Using Neuromodulators to Improve Scar Formation, Keloids, Rosacea, and Antiaging.

BACKGROUND: Botulinum toxin A (BoNT-A) treatment has many uses in dermatology. Its mechanism of action and long-term effects for scar formation, rosacea, and antiaging are still being investigated. OBJECTIVE: To conduct a literature review on BoNT-A to further investigate its use in scar formation, rosacea, and antiaging. METHODS: A literature review was conducted using PubMed on botulinum toxin treatment for scar formation, rosacea, and antiaging. Studies discussing the toxin mechanism of action and treatment algorithm were included. The authors also provided their personal experience in BoNT-A use for these 3 conditions. RESULTS: The mechanism of action of Botulinum toxin A in improving scar formation, rosacea, and antiaging is now better understood. While it is effective in the short term, little is still known about how frequently treatment needs to be repeated and if there are any long-term effects. CONCLUSION: While in vitro studies have supporting evidence on the mechanism of action of BoNT-A on scar formation, rosacea, and antiaging, further studies are needed to identify long-term treatment effects.

Insights into How Plant-Derived Extracts and Compounds Can Help in the Prevention and Treatment of Keloid Disease: Established and Emerging Therapeutic Targets.

Keloid is a disease in which fibroblasts abnormally proliferate and synthesize excessive amounts of extracellular matrix, including collagen and fibronectin, during the healing process of skin wounds, causing larger scars that exceed the boundaries of the original wound. Currently, surgical excision, cryotherapy, radiation, laser treatment, photodynamic therapy, pressure therapy, silicone gel sheeting, and pharmacotherapy are used alone or in combinations to treat this disease, but the outcomes are usually unsatisfactory. The purpose of this review is to examine whether natural products can help treat keloid disease. I introduce well-established therapeutic targets for this disease and various other emerging therapeutic targets that have been proposed based on the phenotypic difference between keloid-derived fibroblasts (KFs) and normal epidermal fibroblasts (NFs). We then present recent studies on the biological effects of various plant-derived extracts and compounds on KFs and NFs. Associated ex vivo, in vivo, and clinical studies are also presented. Finally, we discuss the mechanisms of action of the plant-derived extracts and compounds, the pros and cons, and the future tasks for natural product-based therapy for keloid disease, as compared with existing other therapies. Extracts of Astragalus membranaceus, Salvia miltiorrhiza, Aneilema keisak, Galla Chinensis, Lycium chinense, Physalis angulate, Allium sepa, and Camellia sinensis appear to modulate cell proliferation, migration, and/or extracellular matrix (ECM) production in KFs, supporting their therapeutic potential. Various phenolic compounds, terpenoids, alkaloids, and other plant-derived compounds could modulate different cell signaling pathways associated with the pathogenesis of keloids. For now, many studies are limited to in vitro experiments; additional research and development are needed to proceed to clinical trials. Many emerging therapeutic targets could accelerate the discovery of plant-derived substances for the prevention and treatment of keloid disease. I hope that this review will bridge past, present, and future research on this subject and provide insight into new therapeutic targets and pharmaceuticals, aiming for effective keloid treatment.

Comparison of LeniScar Silicone Stick (AnsCare) With Traditional Silicone Gel (Dermatix Ultra) in Wound Scar Prevention and Removal.

BACKGROUND: As we all know, the numbers of aesthetic surgery are increasing around the world. After the surgery, the scar would be a problematic issue for both the surgeons and the patients. Silicone has proven to be effective for keloids, hypertrophic scars, and prevention of scar formation in many literatures for a long time. In terms of scar prevention, silicone has been used in the form of silicone sheets in early times, which is later improved to be the form of silicone gel with the advantage of easier usage. Although silicone gel has improved greatly in the aspect of appearance and convenience of the silicone sheets, there are still some disadvantages of the gel form. Therefore, the LeniScar silicone stick (AnsCare) is invented. OBJECTIVE: This article aimed to compare the results of scar treatment and prevention of the AnsCare LeniScar Silicone Stick versus the traditional silicone gel (Dermatix Ultra). METHODS: This study was a prospective, nonblinded, randomized clinical study. There were a total of 68 patients from September 2018 to January 2020. Patients were divided into 2 groups with AnsCare (n = 43) and Dermatix (n = 25), who both were required to schedule regular outpatient clinic follow-up, and photographs were taken before use, 1, 2, and 3 months later after the usage for the record. The physician assessed the scar condition by the Vancouver Scar Scale (VSS). The scores of the VSS were further analyzed and compared. RESULTS: The overall P value of total score of VSS was 0.635, which indicates that there is no significant difference in using AnsCare LeniScar Silicone Stick versus Dermatix Ultra silicone gel in terms of scar prevention and treatment. Individual items of VSS such as pliability, height, vascularity, and pigmentation all show no significant statistical difference in the 2 treatment products, with P = 0.980, 0.778, 0.528, and 0.366, respectively. CONCLUSION: Traditional Dermatix Ultra silicone gel has been effective in the treatment of scar formation. AnsCare LeniScar Silicone Stick is statistically not different from the Dermatix Ultra silicone gel when comparing the treatment results of scar prevention. Furthermore, the AnsCare LeniScar Silicone Stick has the advantages of being time-saving with no need to wait for it to dry and application of precise amount to precise location, preventing waste or overuse.

Excision and adjuvant treatment to prevent keloid recurrence. - a systematic review of prospective, clinical, controlled trials.

Keloids are defined as the formation of collagen-rich scar tissue extending beyond the original lesion. Not all keloids respond to conventional treatment with intralesional triamcinolone injections. Recurrence of keloids after primary excision is reported in almost 100% of cases and should therefore always be followed by adjuvant treatment. Currently, consensus on preferred adjuvant treatment in relation to keloid excision is lacking. This study seeks to systematically review evidence on the efficacy of adjuvant treatments in relation to keloid excision. A systematic literature review was conducted on PubMed. Titles, abstracts, and articles were screened and sorted according to defined inclusion- and exclusion criteria. Each study was evaluated according to the Oxford Centre for Evidence-Based Medicine, OCEBM, Levels of Evidence by two independent authors. Seven studies were eligible. Adjuvant treatment methods included intralesional triamcinolone injection, radiotherapy, silicone gel, pressure therapy, verapamil hydrochloride and 5-fluorouracil. While all the included studies reported promising results, two studies showed that minimizing dosages when treating with radiotherapy or triamcinolone should be considered to avoid adverse events. However, a high risk of bias was found in all the included studies.

A comparison of the efficacy of silicone gel containing onion extract and aloe vera to silicone gel sheets to prevent postoperative hypertrophic scars and keloids.

BACKGROUND: Hypertrophic scars and keloids are postsurgery problems. Some studies showed that onion extract and aloe vera might be beneficial for postoperative scars. However, few of the randomized clinical trials were investigated. AIMS: To compare the efficacy of silicone gel containing onion extract and aloe vera (SGOA) to silicone gel sheets (SGS) to prevent postoperative hypertrophic scars and keloids. METHODS: The prospective randomized assessor-blind controlled trial was conducted with 40 patients who had undergone surgery. The patients were divided into two groups: one treated with SGOA, the other with SGS. The patients were evaluated after 1, 2, and 3 months. The objective assessment was to determine the incidences of scarring, erythema, and melanin values using Mexameter, and pliability through Cutometer. The subjective assessment consisted of the patient and observer scar assessment scale (POSAS) and patient satisfaction. RESULTS: After the 12-week follow-up, there was no statistically significant difference in the scarring incidence rate of both groups. There were no statistical differences in the POSAS score, erythema, and melanin value between both groups. Using objective assessment, pliability in the SGOA group was statistically significantly higher compared to the SGS group. Pain and itchiness significantly decreased in both groups. No adverse effects were reported in either group. CONCLUSION: Silicone gel containing onion extract and aloe vera is effective as SGS for postoperative scar prevention.

The Latest Strategy for Keloid and Hypertrophic Scar Prevention and Treatment: The Nippon Medical School (NMS) Protocol.

In 2006, we established a scar/keloid-specialized unit in the Department of Plastic, Reconstructive, and Aesthetic Surgery at Nippon Medical School (NMS) in Tokyo, Japan. In the ensuing 15 years, we treated approximately 2,000 new scar/keloid patients annually. This extensive experience has greatly improved the efficacy of the treatments we offer. Therefore, we discuss here the latest NMS protocol for preventing and treating keloids and hypertrophic scars. While this protocol was optimized for Japanese patients, our experience with a growing body of non-Japanese patients suggests that it is also effective in other ethnicities. The extensive evidence-based experience underlying the NMS protocol suggests that it may be suitable as the foundation of a standard international prevention/treatment algorithm for pathological scars.

THE EFFECT OF PHOTODYNAMIC THERAPY AND PLATELET-ENRICHED PLASMA ON THE HEALING OF SKIN RADIATION ULCERS INFECTED BY STAPHYLOCOCCUS AUREUS. / VPLYV FOTODYNAMIChNOÏ TERAPIÏ TA ZBAGAChENOÏ TROMBOTsYTAMY PLAZMY NA PROTsESY ZAGOIeNNIa PROMENEVYKh VYRAZOK ShKIRY, INFIKOVANYKh STAPHYLOCOCCUS AUREUS.

OBJECTIVE: To determine in experiment the quality of healing of skin radiation ulcers infected with Staphylococcusaureus (S. aureus) under the photodynamic therapy (PDT) administration and the use of platelet-rich plasma (PRP). MATERIALS AND METHODS: The experiment was performed on 95 male WAG rats of 6 months of age, which were divided into three groups. Group 1 included animals in whom a skin radiation ulcers in the thigh area was simulated, followed by application of a 0.2 ml suspension of reference strain of S. aureus to its surface on the 7th day after irradiation. Group 2 included animals with S. aureus-infected skin radiation ulcers, in whom the PET was administered aday after infection contamination. Group 3 included animals with S. aureus-infected skin radiation ulcers, in whomthe PDT was administered a day after infection in the morning, and the PRP was manifold injected in periwound areain the afternoon. The skin with underlying soft tissues from the area of radiation damage were the material for morphological examination. The hematoxylin and eosin, picrofuxin according to van Gizon, Mallory staining wereapplied to micropreparations. A morphometric study was conducted. RESULTS: In animals with skin radiation ulcers, in whom the PDT was administered upon infection with S. aureus(group 2), compared with animals with simulated infected skin radiation ulcers without treatment (group 1), Theactivation (i.e. accelerating) of the healing occurred for the period from the 14th to the 52nd day of experiment dueto the active processes of wound cleansing from necrotized tissues, less pronounced inflammatory changes in thelesion, and active of appearance and maturation of granulation tissue, less pronounced hemodynamic, ischemic andalternative disorders in the dermis, hypodermis, muscle tissue surrounding the wound cavity, activation of proliferative processes in epithelial layer localized in the marginal parts of the wound. Formation of pathological (hypertrophic or keloid) scar of the skin was the result of healing of skin radiation ulcer infected with S. aureus. In animalswith radiation ulcers infected with S. aureus, in the case of PDT and PRP (group 3) the regenerative process wasdirected not only at accelerating the rate of healing, but also on restoration of original structure of the lost parts ofthe skin compared with only PDT administration (group 2). Acceleration of the healing of the infected skin radiation ulcer in animals of groups 2 and 3 was due to similar processes. CONCLUSIONS: Photodynamic therapy activates and accelerates the healing process of skin radiation ulcers infectedwith S. aureus and leads to formation of a pathological scar (hypertrophic or keloid). Healing of the infected S. aureusradiation ulcers occurs more actively upon the photodynamic therapy administration in combination with multipleperiwound injections of the platelet-enriched plasma, compared with only photodynamic therapy administration,and finishes with an organotypic regeneration and almost complete skin recovery.

Efficacy and Safety of Botulinum Toxin Type A in Preventing Postoperative Scars and Improving the Cosmetic Appearance of Scars: A Systematic Review and Meta-Analysis.

BACKGROUND: Scars with poor cosmesis that develop after wound healing may affect normal life. OBJECTIVE: To assess the efficacy and safety of botulinum toxin type A (BTXA) in preventing postoperative hypertrophic scars or keloids. METHODS: A systematic review was performed by searching the PubMed, Cochrane Library, and EMBASE databases from their inception date up to February 2020 for randomized controlled trials (RCTs) evaluating the efficacy of BTXA in preventing hypertrophic scars or keloids. The primary outcome measures included the Vancouver Scar Scale (VSS) score, Visual Analog Scale (VAS) score, scar width, patient satisfaction, and adverse events. RESULTS: Twelve RCTs involving 497 cases (372 patients) were included. The meta-analysis showed significant differences in the VAS score (weighted mean difference [WMD] = 1.31, 95% CI = 1.06 to 1.55, P < .00001), VSS score (WMD = -1.02, 95% CI = -1.72 to -0.32, P = .004), scar width (WMD = -0.18, 95% CI = -0.29 to -0.08, P = .0008), and patient satisfaction (relative risk = 1.25, 95% CI = 1.06-1.49, P = .01). Four studies reported trivial adverse events. CONCLUSIONS: This meta-analysis showed that BTXA was more effective than the control treatment in preventing postoperative scars and improving the cosmetic appearance of facial scars for East Asians, and no serious adverse events were found during the follow-up period. However, there was insufficient evidence to support the use of BTXA for the prevention of scars in patients from other ethnic groups and regions or scars in non-facial areas.

Dipeptidyl Peptidase-4 Inhibitor Reduces the Risk of Developing Hypertrophic Scars and Keloids following Median Sternotomy in Diabetic Patients: A Nationwide Retrospective Cohort Study Using the National Database of Health Insurance Claims of Japan.

BACKGROUND: Hypertrophic scars and keloids, which are abnormalities of fibrosis, often occur in surgical wounds; however, their exact cause and preventive measures are unknown. The administration of dipeptidyl peptidase-4 inhibitors to humans is expected to suppress fibrosis in wounds and minimize hypertrophic scar and keloid formation. METHODS: This study aimed to verify the suppressive effect of dipeptidyl peptidase-4 inhibitors on the formation of hypertrophic scars or keloids using real world data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. It is a retrospective cohort study, and data were extracted from the National Database between April of 2013 and March of 2015. Patients who underwent median sternotomy were included in the study based on their claimed surgical codes. Subjects who were prescribed dipeptidyl peptidase-4 inhibitors constituted the treatment group; subjects who were not prescribed or administered dipeptidyl peptidase-4 inhibitors during that period constituted the nontreatment group. RESULTS: Subjects included 5430 patients throughout Japan (3509 men and 1921 women). Of the 446 subjects who were treated with dipeptidyl peptidase-4 inhibitors within 1 year before the procedure, fewer than 10 (<2 percent) developed either hypertrophic scars or keloids. Of the 4984 subjects who were not treated, 152 (3.05 percent) were at significantly lower risk for hypertrophic scars and keloids (p = 0.04). A logistic regression analysis was performed to adjust for confounding factors, with history of hypertrophic scar formation as the explained variable. CONCLUSION: This study revealed that dipeptidyl peptidase-4 inhibitors suppress the onset of hypertrophic scars or keloids after surgery in humans. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

3d printed custom made pressure clips for ear keloid treatment after surgical excision.

BACKGROUND: The aim of this study is to introduce the efficacy of our 3D printer custom made pressure adjustable clips for preventing keloid recurrence after ear keloid surgical excision. Mechanical pressure is increasingly applied as a means to prevent or treat keloid scars. METHODS: 10 patients were included in the study, and were treated for six months with the 3D custom printed pressure clips after ear keloid excision surgery. The mean follow-up was one year. The primary outcome assessed was the degree of recurrence of keloids, with patient satisfaction as the secondary outcome assessed by subjective history. RESULTS: Keloid scars were reduced in the treated patient group. Patient scarring was decreased. There were no negative side effects observed after the therapy. CONCLUSION: Our 3d printed custom pressure-adjustable earclip model is an effective tool in the prevention of ear keloid recurrence and is associated with high patient satisfaction. The benefits should prompt further study on its value as an adjuvant therapy to surgery in keloid treatment. LEVEL OF EVIDENCE: Level III on the Evidence Rating Scale for Therapeutic Studies.

Continuous tension reduction to prevent keloid recurrence after surgical excision: Preliminary experience in Asian patients.

Surgical excision combined with postoperative radiotherapy is considered one of the most radical but most effective keloid therapeutic option. However, radiotherapy may not be appropriate for all keloid patients. In this study, we propose an alternate approach to prevent keloid recurrence and provide preliminary assessment in clinical efficacy of this treatment for keloids. Forty consecutive patients with different keloid sites underwent excision without postoperative radiation. After surgery, the tension offloading device was used at least 6 months for the purpose of continuous tension reduction at surgery incision. Scars were assessed independently using scar scale at before and 24-month follow-up. Overall, 38 patients completed this research. Clinical results showed that 35 patients achieved healing with an esthetic appearance at 24-month follow-up. Three patients showed relapse and the recurrence rate was 7.9%. Both of VSS (Vancouver Scar Scale) and JSW (Japan Scar Workshop Scar Scale) scores decreased significantly at 24-month follow-up visit than before. No severe complications were reported. Using the tension offloading device could greatly decrease tension on the surgical incision. The technique of continuous tension reduction could be used as an alternative method to prevent keloid recurrence under the condition of without radiotherapy.

Are Prophylactic Measures Necessary to Prevent Recurrence of Penile Keloids?

Keloid scars result from excess collagen deposition in the dermis or subcutaneous tissue in response to surgery or tissue trauma. The penis is a rare site for keloid formation, even in predisposed individuals. Only few cases of penile keloids have been reported so far. In this report, we present penile keloids complicating neonatal circumcision in twin brothers. Risk of recurrence in previous reports and measures to guard against its occurrence are also discussed.

Keloid and Hypertrophic Scar Formation, Prevention, and Management: Standard Review of Abnormal Scarring in Orthopaedic Surgery.

Keloid and hypertrophic scar formation after orthopaedic surgical closure is a complex issue. The nature and location of procedures maximize wound tension, leave foreign bodies, and diminish dermal supply, all potentiating keloid formation. There is little discussion regarding the pathophysiology and management of this recurrent problem in orthopaedic literature. Keloid formation is a fibroproliferative disorder resulting in extensive production of extracellular matrix and collagen, but prevention and treatment is poorly understood. Patient and surgical factors contributing to the development of this condition are discussed. The treatments include both medical and surgical therapies that work at a biologic level and attempt to produce a cosmetic and complication-free management strategy. Medical options that have been investigated include combinations of intralesional steroid therapy, laser therapy, and biologics. Preventive surgical closure and excision remain mainstays of treatment. Radiation therapy has also been used in refractory cases with mixed results. Despite medical therapies and surgical excision aimed at treating the resulting scar, recurrence rate is very high for all modalities that have been studied to this point. Future work is being done to better understand the pathophysiology leading to keloid and hypertrophic scar formation in an effort to find preventive methods as compared to treatment strategies.