Skin microbiome and acne vulgaris: Staphylococcus,a new actor in acne

Propionibacterium acnes (P. acnes), the sebaceous gland and follicular keratinocytes are considered the three actors involved in the development of acne. This exploratory study investigated the characteristics of the skin microbiota in subjects with acne and determined microbiota changes after 28 days of application of erythromycin 4% or a dermocosmetic. Skin microbiota were collected under axenic conditions from comedones, papulo‐pustular lesions and non‐lesional skin areas from subjects with mild to moderate acne according to the GEA grading using swabs. Samples were characterized using a high‐throughput sequencing approach that targets a portion of the bacterial 16S rRNA gene. Overall, microbiota samples from 26 subjects showed an overabundance of Proteobacteria and Firmicutes and an under‐representation of Actinobacteria. Staphylococci were more abundant on the surface of comedones, papules and pustules (P=.004 and P=.003 respectively) than on non‐lesional skin. Their proportions increased significantly with acne severity (P<.05 between GEA‐2 and GEA‐3). Propionibacteria represented less than 2% of the bacteria on the skin surface. At Day 28, only the number of Actinobacteria had decreased with erythromycin while the dermocosmetic decreased also the number of Staphylococci. A significant reduction (P<.05) from Day 0 of comedones, papules and pustules with no significant difference between the products was observed. The bacterial diversity on all sampling areas was similar. The dermocosmetic decreased the number of Actinobacteria and Staphylococcus spp. after 28 days. Staphylococcus remained the predominant genus of the superficial skin microbiota. No significant reduction in Staphylococcus spp. was observed with the topical antibiotic.     

Microorganisms inhabiting follicular contents of facial acne are not only Propionibacterium but also Malassezia spp.

To clarify the relationship between major cutaneous microorganisms (Propionibacterium, Staphylococcus and Malassezia spp.) and acne vulgaris (acne), we examined the microbiota quantitatively in the follicular contents of inflammatory acne and on the facial skin of patients with acne. Fifteen Japanese untreated acne outpatients were studied. The follicular contents from inflammatory acne lesions of the face were collected using a comedo extractor. The skin surface samples were obtained by the swab method from 10 cm² of facial skin. The microbiota was analyzed using polymerase chain reaction. The microbiota in follicular contents was similar to that on the skin surface, namely, there were large populations of Propionibacterium spp., Staphylococcus spp. and Malassezia spp. Moreover, the number of Malassezia spp. on the skin surface was correlated with that of inflammatory acne and that in follicular contents. This study clarified that there are large populations of Propionibacterium spp., Staphylococcus spp. and Malassezia spp. in follicular contents. These results suggest the possibility that not only Propionibacterium acnes but also other cutaneous resident microorganisms are related to acne. Particularly, we considered that Malassezia spp. is closely related.     

Molecular characterization of the skin fungal microbiome in patients with psoriasis

The skin surface is colonized by a wide variety of fungi and bacteria. While many of these organisms, including Malassezia, Candida, Streptococcus and Staphylococcus species, are associated with provocation and/or exacerbation of psoriasis, a detailed analysis of the cutaneous fungal microbiome in psoriatic patients has yet to be performed. To identify the disease‐specific fungal microbiota on psoriatic scale samples, fungal rRNA gene sequences from 12 psoriatic patients and 12 healthy controls were analyzed by pyrosequencing. A total of 317 806 high‐quality sequences were obtained, representing 142 genera. Malassezia species were the most abundant sequences in both populations (46.9 ± 14.0% in psoriasis vs 76.0 ± 14.6% for healthy controls). Principal coordinate analysis revealed that the fungal microbiomes were independent. Although an association between the cutaneous fungal microbiome and psoriasis has yet to be established, our data indicate that the microbiome in patients with psoriasis is independent of that in healthy controls.     

The potential of probiotics for treating acne vulgaris: A review of literature on acne and microbiota

Acne is known as a chronic inflammatory skin disease with sever adverse effects on quality of life in the patients. The increasing resistance to antibiotics has decreased their effectiveness in treating acne. As viable microbial dietary supplements, probiotics provide health benefits through fighting pathogens and maintaining the homeostasis of the gut and skin microbiome. The present article reviewed the potential of probiotics as beneficial microorganisms for treating acne vulgaris. This review of literature was conducted through a bibliographic search of popular databases, including Science Direct, PubMed, Scielo and Medline, using keywords such as probiotics, prebiotics, synbiotics, microbiome, and acne vulgaris to determine potential applications of these beneficial microbiomes in treating acne vulgaris. Acne lesions are associated with increases in proportion of Propionibacterium acnes as a skin commensal bacterium. The environmental studies showed inhibitory effects of probiotics on P. acnes, mediating by antibacterial proteins and bacteriocin‐like inhibitory substances, and their immunomodulatory effects onkeratinocytes and epithelial cells. Probiotics were also found to inhibit cytokine IL‐8 in epithelial cells and keratinocytes, suggesting immunomodulatory activities. Moreover, glycerol fermentation by Staphylococcus epidermidis was found to be a natural skin defense against acne and an overgrowth inhibitor of P. acnes. As an antimicrobial agent in lotions and cosmetic formulations, Lactococcus sp. can decrease the inflammatory mediators that are produced by P. acnes and cause vasodilation, edema, mast cell degranulation and TNF‐alpha release. Oral administration of probiotics was found to constitute an adjuvant therapy to conventional modalities for treating mild‐to‐moderate acne vulgaris.     

Efficacy and safety of silymarin containing antioxidant serum as an adjuvant treatment of mild-to-moderate acne vulgaris: A prospective,open-label pilot study

Background

Silymarin is the active component of milk thistle, which has antioxidant properties by scavenging free radicals and potential comedolytic properties.

Aims

This study aimed to assess the efficacy and safety of 0.5% silymarin-loaded antioxidant serum (SAS) used to treat mild-to-moderate acne.

Patients and Methods

A prospective, open-label pilot study was conducted. We enrolled 22 Korean acne patients who applied the 0.5% SAS on the whole face twice daily while continuing the current anti-acne medications. Grade of acne severity, individual lesion counts, sebum output levels, skin erythema, and melanin pigmentation were assessed.

Results

After a 4-week application, the modified Global Acne Grading Score (mGAGS), Global Evaluation Acne (GEA) scale, and the acne lesion counts were significantly decreased. Sebum secretion, skin pigmentation, and erythema were also reduced during the study period, yet only the melanin pigmentation index reached statistical significance. Subgroup analysis revealed that the patients who took the low-dose oral isotretinoin during the study period showed more noticeable improvements in skin sebum output and melanin pigmentation. Additionally, no adverse event was associated with using the 0.5% SAS.

Conclusion

The 0.5% silymarin-containing antioxidant formulation improved acne's clinical severity and related skin biophysical parameters.     

Characterization of a new acne vulgaris treatment device combining light and thermal treatment methods

Background/purpose: Conventional treatment methods for acne vulgaris have various side effects such as the development of bacterial resistance, phototoxicity, vertigo, gastro‐intestinal problems, and drug eruptions. To minimize such side effects, light and thermal methods have been alternately suggested. This study characterized a new acne vulgaris treatment device (AVTD) that combines both light and thermal methods and evaluated its clinical efficacy. Methods: We characterized the thermal and light properties of the AVTD itself and evaluated its thermal characteristics in ex vivo porcine skin samples. The Arrhenius equation was used to calculate the skin thermal injury coefficient to confirm the skin safety of the AVTD. Finally, the clinical efficacy of the AVDT was evaluated by analyzing cross‐polarization and erythema index images, which were obtained from 13 volunteers undergoing treatment with the AVTD. Results: The temperature of the AVTD itself was maintained at 49.1 °C on the tip and 39.7 °C in the porcine skin samples. The peak intensity of the light‐emitting diode (LED) light was observed at 468 nm. The skin safety of the AVTD was confirmed and 84.2% of the volunteers presented positive treatment results. Conclusion: The treatment of acne using the AVTD resulted in a high treatment rate in a clinical study, minimizing side effects. On the basis of these results, we can be sure that the AVTD may be effectively used for the treatment of acne vulgaris.     

Comparative study of the bactericidal effects of indocyanine green‐ and methyl aminolevulinate‐based photodynamic therapy on Propionibacterium acnes as a new treatment for acne

Acne vulgaris is one of the most common dermatological problems, and its therapeutic options include topical and systemic retinoids and antibiotics. However, increase in problems associated with acne treatment, such as side‐effects from conventional agents and bacterial resistance to antibiotics, has led to greater use of photodynamic therapy. The purpose of this study was to compare the bactericidal effects of indocyanine green‐ and methyl aminolevulinate‐based photodynamic therapy on Propionibacterium acnes. P. acnes were cultured under anaerobic conditions; then they were divided into three groups (control, treated with indocyanine green and treated with methyl aminolevulinate) and illuminated with different lights (630‐nm light‐emitting diode, 805‐nm diode laser and 830‐nm light‐emitting diode). The bactericidal effects were evaluated by comparing each group's colony‐forming units. The cultured P. acnes were killed with an 805‐nm diode laser and 830‐nm light‐emitting diode in the indocyanine green group. No bactericidal effects of methyl aminolevulinate‐based photodynamic therapy were identified. The clinical efficacy of indocyanine green‐based photodynamic therapy in 21 patients was retrospectively analyzed. The Korean Acne Grading System was used to evaluate treatment efficacy, which was significantly decreased after treatment. The difference in the efficacy of the 805‐nm diode laser and 830‐nm light‐emitting diode was not statistically significant. Although the methyl aminolevulinate‐based photodynamic therapy showed no bactericidal effect, the indocyanine green‐based photodynamic therapy has bactericidal effect and clinical efficacy.     

Topical methyl aminolaevulinate photodynamic therapy for treatment of facial acne vulgaris: results of a randomized, controlled study

BACKGROUND: There is a need for alternative treatments for moderate to severe acne vulgaris. Preliminary experience suggests that topical methyl aminolaevulinate photodynamic therapy (MAL-PDT) may have potential. OBJECTIVES: To investigate the efficacy and tolerability of MAL-PDT for treatment of moderate inflammatory facial acne. PATIENTS/METHODS: Thirty patients aged 15-28 years with moderate to severe acne were included in a blinded, prospective, randomized, placebo-controlled multicentre study. Each side of each patient's face was randomly assigned to treatment with MAL (160 mg g1) or placebo cream, applied for 3 h prior to illumination. A second treatment was given 2 weeks later. On each occasion, patients assessed the intensity of pain using a 10-cm visual analogue scale. Inflammatory and noninflammatory acne lesions were counted at baseline and 4 and 10 weeks after the last PDT treatment. The investigator assessed the global severity of acne at baseline (seven patients had severe acne on at least one side of the face) and each study visit using a six-point rating scale. Data were analysed on an intention-to-treat basis, including all 30 patients. RESULTS: There was a statistically significant greater reduction in the total inflammatory lesion count with MAL-PDT compared with placebo PDT at week 12; median reduction 54% [95% confidence interval (CI) 35-64%] vs. 20% (95% CI 8-50%), P = 0.0006. MAL-PDT was associated with more pain than placebo PDT, although intensity varied across centres and was reduced with repeated treatment. Local adverse events were consistent with this treatment modality. CONCLUSIONS: MAL-PDT is effective in the treatment of moderate to severe inflammatory facial acne. Further studies are warranted to optimize this promising procedure.     

Efficacy and tolerability of low-dose spironolactone and topical benzoyl peroxide in adult female acne: A randomized,double-blind,placebo-controlled trial

Effective therapies for adult female acne (AFA) are limited. Oral spironolactone (SPL), 100–200 mg/day, is currently used off-label to treat AFA. However, high-dose SPL results in clinically significant side-effects which prevent widespread use in clinical practice. The efficacy of low-dose spironolactone in AFA is unknown. We examined the efficacy and tolerability of low-dose (25–50 mg/day) oral SPL in Thai women with moderate AFA. A randomized, double-blind, placebo-controlled trial was conducted for 12 weeks. Moderate AFA patients aged between 25 and 45 years received a combination of daily topical benzoyl peroxide (BP) 2.5% plus either SPL 25 mg (SPL25 group), SPL 50 mg (SPL50 group) or placebo. We performed total acne counts and Adult Female Acne Scoring Tool (AFAST) grading at 4-week intervals. The success rate, defined as the proportion of participants achieving a “clear/almost clear” AFAST grade by the end of week 12, was considered as the main outcome. Treatment-related adverse events (TRAE) were recorded. We enrolled 63 participants in the study. The total acne counts decreased significantly in all three groups (P < 0.05) as compared with baseline. Participants in the SPL50 group had a significantly higher success rate than those in the placebo group (P < 0.05). Serum potassium and creatinine levels showed no significant changes with treatment or between groups. A small number of participants in SPL25 and SPL50 reported mild and temporary TRAE, such as menstrual irregularities, breast tenderness and dizziness. The combination of SPL 50 mg/day and topical BP proved effective in improving moderate AFA in Thai women, with an acceptable side-effect profile. We propose this regimen as an option for treating moderate AFA.     

Relationship between quinolone use and resistance of Staphylococcus epidermidis in patients with acne vulgaris

Staphylococcus epidermidis is a bacterium known to inhabit the skin. In treatment of acne vulgaris, the cutaneous milieu is exposed to oral or topical antimicrobials. We previously reported that the antimicrobial resistance of Cutibacterium acnes isolated from acne patients is affected by antimicrobial use. The aim of this study was to investigate the relationship between quinolone use and resistance in skin bacteria, particularly S. epidermidis, from acne patients. A total of 92 and 87 S. epidermidis strains isolated from clinic patients and hospital outpatients with acne vulgaris, respectively, were tested. No significant difference was found between the prevalence of methicillin‐resistant S. epidermidis (MRSE) strains from clinic patients (37.0%) and hospital outpatients (39.1%). The MRSE strains (20.6%, 14/68 strains) showed a significantly higher ratio of high‐level levofloxacin resistance (minimum inhibitory concentrations were 64 to ≥256 μg/mL) compared with methicillin‐susceptible S. epidermidis strains (2.7%, 3/111 strains) (P < 0.01). The rate of levofloxacin resistance in C. acnes strains, which were isolated from the same samples of acne patients, showed a strong positive correlation with that in S. epidermidis strains (r = 0.93, P < 0.01). The high‐level levofloxacin‐resistant strains were frequently found in patients with history of quinolone use compared with those without (P < 0.01). Our data showed for the first time that antimicrobial administration for acne treatment affects the antimicrobial resistance in not only C. acnes but also S. epidermidis. Thus, caution should be exercised in antimicrobial use for acne treatment to prevent increasing antimicrobial resistance in these species.     

A pilot study of the safety and efficacy of picolinic acid gel in the treatment of acne vulgaris

BACKGROUND: Cost limitations, adverse effects or lack of efficacy limit the use of current topical therapies in mild to moderate acne vulgaris. OBJECTIVES: To determine the safety and efficacy of picolinic acid, a novel zinc finger therapy, in the treatment of mild to moderate acne vulgaris. METHODS: Twenty subjects with mild to moderate acne vulgaris were treated at our centre during an open-label study with 10% picolinic acid gel (PCL-016) twice daily to the face over 12 weeks. RESULTS: Fifteen patients completed the 12-week open-label study. A reduction of 58.2% (P < 0.001) in mean total lesion count, 55.5% (P < 0.001) in mean inflammatory lesion count and 59.7% (P < 0.005) in noninflammatory lesion count was seen in this population. No serious adverse events or clinically significant changes in laboratory values were noted. CONCLUSIONS: Results from this study suggest that 10% picolinic acid gel applied twice daily may be safe and effective in the treatment of mild to moderate acne vulgaris.     

Efficacy and tolerability of short contact therapy with tretinoin,clindamycin, and glycolic acid gel in acne: A randomized,controlled, assessor‐blinded two‐center trial: The MASCOTTE study

Retinoids and antibiotics topical treatments are commonly used as first line therapy in mild to moderate acne. However, irritant contact dermatitis is a common side effect of topical retinoids. A strategy to increase local tolerability is the “short contact therapy” (SCT) approach, consisting in the application of the product with the complete removal after 30 to 60 minutes using a non‐aggressive cleanser. A gel containing tretinoin 0.02%, clindamycin 0.8%, and glycolic acid 4% in polyvinyl alcohol (MP‐gel) has shown to be effective as monotherapy in mild to moderate acne with a tolerability profile similar to other topical retinoids. So far, no trials have been performed with this gel comparing the tolerability profile of SCT with standard application therapy (SAT). We conducted a 2‐center randomized parallel groups, controlled, assessor‐blinded study, comparing MP‐gel applied as SCT in comparison with MP‐gel used as SAT (The “MASCOTTE” trial). Forty‐six subjects (nine men and 37 women, mean age 23 ± 4 years, range 18‐31 years) with mild‐to‐moderate acne were enrolled, after their written informed consent in a randomized, parallel groups controlled, assessor‐blinded 8‐week trial. Twenty‐three were assigned to MP‐gel once daily (evening application) using the SCT approach (ie, complete removal of product after 1 hour using a gentle cleanser), and 23 were randomized to the SAT approach with the same gel. The primary endpoint was the evolution of the tolerability score (TS) assessed evaluating four items: erythema, dryness, stinging, and burning, using a 4‐point score scale (from 0: no symptom to 3: severe symptom). Secondary endpoints were the evolution of global acne grading system (GAGS) score (range: from 0 to >39) and the investigator global assessment (IGA of acne severity) score (range from 0 to 4). TS was evaluated at 2, 4, and 8 weeks. GAGS and IGA scores were evaluated at baseline and at week eight. At week eight, an efficacy global score (EGS) (from 1: no efficacy to 4: very good efficacy) and a tolerability global score (TGS) (from 1: very low tolerability to 3: very good tolerability) evaluation were also done. All the evaluations were performed by an investigator unaware of treatment groups allocation (SCT or SAT). Thirty‐eight subjects (83%) completed the 8‐week treatment period. Eight subjects (two in the SCT group and six in the SAT group) dropped out prematurely due to low skin tolerability. In the SCT the TS at week two was 1.3 ± 1.7, in the SAT group TS was significantly higher (3.1 ± 1.7) (P = .028). TS was significantly lower in SCT group vs SAT also at weeks four and eight (P = .01; ANOVA test). The GAGS score at baseline was 19 ± 7 in the SCT group and 23 ± 4 in the SAT group (NS). At week 8 the GAGS score in SCT was significantly reduced to 8.5 ± 2.8 (?55%) (P = .001 vs baseline) and was also significantly lower in comparison with SAT group (8.5 vs 15; P = .0054). The IGA scores at baseline were 1.9 ± 0.6 in SCT and 2.4 ± 0.7 in SAT group. At week eight, in comparison with baseline values IGA score was reduced significantly by 48% in SCT and by 30% in SAT. EGS and TGS were significantly higher (better clinical efficacy and better tolerability) in SCT in comparison with SAT (3.6 ± 0.5 and 2.9 ± 0.3 vs 2.7 ± 0.6 and 1.5 ± 0.7; respectively). This tretinoin, clindamycin, glycolic acid gel, applied as SCT, has shown a better skin tolerability and at least a comparable clinical efficacy in comparison with the standard application modality in the treatment of mild‐to‐moderate acne. The SCT therefore could be an effective treatment strategy which could improve subjects' compliance and adherence.