A influência da toxina botulínica A no aspecto final das cicatrizes resultantes de excisões de lesões tumorais benignas no dorso: um estudo clínico randomizado, duplo-cego e controlado
Data
2024-06-07
Autores
Medina, Rebecca Ignacio Subirá 
Orientadores
Bagatin, Ediléia
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Fundamentos: Conseguir o melhor resultado cosmético possível é sempre uma preocupação do paciente e do cirurgião ao realizar uma cirurgia eletiva para exérese de lesão cutânea. Muitos fatores podem influenciar a aparência final de uma cicatriz, incluindo características de cada paciente e a localização do corpo em que o procedimento é realizado, além de características intrínsecas ao procedimento. Os mecanismos de cicatrização ainda não são completamente compreendidos, e é impossível eliminar completamente as cicatrizes. Por esse motivo, os esforços são direcionados para obter o melhor resultado estético e funcional possível. Para isso, diversas medidas são adotadas pelo médico no intraoperatório ou no pós-cirúrgico. Partindo da diversidade de fatores que podem ser modulados ao longo do processo cicatricial, diversos tratamentos foram propostos para prevenir ou tratar as cicatrizes disfuncionais ou inestéticas. Um destes tratamentos, que foi inicialmente discutido dentro do contexto da cicatrização de feridas no ano 2000, é a toxina botulínica tipo A. Estudos mais recentes exploram o papel da toxina na modulação de diferentes vias inflamatórias da pele, com possível repercussão no aspecto final das cicatrizes. Dentre as principais vias inflamatórias envolvidas no processo de reparo de feridas, o inflamassoma NLRP3 destaca-se por ser um complexo recentemente descrito e de grande relevância clínica, já que sua participação na fisiopatologia de diversas doenças tem sido demonstrada. Objetivos: Avaliar o impacto da toxina botulínica tipo A no resultado estético de cicatrizes resultantes de exéreses de lesões de pele no dorso, bem como avaliar o impacto da toxina botulínica tipo A na expressão do NLRP3 na pele. Métodos: Estudo clínico de intervenção terapêutica, prospectivo, randomizado, duplo cego e controlado. Foram incluídos no estudo 25 participantes, com idades entre 22 e 60 anos, fototipo de Fitzpatrick II a IV, com lesões de pele benignas no dorso (cistos infundibulares e nevos melanocíticos). Todos os participantes foram randomizados de forma cega para o grupo Tratamento (T) ou Controle (C). No primeiro dia de estudo (D0), todos os participantes foram submetidos à cirurgia de exérese fusiforme da lesão no dorso e à intervenção experimental (logo após a exérese cirúrgica). No momento da intervenção, toda a cicatriz foi tratada, com o grupo de tratamento (grupo T) recebendo toxina abobotulínica tipo A (BoNTA) (Dysport, Galderma) e o grupo controle (grupo C) recebendo injeções de solução de NaCl 0,9%, em volumes equivalentes, ambos no plano intradérmico. A dose aplicada foi de 3 unidades internacionais de BoNTA a cada 1cm da ferida operatória, em ambos os lados da linha de sutura - ou o volume equivalente de solução controle. Após um período que variou de 6 a 15 dias depois da cirurgia, todos os participantes foram submetidos à biópsia incisional com punch de 3 mm no ponto central de suas cicatrizes. Todos os participantes foram reavaliados após 6 meses da cirurgia (D180), quando foram avaliados clinicamente através da Escala de Avaliação Cicatricial do Paciente e do Observador (POSAS). A partir dos fragmentos de biópsia obtidos, foram realizadas avaliações de escore inflamatório, Picrosirius e imunohistoquímica com os marcadores NLRP3 e Alfa-SMA. Resultados: Na subescala de avaliação do observador (OSAS) não se verificaram diferenças de médias entre os grupos para nenhum dos seis itens avaliados, escore geral (p=0,145) ou escore "Opinião geral" (p=0,551). Na subescala de avaliação do paciente (PSAS), verificou-se diferenças de médias no item "Coceira na cicatriz" (p=0,018), favorecendo o grupo Tratamento. Entretanto, não se verificaram diferenças de médias do escore geral (p=0,263) e escore opinião geral (p=0,240). Não se verificaram diferenças de médias de largura do fuso cirúrgico (p=0,642), largura da cicatriz em D180 (p=0,572) ou variação relativa da largura da cicatriz em D180 em relação ao do fuso cirúrgico (p=0,123), entre os grupos controle e tratamento. Não se verificaram diferenças significativas no escore inflamatório (p=0,559), tampouco na densitometria vermelha (p=0,544) e densitometria verde (p=0,160) ao exame de Picrosirius red, na expressão tecidual de α-SMA (p=0,325) ou de NLRP3 na epiderme (p=0,571) e na derme (p=0,249), entre os grupos. Conclusão: Após a exérese de lesões de pele benignas no dorso, o tratamento intradérmico com toxina botulínica tipo A não impactou significativamente o resultado estético das cicatrizes, a proporção do infiltrado inflamatório, a remodelação do colágeno dérmico, a expressão de NLRP3 ou a expressão de alfa-SMA.
Introduction: Achieving the best possible cosmetic result is always a concern for the patient and the surgeon when performing elective surgery to excise a skin lesion. Many factors can influence the final appearance of a scar, including characteristics of each patient and the location of the body where the procedure is performed, in addition to characteristics intrinsic to the procedure. The mechanisms of scarring are not yet completely understood, and it is impossible to completely eliminate scars. For this reason, efforts are directed towards obtaining the best aesthetic and functional result. To achieve this, several measures are adopted by the doctor intraoperatively or post-surgery. Based on the diversity of factors that can be modulated throughout the healing process, several treatments have been proposed to prevent or treat dysfunctional or unsightly scars. One of these treatments, which was initially discussed within the context of wound healing in 2000, is botulinum toxin type A. More recent studies explore the role of the toxin in modulating different inflammatory pathways in the skin, with possible repercussions on the final appearance of scars. Among the main inflammatory pathways involved in the wound repair process, the NLRP3 inflammasome stands out for being a recently described complex of great clinical relevance, as its participation in the pathophysiology of several diseases has been demonstrated. Objectives: To evaluate the impact of botulinum toxin type A on the aesthetic result of scars resulting from excision of skin lesions on the back, as well as to evaluate the impact of botulinum toxin type A on the expression of NLRP3 in the skin. Methods: Prospective, randomized, double-blind, controlled clinical study of therapeutic intervention. 25 participants were included in the study, aged between 22 and 60 years, Fitzpatrick phototype II to IV, with benign skin lesions (infundibular cysts and melanocytic nevi) on the back. All participants were blindly randomized to the Treatment (T) or Control (C) group. On the first day of the study (D0), all participants underwent fusiform surgical excision of the lesion on their back and the experimental intervention (immediately after surgical excision). At the time of intervention, the entire scar was treated, with the treatment group (group T) receiving abobotulinum toxin type A (BTA) (Dysport, Galderma) and the control group (group C) receiving injections of 0.9% NaCl solution, in equivalent volumes, both in the intradermal plane. The dose applied was 3 international units of BoNTA for every 1cm of the surgical wound, on both sides of the suture line - or the equivalent volume of control solution. After a period ranging from 6 to 15 days after surgery, all participants underwent incisional biopsy with a 3 mm punch at the central point of their scars. All participants were reassessed 6 months after surgery (D180), when they were clinically evaluated using the POSAS scar assessment scale. From the biopsy fragments obtained, inflammatory score, picrosirius and immunohistochemistry assessments were carried out with the markers NLRP3 and α-SMA. Results: In the observer assessment subscale (OSAS), there were no differences in means between the groups for any of the six items assessed, general score (p=0.145) or "General opinion" score (p=0.551). In the patient subscale (PSAS), there were differences in means in the item "Itching of the scar" (p=0.018), favoring the Treatment group. However, there were no differences in the averages of the general score (p=0.263) and general opinion score (p=0.240). There were no differences in the mean width of the surgical spindle (p=0.642), width of the scar at D180 (p=0.572) or relative variation in the width of the scar at D180 in relation to that of the surgical spindle (p=0.123), between the control and treatment groups. There were no significant differences in the inflammatory score (p=0.559), nor in the red densitometry (p=0.544) and green densitometry (p=0.160) in the Picrosirius red test, in the tissue expression of α-SMA (p=0.325) or of NLRP3 in the epidermis (p=0.571) and in the dermis (p=0.249), between the groups. Conclusion: After excision of benign skin lesions on the back, intradermal treatment with botulinum toxin type A did not significantly impact the aesthetic outcome of the scars, the proportion of inflammatory infiltrate, the remodeling of dermal collagen, the expression of NLRP3 or the expression of alpha- SMA.
Introduction: Achieving the best possible cosmetic result is always a concern for the patient and the surgeon when performing elective surgery to excise a skin lesion. Many factors can influence the final appearance of a scar, including characteristics of each patient and the location of the body where the procedure is performed, in addition to characteristics intrinsic to the procedure. The mechanisms of scarring are not yet completely understood, and it is impossible to completely eliminate scars. For this reason, efforts are directed towards obtaining the best aesthetic and functional result. To achieve this, several measures are adopted by the doctor intraoperatively or post-surgery. Based on the diversity of factors that can be modulated throughout the healing process, several treatments have been proposed to prevent or treat dysfunctional or unsightly scars. One of these treatments, which was initially discussed within the context of wound healing in 2000, is botulinum toxin type A. More recent studies explore the role of the toxin in modulating different inflammatory pathways in the skin, with possible repercussions on the final appearance of scars. Among the main inflammatory pathways involved in the wound repair process, the NLRP3 inflammasome stands out for being a recently described complex of great clinical relevance, as its participation in the pathophysiology of several diseases has been demonstrated. Objectives: To evaluate the impact of botulinum toxin type A on the aesthetic result of scars resulting from excision of skin lesions on the back, as well as to evaluate the impact of botulinum toxin type A on the expression of NLRP3 in the skin. Methods: Prospective, randomized, double-blind, controlled clinical study of therapeutic intervention. 25 participants were included in the study, aged between 22 and 60 years, Fitzpatrick phototype II to IV, with benign skin lesions (infundibular cysts and melanocytic nevi) on the back. All participants were blindly randomized to the Treatment (T) or Control (C) group. On the first day of the study (D0), all participants underwent fusiform surgical excision of the lesion on their back and the experimental intervention (immediately after surgical excision). At the time of intervention, the entire scar was treated, with the treatment group (group T) receiving abobotulinum toxin type A (BTA) (Dysport, Galderma) and the control group (group C) receiving injections of 0.9% NaCl solution, in equivalent volumes, both in the intradermal plane. The dose applied was 3 international units of BoNTA for every 1cm of the surgical wound, on both sides of the suture line - or the equivalent volume of control solution. After a period ranging from 6 to 15 days after surgery, all participants underwent incisional biopsy with a 3 mm punch at the central point of their scars. All participants were reassessed 6 months after surgery (D180), when they were clinically evaluated using the POSAS scar assessment scale. From the biopsy fragments obtained, inflammatory score, picrosirius and immunohistochemistry assessments were carried out with the markers NLRP3 and α-SMA. Results: In the observer assessment subscale (OSAS), there were no differences in means between the groups for any of the six items assessed, general score (p=0.145) or "General opinion" score (p=0.551). In the patient subscale (PSAS), there were differences in means in the item "Itching of the scar" (p=0.018), favoring the Treatment group. However, there were no differences in the averages of the general score (p=0.263) and general opinion score (p=0.240). There were no differences in the mean width of the surgical spindle (p=0.642), width of the scar at D180 (p=0.572) or relative variation in the width of the scar at D180 in relation to that of the surgical spindle (p=0.123), between the control and treatment groups. There were no significant differences in the inflammatory score (p=0.559), nor in the red densitometry (p=0.544) and green densitometry (p=0.160) in the Picrosirius red test, in the tissue expression of α-SMA (p=0.325) or of NLRP3 in the epidermis (p=0.571) and in the dermis (p=0.249), between the groups. Conclusion: After excision of benign skin lesions on the back, intradermal treatment with botulinum toxin type A did not significantly impact the aesthetic outcome of the scars, the proportion of inflammatory infiltrate, the remodeling of dermal collagen, the expression of NLRP3 or the expression of alpha- SMA.
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Citação
MEDINA, Rebecca Ignacio. Subirá A influência da toxina botulínica a no aspecto final das cicatrizes resultantes de excisões de lesões tumorais benignas no dorso: um estudo clínico randomizado, duplo-cego e controlado. 2024. 158 f. Tese (Doutorado em MedicinaTranslacional) – Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2024.