Acne vulgaris is a chronic inflammatory skin disorder, which affects the pilosebaceous units of the skin. Although this disease is normally self-limiting, it affects over 50 million Americans and results in lost productivity and treatment costs exceeding 1.2 billion dollars annually.1 While the exact cause of acne is unknown, its pathogenesis is classified into four factors: increased sebum production, abnormal keratinization, hypercolonization by Propionibacterium acnes, and inflammation.2 Despite numerous treatment options, increasing resistance to antibiotics3 and significant side effect profiles of many other therapeutics has created a need for safer, gentler treatment options. There has been renewed interest in the gut-skin-brain axis theory and the therapeutic role of oral probiotics, as new evidence suggests that gut dysbiosis plays an important role in mediating cutaneous skin inflammation and acne lesions.2 Specifically, strains of Lactobacillus acidophilus and Bifidobacterium bifidum, two strains commonly found in probiotics, have been found to decrease gut permeability and reduce systemic inflammation associated with acne.4 Additionally, in small clinical trials, these strains decreased acne severity and had an supplemental effect on clinical efficacy when used with oral antibiotics.5 Despite these promising results, the lack of large randomized controlled trials with standardized outcome measurements has prevented the adoption of oral probiotics as a viable treatment option by domestic and international dermatological societies. Therefore, this study proposes a randomized control trial to determine whether the adjunctive use of oral probiotics with antibiotics significantly reduces acne severity compared to oral antibiotics alone. We hypothesize that there will be a statistically significant decrease in acne severity scores among those receiving oral probiotics and antibiotics compared to those receiving only antibiotics among adolescents between the ages of 12-24 with moderate to severe acne. We hope that these study results will help provide evidence to incorporate oral probiotics into practice as a safe and efficacious treatment option to those suffering from moderate to severe acne, while advancing our understanding of how mediating gut microbiota can improve acne outcomes.

This randomized clinical study aimed to compare the efficacy of written handouts with that of audio-visual computerized presentations in educating adolescents about acne vulgaris. The study included 101 adolescent patients, aged 13 to 17 years, presenting to a private dermatology practice or one of three pediatric clinics in New Haven, CT. All participants completed a brief enrollment questionnaire to gauge baseline knowledge about acne vulgaris. Subjects were then randomized to receive either a written handout or an audio-visual computerized presentation. Immediately following the intervention, and again at one month, patients were asked to complete identical questionnaires to assess change in knowledge about acne. The main outcome measure was change in knowledge about acne vulgaris, as indicated by performance on pre-intervention, post-intervention, and one-month follow-up questionnaires. Baseline questionnaires were completed by 21 patients in the pilot study and 80 subjects in the revised study; 17 (80.95%) and 77 (96.25%) completed the respective studies. In both the pilot and revised studies, there was no significant difference between intervention groups in terms of baseline knowledge or gain-in-knowledge. Immediately post- intervention, both groups showed significant improvement from baseline (P<.0001 revised study, P<.01 pilot study). At the one-month follow-up, patients in the pilot study randomized to receive the computerized presentation still showed significant gain in knowledge from baseline (p<.05), while those in the handout group did not. Meanwhile, both intervention groups in the revised study continued to show significant gain in knowledge from baseline at one month (p<.0001). From the above results it appears that both written handouts and audio-visual computerized presentations about acne vulgaris confer significant and equivalent benefits in terms of short- and long-term knowledge gains among adolescent patients with acne.

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M.Tech. (Homoeopathy) / Acne vulgaris is a common skin condition, affecting mostly adolescents. This study attempts to demonstrate the effect of the homoeopathically prepared remedy Testis compositum in the treatment of acne vulgaris. Thirty participants were selected for the study, but only 28 completed the study. The study was conducted over a period of 8 weeks. All the participants formed the control group during the first two weeks of the study, and then formed the experimental group for the next six weeks. During the control period, the participants received placebo medication. At the start of the control period, and at two week intervals through the duration of the study, the participants were assessed by counting the acne lesions – only facial Acne vulgaris was assessed during the trial. At the start of the control period, the start of the experimental period, and after completion of all treatment, frontal and bilateral facial photographs were taken to enable visualisation of the changes that occurred during the study. The results were statistically analysed using the t-test, the Wilcoxon test and descriptive statistics. The results show that treatment with Testis compositum had a significant effect in improving acne vulgaris.

Orientador: Juliano Vilaverde Schmitt / Resumo: Fundamentos: Apesar da isotretinoína oral ser um tratamento eficaz para casos graves e persistentes de acne, existe significativa preocupação e controvérsia sobre seus efeitos adversos psicológicos. Por outro lado, a acne apresenta significativo impacto psicossocial nos portadores. Objetivos: Avaliar adolescentes e adultos jovens sob tratamento com isotretinoína oral para acne moderada a grave quanto a sintomas depressivos e suas relações com variáveis demográficas e clínicas. Métodos: Estudo tipo coorte com portadores de acne tratados com isotretinoína oral. Foram avaliados Cardiff Acne Disability Index (CADI), escala de depressão de Beck (EDB), gravidade da acne e cicatrizes e escore de efeitos adversos mucocutâneos (EEAM). Resultados: Foram incluídos 42 pacientes, 43% do sexo feminino, com idade mediana de 18 [1q-3q:16-21], seguidos por um período de 9 [6-9] meses. EDB passou de 7,5 [2-16] pré-tratamento para 1 [0-5] ao final do seguimento (p<0,01), sendo que 43% apresentavam pontuação para depressão leve ou superior pré-tratamento, contra 14% ao final do seguimento (RP=0,33 (IC 95%: 0,15 a 0,76); p<0,01). EDB pré-tratamento associou-se à presença de antecedentes psiquiátricos, menor renda familiar e maior CADI (p<0,05), enquanto durante o tratamento associou-se à maior duração prévia da acne, a maiores EEAM, à menor dose acumulada e a maiores EDB iniciais (p<0,05). Limitações: Perdas de seguimento, não apresentar grupos controle, monocêntrico. Conclusões: Há melhora nos e... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: Despite the effectiveness of oral isotretinoin for severe and persistent acne, there is concern and controversy about its possible psychological adverse effects. On the other hand, acne causes significant psychosocial impact on patients. Objective: Assess treatment with oral isotretinoin for moderate to severe acne in adolescents and young adults regarding depressive symptoms and their relationships with demographic and clinical variables. Methods: Cohort study with patients with acne under treatment with oral isotretinoin. Four aspects were considered: Cardiff Acne Disability Index (CADI), Beck Depression Inventory (BDI), acne and scars severity and Mucocutaneous Adverse Effects Score (MAES). Results: Forty-two participants were included, 43% were female, median age 18 years old [1q-3q:16-21], followed up for 9 [6-9] months. The BDI went from 7.5 [2- 16] before the treatment to 1 [0-5] after the follow up (p<0.01). 43% had score for mild depression or worse before treatment – the number dropped to 14% in the end of the study (RP=0.33 (IC 95%: 0.15 to 0.76); p<0.01). The BDI before treatment correlates to psychiatric history, lower family income and higher CADI (p<0.05), while during the treatment it correlates to the duration of acne, higher MAES, lower cumulative dose and higher initial BDI (p<0.05). Study Limitations: Loss of follow-up, lack of a control group, monocentric. Conclusion: There is improvement on the depression scores when acne vulgaris is treated ... (Complete abstract click electronic access below) / Mestre

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 5 uppsatser.

Acne Vulgaris is a common dermatological condition defined as a chronic inflammatory dermatosis of the pilosebaceous unit that affects more than 17 million Americans.^1 Although it is not considered a dangerous condition, it may drastically impair quality of life and leave a substantial psychological impact.^2 Acne’s multifactorial pathogenesis is typically categorized into four aspects: increased sebum production, altered keratinization, inflammation, and bacterial colonization.^3 Dietary factors contribution to the pathogenesis of acne has remained controversial throughout the literature. However, currently there exists a greater understanding between how diet may influence endocrine factors contributing to acne pathogenesis.^4 Additionally, recent published evidence and public paradigm shifts highlighting the relationship between diet and health have caused a resurgence of this topic, particularly among patients seeking a more gentle, alternate solution to current treatments. Some of the most promising recent correlating evidence supports an association between acne prevalence and dairy consumption, particularly skim milk consumption.^5 It is hypothesized that milk consumption affects the presence of both reproductive, non-reproductive hormones, and growth factors in our body, which may contribute to increased acne prevalence.^6 However, there has been a lack of randomized controlled trials to determine the cause and effects nature of this relationship, as all previous studies are observational.^1 Therefore, this study will conduct a randomized controlled trial to determine the significance between dietary non-fermented dairy consumption and acne prevalence in adolescents. We hypothesize the adaptation of a diet of decreased dairy consumption will decrease the prevalence or severity of acne vulgaris in adolescents between the ages of 13-18. It is our hope that the conclusion of this study will advance our understanding of the dietary correlation between dairy and acne vulgaris in order to provide further insight to guide medical practitioners’ ability to help treat this distressing condition.

Objectives: In this pilot study, our intention was to ascertain what formulation of a carbohydrate-derived fulvic acid (CHD-FA) topical applicator was optimal for patients to use during a larger study where the efficacy of fulvic acid (CHD-FA) in treating moderate acne vulgaris will be investigated. Methods: 15 individuals with inflammatory acne with an acne grade of III or lower were asked to volunteer for the study. They were split into 3 groups. Each group was asked to use a different formulation (a cream base, gel base and wet applicator formulation) each week. After each week, the individuals returned to fill out a questionnaire evaluating the formulation they used that week. They were also examined by the clinician for any possible side effects, and given the next formulation to use for the following week. The trial was 3 weeks long, and after using all 3 formulations the individuals were asked to fill out a final questionnaire evaluating all 3 formulations. The clinician was also asked to fill out a questionnaire giving his/her opinion on the formulations. Results: The results did not give conclusive evidence of one particular formulation being favored above all the others. All the formulations performed more or less equally as well. According to the final questionnaire, 6 out of the 15 individuals were most satisfied with the wet applicator, 4 out of 15 preferred the cream base and 5 out of 15 preferred the gel base. 5 out of 15 individuals were least satisfied with the wet applicator, 3 out of 15 with the cream base, and 7 out of 15 were least satisfied with the gel. While there was no conclusive indication for one particular formulation, there were some common complaints or observations by individuals about each formulation. Most individuals said the wet applicator had an initial burning sensation to the skin upon application, but it disappeared a few seconds after application. Many individuals said they felt the cream base was oily and made the skin appear oily after application. The gel base was said to smell the worst, along with the wet applicator, while the cream smelt the least. A few individuals complained that the gel left a residue on the skin. Conclusion: While the study did not give a clear indication of one particular formulation that was preferred by individuals, it did produce interesting results that can be used to make some of the formulations more favourable. In the main trial, further investigation will be done to optimize the formulation. / Dissertation (MSc)--University of Pretoria, 2010. / Pharmacology / unrestricted

Acne vulgaris is an extremely common disease, affecting large numbers of adolescents and adults, with substantial physical and psychosocial impacts. Antibiotics have been used for many years in the anti-microbial and anti-inflammatory treatment of acne, and have generated reasonable success rates. In recent years, along with a growing popularity of oral contraceptives to reduce unwanted pregnancies, they have also been applied in acne treatment because of their overall anti-androgenic effects. Very little direct comparisons between these two methods have been published, and this study serves as a preliminary measure for the effectiveness of both treatments against each other. Using an extensive literature search of PUBMED and MEDLINE for randomized clinical trials involving antibiotics or oral contraceptives, data were taken and used in an analysis to assess efficiency of both drug groups in the reduction of lesion counts and percentage reduction in inflammatory acne lesions, non-inflammatory lesions, and total lesions based off original baseline counts in each study. A total of 15 studies were used in the analysis. Antibiotics, oral contraceptives, and placebo treatment groups were evaluated at three months’ time, while oral contraceptives and placebo treatments were also continued out to six months to reflect longer trial durations. In all cases, antibiotics were superior to placebo at three months. Oral contraceptives were also superior to all placebo arms at both three and six months, except for in the average percent reduction of total lesions where the placebo at six months is not significantly different than the contraceptives at three months. Antibiotics and contraceptives showed no significant difference between each other at three or six months times, except for the lesion number reduction at three months for inflammatory lesions compared to antibiotics. All comparisons used the average percentage or number reduction, and 95% confidence intervals to determine significance. After three months, antibiotics showed a 45.40% weighted mean reduction in total lesion counts, compared to 36.41% for oral contraceptives at three months and 43.76% at six months. With the confidence intervals, the ranges for significance are 38.40%-52.40%, 31.92%-40.90%, and 33.87%-53.64% respectively, corresponding to an insignificant difference between all three treatments. Percentage changes for both inflammatory and non-inflammatory lesion reductions were also similar in their confidence intervals overlapping. The study showed a surprising similarity between antibiotics and contraceptives in their ability to treat acne, in both inflammatory and non-inflammatory lesions. With the exception of the three month antibiotics out-performing the oral contraceptives at three months’ time for reduction of inflammatory lesions, the percentage reduction was not significantly different, indicating discrepancies with starting numbers. Overall, both treatments were effective in the treatment of acne lesions, but the limitations of oral contraceptives including their utility is confined to women, and the relatively short recommended treatment time for oral antibiotics each have their drawbacks. Oral contraceptives seem to represent a better long term treatment plan for women who are comfortable taking birth control.

A administração oral de isotretinoína (IST) é eficaz no tratamento da acne; no entanto, seu uso está associado a efeitos adversos, como ressecamento da pele, epistaxe, distúrbios imunológicos e psiquiátricos, enquanto a eficácia da aplicação tópica é prejudicada pela intensa irritação causada na pele. Proteger a IST do contato direto com a pele e direcionar sua liberação para os folículos pilosos, local onde a acne se desenvolve, pode reduzir a irritação e aumentar a eficácia do tratamento. O polímero Delonix (DLX), galactomanano natural derivado da semente de Delonix regia, pode ser manipulado para produzir nanopartículas para a liberação direcionada de IST na pele. Desta forma, o objetivo deste estudo foi desenvolver nanopartículas poliméricas de DLX (IST-DLX) contendo IST e avaliar seu potencial para o tratamento tópico da acne. O DLX foi coletado, purificado e caracterizado quanto a composição de monossacarídeos e massa molecular (MM). Nanopartículas DLX sem IST (branco), nanopartículas fluorescentes de DLX (nanopartículas contendo BODIPY (BOD-DLX)) e nanopartículas IST-DLX foram preparadas e caracterizadas por tamanho, índice de polidispersividade (PdI), potencial zeta (pz) e eficiência de encapsulação (EE). O estudo de liberação in vitro das nanopartículas IST-DLX foi realizado utilizando células de difusão e membrana sintética, enquanto a penetração cutânea das nanopartículas BOD-DLX e IST-DLX foi avaliada por microscopia confocal e tape stripping diferencial em pele de orelha de porco dermatomizada, respectivamente. A influência das nanopartículas IST-DLX na modulação de IL-6, IL-10 e TNF-? foi avaliada in vitro utilizando células de macrófagos AMJ-2 estimuladas com lipopolisacarídeos (LPS) e a atividade antimicrobiana foi avaliada em meio de cultura de Propionibacterium acnes. In vivo, as nanopartículas IST-DLX foram avaliadas quanto a penetração e irritação cutânea em ratos Wistar (protocolo de aprovação CEUA-FCFRP nº 17.5.213.60.3). A MM do polímero DLX foi de ~177 kDa, contendo predominantemente manose e galactose na proporção de 6,3:1. O tamanho das nanopartículas IST-DLX, determinado por dispersão de luz, foi entre 215 a 232 nm, PdI < 0,2, pz < -30 mV e EE > 25%. As nanopartículas IST-DLX sustentaram a liberação da IST, com cerca de 37% de IST sendo liberado em 48 h. As imagens de microscopia confocal mostraram que as nanopartículas BOD-DLX concentraram-se na epiderme e nos folículos pilosos em comparação com a solução de BODIPY livre, a qual permeou até a derme. Foi observada uma penetração de IST significativamente maior e descontrolada em todas as camadas da pele de orelha de porco quando a solução de polímero de IST-DLX foi usada em comparação com um acúmulo de IST menor e controlado quando as nanopartículas IST-DLX foram aplicadas. As nanopartículas IST-DLX direcionaram a IST para os folículos pilosos (26%) em comparação com a solução de IST (6,5%) que permeou por todas as camadas da pele. As nanopartículas IST-DLX reduziram significativamente a produção de IL-6 em células de macrófagos estimuladas por LPS, mesmo após 48 h, em comparação com a solução de IST livre, que reduziu significativamente a produção de IL-6 apenas até 24 h. Tanto as nanopartículas ISTDLX quanto a solução de IST livre não inibiram o crescimento de P. acnes. Não foi observado nenhum sinal de eritema nos ratos tratados com nanopartículas IST-DLX, com ou sem irradiação UVA, enquanto os tratados com solução de IST apresentaram eritema. A espessura da epiderme dos ratos tratados com as nanopartículas foi significativamente menor do que daqueles tratados com IST livre, com ou sem irradiação UVA. Conclui-se que as nanopartículas IST-DLX direcionam e sustentam a liberação de IST na pele em concentrações ótimas, modulam a resposta inflamatória da IL-6 e previnem o eritema inflamatório relacionado ao IST in vivo. Sendo assim, o polímero DLX pode ser considerado um polímero promissor para a liberação sustentada e direcionada de fármacos. / Oral isotretinoin (IST) has been effective in acne treatment; however, its use is associated with side effects such as skin dryness, epistaxis, immune disorder and psychiatric concerns while its topical gel application\'s effectiveness is hampered by irritancy. Protecting IST from direct skin contact and targeting its release to the hair follicles where the acne develops can reduce irritation and increase the effectiveness of treatment. Delonix (DLX) polymer is a natural galactomannan derived from Delonix regia seed that may be engineered to yield nanoparticles for IST skin targeting. Therefore, the aim of this study was to develop IST-loaded DLX (IST-DLX) polymeric nanoparticles and assess its skin targeting prospects for acne treatment. DLX was collected, purified and characterized by monosaccharide composition and molecular weight (Mw). Blank DLX nanoparticles, fluorescent DLX nanoparticles (BODIPY-loaded (BOD-DLX) nanoparticles) and IST-DLX nanoparticles were prepared and characterized by size, polydispersibility index (PdI), zeta potential (zp) and encapsulation efficiency (EE). In vitro release study of IST-DLX nanoparticles was performed using diffusion cells and synthetic membrane, while skin targeting of BOD-DLX and IST-DLX nanoparticles were assessed by confocal microscopy and differential tape stripping technique in dermatomed pig ear skin respectively. IST-DLX polymeric nanoparticles\' IL-6, IL-10 and TNF-? modulation was assessed in vitro using lipopolysaccharide (LPS) stimulated AMJ-2 macrophage cells and antimicrobial activity was assessed in Propionibacterium acnes culture medium. IST-DLX nanoparticles\' skin penetration and irritation were evaluated in vivo in Wistar rats (ethics committee approval protocol CEUA-FCFRP nº 17.5.213.60.3). DLX polymer Mw was ~177 kDa, containing predominantly mannose and galactose in ratio 6.3:1. IST-DLX nanoparticles\' size determined by light scattering was between 215 to 232 nm, PdI < 0.2, zp < -30 mV, EE > 25 %. IST-DLX nanoparticles sustained IST release, with about 37% IST being released in 48 h. Confocal images showed that BOD-DLX nanoparticles accumulated in the epidermis and hair follicles as compared to free BODIPY solution which permeated into the dermis. Significantly higher and uncontrolled IST penetration into all layers of pig ear skin with IST-DLX polymer solution was observed as compared to lower, controlled but optimum IST accumulation into the pig ear skin when IST-DLX nanoparticles were used. IST-DLX nanoparticles targeted the hair follicle (26 %) as compared to IST solution (6.5 %) which permeated through all skin layers. IST-DLX polymeric nanoparticles significantly reduced IL-6 production in LPS stimulated macrophage cells at 48 h as compared to free IST solution which significantly reduced IL-6 production only at 24 h. Both IST-DLX nanoparticles and free IST solution did not inhibit P. acnes growth. No sign of inflammatory erythema was observed in IST-DLX nanoparticles treated Wistar rats with or without UVA irradiation as compared to free IST treated ones. Epidermal thickness of rats treated with IST-DLX nanoparticles was significantly smaller than those treated with free IST with or without UVA irradiation. It can be concluded that IST-DLX nanoparticles can target, deliver and sustain IST release to the skin at optimum concentrations, modulate IL-6 inflammatory responses and may prevent IST related inflammatory erythema in vivo. DLX polymer could be promising polymer for drug delivery.