Contribuição para o conhecimento da acne da mulher adulta através de estudo clínico, laboratorial e de qualidade de vida, randomizado e comparativo
Data
2015-11-30
Autores
Rocha, Marco Alexandre Dias da 
Orientadores
Bagatin, Edileia
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Fundamentos: Estudos recentes têm demonstrado um aumento do número de casos de acne em mulheres adultas. Estas pacientes são predominantemente normoandrogênicas e exibem diferenças clínicas, quando comparadas ao grupo mais comumente acometido, os adolescentes. Os tecidos periféricos, neste caso as glândulas sebáceas, atuam convertendo precursores hormonais em substâncias mais potentes que estimulam o aumento da produção do sebo, deixando essas áreas mais propensas à colonização pelo Propionibacterium acnes (P. acnes). Receptores recentemente descobertos, conhecidos como Toll-like receptor 2 (TLR2), expressos em queratinócitos e células inflamatórias, desempenham um papel crucial no desencadeamento da resposta inflamatória na acne ao reconhecer fragmentos do P. acnes. Alguns estudos revelaram que os queratinócitos também exibem o receptor CD1d, conferindo a estas células a função de apresentação de antígenos lipídicos. A redução da atividade androgênica nas glândulas sebáceas através do uso de determinados contraceptivos orais ou a propriedade antibacteriana de certas medicações tópicas poderia contribuir para o controle do processo inflamatório imuno-mediado. Método: foi realizado um estudo de intervenção terapêutica, randomizado e comparativo, incluindo mulheres adultas, de 26 a 44 anos, apresentando acne, sem outras manifestações androgênicas, além de um grupo controle, pareado por idade, de mulheres sadias. As pacientes portadoras de acne (38) foram randomizadas em dois grupos de tratamento: 1) Grupo COC: 20 mulheres tratadas com um contraceptivo oral combinado (COC) contendo etinilestradiol 0,03 mg associado à drospirenona 3 mg, por 24 dias, durante 6 ciclos consecutivos; 2) Grupo AA: 18 mulheres que receberam tratamento tópico com ácido azeláico (AA) 15%, em gel, duas aplicações diárias, por 6 meses. A eficácia foi avaliada por contagem das lesões pelo pesquisador, avaliação fotográfica por dois dermatologistas independentes, questionário de qualidade de vida em acne (Acne-Qol), análise imuno-histoquímica da expressão dos receptores TLR2 e CD1d e pelas dosagens de hormônios androgênicos e de seu principal metabólito, o glicuronato de androsterona (ADT-G). A segurança foi verificada pelo relato e x ocorrência de eventos adversos clínicos. Os dados foram submetidos à análise estatística. Resultados e Conclusões: foram avaliadas as populações ITT e PP (COC, n=20 e 20; AA, n=18 e 14, respectivamente); a apresentação clínica foi característica, de intensidade leve a moderada e distribuição das lesões no terço inferior da face. Houve melhora clínica e da qualidade de vida com as duas opções de tratamento, sem diferença. As análises imuno-histoquímicas revelaram hiperexpressão do TLR2 na epiderme e na glândula sebácea das pacientes com acne, tanto na lesão quanto na região perilesional e sua expressão foi reduzida pelas duas opções terapêuticas. O receptor CD1d apresentou aumento de sua expressão somente na epiderme, tanto na lesão quanto na região perilesional, quando comparado ao grupo controle. As quantificações de dihidrotestosterona (DHT) e ADT-G, realizadas por cromatografia líquida, foram sensíveis em detectar diferenças entre os grupos controle e doença. Porém, somente a dosagem de ADT-G foi útil tanto em detectar esta diferença quanto no acompanhamento da evolução clínica, com redução de seus valores durante o uso do COC. As duas opções terapêuticas foram eficazes, seguras e com boa tolerabilidade para acne da mulher adulta.
Background: Recent studies have shown an increasing number of acne cases in adult women. These patients are predominantly normoandrogenic and show some clinical differences compared with the most commonly affected group, the adolescents. The peripheral tissues, in this case the sebaceous glands, act converting hormonal precursors into more potent substances which increase sebum production, turning these areas more prone to colonization by Propionibacterium acnes (P. acnes). Newly discovered receptors, known as Tolllike 2 (TLR2), expressed in keratinocytes and inflammatory cells play a crucial role in triggering the acne inflammatory response by recognizing P. acnes fragments. Some studies have revealed that keratinocytes also express the CD1d receptor; these molecules have been identified to present lipids. The reduction of androgenic activity in the sebaceous glands through the use of oral contraceptives or the antibacterial property of some topical medications helps the reduction of the immune-mediated inflammation. Method: We performed a therapeutic interventional, randomized and comparative study, including adult women with acne, 26-44 years old; without any other androgenic manifestation as well as a control group matched for age, composed by healthy women. The patients with acne (38) were randomized into two treatment groups: 1) COC Group: 20 women treated with a combined oral contraceptive (COC) containing ethinylestradiol 0.03 mg combined with drospirenone 3 mg, 24 days, during 6 consecutive cycles; 2) AA Group: 18 women who received topical treatment with azelaic acid (AA) 15% gel, twice daily application, for 6 months. Efficacy was assessed by counting the lesions by the researcher, photographic assessment by two independent dermatologists, questionnaire about quality of life in acne (Acne-QoL), immunohistochemical analysis of the expression of TLR2 and CD1d receptor, and the dosages of androgenic hormones and its major metabolite, androsterone glucuronide (ADT-G). Safety was been verified by the report and the observation of clinical adverse events. Data were statistically analyzed. Results and Conclusions: we analyzed the ITT and PP populations (COC, n = 20, 20; AA, n = 18 and 14, respectively); the clinical presentation was characteristic, with signs of mild to moderate intensity and the distribution of lesions in the lower face. There was clinical and quality of life improvement with both treatment options, with no difference. The immunohistochemical analysis revealed overexpression of TLR2 in the epidermis and sebaceous glands of acne patients, both in the lesion and in the perilesional region and its expression was reduced by the therapeutic options. The CD1d receptor showed an increase of its expression only in the epidermis, both in the lesion and in the perilesional region when compared with the control group. The quantification of dihydrotestosterone (DHT) and ADT-G, made by liquid chromatography, was sensitive to detect differences between the control and disease groups. However, only the dosage of ADT-G was useful both in detecting this difference and in monitoring the clinical course, with a reduction of its values with COC. The two treatment options were effective, safe and well tolerated by adult woman presenting acne.
Background: Recent studies have shown an increasing number of acne cases in adult women. These patients are predominantly normoandrogenic and show some clinical differences compared with the most commonly affected group, the adolescents. The peripheral tissues, in this case the sebaceous glands, act converting hormonal precursors into more potent substances which increase sebum production, turning these areas more prone to colonization by Propionibacterium acnes (P. acnes). Newly discovered receptors, known as Tolllike 2 (TLR2), expressed in keratinocytes and inflammatory cells play a crucial role in triggering the acne inflammatory response by recognizing P. acnes fragments. Some studies have revealed that keratinocytes also express the CD1d receptor; these molecules have been identified to present lipids. The reduction of androgenic activity in the sebaceous glands through the use of oral contraceptives or the antibacterial property of some topical medications helps the reduction of the immune-mediated inflammation. Method: We performed a therapeutic interventional, randomized and comparative study, including adult women with acne, 26-44 years old; without any other androgenic manifestation as well as a control group matched for age, composed by healthy women. The patients with acne (38) were randomized into two treatment groups: 1) COC Group: 20 women treated with a combined oral contraceptive (COC) containing ethinylestradiol 0.03 mg combined with drospirenone 3 mg, 24 days, during 6 consecutive cycles; 2) AA Group: 18 women who received topical treatment with azelaic acid (AA) 15% gel, twice daily application, for 6 months. Efficacy was assessed by counting the lesions by the researcher, photographic assessment by two independent dermatologists, questionnaire about quality of life in acne (Acne-QoL), immunohistochemical analysis of the expression of TLR2 and CD1d receptor, and the dosages of androgenic hormones and its major metabolite, androsterone glucuronide (ADT-G). Safety was been verified by the report and the observation of clinical adverse events. Data were statistically analyzed. Results and Conclusions: we analyzed the ITT and PP populations (COC, n = 20, 20; AA, n = 18 and 14, respectively); the clinical presentation was characteristic, with signs of mild to moderate intensity and the distribution of lesions in the lower face. There was clinical and quality of life improvement with both treatment options, with no difference. The immunohistochemical analysis revealed overexpression of TLR2 in the epidermis and sebaceous glands of acne patients, both in the lesion and in the perilesional region and its expression was reduced by the therapeutic options. The CD1d receptor showed an increase of its expression only in the epidermis, both in the lesion and in the perilesional region when compared with the control group. The quantification of dihydrotestosterone (DHT) and ADT-G, made by liquid chromatography, was sensitive to detect differences between the control and disease groups. However, only the dosage of ADT-G was useful both in detecting this difference and in monitoring the clinical course, with a reduction of its values with COC. The two treatment options were effective, safe and well tolerated by adult woman presenting acne.
Descrição
Citação
ROCHA, Marco Alexandre Dias da. Contribuição para o conhecimento da acne da mulher adulta através de estudo clínico, laboratorial e de qualidade de vida, randomizado e comparativo. 2015. 185 f. Tese (Doutorado em Medicina Translacional) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2015.