Investigation of the effect of adapalene 0.3%/benzoyl peroxide 2.5% gel in Korean patients with acne: a randomized, double-blind clinical trial, with a histopathological and immunohistochemical study.

BACKGROUND: Acne vulgaris poses significant physical and psychological challenges worldwide. Data of adapalene 0.3%/benzoyl peroxide 2.5% gel (A0.3/BPO2.5) for acne treatment in Asian patients is limited. METHODS: In this randomized double-blind clinical trial, 49 Korean patients with moderate-to-severe acne and scars were assigned to the A0.3/BPO2.5 (N.=37) or vehicle (N.=12) group. Acne and acne scar severity scores were assessed at baseline and 4, 8, 12, and 24 weeks. The primary outcomes were treatment success rate (reduction of ≥2 Investigator's Global Assessment grade and reaching a grade of 0 or 1) and proportional acne lesion and scar count reduction against the baseline. To assess histological changes, 2-mm punch biopsies were performed at baseline and week 24 on the respective inflammatory lesions or scars. RESULTS: At week 24, the A0.3/BPO2.5 group had a significantly higher treatment success rate than the vehicle group. The total acne count, inflammatory lesion count, and non-inflammatory lesion count percentages (against baselines) with A0.3/BPO2.5 and the vehicle were 12.1% vs. 96.7%, 8.0% vs. 101.2%, and 13.3% vs. 98.9%, respectively (all P<0.001). Scar count percentages (against baselines) with A0.3/BPO2.5 and the vehicle were 27.3% and 96.5%, respectively (P<0.001). Significant elevations in collagen 1 and 3, elastin, CK15, and p63 levels, with increases of 172.7%, 230.6%, 176.5%, 286.2%, and 105.9%, respectively, in comparison to baseline (all P<0.05). No major adverse events leading to discontinuation were observed. CONCLUSIONS: A0.3/BPO2.5 was an effective and safe treatment for acne and acne scars in Asian patients supported by robust histopathological and immunohistochemical evidence.

Adult Female Acne: Managing the Hormones.

Acne is a common inflammatory condition of the skin worldwide. The skin is an endocrine organ and hormones are a key pathogenic factor in all types of acne with a particularly important role in adult female acne pathogenesis and management. In females, we have the unique opportunity to manipulate hormones systemically to successfully manage acne and, more recently with the approval of clascoterone 1% cream, we can target the hormones topically in both genders. The intent of this paper is to provide physicians with an up-to-date clinically relevant review of the role of hormones in acne, the impact of currently available contraceptives and therapies available to target hormones in acne.

An Overview on the Management of Atrophic Acne Scars: The Role of Trifarotene as an Adjunct.

Acne vulgaris is a common, often chronic inflammatory disease that can affect all ages and skin tones. Beyond acute lesions, the sequelae of acne - specifically scarring and dyspigmentation - can be long-lasting, challenging to treat and have substantial psychosocial impact on affected individuals. For acne scarring, treatment modalities include topical, physical, and laser and light therapies, with combination approaches typically yielding optimal outcomes. Trifarotene is a novel fourth generation retinoid with targeted action towards retinoid acid receptor gamma (RAR-γ), the most common isotype found in the epidermis, that has previously been approved for the management of moderate-to-severe facial and truncal acne in individuals over the age of 12 years. Recently, data on trifarotene supports its application in acne scarring. Herein, we provide a succinct review on various treatments for acne scarring and explore how trifarotene and its mechanism of action present an additional topical approach to target atrophic acne scarring.

Advances in polymeric nano-delivery systems targeting hair follicles for the treatment of acne.

Acne is a common chronic inflammatory disorder of the sebaceous gland in the hair follicle. Commonly used external medications cause skin irritation, and the transdermal capacity is weak, making it difficult to penetrate the cuticle skin barrier. Hair follicles can aid in the breakdown of this barrier. As nanomaterials progress, polymer-based nanocarriers are routinely used for hair follicle drug delivery to treat acne and other skin issues. Based on the physiological and anatomical characteristics of hair follicles, this paper discusses factors affecting hair follicle delivery by polymer nanocarriers, summarizes the common combination technology to improve the targeting of hair follicles by carriers, and finally reviews the most recent research progress of different polymer nanodrug-delivery systems for the treatment of acne by targeting hair follicles.

Pilot and quantitative evaluation of the TARGET acne toolkit by UK pharmacy professionals working in general practice.

BACKGROUND: Acne vulgaris (acne) is a common skin condition sometimes needing topical or oral antibiotic treatment. Pharmacists and pharmacy technicians (together known as pharmacy professionals) working in general practice are well placed to ensure their appropriate use. OBJECTIVES: The objectives of this study are to pilot an evidence-based intervention ('How to…' tool) to review treatments in the management of acne and evaluate the capability, opportunity, motivation and behaviour (COM-B) of pharmacy professionals working in general practice before and after the use of this tool. DESIGN, SETTING AND PARTICIPANTS: A quantitative electronic survey was developed asking UK-based pharmacy professionals working in general practice to rate their agreement with 21 predefined statements related to the COM-B model. INTERVENTION: Participants were sent an initial survey, given time to access and use the 'How to…' acne resources and then sent a follow-up survey 2 weeks later. OUTCOME MEASURES: Primary outcome was change in 5-point Likert scale responses to statements on capability, opportunity and motivation in the management of acne. Secondary outcome was the perceived usefulness of the toolkit. RESULTS: 141 pharmacy professionals completed the initial survey; 19 completed the follow-up survey. Significant improvement in the 5-point Likert scale means that responses were observed after implementation of the acne 'How to' resource; capability 3.68 (SD 0.40) versus 4.11 (SD 0.29), t(189) =-5.10, p <0.001; opportunity 3.85 (SD 0.24) versus 4.07 (SD 0.29), t(94)=-2.50, p=0.007 and motivation 4.35 (SD 0.47) versus 4.51 (SD 0.32), t(113)=-2.51, p=0.007. The 'How to' resources were rated as being useful (4.06, SD 0.12) and supportive (4.08, SD 0.18) to help pharmacy professionals in all areas of managing acne. CONCLUSION: The acne 'How to' resources are useful to pharmacy professionals in managing acne in general practice and may improve their capability. Further work is needed with greater numbers of participants to demonstrate generalisability of this outcome.

A new topical biotechnological phytocomplex for truncal mild-moderate acne restores skin microbiota balance.

BACKGROUND: The disruption of the microbial community or dysbiosis alters the functional composition, metabolic activity, and local distribution of the microbiota leading the development of acne. The aim of this study is to evaluate the effect of a lotion containing a biotechnological phytocomplex, niacinamide, and succinic acid in the bacterial diversity of subjects with truncal mild-moderate acne and its clinical benefits due to microbiota changes. MATERIALS AND METHODS: Open, clinical study in 43 subjects with truncal mild-moderate acne treated with a lotion for 8 weeks. Bacterial diversity was analyzed by 16S rRNA gene sequencing of skin samples. Clinical effects were evaluated through IGA acne severity scale, biometric measurements, and safety. RESULTS: After 56 days of product's use, an increase in richness alpha diversity was found (p = 0.005), with a decrease in Cutibacterium acnes relative abundance (66.43% vs. 58.11%, p = 0.009). The clinical results showed a decrease in IGA score (27.59% decrease; p = 0.001), the inflammatory lesions (52.12% decrease, p = 0.006) and erythema (18.33% decrease, p = 0.007), and desquamation index (63.83% decrease, p = 0.02). The responder analysis of the IGA score showed that 60.47% of patients improved by at least one point at day 56. The product was well tolerated along the study. CONCLUSION: The use of the lotion on acneic skin was effective on rebalancing the microbiota, inhibiting biofilm formation and other virulence factors, reducing erythema and desquamation, and improving acne's severity.

A dermocosmetic product containing the sap of oat plantlets and Garcinia mangostana extract improves the clinical signs of acne.

BACKGROUND: Acne vulgaris is a common chronic inflammatory disorder of the pilosebaceous unit, characterized by papules, pustules and/or nodules manifesting primarily on the face and/or upper back that can leave scars, post-inflammatory hyperpigmentation (PIH) and erythema (PIE). OBJECTIVE: To evaluate the anti-inflammatory properties of a protein-free sap extruded from Rhealba® oat plantlets and a Garcinia mangostana extract on Cutibacterium acnes-induced inflammation in vitro and assess the tolerability and efficacy of a dermocosmetic product containing these actives in subjects with mild-to-moderate acne. METHODS: Monocyte-derived dendritic cells (Mo-DCs) from acne patients were stimulated with a planktonic culture of C. acnes and cytokine production was evaluated before and after addition of the test extracts by RT-PCR and ELISA. The clinical study was conducted in subjects with mild-to-moderate acne who applied the product to their face and upper back twice-daily for 2 months. RESULTS: Cutibacterium acnes-induced IL-6, IL-12p40, IL-10 and TNFα synthesis was reduced by the addition of the Garcinia mangostana extract and oat sap in vitro. The clinical study included 54 subjects. The 2-month, twice-daily application of the test product to the whole face and acne-affected areas on the upper back was well tolerated. It led to significant decreases in the number of retentional (-21% for 69% of subjects at D57) and inflammatory (-35% for 79% of subjects at D57) acne lesions, as well as a decrease in Global Acne Evaluation severity scores (2.5 at D1, 2.2 at D29 and 2.1 at D57). The dermatologist also rated the product as effective or very effective in most subjects with PIE (82%; n = 33/40) and PIH (70%; n = 8/11) at D57. CONCLUSION: The actives demonstrated anti-inflammatory effects in vitro, and the dermocosmetic product showed good clinical efficacy and tolerability in subjects with mild-to-moderate acne, supporting the use of this product in acne management.

Investigating the mechanism of PAD in the treatment of acne based on network pharmacology and molecular docking: A review.

Acne is a common and chronic skin condition characterized by high incidence, recurrent symptoms and difficult cure. Summarizing the clinical treatment experience, it was found that the powder for ascending and descending was effective in the treatment of acne. Our aim was to use network pharmacology and molecular docking to reveal the hub genes, biological functions, and signaling pathways of powder for ascending and descending against acne. First, the chemical components and target genes of PAD were sifted using the TCMSP and HERB database. The targets of acne were obtained simultaneously from the CTD, OMIM and GeneCards database. The obtained drug targets and disease targets were imported into the R language software to draw Venn diagrams. Then, the potential targets were imported into the String website to construct a protein interaction network diagram. And Cytoscape software was used for topological analysis to screen the core targets, and the core targets were analyzed by GO functional enrichment and KEGG pathway enrichment. Finally, molecular docking was used to verify the predictions of key genes' reliability. The core targets of the treatment of acne were TNF, GADPH, IL-6 and so on. The results of enrichment analysis showed that the treatment of acne with PAD may be related to TNF signaling pathway and AGE-RAGE signaling pathway. The molecular docking verification showed that the components were well bound to the core targets of acne, and the docking ability of stigmasterol and TNF (-12.73 kcal/mol) was particularly outstanding.

Comparative transcriptome analysis of acne vulgaris, rosacea, and hidradenitis suppurativa supports high-dose dietary zinc as a therapeutic agent.

Acne vulgaris, rosacea, and hidradenitis suppurativa are enduring inflammatory skin conditions that frequently manifest with akin clinical attributes, posing a considerable challenge for their distinctive diagnosis. While these conditions do exhibit certain resemblances, they also demonstrate distinct underlying pathophysiological mechanisms and treatment modalities. Delving into both the molecular parallels and disparities among these three disorders can yield invaluable insights for refined diagnostics, effective management, and targeted therapeutic interventions. In this report, we present a comparative analysis of transcriptomic data across these three diseases, elucidating differentially expressed genes and enriched pathways specific to each ailment, as well as those shared among them. Specifically, we identified multiple zinc-binding proteins (SERPINA1, S100A7, S100A8, S100A9 and KRT16) as consistently highly upregulated genes across all three diseases. Our hypothesis suggests that these proteins could bind and sequester zinc, potentially leading to localized zinc deficiency and heightened inflammation. We identified high-dose dietary zinc as a promising therapeutic approach and confirmed its effectiveness through validation in an acne mouse model.

Isotretinoin-Induced Hypersomnia: A Cross-sectional Study and Literature Review.

BACKGROUND: Isotretinoin is an oral retinoic drug for severe resistant acne cases that has controversially been associated with multiple psychiatric adverse effects. Research has primarily focused on depression and suicidality; however, a few case studies reported hypersomnia and sleep changes after isotretinoin initiation. OBJECTIVE: To assess sleep quality and measure rates of hypersomnia, depression, and anxiety in patients undergoing isotretinoin therapy. METHODS: This cross-sectional study was conducted at outpatient clinics of the university hospital. The rate of self-reported oversleeping was measured. In addition, researchers used the Pittsburgh Sleep Quality Index to assess sleep quality and conducted semistructured clinical interviews to detect depression and anxiety. RESULTS: Of 123 patients with acne on isotretinoin, 77 (62.6%) reported oversleeping. Nearly half (60 patients, 48.8%) were categorized as poor sleepers according to the Pittsburgh Sleep Quality Index. The interviews revealed anxiety and depression percentages among 9.8% and 4.9% of participants, respectively. CONCLUSIONS: Hypersomnia was noticeably high in this study sample; thus, it may cautiously suggest a possible link between isotretinoin and hypersomnia. However, more research is needed to investigate this potential relationship.

Efficacy and Safety of Micronized Isotretinoin Administered Once Daily Without Food in Patients With Recalcitrant Nodular Acne.

INTRODUCTION: Micronized isotretinoin 0.4 to 0.8 mg/kg/day administered in 2 divided doses with or without meals is approved for the treatment of severe nodular acne in patients aged 12 years or older. Although practitioners may suggest once-daily dosing to increase patient compliance, supporting data are limited. METHODS: In this pilot study, patients aged 12 years or older with severe nodular acne (Investigator's Global Assessment [IGA] =>4 and >5 facial nodules) received once-daily micronized isotretinoin 0.4 to 0.8 mg/kg/day without food for 20 weeks. The coprimary efficacy endpoints were changes from baseline in nodular lesion count (NLC) and percentage of patients with a =>90% reduction in NLC at week 24. Secondary endpoints included percentage of patients achieving IGA 0/1; reductions in inflammatory lesion count (ILC) and noninflammatory lesion count (NILC); adverse events (AEs); and severity of erythema, dryness, peeling, oiliness, burning, and pruritus. Analyses included all enrolled patients with the last observation carried forward. RESULTS: Twenty-two of 24 patients completed the study. From baseline to week 24, NLC decreased by a median (quartile [Q]1, Q3) of 6 (5, 7), all patients experienced complete clearance of nodules, 23/24 (96%) patients achieved IGA 0/1, and ILC and NILC decreased by a mean +/- standard deviation of 97.8% +/- 5.7% and 98.4% +/- 6.2%, respectively (all P<0.0001). There were small, significant, early increases in the severity of erythema, dryness, and peeling; 2 patients experienced 3 AEs considered unrelated to treatment. CONCLUSIONS: Once-daily micronized isotretinoin administered without food was efficacious and well tolerated in patients with severe nodular acne.  J Drugs Dermatol. 2024;23(6):423-428.     doi:10.36849/JDD.7863.

Consensus Statements on the Use of Novel Formulations of Isotretinoin: A Modified Delphi Process.

Oral isotretinoin remains a mainstay of treatment for severe, recalcitrant nodular acne. Novel formulations of isotretinoin have been developed over the past decade, including lidose isotretinoin and micronized isotretinoin. It is important to understand the differences between isotretinoin formulations to help guide clinical decision-making and selection of isotretinoin therapy. This study aims to provide evidence-based consensus statements regarding the use of novel formulations of isotretinoin for the treatment of moderate-to-severe acne. The Expert Consensus Group consisted of dermatologists with expertise in the treatment of acne. Voting members met in person to conduct a modified Delphi process; a maximum of 2 rounds of voting were conducted for each consensus statement. A total of 5 statements were generated regarding the use of novel formulations of isotretinoin, addressing the efficacy, tolerability, and side effects of novel isotretinoin formulations. All 5 statements achieved agreement with high consensus. The Expert Consensus Group agrees that individualized selection of isotretinoin therapy is important to maximize efficacy and minimize side effects. Compared to generic isotretinoin, micronized isotretinoin may require lower doses to achieve sufficient plasma concentrations. With the increased bioavailability of micronized formulation, there is no need to calculate cumulative dose; instead, the general recommendation with micronized isotretinoin is to treat for at least 5 months, or longer if needed to achieve clearance. Micronized isotretinoin can be taken in the fed or fasted state and has an acceptable safety profile. J Drugs Dermatol. 2024;23(6):429-432.     doi:10.36849/JDD.7971.

Investigating the Relationship Between Acne and Vasodilatory Medications in a Hospital-Wide Adult Population.

Acne vulgaris is a common chronic dermatological condition characterized by obstruction and inflammation of pilosebaceous units. Recent research on a different dermatologic condition has demonstrated that the use of vasodilatory medications is associated with a decreased relative risk of rosacea. This finding is significant due to the overlapping inflammatory pathways involved in rosacea and acne. Herein, a retrospective cohort study was designed to determine the correlation between vasodilator usage and the risk of developing acne within 5 years, contrasting it with thiazide diuretics, chosen as a control due to its non-vasodilatory antihypertensive mechanism and availability of data. Angiotensin-converting enzyme (ACE) inhibitors (RR, 0.775; 95% CI, 0.727-0.826; P<0.05), angiotensin receptor blockers (ARBs) (RR, 0.739; 95% CI, 0.685-0.797; P<0.05), beta-blockers (BB) (RR, 0.829; 95% CI, 0.777-0.885; P<0.05), and calcium channel blockers (CCB) usage (RR, 0.821, 95% CI, 0.773-0.873; P<0.05) were associated with a significantly lower risk of developing acne within 5 years of initiating therapy compared to thiazide diuretics. It is unclear if thiazide diuretics are more likely to cause acne within the adult population or if vasodilators are protective against the development of acne. Finding mechanisms and therapeutics that lower the risk of developing acne is of significant public health interest, and this study provides a step toward this endeavor. Further research is required to uncover the underlying mechanisms for this reduction in the development of acne.  J Drugs Dermatol. 2024;23(6):446-449.     doi:10.36849/JDD.8362.

Combined low-dose isotretinoin and long-pulsed nd: YAG laser in the treatment of post-acne erythema.

Post-acne erythema (PAE) is a bothering skin condition that emerges from inflammatory acne and persists after its resolution. It is characterized by telangiectasia and erythematous macules. the role of 1064-nm Nd: YAG when combined with low-dose isotretinoin in the acne erythema treatment. forty-eight PAE patients were involved in the study. They were divided into two groups; group (A) patients administering a low dose of oral isotretinoin (10 mg/day) and underwent a total of six two-week interval sessions of 1064 ND-YAG laser treatment, group (B) patients administering a low dose of oral isotretinoin (10 mg/day) only. All adverse effects experienced during the course of therapy were documented, and photos were taken before the start of the treatment and following the end of the treatment duration. Following the completion of the therapeutic intervention, a significant improvement in clinical condition was observed in both groups, with more improvement in group (A) compared to group (B) as evidenced by a notable improvement in the score on the Clinician Erythema Assessment Scale (CEAS) and also a significant decrease in the mean value of optical density of the erythema. combined 1064-nm Nd: YAG with low-dose isotretinoin may be an efficient and secure line in the PAE treatment. Also, the combined therapy had superior results when compared to low-dose isotretinoin alone.

Hair Follicle-Targeted Delivery of Azelaic Acid Micro/Nanocrystals Promote the Treatment of Acne Vulgaris.

Purpose: Acne vulgaris is a chronic inflammatory skin disorder centered on hair follicles, making hair follicle-targeted delivery of anti-acne drugs a promising option for acne treatment. However, current researches have only focused on the delivering to healthy hair follicles, which are intrinsically different from pathologically clogged hair follicles in acne vulgaris. Patients and Methods: Azelaic acid (AZA) micro/nanocrystals with different particle sizes were prepared by wet media milling or high-pressure homogenization. An experiment on AZA micro/nanocrystals delivering to healthy hair follicles was carried out, with and without the use of physical enhancement techniques. More importantly, it innovatively designed an experiment, which could reveal the ability of AZA micro/nanocrystals to penetrate the constructed clogged hair follicles. The anti-inflammatory and antibacterial effects of AZA micro/nanocrystals were evaluated in vitro using a RAW264.7 cell model stimulated by lipopolysaccharide and a Cutibacterium acnes model. Finally, both the anti-acne effects and skin safety of AZA micro/nanocrystals and commercial products were compared in vivo. Results: In comparison to commercial products, 200 nm and 500 nm AZA micro/nanocrystals exhibited an increased capacity to target hair follicles. In the combination group of AZA micro/nanocrystals and ultrasound, the ability to penetrate hair follicles was further remarkably enhanced (ER value up to 9.6). However, toward the clogged hair follicles, AZA micro/nanocrystals cannot easily penetrate into by themselves. Only with the help of 1% salicylic acid, AZA micro/nanocrystals had a great potential to penetrate clogged hair follicle. It was also shown that AZA micro/nanocrystals had anti-inflammatory and antibacterial effects by inhibiting pro-inflammatory factors and Cutibacterium acnes. Compared with commercial products, the combination of AZA micro/nanocrystals and ultrasound exhibited an obvious advantage in both skin safety and in vivo anti-acne therapeutic efficacy. Conclusion: Hair follicle-targeted delivery of AZA micro/nanocrystals provided a satisfactory alternative in promoting the treatment of acne vulgaris.

Antibacterial toner exhibits bactericidal effect against Cutibacterium acnes via keratin and sebum plug penetration.

Cutibacterium acnes is an opportunistic pathogen recognized as a contributing factor to acne vulgaris. The accumulation of keratin and sebum plugs in hair follicles facilitates C. acnes proliferation, leading to inflammatory acne. Although numerous antimicrobial cosmetic products for acne-prone skin are available, their efficacy is commonly evaluated against planktonic cells of C. acnes. Limited research has assessed the antimicrobial effects on microorganisms within keratin and sebum plugs. This study investigates whether an antibacterial toner can penetrate keratin and sebum plugs, exhibiting bactericidal effects against C. acnes. Scanning electron microscopy and next-generation sequencing analysis of the keratin and sebum plug suggest that C. acnes proliferate within the plug, predominantly in a biofilm-like morphology. To clarify the potential bactericidal effect of the antibacterial toner against C. acnes inside keratin and sebum plugs, we immersed the plugs in the toner, stained them with LIVE/DEAD BacLight Bacterial Viability Kit to visualize microorganism viability, and observed them using confocal laser scanning microscopy. Results indicate that most microorganisms in the plugs were killed by the antibacterial toner. To quantitatively evaluate the bactericidal efficacy of the toner against C. acnes within keratin and sebum, we immersed an artificial plug with inoculated C. acnes type strain and an isolate collected from acne-prone skin into the toner and obtained viable cell counts. The number of the type strain and the isolate inside the artificial plug decreased by over 2.2 log and 1.2 log, respectively, showing that the antibacterial toner exhibits bactericidal effects against C. acnes via keratin and sebum plug penetration.