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Scar severity. Keloids and hypertrophic scars are multifactorial disorders that are driven by genetic predisposition, systemic conditions, and local wound conditions.
Source publication
Keloids and hypertrophic scars are fibroproliferative disorders (FPDs) of the skin that result from abnormal healing of injured or irritated skin. They can be called pathological or inflammatory scars. Common causes are trauma, burn, surgery, vaccination, skin piercing, folliculitis, acne, and herpes zoster infection. The pathogenesis of these scar...
Context in source publication
Context 1
... scars are multifactorial disor- ders that are driven by genetic predisposition, systemic conditions, and local wound conditions, including mechanobiological dysregu- lation of the dermis and blood vessels. We propose that the balance between these factors may determine whether a wound becomes a keloid, hypertrophic scar, or normal scar (Figs. 5 and ...
Citations
... Scar occurrence and irritation is frequently attributed to trauma, burns, surgery, vaccination, skin piercing, acne, and herpes zoster. Additionally, these conditions are often accompanied by intermittent pain, persistent itching, and a feeling of constriction 3 . Under normal circumstances, immature scar undergoes a maturation process that may last several months. ...
Background
Scar impairments impose a great economic burden and influence a subject’s well-being and quality of life. Despite that, physiotherapy interventions are poorly investigated.
Objective of the study
Provide a comprehensive overview of studies addressing physiotherapy and conservative non-invasive interventions for skin scar management, summarizing studies based on scar type, localization, patient’s characteristics (e.g., age), safety and tolerance of physical interventions. The realization of an infographic will assist clinicians and patients with scars’ management. Moreover, any knowledge gaps will be identified.
Methods
The review will be conducted following the Joanna Briggs Institute Manual for Evidence Synthesis. MEDLINE Central, PEDro, Embase, Cochrane Library and Central Register of Controlled Trials (CENTRAL) and CINAHL and grey literature (e.g., Google Scholar) will be searched for studies considering physical therapy interventions in scars management. Every study considering conservative non-invasive physiotherapy interventions for scar management will be included. This review will look at studies carried out in any context. Articles written in English or Italian will be considered. No temporal or publication type restrictions will be placed. Selection and extraction of data will be done by three reviewers independently, any discrepancies will be resolved by a fourth reviewer. The results will be illustrated using descriptive statistics and summarized in an infographic.
Ethics and dissemination
No ethics approval will be necessary.
... Furthermore, keloids are associated with intermittent pain, persistent itching and a sensation of contraction. 2 Under normal homeostatic conditions, wound repair is limited in its scope and intensity. Most wounds fully mature within several months to over a year. ...
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.
... Although the ethnic/familial predisposition to keloid is suggestive of a genetic foundation, keloid growth may also be promoted by systemic disease factors and local mechanical forces on the wound/scar. 3,4 To our knowledge, this is the first report of retroauricular keloid caused by ear-loop face mask (ELFM) use. In this case report we discuss the possible etiological mechanisms and management of such lesions. ...
... Indeed, hypertension associates with keloid worsening. 3 Notably, older individuals rarely develop keloids, possibly because of skin slackness and immunosenescence. 4 Evidently however, this could not protect our patient due to the abundance of risk factors in his case. ...
The recent COVID-19 pandemic required many people to wear ear-loop face masks (ELFMs) for protracted periods, and ear injuries have been reported. Here, we report a rare case of a keloid on the right posterior ear that appeared to arise from prolonged ELFM use. A 76-year-old Japanese man presented with a 7.3 × 2.2 × 1.4-cm keloid running from the medial retroauricular sulcus to the posterior lobule. The lack of keloid history suggested the absence of genetic risk factors. The patient reported extensive mask-wearing habits that were augmented by the pandemic. The keloid developed from an ear injury. Although it healed well, it started thickening 2 months later. Because local mechanical forces (eg, pressure/friction) can promote keloid growth, the ELFM may have provoked the keloid. The patient disclosed a history of uncontrolled hypertension and diabetes mellitus, which associate with severe keloids. The whole keloid was removed via total excision, and the defect was closed primarily and subjected to 15Gy/2Fr radiotherapy. The patient was advised to use a different mask type. Twelve months later, the scar had healed without complications or recurrence and with good cosmetic outcomes. Thus, ELFMs can promote retroauricular keloid formation, possibly by imposing local pressure/friction. ELFMs may also raise local skin temperatures and humidity, thereby fostering infection, which can trigger keloids. Hypertension/diabetes may further elevate the risk of EFLM-induced keloid. Thus, an auricular keloid is an unusual complication of prolonged ELFM use. Combination therapy can have excellent outcomes. Patients with keloid risk factors should be advised to use face masks without ear loops.
... 19 In addition, the Japan Scar Workshop Scar Scale 2015 (JSS) 20,21 was developed in Japan as a more reproducible evaluation method with specific photographic examples and is used in clinical practice and research. [22][23][24][25] As evaluation methods have been refined, higher-quality evidence is required. ...
OBJECTIVE: To determine the prophylactic effect of hydrocolloid dressings on hypertrophic scarring in post-cesarean section wounds. METHODS: Patients who underwent cesarean section (C/S) at the authors' hospital and provided informed consent to participate were randomly assigned to the intervention and control groups. The intervention group commenced applying hydrocolloid dressings to the wound on postoperative day 7 or 8 and continued with weekly dressing changes for 6 months. The control group refrained from any dressing application but was followed up. In each group, the condition of the wound was evaluated 6 and 12 months postoperatively using the Japan Scar Workshop Scar Scale 2015, the Patient and Observer Scar Assessment Scale version 2.0, the modified Vancouver Scar Scale, and patient-reported outcomes. RESULTS: During this period, 135 patients underwent C/S at the authors' institution, and 47 (23 in the intervention group and 24 in the control group) were included in the analysis. In all assessment methods, the intervention group scored lower than the control group at 6 and 12 months after C/S. Twelve months after C/S, hypertrophic scarring (Japan Scar Workshop Scar Scale 2015 score of 6-15) was found in 14 of the 47 (29.8%) patients: 11 of 24 (45.8%) in the control group and 3 of 23 (13.0%) in the intervention group. The intervention's relative risk was 0.623 (95% CI, 0.417-0.930). The risk factor for hypertrophic scarring was midline vertical incision, with an odds ratio of 20.53 (95% CI, 4.18-100.92). CONCLUSIONS: The study reveals that the application of hydrocolloid dressings to wounds reduces the risk of hypertrophic scarring after C/S.
... On one facet, the incomplete structural makeup of nascent blood vessels during angiogenesis bestows upon them elevated permeability, facilitating immune cell infiltration and the entry of inflammatory cytokines from microvessels into the extracellular matrix (ECM). This results in heightened local inflammation and promotes the formation of hypertrophic scars (Ogawa and Akaishi, 2016). Moreover, fibronectin in the exudate serves as a substrate for fibroblast attachment and inward growth, providing the matrix. ...
Poor wound healing and pathological healing have been pressing issues in recent years, as they impact human quality of life and pose risks of long-term complications. The study of neovascularization has emerged as a prominent research focus to address these problems. During the process of repair and regeneration, the establishment of a new vascular system is an indispensable stage for complete healing. It provides favorable conditions for nutrient delivery, oxygen supply, and creates an inflammatory environment. Moreover, it is a key manifestation of the proliferative phase of wound healing, bridging the inflammatory and remodeling phases. These three stages are closely interconnected and inseparable. This paper comprehensively integrates the regulatory mechanisms of new blood vessel formation in wound healing, focusing on the proliferation and migration of endothelial cells and the release of angiogenesis-related factors under different healing outcomes. Additionally, the hidden link between the inflammatory environment and angiogenesis in wound healing is explored.
... 8,9 The angiogenic processes of wound healing is regulated by a variety of factors, and one particularly potent proangiogenic mediator is vascular endothelial growth factor (VEGF). 10,11 VEGF is a 40-45 kDa heterodimeric glycoprotein, and it consists of a family of several members including VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, VEGF-F, placenta growth factor (PlGF) and endocrine gland-derived vascular endothelial growth factor (EG-VEGF). 11 VEGF binds to different VEGF Tyrosine Kinase Receptors (VEGFRs) such as VEGFR-1 (flt-1), VEGFR-2 (flk-1) and VEGFR-3 (flt-4), and then activates several intracellular signaling pathways to stimulate mitogenesis and inhibit apoptosis in vascular endothelial cells. ...
Objective
High levels of VEGF and excessive angiogenesis contribute significantly to hypertrophic scar (HS) formation. Our study aimed to preliminarily investigate the effect of axitinib, a selective VEGF receptor tyrosine kinase inhibitor, on angiogenesis of HS and to explore its possible mechanism in a rabbit ear model.
Methods
Ten male New Zealand white rabbits were used to establish HS models and then randomised to the control and axitinib groups. The scar tissues in the two groups were injected with axitinib or normal saline, and they were evaluated after one month of treatment. Macroscopic scar thickness, vascularity and pliability, as well as histopathological analysis including HE staining and Masson staining and scar elevation index (SEI) between two groups were compared. Immunohistochemical staining of CD31 in two groups was conducted to assess the degree of angiogenesis in HS tissue. The protein expression of protein kinase B (AKT) and ribosomal protein S6 kinase (p70S6K) and their phosphorylation levels in both groups were examined by Western blot analysis.
Results
The macroscopic and histological observation showed intralesional axitinib injection significantly reduced scar thickness, vascularity and pliability of HS in the rabbit ear model. The value of SEI in HE assessment was also significantly declined in the axitinib group. Furthermore, immunohistochemical analysis revealed that axitinib suppressed the expression of CD31 in HS tissue, and the mean IOD for blood vessels was significantly lower in the axitinib-treated group. Additionally, axitinib effectively attenuated the protein expression of p70S6K, p-AKT and p-p70S6K by Western blot analysis.
Conclusion
Our study suggests that intralesional injection of axitinib can effectively attenuate HS by reducing angiogenesis in the rabbit ear model, and this inhibitory effect may be mediated by suppression of AKT/p70S6K signaling pathway. It indicates that axitinib may be a promising option for the treatment of HS in the future.
... Angiogenesis is triggered by hypoxia and several cellular cytokines, including VEGF, PDGF, FGF-β, and members of the TGF-β family [137,138]. Ogawa et al. proposed the hypotheses that dysregulated endothelial function increases immune cell infiltration and that inflammatory cytokines enter the ECM from microvessels, thereby increasing local inflammation and promoting keloid formation [139]. VECs isolated from porcine hypertrophic scars were less permeable than normal VECs, and this increased permeability may contribute to the dysregulated endothelial function of micro blood vessels. ...
Keloids are a fibroproliferative skin disorder that develops in people of all ages. Keloids exhibit some cancer-like behaviors, with similar genetic and epigenetic modifications in the keloid microenvironment. The keloid microenvironment is composed of keratinocytes, fibroblasts, myofibroblasts, vascular endothelial cells, immune cells, stem cells and collagen fibers. Recent advances in the study of keloids have led to novel insights into cellular communication among components of the keloid microenvironment as well as potential therapeutic targets for treating keloids. In this review, we summarized the nature of genetic and epigenetic regulation in keloid-derived fibroblasts, epithelial-to-mesenchymal transition of keratinocytes, immune cell infiltration into keloids, the differentiation of keloid-derived stem cells, endothelial-to-mesenchymal transition of vascular endothelial cells, extracellular matrix synthesis and remodeling, and uncontrolled angiogenesis in keloids with the aim of identifying new targets for therapeutic benefit. Video Abstract.
... Формирование рубцовой ткани представляет собой физиологический ответ на повреждение кожных покровов и слизистых оболочек. Дисбаланс между разрушением и синтезом внеклеточного матрикса может привести к чрезмерному рубцеванию и образованию как келоидных, так и гипертрофических рубцов [13,14]. В фазу реорганизации и эпителизации наблюдается равновесие между процессами разрушения временного матрикса и синтеза коллагена. ...
В статье освещены современные научные данные, посвященные анализу методики трансплантации аутологичной жировой ткани. Освещена морфологическая и биохимическая характеристика патологически измененной ткани до выполнения оперативного вмешательства с целью контурной коррекции рубцовой деформации. Собраны современные научные классификации рубцовых изменений кожных покровов. Проведен анализ показаний к применению метода липофилинга. Указаны перспективы использования комбинации лекарственных средств, характеризующихся антиоксидантной активностью. Обозначена возможность биохимической и морфологической оценки локального состояния антиоксидантного статуса реципиентной зоны после классической контурной коррекции в комбинации с использованием антиоксидантов с целью улучшения результатов реабилитации пациентов с рубцовыми деформациями атрофического характера различной этиологии.
The article covers modern scientific data devoted to the analysis of the technique of autologous adipose tissue transplantation. Morphological and biochemical characteristics of the pathologically changed tissue before surgical intervention for scar deformity contouring are highlighted. Modern scientific classifications of cutaneous scar changes have been collected. The analysis of indications for lipofilling method application was carried out. Prospects of using combinations of drugs characterized by antioxidant activity are indicated. The possibility of biochemical and morphological evaluation of local state of antioxidant status of the recipient area after classical contour correction in combination with antioxidants to improve rehabilitation results of patients with atrophic scar deformities of various etiologies is outlined.
... Endothelial dysfunction has also been implicated in keloid disorder; Ogawa and Akaishi proposed that increased vascular permeability caused by endothelial dysfunction may increase local inflammation by allowing increased levels of inflammatory cells and soluble mediators into the tissue.120 A study of vascular function in keloid patients found that they exhibited significantly lower reactive hyperaemia index values and higher augmentation index values, indicators of endothelial function, compared with non-keloid control patients.121 ...
Keloids are disfiguring fibroproliferative lesions that can occur in susceptible individuals following any skin injury. They are extremely challenging to treat, with relatively low response rates to current therapies and high rates of recurrence after treatment. Although several distinct genetic loci have been associated with keloid formation in different populations, there has been no single causative gene yet identified and the molecular mechanisms guiding keloid development are incompletely understood. Further, although it is well known that keloids are more commonly observed in populations with dark skin pigmentation, the basis for increased keloid risk in skin of color is not yet known. Because individuals with dark skin pigmentation are at higher risk for vitamin D deficiency, the role of vitamin D in keloid pathology has gained interest in the keloid research community. A limited number of studies have found lower serum vitamin D levels in patients with keloids, and reduced expression of the vitamin D receptor (VDR) in keloid lesions compared with uninjured skin. Vitamin D has documented anti-inflammatory, anti-proliferative, and pro-differentiation activities, suggesting it may have a therapeutic role in suppression of keloid fibrosis. Here we review the evidence supporting a role for vitamin D and VDR in keloid pathology. This article is protected by copyright. All rights reserved.
... Keloids are scars with an abnormal fibroproliferative wound healing response. They extend beyond the original wound boundaries and usually develop after dermal injury such as trauma, surgery, vaccination, burns, skin piercing, folliculitis, acne, and herpes zoster infection (2). Keloid formation has been theorized to result from altered growth factor regulation, abnormal collagen turnover, genetics, immune dysfunction, sebum reaction, and altered mechanics (3). ...
... Keloid formation has been theorized to result from altered growth factor regulation, abnormal collagen turnover, genetics, immune dysfunction, sebum reaction, and altered mechanics (3). Some lines of evidence suggest that pathologic scars are due to endothelial dysfunction that leads to vascular hyperpermeability during the inflammatory phase of wound healing which allows the flow of inflammatory cells and factors into the dermis, causing excessive local inflammation and fibrotic activity (2). Some systemic diseases like Hypertension have been implicated with keloid formation due to the damaging effect on vascular endothelium(4). ...
... This leads to flow of inflammatory cells and factors into the dermis, resulting in dysfunctional fibroblast activity. Inhibiting this abnormal blood vessel regulation and vascular permeability could be a key therapeutic approach for keloids (2). ...
Keloids are scars that extend beyond the original area of skin damage. They can develop after minor skin trauma in predisposed individuals. Many factors play a role in keloid scar formation, with certain systemic diseases being a risk factor for their development. Diabetes mellitus is a disease that affects a variety of organ systems including the skin. Multiple skin conditions have been implicated directly and indirectly with diabetes mellitus and their presence would often be a sign of insulin resistance or poor glycemic control. Here we present a case of hypertrophic keloid developing in a patient with Type 2 Diabetes Mellitus. The patient had no prior skin trauma, nor did she develop the lesions at the sites of insulin injection. This raises the question of whether hypertrophic keloids might be associated with diabetes mellitus and whether recommendations for DM screening and guidance on use of insulin injections in those patients should be put in place. Key words: Keloids, Hypertrophic, Diabetes, Insulin resistance
