Abnormal metabolism in melanocytes participates in the activation of dendritic cell in halo nevus.

A comprehensive analysis of spatial transcriptomics was carried out to better understand the progress of halo nevus. We found that halo nevus was characterized by overactive immune responses, triggered by chemokines and dendritic cells (DCs), T cells, and macrophages. Consequently, we observed abnormal cell death, such as apoptosis and disulfidptosis in halo nevus, some were closely related to immunity. Interestingly, we identified aberrant metabolites such as uridine diphosphate glucose (UDP-G) within the halo nevus. UDP-G, accompanied by the infiltration of DCs and T cells, exhibited correlations with certain forms of cell death. Subsequent experiments confirmed that UDP-G was increased in vitiligo serum and could activate DCs. We also confirmed that oxidative response is an inducer of UDP-G. In summary, the immune response in halo nevus, including DC activation, was accompanied by abnormal cell death and metabolites. Especially, melanocyte-derived UDP-G may play a crucial role in DC activation.

Analysis of granulysin expression in vitiligo and halo-nevus.

Vitiligo and halo nevus are immune-mediated skin diseases that have a similar pathogenesis and involve cellular cytotoxicity mechanisms that are not yet fully understood. In this study, we investigated the expression patterns of the cytolytic molecule granulysin (GNLY) in different cytotoxic cells in skin samples of vitiligo and halo nevus. Skin biopsies were taken from perilesional and lesional skin of ten vitiligo patients, eight patients with halo nevus and ten healthy controls. We analysed the expression of GNLY by immunohistochemistry in CD8+ and CD56+ NK cells. A significantly higher accumulation of GNLY+, CD8+ GNLY+ and fewer CD56+ GNLY+ cells was found in the lesional skin of vitiligo and halo nevus than in the healthy skin. These cells were localised in the basal epidermis and papillary dermis, suggesting that GNLY may be involved in the immune response against melanocytes. Similarly, but to a lesser extent, upregulation of GNLY+ and CD8+ GNLY+ cells was observed in the perilesional skin of vitiligo and halo nevus compared to healthy controls. In this study, we demonstrated for the first time an increased expression of CD8+ GNLY+ T lymphocytes and CD56+ GNLY+ NK cells in lesions of vitiligo and halo nevus, indicating the role of GNLY in the pathogenesis of both diseases.

Multiple Halo Nevi Induced by Intense Sun Exposure.

We present the case of a 38-year-old male who reported to our practice with multiple newly developed halos around 26 existing nevi on his trunk. The halo nevi developed after the patient, who lived in the northeast, spent 2 months on a lake in Alabama, with intense heat and sun exposure. This case is remarkable in that it points to ultraviolet exposure as one instigating factor in the development of halo nevi, the development of which is incompletely understood.  J Drugs Dermatol. 2023;22(12):e31-e32.  doi:10.36849/JDD.6792e.

Agminated Halo Nevus: A Novel Presentation.

ABSTRACT: Halo nevus is a benign type of melanocytic nevi commonly found in children and manifests as a central pigmented part surrounded by a well-defined hypopigmented area. Halo nevi are commonly located on the trunk. The central nevus may show partial or complete regression, whereas the associated halo may persist or enlarge. The term 'agminated nevus' refers to a cluster of melanocytic nevi restricted to an area of the body and commonly reported with acquired melanocytic nevi, blue nevi, and Spitz nevi. To the best of our knowledge, agminated halo nevus has not been previously described. We hereby report 2 cases with clinical and histopathologic findings consistent with the diagnosis of agminated halo nevus.

Differences in the immune microenvironment between improved and non-improved cases of vitiligo after halo nevus excision.

BACKGROUND: Halo nevus, also called Sutton's nevus, is a nevus cell nevus surrounded by vitiligo thought to be caused by a T-cell mediated immune response to the nevus antigen. The immune microenvironment is mysterious, however, as vitiligo often does not improve even when the nevus cells are removed. OBJECTIVES: To analyze the clinical course and immune microenvironment of patients with halo nevus who had undergone nevus excision. METHODS: We collected 54 halo nevus patients and performed multivariate analysis and immunohistochemical analysis, including multiplexed immune cell phenotyping and spatial single-cell analyses using the PhenoCycler® assay. RESULTS: Multivariate analysis revealed that only the presence or absence of vitiligo vulgaris at the time of consultation was associated with improvement in the surrounding vitiligo following excision. Expression of programmed death-ligand 1 in nevus cells was significantly higher in non-improved cases compared with improved cases. The PhenoCycler® assay revealed that CD107a-positive and CD21-positive cells were more prevalent in improved cases than in non-improved cases. In the improved cases, active cell-cell interactions, centered on CD21-positive cells, were observed, whereas in the non-improved cases, cell-cell interactions were sparse. Instead, a dense infiltration of CD8-positive cells and CD3 and CD4-positive cells was observed in non-improved cases. CONCLUSION: Elucidation of the immune microenvironment of halo nevus is also relevant to melanoma-associated vitiligo and will contribute to our understanding of tumor immunity.

Spontaneous Re-pigmentation of Vitiligo Following Excision of Halo Congenital Melanocytic nevi: An Interesting Case Report

Summary@#Halo nevi (HN) are benign skin lesion that represent melanocytic nevi in which an inflammatory infiltrate develops, resulting in zone of depigmentation around nevus. Although Sutton originally described the lesion in 1916 as leukoderma acquista centrifugum, the lesions were noted earlier as evidenced in the painting by Matthias Grunwald cica 1512-1516. The prevalence of HNs in the general population is 1%, and HNs usually appear in childhood or early adulthood. Up to 26% of patients with HN have vitiligo, but in very few instances is there an association of HN around congenital melanocytic nevi (CMN) and vitiligo. The exact mechanisms responsible for the development of vitiligo and HN and its resolution are unknown. One of the most accepted hypotheses considers that both phenomena are a result of a self-limited immunologic response to pigmented cells, either in the “normal” skin or within the melanocytic lesion. Hereby we present a rare case report of a girl with halo CMN and infraorbital vitiligo. The halo CMN was excised which was followed by spontaneous improvement of vitiligo.

In vivo reflectance confocal microscopy of halo nevi.

INTRODUCTION: Halo nevi named also Sutton's nevi are uncommon melanocytic lesions occurring especially among adolescents. There are two effective diagnostic methods: dermoscopy and in vivo reflectance confocal microscopy (RCM), which can help us to observe many structural elements and characteristic features of Sutton's nevi. OBJECTIVES: The aim of this study was to describe reflectance confocal microscopy features of halo nevi. METHODS: Eleven patients with fourteen halo nevi were examined by FotoFinder Medicam 800 dermoscope and reflectance confocal microscope Viva Scope 1500 between May of 2018 and September of 2019. RESULTS: Dermoscopic examination revealed 78.6% nevi with a globular pattern, while 21.4% showed a homogenous pattern. In RCM, a typical honeycombed pattern was observed in 57.1% of nevi. 42.9% of nevi showed a disarray of the epidermis and presence of dendritic cells. 35.7% of all lesions presented roundish atypical cells in the epidermis. Roundish pagetoid cells in the dermo-epidermal junction were detected in 14.2% of nevi. Non-edged papillae were observed in 50% of lesions. In each nevus, there were dilated vessels. 50% of nevi revealed dense nests in the periphery, although in case of one lesion the dishomogeneous nests were observed. CONCLUSIONS: Halo nevi are important "melanoma simulators" in confocal microscopy.

Aberrant expression of HMB45 and negative PRAME expression in halo nevi.

BACKGROUND: Traditionally, most cutaneous nevi show a gradient of HMB45 (human melanoma black 45) and negative PRAME (preferentially expressed antigen in melanoma) immunostaining, while melanomas often show irregularly positive, diffusely positive or completely negative HMB45 expression, and PRAME immunopositivity. However, we have occasionally observed benign halo nevi with loss of HMB45 gradient, raising diagnostic consideration for melanoma. The purpose of this study was to elucidate the expression pattern of HMB45 and PRAME in nevi with the halo phenomenon (NHP). METHODS: PRAME and HMB45 staining patterns in 20 cases of NHP and 16 cases of conventional nevi were evaluated using light microscopy. An HMB45 gradient was defined as immunopositivity in only superficial melanocytes. HMB45 aberrant expression consisted of superficial and deep immunopositivity. RESULTS: Aberrant HMB45 expression was observed in 10 of 20 NHP (50%). A gradient of HMB45 staining was seen in most conventional nevi, with only one showing focal weak expression in the deep dermis (6.3%). All cases of NHP and conventional nevi showed essentially negative immunostaining by PRAME. CONCLUSION: Aberrant HMB45 expression in NHP is not uncommon and may be a diagnostic pitfall. Negative PRAME immunostaining may be a reassuring finding to help differentiate halo nevus from malignant melanoma.