exigindo diagnóstico antecedendo seu início. Objetivo: Avaliar o desempenho do teste T-SPOT.TB no diagnóstico de infecção tuberculosa latente em pacientes com psoríase. Métodos: Em estudo experimental, prospectivo, analítico, com comparação de grupos,de prevenção primária, para validade de teste diagnóstico, 33 pacientes com psoríase (grupo psoríase) e 30 pacientes com outras doenças dermatológicas (grupo base), atendidos nos Ambulatório de Dermatologia Geral ou de Psoríase do Centro de Estudos Dermatológicos do Recife, da Santa Casa de Misericórdia, entre fevereiro e novembro de 2009, foram submetidos aos testes do PPD e T-SPOT.TB. Para ambos os grupos, admitiu-se inclusão com idade mínima de 18 anos e critérios de exclusão doenças ou condições fisiológicas que comprometessem a competência imunológica, exceto psoríase, para o grupo psoríase. Adotou-se a técnica de Mantoux para o teste do PPD e uma variante simplificada da técnica Enzyme-Linked Immunospot para a determinação de células T efetoras, secretoras de IFN-g em resposta à estimulação pelos antígenos específicos do M. tuberculosis para o teste T-SPOT.TB. As variáveis dependentes foram os resultados do teste T-SPOT.TB contra antígenos ESAT-6, CFP-10, e os resultados do teste do PPD, considerando enduração de 0-4 mm: não reator; 5-9 mm: reator fraco; ≥ 10 mm: reator forte. As variáveis independentes foram: idade, sexo, cor da pele, tempo de evolução da psoríase, ocupação, história de contato intradomiciliar e renda, alcoolismo e gravidade da doença. Foram submetidos a teste Qui quadrado ou exato de Fisher, em nível de significância de 0, 05, assim como ao teste de Mantel-Haenszel, três modelos comparando o teste T-SPOT.TB com teste do PPD, contato intradomiciliar e associação teste do PPD e contato intradomiciliar. A pesquisa foi aprovada pelos Comitês de Ética da Universidade Federal de Pernambuco e Universidade de São Paulo. Resultados: O grupo psoríase diferiu do grupo base quanto a razão de sexo com predomino do masculino (razão=0,7:1; p=0,047); maior idade média 42,1±1,9 anos (contra 34,1±1,4 anos no grupo base, p=0,023); fototipos I e II (p=0,020); menor nível de instrução e renda média mensal e contato intradomiciliar com tuberculose menos freqüente (p=0,001). Os grupos também diferiram quanto à positividade do teste do PPD (maior no grupo base; p=0,001). O teste T-SPOT.TB apresentou sensibilidade e especificidade de 9,1% e 95,5%, no modelo 1, 27,3% e 60%, no modelo 2, e valores de 60% e 53,3%, respectivamente no modelo 3. Foi no modelo 1 do grupo psoríase que o teste TSPOT. TB mostrou a maior concordância e o maior valor de Odds Ratio ponderado pelo teste de Mantel-Haenszel, tendo esses dois parâmetros significância estatística, quando comparados aos outros dois modelos. Conclusões: O teste T-SPOT.TB apresentou maior capacidade de diagnosticar casos negativos para tuberculose latente, constituindo-se numa opção para triagem de pacientes na instituição de terapêutica com imunobiológicos. / Introduction: The therapy for psoriasis was modified by the introduction of immunebiological products that allow better disease control and better quality of life for patients, but promotes increased risk forf latent tuberculosis, requiring diagnosis shortly before its establishment. Purpose: To assess the performance of T-SPOT.TB test for the diagnosis of latent tuberculosis infection in patients with psoriasis. Methods: Within a experimental, prospective, analytic, clinical assay type study, with comparison of groups, to validate a diagnostic test, 33 patients with psoriasis (psoriasis group) and 30 patients with other dermatological diseases (basis group), attempted at General Dermatology and Psoriasis Out-patients Departments of Recife\'s Dermatological Studies Center of Santa Casa de Misericórdia, from February to November 2009, were submitted to PPD and TSPOT. TB tests. For both groups, we admitted 18 years as minimal age for inclusion. The exclusion criteria included disease ou physiological conditions that compromised immunological competence, except psoriasis to psoriasis group. We used Mantoux technique for PPD test and a simplified variant of Enzyme-Linked Immunospot technique to determine effector T cells, secretors of IFN-g in response to M. tuberculosis specific antigens, to T-SPOT.TB test. Dependent variables were the results of T-SPOT.TB test against ESAT-6 and CPF-10 antigens, and the results to PPD test, considering enduration of 0-4 mm as non reactor; 5-10 mm weak reactor and ≥ 10 mm, strong reactor. Independent variables were age, sex, skin color, psoriasis evolution time, occupation, history of intradomiciliar contact and income, alcoolism and disease grade. Three models, comparing T-SPOT.TB test to PPD test, intradomiciliar contact and both, were submitted to Qui Squared test or Exact Fisher Test, at significance level of 0.05, as well as to Mantel- Haenszel test. The research has been approved by Ethics Committee of Universidade Federal de Pernambuco e Universidade de São Paulo. Results: Psoriasis group differed from base group on sex ratio with predominance of male gender (rate=0.7:1; p=0,047), major mean age (42,1 ± 1.9 years against 34,1 ± 1.4 years in basic group, p = 0,023) phototypes I and II (p = 0,020); lower scholarship, income and less frequent intradomiciliar contact with tuberculosis (p = 0,001). The groups also differed on the positivity of PPD test (greater in base group; p = 0,001). T-SPOT.TB test had sensibility and specificity of 9,1% and 95.5%, in model 1; 27,3% and 60%, in model 2, and values of 60% and 53,3% respectively in model 3. Model 1 showed greater concordance and highest value of Odds Ratio test weighted by Mantel-Haenszel test, having these two parameters statistical significance when compared to the other two models. Conclusions: T-SPOT.TB test had great ability to diagnose negative cases for latent tuberculosis, and constitutes an option for screening patients to immunobiological therapy administration.

<p>Vitamin A and metabolites (retinoids) are crucial for normal epidermal maturation. Physiological effects are mediated by retinoic acid (RA) that activates nuclear retinoic acid receptors (RARs) in complexes with retinoid X receptors (RXRs), resulting in altered gene transcription.</p><p>Psoriasis is a common disease with unknown etiology. Lesions display inflammation, hyperproliferation, and disturbed epidermal maturation. Treatments include topical or oral synthetic retinoids that allegedly bind to and activate the RARs.</p><p>The mRNA expression of retinoid receptors RARα/γ and RXRα was studied in normal and psoriatic skin samples. RARα and RXRα were significantly reduced in psoriatic plaques as compared to non-lesional and normal skin. <i>In situ</i> immunofluorescence detection revealed altered distribution patterns of the receptor proteins in lesional skin. All three receptor proteins were more intensely detected in the lower half of the epidermis but were significantly reduced in the superficial epidermis compared to both normal and non-lesional skin. </p><p>In order to evaluate the retinoid signaling system in psoriatic lesions, we compared the effect of topical RA on the expression of the cellular RA-binding protein II (CRABPII) in psoriatic and normal skin. CRABPII was induced by RA on mRNA and protein level in non-lesional and normal skin but not in lesional skin, where the basal expression of CRABPII was already up-regulated.</p><p>Changes in retinoid signaling during keratinocyte differentiation <i>in vitro </i>were studied by measuring retinoid receptor and RAR-ligand levels<i>.</i> Exposure to differentiation-inducing levels of calcium, phorbol myristate acetate (PMA) or interferon-γ (IFNγ) led to increased RAR-ligand levels but PMA and IFNγ caused receptor protein loss due to increased proteasomal degradation. Since an increased IFNγ level is a hallmark of psoriatic inflammation, this might be a cause of altered retinoid signaling in lesional epidermis.</p><p><i>Conclusion:</i> Keratinocyte differentiation is accompanied by alterations in the retinoid signaling system. In psoriatic lesions, this system appears to be dysfunctioning due to reduced retinoid receptor levels, which might be an important event in the pathogenesis of the disease.</p>

Vitamin A and metabolites (retinoids) are crucial for normal epidermal maturation. Physiological effects are mediated by retinoic acid (RA) that activates nuclear retinoic acid receptors (RARs) in complexes with retinoid X receptors (RXRs), resulting in altered gene transcription. Psoriasis is a common disease with unknown etiology. Lesions display inflammation, hyperproliferation, and disturbed epidermal maturation. Treatments include topical or oral synthetic retinoids that allegedly bind to and activate the RARs. The mRNA expression of retinoid receptors RARα/γ and RXRα was studied in normal and psoriatic skin samples. RARα and RXRα were significantly reduced in psoriatic plaques as compared to non-lesional and normal skin. In situ immunofluorescence detection revealed altered distribution patterns of the receptor proteins in lesional skin. All three receptor proteins were more intensely detected in the lower half of the epidermis but were significantly reduced in the superficial epidermis compared to both normal and non-lesional skin. In order to evaluate the retinoid signaling system in psoriatic lesions, we compared the effect of topical RA on the expression of the cellular RA-binding protein II (CRABPII) in psoriatic and normal skin. CRABPII was induced by RA on mRNA and protein level in non-lesional and normal skin but not in lesional skin, where the basal expression of CRABPII was already up-regulated. Changes in retinoid signaling during keratinocyte differentiation in vitro were studied by measuring retinoid receptor and RAR-ligand levels. Exposure to differentiation-inducing levels of calcium, phorbol myristate acetate (PMA) or interferon-γ (IFNγ) led to increased RAR-ligand levels but PMA and IFNγ caused receptor protein loss due to increased proteasomal degradation. Since an increased IFNγ level is a hallmark of psoriatic inflammation, this might be a cause of altered retinoid signaling in lesional epidermis. Conclusion: Keratinocyte differentiation is accompanied by alterations in the retinoid signaling system. In psoriatic lesions, this system appears to be dysfunctioning due to reduced retinoid receptor levels, which might be an important event in the pathogenesis of the disease.

Los receptores Fc-gamma (Fc-gR) median muchas de las funciones inmunes de la IgG. Están presentes en numerosas células del sistema inmune y su activación (tras la unión al fragmento Fc de la IgG) permite el desarrollo de funciones tales como la fagocitosis, la citotoxicidad dependiente de anticuerpos y la liberación de enzimas proteolíticas. Existen polimorfismos genéticos que modifican la afinidad de los Fc-gR y por tanto su capacidad funcional. Estos polimorfismos se han relacionado con enfermedades autoinmunes, infecciosas y con la eficacia de agentes monoclonales. El penfigoide ampolloso (PA) es una patología ampollosa autoinmune caracterizada por el deposito de autoanticuerpos en la membrana basal de la piel. Estos anticuerpos activan a neutrófilos vía el receptor Fc-gR, los cuales liberan enzimas proteolíticas que degradan la membrana basal causando el daño tisular. Los agentes monoclonales han revolucionado el tratamiento de las formas moderadas y graves de psoriasis. Sin embargo, en torno a un 30% de los pacientes no presentarán una respuesta adecuada. En la actualidad no existen factores farmacogenéticos definidos que puedan predecir la respuesta a biológicos en la psoriasis. Teniendo en cuenta el contrastado papel del los Fc-gR en modelos animales de PA, los polimorfismos genéticos de Fc-gR podrían relacionarse a nivel clínico con el PA, tanto como marcadores como modificadores de esta enfermedad. Por otra parte, los polimorfismos de Fc-gR también podrían predecir la respuesta a biológicos en la psoriasis, ya que los agentes empleados (etanercept, infliximab y adalimumab) contienen el fragmento Fc en su estructura. Esta influencia podría venir dada por un aumento en las capacidades citotóxicas de estos agentes, o por una alteración de los mecanismos de eliminación de estos fármacos dependientes del sistema reticuloendotelial. El objetivo de esta tesis fue estudiar la influencia de los polimorfismos de Fc-gR en 2 patologías cutáneas inmunomediadas mediante el estudio genético de grupos de pacientes y controles. Por un lado, se pretendía detectar si los polimorfismos de Fc-gR se asocian al PA o si modifican el pronostico de esta enfermedad, y por otro, si dichos polimorfismos son marcadores farmacogenéticos de respuesta clínica en aquellos pacientes psoriásicos tratados con agentes biológicos. Se realizó estudio genético de los polimorfismos Fc-gRIIA-H131R, Fc-gRIIB-I187T y Fc-gRIIIA-V158F en un grupo de 41 pacientes con PA y un grupo control de 115 individuos sanos y de Fc-gRIIA-H131R y Fc-gRIIIA-V158F en un grupo de 70 pacientes con psoriasis tratados agentes anti-TNF-alfa. Se realizó un análisis retrospectivo de los datos clínicos de los pacientes con PA y una valoración clínica retrospectiva de la respuesta a biológicos en pacientes con psoriasis. En el caso del PA observamos, en un modelo multivariante, una tendencia a la asociación del alelo F de Fc-gRIIIA-V158F con las formas más graves de PA, definidas como la necesidad de añadir tratamiento inmunosupresor. Por otra parte, los pacientes psoriáticos con alelos de alta afinidad (aislados o en combinación) de los polimorfismos a estudio presentaron, de forma independiente, una respuesta terapéutica más rápida a terapia biológica en forma de un porcentaje de superficie corporal afecta menor a las 6-8 semanas de tratamiento, probablemente en relación con una mayor eliminación de células patogénicas con TNF-alfa en membrana. Nuestros resultados tienen implicación clínica ya que, por un lado, los pacientes con PA y presencia del alelo F, podría beneficiarse de la introducción temprana de inmunosupresores y, por otro, la presencia de alelos de alta afinidad en los polimorfismos de Fc-gR podría predecir una respuesta clínica mas precoz en pacientes con psoriasis tratados con biológicos, lo cual puede ser de especial importancia en casos graves. / Fc gamma receptors (Fc-gammaR) mediate most of the immune functions of IgG. There are single-nucleotide polimorphims affecting Fc-gammaR genes that influence affinity and thus functions of Fc-gammaR. These polymorphisms have been linked clinically with infectious and autoimmune disease but also with the degree of response to monoclonal antibodies containing the Fc fragment. Bullous pemphigoid (BP) is an autoimmune disease where pathogenic antibodies bind antigens in the basal membrane of the skin. Such antibodies activate neutrophils through Fc-gammaR, which make these cells liberate proteolytic enzymes that cause tissue injury and blisters in the skin. Monoclonal agents have improved greatly the outcome of patients with psoriasis. However up to 30% does not achieve a significant response. There are not currently pharmacogenetic markers that could predict the outcome of biological therapy in psoriasis. The main objective of this thesis was to study the influence of Fc-gammaR polymorphisms in 2 immune-mediated skin diseases: a) a possible influence, in terms of susceptibility or disease modification, of Fc-gammaR polymorphisms in BP; and b) the potential role of Fc-gammaR polymorphisms as pharmacogenetic markers in patients with psoriasis treated with anti-TNF-alpha therapy. We performed the determination of the genotype of Fc-gammaRIIA-H131R, Fc-gammaRIIB-I187T and Fc-gammaRIIIA-V158F in 41 patients with BP and 115 controls and Fc-gammaRIIA-H131R and Fc-gammaRIIIA-V158F genotypes in 70 patients with psoriasis that underwent anti-TNF-alpha treatment. Clinical charts were reviewed in order to establish correlations. In the BP study, we observed an association between the presence of Fc-gammaRIIIA-158F with the most severe forms of BP, defined as the need for immunosuppressants. With regard to the psoriasis study, we detected that patients with high affinity alleles (alone or in combination) presented a quick response to biologics, measured as a lower body surface area affected in the week 6-8. Our results present clinical implications, since for example, patients with BP harboring the F allele may benefit from an early introduction of immunosuppressants. On the other hand, the presence of Fc-gammaR high affinity alleles may predict an early response to biologics in psoriasis, which may be critical especially in severe cases.

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

- / -

Introdução: A literatura tem demonstrado que a presença de distúrbios emocionais nos cuidadores de crianças com dermatoses crônicas influenciam no curso e tratamento da doença. A ansiedade e a depressão estão entre os diagnósticos psiquiátricos mais relacionados, porém a maioria das publicações afere esta relação de forma indireta, através de escalas de qualidade de vida e não de escalas diretas para ansiedade e depressão. Objetivo: Avaliar a presença de ansiedade e depressão nos cuidadores de pacientes pediátricos com dermatite atópica, vitiligo ou psoríase e correlacioná-las à qualidade de vida dos pacientes, à extensão corporal total da doença e à área acometida exposta à visualização. Materiais e Métodos: Amostra composta por 118 pacientes com dermatite atópica, vitiligo e psoríase acompanhados pelo principal responsável por seus cuidados diários. A avaliação da ansiedade nos cuidadores foi realizada através da Escala de Hamilton de Ansiedade e a depressão através do Inventário de Beck para Depressão. Foi aplicado o Índice de Qualidade de Vida na Dermatologia Infantil. Aferiu-se a superfície corporal total acometida pela doença em áreas expostas à visualização através do modelo humano para queimados. Resultados: Ansiedade foi verificada em 36% dos cuidadores do grupo de pacientes com dermatite atópica, em 36% do grupo com psoríase e 42% do grupo com vitiligo. Depressão ocorreu em 36% dos cuidadores de pacientes com dermatite atópica, 36% dos responsáveis pelos pacientes com psoríase, e em 26% dos cuidadores de pacientes com vitiligo. Observou-se uma correlação significativa entre a pior qualidade de vida dos pacientes com vitiligo e a presença de depressão e ansiedade nos seus cuidadores. Quanto maior a superfície corporal total comprometida pela psoríase maior o índice de depressão e ansiedade nos seus cuidadores, e quanto maior superfície corporal em áreas expostas à visualização nos pacientes com vitiligo, maior a presença de ansiedade nos seus cuidadores. Na análise comparativa da qualidade de vida entre os três grupos de pacientes portadores de dermatoses, verificou-se que os pacientes com dermatite atópica e psoríase têm qualidade de vida significativamente piores que os portadores de vitiligo. Conclusão: A presença de ansiedade e depressão nos cuidadores de pacientes com vitiligo foi significativamente relacionada a uma pior qualidade de vida dos pacientes e a uma maior extensão da doença exposta à visualização. Entre os cuidadores de pacientes com psoríase, observaram-se maiores índices de depressão e ansiedade diante da maior superfície corporal total comprometida pela doença. Porém, os piores escores de qualidade de vida foram identificados entre os pacientes atópicos. Assim, acreditamos que distúrbios emocionais tendem a estar presentes no nicho familiar de crianças portadoras das dermatoses crônicas estudadas. / Introduction: The literature has shown that the presence of emotional disturbances in caregivers of children with skin diseases affects the course and treatment of the disease. Anxiety and depression are among the most frequently reported psychiatric diagnoses related to this fact. However, most publications have attempted to gauge this relationship indirectly by using quality of life scales rather than direct scales developed for the evaluation of anxiety and depression. Objective: To evaluate the presence of anxiety and depression in caregivers of 118 pediatric patients with chronic skin disorders, exemplified by atopic dermatitis, psoriasis and vitiligo, and correlate them to the quality of life of the patients, total body area affected by the disease and the extent of that affected area exposed to view. Methods: The sample consisted of patients with atopic dermatitis, vitiligo and psoriasis accompanied by their main caregiver. The levels of anxiety and depression in the caregivers were assessed using the Hamilton Anxiety Scale and the Beck Depression Inventory, respectively. The validated for Portuguese Children's Dermatology Life Quality Index was applied. The total body surface affected by the disease and the area exposed to view were measured using the human model for burn patients. Results: Anxiety was observed in 36% of the caregivers of the patients with atopic dermatitis, 36% of those of children affected by psoriasis and 42% of those responsible for pediatric patients with vitiligo. Depression occurred in 36% of the caregivers of patients with atopic dermatitis, 36% of those of children affected by psoriasis and 26% of those responsible for pediatric patients with vitiligo affected. There was a significant correlation between poor quality of life scores in patients with vitiligo and the presence of depression and anxiety in their caregivers. The greater the total body surface affected by psoriasis the higher the rate of depression and anxiety in their caregivers. For vitiligo, extensive surface body area corresponded to more intense anxiety in their caregivers. In the comparative analysis of the quality of life between the three groups of dermatoses, the quality of life of patients with atopic dermatitis and psoriasis was significantly worse than for those affected by vitiligo. Conclusion: The presence of anxiety and depression in caregivers of patients with vitiligo was significantly related to the lower quality of life of the patients and the greater extent of disease exposed to view. Among caregivers of patients with psoriasis, the larger total body surface affected by the disease, the higher were the observed levels of depression and anxiety. However, the worst quality of life scores were identified among atopic patients. Thus, we believe that emotional disorders tend to be present in the close family of children with the studied chronic skin diseases.