Treatment of three hereditary leiomyomatosis patients with cryotherapy

Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is an autosomal dominant disorder characterized by cutaneous leiomyomas (CLM), uterine leiomyomas, and the increased risk of renal cell carcinoma. Piloleiomyomas develop from the arrectorpili muscle and are usually painful. For 22% of the affected patients, the pain is reported to impair their life quality. Since there are few case reports about cryotherapy for cutaneous leiomyomas in the literature, we have decided to present three patients who had painful cutaneous leiomyomas treated with cryotherapy.     

CRUSTED PILOLEIOMYOMA WITH MENTAL RETARDATION: A RARE ASSOCIATION

Piloleiomyoma is an uncommon benign smooth muscle neoplasm arising from arrector pili muscle. It is clinically defined by the presence of solitary or multiple reddish brown, dome-shaped, smooth papules or nodules, ranging in size from a few millimeters to a centimeter. The patients are otherwise healthy; but mental retardation developing in some patients with multiple Piloleiomyomas has been emerging as an intriguing matter for analysis by the scientists. In this case report, a mentally retarded patient with Piloleiomyoma is described, who, besides the characteristic smooth and dome-shaped lesions on the anterolateral aspect of the dorsum of the right foot, had developed crusting on one of the largest lesions. The histopathological features were consistent with Piloleiomyoma. The occurrence of Piloleiomyoma in a mentally retarded child and its unusual crusted nature has been rarely reported. The association between Piloleiomyoma and mental retardation is further stressed in this case report.     

Multiple piloleiomyomas associated with solitary angioleiomyoma.

A 58 year-old male had reddish scattered papules strictly confined to the right side of his upper back and neck, right shoulder, and right upper arm. Additionally, he also noticed a subcutaneous nodule on his left thigh. Histopathological examinations revealed that the papules on the back, nape of the neck, shoulder, and arm were multiple piloleiomyomas, as shown by the proliferation of bundles of smooth muscles in the dermis. The subcutaneous nodule of the thigh was angioleiomyoma with a well-circumscribed lesion composed of smooth muscles and blood vessels. Ipsilaterality and segmentality of the distribution of the papules of piloleiomyomas and probable family history that his mother had similar papules with a similar distribution suggest the nevoid character of our case. Piloleiomyomas are often reported to be associated with leiomyoma of the uterus or other organs. This is the first reported case of multiple piloleiomyomas with solitary angioleiomyoma in the literature.     

The response of distant uninvolved psoriatic skin to standardised injury is not different from that in normal skin.

The epidermis of uninvolved psoriatic skin is characterised by a slight hyperproliferation and an increase in inflammatory parameters, whereas no differentiation abnormalities are seen. Data with respect to the response of distant uninvolved psoriatic skin to standardised injury are not uniform. In this study, a recently developed multiparameter flow cytometric assay was used to compare the response to tape stripping of uninvolved psoriatic and normal skin. With this method, a parameter for proliferation, differentiation and inflammation was measured simultaneously. Concerning these parameters, no statistically significant differences were found between uninvolved psoriatic skin and normal skin. The mechanism that underlies hyperproliferation in distant uninvolved psoriatic skin does not indicate an intrinsic abnormality in keratinocytes. Inflammatory signals might play a role in this process.     

Pathophysiology and management of sensitive skin: position paper from the special interest group on sensitive skin of the International Forum for the Study of Itch (IFSI)

The special interest group on sensitive skin of the International Forum for the Study of Itch previously defined sensitive skin as a syndrome defined by the occurrence of unpleasant sensations (stinging, burning, pain, pruritus and tingling sensations) in response to stimuli that normally should not provoke such sensations. This additional paper focuses on the pathophysiology and the management of sensitive skin. Sensitive skin is not an immunological disorder but is related to alterations of the skin nervous system. Skin barrier abnormalities are frequently associated, but there is no cause and direct relationship. Further studies are needed to better understand the pathophysiology of sensitive skin – as well as the inducing factors. Avoidance of possible triggering factors and the use of well-tolerated cosmetics, especially those containing inhibitors of unpleasant sensations, might be suggested for patients with sensitive skin. The role of psychosocial factors, such as stress or negative expectations, might be relevant for subgroups of patients. To date, there is no clinical trial supporting the use of topical or systemic drugs in sensitive skin. The published data are not sufficient to reach a consensus on sensitive skin management. In general, patients with sensitive skin require a personalized approach, taking into account various biomedical, neural and psychosocial factors affecting sensitive skin.     

Prenatal human skin expresses the antimicrobial peptide RNase 7

Antimicrobial peptides and proteins (AMPs) play important roles in skin immune defense due to their capacity to inhibit growth of microbes. During intrauterine life, the skin immune system has to acquire the prerequisites to protect the newborn from infection in the hostile environment after birth, which includes the production of skin AMPs. The aim of this study was to analyze the expression of RNase 7, HBD-2/3 and psoriasin during human skin development, thus, providing a deeper insight about the maturity of a fundamental component of the innate immune system. We found low RNase 7 expression levels in the periderm but no expression of HBD-2/3 and psoriasin in first trimester human skin using immunohistochemistry. At the end of the second trimester, RNase 7 is expressed weakly in all epidermal layers with a marked signal in the stratum corneum. HBD-3 and psoriasin are focally expressed while HBD-2 is not detectable. Analysis of supernatants from cultured prenatal skin cells showed that in contrast to adult control, RNase 7 and psoriasin are not found in prenatal skin, suggesting that AMPs are detectable but are not secreted. This study shows the differential expression of AMPs in developing, non-perturbed human prenatal skin. It is conceivable that the combined expression of RNase 7, HBD-3 and psoriasin in fetal skin constitutes a developmental program to exert a broad spectrum of antimicrobial activity to maintain sterility in the amniotic cavity.     

Role of Erbium:YAG laser in the treatment of aged skin

Laser resurfacing procedures in actinic skin damage and the treatment of disorders associated with skin ageing are becoming more popular. For both purposes Erbium:YAG laser-technology enables us to perform a highly precise skin ablative work, which can be most helpful in the removal of circumscribed skin lesions of ageing skin as well as in larger skin resurfacing procedures. In most circumstances, superficial skin ablation is not technically demanding, is not associated with major discomfort, and can be controlled with precision. Tissue sparing ablation is of special value in the treatment of disorders in atrophic skin of elderly patients or in more delicate areas, where it can avoid prolonged healing and unwarranted side-effects.     

老年人皮肤生物物理特性的改变及其意义

随着机体的衰老,各器官(包括皮肤)的生物功能发生变化。在皮肤,这些生物功能的改变通常体现在皮肤生物物理特性的变化。与年轻者相比,老年皮肤的共振传导速度加快、pH升高、弹性降低、皮脂减少、角质层含水量减少以及表皮通透屏障功能降低等。测量老年皮肤生物物理特性的变化不仅有利于了解其皮肤的生物功能,也有助于对某些皮肤治疗和保健品的研发及疗效的评估。     

Skin surface pH, stratum corneum hydration, trans-epidermal water loss and skin roughness related to atopic eczema and skin dryness in a population of primary school children

Non-invasive investigations of skin morphology and function are standard tools to study the pathophysiology of several cutaneous disorders, yet they have not been used in population-based epidemiological studies. Here we examined skin surface pH, stratum corneum hydration, trans-epidermal water loss (TEWL) and skin roughness by profilometry in a study population comprising 377 primary school children (8-9 years old) as part of a multicentre survey on risk factors for allergic diseases in school children. Skin surface pH showed significant higher values (p=0.029) in the group with atopic eczema (n=45) compared with the group without atopic eczema; all other parameters did not differ significantly between children with and without atopic eczema. With increasing skin dryness there was a significant increase in pH values (p=0.004). Stratum corneum hydration showed a significant decrease with increasing dryness (p<0.001). Measurement of skin roughness also revealed a significant linear relationship with skin dryness (p=0.02). It is concluded that measurement of skin surface pH, corneometry and profilometry are useful non-invasive techniques to objectively assess skin dryness in epidemiological studies regarding atopic skin disease.     

A strategy for skin irritation testing.

Skin irritation safety testing and risk assessment for new products, and the ingredients they contain, is a critical requirement before market introduction. In the past, much of this skin testing required the use of experimental animals. However, new current best approaches for skin corrosion and skin irritation testing and risk assessment are being defined, obviating the need for animal test methods. Several in vitro skin corrosion test methods have been endorsed after successful validation and are gaining acceptance by regulatory authorities. In vitro test methods for acute, cumulative (repeat exposure), and chronic (prolonged exposure) skin irritation are under development. Though not yet validated, many are being used successfully for testing and risk assessment purposes as documented through an expanding literature. Likewise, a novel acute irritation patch test in human subjects is providing a valid and ethical alternative to animal testing for prediction of chemical skin irritation potential. An array of other human test methods also have been developed and used for the prediction of cumulative/chronic skin irritation and the general skin compatibility of finished products. The development of instrumental methods (e.g., transepidermal water loss, capacitance, and so on) has provided the means for analyzing various biophysical properties of human skin and changes in these properties caused by exposure to irritants. However, these methods do not directly measure skin inflammation. A recently introduced skin surface tape sampling procedure has been shown to detect changes in skin surface cytokine recovery that correlate with inflammatory skin changes associated with chemical irritant exposures or existing dermatitis. It holds promise for more objective quantification of skin irritation events, including subclinical (sensory) irritation, in the future.     

Neue Erkenntnisse zur Pathogenese der empfindlichen Haut

Many persons in the developed countries report sensitive skin. Persons with sensitive skin have a predisposition to several skin diseases, most importantly dry skin, but also atopy, seborrheic dermatitis, acne vulgaris, rosacea, and perioral dermatitis. Their complaints may be triggered by environmental factors such as low temperature, wind, high temperature, sun exposure and stress. Various skin care products and cosmetics are not tolerated. A disturbed skin barrier function and reduced stratum corneum water content are most important in the pathophysiology of sensitive skin. Environmental factors and cosmetics may induce irritation of the skin because of the disturbed skin barrier. Of further importance for the pathogenesis are neurogenic factors including stress and hyper-excitability. Mechanisms in signal transduction involve cytokines and neurotransmitters, but the exact pathways are unknown.     

Dermatoscopy: an overview of subsurface morphology

Within the past two decades, an exponential number of publications have emerged on the topic of dermatoscopy, most, if not all, reporting the benefits of using a dermatoscope. Dermatoscopy has been promoted to be useful in diagnosing not only pigmented skin lesions but also a wide range of skin conditions that are infectious, hamartomatous, and inflammatory in nature. Whether or not dermatoscopy truly has a relevant diagnostic role in such a wide range of skin conditions remains to be proven. The diagnostic technique, however, has fundamentally changed the way pigmented lesions are evaluated by dermatologists, as it offers a more methodical and disciplined approach to evaluate them. This review highlights the contribution of dermatoscopy with respect to morphologic characterization and evaluation of pigmented skin lesions.     

Dermatologic reactions to disinfectant use during the COVID-19 pandemic

Infection preventive practice of using disinfectants against SARS-CoV-2 has become the new normal due to the COVID-19 pandemic. Although disinfectants may not be applied directly to the human body, it remains at high risk of exposure including close skin contact on disinfected surfaces or during handling. This dermal contact, on a regular basis, can induce hazardous skin reactions like irritation, inflammation, and burning in severe conditions. Disinfectants are germicide chemicals that can penetrate the skin and create skin reactions that are usually regarded as irritant and allergic contact dermatitis. More importantly, disinfectants can react with skin components (proteins and lipids) to facilitate their skin penetration and disrupt the skin barrier function. Whereas the antimicrobial actions of disinfectants are well understood, much less is known regarding their dermatologic reactions, including but not limited to irritation and hypersensitivity. We reviewed the skin reactions created by those disinfectants against SARS-CoV-2 approved by the European Chemical Agency and the US Environmental Protection Agency.     

Aging- and photoaging-dependent changes of enzymic and nonenzymic antioxidants in the epidermis and dermis of human skin in vivo.

This is a comprehensive study of the changes in major antioxidant enzymes and antioxidant molecules during intrinsic aging and photoaging processes in the epidermis and dermis of human skin in vivo. We show that the activities of superoxide dismutase and glutathione peroxidase are not changed during these processes in human skin in vivo. Interestingly, the activity of catalase was significantly increased in the epidermis of photoaged (163%) and naturally aged (118%) skin (n = 9), but it was significantly lower in the dermis of photoaged (67% of the young skin level) and naturally aged (55%) skin compared with young (n = 7) skin. The activity of glutathione reductase was significantly higher (121%) in naturally aged epidermis. The concentration of alpha-tocopherol was significantly lower in the epidermis of photoaged (56% of young skin level) and aged (61%) skin, but this was not found to be the case in the dermis. Ascorbic acid levels were lower in both epidermis (69% and 61%) and dermis (63% and 70%) of photoaged and naturally aged skin, respectively. Gluta thione concentrations were also lower. Uric acid did not show any significant changes. Our results suggest that the components of the antioxidant defense system in human skin are probably regulated in a complex manner during the intrinsic aging and photoaging processes.     

Regulation of adrenomedullin secretion in cultured human skin and oral keratinocytes

Adrenomedullin, a potent vasoactive peptide, is actively secreted from primary cultures of human oral and skin keratinocytes, but nothing is known of the regulation of its release. This study describes the effects of a range of substances on adrenomedullin production from cultures of oral and skin keratinocytes. We have established that keratinocytes do not store adrenomedullin but secrete it constitutively. Cytokines interleukin-1alpha and -1beta, tumor necrosis factor-alpha and -beta, and the bacterial product, lipopolysaccharide, significantly stimulate adrenomedullin secretion from oral but not skin keratinocytes. Both transforming growth factor-beta1 and interferon-gamma are potent suppressors of adrenomedullin secretion from both cell types, as are forskolin, di-butyryl cyclic adenosine monophosphate, and adrenocorticotropin. The peptides thrombin and endothelin-1 increase adrenomedullin production, particularly from skin keratinocytes. These findings indicate that there are differences in the regulation of adrenomedullin production between oral and skin keratinocytes and that oral keratinocytes are particularly responsive to the action of inflammatory cytokines. This raises the possibility that adrenomedullin may serve a different functions in oral mucosa and skin.     

Psoriasiform changes in guinea-pig skin from propranolol

Psoriasiform eruptions of the skin are recognized as a not uncommon adverse effect of practolol and other β-adrenergic blocking drugs. Topical application of propranolol to guinea-pig skin causes thickening of the skin with histological changes strikingly resembling psoriasis in man. These findings suggest that propranolol has a direct pharmacological effect on the skin.     

In vivo epiluminescence microscopy of pigmented skin lesions. I. Pattern analysis of pigmented skin lesions

The importance of recognizing early melanoma is generally accepted. Because not all pigmented skin lesions can be diagnosed correctly by their clinical appearance, additional criteria are required for the clinical diagnosis of such lesions. In vivo epiluminescence microscopy provides for a more detailed inspection of the surface of pigmented skin lesions, and, by using the oil immersion technic, which renders the epidermis translucent, opens a new dimension of skin morphology by including the dermoepidermal junction into the macroscopic evaluation of a lesion. In an epiluminescence microscopy study of more than 3000 pigmented skin lesions we have defined morphologic criteria that are not readily apparent to the naked eye but that are detected easily by epiluminescence microscopy and represent relatively reliable markers of benign and malignant pigmented skin lesions. These features include specific patterns, colors, and intensities of pigmentation, as well as the configuration, regularity, and other characteristics of both the margin and the surface of pigmented skin lesions. Pattern analysis of these features permits a distinction between different types of pigmented skin lesions and, in particular, between benign and malignant growth patterns. Epiluminescence microscopy is thus a valuable addition to the diagnostic armamentarium of pigmented skin lesions at a clinical level.     

Suppressor cell activation and enhanced skin allograft survival after tumor promotor but not initiator induced depletion of cutaneous Langerhans cells

During chemical carcinogenesis Langerhans cells (LC) are depleted from the epidermis, disrupting the normal immunological functions of the skin. Tumor promotors but not initiators, have been shown to deplete adenosine triphosphatase (ATPase)-positive LC from the skin and therefore the cutaneous immune system may be impaired during tumor promotion but not initiation. The present study shows that the tumor promotor 12-O-tetradecanoylphorbol 13-acetate (TPA) but not the initiator urethane depletes Ia-positive LC from BALB/c murine ear epidermis, and beta-glucuronidase-positive LC from C57BL mouse tail skin. Sensitization with 2,4-dinitrofluorobenzene (DNFB) through urethane-treated skin resulted in a normal contact sensitivity response when the mice were challenged 5 days later. In contrast, tolerance resulted from sensitization through TPA-treated skin as a result of the generation of suppressor cells. In addition, TPA but not urethane-treated C57BL mouse tail skin survived for an extended time when grafted onto histoincompatible BALB/c mice. Therefore, impairment of the normal immunological functions of skin resulted from treatment with the tumor promotor TPA but not the tumor initiator urethane, which suggests that a loss of LC during tumor promotion may impair immunological protection against skin tumors.     

Are computers better diagnosticians than dermatologists? A discussion of how artificial intelligence can help in diagnosing skin lesions

Skin cancers are the most common cancers in the UK. Malignant Melanoma (MM) is the most dangerous type of skin cancer. Primary Care Physicians (GPs) often have difficulty in distinguishing harmless skin blemishes from MM, leading to many patients being referred to dermatology departments. There have been enormous advances recently in the application of computer-based Artificial Intelligence (AI) to the field of image analysis. This paper from four authors in London (UK) explores the current position of AI systems in analysing skin lesions (affected patches of skin). Important AI concepts such as convolutional neural networks (CNN) and “deep learning” are explained. By exposing AI systems to hundreds of thousands of pictures of skin lesions, it is possible to “train” them to recognise lesions with a high degree of accuracy. Skin cancer detection, particularly melanoma detection, has now been tested by numerous different groups with multiple AI systems; the most successful ones are generally “convolutional neural networks”. When comparing their performance to dermatologists who are presented with photographs of skin lesions, these AI systems perform similarly, if not better, at identifying whether something is a melanoma or a benign (non-cancerous) mole. However, these programmes are limited by the data sets on which they have been “trained”; for example, a lot of the datasets are trained on Caucasian skin, and will perform less well when detecting melanoma in skin of colour, as they may not have been exposed to enough of this type of image to perform well. They have also not been shown to be particularly useful for diagnosing other types of skin conditions yet and they are not able to provide any kind of explanation for their classification. Because of these limitations, it is unlikely that they will replace dermatologists. The legal framework for AI systems also doesn't allow them to take responsibility for decisions, so responsibility for diagnosis still falls to a responsible clinician. However, in the near future they may well prove to be extremely useful in aiding GPs in making clinical decisions about skin lesions, particularly with regards to urgent referrals to dermatology. Linked Article:   Du-Harpur et al. Br J Dermatol 2020; 183 :423–430 .     

In the shadow of the wrinkle: theories

As time passes, wrinkles typically appear. These skin depressions that become deeper and deeper draw more and more coarser lines on almost all the visible parts of aging individual's skin. They are indeed the most obvious and maybe disliked signs of skin aging, and thus, preventing and treating them are a major topic for dermo-cosmetic laboratories. However, the cause and occurrence mechanism of these simplistic looking lines are not yet fully understood. Wrinkling is thought to be a complex biophysical process resulting from repeated strains on a progressively, structurally and biochemistry altered aging skin with impaired mechanical properties. Focus is made on the specific histological features of the wrinkle compared to the surrounding aging skin. The numerous age-related changes in human skin that are supposed to be involved in wrinkling are briefly reviewed, and the current theories on wrinkle formation linked to these changes are also discussed.