Expression of inflammatory and fibrogenetic markers in acne hypertrophic scar formation: focusing on role of TGF-ß and IGF-1R.

Acne vulgaris is a universal skin disease and it may leave a scar when the original skin lesion disappears. These scars can cause cosmetic problems and psychological burden, leading to poor quality of life of patients. Acne scars are classified into atrophic scars and hypertrophic scars. As most of the acne scars are atrophic, many studies have been conducted focusing on the treatment of atrophic lesions. This study was conducted to investigate the underlying pathogenesis of acne hypertrophic scars by identifying roles of fibrogenetic and inflammatory markers. Skin biopsy samples were obtained from hypertrophic scars of face and back and from adjacent normal tissues as control group. Some samples from back were immature hypertrophic scars and the other samples were in mature stages. Immunohistochemistry staining and quantitative PCR were performed for fibrogenetic and inflammatory markers. Both in mature and immature hypertrophic scars, vimentin and α-SMA were increased. Production of TGF-ß3 protein as well as transcription of TGF-ß3 was also significantly elevated. In contrast, expression of TGF-ß1 showed no increase. Instead, expression levels of SMAD2 and SMAD4 were increased. Elevations of CD45RO, TNF-α and IL-4 and reduction of IL-10 were observed. In immature hypertrophic scars, IGF-1R and insulin-degrading enzyme expression were increased. Increased apoptosis was observed in immature stages of hypertrophic scars but not in mature stages. Elevations of TGF-ß3, SMAD2 and SMAD4 in hypertrophic scars and increase of IGF-1R in immature stages may give some clues for acne hypertrophic scar formation.

Combination of platelet rich plasma in fractional carbon dioxide laser treatment increased clinical efficacy of for acne scar by enhancement of collagen production and modulation of laser-induced inflammation.

BACKGROUND: Platelet-rich plasma (PRP) which contains large amounts of growth factors has been tried to enhance therapeutic efficacy of laser treatment for acne scar with unknown underlying mechanism. OBJECTIVES: The present study was conducted to investigate the molecular mechanism of increased clinical efficacy of PRP when combined with fractional laser treatment for treating acne scars. METHODS: Subjects with mild to moderate acne scars were treated with two sessions of fractional CO2 laser therapy given with and without co-administration of PRP. Skin biopsy specimens were obtained at baseline, 1, 3, 7, and 28 days for investigation of molecular profiles associated with skin changes produced by laser plus PRP treatment. RESULTS: The PRP treatment increased clinical efficacy with decreased severity of adverse effects such as erythema, swelling and oozing. Productions of TGFß1 and TGFß3 proteins were more highly elevated on the PRP-treated side of the face compared to the control side at day 28. Furthermore, PRP-treated side showed significant increase of c-myc, TIMP, and HGF expression. Experimental fibroblast culture model was also used. PRP administration after laser irradiation increased expressions of p-Akt, TGFß1, TGFß3, ß-catenin, collagen 1, and collagen 3 in both dose-dependent and time dependent manners in fibroblast. Moreover, we acquired clinical and histological data through randomized control clinical trial. CONCLUSION: Taken together with human study results combined with the data from cell experiments we suggest that PRP treatment increased fibrogenetic molecules induced by fractional CO2 laser, which have association with clinical effect. Lasers Surg. Med. 50:302-310, 2018. © 2017 Wiley Periodicals, Inc.

Seeking new acne treatment from natural products, devices and synthetic drug discovery.

Despite lots of research on the pathogenesis of acne, the development of new therapeutic agents is still stagnant. Conventional agents which target multiple pathological processes have some serious side effects and this makes seeking new treatment options important for treating acne. As new therapeutic options, researchers are focusing on natural products, synthetic drugs and devices. From natural products, epigallocatechin-3 gallate, lupeol, cannabidiol and Lactobacillus fermented Chamaecyperis obtusa were reported to be possible candidates for novel drugs, targeting multiple pathogenic factors. Synthetic anti-P.acnes agent, nitric oxide nanoparticles and α-mangostin nanoparticles are shown to be effective in acne treatment. Device or procedural methods such as fractional microneedling radiofrequency, cryolysis, photothermolysis and daylight photodynamic therapy have potential as new treatment options for acne. Further large clinical trials comparing these new treatments with existing agents will be necessary in the future.

Analysis of Korean acne patients according to age groups based on two multicenter studies.

Along with increasing public concerns on acne and its complications, increasing treatment options seem to lead more acne patients to clinics globally, including Korea. The aim of the present study was to investigate the number and distribution of acne patients according to age group by analyzing number and age of outpatients from several general hospitals in Korea. Two retrospective multicenter studies including 14 general hospitals for a maximum of 10 years were conducted by medical chart review of acne patients. During the last 10 years, total acne patients have increased by 60% in number and patients under the age of 19 years have doubled. Adult acne patients (aged >18 years) accounted for the biggest portion in total acne patients at over 80%. Although upper grade of elementary school patients (aged 10-12 years) accounted for the biggest portion among the childhood acne patients, children under 10 years have also increased rapidly by 73% during the last 10 years. Childhood acne patients (aged <13 years) accounted for 11% of total acne patients. We found that acne patients were increasing consistently and the portion of those aged under 19 years is getting bigger. Additionally, childhood acne patients have increased remarkably.

Comparison between Er:YAG laser and bipolar radiofrequency combined with infrared diode laser for the treatment of acne scars: Differential expression of fibrogenetic biomolecules may be associated with differences in efficacy between ablative and non-ablative laser treatment.

BACKGROUND AND OBJECTIVE: Fractional Er:YAG minimizes the risk associated with skin ablation. Infrared diode laser and radiofrequency have suggested comparable improvements in acne scar. We compared the clinical efficacy of Er:YAG laser and bipolar radiofrequency combined with diode laser (BRDL) for the treatment of acne scars. Moreover, acute molecular changes of cytokine profile associated with wound healing have been evaluated to suggest mechanisms of improvement of acne scar. STUDY DESIGN: Twenty-four subjects with mild-to-moderate acne scars were treated in a split-face manner with Er:YAG and BRDL, with two treatment sessions, 4 weeks apart. Objective and subjective assessments were done at baseline, 1, 3, 7 days after each treatment and 4 weeks after last treatment. Skin biopsy specimens were obtained at baseline, 1, 3, 7, 28 days after one session of treatment for investigation of molecular profile of acute skin changes by laser treatment. RESULTS: Investigator's Global Assessment representing the improvement degree shows 2.1 (50%) in fractional Er:YAG and 1.2 (25%) in BRDL. Er:YAG induced the later and higher peak expression of TGFßs and collagenases, whereas BRDL induced earlier and lower expression of TGFß and collagenases, relatively. PPARγ dropped rapidly after a peak in Er:YAG-treated side, which is associated with tissue inhibitor of metalloproteinase (TIMP) expression. We observed higher expression of TIMP after Er:YAG treatment compared with BRDL by immunohistochemistry, which may be associated with the expression of upregulation of collagen fibers. CONCLUSION: The superior efficacy of Er:YAG to BRDL in the treatment of acne scars may be associated with higher expression of collagen which is associated with differential expression of TGFßs, collagenases, PPARγ, and TIMP. Lasers Surg. Med. 49:341-347, 2017. © 2016 Wiley Periodicals, Inc.

Clinical and Histologic Effects of Fractional Microneedling Radiofrequency Treatment on Rosacea.

BACKGROUND: Fractional microneedling radiofrequency (FMR) is an emerging treatment modality, but its effect on rosacea has not been studied yet. OBJECTIVE: To investigate the potential impact of FMR treatment on clinical improvement and histologic changes in rosacea patients. MATERIALS AND METHODS: A 12-week, prospective, randomized, split-face clinical trial was conducted. Two sessions of FMR were performed on one side of the cheeks with 4-week interval and the other side remained untreated. Erythema index from DermaSpectrometer and a* value from Spectrophotometer CM-2002 were measured at each visit for the objective measurement of erythema. Histologic analysis of skin samples was also carried out. RESULTS: Clinical evaluation and photometric measurement revealed the reduction of redness in the treated side compared with untreated side and baseline. Erythema index decreased 13.6% and a* value decreased 6.8% at Week 12 compared with baseline. Reduced expression of markers related to inflammation, innate immunity, and angiogenesis was observed in immunohistochemical staining of tissue obtained after FMR treatment. CONCLUSION: Fractional microneedling radiofrequency treatment showed modest clinical and histologic improvement of rosacea, and it might be used as an alternative or in combination with other treatment methods.

Clinical manifestation and associated factors of seborrheic dermatitis in Korea.

UNLABELLED: Systematic investigations of clinical manifestation and factors associated with the severity of seborrheic dermatitis (SD) have rarely been reported in Asia. We investigated the clinical manifestation and associated factors of SD. Patients were asked to fill a self-questionnaire including symptom severity and aggravating factors. We evaluated objective severity and involved sites of SD. Patients were categorized into three groups; young age group (age <30), middle age group (30≤ age <60), and old age group (age ≥60) and we compared clinical features among them. RESULTS: Among 253 patients included, scalp was the most frequently involved site and the most frequently reported aggravating factor was psychological stress. Different age groups have distinct clinical features and severity. Severity of SD decreased with age and patients in the old age group had less frequent involvement of the lower face. Risk factors of scalp involvement were male gender, disease duration ≥7 years and a history of acne. We investigated associated factors of SD and observed different clinical features between the age groups. We suggest that the adult form of SD can be categorized into three groups; young age SD, middle age SD and old age SD.

Cross-sectional survey of awareness and behavioral pattern regarding acne and acne scar based on smartphone application.

BACKGROUND: Although acne scar is a permanent sequela that may be induced by improper management of active acne lesion, patient behavior patterns and awareness regarding acne are unclear. The aim of this study was to identify awareness and behavioral patterns concerning acne and acne scar of people having acne and differences between those with and without acne scars. METHODS: The survey was performed via smartphone application for 900 participants in their second to fourth decade having current or previous acne lesions. They were further categorized into two groups based on the presence of acne scar (scar and scarless groups) with no statistical difference in demographic composition. RESULTS: The mean age of all participants was 24.6 ± 5.3. The scar group had a longer disease duration (4.9 years) than those of the scarless group (2.2 years). Participants in the scar group thought that acne scarring affected psychosocial aspects more negatively compared with those in the scarless group. Participants in the scarless group visited dermatology clinics earlier than those in the scar group. In the scar group, 62.1% of participants have never had their acne scars treated medically. Most (88.6%) participants from both groups believed that non-dermatologic treatment caused side effects or aggravated their acne. CONCLUSIONS: Participants with acne scars tended to treat their acne and acne scars improperly, which could negatively affect their daily lives. Acne scars are sequelae of acne and should be regarded as a distinct disease entity, requiring a patient's early visit to dermatologic clinics.

Fractional Microneedling Radiofrequency Treatment for Acne-related Post-inflammatory Erythema.

Post-inflammatory erythema is a common result of acne inflammation and is cosmetically unacceptable without effective treatment. Fractional microneedling radiofrequency (FMR) has potential for treatment of post-inflammatory erythema. The aim of this study was to evaluate the efficacy and safety of this treatment. A retrospective chart review was undertaken of 25 patients treated with 2 sessions of radiofrequency at 4-week intervals and 27 patients treated with oral antibiotics and/or topical agents. Efficacy was assessed through an investigator's global assessment of photographs, and the analysis of erythema with image analysis software and photometric devices. Histological changes resulting from the treatment were evaluated by skin biopsy. FMR treatment resulted in significant improvements in erythema with no severe adverse effects. Histological study revealed a reduction in vascular markers and inflammation. FMR is a safe and effective treatment for post-inflammatory erythema, with potential anti-inflammatory and anti-angiogenetic properties.

Comparison of fractional microneedling radiofrequency and bipolar radiofrequency on acne and acne scar and investigation of mechanism: comparative randomized controlled clinical trial.

Fractional microneedling radiofrequency (FMR) is one of the promising methods in acne treatment. Moreover, bipolar radiofrequency (BR) generates heat thereby which induces neocollagenosis. FMR may have the potential to be a safe and effective treatment for the patients both with acne and acne scar. This study was performed to compare the efficacy and safety of FMR and BR in acne and acne scar treatment. Furthermore, mechanism of the FMR treatment was investigated through skin tissues obtained from subjects. Twenty subjects with mild-to-moderate acne and acne scars were treated in a split-face manner with FMR and BR. Two sessions of treatment was done 4 weeks apart in a total 12-week prospective single-blind, randomized clinical trial. Clinical assessment and sebum measurement were carried out for the evaluation of efficacy and safety. Skin tissues were acquired for investigation of molecular changes. FMR was more effective for acne scar especially in icepick and boxcar scar compared to BR. Both inflammatory and non-inflammatory acne lesions decreased by 80 and 65 % in the FMR-treated side at the final visit of 12 weeks, respectively. FMR treatment resulted in significant reduction of sebum excretion. Both treatments showed no severe adverse effects other than erythema. The FMR showed superior efficacy in acne and acne scar compared with BR. Increased expression of TGFß and collagen I and decreased expression of NF-κB, IL-8 are suggested to involve in the improvement of acne scar and acne lesion by FMR.

Do tutorials on application method enhance adapalene-benzoyl peroxide combination gel tolerability in the treatment of acne?

Fixed-dose combination adapalene 0.1% and benzoyl peroxide 2.5% gel (A-BPO) has rarely been studied for Asian acne patients, while they have complained of local irritations more often when applying individual components. In this study, we compared A-BPO gel with benzoyl peroxide (BPO) in terms of efficacy and tolerability in Korean patients first, and assessed the clinical benefit of a dermatological tutorial on application technique in reducing irritations for A-BPO. This study was conducted as a single-blind controlled split-face trial for a 12-week period. Each half facial side of 85 patients was randomly assigned to either A-BPO or BPO. Success rate, lesion counts and safety profiles were evaluated (analysis I). During initial assignment, all patients were further randomized to either dermatological tutorial (DT) or non-tutorial (NT) subgroups depending on the presence of dermatologists' tutorials for application methods to their A-BPO sides. Clinical data of the A-BPO side was compared between two subgroups (analysis II). As a result, A-BPO gel outperformed BPO, demonstrating better efficacy in success rates and lesion counts as early as 1 week. However, A-BPO proved significantly less tolerable compared with both BPO and previous A-BPO data from Caucasians. Bioengineering measurements further confirmed clinical data (analysis I). The DT subgroup achieved much better tolerability with comparable therapeutic efficacies compared with the NT subgroup (analysis II). In conclusion, A-BPO demonstrated higher efficacies in acne compared with BPO in Korean patients, while skin irritation levels were notable concurrently. Dermatologists' education for application methods would significantly decrease these side-effects, maintaining superior efficacy levels.

Activity-guided purification identifies lupeol, a pentacyclic triterpene, as a therapeutic agent multiple pathogenic factors of acne.

Acne vulgaris is a nearly universal cutaneous disease characterized by multifactorial pathogenic processes. Because current acne medications have various side effects, investigating new pharmacologically active molecules is important for treating acne. As natural products generally provide various classes of relatively safe compounds with medicinal potentials, we performed activity-guided purification after a series of screenings from the extracts of five medicinal plants to explore alternative acne medications. Lupeol, a pentacyclic triterpene, from the hexane extract of Solanum melongena L. (SM) was identified after instrumental analysis. Lupeol targeted most of the major pathogenic features of acne with desired physicochemical traits. It strongly suppressed lipogenesis by modulating the IGF-1R/phosphatidylinositide 3 kinase (PI3K)/Akt/sterol response element-binding protein-1 (SREBP-1) signaling pathway in SEB-1 sebocytes, and reduced inflammation by suppressing the NF-κB pathway in SEB-1 sebocytes and HaCaT keratinocytes. Lupeol exhibited a marginal effect on cell viability and may have modulated dyskeratosis of the epidermis. Subsequently, histopathological analysis of human patients' acne tissues after applying lupeol for 4 weeks demonstrated that lupeol markedly attenuated the levels of both the number of infiltrated cells and major pathogenic proteins examined in vitro around comedones or sebaceous glands, providing solid evidence for suggested therapeutic mechanisms. These results demonstrate the clinical feasibility of applying lupeol for the treatment of acne.

Comparison of clinical and histological effects between lactobacillus-fermented Chamaecyparis obtusa and tea tree oil for the treatment of acne: an eight-week double-blind randomized controlled split-face study.

BACKGROUND: Screening of natural compounds for the development of anti-acne therapeutic agents has been steadily required considering various side effects of acne medications. However, previous studies have mainly focused on experimental tests without clinical trials and histopathological analysis. OBJECTIVES: To compare the clinical efficacy, safety and histopathological changes between Lactobacillus-fermented Chamaecyparis obtusa (LFCO) and existing tea tree oil (TTO). METHODS: A total of 34 patients were instructed to apply 5% LFCO to the involved areas of a randomly allocated side and 5% TTO extract to the other side for 8 weeks in a double-blind split-face clinical trial. RESULTS: After 8 weeks, inflammatory acne lesions were reduced by 65.3% on the LFCO side and by 38.2% on the TTO side. LFCO was also superior to TTO in the onset time of efficacy (p < 0.05). The LFCO side further demonstrated improvement for non-inflammatory lesions (52.6%, p < 0.05), decreased size of sebaceous glands and sebum output reductions. Patients' subjective satisfaction was also higher without severe adverse reactions. Protein expressions of nuclear factor κB decreased earlier on the LFCO side, and those of interleukin-1α (IL-1α), IL-8, insulin-like growth factor 1 receptor and sterol regulatory element-binding protein 1 decreased subsequently. Ultra-performance liquid chromatography/high-resolution mass spectrometry further demonstrated that the contents of dihydroxybenzoic acid, taxifolin and quercetin were increased in LFCO after fermentation. CONCLUSIONS: LFCO treatment was rapid and effective for treating acne lesions compared to TTO. Histopathological findings correlated well with the clinical acne grade and treatment response. This novel natural compound appears to be effective and safe for acne treatment.

Clinical effect of bovine amniotic membrane and hydrocolloid on wound by laser treatment: prospective comparative randomized clinical trial.

Bovine amniotic membrane (BAM) has been regarded as an ideal dressing material because it accelerates epithelization and has anti-inflammatory, anti-angiogenic, and strong analgesic effects. To evaluate the clinical effects of BAM and compare them to that of hydrocolloid dressings on wounds created by ablative laser treatments, 49 subjects with nevi or scars requiring ablative laser treatment were evaluated. To compare efficacy, we divided the body into six areas and included patients with two or more similar skin lesions in the same body area. After ablative laser treatments, BAM and hydrocolloid dressing were applied to the wounds with random allocation. Clinical assessments were performed at baseline, 1, 4, 6, 8, 11, and 13 days after treatment. Histologic changes were assessed by skin biopsy. BAM treatment induced faster epithelization than hydrocolloid treatment (6.7 vs. 9.2 days). Erythema and oozing faded more quickly, and the satisfaction score was higher in BAM-treated sites than it was in hydrocolloid-treated sites, without severe adverse effects. Histologic analysis confirmed epithelization and immunohistochemistry revealed different growth factor profiles between the two treatment modalities. BAM benefits wound healing following ablative laser treatment.

Development and evaluation of an automatic acne lesion detection program using digital image processing.

BACKGROUND/PURPOSE: Existing acne grading methods, which depend on overall impression, require a long training period and there is a high degree of variability among raters, including trained dermatologists. The use of lesion count provides fair reproducibility but the method is time consuming. New technologies in photographic equipment and software allow solutions to the problem of acne evaluation. This study was conducted to develop the automatic acne lesion program and evaluation of its usefulness. METHODS: We made the conditions to optimize characterization of acne lesions and developed the counting program. Twenty-five volunteers with acne lesions were enrolled. Automated lesion counting for five subtypes of acne (papule, nodule, pustule, whitehead comedone, and blackhead comedone) was performed with image processing. The usefulness of the automatic lesion count program was assessed by a comparison with manual counting performed by an expert dermatologist. RESULTS: In a comparison with manual counting performed by an expert dermatologist, the sensitivity and positive predictive value of the lesion-counting program was greater than 70% for papules, nodules, pustules, and whitehead comedo. In a comparison with manual counting, findings with the use of the lesion-counting program were well correlated for papules, nodules, pustules, and whitehead comedo (r > 0.9). CONCLUSION: Automatic lesion-counting program can be a useful tool for acne severity evaluation.