Papel das interleucinas na acne da mulher adulta associada ou não a fatores de risco para síndrome metabólica e modificação após tratamento: estudo clínico randomizado e comparativo
Data
2024-11-12
Orientadores
Bagatin, Ediléia 
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Fundamentos: Em vários países, pesquisas recentes têm demonstrado aumento na prevalência da acne da mulher adulta (AMA), definida como a acne que surge em mulheres com mais de 25 anos. Essa doença traz algumas particularidades e desafios, como maior impacto na qualidade de vida (QV) e cronicidade. A inflamação desempenha um papel essencial no desenvolvimento da acne. Os aspectos imunológicos da acne ainda não são completamente compreendidos, principalmente na AMA. Objetivos: Avaliação clínica e laboratorial de pacientes com AMA, incluindo abordagem a respeito de QV, e investigando possíveis correlações com a síndrome metabólica. Analisar as interleucinas (IL) 6, 8, 10 e 17 e avaliação histológica e de imuno-histoquímica desses marcadores, antes e depois de dois tratamentos diferentes na população de AMA. Métodos: Após aprovação pelo Comitê de Ética em Pesquisa Institucional, assinatura do Termo de Consentimento Livre e Esclarecido e Termo de Autorização para Fotografia, foi realizado estudo terapêutico prospectivo, randomizado, incluindo 40 mulheres, com idade superior a 25 anos, apresentando acne facial leve a moderada. Elas foram randomizadas em dois grupos de tratamento: 1- gel de ácido azelaico a 15% duas vezes ao dia; 2- espironolactona 100 miligramas/dia, ambas por seis meses. As pacientes foram avaliadas clinicamente em visitas mensais. No início e no final dos tratamentos, responderam ao questionário de QV em acne, (Acne-QoL-BR); foram fotografadas (Visia®); foram coletados exames gerais e para analisar quantitativamente as ILs, usando o ensaio Cytometric Bead Array (CBA). Foram submetidas a duas biópsias de pele, com punch de 3 mm, na região submandibular, uma coincidente com lesão inflamatória (biópsia 1) e outra em área de pele perilesional (biópsia 2), clinicamente normal, e uma terceira biópsia no local tratado (biópsia 3), após os seis meses, próximo à lesão inflamatória inicial. As lâminas foram digitalizadas e, por meio de fotomicrografias, submetidas à avaliação por escore inflamatório e análise da expressão das ILs pelo software ImageJ. Resultados: A média de idade foi de 32,5 (DP: 5,42); 85% apresentavam acne persistente. Pela avaliação global do investigador (IGA) ambos os tratamentos resultaram em significativa melhora clínica (p<0,0001), sem diferença entre eles. Após o tratamento independente do grupo, houve melhora significativa no escore total e em todos os domínios do Acne-QoL-BR (p<0,001). No início do estudo, não foi detectado aumento de ILs, exceto IL-6 em mulheres obesas (p=0,0016). Em relação à avaliação histológica, a pele lesionada apresentou presença intensa de infiltrado inflamatório na derme. Houve intensa imunorreatividade para IL-6 e IL-8, observada nos infiltrados inflamatórios da pele com lesão, com diminuição após ambos os tratamentos. A imunorreatividade para IL-17 não mostrou muita diferença na intensidade de sua expressão. Houve intensa imunorreatividade para IL-10 antes e após os tratamentos. Conclusões: Houve melhora do IGA com ambos os tratamentos, demonstrando eficácia clínica. Acne-QoL-BR é útil para quantificar o impacto da acne e deve ser usado como parâmetro de eficácia em ensaios clínicos. Os níveis séricos de ILs não aumentam na AMA leve a moderada. A IL-6 está aumentada em mulheres obesas, provavelmente devido à obesidade, como uma doença inflamatória sistêmica. Houve hiperexpressão de IL-6 e IL-8 em área de pele com lesão de acne e essa expressão foi reduzida de forma significativa com as duas opções terapêuticas, sem diferença estatística entre elas.
Background: In several countries, recent research has demonstrated an increase in the prevalence of acne in adult female acne (AFA), defined as acne that appears in women over 25 years of age. This disease brings some particularities and challenges, such as a greater impact on quality of life (QoL) and chronicity. Inflammation plays an essential role in the development of acne. The immunological aspects of acne are still incompletely understood, specially in AFA. Objectives: Clinical and laboratory evaluation of patients with AFA, QoL assessment, and to investigate possible correlations with metabolic syndrome. To analyze serum interleukins (IL) 6, 8, 10 and 17 and histological and immunohistochemical evaluation of these markers, before and after two different treatments in the AFA population. Methods: After approval by the Institutional Research Ethics Committee, signing of the Free and Informed Consent Form and Photography Authorization Form, a prospective, randomized therapeutic study was carried out, including 40 women, over the age of 25 years, with mild to moderate facial acne. They were randomized into two treatment groups: one -15% azelaic acid gel twice a day; two - spironolactone 100 mg/day, both for 6 months. Patients were clinically evaluated at monthly visits. At the beginning and end of treatments, they answered the acne quality of life questionnaire (Acne-QoL-BR); were photographed (Visia®); general exams were collected and to quantitatively analyze the ILs using the Cytometric Bead Array assay. They also performed 2 skin biopsies, with a 3 mm punch, in the submandibular region, one coinciding with an inflammatory lesion (biopsy 1) and another in the perilesional skin area (biopsy 2), clinically normal, and a third biopsy at the treated site (biopsy 3), after 6 months, close to the initial inflammatory lesion. The slides were digitalized and, using photomicrographs, submitted to evaluation by inflammatory score and analysis of interleukin expression using the ImageJ software. Results: The average age was 32.5 (SD: 5.42); 85% had persistent acne. According to the investigator's global assessment (IGA), both treatments resulted in significant clinical improvement (p<0.0001), with no difference between them. After treatment regardless of the group, there was a significant improvement in the total score and in all domains of the Acne-QoL-BR (p< 0.001). At the beginning of the study, no increase in serum interleukins was detected, except for IL-6 in obese women (p=0.0016) and in patients with an abdominal circumference above 88 cm (p=0.0022). Serum ILs did not change significantly after treatment, despite clinical improvement. Regarding histological evaluation, the injured skin showed an intense presence of inflammatory infiltrate in the dermis. There was intense immunoreactivity for IL-6 and IL-8 observed in the inflammatory infiltrates of the injured skin in relation to the peri-injury and post-treatment skin. Immunoreactivity for IL-17 did not show much difference in the intensity of its expression. There was intense immunoreactivity for IL-10 before and after treatments. Conclusions: There was an improvement in IGA with both treatments, demonstrating clinical efficacy.Acne-QoL-BR is useful for quantifying the impact of acne and should be used as an efficacy parameter in clinical trials. Serum interleukin levels do not increase in mild to moderate AMA. IL-6 is increased in obese women, probably due to obesity as a systemic inflammatory disease. There was hyperexpression of IL-6 and IL-8 in the area of skin with acne lesions and this expression was significantly reduced with both therapeutic options, with no statistical difference between them.
Background: In several countries, recent research has demonstrated an increase in the prevalence of acne in adult female acne (AFA), defined as acne that appears in women over 25 years of age. This disease brings some particularities and challenges, such as a greater impact on quality of life (QoL) and chronicity. Inflammation plays an essential role in the development of acne. The immunological aspects of acne are still incompletely understood, specially in AFA. Objectives: Clinical and laboratory evaluation of patients with AFA, QoL assessment, and to investigate possible correlations with metabolic syndrome. To analyze serum interleukins (IL) 6, 8, 10 and 17 and histological and immunohistochemical evaluation of these markers, before and after two different treatments in the AFA population. Methods: After approval by the Institutional Research Ethics Committee, signing of the Free and Informed Consent Form and Photography Authorization Form, a prospective, randomized therapeutic study was carried out, including 40 women, over the age of 25 years, with mild to moderate facial acne. They were randomized into two treatment groups: one -15% azelaic acid gel twice a day; two - spironolactone 100 mg/day, both for 6 months. Patients were clinically evaluated at monthly visits. At the beginning and end of treatments, they answered the acne quality of life questionnaire (Acne-QoL-BR); were photographed (Visia®); general exams were collected and to quantitatively analyze the ILs using the Cytometric Bead Array assay. They also performed 2 skin biopsies, with a 3 mm punch, in the submandibular region, one coinciding with an inflammatory lesion (biopsy 1) and another in the perilesional skin area (biopsy 2), clinically normal, and a third biopsy at the treated site (biopsy 3), after 6 months, close to the initial inflammatory lesion. The slides were digitalized and, using photomicrographs, submitted to evaluation by inflammatory score and analysis of interleukin expression using the ImageJ software. Results: The average age was 32.5 (SD: 5.42); 85% had persistent acne. According to the investigator's global assessment (IGA), both treatments resulted in significant clinical improvement (p<0.0001), with no difference between them. After treatment regardless of the group, there was a significant improvement in the total score and in all domains of the Acne-QoL-BR (p< 0.001). At the beginning of the study, no increase in serum interleukins was detected, except for IL-6 in obese women (p=0.0016) and in patients with an abdominal circumference above 88 cm (p=0.0022). Serum ILs did not change significantly after treatment, despite clinical improvement. Regarding histological evaluation, the injured skin showed an intense presence of inflammatory infiltrate in the dermis. There was intense immunoreactivity for IL-6 and IL-8 observed in the inflammatory infiltrates of the injured skin in relation to the peri-injury and post-treatment skin. Immunoreactivity for IL-17 did not show much difference in the intensity of its expression. There was intense immunoreactivity for IL-10 before and after treatments. Conclusions: There was an improvement in IGA with both treatments, demonstrating clinical efficacy.Acne-QoL-BR is useful for quantifying the impact of acne and should be used as an efficacy parameter in clinical trials. Serum interleukin levels do not increase in mild to moderate AMA. IL-6 is increased in obese women, probably due to obesity as a systemic inflammatory disease. There was hyperexpression of IL-6 and IL-8 in the area of skin with acne lesions and this expression was significantly reduced with both therapeutic options, with no statistical difference between them.
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Citação
BOMFIM, Diogo Pazzini. Papel das interleucinas na acne da mulher adulta associada ou não a fatores de risco para síndrome metabólica e modificação após tratamento: estudo clínico randomizado e comparativo. 2024. 138 f. Tese (Doutorado em Medicina Translacional) - Escola Paulista de Medicina, Universidade Federal de Paulo (UNIFESP), São Paulo, 2024.