高频超声弹性成像对基底细胞癌的诊断

目的：探讨高频超声剪切波弹性成像在皮肤基底细胞癌中的应用价值。方法：收集我院2017年3月至2018年12月于本院临床皮肤科因皮肤黑色占位性皮损就诊，同意接受超声检查及手术治疗的患者。结果：共收集患者108例，病理确诊基底细胞癌62例，良性对照病例46例，高频超声弹性成像对基底细胞癌诊断符合率为98.15%。高频超声弹性成像主要表现为基底细胞癌皮损表皮增厚、毛糙或不同程度的表皮缺损改变，可见多发的点状强回声，点状强回声后方无声影，后方有轻微声衰减，内血流信号多少不一，平均杨氏模量为（36.3±8.3）kpa，与周围正常组织弹性应变比约7.4±3.2。结论：高频超声剪切波弹性成像对皮肤基底细胞癌有较高的诊断能力。     

Lesion classification using skin patterning

Background/aims: The observation that skin line patterning tends to be disrupted by malignant but not non‐malignant skin lesions suggests that this could be used as an aid to lesion differentiation. Since recognised differentiating features can be obtained from the simply‐captured white light optical image, the possibility of using such images for skin pattern disruption detection is worth exploring. Methods: The skin pattern has been extracted from optical images by high‐pass filtering and profiles of local line strength variation with the angle estimated using a new consistent high‐value profiling technique. The resultant profile images have been analysed using a novel region‐based agglomerative clustering technique (mRAC) and also a local variance measurement. A measure based on the relationship between the classification results and an intensity‐based segmentation was calculated, and this represented the disruption of the skin line patterning. Results: A set of images containing a variety of histologically confirmed malignant and non‐malignant lesions was analysed. The computed textural disruption figure was compared to both the histological diagnosis and to a visual estimate of patterning disruption for each image. It was demonstrated that lesion separation could be achieved by both analysis methods, with a good correlation with visual estimate of disruption and with mRAC providing the best performance. Conclusions: It was concluded that the acquisition and modelling of skin line patterning from clinical images of skin lesions had been successfully achieved and that the analysis of the resulting data provided an assessment of pattern disruption that is both consistent with visual inspection and effective in presenting information useful for discrimination between melanoma and benign naevi lesion examples.     

A new device for assessing changes in skin viscoelasticity using indentation and optical measurement

Background/aims: Skin is a viscoelastic material, comprised of fluidic and fibrous components. Changes in viscoelasticity can arise due to a number of conditions including dehydration, swelling (associated with injury or disease), impaired heart function, rehydration therapy, ageing, scarring, sun exposure and genetic conditions affecting connective tissue. Quantification of changes in skin viscoelasticity due to these processes is of great clinical interest in the fields of therapy monitoring, wound healing and disease screening. However, devices currently available to measure aspects of the mechanical properties of skin have limitations in ease‐of‐use, accessibility, and depth of measurement. This paper describes a new technique to follow changes in the viscoelasticity of the skin, using a novel approach to an indentation manoeuvre. The device is portable, low‐cost and easy to use while at the same time providing rich information on the mechanical response of the skin. Methods: The method proposed optically tracks the skin's recovery from an initial strain, made with a novel linear indentor, using diffuse side‐lighting and a CCD video camera. Upon indentation, the skin's elastin fibres are stretched and fluid is displaced from the compressed region. When the indentor is removed, the rate of recovery of the skin from this imprint is therefore principally dependent on its hydration and elasticity. Using the blue colour plane of the image and polarisation filtering, it is possible to examine the surface topography only, and track the decay of the imprint over time. Results: The decrease in size of the imprint over time (decay curve) recorded by the device is shown to agree with the theoretical predictions of an appropriate viscoelastic model of skin mechanical behaviour. The contributors to the response measured using the indentation device are fully characterised and evaluated using separate measurement techniques including high‐frequency ultrasound, polarisation spectroscopy and optical coherence tomography. Conclusion: The device developed is capable of tracking the viscoelastic response of skin to minimal indentation. The high precision achieved using low‐cost materials means that the device could be a viable alternative to current technologies.     

Mitochondria and skin disease

Summary In addition to the 3 billion base pair nuclear genome, each human cell contains thousands of copies of a small, 16.5 kb circular molecule of double stranded DNA: mitochondria have their own DNA (mtDNA) which generally accounts for only 1% of the total cellular nucleic acid content. Therefore why should anyone, particularly in the field of dermatology, have an interest in this cytoplasmic organelle and its DNA? This review will address this question; there are three principle reasons: (i) mitochondria have a crucial role both in energy production and the viability of the cell and recently mitochondria have been implicated in programmed cell death (apoptosis). Although much smaller than the nuclear genome, mtDNA is equally important. MtDNA defects and the resulting mitochondrial dysfunction is an important contributor to human degenerative diseases, ageing and cancer; (ii) mtDNA is a significant target of ultraviolet radiation and current work shows that it may be useful as a candidate biomarker of cumulative exposure in skin; and (iii) there is a broad spectrum of skin manifestations that are signs of mitochondrial disorders; in addition, the frequency of skin findings in these syndromes is probably under‐reported.     

Skin pattern analysis for lesion classification using local isotropy

Background/purpose: The observation that skin pattern tends to be disrupted by malignant skin lesions, but not by benign ones suggests that measurements of skin pattern disruption on simply captured white light optical clinical (WLC) skin images could be a useful contribution to a diagnostic feature set. Previous work, which generated a flow field of skin pattern using a measurement of local line direction and intensity, was encouraging. The aim of this paper is to investigate the possibility of extracting new features using local isotropy metrics to quantify the skin pattern disruption. Methods: The skin pattern was extracted from WLC skin images by high‐pass filtering. A local tensor matrix was computed. The local isotropy was measured by the condition number of the local tensor matrix. The difference of this measure over the lesion and normal skin areas, combined with the local line direction and the ABCD features, was used as a lesion classifier. Results: A set of images of malignant melanoma and benign naevi was analysed. A one‐dimensional scatter plot showed the potential of a local isotropy metric, showing an area of 0.70 under the receiver operating characteristic (ROC) curve. A two‐dimensional scatter plot, combined with the local line direction, indicated enhancement of the classification performance, showing an area of 0.89 under the ROC curve. A three‐dimensional scatter plot combined with the local line direction and the ABCD features, using principal component analysis, demonstrated excellent separation of benign and malignant lesions. An ROC plot for this case enclosed an area of 0.96. Conclusion: The experimental results show that the local isotropy metric has a potential to increase lesion classifier accuracy. Combined with the local line direction and the ABCD features, it is very promising as a method to distinguish malignant melanoma from benign lesions.     

Cumulative irritation patch test of sanitary pads on sensitive skin

Background Tools are needed to assess the effects of various products on sensitive skin. Aim To investigate the cutaneous compatibility of various sanitary pads in people with self‐declared sensitive skin. Patients/methods Eight subjects, who considered their skin to be sensitive and who reported adverse skin responses to everyday products or clothing, were patch tested on the arm with two, low‐irritancy sanitary pads for four consecutive 24‐hour periods. Test products differed only in their surface covering. Sodium lauryl sulfate solution (0.1% w/v) and physiological saline served as standard irritant and nonirritant controls, respectively. Skin irritation (erythema) was graded after each 24‐hour period. Results No significant difference in skin erythema scores was observed between groups (scores on day 4: 1.06 ± 0.11 vs. 1.25 ± 0.13, on a five‐point scale, P < 0.05). The temporal development of cumulative irritation associated with the pads was comparable to that observed with the nonirritant control (a plateau in maximal group scores) and distinct from that of the irritant control (continuously rising scores). Conclusion Sanitary pads under investigation elicited negligible cumulative irritation in a four‐day patch test on subjects with self‐declared sensitive skin. The temporal pattern of cumulative response was consistent with the inherently low irritation potential of the products.     

Reflectance confocal microscopy criteria of lichen planus‐like keratosis

Background Lichen planus‐like keratosis (LPLK) may be difficult to differentiate from melanoma and other skin cancers on sun‐damaged skin based on clinical and dermoscopic examination. Reflectance confocal microscopy (RCM) allows evaluation of skin lesions at high resolution. Objectives The aim of this study was to identify criteria for specific diagnosis of LPLK using in vivo RCM. Methods Lesions included in the study were derived from patients presenting for skin examination at a private dermatology practice specializing in skin cancer. We retrospectively analysed RCM features of 28 biopsy‐proven LPLK and compared them to RCM findings in skin cancers on sun‐damaged skin, including five in situ squamous cell carcinomas, six actinic keratoses, seven superficial basal cell carcinomas and eight melanomas. Results The main RCM features of LPLK and their relative frequencies were: (i) typical honeycomb pattern of the spinous layer (78.6%); (ii) elongated cords and/or bulbous projections at the dermal‐epidermal junction (75%); and (iii) numerous plump‐bright cells and/or bright stellate spots in the superficial dermis (92.9%). These RCM features correlated with the following histopathological findings respectively: (i) spinous‐granular layers without significant atypia of keratinocytes; (ii) elongated, bulbous rete ridges; and (iii) dense infiltration of melanophages and lymphocytes in superficial dermis. We propose diagnostic criteria that classify correctly 71.4% of LPLK, while avoiding misclassification of any of the skin cancers in the present series as LPLK. Conclusions We identified RCM criteria for diagnosis of LPLK that correlate well with histopathological findings and that allow differentiation of LPLK from skin cancer.     

Microphthalmia with Linear Skin Defects Syndrome

Abstract: Microphthalmia with linear skin defects (MLS) or microcornea, dermal aplasia and sclerocornea (MIDAS) syndrome is a rare X‐linked‐dominant disorder. We present a patient with agenesis of corpus callosum, ocular abnormalities, and multiple skin defects. The cytogenetic studies of the MLS critical region (Xp22.2) were normal, but a skewed X‐chromosome inactivation pattern (85:15) was observed.     

A Pediatric Case of Sclerodermatous Graft‐Versus‐Host Disease Responsive to Ultraviolet A1 Phototherapy

Graft‐versus‐host disease (GVHD) is one of the major complications after hematopoietic stem cell transplantation and is responsible for post‐therapeutic morbidity, mortality, and poor quality of life of recipients. Sclerodermatous graft‐versus‐host disease (sGVHD) is a rare variant of chronic GVHD characterized by deposition of collagen in the skin and other soft tissues and resulting in loss of range of motion and functional capabilities. Treatment of sGVHD is challenging and largely limited by systemic side effects. Ultraviolet A1 phototherapy has been reported to be effective in connective tissue disorders, including sGVHD. We report a case of sGVHD in a 15‐year‐old girl that was resistant to traditional therapy but showed improvement in cutaneous symptoms with ultraviolet A1 phototherapy three times a week for 6 weeks (10 J/cm² single dose, 180 J/cm² cumulative dose).     

Differences in the surface and subsurface reflection characteristics of facial skin by age group

Background/purpose: The age‐dependent changes of facial skin imperfections such as spot or wrinkles have been investigated repeatedly by means of various objective measurements. However, the age‐dependent changes in the optical‐reflection characteristics that create a perception of a shine or a glow of the skin have received little attention. We evaluated the age dependence of the optical‐reflection characteristics of the surface and subsurface facial skin layers of three age groups. Methodology: The facial skin of 83 Japanese females ranging in age from 20 to 49 years was examined using a high‐resolution digital camera equipped with a linear polarizing filter under polarized illumination. Surface and subsurface reflection components were extracted by means of an image‐processing technique. In addition to the reflection characteristics, skin hydration, the melanin index, and the hemoglobin index were also measured. Results: Significant age‐dependent changes were found in the evenness of the surface reflection and in the intensity of the subsurface reflection. In contrast, no difference was observed in the intensity of the surface reflection or in the evenness of the subsurface reflection. The melanin index showed a significant age‐dependent difference, with a trend similar to that of the subsurface reflection intensity, but the skin hydration and hemoglobin index showed no difference by age group. Conclusion: Surface and subsurface reflection characteristics show age‐dependent changes. Younger skin has a greater subsurface reflectivity and a more even surface reflectivity. These optical characteristics of the skin might be related to the perception of consumers that younger skin is brighter and more radiant with an internal glow, whereas aged skin is shinier or glossier.     

A prospective study of the incidence of skin cancer and its risk factors in a Spanish Mediterranean population of kidney transplant recipients

BACKGROUND: Skin cancer is the most common malignancy occurring in kidney transplant recipients (KTRs). OBJECTIVES: Our purpose was to investigate, prospectively, the cumulative incidence of cancerous and precancerous skin lesions as well as their risk factors in a close follow-up population of KTRs from a Mediterranean area of Spain. PATIENTS AND METHODS: One hundred and seventy-four consecutive KTRs were examined at the moment of transplant and then at 6-month intervals. The cumulative incidence of skin cancer was computed. To analyse the role of potential risk factors (age at transplantation, cause of renal failure, duration of pretransplant dialysis, type of immunosuppressive regimen, sun-reactive skin type and history of occupational sun exposure), the Cox regression method was used. RESULTS: After a median follow-up of 72 months (range, 12-140), 39 patients (25.3%) developed 142 tumours [84 basal cell carcinoma (BCC) and 58 squamous cell carcinoma (SCC)]. The BCC/SCC ratio was 1.4 : 1. The cumulative incidence for skin cancer was 13% after 3 years of graft survival, increasing to 27.5% at 6 years and 48% at 10 years. Only age at the time of transplantation and occupational sun exposure had statistical significance as risk factors (P < 0.001). CONCLUSIONS: Our study confirms the high incidence of non-melanoma skin cancer among KTRs in a Mediterranean population with occupational sun exposure and the patient's age at the time of transplantation being the main risk factors. We believe that all organ transplant programs should provide educational information about protecting oneself from the sun as well as include follow-up visits by dermatologists in order to facilitate early diagnosis and treatment of skin cancer.     

Recognizing the impact of ambient air pollution on skin health

Ambient air pollution is a known public health hazard that negatively impacts non‐cutaneous organs; however, our knowledge regarding the effects on skin remains limited. Current scientific evidence suggests there are four mechanisms by which ambient air pollutants cause adverse effects on skin health: (i) generation of free radicals, (ii) induction of inflammatory cascade and subsequent impairment of skin barrier, (iii) activation of the aryl hydrocarbon receptor (AhR) and (iv) alterations to skin microflora. In this review, we provide a comprehensive overview on ambient air pollutants and their relevant sources, and highlight current evidence of the effects on skin.     

Skin colorimetric parameters involved in skin age perception

Background/purpose: Age perception is based on a number of facial attributes such as wrinkles, skin gravity effects, feature lines, and skin optical appearance. The colorimetric and optical diffusion properties of skin have been compared with the consumer interpretation of ‘skin age’ of cheek area pictures without wrinkles or feature lines. Methods: Controlled lighting images of skin were taken with the Visia CR. Skin sections from the cheek area were selected without eye region wrinkles or naso‐labial lines for consumer interpretation. These same skin sections were analyzed for optical roughness and colorimetric parameters in the LCH color space, by distinguishing several roughness parameters according to their physical scale. Results: Three main optical parameters of skin were found to influence the consumer's interpretation of skin ‘visual age’: the chroma (color saturation), lightness, and the local light‐diffusing ability of skin. For the chroma and lightness, mainly large‐scale inhomogeneities in the 0.8–2 cm^?1 range are taken into account by the consumer. Surprisingly, variations in the skin hue show a total absence of correlation with the consumer grading.     

Seemingly healthy skin in atopic dermatitis: observations with the use of high‐frequency ultrasonography,preliminary study

Background: Atopic dermatitis (AD) is a chronic, relapsing skin disorder which is strictly determined by the epidermal barrier function. In previous studies, there is conclusive evidence that normal‐looking, nonlesional skin presents meaningful barrier function defect and a sub‐clinical eczematous skin reaction. Aim: The authors intended to visualize nonlesional AD skin with the use of high frequency ultrasonography to show that the normal‐looking, nonlesional skin may present significant abnormalities in USG examination. Methods: We have performed analysis with the use of high‐frequency 20 MHz skin sonography in the cases of 15 AD patients of the Department of Dermatology, Medical University, Poznań, Poland. The clinical score has been evaluated on the basis of W‐AZS index and EASI. The results were presented in the form of ultrasonographic images. Results: High frequency ultrasonography revealed an echopoor band within nonlesional skin of six (40%) examined AD patients and in all cases within skin lesions. Conclusion: Our results indicate the significant role of skin ultrasonography in the complete clinical evaluation of patients with AD, which may serve as an element in selection of the most appropriate topical treatment. An echopoor band beneath the echo entry within nonlesional skin of some AD patients may reflect subclinical eczematous reaction and the readiness for the development of typical skin lesions. For this purpose, we suggest to name an intact skin in AD as seemingly healthy skin.     

Infant Skin Microstructure Assessed In Vivo Differs from Adult Skin in Organization and at the Cellular Level

Abstract: Functional differences between infant and adult skin may be attributed to putative differences in skin microstructure. The purpose of this study was to examine infant skin microstructure in vivo and to compare it with that of adult skin. The lower thigh area of 20 healthy mothers (ages 25–43) and their biological children (ages 3–24 months) was examined using in vivo noninvasive methods including fluorescence spectroscopy, video microscopy, and confocal laser scanning microscopy. Stratum corneum and supra‐papillary epidermal thickness as well as cell size in the granular layer were assessed from the confocal images. Adhesive tapes were used to remove corneocytes from the outer‐most layer of stratum corneum and their size was computed using image analysis. Surface features showed differences in glyph density and surface area. Infant stratum corneum was found to be 30% and infant epidermis 20% thinner than in adults. Infant corneocytes were found to be 20% and granular cells 10% smaller than adult corneocytes indicating a more rapid cell turnover in infants. This observation was confirmed by fluorescence spectroscopy. Dermal papillae density and size distribution also differed. Surprisingly, a distinct direct structural relationship between the stratum corneum morphology and the dermal papillae was observed exclusively in infant skin. A change in reflected signal intensity at ～100 μm indicating the transition between papillary and reticular dermis was evident only in adult skin. We demonstrate in vivo qualitative and quantitative differences in morphology between infant and adult skin. These differences in skin microstructure may help explain some of the reported functional differences.     

Comparison of 2‐D shear wave elastography with clinical score in localized scleroderma: A new method to increase the diagnostic accuracy

There is no established diagnostic criteria or widely accepted severity classification of localized scleroderma (LS) by imaging. Acoustic radiation force impulse (ARFI) technology by normalized mean shear wave velocity (SWV) may be as a probing tool for diagnosing and staging LS accurately and objectively. Fifty‐six patients with LS of inflammatory (n = 21), sclerotic (n = 24) and atrophic (n = 11) stage and 30 healthy controls were evaluated on the basis of pathological results. Dermal thickness, ARFI quality (elastography score) and quantity (mean SWV) were measured by ultrasonography (US), diagnosis and stage performances of LS using the dermal thickness, elastography score and mean SWV compared with modified localized scleroderma skin severity index (mLoSSI) were evaluated. Significant differences in the dermal thickness, elastography score and mean SWV were found between the normal adult and LS patients; for diagnosing LS, the area under the receiver–operator curves (AUROC) of the dermal thickness, elastography score, mean SWV and mLoSSI were 0.93 ± 0.03, 0.95 ± 0.01, 0.93 ± 0.03 and 0.93 ± 0.02, respectively. Compared with the dermal thickness, the elastography score and mLoSSI, the AUROC and the specificities of mean SWV for differentiating sclerotic from inflammatory stage and atrophic from sclerotic LS increased significantly, especially by normalized mean SWV (AUROC, 0.84 ± 0.06 and 0.83 ± 0.07; specificity, 85.71% and 91.67%). As non‐invasive methods, mean SWV and dermal thickness by US may provide reliable information to diagnose and stage LS compared with mLoSSI especially by normalized mean SWV.     

Validation of a non‐contact technique for local skin temperature measurements

Here we propose to quantify local temperature variations using thermal imaging to assess the effect of dermatological lasers. Objectives: To quantify the temperature raise induced by laser application and to differentiate the effects of a potassium titanyl phosphate (KTP) laser and an intense pulsed light (IPL). Methods: A randomized comparative study was performed on 10 adult volunteers with symmetrical rosacea treated by KTP laser or IPL. Skin temperature measurements were performed on inclusion, immediately after laser treatment and 3 min after thermal water application, using a high‐resolution (0.08 °C) infrared thermal video camera. Results: KTP laser treatment induced a significant rise in local skin temperature whereas no significant change was revealed by the IPL treatment. The infrared camera is a reliable and reproducible technique that allows a follow‐up of skin temperature without skin contact. Conclusion: Thermography using an infrared camera could potentially be applied in clinical pharmacology for inflammatory reactions or scarring processes.     

Analysis of human face skin surface molecules in situ by Fourier‐transform infrared spectroscopy

Background/purpose: For medical and dermatological researchers, it is important to realize the molecular dynamics and its control in the stratum corneum (SC) of human skin, which may be related to some skin abnormalities such as atopic dermatitis and skin pruritus. We have tried to analyze the periodic molecular dynamics of the outermost layers of SC in vivo. Methods: We measured the skin surface molecules of human face in situ non‐invasively using a Fourier‐transform infrared (FTIR) spectroscopy system attached with a newly designed attenuated total reflection (ATR) probe. The water‐extracted components from the SC were also analyzed using mass spectrometry, an enzymatic assay and high‐performance liquid chromatography characterization. Results: The infrared spectral changes of some components on the face skin at around 1000–1200 cm^?1 with circa‐monthly rhythms were observed when monitored for 10 months, and the components also showed a seasonal change. The analysis of different FTIR spectrum of the changeable components with circa‐monthly rhythm suggested the presence of a lactate compound. The presence of magnesium lactate in a conjugated form was detected in the water extract of SC. Conclusion: We demonstrate that the periodically changed components of the human face skin contained magnesium lactate conjugate as a major component.     

Impairment of skin barrier function via cholinergic signal transduction in a dextran sulphate sodium‐induced colitis mouse model

Dry skin has been clinically associated with visceral diseases, including liver disease, as well as for our previously reported small intestinal injury mouse model, which have abnormalities in skin barrier function. To clarify this disease‐induced skin disruption, we used a dextran sulphate sodium (DSS)‐induced colitis mouse model. Following treatment with DSS, damage to the colon and skin was monitored using histological and protein analysis methods as well as the detection of inflammatory mediators in the plasma. Notably, transepidermal water loss was higher, and skin hydration was lower in DSS‐treated mice compared to controls. Tumor necrosis factor‐alpha (TNF‐α), interleukin 6 and levels were also upregulated in the plasma, and a decrease in body weight and colon length was observed in DSS‐treated mice. However, when administered TNF‐α antibody or an iNOS inhibitor, no change in skin condition was observed, indicating that another signalling mechanism is utilized. Interestingly, the number of tryptase‐expressing mast cells, known for their role in immune function via cholinergic signal transduction, was elevated. To evaluate the function of cholinergic signalling in this context, atropine (a muscarinic cholinoceptor antagonist) or hexamethonium (a nicotinic cholinergic ganglion‐blocking agent) was administered to DSS‐treated mice. Our data indicate that muscarinic acetylcholine receptors (mAChRs) are the primary receptors functioning in colon‐to‐skin signal transduction, as DSS‐induced skin disruption was suppressed by atropine. Thus, skin disruption is likely associated with DSS‐induced colitis, and the activation of mast cells via mAChRs is critical to this association.