Seborreia e dermatite seborreica: estudo clínico-laboratorial, comparativo e randomizado sobre eficácia e segurança da isotretinoína oral em dose baixa e identificações fenotípica e genotípica do gênero malassezia spp
Data
2014-06-30
Autores
Kamamoto, Cristhine de Souza Leão 
Orientadores
Bagatin, Edileia
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Fundamentos: o uso off label da isotretinoína oral para seborreia e dermatite seborreica foi relatado na literatura em estudos abertos em combinação com medicações tópicas. Quando utilizada a dose convencional, apresenta ação anti-inflamatória e reduz a secreção do sebo e volume da glândula sebácea. Considerando tais propriedades, acredita-se que possa controlar a seborreia e dermatite seborreica em dose baixa. Objetivos: avaliar a eficácia e segurança da isotretinoína oral em dose baixa na redução da secreção sebácea e no controle da seborreia/dermatite seborreica moderada a grave, da face e couro cabeludo, comparada ao tratamento tópico anti-seborreico; quantificar a secreção sebácea (medição da secreção sebácea) na face e/ou couro cabeludo; analisar a hidratação da pele da face; verificar o impacto dos tratamentos na qualidade de vida e realizar as identificações fenotípica e genotípica de amostras de leveduras do gênero Malassezia obtidas da superfície cutânea do couro cabeludo, antes e após os tratamentos. Métodos: estudo de intervenção terapêutica, randomizado e comparativo incluiu homens e mulheres, de 18 a 40 anos, com seborreia/dermatite seborreica moderada a grave, após verificação de critérios de seleção. Foram constituídos dois grupos randomizados para tratamento: (a) isotretinoína oral (ISO), 10 mg/dia, em dias alternados e (b) xampu e sabonete anti-seborreicos (XAMPU) três vezes por semana durante seis meses. A eficácia foi avaliada pela opinião do participante da pesquisa, escore clínico de gravidade (escore total e sinais clínicos), medição da secreção sebácea pelo Sebumeter® nas fases pré, meio e após tratamento e qualidade de vida antes e ao final do tratamento. A segurança foi verificada pelo relato e ocorrência de eventos adversos clínico-laboratoriais e pela medição da hidratação da pele. A população intention-to-treat foi submetida à análise estatística. A coleta de escamas/sebo do couro cabeludo foi realizada e incubados no meio de Dixon modificado a 32 º C. Procedeu-se às identificações fenotípica e genotípica. O seqüenciamento do DNA utilizou primers para as regiões ITS e D1/D2 do DNA ribossomal. Resultados: os participantes dos grupos ISO (n=25) e XAMPU (n=20) apresentaram idade média de 28,7 ± 5,8 e 29,8 ± 6,5 respectivamente, e a associação entre seborreia/dermatite seborreia correspondeu ao diagnóstico clínico mais frequente; houve melhora na opinião dos participantes, do escore clínico de gravidade e redução de produção de sebo do couro cabeludo sem diferenças entre os tratamentos. Na face, o nível de secreção sebácea foi menor no grupo ISO. Houve melhora clínica da qualidade de vida nos dois grupos e os eventos adversos foram previsíveis, de intensidade leve em sua maioria, e bem controlados. M. globosa e M. restricta foram as espécies predominantes isoladas no couro cabeludo em ambos os grupos antes e após os tratamentos. Outras espécies fúngicas que não Malassezia também foram identificadas. Limitações: pequeno número de participantes; dose baixa de isotretinoína sem considerar peso e falta de seguimento prolongado. Conclusões: dose baixa de isotretinoína oral foi eficaz e segura para seborreia/dermatite seborreica moderada a grave, com redução significante da taxa de secreção sebácea. Entretanto, não foi superior ao tratamento tópico. As Malassezia spp. colonizaram a pele do couro cabeludo em ambos os grupos mesmo após tratamento.
Background: the off-label use of oral isotretinoin for treatment of seborrhea and/or seborrheic dermatitis was reported by uncontrolled studies in topical treatment combination. The conventional dose reduces the sebum production, glandular’s size and possesses anti-inflammatory properties. According to its properties, seborrhea and/or seborrheic dermatitis could be controlled by low dose of oral isotretinoin. Objectives: to determine efficacy and safety of low-dose oral isotretinoin in the treatment of moderate to severe seborrhea and/or seborrheic dermatitis on the scalp and the face, compared to topical treatment; to verify sebum production rate on the scalp and face; to analyse skin hydration; to verify the quality of life assessment and to perform the phenotypic identification followed by genotypic identification of the Malassezia spp. on the scalp samples before and after treatment. Methods: therapeutic interventional, randomized and comparative study included 18 to 40-year-old men and women, with moderate to severe seborrhea/seborrheic dermatitis on the scalp and face after exclusion and inclusion criteria verification. The subjects were divided into two randomized groups of treatment: (a) oral isotretinoin (ISO), 10 mg, every other day and (b) anti-seborrheic topical treatment (XAMPU) three times a week over six months. Efficacy outcomes included subject’s assessment, clinical severity score (total score and clinical signs), sebum production measure by Sebumeter® before, during and after treatments, and quality of life assessment prior to and in the end of therapy. Safety data included clinical and laboratory adverse events and skin hydration measure. The intention-to treat population was analyzed by statistical tests. The collection of scales/sebum of the scalp was performed and seeded in the middle of modified Dixon and incubated at 32ºC. The phenotypic identification was performed followed by genotypic identification. The samples used PCR primers for the ITS and D1/D2ribossomal DNA followed by sequencing of the samples. Results: The ISO’s subjects (n =25) and the XAMPU’s subjects (n= 20) were 28.7 ± 5.8 e 29.8 ± 6.5 mean aged respectively and the seborrhea associated to seborrheic dermatitis was the most frequent clinical diagnosis. Subject’s assessment, clinical severity score and quality of life were improved in both groups with no difference. The face’s sebum rate was lower in ISO group than XAMPU. The sebum production was reduced in both groups. Adverse events were mild and controlled. M. globosa and M. restricta were the most frequent species isolated on the scalp prior to and after therapy and the other nonMalassezia species were identified. Limitations: The small number of subjects, weigth not considered as a parameter for dose and lack of prolonged clinical follow-up. Conclusions: Low-dose oral isotretinoin was considered safe and efficient for moderate to severe seborrhea/seborrheic dermatitis after six months treatment. However, it was not superior to the topical treatment. The Malassezia spp. colonized the scalp even after treatment in both groups.
Background: the off-label use of oral isotretinoin for treatment of seborrhea and/or seborrheic dermatitis was reported by uncontrolled studies in topical treatment combination. The conventional dose reduces the sebum production, glandular’s size and possesses anti-inflammatory properties. According to its properties, seborrhea and/or seborrheic dermatitis could be controlled by low dose of oral isotretinoin. Objectives: to determine efficacy and safety of low-dose oral isotretinoin in the treatment of moderate to severe seborrhea and/or seborrheic dermatitis on the scalp and the face, compared to topical treatment; to verify sebum production rate on the scalp and face; to analyse skin hydration; to verify the quality of life assessment and to perform the phenotypic identification followed by genotypic identification of the Malassezia spp. on the scalp samples before and after treatment. Methods: therapeutic interventional, randomized and comparative study included 18 to 40-year-old men and women, with moderate to severe seborrhea/seborrheic dermatitis on the scalp and face after exclusion and inclusion criteria verification. The subjects were divided into two randomized groups of treatment: (a) oral isotretinoin (ISO), 10 mg, every other day and (b) anti-seborrheic topical treatment (XAMPU) three times a week over six months. Efficacy outcomes included subject’s assessment, clinical severity score (total score and clinical signs), sebum production measure by Sebumeter® before, during and after treatments, and quality of life assessment prior to and in the end of therapy. Safety data included clinical and laboratory adverse events and skin hydration measure. The intention-to treat population was analyzed by statistical tests. The collection of scales/sebum of the scalp was performed and seeded in the middle of modified Dixon and incubated at 32ºC. The phenotypic identification was performed followed by genotypic identification. The samples used PCR primers for the ITS and D1/D2ribossomal DNA followed by sequencing of the samples. Results: The ISO’s subjects (n =25) and the XAMPU’s subjects (n= 20) were 28.7 ± 5.8 e 29.8 ± 6.5 mean aged respectively and the seborrhea associated to seborrheic dermatitis was the most frequent clinical diagnosis. Subject’s assessment, clinical severity score and quality of life were improved in both groups with no difference. The face’s sebum rate was lower in ISO group than XAMPU. The sebum production was reduced in both groups. Adverse events were mild and controlled. M. globosa and M. restricta were the most frequent species isolated on the scalp prior to and after therapy and the other nonMalassezia species were identified. Limitations: The small number of subjects, weigth not considered as a parameter for dose and lack of prolonged clinical follow-up. Conclusions: Low-dose oral isotretinoin was considered safe and efficient for moderate to severe seborrhea/seborrheic dermatitis after six months treatment. However, it was not superior to the topical treatment. The Malassezia spp. colonized the scalp even after treatment in both groups.
Descrição
Citação
KAMAMOTO, Cristhine de Souza Leão. Seborreia e dermatite seborreica: estudo clínico-laboratorial, comparativo e randomizado sobre eficácia e segurança da isotretinoína oral em dose baixa e identificações fenotípica e genotípica do gênero malassezia spp. 2014. Tese (Doutorado) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2014.