Familial Spontaneous Keloids: Examining Thoracic Manifestations in Two Brothers.

Keloids are complex fibroproliferative disorders with diverse clinical presentations. Spontaneous keloids (SKs) represent a rare subtype that emerges without any known preceding traumatic event. This report presents a case of familial spontaneous keloids appearing on the thoracic region in two brothers with no prior history of trauma or keloid occurrence in other family members. The lesions exhibited progressive growth over several years but responded to cycles of triamcinolone treatment. This case underscores an unusual spontaneous occurrence of keloids in the thoracic region of two siblings, highlighting the potential genetic predisposition in the aetiology of these lesions. Additionally, this instance reinforces the concept that keloids can develop spontaneously without any apparent trauma in the affected area.

Safety and efficacy of intralesional bleomycin for keloids and hypertrophic scars: A systematic review and meta-analysis.

BACKGROUND: Bleomycin, originally an antitumor drug, was explored as a pathological scar treatment in the mid-1990s. However, its efficacy and safety profile varies among individuals. AIMS: This study aimed to assess topical bleomycin's efficacy and safety in treating hypertrophic scars and keloids. METHODS: We reviewed randomized controlled trials (RCTs) and controlled clinical trials (CCTs) published in English, comparing intralesional bleomycin to placebos or common intralesional scar treatments. Primary outcomes included percentage change in scar improvement, pigmentation, recurrence, atrophy, pain, telangiectasia, ulceration, patient self-assessment, and observer assessment (>50%). RESULTS: Six trials met the criteria. Bleomycin significantly improved scar reduction compared to triamcinolone (p < 0.05). There was no significant difference in pigmentation (p = 0.05) and recurrence (p = 0.21) compared to other treatments. In terms of safety, bleomycin caused less skin atrophy (p < 0.01) and telangiectasia (p < 0.01) but more pain (p = 0.03) than other treatments. CONCLUSIONS: Bleomycin was more effective than TAC, 5-FU, or TAC combined with 5-FU for treating keloids and hypertrophic scars with lower skin atrophy and telangiectasia risks. However, it may cause more pain than 5-FU or TAC. Further comprehensive studies, including RCTs, are required for objective analysis.

A Prospective Study of Patients Presenting With Pre-sternal Keloids.

INTRODUCTION: Keloid represents a pathological form of scarring. They are very common in the anterior chest area; nearly 50% of all keloids occur in this location. One of the reasons for this is that folliculitis and acne, known for triggering the development of keloids, are common on the anterior chest. The other reason is the tension load in this area due to the frequent movements of the upper limbs and the respiratory movements. These movements stretch the skin of the anterior chest horizontally. When this cyclical tension is imposed on the anterior chest wounds, there is an exacerbation and prolongation of the inflammation in the reticular dermis of the wound. These stresses induce the growth of keloids along the prevailing lines of skin tension. MATERIALS AND METHODS: We performed a prospective study in which patients were recruited over a period of one year. Patients presenting with symptomatic pre-sternal keloids and requesting treatment but were unwilling to undergo surgical intervention were included in this study. Patients with a history of previous thoracic surgery were excluded. Baseline assessment and documentation of the lesion were performed. The study patients received three sessions of intralesional injections of a combination of triamcinolone acetonide and hyaluronidase at four weekly intervals. The final assessment was performed four weeks after the third session. RESULTS: The study included 47 lesions in 47 patients with ages of the patients ranging from 16 to 70 years. Pre-sternal keloids were found to be more common among males than females, with a male-to-female ratio of 2.35:1. Patients presented with pre-sternal keloids that had been present for varying periods ranging from three to 81 months. All of our 47 patients completed the three sessions of the treatment. Following the treatment, there was an improvement in the patient's symptoms, as evidenced by the reduction in the mean pruritis scores and pain scores. There was an overall reduction in the size of the lesion. The decrease in the height of the lesions was more evident than the reduction in the craniocaudal or transverse dimensions of the lesions. There were improvements in Vancouver Scar Scale (VSS) vascularity scores and pliability scores following the treatment. CONCLUSION: We conclude that pre-sternal keloids should be considered as a distinct clinico-pathological entity. There are differences with regard to pathogenesis, clinical presentation, and management when compared to keloids elsewhere. Treatment with intralesional injections of a combination of triamcinolone acetonide and hyaluronidase effectively relieves the symptoms and may be considered in patients not willing to undergo surgical intervention. Recurrences can occur and need further treatments.

Causal relationship between gut microbiota and pathological scars: a two-sample Mendelian randomization study.

Background: Pathological scars, including keloids and hypertrophic scars, represent a significant dermatological challenge, and emerging evidence suggests a potential role for the gut microbiota in this process. Methods: Utilizing a two-sample Mendelian randomization (MR) methodology, this study meticulously analyzed data from genome-wide association studies (GWASs) relevant to the gut microbiota, keloids, and hypertrophic scars. The integrity and reliability of the results were rigorously evaluated through sensitivity, heterogeneity, pleiotropy, and directionality analyses. Results: By employing inverse variance weighted (IVW) method, our findings revealed a causal influence of five bacterial taxa on keloid formation: class Melainabacteria, class Negativicutes, order Selenomonadales, family XIII, and genus Coprococcus2. Seven gut microbiota have been identified as having causal relationships with hypertrophic scars: class Alphaproteobacteria, family Clostridiaceae1, family Desulfovibrionaceae, genus Eubacterium coprostanoligenes group, genus Eubacterium fissicatena group, genus Erysipelotrichaceae UCG003 and genus Subdoligranulum. Additional sensitivity analyses further validated the robustness of the associations above. Conclusion: Overall, our MR analysis supports the hypothesis that gut microbiota is causally linked to pathological scar formation, providing pivotal insights for future mechanistic and clinical research in this domain.

Ear keloid and epidermal cyst following auricular cartilage harvest for rhinoplasty: A case report.

BACKGROUND: This case report highlights a rare instance of concurrent keloid and epidermal cyst development at an ear cartilage harvest site following rhinoplasty in a 25-year-old woman. Both conditions, which typically stem from skin trauma, seldom occur together, demonstrating the exceptional characteristics of this case. CASE SUMMARY: The patient underwent successful surgical removal of both the keloid and the epidermal cyst. Postoperative treatment included the use of silicone sheets, gel, and oral tranilast to reduce scarring. No recurrence was observed over a 6-mo follow-up period, indicating effective management of the condition. CONCLUSION: The effective management of complex skin trauma cases underscores the need for individualized treatment strategies in plastic surgery.

Efficacy and Safety of Corticosteroid in Combination with 5-Fluorouracil in the Treatment of Keloids and Hypertrophic Scars: A Systematic Review and Meta-analysis.

BACKGROUND: Addressing hypertrophic scars and keloids poses a significant challenge in the realm of preventive and curative medicine. Combination corticosteroid with 5-fluorouracil (5-FU) is presumed to enhance the treatment of hypertrophic scars and keloids, although supportive evidence is lacking. This study is aimed at comparing the efficacy and safety profile of a combined corticosteroid and 5-FU regimen in treating hypertrophic scars and keloids. METHODS: A comprehensive search was conducted for pertinent studies across various databases, including Web of Science, PubMed, Google Scholar, Cochrane Library, and Medline. The calculation of weighted mean difference (WMD), risk ratios (RR), odds ratios (OR), and 95% confidence intervals (CIs) was executed. Additionally, the Cochrane Collaboration's Risk of Bias Tool was utilized to evaluate potential bias risks. RESULTS: A total of 15 studies were involved. The effectiveness based on patient self-assessment and the effectiveness based on observer assessment were significantly higher in the corticosteroid+5-FU group compared to those treated with control. A meta-analysis of scar height showed that the corticosteroid+5-FU group performed better than the control group (WMD = -0.38, 95% CI -0.58 to -0.18). There was no significant difference between the corticosteroid+5-FU group and the control group in improving scar vascularity, pliability and pigmentation. The result revealed that the corticosteroid+5-FU group of patients had less adverse effect of hypopigmentation, skin atrophy and telangiectasia than the control group. CONCLUSION: The combined use of corticosteroids and 5-FU appears to be a more effective strategy for the treatment and prevention of hypertrophic scars and keloids, as evidenced by greater improvements in scar height and overall effectiveness, coupled with a reduced incidence of side effects. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Can Electrical Stimulation Prevent Recurrence of Keloid Scars? A Scoping Review.

Objective: Keloids represent a symptomatic, aberrant healing process that is difficult to treat with high recurrence rates spanning from 55% to 100% if treated via excision without adjuvant therapy. Electrical stimulation (ES) has demonstrated findings that suggest it could reduce the recurrence rate of keloids after resection. Therefore, the aim of this study is to conduct a scoping review to investigate ES as an adjuvant therapy for decreasing keloid recurrence after excision. Approach: A scoping review was performed using PubMed and Web of Science databases. The search strategy encompassed terms linking keloids and various aspects of electrical stimulation. Results: Our search yielded 2,229 articles, of which 115 articles were analyzed as full text and 1 article met inclusion criteria. Despite this, ES has demonstrated other evidence that suggests its utility. ES has been shown to counter keloidic features by reducing mast cell counts, shifting wound composition from M2 to M1 macrophages, promoting angiogenesis, and controlling fibroblast orientation and location. An alternating current will orient fibroblasts perpendicular to the current without unintended migration. Innovation: Our study indicates that, based on a compilation of clinical and preclinical in vitro data, the optimal scenario for ES in the role of keloid treatment is after excision with a biphasic pulsed application and square waveform. Conclusions: ES could serve as a multifaceted, adjuvant treatment after keloid excision, steering the healing process away from keloid-associated characteristics. Its cost-effectiveness means it could be adopted globally, providing a strategy to mitigate the burden of keloids irrespective of other available treatments or economic conditions.

Successful treatment of Giant keloid on the right toes using trepanation combined with superficial radiotherapy (SRT-100): a case report with literature review.

In dermatology, a keloid is one of the most common skin morphological abnormalities caused by excessive proliferation of fibroblasts. Keloids that are large or occur near important joint sites often cause varying degrees of physiological dysfunction in patients, therefore requiring medical treatment. A boy with congenital syndactyly developed huge keloids at the surgical site after undergoing surgical correction treatment. After treatment using trepanation combined with superficial radiotherapy (SRT-100) in our hospital, most of the boy's keloids shrank and flattened. The affected foot returned to its normal appearance, and the boy could wear shoes normally. The boy did not complain of pain, numbness, or any other distinctive discomfort after completing the treatment. This suggested that the combination of trepanation and SRT-100 may be one of the options for treating hypertrophic keloids that cannot be treated by surgical excision.

Unlocking the potential of tranilast: Targeting fibrotic signaling pathways for therapeutic benefit.

Fibrosis is the excessive deposition of extracellular matrix in an organ or tissue that results from an impaired tissue repair in response to tissue injury or chronic inflammation. The progressive nature of fibrotic diseases and limited treatment options represent significant healthcare challenges. Despite the substantial progress in understanding the mechanisms of fibrosis, a gap persists translating this knowledge into effective therapeutics. Here, we discuss the critical mediators involved in fibrosis and the role of tranilast as a potential antifibrotic drug to treat fibrotic conditions. Tranilast, an antiallergy drug, is a derivative of tryptophan and has been studied for its role in various fibrotic diseases. These include scleroderma, keloid and hypertrophic scars, liver fibrosis, renal fibrosis, cardiac fibrosis, pulmonary fibrosis, and uterine fibroids. Tranilast exerts antifibrotic effects by suppressing fibrotic pathways, including TGF-ß, and MPAK. Because it disrupts fibrotic pathways and has demonstrated beneficial effects against keloid and hypertrophic scars, tranilast could be used to treat other conditions characterized by fibrosis.

Intralesional 5-Fluorouracil for Keloids: A Systematic Review.

Keloids are benign, fibroproliferative dermal tumours, often arising after trauma, that are more common in darker skin types. Numerous therapeutic options have been employed for the treatment of keloids; however, there is no one gold standard approach. Five-fluorouracil, a potent chemotherapeutic agent, has emerged as a promising therapeutic option. Therefore, this systematic review, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focused on providing a broad overview of the use of 5-fluorouracil for the management of keloids. Forty studies (2325 patients) met inclusion criteria and investigated 5-fluorouracil for keloid management, with 19 studies (1043 patients) including a 5-fluorouracil monotherapy group. Five-fluorouracil monotherapy demonstrated consistent keloid improvement with >254 keloids injected across various anatomical regions. Five-fluorouracil monotherapy was most often compared to intralesional triamcinolone acetonide, utilizing the Patient and Observer Scar Assessment Scale and the Vancouver Scar Scale. The most common keloid parameters assessed were height, size, volume, width, length, induration, pruritus, and erythema. Five-fluorouracil monotherapy exhibited substantial improvements, with weight averages of 73% of patients experiencing >25% improvement and 67% achieving >50% improvement. Relapse rate was 16% at 27 weeks after 5-fluorouracil monotherapy treatment. Limitations included potential selection bias, language restrictions, and heterogenous data analysis among studies. Overall, our findings underscore the potential effectiveness of 5-fluorouracil monotherapy in the management of keloids, with an encouraging safety profile. Larger prospective trials are needed to determine optimal therapy or combination therapy for the management of keloids. This detailed compilation of treatment protocols, outcomes, and relapse rates stand as a valuable resource for further research and clinical applications.

Effective keloid management using a combinatorial continuous-wave and repeat fractionated ablative CO2 laser regimen.

BACKGROUND: Keloids are benign proliferative scars that form as a result of dysregulated growth and collagen deposition in response to cutaneous injury. Laser therapies have emerged as promising options for the treatment of keloids, with performance varying by laser type and lesion characteristics. PURPOSE: To assess the combined continuous wave and repetitive fractionated CO2 laser treatment of keloids. METHODS: A retrospective chart review of 22 cases of keloid scars treated with combined CO2 laser modes. A single session of continuous wave followed by five sessions of fractional delivery. Efficacy was assessed using the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver Scar Scale. The Numeric Rating Scale was used to assess patient satisfaction and pain. RESULTS: Most patients were female (77.3%) with skin type IV (72.7%), age was 24.3 ± 9.3 years, most keloids were located on the earlobe (56.5%) or arm or hand (17.4%), size ranged from 5 to 10 cm, and time since injury ranged from 3 months to 35 years. No serious adverse events were reported. At 6 months, significant improvements from baseline occurred in all characteristics, scar color (4.8 ± 2.8 to 1.9 ± 1.1), rigidity (5.0 ± 2.8 vs. 5.4 ± 2.8), thickness (5.4 ± 2.8 vs. 2.0 ± 1.1), and irregularity (5.9 ± 2.4 vs. 1.9 ± 0.9). The Vancouver scores followed a similar trend. Patient-rated overall improvement from 37 ± 17.6 at baseline to 16.1 ± 8.5 at 6 months, and improvement in associated pain and pruritus. CONCLUSION: Combination of two ablative laser delivery modes within a single laser platform provided for effective and safe keloid management and left patients highly satisfied.

Acne-induced pathological scars: pathophysiology and current treatments.

Acne is a common chronic inflammatory dermatosis that can lead to pathological scars (PSs, divided into hypertrophic scars and keloids). These kinds of abnormal scars seriously reduce the quality of life of patients. However, their mechanism is still unclear, resulting in difficult clinical prevention, unstable treatment effects and a high risk of recurrence. Available evidence supports inflammatory changes caused by infection as one of the keys to abnormal proliferation of skin fibroblasts. In acne-induced PSs, increasing knowledge of the immunopathology indicates that inflammatory cells directly secrete growth factors to activate fibroblasts and release pro-inflammatory factors to promote the formation of PSs. T helper cells contribute to PSs via the secretion of interleukin (IL)-4 and IL-13, the pro-inflammatory factors; while regulatory T cells have anti-inflammatory effects, secrete IL-10 and prostaglandin E2, and suppress fibrosis production. Several treatments are available, but there is a lack of combination regimens to target different aspects of acne-induced PSs. Overall, this review indicates that the joint involvement of inflammatory response and fibrosis plays a crucial role in acne-induced PSs, and also analyzes the interaction of current treatments for acne and PS.

The effects of systemic diseases, genetic disorders and lifestyle on keloids.

Keloid are a fibroproliferative disorder caused by abnormal healing of skin, specifically reticular dermis, when subjected to pathological or inflammatory scars demonstrating redness, elevation above the skin surface, extension beyond the original wound margins and resulting in an unappealing cosmetic appearance. The severity of keloids and risk of developing keloids scars are subjected to elevation by other contributing factors such as systemic diseases, general health conditions, genetic disorders, lifestyle and natural environment. In particular, recently, daily physical work interpreted into mechanical force as well as the interplay between mechanical factors such as stress, strain and stiffness have been reported to strongly modulate the cellular behaviour of keloid formation, affect their location and shape in keloids. Herein, we review the extensive literature on the effects of these factors on keloids and the contributing predisposing mechanisms. Early understanding of these participating factors and their effects in developing keloids may raise the patient awareness in preventing keloids incidence and controlling its severity. Moreover, further studies into their association with keloids as well as considering strategies to control such factors may help clinicians to prevent keloids and widen the therapeutic options.

Inyección local de toxina botulínica para la prevención de cicatrices hipertróficas y queloides: un protocolo para una revisión panorámica

Introducción: Las cicatrices hipertróficas (CH) y queloides (QU) corresponden al resultado de una cicatrización patológica en la piel, que afectan la calidad de vida de quienes las presentan. Su tratamiento considera diversas intervenciones, muchas de las cuales son de alto costo y/o poco predecibles. Entre ellas, la toxina botulínica (TB) podría tener un efecto a nivel preventivo, aunque los resúmenes de evidencia presentan resultados disímiles. Por esto, proponemos sintetizar la evidencia proveniente de revisiones sistemáticas (RS) y metaanálisis (MA) de ensayos clínicos aleatorizados (ECA) sobre los efectos de la inyección local de TB en la prevención de CH y QU en pacientes que recibieron o recibirán un trauma quirúrgico en la piel. Métodos y análisis: Revisión panorámica siguiendo la declaración PRIOR. Ejecutaremos la búsqueda en la base de datos Epistemonikos. Realizaremos la selección de estudios, extracción de datos y evaluación de la calidad de las RS por duplicado. Compararemos las revisiones a través de matrices de evidencia, incluyendo las RS que aborden una pregunta similar y los ECA incluidos en estas. Estimaremos la superposición entre revisiones mediante el método de área cubierta y área cubierta corregida. Ética y difusión: No se requiere aprobación ética. Esta revisión se publicará después de un proceso de revisión por pares. Sus resultados podrían ser utilizados por personal de salud para informar decisiones individuales y por tomadores de decisión de servicios de salud para guiar la asignación de recursos.

Introduction: Hypertrophic scars (HS) and keloids (KE) result from an aberrant reparative process in the skin, impacting the quality of life of those who are affected by them. Their treatment consists of different interventions, many of which are costly and/or have unpredictable results. Among them, botulinum toxin (BT) might have a preventive effect, although current evidence summaries show varying results. Therefore, we aim to synthesize the evidence coming from systematic reviews (SRs) and meta-analyses (MA) of randomized controlled trials (RCTs) on the effects of local injection of TB in the prevention of HS and KE formation in patients after a surgical wound of the skin. Methods and analysis: This will be an overview of SRs following PRIOR statement. We will conduct the search in Epistemonikos Database. Two reviewers will independently conduct the screening of articles for inclusion, quality appraisal and data extraction. We will compare the SRs using an evidence matrix, including SRs that address this topic, and the RCTs included in them. We will estimate the overlap between them using the covered area method and corrected covered area index. Ethics and dissemination: Ethics approval is not required. This review will be published after a peer-review process. The results will inform areas of future research and could be used by health personnel to make individual decisions, and by healthcare managers, administrators, and policymakers to guide resource allocation.

Identification of Collagen-Suppressive Agents in Keloidal Fibroblasts Using a High-Content, Phenotype-Based Drug Screen.

Keloids are characterized by excessive extracellular collagen and exaggerated scarring. Large-volume lesions can be functionally debilitating, therapeutically intractable, and psychologically devastating. A key barrier to translational momentum for novel antikeloid agents is the lack of a faithful high-content screen. We devised, to our knowledge, a previously unreported phenotype-based assay that measures secreted collagen by keloidal fibroblasts in tissue hypoxic conditions (1% oxygen). Four keloidal fibroblasts and 1 normal dermal fibroblast line were exposed to 199 kinase inhibitors. Of 199 kinase inhibitors, 41 (21%) and 71 (36%) increased and decreased the CI¯norm (mean collagen inhibition normalized to viability) by more than 10%, respectively. The most collagen suppressive agents were CGP60474 (CI¯norm = 0.36), KIN001-244 (CI¯norm = 0.55), and RAF265 (CI¯norm = 0.58). The top candidate, CGP60474, consistently abolished collagens I and VII production, exhibited minimal global toxicity, and induced a fivefold increase in phosphorylated extracellular signal-regulated kinase. This proof-of-concept high-content screen can identify drugs that appear to target critical keloidal pathophysiology-collagen secretion.

Laser-Assisted Drug Delivery in the Treatment of Hypertrophic Scars and Keloids: A Systematic Review.

Hypertrophic scars and keloids are the results of an exaggerated healing process and are often associated with significant patient morbidity. Fractional ablative lasers create microchannels in the skin and penetrate into the substance of the scar, inducing a normal healing response in zones of created damage. Focal delivery of scar-modulating agents into the scar through these microchannels-a process termed laser-assisted drug delivery (LADD)-is a promising and developing treatment modality. In this systematic review, we aim to critically examine the evidence of LADD in the treatment of hypertrophic scars and keloids. The evidence suggests that LADD improves outcomes in hypertrophic scars and keloids. LADD is a more effective treatment modality than the topical application of agents in hypertrophic scars and equally effective as the intralesional injection of agents in keloids. There were few reports of adverse events. Evidence supports the use of LADD as an adjunct to non-surgical measures or a treatment modality to be used before more invasive measures such as surgical excision. However, the quality of evidence supporting this conclusion is inconsistent and lacks power. Additional studies are required to optimize dosages, laser settings, and agent choices for the treatment of these lesions.

Demographics, clinical characteristics, and treatment patterns among keloid patients: United States Electronic Health Records (EHR) Database Study.

INTRODUCTION: There is limited epidemiologic evidence on keloids using real-world data, especially in the United States (US) across race and ethnicity. METHODS: We conducted a retrospective cohort study using Cerner Real-World Data, between 2015 and 2021, to describe the demographic and clinical characteristics of US adults with keloids. Keloids were identified using a combination of ICD-10 and (Systemized Nomenclature of Medicine-Clinical Terms [SNOMED] codes). Demographics (including race and ethnicity), clinical characteristics, treatment patterns, and healthcare utilization were compared across keloid and non-keloid populations. RESULTS: Among 5,457 keloid patients identified in the study, the majority were female (61.8%) with a mean age of 34.2 years and of non-Hispanic Black, Hispanic, and Asian descent (P < 0.001). Relative to non-keloid cohorts, patients with keloids had significantly higher rates of integumentary, cardiorespiratory, general, auditory, and ocular surgeries and burns (all P < 0.05). Patients with keloids were also more likely to have comorbidities like obesity, hypertension, hyperlipidemia, and diabetes (P < 0.05) when compared to those with no keloids. A large proportion of keloids were untreated; among those treated, the most common keloid treatments were medication therapy (51.5%) and surgical excision (10.6%). Non-Hispanic Black and Hispanic keloid patients were significantly more likely to receive medication therapy and surgical excision (P < 0.001) compared to keloid patients of other races or ethnicities. CONCLUSIONS: This study provided real-world insights into the keloid population in the US. Our findings emphasize the high burden of keloids and its substantial impact on ethnic minorities. Given high keloid recurrence rates and limited standardized treatments for keloids, further research into keloids is crucial to the development of keloid-specific therapeutic options.