Estudo clínico prospectivo, duplo cego, fatorial, randomizado, controlado por placebo, para avaliação dos efeitos do uso oral e/ou tópico do colágeno hidrolisado na dermatoporose: caracterização clínica, histológica e imunohistoquímica dos estágios iniciais da dermatoporose primária
Data
2020-01-30
Autores
Guadanhim, Lilia Ramos dos Santos [UNIFESP]
Orientadores
Bagatin, Ediléia [UNIFESP]
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: O termo Dermatoporose (DP) define a síndrome da insuficiência cutânea crônica, caracterizada por atrofia cutânea, púrpura senil, pseudocicatrizes estreladas, podendo haver lacerações e hematoma dissecante. Pode atingir mais de 50% da população acima de 80 anos. Ainda não há um tratamento considerado padrão ouro para a DP. Há indícios de que a suplementação oral com colágeno hidrolisado (CH) promova síntese de colágeno na pele. Até o momento não existem estudos sobre colágeno hidrolisado tópico, mas há potenciais benefícios para idosos com DP, uma vez que o esse componente está reduzido na pele atrófica. Objetivos: 1) Verificar os efeitos histológicos, imunohistoquímicos, em parâmetros viscoelásticos, ultrassonográficos, qualidade de vida e opinião do paciente e investigador, do CH tópico e/ou oral comparado ao placebo na dermatoporose, particularmente em relação ao tecido colágeno dérmico. 2) Caracterizar a DP primária, nos seus estágios iniciais, com relação aos aspectos clínicos, histológicos, imunohistoquímicos, parâmetros viscoelásticos, achados no ultrassom de alta frequência e qualidade de vida. Casuística e Métodos: 60 mulheres, ≥ 60 anos, com DP leve nos antebraços, sem queratoses actínicas, fototipos II e III. O estudo foi delineado em 2 etapas: 1) Estudo clínico de intervenção terapêutica, randomizado, fatorial, duplo-cego e placebo controlado para verificar os efeitos do CH tópico e/ou oral comparado ao placebo na dermatoporose. As pacientes receberam CH oral 5g/dia ou placebo, além de tópicos contendo placebo ou CH tópico, em serum 2,5% para uso 1x/dia por 6 meses nos antebraços. 2) Estudo transversal diagnóstico; Ambas as fases incluíram as mesmas pacientes. Resultados: Foram incluídas 56 mulheres, idades entre 60 e 93 anos, com DP estágio I, com atrofia cutânea, púrpura senil e pseudocicatrizes estreladas. Não houve efeito dos tratamentos tópico ou oral, nem da interação entre eles na espessura da epiderme viável e total e na marcação por Picrosirius red, colágeno I e elastina. Nos períodos observados, não houve diferença entre os tratamentos orais com relação aos parâmetros viscoelásticos e os aspectos ultrassonográficos não tiveram aumento acima de 10%. Os tratamentos não diferiram quanto à percepção de melhora e nem quanto ao impacto na qualidade de vida. A análise dos resultados da avaliação cega pelo investigador e dois observadores independentes através de fotografias mostrou baixa concordância entre os escores. A média da espessura da epiderme total foi de 87 ±36,06μm e da epiderme viável foi de 49 ±20,98 μm. Na análise quantitativa da pele dos antebraços, a marcação para picrosirius red, colágeno I e elastina foi de 45,24±8,30, 40,87±12,02 e 19,17±14,49 respectivamente. Os parâmetros viscoelásticos observados foram, na média, R2=0,62±0,10, R5=0,70±1,02, R5=0,84±3,19, R7=0,36±0,09. Os parâmetros ultrassonográficos evidenciaram espessura da derme superior de 0,55±0,09mm e da derme total de 1,15±0,19mm, ecogenicidade da derme superior de 57±15,64% e da derme total de 64,5±11,76% e intensidade de pixels na derme superior em 39±11,71% e da derme total de 47±10,54%. O impacto da DP na qualidade de vida das pacientes foi baixo segundo DLQI. Conclusões: A suplementação com peptídeos bioativos de colágeno não teve efeito nas avaliações histológica e imuno-histoquímica. Não foram observados benefícios do CH oral e/ou tópico nas medidas da elasticidade da pele, na densidade e ecogenicidade dérmicas. Na opinião das participantes houve melhora nos sinais clínicos, sem diferenças entre grupos. As avaliações clínicas não mostraram diferença entre os grupos. O impacto da dermatoporose, em estágio inicial, na qualidade de vida não se modificou com os tratamentos. A dermatoporose primária num estágio inicial foi caracterizada pela presença de atrofia cutânea de intensidade variável, púrpura senil e pseudocicatrizes estreladas.
Introduction: The term Dermatoporosis (DP) defines the chronic cutaneous insufficiency syndrome, characterized by cutaneous atrophy, senile purpura, stellate pseudo scars, with or without lacerations and dissecting hematoma. It can reach over 50% of the population over 80 years. There is no treatment considered gold standard for DP. There is evidence that oral supplementation with hydrolyzed collagen (CH) promotes collagen synthesis in the skin. To date, there are no studies on topical hydrolyzed collagen, but there are potential benefits for elderly people with DP as this component is reduced in atrophic skin. Objectives: 1) To verify the histological and immunohistochemical effects; viscoelastic and ultrasound parameters; quality of life and opinion of the patient and investigator of topical and / or oral CH compared with placebo in dermatoporosis, particularly in relation to dermal collagen tissue. 2) To characterize primary DP in its early stages, regarding clinical, histological, immunohistochemical, viscoelastic parameters, high frequency ultrasound findings and quality of life. Patients and Methods: 60 women, ³ 60 years old, with mild forearm DP, without actinic keratoses, phototypes II to VI. The study was designed in 2 stages: 1) Randomized, double-blind, factorial, placebo-controlled clinical intervention study to verify the effects of topical and / or oral CH compared with placebo on dermatoporosis. Patients received oral CH 5g / day or placebo, plus topics containing placebo or topical CH, in 2.5% serum for 1x / day use for 6 months on the forearms. 2) Cross-sectional diagnostic study; Both phases included the same patients. Results: 56 women, aged 60 to 93 years, with stage I DP, with cutaneous atrophy, senile purpura and stellate pseudoscars were included. The clinical study on the influence of CH showed that there was no effect of topical or oral treatments, nor of the interaction between them on the viable and total epidermis thickness and Picrosirius red, collagen I and elastin marking. During the observation period, there was no difference between oral treatments regarding viscoelastic parameters and the ultrasound aspects did not increase more than 10%.The treatments did not differ in terms of perceived improvement or impact on quality of life. Analysis by the investigator and two independent observers through photographs showed poor agreement between the scores. The average thickness of the total epidermis was 87±36,06µm and of the viable epidermis was 49 µm±20,98. In the quantitative analysis of the forearm skin, the marking for picrosirius red, collagen I and elastin was 45.24±8.30, 40.87±12.02 and 19.17±14.49 respectively. The viscoelastic parameters observed were, on average, R2 = 0.62±0.10, R5 = 0.79±1.02, R5 = 0.84±3.19, R7 = 0.36±0.09. The ultrasound parameters showed upper dermis thickness of 0.55±0.09 mm and total dermis of 1.15±0.19mm, echogenicity of upper dermis of 57 ±15.64% and total dermis of 64.5±11.76% and pixel intensity in the upper dermis of 39±11.71% and the total dermis of 47±10.54%. The impact of DP on patients' quality of life was low according to DLQI. Conclusions: Bioactive collagen peptide supplementation had no effect in histological and immunohistochemical evaluations. No benefits of oral and /or topical CH were observed in the measurements of skin elasticity, dermal density and echogenicity. In the opinion of the participants there was improvement in clinical signs, without differences between groups. Clinical evaluations showed no difference between groups. The impact of early-stage dermatoporosis on quality of life did not change with treatments. Primary dermatoporosis at an early stage was characterized by the presence in variable intensity of cutaneous atrophy, senile purpura and stellate pseudoscars.
Introduction: The term Dermatoporosis (DP) defines the chronic cutaneous insufficiency syndrome, characterized by cutaneous atrophy, senile purpura, stellate pseudo scars, with or without lacerations and dissecting hematoma. It can reach over 50% of the population over 80 years. There is no treatment considered gold standard for DP. There is evidence that oral supplementation with hydrolyzed collagen (CH) promotes collagen synthesis in the skin. To date, there are no studies on topical hydrolyzed collagen, but there are potential benefits for elderly people with DP as this component is reduced in atrophic skin. Objectives: 1) To verify the histological and immunohistochemical effects; viscoelastic and ultrasound parameters; quality of life and opinion of the patient and investigator of topical and / or oral CH compared with placebo in dermatoporosis, particularly in relation to dermal collagen tissue. 2) To characterize primary DP in its early stages, regarding clinical, histological, immunohistochemical, viscoelastic parameters, high frequency ultrasound findings and quality of life. Patients and Methods: 60 women, ³ 60 years old, with mild forearm DP, without actinic keratoses, phototypes II to VI. The study was designed in 2 stages: 1) Randomized, double-blind, factorial, placebo-controlled clinical intervention study to verify the effects of topical and / or oral CH compared with placebo on dermatoporosis. Patients received oral CH 5g / day or placebo, plus topics containing placebo or topical CH, in 2.5% serum for 1x / day use for 6 months on the forearms. 2) Cross-sectional diagnostic study; Both phases included the same patients. Results: 56 women, aged 60 to 93 years, with stage I DP, with cutaneous atrophy, senile purpura and stellate pseudoscars were included. The clinical study on the influence of CH showed that there was no effect of topical or oral treatments, nor of the interaction between them on the viable and total epidermis thickness and Picrosirius red, collagen I and elastin marking. During the observation period, there was no difference between oral treatments regarding viscoelastic parameters and the ultrasound aspects did not increase more than 10%.The treatments did not differ in terms of perceived improvement or impact on quality of life. Analysis by the investigator and two independent observers through photographs showed poor agreement between the scores. The average thickness of the total epidermis was 87±36,06µm and of the viable epidermis was 49 µm±20,98. In the quantitative analysis of the forearm skin, the marking for picrosirius red, collagen I and elastin was 45.24±8.30, 40.87±12.02 and 19.17±14.49 respectively. The viscoelastic parameters observed were, on average, R2 = 0.62±0.10, R5 = 0.79±1.02, R5 = 0.84±3.19, R7 = 0.36±0.09. The ultrasound parameters showed upper dermis thickness of 0.55±0.09 mm and total dermis of 1.15±0.19mm, echogenicity of upper dermis of 57 ±15.64% and total dermis of 64.5±11.76% and pixel intensity in the upper dermis of 39±11.71% and the total dermis of 47±10.54%. The impact of DP on patients' quality of life was low according to DLQI. Conclusions: Bioactive collagen peptide supplementation had no effect in histological and immunohistochemical evaluations. No benefits of oral and /or topical CH were observed in the measurements of skin elasticity, dermal density and echogenicity. In the opinion of the participants there was improvement in clinical signs, without differences between groups. Clinical evaluations showed no difference between groups. The impact of early-stage dermatoporosis on quality of life did not change with treatments. Primary dermatoporosis at an early stage was characterized by the presence in variable intensity of cutaneous atrophy, senile purpura and stellate pseudoscars.