The use of lasers in Becker's naevus: An evidence-based review

Becker's naevus is a hamartoma that often appears during puberty. Clinically this presents with a pigmented and often hairy patch most often on the shoulders. Treatment has always been challenging and lasers are often used with mixed results. This article reviews the evidence of all the laser treatments used in Becker's naevus and analyses the findings from the published studies and trials.     

白癜风患者血浆三种神经肽测定及其临床意义

目的：β内啡肽（β－EP）、神经肽Y（NPY）及降钙素基因相关肽（CGRP）是重要的神经递质,同时也可作为免疫调节因子发挥作用。本研究旨在观察这些神经肽是否可能与白癜风的发病有关。方法：用放射免疫分析法测定40例白癜风处于进展期或稳定期的不同类型患者血浆3种神经肽浓度,并与23例正常对照作比较。结果：寻常型（局限性与泛发性）、节段型、进展期和稳定期白癜风患者血浆β－EP、NPY水平均较正常对照组显著增高;进展期白癜风NPY比稳定期显著提高;泛发性及进展期白癜风血浆CGRP比正常对照组显著增高。结论：结果表明上述三种神经肽与白癜风的发病可能存在一定关系,开发神经肽拮抗剂对于白癜风的治疗可能成为一种新的途径。     

Time course effect and sequential morphological changes of subepidermal nerve fibers in guinea pig skin after application of histamine ointment: a laser scanning confocal fluorescence microscopic and electron microscopic study

This study was undertaken to elucidate the morphological effects of histamine on subepidermal nerve fibers. A 10% histamine ointment was topically applied to the back skin of 17 adult male Hartley guinea pigs. Biopsy specimens were obtained at times from 5 min to 24 h, and were examined by conventional immunofluorescence (IF), laser scanning confocal fluorescence microscopy (LSCM) and transmission electron microscopy. On IF and LSCM, marked diminutions in the immunoreactivity of protein gene product 9.5-immunoreactive (PGP 9.5-IR) fibers as well as of substance P-immunoreactive (SP-IR) and calcitonin gene-related peptide-immunoreactive (CGRP-IR) substances were observed 5 min after histamine application. By 30 min, immunoreactivity of PGP 9.5, SP and CGRP was completely lost. By 2 h, however, immunoreactivity of PGP 9.5-IR fibers and CGRP-IR substances started to show recovery. By 4 h, immunoreactivity of PGP 9.5, SP and CGRP had almost recovered, but the recovery time for each substance was slightly different (PGP 9.5 first, CGRP next, and SP last). By 6 h after histamine application, immunoreactivity of all these substances had fully recovered. Ultrastructurally, 5 min after histamine application, axonal and mitochondrial swelling and glycogen deposition were seen in the axons of subepidermal nerve fibers. By 30 min, severe axonal degeneration had occurred in some of the axons. It was only by 4 to 6 h that almost normal ultrastructural features were observed. Schwann cells and perineurial cells did not show any pathological changes. These findings demonstrate that 10% histamine ointment produced organic changes in the axons in the subepidermal nerve fibers of guinea pig skin, but these morphological changes were short-lived, reversible and transitory.     

Ontogeny of nerves and neuropeptides in skin of rat: An immunocytochemical study

Abstract The sequence of maturation of nerves and appearance of neuropeptides was investigated in skin from fetal and neonatal rats by immunocytochemistry using antisera to protein gene product 9.5, substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY). Immunoreactivity for PGP 9.5 appeared on fetal day 16 in face and nose, somewhat later (fetal day 19) in paws and tail. The sensory neuropeptides, CGRP/substance P (fetal day 19 and postnatal day 1, respectively) appeared earlier than the autonomic peptides VIP and NPY (postnatal day 7). Thus, the study shows that neuropeptides do not appear simultaneously with nerves and that the development is rostrocaudal.     

[Translated article] Melanoma Arising in Plaque-Type Blue Nevus and Dermal Melanocytosis: Diagnostic and Prognostic Value of BAP1

Melanoma arising in blue nevus, also known as melanoma ex blue nevus, is a specific form of melanoma whose genetic profile is different to that of other cutaneous melanomas and surprisingly similar to that of uveal melanoma. Although melanoma ex blue nevus can appear de novo, it usually arises in a pre-existing blue nevus or dermal melanocytosis. Not all nodular lesions arising in association with blue nevus or dermal melanocytosis are melanomas, however, and because clinical and histologic findings may be insufficient for a definitive diagnosis, additional studies such as comparative genomic hybridization are important. Detection of chromosomal aberrations supports a diagnosis of malignancy. Studies of the BAP1 gene are particularly useful in this setting because loss of expression is indicative of melanoma. We present 3 cases on the spectrum of blue nevus to melanoma ex blue nevus that were studied using molecular biology techniques.     

Cryosurgery and Topical Fluorouracil: A Treatment Method for Widespread Basal Cell Epithelioma in Basal Cell Nevus Syndrome

A 58-year-old man with basal cell nevus syndrome had variously sized basal cell epitheliomas (BCEs), mostly of the superficial type, on his chest, back, and lumbar areas. BCEs on the lumbar area were treated with 5-fluorouracil (5-FU) cream which was applied daily under occlusive dressings (ODT). Complete erosion occurred in the center, but not at the periphery of the lesions. In the latter regions, BCE remained. Then cryosurgery (cryo) followed by topical 5-FU (cryo + 5-FU) was tried to treat the peripheral, non-eroded lesions; this caused complete erosions. Biopsy specimens obtained 6 months after epithelization did not show any evidence of recurrence. We also tried either cryo alone or cryo + 5-FU on the chest lesions, and either 5-FU alone or cryo + 5-FU on the abdominal lesions. Cryo alone or 5-FU alone could not clear BCE, but cryo + 5-FU could. These results suggest that the cryo + 5-FU was the most effective of these therapies.     

错配修复基因hMLH_1和hMSH_2蛋白在正常皮肤黑素细胞痣和皮肤恶性黑素瘤中的检测

目的检测DNA错配修复基因hMLH1和hMSH2蛋白在正常皮肤、黑素细胞痣和皮肤恶性黑素瘤(CMM)中的水平,探讨其在皮肤黑素瘤发生、发展中的可能作用。方法用免疫组化SP法检测20例正常皮肤、30例黑素细胞痣和57例原发性CMM中hMLH1和hMSH2蛋白的水平。结果①正常皮肤的表皮、皮肤附属器和黑素细胞痣的细胞核中,hMLH1和hMSH2蛋白强阳性,这两种蛋白在正常皮肤和黑素细胞痣无显著性差异(P>0.05);②在57例CMM中,hMLH1蛋白阳性35例(61.40%),hMSH2蛋白阳性32例(56.14%),这两种错配修复蛋白在CMM中的阳性率和阳性强度显著低于其在正常皮肤和黑素细胞痣中的水平(P均<0.005);③在CMM中,随Clark分级升高,hMLH1和hMSH2蛋白的阳性率和阳性强度逐渐降低。结论错配修复基因hMLH1和hMSH2蛋白在维护正常皮肤和皮肤附属器细胞基因组稳定性中可能发挥了重要作用,其异常可能参与了CMM发生和发展的过程。     

Distribution density of intraepidermal nerve fibers in normal human skin

A total of 74 specimens was obtained from the normal human skin of patients from 3 to 90 years old. The specimens were roughly classified into 5 groups: 15 for the face group from the face; 15 for the abdomen group from the abdomen; 13 for the back group from the back; 14 for the arm group from the upper arm and forearm; and 17 for the leg group from the thigh and lower leg. They were all fixed in 4% paraformaldehyde and 14% saturated picric acid. Cryostat sections were examined by the immunoperoxidase method and indirect immunofluorescence (IF). Primary antibodies against neurofilament, neuron-specific enolase, protein gene product 9.5 (PGP 9.5) and S-100 protein were used. The most effective method was found to be the combination of IF with PGP 9.5; it visualized the intraepidermal nerve fibers easily and clearly. Of the 74 specimens, 32 (43%) had intraepidermal PGP 9.5-immunoreactive (or nerve) fibers (IPIF), and 42 (57%) did not have any. With reference to the different skin locations, the maximal rate of specimens having IPIF was 57% in the arm group, and the minimum was 23% in the back group. IPIF positive specimens had approximate surface lengths of 6 mm, in which the existence number of the IPIF was 1 to 75. Their distribution density per 1000 epidermal basal cells was highest at 9.63 in the arm group and lowest at 2.89 in the back group. Their thickness was 2.94 +/- 0.83 microns with no significant differences among the five groups. We concluded that intraepidermal nerve fibers may not be distributed evenly in the hairy portions of normal human skin, but they may be present focally. Physiologically, two-point discrimination of itch may be explained by the distribution mode of intraepidermal nerve fibers.     

The Vascular Space-like Structure in Melanocytic Nevus Is Not an Injection Artifact: Report of a Case and an Experimental Study

Melanocytic nevi may microscopically associate with clefts or slits of the nests resembling lymphatic or vascular spaces. This unique histologic feature has been known as an artifact of injection or tissue-processing. We present a case of melanocytic nevus with a prominent vascular space-like structure. We also studied whether intralesional injection of local anesthetic could reproduce similar histologic findings. A 45-year-old Japanese female visited us with a solitary, brownish papule on the chest. Histology revealed numerous nests composed of round to oval-shaped nevus cells throughout the entire dermis. In the mid-dermis, nevus cells were lined up in a layer anastomosing and forming a vascular space-like structure. These nevus cells were uniformly stained with vimentin and S100 protein but not with factor VIII-related antigen. They were also positively immunoreactive with anti-type IV collagen and anti-fibronectin. There were no significant differences in staining intensity in the nevus cells between the solid portion and the vascular space-like structure. In the experimental study, eight melanocytic nevi were removed under local anesthesia. The local anesthetic solution was then injected into the excised nevus. Intralesional injection of a considerable volume of local anesthetic was capable of causing slits or clefts of the nests and dermal edema; however, it failed to reproduce a vascular space-like structure similar to that in the present case. These findings suggest that a vascular space-like structure in melanocytic nevus is not caused by the injection alone. Some other factor(s) may play a major role in the development of such structures in melanocytic nevus.     

The Importance of Collagen Tissue in Papular Elastorrhexis,Eruptive Collagenoma,and Nevus Anelasticus

BackgroundPapular elastorrhexis (PE), eruptive collagenoma (EC), and nevus anelasticus (NA) are described as multiple small papules with decrease, fragmentation, or lack of dermal elastic fibers. These diseases are suggested to be the same entity. The change of collagen fibers in the conditions has not been addressed to date.ObjectiveWe compared the clinical features of the 3 diseases and investigated changes in the collagen fibers involved.MethodsTwenty-four cases of PE, 12 cases of EC, and 2 cases of NA found in PubMed and the Korean database were reviewed. Changes in dermal collagen fibers in 10 cases with histological figures were investigated.ResultsThere were significant similarities between the 3 entities in terms of their clinical features. Four patients with PE and 2 with EC with fine, dense collagen fibers were women who had multiple white to hypopigmented, slightly indurated to firm, millimeter-size papules on the trunk and/or extremities that progressed gradually after developing in the patients'' first to third decades.ConclusionThe 3 conditions are the same clinical entity in our opinion; such cases with fine, dense collagen manifest typical features.     

Increased innervation of the vulval vestibule in patients with vulvodynia

BACKGROUND: Vulval vestibulitis is a condition characterized by the sudden onset of a painful burning sensation, hyperalgesia, mechanical allodynia, and occasionally pruritus, localized to the region of the vulval vestibulus. It is considered the commonest subset of vulvodynia. Pain precipitated in the absence of nociceptor stimuli might be triggered by previous peripheral nerve injury, or by the release of neuronal mediators, which set off inappropriate impulses in nonmyelinated pain fibres sensitizing the dorsal horn neurones. The pathophysiology of vulval vestibulitis is still unclear. OBJECTIVES: The objective of this study was to evaluate the nerve fibre density and pattern, in specimens of vulval vestibulus, in normal subjects and in patients with vestibulitis, and provide objective diagnostic criteria for this condition. Methods Twelve patients with a history of the vestibulitis type of vulvodynia, and eight normal subjects underwent biopsy of the posterior wall of the vulval vestibule. Quantitative immunohistochemistry was performed, using antisera to the general neuronal marker protein gene product (PGP) 9.5, and to the neuropeptide calcitonin gene-related peptide (CGRP), on 15- microm sections. RESULTS: There was a statistically significant increase of density and number of PGP 9.5 immunoreactive in the papillary dermis of patients with vulvodynia of the vestibulitis type, compared with those of controls. However, the distribution pattern of the innervation showed no significant change. There were no significant differences in CGRP staining between patients and controls. CONCLUSIONS: It is concluded that the increase of PGP 9.5 immunoreactive nerve fibres, in patients with vulvodynia, may be either secondary to nerve sprouting, or may represent neural hyperplasia. Increased innervation may be applied as an objective diagnostic finding in vulval vestibulitis syndrome.     

降钙素基因相关肽在银屑病斑块型皮损的分泌与表达

为了解精神心理刺激诱发加重银屑病的原因,探讨神经肽在银屑病发病机理中的作用,研究了降钙素基因相关肽（ＣＧＲＰ）在银悄病皮损中的分泌与表达,并确定ＣＧＲＰ作用的靶细胞,应用特异性放射免疫反相法分析,测定３２例建党型银屑病慢性斑块型皮损组织提取液中ＣＧＲＰ的含量,用抗生物素蛋白－生物素－过氧化物酶复合法和兔抗人ＣＧＲＰ抗体进行免疫组化染色,观察ＣＧＲＰ分泌表达的部位和作用的靶细胞。结果建党型银屑病慢性     

Density and fine structure of peripheral nerves in various skin lesions of atopic dermatitis

The density and fine structure of the peripheral nerve system in various skin lesions of 64 patients with atopic dermatitis (AD) was quantitatively analyzed by immunohistochemical staining with antibodies directed against protein gene product (PGP) and substance P (SP). The density of PGP-positive peripheral nerves was 2.5 × 10 ³ μm ² /Δs (Δs = 0.24 mm ² selected area) in early acute lesions, 3.8 × 10 ³ μm ² /Δs in subacute lesions, 4.9 × 10 ³ μm ² /Δs in lichenified lesions and 7.1 × 10 ³ μm ² /Δs in prurigo lesions of AD. The density of nerve fibers in subacute, lichenified and prurigo lesions was significantly higher than in uninvolved skin of AD patients (2.0 × 10 ³ μm ² /Δs). Electron microscopically, bulging of axons with many mitochondria and a loss of their surrounding sheath of Schwann cells suggests that the free nerve endings in skin lesions of AD are in an active state of excitation. Many pinocytotic vesicles in the periphery of basal keratinocytes facing nerve endings which contained many neurovesicles suggests reciprocal effects between keratinocytes and nerve endings. The number of SP-positive nerve fibers in AD lesions was far less than one-tenth of the number of PGP-positive nerve fibers. Received: 2 April 1996     

Woolly hair nevus caused by somatic mutation and Costello syndrome caused by germline mutation in HRAS: Consider parental mosaicism in prenatal counseling

Germline mutations in HRAS cause Costello syndrome (CS), while mosaic mutations in HRAS show a variability of phenotypes, ranging from mild features such as keratinocytic epidermal nevus (KEN), sebaceous nevus (SN), woolly hair nevus (WHN) with KEN, to severe manifestations of CS with cutis laxa. We report two individuals. The first was a 2-year-old boy with woolly hair nevus (WHN) without any other cutaneous involvement, in whom somatic HRAS mutation (c.34G>A; p.Gly12Ser) was identified in his affected scalp and hair follicle specimens. This is the first reported WHN type 1 (no cutaneous involvement) patient caused by somatic HRAS mutation. The other individual was a 12-year-old girl with CS caused by germline HRAS mutation (c.34G>A), that manifested with coarse face, palmoplantar keratoderma, deep palmar and plantar creases, hyperpigmented patches, asymmetry and deformity of lower limbs, atopic dermatitis, as well as mental retardation. Of note, a linear hyperpigmented plaque was observed in her father’s lumbosacral region. Although the father refused to provide semen and skin tissue for further examination, this reminds us of possible mosaicism in parents of individuals with germline de novo HRAS mutation and underlines the importance of parental evaluation for prenatal counseling.     

BRAF(V600E)基因突变与儿童先天性色素痣的增殖活性及组织病理学特征的相关性研究

目的:明确先天性色素痣(congenital melanocytic nevi, CMN)中BRAF(V600E)基因突变对其增殖活性和组织病理学的影响。方法:回顾分析2018年12月至2020年12月我院皮肤科诊治的185例CMN患儿,所有患儿均进行基因检测、病理检查和Ki67免疫组化检测。根据基因检测结果是否存在BRAFV600E突变,将入选患儿分为突变组和对照组,然后再根据性别、年龄、皮损大小和皮损部位进行配对后进一步研究。结果:突变组Ki67指数、痣细胞累及深度、痣细胞巢个数、痣细胞巢大小与对照组比较差异均有统计学意义(均P<0.05)。与BRAF V600E阴性的CMN相比,BRAF(V600E)阳性CMN通常在表真皮交界部位形成黑素细胞巢,且巢较大。痣细胞累及深度和痣细胞巢个数与Ki67指数之间成正相关(均P<0.05)。结论:BRAF(V600E)基因突变使CMN的增殖活性明显升高,并对其组织病理学有特殊的影响。     

皮肤鳞状细胞癌的细胞凋亡及某些凋亡相关基因产物的表达

目的观察皮肤鳞状细胞癌（ＳＣＣ）的细胞凋亡及ｐ５３、ｂｃｌ ２、Ｂａｘ和Ｆａｓ蛋白的表达。方法采用ＴＵＮＥＬ法和免疫组化染色。结果在２２例ＳＣＣ病变组织中,均可见到细胞凋亡,分化差、核分裂像多的ＳＣＣ中凋亡细胞较多,而分化好、核分裂像少的ＳＣＣ中则凋亡细胞少。在２７例ＳＣＣ中,１６例ｐ５３阳性表达,１４例ｂｃｌ ２阳性,１９例Ｂａｘ阳性,６例Ｆａｓ阳性。结论ＳＣＣ的发生与细胞凋亡及某些凋亡相关基因产物的异常表达有关。     

Detection of the levels of neuropeptides, ACTH and cortisol in the blood of patients with polymyositis/dermatomyositis and their significance

Recent research has shown that the neuroendocrine system can regulate the function of the immune system and that ACTH and cortisol play important roles in maintaining the immune homeostasis. Polymyositis and dermatomyositis (PM/DM) are autoimmune diseases with unclear pathogeneses closely related with immune disorders, so we detected the levels of neuropeptide Y (NPY), beta-endorphin (beta-EP), calcitonin gene-related peptide (CGRP), adrenocoricotropic hormone (ACTH), and cortisol in blood of patients with PM/DM to investigate the relationship between these indices and the pathogenesis of PM/DM. The detection of NPY, beta-EP, CGRP, and ACTH concentrations in plasma and cortisol in serum of 28 cases of PM/DM was carried out using radioimmunoassay methods, and the results were compared with those of 20 normal controls. The levels of NPY in the plasma of PM/DM was significantly higher than those of the controls, while beta-EP, CGRP and ACTH were significantly lower than those of the controls, and cortisol was not significantly different before treatment. Linear correlation analysis indicated that NPY was significantly positively correlated with CPK, and beta-EP and CGRP were significantly negatively correlated with CPK. There were no significant correlations among cortisol ACTH, and CPK and no significant correlations between NPY, beta-EP, CGRP, ACTH, cortisol and age or duration of disease before treatment. After treatment for three months, NPY, beta-EP and CGRP tended to become normal and no longer significantly different from the control values. However, ACTH fell further and was significantly lower than the level before treatment. Therefore the increase in NPY and the decreases in beta-EP, CGRP, and ACTH in the plasma of PM/DM patients may be related to the pathogenesis of PM/DM.     

Cutaneous manipulation of vascular growth factors leads to alterations in immunocytes, blood vessels and nerves: Evidence for a cutaneous neurovascular unit

Background

Skin cells produce soluble factors which influence keratinocyte proliferation, angiogenesis, nerve innervation and immunocyte response.

Objective

To test the hypothesis that epidermal-dermal interactions influence neural outgrowth, vascular survival, immunocyte recruitment and keratinocyte proliferation.

Methods

We genetically manipulated the epidermis to express excess vascular endothelial growth factor (VEGF) and/or angiopoietin-1 (Ang1) and then examined the epidermal and dermal phenotypes. We compared these findings with those occurring following overexpression of the Ang1 receptor Tie2 in endothelial cells or keratinocytes.

Results

Keratinocyte-overexpression of Ang1 resulted in increased epidermal thickness compared to control littermates. Keratinocyte-specific overexpression of Ang1 or VEGF increased dermal angiogenesis compared to control animals and combined Ang1-VEGF lead to further increases. Cutaneous leukocyte examination revealed increases in CD4⁺ T cell infiltration in mice with keratinocyte-specific overexpression of Ang1, VEGF and Ang1-VEGF combined; in contrast only keratinocyte-specific Ang1 overexpression increased cutaneous F4/80⁺ macrophage numbers. Interestingly, combined keratinocyte-derived Ang1-VEGF overexpression reduced significantly the number of F4/80⁺ and Cd11c⁺ cells compared to mice overexpressing epidermal Ang1 alone. Endothelial cell-specific Tie2 overexpression increased dermal angiogenesis but failed to influence the epidermal and immune cell phenotypes. Keratinocyte-specific Tie2 expressing mice had the highest levels of CD4⁺, CD8⁺ and CD11c⁺ cell numbers and acanthosis compared to all animals. Finally, increases in the number of cutaneous nerves were found in all transgenic mice compared to littermate controls.

Conclusion

These findings demonstrate that change to one system (vascular or epidermal) results in change to other cutaneous systems and suggest that individual molecules can exert effects on multiple systems.