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.

The halo nevus is characterized by a ring of depigmentation appearing around an acquired or congenital melanocytic nevus. When observed in children, halo nevi are generally not a cause of concern. However, adult-onset halo nevi have an associated risk of primary cutaneous melanoma that corresponds to the risk of melanoma in patients with atypical nevi or a personal/familial history of melanoma. Thus, new-onset halo nevi in adults requires close follow-up and monitoring for malignancy. Herein we present a case of an adult patient who received sequential digital dermoscopy, reflectance confocal microscopy, and pigmented lesion assay gene expression profiling to monitor two halo nevi over a three-month period.

Perinevoid alopecia (PA) is a rare variant of alopecia areata (AA) associated with a central pigmented nevus. In this study, we reported two cases of PA and reviewed 14 cases from 11 studies in the literature. In one of our cases, PA was combined with a halo nevus and white terminal hairs were spared in the hair loss patch, which was rarely reported in the literature. It is implicated that antigens from melanocytes might be involved in the development of AA in PA.

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.
OBJECTIVE: 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.
CONCLUSIONS: Elucidation of the immune microenvironment of halo nevus is also relevant to melanoma-associated vitiligo and will contribute to our understanding of tumor immunity.

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Halo nevus (HN) is benign skin condition with a central melanocytic nevus, surrounded by an area or halo of depigmentation. It is the result of immunological response of the body toward the nevus, which destroys the melanocytes in surrounding skin, leading to the depigmented halo. An increased frequency of HN in patients with vitiligo is observed. It is more commonly seen in children or young adults of either sex, particularly on the trunk, less commonly on the face, neck, and limbs. We present a rare case of HN which was present on the lower eyelid associated with poliosis, diagnosed with dermatoscopy.

Immunotherapy with checkpoint inhibitors significantly improves the outcome for stage III and IV melanoma. Cutaneous adverse events during treatment are often reported. We herein aim to review the principal pigmentation changes induced by immune check-point inhibitors: the appearance of vitiligo, the Sutton phenomenon, melanosis and hair and nail toxicities.

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.
CONCLUSIONS: 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.

BACKGROUND: The extent and disease severity, duration and other associated prognostic cofactors in vitiligo in adults may vary with the age of onset (before or after 10 years of age).
OBJECTIVE: To compare extent and disease severity, duration and other cofactors in adults with early-onset and late-onset vitiligo.
METHODS: The medical records of 408 (M:F 1:1.1) adults aged 20-75 years diagnosed with vitiligo between January 2016 and December 2019 were examined retrospectively. The extent and severity of vitiligo were defined. Characteristics of vitiligo with early onset and late onset were compared statistically and odds ratios calculated for risk assessment.
RESULTS: 31 (7.6%, M:F 1:2.4) patients had early-onset vitiligo, and 377 (92.4%, M:F 0.8:1) patients had later-onset vitiligo. Compared to late onset, patients with early-onset vitiligo had a significant number of males (71% vs 45.9%), higher percentages of body surface area involvement and moderate to extremely severe disease (29% vs 10.6%), longer duration of disease (41.9% vs 9%), Koebner\'s phenomenon (48.4% vs 15.6%) and halo nevus (9.7% vs 1.9%). Differences between the two groups were not significant for types of vitiligo, family history of vitiligo and presence of cutaneous and systemic/autoimmune diseases.
CONCLUSIONS: The adults, males in particular, with generalised vitiligo (>10% BSA involvement) appear to have an early onset and a prolonged clinical course. The presence of Koebner\'s phenomenon and halo nevus in patients with early-onset vitiligo was other poor prognostic factors compared to patients with late-onset vitiligo. The retrospective, hospital-based cross-sectional design and small sample size for stratification remain major limitations.

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