Para verificar a contribuição da audiometria em altas freqüências (9 a 20 kHz) e das emissões otoacústicas - produto de distorção para a identificação de alterações auditivas em indivíduos com desordem pigmentar do tipo vitiligo, 30 indivíduos portadores de vitiligo foram avaliados audiologicamente, e comparados a um grupo controle. Tanto para as altas freqüências (9 a 20 kHz) como para as emissões otoacústicas foram observadas diferenças significantes entre os grupos, que não foram evidenciadas na audiometria convencional (0,25 a 8 kHz). Os resultados sugerem prejuízo nas funções auditivas para o grupo com desordem pigmentar do tipo vitiligo. / In order to verify the contribution of the high frequency audiometry (9 to 20 kHz) and distortion product- otoacoustic emissions for the identification of auditory impairments in individuals with pigmentary disorder type vitiligo, 30 individuals with vitiligo were evaluated, and compared with a control group. As much for the high frequencies (9 the 20 kHz) as for the otoacoustic emissions, significant differences were observed between the groups, that were not evidenced in the conventional audiometry (0,25 the 8 kHz). The results suggest damage in the auditory functions for the group with pigmentary disorder type vitiligo

O RNA de interferência (RNAi) é um processo envolvido com o silenciamento pós-transcricional de genes, sendo elucidado por moléculas de RNAs de dupla fita de 21-25 nucleotídeos, os small interfering RNA (siRNA), que ocorre naturalmente em uma ampla variedade de animais, plantas e microrganismos. Esse processo têm demonstrado potencial utilização para o tratamento de doenças em que se observa a super-expressão de genes, pois apresentam diversas vantagens como possibilidade de se utilizar esse mecanismo regulatório apenas pelo conhecimento da sequência do gene terapêutico, menores efeitos tóxicos e alta especificidade. Contudo, o principal desafio consiste no desenvolvimento de vetores seguros e eficazes que permitem a utilização do siRNA como terapia, visto que permitem a proteção do siRNA contra degradação enzimática, apresentam meia-vida prolongada na corrente sanguínea e propiciam um efetivo escape endossomal. Nesse sentido, nanopartículas de cristais líquidos associados ao polímero catiônico polietilenoimina (PEI) foram avaliadas como potenciais vetores não-virais para o siRNA específico para a proteína-1 relacionada à tirosinase (TRP-1), como alternativa para o tratamento tópico do vitiligo. Para isso, os cristais líquidos contendo o PEI foram complexados ao siRNA e avaliados quanto à estrutura líquido cristalina por microscopia de luz polarizada e por difração de raios-X a baixo ângulo (SAXS), tamanho de partícula/polidispersividade, potencial zeta e eficiência de complexação. A citotoxicidade dos sistemas foi avaliada em melanócitos melan-A pelo ensaio do MTT e por citometria de fluxo e, a avaliação da transfecção celular foi realizada por microscopia de fluorescência e por citometria de fluxo. Os diferentes sistemas contendo o polímero PEI apresentaram estruturas líquido cristalinas de fase hexagonal e de fase lamelar pela análise por SAXS, no entanto, a análise sob microscopia de luz polarizada, demonstrou estruturas de fase hexagonal, lamelar e isotrópica. A análise do tamanho de partícula mostrou a presença de sistemas nanoestruturados que foram capazes de se complexar ao siRNA na concentração de 10 ?M. Os estudos em cultura de célula demonstraram a maior viabilidade das células melan-A após tratamento com as nanodispersões líquido cristalinas formadas por monoleína (MO), ácido oleico (AO) e PEI, em relação ao polímero catiônico PEI em sua forma livre. Em relação à transfecção celular por microscopia de fluorescência e por citometria de fluxo foi possível observar a elevada eficiência de transfecção das nanodispersões líquido cristalinas formadas pelo sistema MO:AO:PEI. Resultados de inibição da expressão da proteína TRP-1 foram observadas em células melan-A por Western Blotting, após administração das nanodispersões líquido cristalinas associadas ao siRNA-TRP-1 específico. As nanodispersões liquido cristalinas estudas também proporcionaram maior liberação de siRNA na pele em modelo animal. Esses resultados, demonstram a potencial utilização desses sistemas para a terapia anti-sense de doenças cutâneas como o vitiligo, representando assim, uma importante contribuição para a terapia gênica tópica desta doença / The RNA interference (RNAi) is a process involved with the post-transcriptional gene silencing being elucidated by double-stranded RNA molecules of 21-25 nucleotides, the small interfering RNA (siRNA) that occurs naturally in a wide variety of animals, plants and microorganisms. This process has shown potential use for the treatment of diseases in which there is overexpression of genes, as they offer several advantages such as the possibility of using this regulatory mechanism just by knowing the sequence of the therapeutic gene, lower toxicity and high specificity. However, the main challenge is to develop safe and effective vectors that enable the use of siRNA as a therapy, since they allow the protection of siRNA against enzymatic degradation, have prolonged half-life in the bloodstream and provide an effective endosomal escape. Accordingly, liquid crystal nanoparticles associated with the cationic polymer polyethylenimine (PEI) were evaluated as potential non-viral vectors for specific siRNA for the protein related to tyrosinase-1 (TyRP-1) as an alternative for the topical treatment of vitiligo. For this, the liquid crystals containing PEI were complexed to siRNA and evaluated for liquid crystalline structure by polarized light microscopy and X-ray diffraction (SAXS), particle size / polydispersity index, zeta potential and complexation efficiency. The cytotoxicity of the systems was evaluated by MTT assay and flow cytometry in melan-A melanocytes and the evaluation of cellular uptake was performed by fluorescence microscopy and flow cytometry. The different systems containing the polymer PEI exhibited liquid crystalline structures of hexagonal and lamellar phases by SAXS analysis, however, the analysis under polarized light microscopy showed liquid crystalline structures of hexagonal phase, lamellar and isotropic. The analysis of particle size showed the presence of nanostructured systems that were capable of complexing to the siRNA at concentration of 10 ?M. Studies in cell culture demonstrated a higher viability of melan-A cells after treatment with the liquid crystalline nanodispersions formed by monolein (MO), oleic acid (OA) and PEI in relation to the cationic polymer PEI in its free form. Regarding cellular uptake by fluorescence microscopy and flow cytometry was observed the high efficiency in uptake melan-A cells mediated by liquid crystalline nanodispersions formed by system MO:OA:PEI. Results inhibition of the expression of TyRP-1 protein were observed by Western Blotting in melan-A cells, after administration of liquid crystalline nanodispersions associated with specific siRNA-TyRP-1. The liquid crystalline nanodispersions evaluated also provided greater release of siRNA in the skin in an animal model. These results demonstrate the potential use of these systems for antisense therapy of skin diseases such as vitiligo, thus representing, an important contribution to the topical gene therapy for this disease

O objetivo do presente trabalho foi avaliar a ação melanogênica das furanocumarinas, psoraleno e bergapteno assim como do extrato seco das raízes de Brosimum gaudichaudii Trécul, contendo 1,2 % m/m de psoraleno, e 5,2 % m/m de bergapteno. A toxidade celular in vitro foi avaliada pelo teste de incorporação do vermelho neutro em quatro linhagens de células diferentes (fibroblastos-L929, queratinócitos-HaCat, Melanoma-B16F10, e melanócitos-Melam-A) e apresentou resposta dose dependente tanto para os fármacos puros quanto para o extrato de B. gaudichaudii. Quando expostas à radiação ultravioleta do tipo A e B houve aumento da toxicidade, proporcional a dose de radiação. A mutagenicidade e genotoxicidade realizas pelos ensaios de micronúcleo e cometa, mostrou que os compostos são genotóxicos e mutagênicos em doses >= 150 ?g.mL-1.A síntese de melanina in vitro realizada em cultura de melanoma B16F10 foi dependente da dose e do tempo de exposição aos fármacos e UV. Nas concentrações máximas usadas (48 ?g.mL-1 de psoraleno, 104 ?g.mL-1 de bergapteno e 0,5 mg.mL-1 de extrato) o psoraleno aumentou a produção de melanina em 26 %, o bergapteno em 69 %, e o extrato de B.gaudichaudii em 163 %. Quando utilizado mistura equivalente 6 ?g.mL-1 de psoraleno e 26 ?g.mL-1 de bergapteno a presente em 0,5 mg.mL-1 de extrato a produção de melanina foi de 61%. A atividade da tirosinase em culturas de B16F10, tratadas com 20 ?g.mL-1 de psoraleno ou bergapteno, quando comparada ao grupo não tratado aumentou em 13% a atividade enzimatica , quando associados foi de 37%, e 0,5 mg.mL-1 de extrato em 54,1%. Com o ensaio de microdiálise in vivo observou-se que os fármacos são rapidamente absorvidos pela pele e distribuídos no plasma. Ambos os composto apresentaram um cinética linear . O estudo de produção de melanina in vivo confimou que a radiação estimula a produçao de melanina assim como o extrato de B.Gaudichaudii, e quando associados (PUVA) a sintese de melanina foi 143% maior em comparação ao controle negativo. Os resultados destre trabalho mostrou a capacidade de pgmentaçao dos fármacos assim como do B.Gaudichaudii, revelando ainda o sinergismo entre psoraleno e bergapteno. / The objective of this study was to evaluate the melanogenic action of furanocoumarins, namely, psoralen and bergapten, as extract of Brosimum gaudichaudii Trécul containing 1.2% m / m (psoralen), 5.2% m / m (bergapten) . The cellular toxicity (in vitro) was evaluated by neutral red incorporation test in four different cell lines (fibroblasts, L929, keratinocytes, HaCaT, melanoma, B16F10, and melanocyte- Melam-A) and showed dose dependent response to both extracted compounds, as well as the whole extract of B. gaudichaudii. The ultraviolet radiation type A and B increased the toxicity associated with the compounds and severity of toxicity was proportional to the radiation dose. The mutagenicity and genotoxicity evaluated by the micronucleus test and comet showed that the compounds are genotoxic and mutagenic compounds at concentrations >= 150 ?g/mL. The in vitro melanin synthesis, performed in melanoma B16F10, was dose, duration and UV dependent. In the maximum concentration used (48 ?g/mL psoralen, 104 ?g/mL bergapten and 0.5 mg.mL-1 extract) psoralen increased melanin synthesis by 26%, bergapten by 69% and the B.gaudichaudii extract by 163%. When administered as an equivalent mixture of 6 ?g/mL psoralen and 26 ?g/mL of bergapten to 0.5 mg/mL of extract, melanin synthesis was increased by 61%. The enzymatic activity of tyrosinase in B16F10 cultures treated with 20 ?g/mL of psoralen or bergapten, when compared to non-treated group, increased by 13%; the increases were 37% and 54.1% in the two-compound mixture and 0.5 mg/mL of whole extract. The in vivo microdialese test in rats showed that the drugs are quickly absorbed through the skin and distributed in plasma. Both compound exhibited linear kinetics. The in vivo evaluation also showed that melanin production was stimulated by UV radiation as well as B.Gaudichaudii extract. When combined with PUVA, melanin synthesis was 143% higher compared to the negative control

Orientador: Elemir Macedo de Souza / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-18T22:06:21Z (GMT). No. of bitstreams: 1 Franca_AndreaFernandesEloydaCosta_D.pdf: 3442848 bytes, checksum: 1ed0dba42432e3b03b1b7c6c386bdf41 (MD5) Previous issue date: 2011 / Resumo: O lúpus eritematoso (LE) é uma doença auto-imune com espectro clínico variado. O lúpus eritematoso cutâneo (LEC) inclui o lúpus eritematoso agudo (LECA), o subagudo (LECSA) e o crônico (LECC). Lesões acrômicas podem ocorrer durante a evolução do LE, embora nunca tenham sido estudadas histologicamente. O objetivo deste trabalho é descrever os achados clínicos, laboratoriais e histológicos das lesões acrômicas no LE. Foram selecionados 12 pacientes com LE de um grupo de 220 atendidos no período de 2005 a 2008, sendo sete com LECC e cinco com LECSA. Doze pacientes com vitiligo e 10 controles de pele sã foram usados para comparação. As alterações histológicas encontradas foram: infiltrado inflamatório (75%); hiperceratose e espessamento da zona da membrana basal (ZMB) (66,7%); retificação da epiderme (58,3%); ceratinócitos apoptóticos epidérmicos, elastose e telangectasias (50%); fibrose (41,7%); degeneração vacuolar da ZMB (33,3%); rolhas córneas (16,7%). O diagnóstico histológico de LE foi possível em quatro casos. Melanina pela coloração de Fontana Masson (FM) foi vista em cinco casos e incontinência pigmentar em quatro. Melanócitos foram evidenciados em amostras de cinco doentes através da reação imunohistoquímica pelo HMB45 e Melan-A, com diferença estatística em relação aos controles. Quando comparado ao vitiligo, a diferença foi estatisticamente significante para os achados histológicos: ceratinócitos apoptóticos epidérmicos (p=0,014), espessamento da ZMB (p=0,009) e fibrose (p=0,037). Em relação à quantificação dos melanócitos, não houve diferença estatística entre o grupo LE e vitiligo usando os anticorpos Melan-A e HMB45. Concluímos que as lesões acrômicas no LE correspondem a lesões residuais, decorrentes de processo inflamatório liquenóide prévio que destrói os melanócitos. Não é possível diferenciar as lesões vitiligóides das duas dermatoses pela presença ou ausência de melanócitos, embora a repigmentação seja possível em ambas as doenças devido a presença de melanogênese ativa comprovada pela positividade pelo HMB45 / Abstract: Lupus Erythematosus (LE) is an autoimmune disorder with multiple clinical manifestations. Skin damage is a hallmark of the disease. Cutaneous LE (CLE) includes acute LE (ACLE), subacute LE (SCLE) and chronic LE (CCLE). Although achromic lesions are often found in patients with LEC, there are no detailed data about the histological features of such lesions. Therefore, we designed this study to determine clinical, laboratorial and histological profile of patients with LEC presenting achromic lesions. Between 2005 and 2008, we identified 12 individuals with LEC and acromic lesions from a larger group of 220 patients with LEC that were followed at the Dermatology outpatient clinic. There were seven patients with LECC and five with LECSA. Twelve patients with chronic stable vitiligo and 10 controls of unaffected skin were used for comparison. The most frequent histological abnormalities found in LEC-related achromic lesions were inflammatory infiltrates (75%); hyperkeratosis and thickening of the basement membrane (BM) (66.7%); epidermal flattening (58.3%); apoptotic epidermal keratinocytes, elastosis and vasodilation (50%); fibrosis (41.7%); hydropic degeneration of the basal cells (33.3%); follicular plugging (16.7%). These achromic lesions retained histological features that enabled the diagnosis of CLE to be established in four patients. Fontana Masson (FM) staining was positive for melanin in five cases and revealed pigmentary incontinence in four. Immunohistochemistry for HMB45 and Melan-A identified melanocytes in five CLE-related achromic lesions. Melanocyte counts were significantly smaller in achromic lesions when compared to unaffected skin samples. When compared to vitiligo, CLE-related achromic lesions showed more frequently apoptotic epidermal keratinocytes (p=0,014), thickening of the BM (p=0,009) and fibrosis (p=0,037). Melanocyte counts according to immunohistochemistry were similar in CLE and vitiligo groups. Our results indicate that CLE-related achromic lesions represent residual scars due to chronic lichenoid inflammation that leads to melanocyte destruction. Melanocyte count does not help to distinguish CLE-related achromic lesions and true vitiligo lesions. Despite this, HMB45 staining was sometimes positive in both conditions, which indicates active melanogenesis and suggests that repigmentation may be possible at least for some individuals / Doutorado / Clinica Medica / Doutor em Clínica Médica

The entire epidermis of patients with vitiligo exhibits accumulation of up to 10-3M concentrations of hydrogen peroxide (H₂O₂) (Schallreuter, Moore et al. 1999). Over the last decade our group and others have focused on the effect of H₂O₂-mediated oxidative stress on the function of many proteins and peptides due to oxidation of target amino acid residues in their structure including L-methionine, L-tryptophan, L-cysteine and seleno cysteine (Rokos, Beazley et al. 2002; Gillbro, Marles et al. 2004; Hasse, Kothari et al. 2005; Schallreuter, Chavan et al. 2005; Spencer, Chavan et al. 2005; Chavan, Gillbro et al. 2006; Elwary, Chavan et al. 2006; Gibbons, Wood et al. 2006; Schallreuter, Bahadoran et al. 2008; Shalbaf, Gibbons et al. 2008; Wood, Decker et al. 2009). Moreover, it was shown that patients with vitiligo possess up regulated wild type functioning p53 protein in their skin (Schallreuter, Behrens- Williams et al. 2003). The reason behind this up regulation has remained unclear (Schallreuter, Behrens-Williams et al. 2003). Therefore the aim of this thesis was to get a better understanding of these puzzling data. Along this project different techniques have been used including Western blot, dot blot, immuno precipitation, immuno fluorescence, EMSA and computer modelling. In this thesis we confirmed the previous result on up regulation of p53 in vitiligo and we showed that p90MDM2, the master regulator for p53 protein is not different in patients and healthy controls. Therefore we decided to test for expression of p76MDM2 which mediates the inhibition of p90MDM2-p53 binding. Our results show for the first time the presence and over expression of p76MDM2 protein in vitiligo compared to 3 healthy individuals. This result could provide an explanation, why up regulated p53 is not degraded in this disease. Since epidermal H₂O₂ accumulation has been extensively documented in vitiligo, we wanted to know whether other ROS could also contribute to the overall oxidative stress in this scenario. Therefore we turned our interest to nitric oxide (NO) and its possible effects on p53 protein. In order to elucidate this role in more detail, the expression levels of epidermal nitric oxide synthesase (iNOS) and the oxidation product of NO and O2 - i.e peroxynitrite (ONOO-) were investigated. Our data revealed over expression of iNOS and nitrated tyrosine residues, the foot print for ONOO-. Moreover, we show for the first time the presence of abundant nitration of p53 protein in vitiligo. In addition using purified p53 from E. coli strain (BL21/DE3) and mutant p53 protein from HT-29 cells (colon cancer cells), we show that nitration takes place in a dose and time dependent manner. On this basis we investigated the effect of both H₂O₂ and ONOO- on p53-DNA binding capacity employing EMSA, since this is the most acceptable technique to follow the binding between proteins and DNA. Our results revealed that ONOO- abrogated p53-DNA binding capacity at concentrations >300 μM, meanwhile oxidation of p53 protein with H₂O₂ at the same concentrations does not affect binding capacity. Importantly, a much higher p53- DNA binding capacity was observed after exposure to both ONOO- and H₂O₂. Taken together, p53 is regulated by both ROS (H₂O₂) and RNS (ONOO-). Next we identified the presence of phosphorylated and acetylated p53 in vitiligo. Phosphorylation of ser 9 and ser 15 residues of the protein are associated with over expressed ATM protein kinase, while acetylation of lys 373, 382 residues correlates with increased PCAF expression. We show that up regulated p53 is associated with over expressed p21 (cyclin dependent kinase inhibitor 1) and induced PCNA 4 expression. Hence, we can conclude that p53 in patients with vitiligo is up regulated, activated and functional. Finally we show up regulated BCL-2 supporting the long voiced absence of increased apoptosis in vitiligo. Given that patients with vitiligo have no increased risk for solar induced skin cancer and increased photo damage (Calanchini-Postizzi and Frenk 1987; Westerhof and Schallreuter 1997; Schallreuter, Tobin et al. 2002), despite the presence of increased DNA damage as evidenced by increased 8-oxoG levels in the skin and in the plasma, our findings suggest that both p53 and PCNA provide a powerful machinery to mediate DNA repair via hOgg1, APE1 and DNA polymerase ß (Shalbaf 2009). On this basis it is tempting to conclude that DNArepair is the overriding mechanism to combat oxidative stress in this disease.

Introdução: O vitiligo é uma doença da pele frequente que afeta cerca de 1% da população em todo o mundo. Ocorre em pessoas de qualquer idade ou etnia, e mais da metade dos pacientes desenvolvem a doença antes dos 20 anos de idade. O vitiligo pode afetar negativamente a qualidade de vida (QoL) do paciente. Um questionário de qualidade de vida específico para vitiligo foi desenvolvido e validado na língua inglesa: the vitiligo-specific quality-of-life instrument (VitiQoL). Objetivo: O objetivo deste estudo é avaliar a QoL em pacientes adultos com o VitiQoL e o DLQI e pediátricos com o CDLQI em uma amostra de pacientes com vitiligo no sul do Brasil. Métodos: Na primeira etapa, o instrumento foi traduzido, adaptado culturalmente e validado para o português falado no Brasil (VitiQoL-PB). Após, foram incluídos pacientes selecionados no Ambulatório de Dermatologia do Hospital de Clínicas de Porto Alegre e numa clínica privada de Porto Alegre. Foi realizada amostragem de conveniência de casos consecutivos. A qualidade de vida de pacientes pediátricos foi avaliada com o questionário CDLQI. Em pacientes adultos foram aplicados o VitiQoL – PB e o DLQI. Resultados: Observou-se uma forte correlação entre os escores do total de VitiQoL e o DLQI (r = 0,81; p <0,001). O fator que mais contribuiu para a pontuação final do VitiQoL foi estigma. Em nossa amostra, as mulheres apresentaram escores mais elevados do que os homens (p <0,05). Problemas psiquiátricos foram associados com uma pior qualidade de vida. Na população pediátrica, a mediana do escore do CDLQI foi 3 (intervalo interquartil 1,3-7,3). Houve uma correlação estatisticamente significativa entre a idade da criança e o escore no CDLQI (rs = 0,41, p = 0,044). Não houve diferença entre meninos e meninas (p = 0,219). Conclusão: Este estudo confirma não só que o VitiQoL é fácil de administrar, como também, acrescenta informações importantes sobre o impacto do vitiligo na América do Sul. Instrumentos genéricos são úteis e permitem comparações com outras dermatoses, mas não são suficientemente específicos para detectar nuances na maneira como os pacientes lidam com o vitiligo. A autoestima dos pacientes é muito afetada e a estigmatização está bastante presente. Há grupos de pacientes que são mais vulneráveis ao impacto da doença, como as mulheres, os adolescentes e os pacientes com doenças psiquiátricas. / Background: Vitiligo is a common skin disease that has been reported to affect approximately 1 % of the population worldwide. It affects people of any age or ethnicity, more than half of who develop it before the age of 20 years. Vitiligo can negatively affect patient’s quality of life (QoL). A specific questionnaire for vitiligo has been developed and validated in the English language: the vitiligo-specific quality-of-life instrument (VitiQoL). Objective: The aim of this study was to access the QoL in adult patients through VitiQoL and DLQI and pediatric patients through CDLQI in a sample of patients with vitiligo in Southern Brazil. Methods: In the first phase of the study the instrument was translated, cultural adapted and validated into Brazilian Portuguese (VitiQoL-PB). Then patients were selected from a Dermatological Outpatient Clinic from Hospital de Clínicas de Porto Alegre and from a Private Practice in Porto Alegre. In this study, we used convenience sampling of consecutive cases. The QoL of pediatric patients was performed using the CDLQI questionnaire. In adult patients we applied the VitiQoL – PB and the DLQI. Results: A strong correlation between the scores of the total VitiQoL and DLQI was observed (r = 0.81; p <0.001). The factor that most contributed to the final score of VitiQoL was stigma. In our sample, women had higher scores than men (p<0,05). Psychiatric problems were associated with lower QoL. In the pediatric population, the median score of CDLQI was 3 (interquartile range 1.3 to 7.3). There was a statistically significant correlation between the child's age and the score on CDLQI (rs = 0.41, p = 0.044). There was no difference between boys and girls (p = 0.219). Conclusion: This study confirms that VitiQoL is easy to administer and adds important information about the impact of vitiligo on a South American population. Generic instruments are useful and allow comparisons with other dermatoses, but are not specific enough to detect nuances in how patients deal with the overall vitiligo burden. Self-esteem of patients is greatly affected and stigmatization is very present in the disease. There are groups of patients that are more vulnerable to the impact of the disease, like women, patients with psychiatric diseases and adolescents.

Introdução: O vitiligo é uma doença da pele frequente que afeta cerca de 1% da população em todo o mundo. Ocorre em pessoas de qualquer idade ou etnia, e mais da metade dos pacientes desenvolvem a doença antes dos 20 anos de idade. O vitiligo pode afetar negativamente a qualidade de vida (QoL) do paciente. Um questionário de qualidade de vida específico para vitiligo foi desenvolvido e validado na língua inglesa: the vitiligo-specific quality-of-life instrument (VitiQoL). Objetivo: O objetivo deste estudo é avaliar a QoL em pacientes adultos com o VitiQoL e o DLQI e pediátricos com o CDLQI em uma amostra de pacientes com vitiligo no sul do Brasil. Métodos: Na primeira etapa, o instrumento foi traduzido, adaptado culturalmente e validado para o português falado no Brasil (VitiQoL-PB). Após, foram incluídos pacientes selecionados no Ambulatório de Dermatologia do Hospital de Clínicas de Porto Alegre e numa clínica privada de Porto Alegre. Foi realizada amostragem de conveniência de casos consecutivos. A qualidade de vida de pacientes pediátricos foi avaliada com o questionário CDLQI. Em pacientes adultos foram aplicados o VitiQoL – PB e o DLQI. Resultados: Observou-se uma forte correlação entre os escores do total de VitiQoL e o DLQI (r = 0,81; p <0,001). O fator que mais contribuiu para a pontuação final do VitiQoL foi estigma. Em nossa amostra, as mulheres apresentaram escores mais elevados do que os homens (p <0,05). Problemas psiquiátricos foram associados com uma pior qualidade de vida. Na população pediátrica, a mediana do escore do CDLQI foi 3 (intervalo interquartil 1,3-7,3). Houve uma correlação estatisticamente significativa entre a idade da criança e o escore no CDLQI (rs = 0,41, p = 0,044). Não houve diferença entre meninos e meninas (p = 0,219). Conclusão: Este estudo confirma não só que o VitiQoL é fácil de administrar, como também, acrescenta informações importantes sobre o impacto do vitiligo na América do Sul. Instrumentos genéricos são úteis e permitem comparações com outras dermatoses, mas não são suficientemente específicos para detectar nuances na maneira como os pacientes lidam com o vitiligo. A autoestima dos pacientes é muito afetada e a estigmatização está bastante presente. Há grupos de pacientes que são mais vulneráveis ao impacto da doença, como as mulheres, os adolescentes e os pacientes com doenças psiquiátricas. / Background: Vitiligo is a common skin disease that has been reported to affect approximately 1 % of the population worldwide. It affects people of any age or ethnicity, more than half of who develop it before the age of 20 years. Vitiligo can negatively affect patient’s quality of life (QoL). A specific questionnaire for vitiligo has been developed and validated in the English language: the vitiligo-specific quality-of-life instrument (VitiQoL). Objective: The aim of this study was to access the QoL in adult patients through VitiQoL and DLQI and pediatric patients through CDLQI in a sample of patients with vitiligo in Southern Brazil. Methods: In the first phase of the study the instrument was translated, cultural adapted and validated into Brazilian Portuguese (VitiQoL-PB). Then patients were selected from a Dermatological Outpatient Clinic from Hospital de Clínicas de Porto Alegre and from a Private Practice in Porto Alegre. In this study, we used convenience sampling of consecutive cases. The QoL of pediatric patients was performed using the CDLQI questionnaire. In adult patients we applied the VitiQoL – PB and the DLQI. Results: A strong correlation between the scores of the total VitiQoL and DLQI was observed (r = 0.81; p <0.001). The factor that most contributed to the final score of VitiQoL was stigma. In our sample, women had higher scores than men (p<0,05). Psychiatric problems were associated with lower QoL. In the pediatric population, the median score of CDLQI was 3 (interquartile range 1.3 to 7.3). There was a statistically significant correlation between the child's age and the score on CDLQI (rs = 0.41, p = 0.044). There was no difference between boys and girls (p = 0.219). Conclusion: This study confirms that VitiQoL is easy to administer and adds important information about the impact of vitiligo on a South American population. Generic instruments are useful and allow comparisons with other dermatoses, but are not specific enough to detect nuances in how patients deal with the overall vitiligo burden. Self-esteem of patients is greatly affected and stigmatization is very present in the disease. There are groups of patients that are more vulnerable to the impact of the disease, like women, patients with psychiatric diseases and adolescents.

Introdução: O vitiligo é uma doença da pele frequente que afeta cerca de 1% da população em todo o mundo. Ocorre em pessoas de qualquer idade ou etnia, e mais da metade dos pacientes desenvolvem a doença antes dos 20 anos de idade. O vitiligo pode afetar negativamente a qualidade de vida (QoL) do paciente. Um questionário de qualidade de vida específico para vitiligo foi desenvolvido e validado na língua inglesa: the vitiligo-specific quality-of-life instrument (VitiQoL). Objetivo: O objetivo deste estudo é avaliar a QoL em pacientes adultos com o VitiQoL e o DLQI e pediátricos com o CDLQI em uma amostra de pacientes com vitiligo no sul do Brasil. Métodos: Na primeira etapa, o instrumento foi traduzido, adaptado culturalmente e validado para o português falado no Brasil (VitiQoL-PB). Após, foram incluídos pacientes selecionados no Ambulatório de Dermatologia do Hospital de Clínicas de Porto Alegre e numa clínica privada de Porto Alegre. Foi realizada amostragem de conveniência de casos consecutivos. A qualidade de vida de pacientes pediátricos foi avaliada com o questionário CDLQI. Em pacientes adultos foram aplicados o VitiQoL – PB e o DLQI. Resultados: Observou-se uma forte correlação entre os escores do total de VitiQoL e o DLQI (r = 0,81; p <0,001). O fator que mais contribuiu para a pontuação final do VitiQoL foi estigma. Em nossa amostra, as mulheres apresentaram escores mais elevados do que os homens (p <0,05). Problemas psiquiátricos foram associados com uma pior qualidade de vida. Na população pediátrica, a mediana do escore do CDLQI foi 3 (intervalo interquartil 1,3-7,3). Houve uma correlação estatisticamente significativa entre a idade da criança e o escore no CDLQI (rs = 0,41, p = 0,044). Não houve diferença entre meninos e meninas (p = 0,219). Conclusão: Este estudo confirma não só que o VitiQoL é fácil de administrar, como também, acrescenta informações importantes sobre o impacto do vitiligo na América do Sul. Instrumentos genéricos são úteis e permitem comparações com outras dermatoses, mas não são suficientemente específicos para detectar nuances na maneira como os pacientes lidam com o vitiligo. A autoestima dos pacientes é muito afetada e a estigmatização está bastante presente. Há grupos de pacientes que são mais vulneráveis ao impacto da doença, como as mulheres, os adolescentes e os pacientes com doenças psiquiátricas. / Background: Vitiligo is a common skin disease that has been reported to affect approximately 1 % of the population worldwide. It affects people of any age or ethnicity, more than half of who develop it before the age of 20 years. Vitiligo can negatively affect patient’s quality of life (QoL). A specific questionnaire for vitiligo has been developed and validated in the English language: the vitiligo-specific quality-of-life instrument (VitiQoL). Objective: The aim of this study was to access the QoL in adult patients through VitiQoL and DLQI and pediatric patients through CDLQI in a sample of patients with vitiligo in Southern Brazil. Methods: In the first phase of the study the instrument was translated, cultural adapted and validated into Brazilian Portuguese (VitiQoL-PB). Then patients were selected from a Dermatological Outpatient Clinic from Hospital de Clínicas de Porto Alegre and from a Private Practice in Porto Alegre. In this study, we used convenience sampling of consecutive cases. The QoL of pediatric patients was performed using the CDLQI questionnaire. In adult patients we applied the VitiQoL – PB and the DLQI. Results: A strong correlation between the scores of the total VitiQoL and DLQI was observed (r = 0.81; p <0.001). The factor that most contributed to the final score of VitiQoL was stigma. In our sample, women had higher scores than men (p<0,05). Psychiatric problems were associated with lower QoL. In the pediatric population, the median score of CDLQI was 3 (interquartile range 1.3 to 7.3). There was a statistically significant correlation between the child's age and the score on CDLQI (rs = 0.41, p = 0.044). There was no difference between boys and girls (p = 0.219). Conclusion: This study confirms that VitiQoL is easy to administer and adds important information about the impact of vitiligo on a South American population. Generic instruments are useful and allow comparisons with other dermatoses, but are not specific enough to detect nuances in how patients deal with the overall vitiligo burden. Self-esteem of patients is greatly affected and stigmatization is very present in the disease. There are groups of patients that are more vulnerable to the impact of the disease, like women, patients with psychiatric diseases and adolescents.

no / Vitiligo is an acquired, idiopathic skin disease characterized by the mostly progressive loss of the inherited skin color leading to white patches and in some cases to total depigmentation. The course of this ancient disease is still unknown. The worldwide prevalence range is 0.5-1%. The disease burden includes stigmatization, depression, impaired quality of life, lack of self-confidence, embarrassment and self-consciousness. To the best of our knowledge, the extent to which this chronic disease may exert an influence upon the life course of affected individuals has, to date, not been investigated. The material presented herein is the result of an accurate analysis of published literature. Moreover, we included our own data collected in two studies. To apply the concept of cumulative life course impairment in vitiligo, we looked at possible trigger factors, role of patient's age and the age at disease onset, disease duration and stigmatization. Stigmatization had the strongest impact. It is common in patients with an early disease onset, often leading to other disturbances. Our data revealed that older patients or those with a disease onset later in life adjust better to this chronic skin disorder and that they are less socially avoidant. However, long disease duration can also lead to impaired quality of life and obsession, while this group seems to be less depressed or embarrassed. Results from our own work with peer groups of these patients strongly support a positive long-lasting effect of treatment on quality of life of children, adolescents and adults. To which extent vitiligo may contribute to a cumulative life course impairment remains to be shown.

No / Background  Vitiligo is an acquired, non-contagious depigmentation disorder involving a patchy loss of skin color. It often leads to stigmatization, embarrassment, and reduced quality of life (QoL) in adult patients. Little is known about children’s reactions. Objectives  This study aimed to explore disease-related QoL and experiences in a multinational group of children and adolescents. Methods  Quality of life, disease-related experiences and behavior, and sociodemographic data were examined in 24 boys and 50 girls (age range: 7–17 years) using the Children’s Dermatology Life Quality Index (CDLQI) and additional questions. Eighteen children without skin disorders served as age-, sex- and skin color-matched controls. Results  The mean disease duration was 3.5 years. The most common sites of onset were the trunk, legs, and head and neck. Overall, 35.1% of the 74 subjects reported a positive family history, 91.9% had visited a doctor, and 75.7% had received treatment. Two-thirds (66.2%) were distressed by their vitiligo, and 93.2% had experienced low-key stigmatization, 44.6% nasty comments, and 21.7% bullying. A total of 24.4% had concealed their disease, and 29.7% had avoided situations because of vitiligo. Frequency of stigmatization influenced avoidant behavior. Parents, particularly mothers, and friends were important sources of support. Patients and controls had similar numbers of friends and leisure time activities. The mean CDLQI score of the group was low (2.8). Higher CDLQI scores were related to stigmatization, hiding of white spots, facial depigmentation, avoidance of situations, and a vitiligo-negative family history. Conclusions  Disease-related stigmatization, negative experiences, and avoidant behavior affect QoL. Therefore, the CDLQI should be combined with other instruments to screen for disease burden. These results call for the careful evaluation of young patients with vitiligo.