几种色素减退性皮肤病的共聚焦激光扫描显微镜图像特点

目的 观察白癜风、无色素痣、进行性斑状色素减少症、贫血痣的活体共聚焦激光扫描显微镜（CLSM）特征。方法 用CLSM观察同一层面（基底层真表皮交界处）皮损处、交界处及白斑周边正常皮肤的镜下特征。结果 进展期白癜风白斑区部分区域色素完全缺失,部分区域可见残存色素环,残存之色素环结构欠完整且色素含量降低;交界处界限模糊;白斑周边正常皮肤可见部分色素环失去完整性。稳定期白癜风白斑处色素完全消失;交界处界限清晰;白斑周边正常皮肤色素环完整,折光明亮;恢复期可见到树突状、折光明亮的黑素细胞。无色素痣和进行性斑状色素减少症的CLSM表现相似：白斑处色素环结构完整,色素含量降低,折光减弱。贫血痣白斑处色素环结构和色素含量与周边正常皮肤无明显差异。结论 结合临床表现,CLSM可以作为鉴别诊断白癜风、无色素痣、进行性斑状色素减少症、贫血痣的一种辅助方法。     

Histopathologic features in vitiligo

Nevus depigmentosus is a congenital disorder characterized by a nonprogressive hypopigmented lesion, which may not be apparent at birth. Thus, it is sometimes difficult to differentiate vitiligo from nevus depigmentosus only by clinical features. We postulated that the histologic changes in lesional and perilesional skin might be different in the 2 conditions. We took biopsies from both lesional and perilesional skin of 100 cases of vitiligo to assess the number of melanocytes, the amount of melanin, dermal inflammatory infiltrate, and other changes. We compared them with 30 cases of nevus depigmentosus. Histologically, lesions of vitiligo showed more basal hypopigmentation and dermal inflammation than perilesional normal skin. With Fontana-Masson staining, 16% of cases of vitiligo showed the presence of melanin. The ratio of pigmented area to epidermal area was 0.06% in vitiligo, whereas 17% in perilesional normal skin and 8.9% in nevus depigmentosus. In NKI/beteb staining, 12% of vitiligo showed the presence of melanocytes, and their average number was 7.68 per square millimeter. The number of melanocytes was also decreased in nevus depigmentosus but not as much as in vitiligo. We also confirmed the presence of melanocytes in 1 of 3 cases of vitiligo by electron microscopy. In conclusion, there are a few melanocytes and melanin in some cases of vitiligo. Therefore, the diagnosis of vitiligo should be made considering these points.     

体外培养节段型白癜风样无色素痣皮损黑素细胞及其临床意义

【摘要】 目的 评价负压吸疱表皮黑素细胞培养对节段型白癜风样无色素痣的辅助诊断价值。方法 收集2019年6月至2020年3月于杭州市第三人民医院皮肤科依据Coupe标准临床诊断的8例节段型白癜风样无色素痣患者,进行伍德灯、反射式共聚焦显微镜（RCM）检查,308 nm准分子激光试验,负压吸疱获取表皮黑素细胞并培养,记录结果。结果 8例患者中,6例皮损伍德灯下可见荧光,4例RCM下可见色素环完整性缺失,5例经308 nm准分子激光照射试验后未见复色反应。8例患者体外培养的皮损黑素细胞硫酸亚铁染色均阳性,经消化离心后沉淀呈黄白色,电镜下黑素细胞胞质内可见Ⅰ~ Ⅲ期黑素小体;皮损对侧同一解剖部位正常皮肤黑素细胞沉淀则呈黑色,电镜下黑素细胞胞质内可见Ⅰ~ Ⅳ期黑素小体。结论 负压吸疱表皮黑素细胞培养有助于诊断节段型白癜风样无色素痣。     

Role of In Vivo Reflectance Confocal Microscopy in Determining Stability in Vitiligo: A Preliminary Study

Background:

Vitiligo is an acquired pigmentary disorder. In vivo reflectance confocal microscopy (RCM) reproducible imaging technique has already been reported to be useful in the diagnosis of other skin diseases.

Objective:

To define RCM features of vitiligo on different clinical stages.

Materials and Methods:

A total of 125 patients with a clinical diagnosis of vitiligo were included in this study. After informed consent, lesional skins of those vitiligo patients were characterized by using RCM. Five patients with inflammatory cell infiltration observed at the edge of skin lesions and another 5 patients without inflammatory cell infiltration were selected. Biopsies were performed at same sites of the RCM examination areas for histological and immune-histological analysis.

Results:

In the active stage of vitiligo, the RCM examination revealed that the bright dermal papillary rings presented at the dermoepidermal junction level in normal skin lost their integrity or totally disappeared, border between vitiligo lesion and normal skin became unclear, and highly refractile cells that referred to infiltrated inflammatory cells could be seen within the papillary dermis at the edge of the lesions. In the stable stage of vitiligo, the RCM showed a complete loss of melanin in lesional skin and a clear border between lesional and normal skin.

Conclusion:

A simple clinical examination with RCM may reliably and efficiently allow evaluation of the stability status of vitiligo lesions.     

In vivo reflectance confocal microscopy for the differential diagnosis between vitiligo and nevus depigmentosus

Background Nevus depigmentosus (ND) is frequently confused with vitiligo. Differential diagnosis can be difficult. In vivo reflectance confocal microscopy (RCM) is a noninvasive technique for real‐time en face imaging of the superficial layers of the skin down to the superficial dermis with cellular level resolution close to conventional histopathology. In this study, we tried to use this new technology to study the features of the distribution of pigment cells of these two hypopigmentation disorders and then concluded the differential features. Methods Sixty vitiligo patients and 62 ND patients were enrolled in the study. Three points in each patient (lesional, margin of the lesions and adjacent non‐ lesional points) were examined with RCM. The gray value of image was quantified using software, and we calculated the relative gray value. Results The RCM image feature was different between vitiligo and ND patients. The differential diagnosis was made based on the following four RCM features: complete absence of pigment cells; the distribution of pigment cells; the margins; and the relative gray value. Conclusion RCM can be used as an auxiliary diagnostic tool for the differential diagnosis between vitiligo and ND.     

Application of a pigment measuring device – Mexameter®– for the differential diagnosis of vitiligo and nevus depigmentosus

Background/purpose: Vitiligo and nevus depigmentosus (ND) present similar hypopigmented macules with significantly different prognoses. Although the distinction between the two diseases is important, differential diagnosis relies on medical history and physical examination, which is far from decisive in some cases. The Mexameter^® is an objective skin color-measuring device, and has been reported to provide a reproducible and sensitive means of quantifying small skin color differences. In this study, we investigated the usefulness of a Mexameter^® for discriminating these diseases.
Methods: A selection of 202 hypopigmented skin lesions (182 from vitiligo and 20 from ND) were the objects of this study. Using a Mexameter, MIs were obtained from lesions and symmetrically located control skin. RMIs, ratios of the MIs of lesional skins to control skins, were calculated.
Results: The mean MIs and RMIs were significantly different for vitiligo and ND. The mean RMI of ND lesions was 74±13, which was significantly higher than that of vitiligo lesions (50±24). No ND lesion had an RMI of <50%.
Conclusion: This study shows that the Mexameter^®, an objective pigment-measuring device, can be used to achieve a more accurate diagnosis of hypopigmentary disorders, and that the relative melanin index (RMI), which represents the relative pigment levels, might be a more effective parameter than the melanin index (MI) itself for comparing pigmentation differences.     

Clinical differences between segmental nevus depigmentosus and segmental vitiligo

Segmental nevus depigmentosus and segmental vitiligo can be difficult to differentiate from each other. Differential diagnosis of these two diseases is important because they have significantly different prognoses and psychological effects. The purpose of this study is to identify clinical clues that may be helpful in differentiating these two diseases. We enrolled 63 patients with segmental nevus depigmentosus and 149 patients with segmental vitiligo. Sex, age of onset, sites involved, dermatomal distribution, margin of lesion and presence of poliosis were evaluated in both groups. The age of onset was less than 10 years in 96.8% of segmental nevus depigmentosus and 28.9% of segmental vitiligo cases. Trunk (36.5%) and cervical (38.1%) dermatomes were the most commonly involved in segmental nevus depigmentosus and face (67.1%) and trigeminal (64.4%) dermatomes in segmental vitiligo. The average number of dermatomes involved in truncal lesions was different in segmental nevus depigmentosus and segmental vitiligo (2.71 vs 1.62, P = 0.001). Segmental vitiligo on the face, neck and trunk appeared closer to the axis than segmental nevus depigmentosus (P < 0.001). Segmental nevus depigmentosus and segmental vitiligo showed significantly different margins (90.5% and 41.6% serrated, respectively; P < 0.001). We observed clinical differences between patients with segmental nevus depigmentosus and those with segmental vitiligo. Distribution (site, distance to axis, dermatome), vertical width, margin of lesion and presence of poliosis can be helpful in differentiating segmental nevus depigmentosus and segmental vitiligo.     

儿童无色素性痣106例临床分析

为了解无色素性痣的临床特征，分析总结了106例儿童无色素性痣的临床特点，对其中10例做了组织学检查。结果显示本病发病年龄早，79.2%白斑于1岁内发现：躯干部最常见，占43.4%；局限型占60.4%，节段型占39.6%；66.0%白斑边缘很不规则，部分呈锯齿状或泼溅状。组织病理学显示基底层黑素细胞数目无明显减少。其临床特征及组织学改变与其它局限性白斑不同。     

双侧太田痣合并贫血痣一例

患儿，女，9岁。面部色斑9年。皮肤科查体符合太田痣和贫血痣表现。太田痣采用调Q激光处理，治疗后2年复诊，面部褐青色斑片消失。贫血痣未处理。     

Pigmentary disorders in oriental skin

Brown hyperpigmented disorders may be melanotic in which there is a normal number of epidermal melanocytes but melanin pigment is increased in the epidermis (eg, melasma), melanocytotic, in which melanocytes are increased (eg, café-au-lait macules), and nonmelanotic hyperpigmentation (eg, minocycline pigmentation). Blue hyperpigmented disorders may also be melanotic in which there is a normal number of epidermal melanocytes, but melanin pigment is present in the upper dermis (eg, gray/slate pigmentation in Riehl's melanosis), melanocytotic in which melanocytes are present in both the epidermis and dermis (eg, blue pigmentation in Nevus Ota and Mongolian spot), and nonmelanotic hyperpigmentation in which pigment is present in the deep dermis (eg, blue pigmentation in tattoos). Hypomelanosis (leukoderma) may be divided histopathologically into melanocytopenic disorders on which melanocytes are absent (eg, Vogt-Koyanagi-Harada syndrome and vitiligo), melanopenic disorders in which melanocytes are present but melanin is reduced (eg, nevus depigmentosus and incontinentia pigmenti achromians), and nonmelanotic disorders in which melanin pigmentation is unaffected (nevus anemicus) and the pigmentary abnormality is caused by something other than melanin. There are numerous pigmentary disorders in the oriental skin, and some of them are either characteristic to or established in the orientals. Importantly, a number of congenital hypermelanotic and hypomelanotic diseases (eg, nevus depigmentosus, incontinentia pigmenti, and incontinentia pigmenti achromians, take a distribution following to the Blaschko's line.     

Pityriasis alba revisited: perspectives on an enigmatic disorder of childhood

Pityriasis alba (PA) is a localized hypopigmented disorder of childhood with many existing clinical variants. It is more often detected in individuals with a darker complexion but may occur in individuals of all skin types. Atopy, xerosis, and mineral deficiencies are potential risk factors. Sun exposure exacerbates the contrast between normal and lesional skin, making lesions more visible and patients more likely to seek medical attention. Poor cutaneous hydration appears to be a common theme for most risk factors and may help elucidate the pathogenesis of this disorder. The end result of this mechanism is inappropriate melanosis manifesting as hypopigmentation. It must be differentiated from other disorders of hypopigmentation, such as pityriasis versicolor alba, vitiligo, nevus depigmentosus, and nevus anemicus. Alleviation of the various risk factors via patient education on proper skin care and hygiene, use of lubricants and emollients, topical corticosteroid therapy in the presence of inflammation, and the novel administration of topical anti-inflammatory drugs such as calcineurin inhibitors can play a crucial role in promoting remission or resolution.     

Nevus depigmentosus: review of a mark of distinction

Nevus depigmentosus (ND), also known as nevus achromicus or achromic nevus, is an uncommon congenital hypomelanosis of the skin that is often characterized as being nonprogressive and having serrated borders. It needs to be distinguished from other hypopigmented skin conditions such as nevus anemicus, hypomelanosis of Ito, Fitzpatrick patches (ash leaf spots) of tuberous sclerosis, vitiligo, indeterminate leprosy, and pigment demarcation lines. Treatment may be desired for aesthetic and possible psychosocial considerations. We review and update knowledge about ND and its simulants.     

The role of reflectance confocal microscopy in the diagnosis and management of pigmentary disorders: A review

Background

Reflectance confocal microscopy (RCM) has quickly transitioned from a research tool to an adjunct diagnostic bedside tool, providing the opportunity for noninvasive evaluation of skin lesions with histologic resolution. RCM is an optical imaging technique that uses near-infrared excitation wavelengths and safe low-power lasers. En-face images of different skin layers (up to the superficial dermis) are acquired in grayscale based on the reflective indices of tissue components. Melanin has the highest reflective index (contrast) and appears bright on RCM.

Aims

We present a review of the current literature on the use of RCM in the diagnosis and management of pigmentary disorders.

Methods

We reviewed PubMed and Ovid Medline databases from January 2000 to June 2021, using MeSH key terms: “reflectance confocal microscopy, confocal laser scanning microscopy, pigmentary disorders, treatment, melasma, vitiligo, freckles, solar lentigo, lentigo, tattoo, complications, melanoma, skin cancers, pigmented lesions, post inflammatory, melanin, photoaging” to identify studies and review articles discussing the use of RCM in the diagnosis and management of pigmentary disorders.

Results

RCM findings of pigmentary disorders were divided into the following categories: (1) disorders of increased pigmentation (post-inflammatory hyperpigmentation, melasma, Riehl's melanosis, solar lentigines, ephelides, hori nevus, naevus of Ota, café-au-lait macules, melanocytic nevus, melanoma, nevus spilus, labial mucosal melanosis, and mucosal melanoma), (2) disorders of decreased pigmentation or depigmentation (post-inflammatory hypopigmentation, vitiligo, nevus depigmentosus, halo nevus), and (3) exogenous pigmentation (tattoo, ochronosis).

Conclusion

RCM has been explored and proven valuable for the evaluation and management of pigmentary disorders including melasma, vitiligo, solar lentigines, tattoo, and tattoo-related complications.     

Preliminary evaluation of vitiligo using in vivo reflectance confocal microscopy

BACKGROUND: Vitiligo is the most common pigmentary disorder with a global incidence from 0.1% to 2% in different geographical areas. Histopathology and histochemistry have shown the reduction of melanocytes in achromic patches, but microscopic changes of lesional and non-lesional skin are still not completely understood. Reflectance confocal microscopy (RCM), based on the different light reflectance index of cutaneous structures, allowed in vivo, en face microscopic evaluation of superficial skin layers with a resolution similar to skin histology. AIM: The purpose of this study was to evaluate RCM features of lesional and non-lesional skin of vitiligo patients. Moreover, re-pigmented areas were taken into consideration in order to evaluate melanocyte response to ultraviolet B (UVB) radiation. SUBJECTS AND METHODS: Sixteen patients of different phototypes affected by active non-segmental vitiligo and 10 controls were enrolled in the study. In vivo skin imaging was done using a commercially available RCM (Lucid, Vivascope 1500. Re-pigmented areas from 6 to 16 patients (after UVB narrow-band therapy) were also examined. RESULTS: Vitiligo lesions showed the disappearance of the bright rings normally seen at the dermo-epidermal junction. Moreover, non-lesional skin of vitiligo patients showed unexpected changes as the presence of half-rings or scalloped border-like features of the bright papillary rings. In re-pigmented areas after UVB narrow band therapy, the presence of activated, dendritic melanocytes was seen. CONCLUSIONS: Considering our results, and following further studies, RCM clinical applications could be used in the therapeutic monitoring and evaluation of the evolution of vitiligo.     

Epidermal changes in active vitiligo.

Light and electron-microscopic studies were performed on the vitiligo and adjacent, normal appearing skin from 97 patients with actively spreading vitiligo and 19 patients with stable vitiligo. The vitiliginous skin revealed complete loss of pigment and melanocytes. In addition to degenerative changes in melanocytes, vacuolar changes of basal cells, epidermal infiltration of lymphocytes, dermal infiltration of lymphocytes, and melanophages in the upper dermis were also seen in the normal appearing skin adjacent to vitiliginous skin. These epidermal and dermal changes are more prominent in the skin of actively spreading vitiligo than in stable vitiligo. These findings suggest that the adjacent, normal appearing skin of actively spreading vitiligo shows some characteristic histopathologic findings, especially in the epidermis, indicating that cellular immunity could be involved in the pathogenesis of vitiligo.     

临床特征和皮肤CT特征判定白癜风分期

目的 采用临床特征和皮肤CT特征来判定白癜风分期。 方法 200例白癜风患者按照临床特征问卷和皮肤CT特征进行分期： ＞ 2分为快速进展期,1 ~ 2分为缓慢进展期, < 1分为稳定期。选择进展期和稳定期白癜风患者各5例,在皮肤CT检测的区域进行HE染色分析。 结果 用临床特征和皮肤CT特征判定200例白癜风患者的分期,差异无统计学意义。临床特征：进展期为白斑边缘隆起或与周围正常皮肤边界不清,三色白癜风,皮损颜色呈灰白色或浅白色;稳定期为白斑区与正常皮肤边界清晰,皮损颜色呈乳白色或瓷白色,可见色素岛。皮肤CT：进展期为表真皮交界处色素环失去完整性,与周边正常皮肤边界不清,在表真皮交界、边缘处可以看到高折光性细胞。稳定期为表真皮交界处色素环完全缺失,与周边正常皮肤边界清,有树突状高折射光的黑素细胞存在。HE染色结果显示,进展期在真皮乳头层内的病灶的边缘可见大量的CD8T淋巴细胞。稳定期在真皮乳头层内的病灶边缘未见CD8T淋巴细胞。 结论 临床特征和皮肤CT特征可以用来判定白癜风的分期,结果与进展期组织病理学基本一致。     

Regulatory T‐cell cytokines in patients with nonsegmental vitiligo

In the etiopathogenesis of vitiligo, the role of suppressor cytokines, such as transforming growth factor‐β (TGF‐β) and interleukin‐10 (IL‐10), associated with regulatory T‐cells (Treg) is not completely known. In this study, the role of Treg‐cell functions in the skin of patients with nonsegmental vitiligo was investigated. Lesional and nonlesional skin samples from 30 adult volunteers ranging in age from 18 to 36 years with nonsegmental vitiligo were compared with normal skin area excision specimens of 30 benign melanocytic nevus cases as controls. All samples were evaluated staining for forkhead box P3 (Foxp3), TGF‐β, and IL‐10 using the standardized streptavidin–biotin immunoperoxidase immunohistochemistry method. Foxp3 expression was lower in lesional vitiligo skin specimens compared to controls; it was also lower in lesional vitiligo specimens than nonlesional vitiligo specimens. IL‐10 levels were lower in lesional vitiligo specimens compared to the controls, whereas IL‐10 expression was significantly lower in lesional specimens compared with nonlesional specimens. TGF‐β expression was higher in both lesional and nonlesional skin specimens of patients with vitiligo compared to controls. TGF‐β expression was lower in lesional skin specimens than nonlesional skin specimens. In addition, there was no significant correlation between Foxp3 expression with TGF‐β and IL‐10 expressions in lesional skin specimens in the vitiligo group. In this study, results supporting the contribution of Treg cells and IL‐10 deficiency to the autoimmune process were obtained. Therefore, future studies are necessary to demonstrate the definitive role of Treg‐cell functions in the etiopathogenesis of vitiligo.     

反射式共聚焦显微镜联合皮肤镜对黑素细胞痣的诊断价值评估

目的 评估皮肤镜与反射式共聚焦显微镜(RCM)单独或联合对黑素细胞痣的诊断价值.方法 收集临床拟诊黑素细胞痣的患者37例,对皮损先进行皮肤镜、RCM检查,再经组织病理学检查确诊.总结黑素细胞痣的影像学特征,计算不同检查诊断黑素细胞痣的敏感度、特异度、阳性预测值、阴性预测值、正确率,分析皮肤影像技术与组织病理学诊断的一致性.结果 皮肤镜和RCM检查结果示真皮内痣细胞的形态结构可分为两种:(a)真皮乳头层不融合、高折光、圆形的痣细胞,皮肤镜下表现为褐色或浅褐色均质模式,见于5处皮损;(b)真皮乳头内不规则、高折光的痣细胞团块,皮肤镜表现为鹅卵石模式或球状模式,见于31处皮损.在诊断黑素细胞痣方面,RCM结合皮肤镜的敏感度、特异度、正确率、阳性预测值、阴性预测值分别为91.7％、87.5％ 、90.9％ 、97.1％ 、70％,RCM为86.1％ 、75％ 、84％ 、93.9％ 、54.5％,皮肤镜为77.8％ 、87.5％ 、75％ 、96.3％ 、41.2％.除特异度与皮肤镜相同外,RCM结合皮肤镜的其他指标均高于二者单独应用;RCM敏感度、正确率、阴性预测值高于皮肤镜,特异度、阳性预测值低于皮肤镜.RCM结合皮肤镜或单用RCM与组织病理诊断结果之间差异无统计学意义(x2值分别为0.25、0.57,P值分别为0.63、0.45),Kappa值分别为0.72、0.53;皮肤镜与病理诊断结果之间差异有统计学意义(x2=5.81,P=0.012).结论 RCM联合皮肤镜较二者单独使用能更准确地诊断黑素细胞痣.     

Acquired patch-type blue nevus with overlying vitiligo: a case report

Background Blue nevi are a group of congenital and acquired dermal melanocytoses characterized by a blue‐gray appearance on the skin. The common blue nevus and cellular blue nevus are the most common subtypes. Patch‐type blue nevus is rather rare. Observations We describe a 77‐year‐old Chinese male with a 6 × 8‐cm non‐palpable blue patch overlaid by a depigmented patch on the back of the left scalp. Histological examination of the blue‐gray patch showed numerous spindled and elongated bipolar dendritic melanocytes in the upper reticular dermis and an absence of epidermal melanocytes. Immunohistochemically, these dendritic melanocytes were positive for S‐100 and HMB‐45. A diagnosis of a patch‐type blue nevus with overlying vitiligo was made after the biopsy. Conclusions The patient presents an unusual manifestation of patch‐type blue nevi with overlying vitiligo. To the best of our knowledge, these features have not been previously described.     

先天性色素痣合并白癜风2例

报告2例白癜风合并先天性色素痣。例1的初发白斑在左上肢先天性毛痣周围,表现为晕痣,1个月后身体其他部位出现多发白斑;例2为节段型白癜风患者,除了在身体其他部位出现白斑外,在右足背先天性色素痣周围出现白斑,表现为痣周围白癜风。白癜风合并先天性色素痣这一现象值得进一步研究。