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Skin scarring is a frequent complication of the wound healing process. Bacterial contamination and prolonged inflammation in wounds are thought to play significant roles during scar formation, but little is known about their specific mechanisms of action. In this study, hypertrophic scar derived fibroblasts (HSFs) and paired normal skin derived fibroblasts (NSFs) were used to evaluate the effects of lipopolysaccharide (LPS) on inflammation-induced skin scarring and explore the inflammation-mediated mechanism of activity of LPS on dermal fibroblasts. LPS was found to significantly upregulate the expression of the proinflammatory molecules TLR4, Myd88, TRAF6, and p65, and the fibrosis-related proteins Col I, Col III, and α-SMA, in NSFs. Blocking Myd88 expression with T6167923 downregulated the expression of Col I, Col III, and α-SMA, whereas activating Myd88 expression with CL075 significantly upregulated their expression in LPS-treated NSFs. LPS was found to delay wound healing and increase skin scarring in cell and mouse models. These results showed that LPS could induce scar formation through the TLR4/Myd88 signaling pathway in dermal fibroblasts, suggesting that the downregulation of excessive inflammation in wound tissues inhibits skin scarring and improves scar appearance. • LPS-mediated fibroblast inflammation plays an important role during scar formation. • LPS activated NSFs to produce inflammation-, fibrosis-related molecules, and could transform NSFs into HSFs. • LPS induced scar formation through the TLR4/Myd88 inflammatory signaling pathway in dermal fibroblasts. [ABSTRACT FROM AUTHOR]

Excessive skin scarring affects over 100 million patients worldwide, with effects ranging from cosmetic to systemic problems, and an effective treatment is yet to be found. Ultrasound-based therapies have been used to treat a variety of skin disorders, but the exact mechanisms behind the observed effects are still unclear. The aim of this work was to demonstrate the potential of ultrasound for the treatment of abnormal scarring by developing a multi-well device based on printable piezoelectric material (PiezoPaint™). First, compatibility with cell cultures was evaluated using measurements of heat shock response and cell viability. Second, the multi-well device was used to treat human fibroblasts with ultrasound and quantify their proliferation, focal adhesions, and extracellular matrix (ECM) production. Ultrasound caused a significant reduction in fibroblast growth and ECM deposition without changes in cell viability or adhesion. The data suggest that these effects were mediated by nonthermal mechanisms. Interestingly, the overall results suggest that ultrasound treatment would a be beneficial therapy for scar reduction. In addition, it is expected that this device will be a useful tool for mapping the effects of ultrasound treatment on cultured cells. [ABSTRACT FROM AUTHOR]

Objective To determine whether double transverse incisions could provide superior cosmetic and functional outcomes, including rates of dysphagia and dysphonia, compared with longitudinal incisions in patients undergoing anterior cervical spine surgery (ACSS) involving ≥ 3 levels. Methods A total of 62 consecutive patients who underwent ACSS involving ≥ 3 levels were included in this study. They consist of 33 with longitudinal incisions (L group) and 29 with double transverse incisions (DT group). We recorded functional outcome measures including the Bazaz score for postoperative dysphagia and the Voice Handicap Index-10 (VHI-10) for postoperative dysphonia. The Vancouver Scar Scale (VSS) and the patient and observer scar assessment scale (POSAS) were used to evaluate postoperative skin scarring. Results Cosmetic results, as assessed using the VSS and POSAS, were significantly better in the DT than in the L group at most follow-up time points (p < 0.01 each). Dysphagia rates were significantly lower in the DT group than in the L group during the late postoperative period from 6 months until final 2 years of follow-up (p < 0.01 each). There were no significant different results between the 2 groups in terms of dysphonia. Conclusion A double transverse incision can be a feasible option when performing ACSS involving ≥ 3 levels, providing better cosmesis and lower rates of persistent dysphagia than with a longitudinal incision.

The skin is home to an assortment of fibroblastic lineages that shape the wound repair response toward scars or regeneration. In this review, we discuss the distinct embryonic origins, anatomic locations, and functions of fibroblastic lineages, and how these distinct lineages of fibroblasts dictate the skin's wound response across injury depths, anatomic locations, and embryonic development to promote either scarring or regeneration. We highlight the supportive role of the fascia in dictating scarring outcomes; we then discuss recent findings that indicate fascia mobilization by its resident fibroblasts supersede the classical de novo deposition program of wound matrix formation. These recent findings reconfigure our traditional view of wound repair and present exciting new therapeutic avenues to treat scarring and fibrosis across a range of medical settings. [ABSTRACT FROM AUTHOR]

Excessive skin scarring affects over 100 million patients worldwide, with effects ranging from cosmetic to systemic problems, and an effective treatment is yet to be found. Ultrasound-based therapies have been used to treat a variety of skin disorders, but the exact mechanisms behind the observed effects are still unclear. The aim of this work was to demonstrate the potential of ultrasound for the treatment of abnormal scarring by developing a multi-well device based on printable piezoelectric material (PiezoPaint™). First, compatibility with cell cultures was evaluated using measurements of heat shock response and cell viability. Second, the multi-well device was used to treat human fibroblasts with ultrasound and quantify their proliferation, focal adhesions, and extracellular matrix (ECM) production. Ultrasound caused a significant reduction in fibroblast growth and ECM deposition without changes in cell viability or adhesion. The data suggest that these effects were mediated by nonthermal mechanisms. Interestingly, the overall results suggest that ultrasound treatment would a be beneficial therapy for scar reduction. In addition, it is expected that this device will be a useful tool for mapping the effects of ultrasound treatment on cultured cells.

Inflammation plays an active role during the wound healing process. There is a direct association between the extent of injury as well as inflammation and the amount of subsequent cutaneous scarring. Evidence to date demonstrates that high levels of inflammation are associated with excessive dermal scarring and formation of abnormal pathological scars such as keloids and hypertrophic scars. In view of the multiple important cell types being involved in the inflammatory process and their influence on the extent of scar formation, many scar therapies should aim to target these cells in order to control inflammation and by association help improve scar outcome. However, most current treatment strategies for the management of a newly formed skin scar often adopt a watch-and-wait approach prior to commencing targeted anti-inflammatory therapy. Moreover, most of these therapies have been evaluated in the remodelling phase of wound healing and the evaluation of anti-inflammatory treatments at earlier stages of healing have not been fully explored and remain limited. Taken together, in order to minimise the risk of developing a poor scar outcome, it is clear that adopting an early intervention prior to skin injury would be optimal, however, the concept of pre-emptively priming the skin prior to injury has not yet been thoroughly evaluated. Therefore, the aim of this review was to evaluate the available literature regarding scar therapies that aim to target inflammation which are commenced prior to when a scar is formed or immediately after injury, with a particular focus on the role of pre-emptive priming of skin prior to injury in order to control inflammation for the prevention of poor scarring outcome. [ABSTRACT FROM AUTHOR]

Inflammation plays an active role during the wound healing process. There is a direct association between the extent of injury as well as inflammation and the amount of subsequent cutaneous scarring. Evidence to date demonstrates that high levels of inflammation are associated with excessive dermal scarring and formation of abnormal pathological scars such as keloids and hypertrophic scars. In view of the multiple important cell types being involved in the inflammatory process and their influence on the extent of scar formation, many scar therapies should aim to target these cells in order to control inflammation and by association help improve scar outcome. However, most current treatment strategies for the management of a newly formed skin scar often adopt a watch-and-wait approach prior to commencing targeted anti-inflammatory therapy. Moreover, most of these therapies have been evaluated in the remodelling phase of wound healing and the evaluation of anti-inflammatory treatments at earlier stages of healing have not been fully explored and remain limited. Taken together, in order to minimise the risk of developing a poor scar outcome, it is clear that adopting an early intervention prior to skin injury would be optimal, however, the concept of pre-emptively priming the skin prior to injury has not yet been thoroughly evaluated. Therefore, the aim of this review was to evaluate the available literature regarding scar therapies that aim to target inflammation which are commenced prior to when a scar is formed or immediately after injury, with a particular focus on the role of pre-emptive priming of skin prior to injury in order to control inflammation for the prevention of poor scarring outcome.

The aim of this article was to report the presentation and management of a clinical case with neurological and facial skin complications secondary to the extrusion of sodium hypochlorite and calcium hydroxide into the facial soft tissues during root canal treatment. An adult male patient was referred to the endodontic clinic after inadvertent extrusion of sodium hypochlorite and calcium hydroxide into the periapical tissues during root canal treatment. The severe clinical consequences, with particular emphasis on nerve deficit and soft tissue are discussed and its management is highlighted. Early and aggressive treatment is advocated following such incidents in order to reduce potentially serious complications. This article demonstrates the possible detrimental effect of extrusion of sodium hypochlorite and calcium hydroxide intracanal dressing into the periradicular and adjacent soft tissues. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) are an important immune cell type in the skin and play an active role during wound healing. MCs produce mediators that can enhance acute inflammation, stimulate re-epithelialisation as well as angiogenesis, and promote skin scarring. There is also a link between MCs and abnormal pathological cutaneous scarring, with increased numbers of MCs found in hypertrophic scars and keloid disease. However, there has been conflicting data regarding the specific role of MCs in scar formation in both animal and human studies. Whilst animal studies have proved to be valuable in studying the MC phenomenon in wound healing, the appropriate translation of these findings to cutaneous wound healing and scar formation in human subjects remains crucial to elucidate the role of these cells and target treatment effectively. Therefore, this perspective paper will focus on evaluation of the current evidence for the role of MCs in skin scarring in both animals and humans in order to identify common themes and future areas for translational research.

Mast cells (MCs) are an important immune cell type in the skin and play an active role during wound healing. MCs produce mediators that can enhance acute inflammation, stimulate re-epithelialisation as well as angiogenesis, and promote skin scarring. There is also a link between MCs and abnormal pathological cutaneous scarring, with increased numbers of MCs found in hypertrophic scars and keloid disease. However, there has been conflicting data regarding the specific role of MCs in scar formation in both animal and human studies. Whilst animal studies have proved to be valuable in studying the MC phenomenon in wound healing, the appropriate translation of these findings to cutaneous wound healing and scar formation in human subjects remains crucial to elucidate the role of these cells and target treatment effectively. Therefore, this perspective paper will focus on evaluation of the current evidence for the role of MCs in skin scarring in both animals and humans in order to identify common themes and future areas for translational research. [ABSTRACT FROM AUTHOR]

Keloids are considered as benign fibroproliferative skin tumors growing beyond the site of the original dermal injury. Although traditionally viewed as a form of skin scarring, keloids display many cancer-like characteristics such as progressive uncontrolled growth, lack of spontaneous regression and extremely high rates of recurrence. Phenotypically, keloids are consistent with non-malignant dermal tumors that are due to the excessive overproduction of collagen which never metastasize. Within the remit of keloid pathobiology, there is increasing evidence for the various interplay of neoplastic-promoting and suppressing factors, which may explain its aggressive clinical behavior. Amongst the most compelling parallels between keloids and cancer are their shared cellular bioenergetics, epigenetic methylation profiles and epithelial-to-mesenchymal transition amongst other disease biological (genotypic and phenotypic) behaviors. This review explores the quasi-neoplastic or cancer-like properties of keloids and highlights areas for future study.

Keloids are considered as benign fibroproliferative skin tumors growing beyond the site of the original dermal injury. Although traditionally viewed as a form of skin scarring, keloids display many cancer-like characteristics such as progressive uncontrolled growth, lack of spontaneous regression and extremely high rates of recurrence. Phenotypically, keloids are consistent with non-malignant dermal tumors that are due to the excessive overproduction of collagen which never metastasize. Within the remit of keloid pathobiology, there is increasing evidence for the various interplay of neoplastic-promoting and suppressing factors, which may explain its aggressive clinical behavior. Amongst the most compelling parallels between keloids and cancer are their shared cellular bioenergetics, epigenetic methylation profiles and epithelial-to-mesenchymal transition amongst other disease biological (genotypic and phenotypic) behaviors. This review explores the quasi-neoplastic or cancer-like properties of keloids and highlights areas for future study. [ABSTRACT FROM AUTHOR]

Abnormal scarring and its accompanying esthetic, functional, and psychological sequelae still pose significant challe nges. To date, there is no satisfactory prevention or treatment option for hypertrophic scars (HSs), which is mostly due to not completely comprehending the mechanisms underlying their formation. That is why the apprehension of regular and controlled physiological processes of scar formation is of utmost importance when facing hypertrophic scarring, its pathophysiology, prevention, and therapeutic approach. When treating HSs and choosing the best treatment and prevention modality, physicians can choose from a plethora of therapeutic options and many commercially available products, among which currently there is no efficient option that can successfully overcome impaired skin healing. This article reviews current therapeutic approach and emerging therapeutic strategies for the management of HSs, which should be individualized, based on an evaluation of the scar itself, patients’ expectations, and practical, evidence-based guidelines. Clinicians are encouraged to combine various prevention and treatment modalities where combination therapy that includes steroid injections, 5-fluorouracil, and pulsed-dye laser seems to be the most effective. On the other hand, the current therapeutic options are usually empirical and their results are unreliable and unpredictable. Therefore, there is an unmet need for an effective, targeted therapy and prevention, which would be based on an action or a modulation of a particular factor with clarified mechanism of action that has a beneficial effect on wound healing. As the extracellular matrix has a crucial role in cellular and extracellular events that lead to pathological scarring, targeting its components mostly by regulating bone morphogenetic proteins may throw up new therapeutic approach for reduction or prevention of HSs with functionally and cosmetically acceptable outcome.

A number of equivalent-skin models are available for investigation of the ex vivo effect of topical application of drugs and cosmaceuticals onto skin, however many have their drawbacks. With the March 2013 ban on animal models for cosmetic testing of products or ingredients for sale in the EU, their utility for testing toxicity and effect on skin becomes more relevant. The aim of this study was to demonstrate proof of principle that altered expression of key gene and protein markers could be quantified in an optimised whole tissue biopsy culture model. Topical formulations containing green tea catechins (GTC) were investigated in a skin biopsy culture model ( n = 11). Punch biopsies were harvested at 3, 7 and 10 days, and analysed using qRT-PCR, histology and HPLC to determine gene and protein expression, and transdermal delivery of compounds of interest. Reduced gene expression of α-SMA, fibronectin, mast cell tryptase, mast cell chymase, TGF-β1, CTGF and PAI-1 was observed after 7 and 10 days compared with treated controls ( p < 0.05). Histological analysis indicated a reduction in mast cell tryptase and chymase positive cell numbers in treated biopsies compared with untreated controls at day 7 and day 10 ( p < 0.05). Determination of transdermal uptake indicated that GTCs were detected in the biopsies. This model could be adapted to study a range of different topical formulations in both normal and diseased skin, negating the requirement for animal models in this context, prior to study in a clinical trial environment. [ABSTRACT FROM AUTHOR]

The CCN family of matricellular signaling proteins is emerging as a unique common link across multiple diseases and organs related to injury and repair . They are now being shown to play a central role in regulating the pathways to the initiation and resolution of normal wound healing and fibrosis in response to multiple forms of injury. Similarly, it is also emerging that they play a key role in regulating the establishment, growth, metastases and tissue regeneration in many forms of cancer via the interaction of cancer cells with the tumor stroma. Evidence has been recently provided that these proteins do not act independently but are co-regulated working in a yin/yang manner to alter the outcome of both normal physiological processes as well as pathology. The purpose of this review is to twofold. First, it will summarize work to date supporting CCN2 as a therapeutic target in the formation and progression of renal, skin, and other organ fibrosis, as well as cancer stroma formation. Second, it will highlight recent evidence for CCN3 as a counter-regulator and a potential therapeutic agent in these diseases with an exciting, novel potential to both treat and then restore tissue homeostasis in those afflicted by these devastating disorders. [ABSTRACT FROM AUTHOR]

Significance: The cutaneous repair process naturally results in different types of scarring that are classified as normal or pathological. Affected individuals are often affected from an esthetic, physical (functional), and psychosocial perspective. The distinct nature of scarring in humans, particularly the formation of pathological scars, makes the study of skin scarring a challenge for researchers in this area. Several established experimental models exist for studying scar formation. However, the increasing development and validation of newly emerging models have made it possible to carry out studies focused on different variables that influence this unique process. Recent Advances: Experimental models such as in vitro , ex vivo , and in vivo models have obtained different degrees of success in the reproduction of the scar formation in its native milieu and true environment. These models also differ in their ability to elucidate the molecular, cellular, and structural mechanisms involved in scarring, as well as for testing new agents and approaches for therapies. The models reviewed here, including cells derived from human skin and in vivo animal models, have contributed to the advancement of skin scarring research. Critical Issues and Future Directions: The absence of experimental models that faithfully reproduce the typical characteristics of the different types of human skin scars makes the improvement of validated models and the establishment of new ones a critical unmet need. The fields of wound healing research combined with tissue engineering have offered newer alternatives for experimental studies with the potential to provide clinically useful knowledge about scar formation.

Wound healing after dermal injury is an imperfect process, inevitably leading to scar formation as the skin re-establishes its integrity. The resulting scars have different characteristics to normal skin, ranging from fine-line asymptomatic scars to problematic scarring including hypertrophic and keloid scars. Scars appear as a different colour to the surrounding skin and can be flat, stretched, depressed or raised, manifesting a range of symptoms including inflammation, erythema, dryness and pruritus, which can result in significant psychosocial impact on patients and their quality of life. In this paper, a comprehensive literature review coupled with an analysis of levels of evidence (LOE) for each published treatment type was conducted. Topical treatments identified include imiquimod, mitomycin C and plant extracts such as onion extract, green tea, Aloe vera, vitamin E and D, applied to healing wounds, mature scar tissue or fibrotic scars following revision surgery, or in combination with other more established treatments such as steroid injections and silicone. In total, 39 articles were included, involving 1703 patients. There was limited clinical evidence to support their efficacy; the majority of articles ( n = 23) were ranked as category 4 LOE, being of limited quality with individual flaws, including low patient numbers, poor randomisation, blinding, and short follow-up periods. As trials were performed in different settings, they were difficult to compare. In conclusion, there is an unmet clinical need for effective solutions to skin scarring, more robust long-term randomised trials and a consensus on a standardised treatment regime to address all aspects of scarring. [ABSTRACT FROM AUTHOR]

All species have evolved mechanisms of repair to restore tissue function following injury. Skin scarring is an inevitable and permanent endpoint for many postnatal organisms except for non-amniote vertebrates such as amphibians, which are capable of tissue regeneration. Furthermore, mammalian foetuses through mid-gestation are capable of rapid wound repair in the absence of scar formation. Notably, excessive cutaneous scar formation, such as hypertrophic and keloid scars, is a species limited clinical entity as it occurs only in humans, although wounds on the distal limbs of horses are also prone to heal with fibroproliferative pathology known as equine exuberant granulation tissue. Currently, there are no reliable treatment options to eradicate or prevent scarring in humans and vertebrates. The limited number of vertebrate models for either hypertrophic or keloid scarring has been an impediment to mechanistic studies of these diseases and the development of therapies. In this viewpoint essay, we highlight the current concepts of regenerative, scar-free and scar-forming healing compared across a number of species and speculate on areas for future research. Furthermore, in-depth investigative research into the mechanisms of scarless repair may allow for the development of improved animal models and novel targets for scar prevention. As the ability to heal in both a scarless manner and propensity for healing with excessive scar formation is highly species dependent, understanding similarities and differences in healing across species as it relates to the regenerative process may hold the key to improve scarring and guide translational wound-healing studies. [ABSTRACT FROM AUTHOR]

Striae distensae (SD) are cutaneous lesions often presenting post-pregnancy with atrophy and flattening of the epidermis. SD is poorly understood and treatment remains ill-defined. Our aim was to assess the effect of topical application of silicone gel compared with placebo on SD using non-invasive devices and by immunohistochemical analysis of sequential tissue biopsies in a double-blind controlled trial. Twenty volunteers massaged silicone and placebo gels into separate sides of the abdomen, daily for 6 weeks. Objective non-invasive imaging plus subjective self-assessment of SD were performed on days 0, 21, 42, 90, in addition to tissue biopsies on days 0 and 42. Non-invasive imaging demonstrated an increase in melanin and a decrease in haemoglobin, collagen and pliability over the 6-week period on both sides. Additionally, collagen levels in SD were significantly higher ( p value = 0.001) and melanin levels lower ( p value = 0.048) with silicone gel compared with placebo. Histological analysis revealed epidermal flattening with a reduction of rete ridges in SD on both sides. Vascular count significantly decreased with placebo gel ( p = 0.002). Corroborating the clinical results, melanin levels increased, whilst collagen type 1 and elastin decreased on both sides. Non-invasive techniques showed that the application of silicone gel increased collagen levels and reduced pigmentation compared with placebo. However, both clinical and histological data revealed that melanin increased whilst collagen, elastin and pliability decreased over the 6-week period with both gels. Furthermore, vascularity significantly decreased with placebo gel. These findings provide preliminary evidence of the utility of topical gels in the clinical management of SD. [ABSTRACT FROM AUTHOR]

Objective: To determine whether double transverse incisions could provide superior cosmetic and functional outcomes, including rates of dysphagia and dysphonia, compared with longitudinal incisions in patients undergoing anterior cervical spine surgery (ACSS) involving ≥ 3 levels., Methods: A total of 62 consecutive patients who underwent ACSS involving ≥ 3 levels were included in this study. They consist of 33 with longitudinal incisions (L group) and 29 with double transverse incisions (DT group). We recorded functional outcome measures including the Bazaz score for postoperative dysphagia and the Voice Handicap Index-10 (VHI-10) for postoperative dysphonia. The Vancouver Scar Scale (VSS) and the patient and observer scar assessment scale (POSAS) were used to evaluate postoperative skin scarring., Results: Cosmetic results, as assessed using the VSS and POSAS, were significantly better in the DT than in the L group at most follow-up time points (p < 0.01 each). Dysphagia rates were significantly lower in the DT group than in the L group during the late postoperative period from 6 months until final 2 years of follow-up (p < 0.01 each). There were no significant different results between the 2 groups in terms of dysphonia., Conclusion: A double transverse incision can be a feasible option when performing ACSS involving ≥ 3 levels, providing better cosmesis and lower rates of persistent dysphagia than with a longitudinal incision.

Recent studies highlighted the beneficial effects of a novel electrical stimulation waveform, the degenerate wave (DW), on skin fibroblasts and symptomatic skin scarring. However, no study to date has investigated the role of DW on acute cutaneous wounds. Therefore, we evaluated this in a trial using a temporal punch biopsy model. Twenty healthy volunteers had a biopsy performed on day 0 (left arm) and day 14 (right arm). On day 14, DW was applied. Participants were randomised into two groups. Objective non-invasive assessments were performed on days 0, 7, 14, 60 and 90 using spectrophotometric intracutaneous analysis and full-field laser perfusion imaging. There were statistically significant increases in mean flux on day 14 (P = 0.027) in the post-DW arm. Haemoglobin levels increased on day 7 for the post-DW arm compared to without DW (P = 0.088). Differences in melanin levels were higher post-DW on the left arm between randomised groups on day 90 (P = 0.033). Haemoglobin levels in the vascular ring increased significantly from day 7 to 90 (P < 0.001 for post-DW and without DW arms). This study, for the first time, shows that DW increases blood flow and haemoglobin levels in acute healing wounds without affecting wound closure time and may have potential application in enhancing acute cutaneous healing. [ABSTRACT FROM AUTHOR]

Summary: Greater objective scar severity and visibility should intuitively cause greater psychosocial distress for patients. Previous research is contradictory and has employed non-validated scar severity measures whilst neglecting patient-rated severity. The aim of this study was to assess the effects of objective and patient-rated scar severity, scar type and location on psychosocial distress. Skin scars were quantitatively assessed on two independent occasions using the ‘Manchester Scar Scale’ (MSS) – a validated measure. Scars were scored twice independently. Patients also rated their scars (from ‘very good’ [zero] to ‘poor’ [four]) and good completed the Derriford Appearance Scale (DAS24) and Dermatology Life Quality Index (DLQI). Eighty-two patients, with an average±SD (range) age of 34±15 (16–65) years were recruited. Mean psychosocial questionnaire scores were: DAS24 45.5±17.8 (15–91); DLQI 7.5±6.7 (0–26). Participants had 1.9±1.5 (1–8) scars with an MSS score of 31.3±24.0 (6.6–162.0) and subjective score of 2.6±1.2 (0–4). Correlation between psychosocial distress and objective severity was not significant (DAS24 0.14 p =0.11; DLQI 0.16 p =0.06). Correlation between psychosocial distress and subjective severity was significant (DAS24 0.48 p <0.0001; DLQI 0.46 p <0.0001). Patients with non-visible scars experienced greater psychosocial distress than patients with visible scars (DAS24 9.7 p =0.046; DLQI 4.2 p =0.014). Scar type was unrelated to psychosocial distress. Patient-rated scar severity and scar visibility are correlated with psychosocial distress rather than clinician''s objective severity rating or scar type. Although counter-intuitive, results are consistent with research into other disfiguring conditions and patient self-assessment should therefore form an integral part of clinical assessment. [Copyright &y& Elsevier]

Objectives/Hypothesis: To determine the efficacy of interventions to improve and monitor skin scarring, a valid assessment instrument must be used. Current tools used for the evaluation of skin scarring employ equal appearing interval (EAI) scales that assume scar dimensions conform to linear models. Some scar features meet these assumptions, whereas others may not be accurately described. This study determined if current methods of scar evaluation validly characterize inherent features of scars, and in doing so, empirically validate if specific scar dimensions were best represented by linear or nonlinear mathematical models. Study Design: Prospective, randomized, cross-over trial. Methods: Twenty-seven observers evaluated 30 scar photos utilizing both EAI and direct magnitude estimation (DME) scaling methods. The method of scaling and the assessed dimensions of vascularity, pigmentation, thickness, pliability, and surface area were randomized. EAI and DME data were evaluated to identify whether each scar dimension conformed to linear or curvilinear mathematical models. Results: Best-fit analysis revealed the dimensions of vascularity and pigmentation to be more accurately described using curvilinear functions, whereas pliability, thickness and surface area were best defined using linear models. Conclusions: The scar dimension under assessment must be considered when attempting to validly apply an assessment instrument. Several commonly evaluated dimensions of skin scarring are not appropriately characterized using linear EAI scales. Thus, present assessment instruments must be revised to account for this aberration to allow for a valid means of objectively evaluating skin scarring. Laryngoscope, 2009 [ABSTRACT FROM AUTHOR]

Summary: Background: Surprisingly little is known about how skin scars affect patients'' lives, though specialist clinical impressions suggest their impact is related to both their physical and psychosocial effects. Facial scars have been shown to cause high levels of anxiety and self-consciousness, but further work has been neglected. We aimed to explore the influence of skin scars on patients'' quality of life (QoL) and identify potential implications for clinical practice. Methods: We adopted a needs-based approach to QoL and conducted semi-structured interviews with scar patients at a specialist clinic. Transcribed data underwent interpretative phenomenological analysis to identify common themes in individuals'' personal experiences. Results: Thirty-four scar patients (24 women; aged 14–70 years, mean=35.7 years, SD=17.9 years) with a wide range of scar type, severity and onset were recruited. Five hundred and seventy-three statements were identified from interview transcripts relating to need impairment by skin scars. These were subsequently classified into 44 themes covering five main areas: physical comfort and functioning; acceptability to self and others; social functioning; confidence in the nature and management of the condition; emotional well-being. The majority of respondents were unhappy with their scar''s appearance due to their perceived stigma and psychological associations, and thus adopted different coping behaviours to hide or compensate for them. Often this made them unsociable and interfered with their communication skills, personal relationships, work life and leisure activities. Concerns about the diagnosis and persistent nature of scars were common, whilst unempathic management by general physicians and frustrations of current treatment compounded distress. Conclusions: There are five main areas of impact on the needs of scar patients that should be addressed in their management, which are greater and more complex than previously considered. Support services should be made available, along with clinician and public education to improve management and help reduce patient distress. A need for a carefully designed measure of scar-related QoL is also indicated, for use in clinical settings and trials. [Copyright &y& Elsevier]

Keloid disease (KD) is a fibroproliferative dermal tumour of unknown aetiology. The increased familial clustering in KD, its increased prevalence in certain races and increased concordance in identical twins suggest a strong genetic predisposition to keloid formation. The highest incidence of keloids is found in the black population, where it has been estimated around 4–6% and up to 16% in random samples of black Africans. SMAD genes 3, 6 and 7 were investigated as candidate genes in Jamaican patients with keloid scars ( n = 183) and a matched control population ( n = 121) because of their previously reported involvement in fibrotic disorders and to determine if they were associated with keloid disease susceptibility. Thirty Five SNPs across these genes were genotyped using Time-of-Flight Mass Spectrometry (MALDI-TOF MS) and iPLEX assay. Linkage disequilibrium (LD) was established between several of the SNPs investigated. In the Jamaican population, the SMAD SNPs investigated for this study were not strongly associated with increased risk of developing KD. Identification of genetic markers in candidate genes such as the SMAD family may be of significant importance in diagnosis, prognosis and development of new therapies in the management of keloid scarring. [ABSTRACT FROM AUTHOR]

Abstract: Keloids are benign fibroproliferative diseases of unknown aetiology. They occur as a result of derangement of the normal wound healing process in susceptible individuals. Although several factors have been postulated in the aetiopathogenesis of this condition, there has been growing evidence to suggest a role for Transforming Growth Factor beta (TGFβ) family members in its pathogenesis. TGFβ has also been found to be associated with fibrotic diseases affecting different organs of the body including liver, kidney, lung as well as skin. In this review article, we will discuss the morphology and mechanism of action of TGFβ and its isoforms and present the most up to date literature discussing the role of TGFβ isoforms, their receptors, and intracellular signalling pathways (the SMAD pathway) in the pathogenesis of keloid disease. Understanding the role of TGFβ in keloid disease could lead to the development of clinically useful therapeutic modalities for treatment of this condition. [Copyright &y& Elsevier]

Significance: Keloid scarring is cosmetically disfiguring, psychosocially distressing, and can be physically disabling. The pathophysiology of keloid formation is poorly understood and subsequently, treatment options are ill defined, limited, and largely unsatisfactory. Therefore, in view of its unsatisfactory and recalcitrant management, keloid therapy is often seen as a financial burden affecting both patients and the health care systems. Recent Advances: Increased research on the genetic and epigenetic mechanisms in keloids has broadened our understanding of keloid pathobiology. Epigenetic mechanisms, mainly DNA methylation, histone modification, and noncoding RNAs, are currently being widely investigated. Advances in genetic sequencing technology and reduced cost have aided this endeavor. Studies on blood and patient-derived keloid tissue are being done with therapeutic agents targeting epigenetic and genetic markers with the shared goal of identifying the pathways underlying the initiation and maintenance of keloids. These advances have informed us of multiple complex molecular pathways implicated in keloids, which are yet to be fully elucidated. Critical Issues: Improved understanding of the genetic and epigenetic causes implicated in keloids will enhance our knowledge of this enigmatic disorder and likely lead to the development of therapeutic targets based on the available clinical and experimental studies. Due to the incomplete knowledge of molecular targets involved in keloid scarring pathways, therapeutics is still lagging for this clinically and scientifically important condition. Future Directions: Focused research on the identification of molecular targets and mechanistic pathways implicated in keloids is required to generate novel antifibrotic therapeutic options to decrease or eradicate recurrence of the disease as well as associated morbidity and improve the quality of life of those affected with keloids.

Significance: Many treatments are utilized in the management of skin scarring; however, difficulties arise due to the high rates of recurrence and the identification of treatment efficacy in each patient, in particular, in the case of raised dermal scarring. Therefore, evaluation of treatments and the provision of objective scar assessment pre-therapy and post-therapy is of paramount importance to identify changes in scar characteristics using noninvasive devices. Recent Advances: There have been a number of emerging noninvasive objective quantitative devices, which assess specific scar parameters such as pliability, volume, color, perfusion, and depth. These can include three-dimensional imaging, optical coherence tomography, in vivo confocal microscopy, full-field laser perfusion imaging, and spectrophotometric intracutaneous analysis. Critical Issues: Clinical assessment and grading scales are most commonly used to assess scarring; however, there is a need for more objective quantitative measures to monitor their maturation and response to therapy. Currently, there is no consensus as to which objective measuring device is most optimal when assessing skin scarring. There is a need for a predictor tool that allows early implementation of treatment and addresses diagnosis, therapy, and prognosis. Future Directions: Validation of noninvasive objective scar assessment tools is essential as well as further development of technologies. There are currently more modalities that assess physical scar characteristics and only few that measure the physiological parameters. Therefore, the development of a technology that quantifies the metabolic and cellular activity in skin scars is necessary to allow for bespoke strategies for each patient.