Background Noninvasive quantitative assessment of dermal fibrosis remains a challenge. Optical coherence tomography (OCT) and high-frequency ultrasound (HFUS) can accurately measure structural and physiological changes in skin. Objectives To perform quantitative analysis of cutaneous fibrosis. Methods Sixty-two healthy volunteers underwent multiple sequential skin biopsies (day 0 and 1-8 weekly thereafter), with OCT and HFUS measurements at each time point supported with immunohistomorphometry analysis. Results HFUS and OCT provided quantitative measurements of skin thickness, which increased from uninjured skin (1 center dot 18 and 1 center dot 2 mm, respectively) to week 1 (1 center dot 28 mm, P = 0 center dot 01; 1 center dot 27 mm, P = 0 center dot 02), and compared favourably with haematoxylin and eosin. Spearman correlation showed good agreement between techniques (P < 0 center dot 001). HFUS intensity corresponded to dermal density, with reduction from uninjured skin (42%) to week 8 (29%) (P = 0 center dot 02). The OCT attenuation coefficient linked with collagen density and was reduced at week 8 (1 center dot 43 mm, P < 0 center dot 001). Herovici analysis showed that mature collagen levels were highest in uninjured skin (72%) compared with week 8 (42%, P = 0 center dot 04). Fibronectin was greatest at week 4 (0 center dot 72 AU) and reduced at week 8 (0 center dot 56 AU); and alpha-smooth muscle actin increased from uninjured skin (11 center dot 5%) to week 8 (67%, P = 0 center dot 003). Conclusions Time-matched comparison images between haematoxylin and eosin, OCT and HFUS demonstrated that epidermal and dermal structures were better distinguished by OCT. HFUS enabled deeper visualization of the dermis including the subcutaneous tissue. Choice of device was dependent on the depth of scar type, parameters to be measured and morphological detail required in order to provide better objective quantitative indices of the quality and extent of dermal fibrosis.
伤口愈合过程可导致瘢痕形成,其在损伤后取代正常组织。有许多瘢痕治疗可用,但都无法完全去除瘢痕,而且许多可导致不良结局。因此,为了评估目前的治疗,以及研究开发新的瘢痕治疗方法,需要可在每个伤口愈合阶段提供数值的设备。评估皮肤纤维化(瘢痕形成)仍然是一项挑战。因此本研究的目的在于明确高频超声波 (HFUS) 和光学相干断层扫描 (OCT) 设备是否能够在伤口愈合过程中提供皮肤纤维化的数值指标(评分)。为实现这一目的,在英国曼彻斯特招募了 62 名健康志愿者,并在 8 周里进行小型上内臂皮肤活检。他们每周用 HFUS 和 OCT 设备进行一次测量,并通过实验室分析予以支持。两种设备都能提供皮肤厚度的数值测量,而且测量示值与实验室测量数值类似。设备软件也提供了与(构成皮肤结构的)皮肤胶原蛋白量相关的测量值。对不同类型胶原蛋白的实验室分析对此提供了支持。两种技术都能够识别皮肤内的不同结构,但深度和分辨率因所使用的设备而异。由于分辨率原因,OCT 所示的皮肤结构更佳,然而 HFUS 可使研究者看到更深层的皮肤。总而言之,设备的选择很重要,因为这将因伤口或瘢痕的类型、大小和深度,以及要研究或监测的特定因素而异。
The wound healing process can result in the formation of a scar, which replaces normal tissue after injury. Many scar treatments are available but none can totally erase a scar and many can result in a poor outcome. Therefore, in order to evaluate current treatments, as well as research to develop new methods for treating scars, devices which give numerical values at each stage of wound healing are needed. Assessing skin fibrosis (scarring) remains a challenge. This study therefore aimed to find out if high frequency ultrasound (HFUS) and optical coherence tomography (OCT) devices were able to provide a numerical indicator (score) of skin fibrosis over the course of wound healing. This was achieved by recruiting 62 healthy volunteers in Manchester, United Kingdom and carrying out small skin biopsies to their upper inner arms over eight weeks. They had measurements taken each week by HFUS and OCT and this was supported by laboratory analysis. Both devices were able to provide numerical measurements for skin thickness and this was shown to be similar to laboratory measurements. The device software also gave measurements that linked with the amount of collagen in the skin (which gives skin its structure). This was supported by laboratory analysis of different types of collagen. Both techniques were able to identify different structures within the skin but at different depths and resolutions depending upon which device was used. Skin structures were better seen by OCT due to the resolution, whilst HFUS allowed the researchers to see the deeper skin layers. In conclusion, the choice of device is important as this would depend on the type, size and depth of the wound or scar, and specific factors to be investigated or monitored.
Striae distensae (SD) are common dermal lesions, with significant physical and psychological impact. Many therapeutic modalities are available but none can completely eradicate SD. The most common therapy is the application of topicals used both therapeutically and prophylactically. Even though there are many commercially available topical products, not all have sufficient level of evidence to support their continued use in SD. The aim here was to assess the evidence for the use of topicals in SD and to propose a structured approach in managing SD. A systematic search of published literature and manufacturer website information for topicals in SD was carried out. The results showed that there are few studies (n=11) which investigate the efficacy of topicals in management of SD. Trofolastin and Alphastria creams demonstrated level-2 evidence of positive results for their prophylactic use in SD. Additionally, tretinoin used therapeutically showed varying results whilst cocoa butter and olive oil did not demonstrate any effect. Overall, there is a distinct lack of evidence for each topical formulation. The majority of topicals failed to mention their effect on early vs. later stages of SD (striae rubrae compared to striae albae) and their role in both prevention and treatment. In conclusion, there is no topical formulation, which is shown to be most effective in eradicating or improving SD. A structured approach in identification and targeted management of symptoms and signs with the appropriate topical is required. Randomized controlled trials are necessary to assess the efficacy of topical products for treatment and prevention of different stages of SD.
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.
Striae distensae (SD) are common dermal lesions, with significant physical and psychological impact. Many therapeutic modalities are available but none can completely eradicate SD. The most common therapy is the application of topicals used both therapeutically and prophylactically. Even though there are many commercially available topical products, not all have sufficient level of evidence to support their continued use in SD. The aim here was to assess the evidence for the use of topicals in SD and to propose a structured approach in managing SD. A systematic search of published literature and manufacturer website information for topicals in SD was carried out. The results showed that there are few studies (n = 11) which investigate the efficacy of topicals in management of SD. Trofolastin and Alphastria creams demonstrated level-2 evidence of positive results for their prophylactic use in SD. Additionally, tretinoin used therapeutically showed varying results whilst cocoa butter and olive oil did not demonstrate any effect. Overall, there is a distinct lack of evidence for each topical formulation. The majority of topicals failed to mention their effect on early vs. later stages of SD (striae rubrae compared to striae albae) and their role in both prevention and treatment. In conclusion, there is no topical formulation, which is shown to be most effective in eradicating or improving SD. A structured approach in identification and targeted management of symptoms and signs with the appropriate topical is required. Randomized controlled trials are necessary to assess the efficacy of topical products for treatment and prevention of different stages of SD.
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.