Low-Frequency Ultrasound Sensitive Piezo1 Channels Regulate Keloid-Related Characteristics of Fibroblasts.

Keloids are benign fibroproliferative tumors that severely diminish the quality of life due to discomfort, dysfunction, and disfigurement. Recently, ultrasound technology as a noninvasive adjuvant therapy is developed to optimize treatment protocols. However, the biophysical mechanisms have not yet been fully elucidated. Here, it is proposed that piezo-type mechanosensitive ion channel component 1 (Piezo1) plays an important role in low-frequency sonophoresis (LFS) induced mechanical transduction pathways that trigger downstream cellular signaling processes. It is demonstrated that patient-derived primary keloid fibroblasts (PKF), NIH 3T3, and HFF-1 cell migration are inhibited, and PKF apoptosis is significantly increased by LFS stimulation. And the effects of LFS is diminished by the application of GsMTx-4, the selective inhibitor of Piezo1, and the knockdown of Piezo1. More importantly, the effects of LFS can be imitated by Yoda1, an agonist of Piezo1 channels. Establishing a patient-derived xenograft keloid implantation mouse model further verified these results, as LFS significantly decreased the volume and weight of the keloids. Moreover, blocking the Piezo1 channel impaired the effectiveness of LFS treatment. These results suggest that LFS inhibits the malignant characteristics of keloids by activating the Piezo1 channel, thus providing a theoretical basis for improving the clinical treatment of keloids.

An analysis of keloid patient questions on Reddit.

Reddit is one of the world's leading social media platforms, fostering active community discussions on a variety of topics including keloids. The prevalence and reach of conversations on Reddit underscore the need to investigate and understand patient perspectives and gaps in knowledge. Herein, we present an in-depth analysis of questions and concerns of Reddit users on keloids, offering valuable insights into patient experiences, knowledge gaps and treatment preferences. The study presents a distinct approach by harnessing the power of social media data to understand patient perspectives, which may not be readily apparent in clinical settings. All posts on the 'Hot' page of the subreddit r/Keloids were analyzed. Questions were categorized and subcategorized to reveal common themes. A total of 644 questions from 513 posts between 26 March 2017 and 28 August 2023 were identified and analyzed. Reddit users most frequently asked questions regarding keloid management (57.5%). Other common categories included uncertainty regarding diagnosis or symptoms (15.1%), living with keloids (7.5%) and causes or triggers (6.2%). This analysis highlights critical areas of patient knowledge gaps and potential misconceptions regarding keloids. For dermatologists, understanding these patient questions is crucial. Such insights allow for patient-centric education and treatments, ensuring more effective and comprehensive care.

Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets.

Pathological scarring resulting from traumas and wounds, such as hypertrophic scars and keloids, pose significant aesthetic, functional and psychological challenges. This study provides a comprehensive transcriptomic analysis of these conditions, aiming to illuminate underlying molecular mechanisms and potential therapeutic targets. We employed a co-expression and module analysis tool to identify significant gene clusters associated with distinct pathophysiological processes and mechanisms, notably lipid metabolism, sebum production, cellular energy metabolism and skin barrier function. This examination yielded critical insights into several skin conditions including folliculitis, skin fibrosis, fibrosarcoma and congenital ichthyosis. Particular attention was paid to Module Cluster (MCluster) 3, encompassing genes like BLK, TRPV1 and GABRD, all displaying high expression and potential implications in immune modulation. Preliminary immunohistochemistry validation supported these findings, showing elevated expression of these genes in non-fibrotic samples rich in immune activity. The complex interplay of different cell types in scar formation, such as fibroblasts, myofibroblasts, keratinocytes and mast cells, was also explored, revealing promising therapeutic strategies. This study underscores the promise of targeted gene therapy for pathological scars, paving the way for more personalised therapeutic approaches. The results necessitate further research to fully ascertain the roles of these identified genes and pathways in skin disease pathogenesis and potential therapeutics. Nonetheless, our work forms a strong foundation for a new era of personalised medicine for patients suffering from pathological scarring.

Pruritus in keloid scars: mechanisms and treatments.

Keloids occur after cutaneous injury and can cause distress due to physical appearance and associated symptoms such as pain and pruritus. Keloid-associated pruritus is a common manifestation and has negative impacts on quality of life. The mechanism underlying this type of pruritus is multifactorial and thought to involve small nerve fiber damage, neurogenic inflammation, and a Th2-predominant inflammatory response. Various agents have been shown to reduce keloid pruritus, including intralesional corticosteroids, botulinum toxin A, 5-fluorouracil, and bleomycin. Other treatment modalities such as cryotherapy and hyperbaric oxygen therapy are also effective. Future treatments targeting the mechanisms involved in keloid-associated itch could provide improvements in pruritus and quality of life in these patients, but further studies on the efficacy of these agents are needed.

Fibrosis in burns: an overview of mechanisms and therapies.

Scar development remains a common occurrence and a major healthcare challenge affecting the lives of millions of patients annually. Severe injuries to the skin, such as burns can lead to pathological wound healing patterns, often characterized by dermal fibrosis or excessive scarring, and chronic inflammation. The two most common forms of fibrotic diseases following burn trauma are hypertrophic scars (HSCs) and keloids, which severely impact the patient's quality of life. Although the cellular and molecular mechanisms are similar, HSC and keloids have several distinct differences. In this review, we discuss the different forms of fibrosis that occur postburn injury, emphasizing how the extent of burn influences scar development. Moreover, we highlight how a systemic response induced by a burn injury drives wound fibrosis, including both the role of the inflammatory response, as well as the fate of fibroblast during skin healing. Finally, we list potential therapeutics aimed at alleviating pathological scar formation. An understanding of the mechanisms of postburn fibrosis will allow us to effectively move studies from bench to bedside.

Comparing intralesional triamcinolone and verapamil-triamcinolone injections in keloids: A single-blinded randomised clinical trial.

INTRODUCTION: In this clinical trial, we investigated the efficacy of two treatment methods for keloids resulting from surgical incisions: intralesional triamcinolone injections alone versus in combination with verapamil. MATERIAL AND METHODS: Patients were divided into two groups: one received triamcinolone alone (Group T) and the other received a triamcinolone-verapamil blend (Group VT). Regular treatments were conducted until the keloids were nearly flat or for a maximum of eight sessions. RESULTS: Both groups showed significant improvements, but Group VT saw quicker resolution of skin redness and needed fewer sessions. Though the Vancouver Scar Scale (VSS) scores were generally similar across both groups, Group VT exhibited greater improvements, leading to lower final scores. The VT group also attained normal scar flexibility faster than the T group. CONCLUSION: These findings suggest that the combination of verapamil and triamcinolone provides a more effective treatment for keloids, thereby highlighting the potential of verapamil in scar reduction.

Therapy of pathological scars.

A scar develops following the appearance of a deep tissue defect as part of the physiological wound healing process. The initial inflammatory response is followed by proliferation of connective tissue cells, which form fibrosis as a final tissue substitute. Disorders can occur at all stages of the process and are most commonly manifested as impaired wound healing or the formation of atrophic and hypertrophic scars or keloids. The focus of this article is on the treatment of pathologic scars, which are an indication for therapy due to functional limitations, complaints, and stigmatization, among other reasons. Conservative medical, physical, surgical and laser therapeutic approaches are pursued. The basis for this is an understanding of the pathophysiological mechanisms and factors influencing the choice of therapy, as well as an interdisciplinary and interprofessional therapeutic approach.

Effectiveness of various methods of manual scar therapy.

BACKGROUND: The skin is a protective barrier of the body against external factors, and its damage leads to a loss of integrity. Normal wound healing results in a correct, flat, bright, and flexible scar. Initial skin damage and patient specific factors in wound healing contribute that many of these scars may progress into widespread or pathologic hypertrophic and keloid scars. The changes in cosmetic appearance, continuing pain, and loss of movement due to contracture or adhesion and persistent pruritis can significantly affect an individual's quality of life and psychological recovery post injury. Many different treatment methods can reduce the trauma and surgical scars. Manual scar treatment includes various techniques of therapy. The most effectiveness is a combined therapy, which has a multidirectional impact. Clinical observations show an effectiveness of manual scar therapy. MATERIAL AND METHODS: The aim of this work was to evaluate effectiveness of the scar manual therapy combined with complementary methods on the postoperative scars. Treatment protocol included two therapies during 30 min per week for 8 weeks. Therapy included manual scar manipulation, massage, cupping, dry needling, and taping. RESULTS: Treatment had a significant positive effect to influence pain, pigmentation, pliability, pruritus, surface area, and scar stiffness. Improvement of skin parameters (scar elasticity, thickness, regularity, color) was also noticed. CONCLUSION: To investigate the most effective manual therapy strategy, further studies are needed, evaluating comparisons of different individual and combined scar therapy modalities.

[Status of diagnosis and treatment of hypertrophic scar and keloid].

In recent years, many high-quality studies have been conducted on the pathomechanism and treatment of hypertrophic scar and keloid. This article briefly summarizes the status in these two aspects. Hypertrophic scar and keloid belong to pathological scar, which is characterized by fibrous dysplasia of reticular layer of dermis. This abnormal hyperplasia is due to the chronic inflammatory reaction in the dermis caused by injury. Some risk factors affect the process and outcome of the scar by increasing the intensity and duration of the inflammatory reaction. It is effective to understand the relevant risk factors to conduct patient education and prevent the occurrence of pathological scars. In view of these risk factors, a comprehensive treatment system, including multiple methods, has been established. Recent high-quality clinical research has provided evidence-based medical evidence for these treatments and prevention methods, which has confirmed the effectiveness and safety of the system.

Epidermal Potentiation of Dermal Fibrosis: Lessons from Occlusion and Mucosal Healing.

Fibrotic skin conditions, such as hypertrophic and keloid scars, frequently result from injury to the skin and as sequelae to surgical procedures. The development of skin fibrosis may lead to patient discomfort, limitation in range of motion, and cosmetic disfigurement. Despite the frequency of skin fibrosis, treatments that seek to address the root causes of fibrosis are lacking. Much research into fibrotic pathophysiology has focused on dermal pathology, but less research has been performed to understand aberrations in fibrotic epidermis, leading to an incomplete understanding of dermal fibrosis. Herein, literature on occlusion, a treatment modality known to reduce dermal fibrosis, in part through accelerating wound healing and regulating aberrant epidermal inflammation that otherwise drives fibrosis in the dermis, is reviewed. The review focuses on epidermal-dermal crosstalk, which contributes to the development and maintenance of dermal fibrosis, an underemphasized interplay that may yield novel strategies for treatment if understood in more detail.

Prevalence, exposure and the public knowledge of keloids on four continents.

INTRODUCTION: Keloid scars are associated with physical and psychological sequelae. No studies have investigated the general public's understanding of keloids. Targeted, short educational interventions in susceptible individuals may aid understanding of the condition and compliance with treatment. We aimed to identify the population with the highest prevalence and lowest knowledge. METHODS: We surveyed four countries to determine the public's understanding of keloids. A quantitative, subjective and cross-sectional street survey was designed using the knowledge, attitudes and practice model principles. The target populations were cities in Ghana, Australia, Canada and England. Surveyors used a hybrid stratified/convenience sampling method. Primary outcomes were prevalence, exposure to keloids as an entity and overall keloid knowledge score compared across demographic groups. Study data have been made fully available for reproducibility and education (https://doi.org/10.17605/OSF.IO/3KZ5E). RESULTS: There were 402 respondents, with a median age of 32 (interquartile range 25-45.25) years, of which 193 were females. The survey was carried out between June 2015 and October 2017. The prevalence of self-identified keloids was 11% in Ghana, 6% in Australia, 2% in Canada and 7% in England. Prevalence, exposure and knowledge were higher in the Ghanaian population. CONCLUSIONS: There was association between knowledge, prevalence and the exposure to keloids as an entity. Findings may suggest targeting public health campaigns towards populations where knowledge is lowest, and exposure to and prevalence of keloids are the highest.

Silicone gel sheeting for treating keloid scars.

BACKGROUND: Keloid scarring is one of the most common types of pathological scarring. Keloid scars that fail to heal can affect a person's physical and psychological function by causing pain, pruritus, contractures, and cosmetic disfigurement. Silicone gel sheeting (SGS) is made from medical-grade silicone reinforced with a silicone membrane backing and is one of the most commonly used treatments for keloid scars. However, there is no up-to-date systematic review assessing the effectiveness of SGS for keloid scars. A clear and rigorous review of current evidence is required to guide clinicians, healthcare managers and people with keloid scarring. OBJECTIVES: To assess the effectiveness of silicone gel sheeting for the treatment of keloid scars compared with standard care or other therapies. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was December 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that recruited people with any keloid scars and assessed the effectiveness of SGS. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessment, data extraction and GRADE assessment of the certainty of evidence. We resolved initial disagreements by discussion, or by consulting a third review author when necessary. MAIN RESULTS: Two studies met the inclusion criteria. Study sample sizes were 16 and 20 participants. The trials were clinically heterogeneous with differences in causes for scarring (e.g. surgery, infected wounds, and trauma), site (e.g. chest and back), and ages of scars. The duration of follow-up was three and four and a half months. The included studies reported three comparisons; SGS compared with no treatment, SGS compared with non-silicone gel sheeting (a dressing similar to SGS but which does not contain silicone), and SGS compared with intralesional injections of triamcinolone acetonide. One trial had a split-body design and one trial had an unclear design (resulting in a mix of paired and clustered data). The included studies reported limited outcome data for the primary review outcome of scar severity measured by health professionals and no data were reported for severity of scar measured by patients or adverse events. For secondary outcomes some data on pain were reported, but health-related quality of life and cost-effectiveness were not reported. Both trials had suboptimal outcome reporting, thus many domains in the risk of bias were assessed as unclear. All evidence was rated as being very low-certainty, mainly due to risk of bias, indirectness, and imprecision.  SGS compared with no treatment Two studies with 33 participants (76 scars) reported the severity of scar assessed by health professionals, and we are uncertain about the effect of SGS on scar severity compared with no treatment (very low-certainty evidence, downgraded once for risk of bias, once for inconsistency, once for indirectness, and once for imprecision). We are uncertain about the effect of SGS on pain compared with no treatment (21 participants with 40 scars; very low-certainty evidence, downgraded once for risk of bias, once for inconsistency, once for indirectness, and once for imprecision). No data were reported for other outcomes including scar severity assessed by patients, adverse events, adherence to treatment, health-related quality of life and cost-effectiveness. SGS compared with non-SGS One study with 16 participants (25 scars) was included in this comparison. We are uncertain about the effect of SGS on scar severity assessed by health professionals compared with non-SGS (very low-certainty evidence, downgraded once for risk of bias, once for indirectness, and once for imprecision). We are also uncertain about the effect of SGS on pain compared with non-SGS (very low-certainty evidence, downgraded once for risk of bias, once for indirectness, and once for imprecision). No data were reported for other outcomes including scar severity assessed by patients, adverse events, adherence to treatment, health-related quality of life and cost-effectiveness. SGS compared with intralesional injections of triamcinolone acetonide One study with 17 participants (51 scars) reported scar severity assessed by health professionals, and we are uncertain about the effect of SGS on scar severity compared with intralesional injections of triamcinolone acetonide (very low-certainty evidence, downgraded once for risk of bias, once for indirectness, and once for imprecision). This study also reported pain assessed by health professionals among 5 participants (15 scars) and we are uncertain about the effect of SGS on pain compared with intralesional injections of triamcinolone acetonide (very low-certainty evidence, downgraded once for risk of bias, once for indirectness, and twice for imprecision). No data were reported for other outcomes including scar severity assessed by patients, adverse events, adherence to treatment, health-related quality of life and cost-effectiveness. AUTHORS' CONCLUSIONS: There is currently a lack of RCT evidence about the clinical effectiveness of SGS in the treatment of keloid scars. From the two studies identified, there is insufficient evidence to demonstrate whether the use of SGS compared with no treatment, non-SGS, or intralesional injections of triamcinolone acetonide makes any difference in the treatment of keloid scars. Evidence from the included studies is of very low certainty, mainly driven by the risk of bias, indirectness, and imprecision due to small sample size. Further well-designed studies that have good reporting methodologies and address important clinical, quality of life and economic outcomes are required to reduce uncertainty around decision-making in the use of SGS to treat keloid scars.

The Detroit Keloid Scale: A Validated Tool for Rating Keloids.

Background: Comparing keloid treatment modalities and assessing response to treatments may be predicted by a better classification system. Objectives: To develop and validate the Detroit Keloid Scale (DKS), a standardized method of keloid assessment. Methods: Forty-seven physicians were polled to develop the DKS. The scale was validated in 52 patients against the Vancouver Scar Scale (VSS), Patient and Observer Scar Assessment Scale (POSAS), and Dermatology Life Quality Index (DLQI). Results: The inter-rater reliability was "substantial" for observer DKS and only "moderate" for VSS and observer POSAS (intraclass correlation coefficient were 0.80, 0.60, and 0.47, respectively). Pearson's correlation indicated "moderate" association between observer DKS with observer POSAS (ρ = 0.56, p < 0.001) and "substantial" relationship between observer DKS and VSS (ρ = 0.63, p < 0.001). Pearson's correlation indicated "moderate" association between patient portion of DKS and patient portion of POSAS and patient portion of the DKS and DLQI (0.61 and 0.60, respectively, p < 0.05). DKS total score consistently showed significant "substantial" relationship with POSAS total score (ρ = 0.65, p < 0.001). Conclusions: The DKS offers a validated keloid-specific outcome measure for comparing keloid treatments.

Combination Therapy for a Severe Axillary Keloid with Abscesses: A Case Report.

Keloids are laterally growing fibroproliferative skin disorders. Severe keloids spread widely, sometimes over joints, thus significantly limiting motor function. They are associated with recurrent, very painful draining infections. Here, we report a case of a giant keloid that was successfully treated by combination therapy comprising surgery (partial resection followed by local flap transposition) and subsequent radiotherapy and steroid-plaster therapy. The keloid was first noticed when the patient was 7 years old at the site of a Bacille Calmette-Guérin vaccination she had received on her left shoulder in infancy. The keloid grew rapidly and widely after adulthood. A malignant tumor was suspected at another hospital, but a biopsy at age 45 years indicated the lesion was a keloid. Later, the keloid grew from the shoulder onto the chest and back and over the anterior axilla. At age 62 years, the patient was referred to our hospital. Under general anesthesia, the keloid was partially resected and the wound was covered with a local flap. Postoperative radiotherapy was performed 1 week later. The residual keloid was treated for 18 months with steroid tape. At 18 months after surgery, no recurrence of the keloid was observed. The patient had no pain or movement restriction. She was extremely satisfied with the results and considered the treatment to have improved her quality of life. While a standard strategy for severe keloid remains to be established, combination therapy comprising surgery, postoperative radiotherapy, and steroid-plaster therapy that aims to reduce inflammation and skin tension may be an option.

Keloids and Hypertrophic Scars.

Keloids and hypertrophic scars are abnormal responses to wound-healing. While hypertrophic scars remain limited to the areas of trauma, keloids most often develop over several years, growing out from the limits of the initial wound area. Both lesions may cause itching, burning, and pain, and they may lead to significant impairment of self-esteem, socialization, and quality of life. Although they might be observed in all races, they are far more common in Africans and African descendants than in Caucasians.We extensively reviewed their treatment, including compression with pressure garments, occlusion with siliconized and non-siliconized gel sheets, gels, corticosteroid and antineoplastic injections, and the use of lasers and intense pulsed light (IPL) therapy. We also reviewed new therapies, including botulinum toxin injection, and addressed outcomes of various studies. (SKINmed. 2022;20:432-443).

The Inhibition of Adipose-Derived Stem Cells on the Invasion of Keloid Fibroblasts.

Background: Keloids represent the dysregulation of cutaneous wound healing caused by aberrant fibroblast activities. Adipose-derived stem cells have been recognized as a promising treatment for keloids. However, the molecular mechanisms have not been fully elucidated. Objectives: to explicitly demonstrate the relationship between adipose-derived stem cells alleviating keloids and alterations of Col-1, Col-3, CTGF, and P-4-HB. Methods: Skin biopsies were obtained from 10 keloid patients and 9 healthy volunteers. Fibroblasts isolated from all samples were divided into two groups, one co-cultured with adipose-derived stem cells and the other grown independently. We compared the wound-healing rates, fibroblast survival rates, apoptosis rates, mRNA expressions, and protein levels of Col-1, Col-3, CTGF, and P-4-HB between separated groups. Results: We found no significant differences between normal fibroblasts and keloid fibroblasts in terms of wound-healing rate, survival rate, or apoptosis rate at the baseline. With adipose-derived stem cells, wound-healing rate and survival rate of normal fibroblasts were promoted, whereas in keloid fibroblasts, they were reduced. The apoptosis rate of normal fibroblasts and keloid fibroblasts were restrained, with the restraint in keloid fibroblasts being more evident. The protein levels of Col-3, CTGF, and P-4-HB were lower in keloid fibroblasts co-cultured with adipose-derived stem cells than in normal fibroblasts under similar conditions. Conclusions: Adipose-derived stem cells strongly suppressed keloid fibroblasts' proliferative and invasive behavior. However, adipose-derived stem cells negatively regulated keloid fibroblast apoptosis. Adipose-derived stem cells can be a potential keloid therapy worth further investigation.

[Treatment of keloids at the ear]. / Therapie von Keloiden am Ohr.

Keloids belong to the group of fibroproliferative diseases and clinically often present with functional and cosmetic impairment of the patient, as well as with pruritus and pain. The pathogenesis of keloids has not been definitively clarified and treatment is often protracted and less than satisfactory. A variety of therapeutic options are available for treatment of keloids; however, the evidence base is small due to studies with low case numbers. Use of multimodal treatment concepts seems to be promising and has shown good results, especially in the treatment of auricular keloids.

Keloid therapy: A neoteric comparative study.

BACKGROUND: Keloids are considered disorders of fibroproliferation characterized by accumulation of collagen fibers in hypodermis and dermis, caused by inflammation, surgery, and trauma. OBJECTIVES: The main goal of the study was to approach a better modality for the treatment of keloids by comparing the effects and the side effects of intralesional cryotherapy and intralesional injection of bleomycin. METHODS: This interventional, comparative clinical trial was conducted on 60 cases and was divided equally into the group (A), combined group who were subjected to intralesional bleomycin followed by cryotherapy in the same session, group (B) who were subjected to intralesional injection of bleomycin, and group (C) intralesional cryotherapy. All cases were subjected to clinical examination, complete history taking, dermatological examination, examination, and evaluation of scar lesion using the Vancouver scar scale. RESULTS: There was a statistically significant decrease in pliability among the combined group. Also, pliability decreased in the bleomycin group and cryotherapy, but this decrease wasn't statistically significant. Our results revealed that there was a statistically significant decrease in lesion height among all the studied groups, but the decrease was more among the combined group. CONCLUSION: Intralesional cryotherapy was effective as intralesional bleomycin. Combined therapy was a valid and more effective technique with few adverse effects than either alone for keloids as it achieved a decrease in volumes of scars or accompanied symptoms.

[Treatment of keloids]. / Therapie von Keloiden.

Keloids belong to the group of fibroproliferative diseases and clinically often present with functional and cosmetic impairment of the patient, as well as with pruritus and pain. The pathogenesis of keloids has not been definitively clarified and treatment is often protracted and less than satisfactory. A variety of therapeutic options are available for treatment of keloids; however, the evidence base is small due to studies with low case numbers. Use of multimodal treatment concepts seems to be promising and has shown good results, especially in the treatment of auricular keloids.