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Introduction: Idiopathic guttate hypomelanosis (IGH) is a common leukodermic dermatosis that primarily affects middle-aged and elderly adults. This study evaluates the dermoscopic features of IGH and their correlation with histopathological findings., Methods: In the present study, 100 patients with IGH were evaluated. Each patient underwent a comprehensive clinical history assessment along with a dermatological and physical examination. Dermoscopic examination was performed, followed by a histopathological examination to confirm the diagnosis., Results: The mean age of the participants was 64.67 ± 9.59 years, with 53% being male. The most prevalent dermoscopic pattern observed was nebuloid (33.3%), followed by petaloid (26.7%), and both amoeboid and feathery patterns were seen in equal proportions (20% each). The abdomen (33%) and legs (27%) were the most common sites for IGH lesions. Histopathological examination revealed features such as basket weave hyperkeratosis, atrophic epidermis in some lesions, reduced melanin globules or melanocytes, skip lesions, and flattening of rete ridges across all dermoscopic patterns., Conclusion: IGH is characterized by distinct dermoscopic patterns, including amoeboid, feathery, nebuloid, and petaloid types. When these patterns are interpreted within the clinical context and corroborated with histopathological findings, they aid in the accurate diagnosis of IGH and its differentiation from other hypopigmented and depigmented dermatoses. Dermoscopy can be considered an adjunctive tool to confirm the diagnosis of IGH.

Background: Diagnosis of cutaneous hypopigmentation can sometimes be challenging. Dermoscopy may play a role in identifying hypo or-depigmented dermatoses. The aim was to investigate which dermoscopic criteria represent potent indicators for the diagnosis of vitiligo, nevus depigmentosus, pityriasis alba, hypopigmented pityriasis versicolor, idiopathic guttate hypomelanosis, hypopigmented mycosis fungoides (MF), lichen sclerosus et atrophicus and ash leaf hypopigmented macules of tuberous sclerosis, and evaluate their diagnostic accuracy. 168 individuals diagnosed with one of these hypopigmented disorders were evaluated for the presence or absence of predetermined dermoscopic criteria. Evaluation of dermatoscopic characteristics in each condition and analysis for sensitivity and specificity of dermatoscopic diagnosis in these hypopigmented lesions was performed. The starburst pattern, micro-koebnerization, and trichrome pattern were unique to vitiligo diagnosis. Vitiligo had higher comet-tail appearance, perifollicular pigmentation, and perilesional hyperpigmentation than other hypopigmented illnesses. Other hypopigmented lesions had greater incidence of amoeboid pattern, faint or diminished pigment network, islands of pigmentation, ill-defined boundaries, pseudopods, and widespread scaling than vitiligo. Finally, perifollicular scaling, comedo-like openings, blue-gray specks, and fibrotic regions excluded vitiligo. Dermoscopy can help identify common hypopigmented skin lesions and reduce the need for skin biopsy. Nevus depigmentosus, pityriasis alba and idiopathic guttate hypomelanosis were the top three hypopigmented dermatoses that could be diagnosed by dermoscopy with 100% sensitivity. Vitiligo was in the second rank (94.7%), followed by lichen sclerosis et atrophicus (93.3%) then hypopigmented MF at 81.2% sensitivity. Dermoscopy sensitivity was lowest in pityriasis versicolor and ash leaf macules of tuberous sclerosis (52.6% and 46.7%, respectively)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Dermoscopy has seen increased use in the diagnosis of hypopigmentary disorders. As a quick and effective adjunct to the clinician's toolbox, dermoscopy offers the opportunity to differentiate between hypopigmentary lesions that ostensibly present with clinically similar morphology on the macroscopic scale. The focus of this article is to review the various dermoscopic signs and patterns that have been elucidated for these disorders., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objectives : Amelanotic/hypomelanotic melanomas (AHMs) account for 2-8% of all cutaneous melanomas. Due to their clinical appearance and the lack of specific dermoscopic indicators, AHMs are challenging to diagnose, particularly in thinner cutaneous lesions. The aim of our study was to evaluate the clinicopathological and dermoscopic features of thin AHMs. Identifying the baseline clinical-pathological features and dermoscopic aspects of thin AHMs is crucial to better understand this entity. Materials and Methods : We divided the AHM cohort into two groups based on Breslow thickness: thin (≤1.00 mm) and thick (>1.00 mm). This stratification helped identify any significant clinicopathological differences between the groups. For dermoscopic analysis, we employed the "pattern analysis" approach, which involves a simultaneous and subjective assessment of different criteria. Results : Out of the 2.800 melanomas analyzed for Breslow thickness, 153 were identified as AHMs. Among these, 65 patients presented with thin AHMs and 88 with thick AHMs. Red hair color and phototype II were more prevalent in patients with thin AHMs. The trunk was the most common anatomic site for thin AHMs. Patients with thin AHMs showed a higher number of multiple melanomas. Dermoscopic analysis revealed no significant difference between thin AHMs and thick AHMs, except for a more frequent occurrence of residual reticulum in thin AHMs. Conclusions : Thin AHMs typically affect individuals with lower phototypes and red hair color. These aspects can be related to the higher presence of pheomelanin, which provides limited protection against sun damage. This also correlates with the fact that the trunk, a site commonly exposed to intermittent sun exposure, is the primary anatomical location for thin AHMs. Multiple primary melanomas are more common in patients with thin AHMs, likely due to an intrinsic predisposition as well as greater periodic dermatologic follow-ups in this class of patients. Apart from the presence of residual reticulum, no other significant dermoscopic differences were observed, complicating the differential diagnosis between thin and thick AHMs based on dermoscopy alone.

Epidermal melanin unit integrity is crucial for skin homeostasis and pigmentation. Epidermal growth factor (EGF) receptor (EGFR) is a pivotal player in cell growth, wound healing, and maintaining skin homeostasis. However, its influence on skin pigmentation is relatively unexplored. This study investigates the impact and underlying mechanisms of EGFR inhibitors on skin pigmentation. We evaluated EGF and EGFR expression in various skin cells using quantitative real-time PCR, Western blot, and immunofluorescence. EGF and EGFR were predominantly expressed in epidermal keratinocytes, and treatment with the EGFR tyrosine kinase inhibitors (EGFR-TKIs) gefitinib and PD153035 significantly increased stem cell factor (SCF) and endothelin-1 (ET-1) expression in cultured keratinocytes. Enhanced melanocyte migration and proliferation were observed in co-culture, as evidenced by time-lapse live imaging and single-cell tracking assays. Furthermore, topical application of gefitinib to guinea pig dorsal skin induced increased pigmentation and demonstrated efficacy in mitigating rhododendrol-induced leukoderma. Suppression of EGF signaling indirectly enhanced skin pigmentation by upregulating SCF and ET-1 in epidermal keratinocytes. This novel mechanism highlights the pivotal role of EGF signaling in regulating skin pigmentation, and topical EGFR-TKI therapy at an appropriate dose may be a promising approach for depigmentation disorder management., (© 2024 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)

Neuromelanin hypopigmentation within substantia nigra pars compacta (SNc) reflects the loss of pigmented neurons, which in turn contributes to the dysfunction of the nigrostriatal and striato-cortical pathways in Parkinson's disease (PD). Our study aims to investigate the relationships between SN degeneration manifested by neuromelanin reduction, functional connectivity (FC) among large-scale brain networks, and motor impairment in PD. This study included 68 idiopathic PD patients and 32 age-, sex- and education level-matched healthy controls who underwent neuromelanin-sensitive magnetic resonance imaging (MRI), functional MRI, and motor assessments. SN integrity was measured using the subregional contrast-to-noise ratio calculated from neuromelanin-sensitive MRI. Resting-state FC maps were obtained based on the independent component analysis. Subsequently, we performed partial correlation and mediation analyses in SN degeneration, network disruption, and motor impairment for PD patients. We found significantly decreased neuromelanin within SN and widely altered inter-network FCs, mainly involved in the basal ganglia (BG), sensorimotor and frontoparietal networks in PD. In addition, decreased neuromelanin content was negatively correlated with the dorsal sensorimotor network (dSMN)-medial visual network connection (P = 0.012) and dSMN-BG connection (P = 0.004). Importantly, the effect of SN neuromelanin hypopigmentation on motor symptom severity in PD is partially mediated by the increased connectivity strength between BG and dSMN (indirect effect =  - 1.358, 95% CI: - 2.997, - 0.147). Our results advanced our understanding of the interactions between neuromelanin hypopigmentation in SN and altered FCs of functional networks in PD and suggested the potential of multimodal metrics for early diagnosis and monitoring the response to therapies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Vitiligo is an autoimmune skin disease of multiple etiology, for which there is no complete cure. This chronic depigmentation is characterized by epidermal melanocyte loss, and causes disfigurement and significant psychosocial distress. Mouse models have been extensively employed to further our understanding of complex disease mechanisms in vitiligo, as well as to provide a preclinical platform for clinical interventional research on potential treatment strategies in humans. The current mouse models can be categorized into three groups: spontaneous mouse models, induced mouse models, and transgenic mice. Despite their limitations, these models allow us to understand the pathology processes of vitiligo at molecule, cell, tissue, organ, and system levels, and have been used to test prospective drugs. In this review, we comprehensively evaluate existing murine systems of vitiligo and elucidate their respective characteristics, aiming to offer a panorama for researchers to select the appropriate mouse models for their study., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest The authors declare no conflicts of interest.

Diffuse hyperpigmentation with guttate hypopigmentation (DHGH) is a new acquired pigmentary disorder. Only a few cases have previously been reported in the Chinese population, in Chinese. To summarise the clinical, dermoscopic, and histopathological findings of DHGH in the English literature, to improve the recognition and management of this condition. This was a retrospective study to summarise the clinical, dermoscopic, and pathological findings of nine cases of DHGH. All nine patients with DHGH were female. The age at onset varied from 6 to 24 years (median 17 years). Patients were generally in good health without systemic disease. The lesions were often generalised to the trunk and extremities without any discomfort. Typical lesions were characterised by multiple uniform hypopigmented spots, 2-5 mm in diameter, irregularly distributed over diffuse hyperpigmentation. Dermoscopy revealed multiple blurred patchy areas of brownish pigmentation, sparse linear and dotted vessels, and perifollicular pigmentation on a white to bright white background, surrounded by brown hyperpigmentation. Histopathological findings included mild abnormal pigment of the epidermis, focal vacuolar degeneration of the basal cells, mild pigment incontinence and perivascular lymphocytic infiltration in the dermis. DHGH is a new entity with distinctive clinical manifestations that differ from those of other known pigmentary disorders. So far, DHGH has only been reported in the Chinese population. It may not be uncommon and has not received much attention due to the few reports. The aetiology and pathogenesis of DHGH are still unknown and require further investigation.

Objective: While studies suggested that locus coeruleus (LC) neurodegeneration contributes to sleep-wake dysregulation in Alzheimer's disease (AD), the association between LC integrity and circadian rest-activity patterns remains unknown. Here, we investigated the relationships between 24-hour rest-activity rhythms, cognitive trajectories, and autopsy-derived LC integrity in older adults with and without cortical AD neuropathology., Methods: This retrospective study leveraged multi-modal data from participants of the longitudinal clinical-pathological Rush Memory and Aging Project. Indices of 24-hour rest-activity rhythm fragmentation (intradaily variability) and stability (interdaily stability) were extracted from annual actigraphic recordings, and cognitive trajectories were computed from annual cognitive evaluations. At autopsy, LC neurodegeneration was determined by the presence of hypopigmentation, and cortical AD neuropathology was assessed. Contributions of comorbid pathologies (Lewy bodies, cerebrovascular pathology) were evaluated., Results: Among the 388 cases included in the study sample (age at death = 92.1 ± 5.9 years; 273 women), 98 (25.3%) displayed LC hypopigmentation, and 251 (64.7%) exhibited cortical AD neuropathology. Logistic regression models showed that higher rest-activity rhythm fragmentation, measured up to ~7.1 years before death, was associated with increased risk to display LC neurodegeneration at autopsy (odds ratio [OR] = 1.46, 95% confidence interval [CI 95% ]: 1.16-1.84, p BONF  = 0.004), particularly in individuals with cortical AD neuropathology (OR = 1.56, CI 95% : 1.15-2.15, p BONF  = 0.03) and independently of comorbid pathologies. In addition, longitudinal increases in rest-activity rhythm fragmentation partially mediated the association between LC neurodegeneration and cognitive decline (estimate = -0.011, CI 95% : -0.023--0.002, p BONF  = 0.03)., Interpretation: These findings highlight the LC as a neurobiological correlate of sleep-wake dysregulation in AD, and further underscore the clinical relevance of monitoring rest-activity patterns for improved detection of at-risk individuals. ANN NEUROL 2024;95:653-664., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Excessive oxidative stress is thought to play pathologic roles in cellular senescence and autoimmune disorders by inducing inflammation and breaking down immune tolerance. In this study, we sought to identify the factors linking oxidative stress to autoimmunity and cellular senescence in vitiligo, where elevated oxidative stress plays an important role. RNA sequencing analysis of hydrogen peroxide-treated melanocytes revealed upregulation of ISG15. The upregulation of ISG15 was observed in vitiligo skin tissues as well as in the blood of patients with vitiligo, whereas USP18 downregulation was observed in vitiligo melanocytes and vitiligo skin tissues. Oxidative stress induced hypermethylation of the USP18 promoter region in keratinocytes and melanocytes, and USP18 promoter hypermethylation was also confirmed in vitiligo skin tissues. Our results indicate that USP18 promoter hypermethylation caused by oxidative stress increases ISG15 expression in keratinocytes and melanocytes along with senescence changes, leading CD8+ T cells to produce IFN-γ, the main pathogenic cytokine in vitiligo. Therefore, the ISG15-USP18 network may be important in oxidative stress-induced autoimmunity and cellular senescence in vitiligo pathogenesis., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Chemical leucoderma is defined as hypopigmentation or vitiligo-like hypomelanosis caused by repeated chemical exposure, and the diagnosis can be made clinically. Chemical leucoderma induced by fentanyl transdermal patches is rare. This case report involves a 53-year-old man with chronic back pain caused by herniated nucleus pulposus at the L4-L5 level. The patient had used fentanyl transdermal patches for about 2 years. Depigmented lesions were observed in the areas where fentanyl transdermal patches had been applied. Chemical leucoderma was the most likely diagnosis. There remains a debate regarding whether there is a fentanyl dose-response relationship and whether the duration of exposure is relevant. Spontaneous repigmentation may occur after discontinuing the chemical exposure, and follow-ups are recommended to monitor whether spontaneous repigmentation occurs. Additionally, several treatment options have been proposed as specific treatments for chemical leucoderma, including psoralens, corticosteroids, calcineurin inhibitors, immunosuppressive agents and phototherapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Mitochondria has emerged as a potential modulator of melanocyte function other than just meeting its cellular ATP demands. Mitochondrial DNA defects are now an established cause of maternal inheritance diseases. Recent cellular studies have highlighted the mitochondrial interaction with other cellular organelles that lead to disease conditions such as in Duchenne muscular dystrophy, where defective mitochondria was found in melanocytes of these patients. Vitiligo, a depigmentory ailment of the skin, is another such disorder whose pathogenesis is now found to be associated with mitochondria. The complete absence of melanocytes at the lesioned site in vitiligo is a fact; however, the precise mechanism of this destruction is still undefined. In this review we have tried to discuss and link the emerging facts of mitochondrial function or its inter- and intra-organellar communications in vitiligo pathogenesis. Mitochondrial close association with melanosomes, molecular involvement in melanocyte-keratinocyte communication and melanocyte survival are new paradigm of melanogenesis that could ultimately account for vitiligo. This definitely adds the new dimensions to our understanding of vitiligo, its management and designing of future mitochondrial targeted therapy for vitiligo., (© 2023 European Academy of Dermatology and Venereology.)

Vitiligo is a common chronic skin disease which has an adverse impact on patients' life. Its pathogenesis is complex, involving autoimmunity and oxidative stress (OS). Autoimmunity leads to the loss of epidermal melanocytes and the formation of the depigmented patches of the disease. Treatment of vitiligo should control the exaggerated immune response to arrest the progress of active disease, and then promote melanocytes to repigmentation. Wnt/β-catenin signalling pathway has been of recent interest in vitiligo. Wnt/β-catenin signalling pathway is downregulated in vitiligo. Upregulation of Wnt/β-catenin signalling possibly control vitiligo autoimmune response by protecting melanocyte from OS damage, inhibiting CD8 + T cell effector cell differentiation and enhancing Treg. Wnt/β-catenin signalling plays a critical role in the melanocyte regeneration by driving the differentiation of melanocyte stem cells (McSCs) into melanocytes. Promoting Wnt/β-catenin signalling can not only arrest the progress of active disease of vitiligo but also promote repigmentation. Some of the main effective therapies for vitiligo are likely to work by activating Wnt/β-catenin signalling. Agents that can enhance the effect of Wnt/β-catenin signalling may become potential candidates for the development of new drugs for vitiligo treatment., (© 2023 European Academy of Dermatology and Venereology.)

Background: Hypopigmented mycosis fungoides (HMF) is a relatively rare subtype of mycosis fungoides (MF). The diagnosis of HMF can be quite challenging in case of insufficient diagnostic criteria due to the diverse conditions that present with hypopigmented lesions. This study aimed to evaluate the usefulness of the assessment of the basement membrane thickness (BMT) in the diagnosis of HMF., Methods: A retrospective study was conducted on biopsy specimens of 21 HMF and 25 non-HMF cases who presented with hypopigmented lesions. The thickness of the basement membrane was evaluated in periodic acid-Schiff (PAS)-stained sections., Results: The mean BMT was significantly higher in the HMF group than in the non-HMF group (P < 0.001). The best cut-off value of mean BMT for the detection of HMF verified in ROC analysis was 32.7 μm (P < 0.001) with a sensitivity of 85.7% and a specificity of 96%., Conclusion: Evaluation of BMT can be a useful tool to distinguish HMF from other causes of hypopigmented lesions in doubtful cases. We suggest the use of " BMT more than 33 μm" as a histopathologic criterion of HMF., (© 2023 the International Society of Dermatology.)

Background: Acral speckled hypomelanosis is a very rare pigmentation disorder that appears early in life with hypopigmented macules on background of normal skin, occurring on the acral parts., Case Report: We report a 9-year-old female patient with a 3-year duration of progressive, hypopigmented, confetti-like macules occurring symmetrically on the dorsum of both hands and feet. Biopsy showed normal number of melanocytes with no evidence of macromelanosomes using special stains for melanocytes., Conclusion: Acral speckled hypomelanosis is a relatively, recently, discovered entity, with only 9 cases reported to date, and our case is the 10th. The exact etiopathogenesis is not yet known., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Backgroud: Idiopathic guttate hypomelanosis (IGH) is a common skin disorder with no standard treatment., Objective: Assess the efficacy and safety of 5-fluorouracil (5FU) compared with saline, delivered using a tattoo machine, to repigment IGH lesions., Methods: This split-body randomized single-blinded trial recruited adults with symmetrical IGH lesions. A tattoo machine was used to deliver 5FU in IGH lesions of 1 limb and saline in the contralateral limb. Outcomes were the number of achromic lesions 30 days after treatment compared with baseline, patient satisfaction, and local or systemic adverse events., Results: Twenty-nine patients (28 women) were included. The median number of achromic lesions decreased significantly in 5FU-treated limbs (baseline: 32, interquartile range (IQR) 23-37 × post-treatment: 12, IQR 6-18, p = .000003) and saline-treated limbs (baseline: 31, IQR 24-43 × post-treatment: 21, IQR 16-31, p = .000006), but reduction was significantly more pronounced in 5FU-treated limbs ( p = .00003). All participants were satisfied or very satisfied with results on 5FU-treated limbs. There were no adverse events., Conclusion: 5-fluorouracil delivery using a tattoo machine was more effective than saline to repigment IGH lesions, with high patient satisfaction and no adverse events.Clinicaltrials.gov : NCT02904564., (Copyright © 2023 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Our objective was to describe the clinical, histological characteristics, and disease outcome of a cohort of mycosis fungoides (MF) diagnosed during childhood including disease status at adulthood., Methods: This is a retrospective multicentre survey of patients aged under 18 years at diagnosis with histologically confirmed MF. Patients' clinical and histological characteristics, treatments, and disease outcome (for patients followed for more than 12 months) were analysed., Results: Forty-six patients were included (median age at diagnosis: 11 years; M:F sex ratio: 3:1) with 39 (85%) followed for at least 12 months. Thirty-nine patients (85%) had stage I MF. Hypopigmented patches were observed in 48% and folliculotropism in 43% patients. Immunophenotype of the skin infiltrate was predominantly CD8+ in 17% of patients. Initial management included a wait-and-see strategy in 6/39 (15%), skin-directed treatment in 27 (69%), and systemic treatment in 6 (15%) patients, respectively, with partial or complete clinical response (PR or CR) observed in 28 patients (72%). 14/39 patients (36%) relapsed after initial response. After a median follow-up period of 54 months, disease status at last news was PR or CR in 31/39 (79%), stable disease in 6 (15%), and progression in 2 (5%) patients. Histological transformation was observed in 3/39 (8%). Of the 15 patients followed until adulthood, 13 (87%) had persistent MF., Discussion: This survey confirms the high frequency of hypopigmented and folliculotropic lesions and of CD8+ immunophenotype compared to adult MF patients. The long-term course is usually indolent but transformation may occur sometimes long after disease onset and the disease may persist during adulthood., (© 2022 S. Karger AG, Basel.)

Background/objectives: Pityriasis lichenoides chronica (PLC) lesions are reported to subside with post-inflammatory hypopigmentation (PIH); hence, the most widely perceived nature of hypopigmented macules in PLC is PIH. However, to the best of our knowledge, no studies describing histopathological findings in these lesions are reported in literature. The aim of this study is to evaluate the hypopigmented lesions encountered in PLC patients and to shed light on their histopathological features., Methods: A cross-sectional observational study included twenty-one patients with PLC recruited in a period of twelve months. Clinical characteristics of each patient were collected. A skin biopsy from hypopigmented lesions whenever present was taken and assessed with routine haematoxylin and eosin stain., Results: Seventeen patients (81%) were less than 13 years old. Most patients (85.7%) demonstrated diffuse distribution of lesions. Hypopigmented lesions were present on the face in 12 (57.14%) patients. Histopathologically, hypopigmented lesions showed features of post-inflammatory hypopigmentation in 19% of patients, residual PLC in 52.4% and active PLC 28.6% of patients., Conclusion: Hypopigmented lesions in PLC were noted mainly in younger ages, histopathologically they may show features of active or residual disease, beyond post-inflammatory hypopigmentation. Consequently active treatment for patients presenting predominantly with hypopigmented lesions could be required to control the disease., (© 2021 Australasian College of Dermatologists.)

Vitiligo is an acquired, chronic, and progressive depigmentation or hypopigmentation characterized by the destruction of melanocytes and the occurrence of white patches or macules in the skin, mucosal surface of eyes, and ears. Melanocytes are the melanin pigment-producing cells of the skin which are destroyed in pathological conditions called vitiligo. Approximately 0.5 - 2.0% of the population is suffering from vitiligo, and a higher prevalence rate of up to 8.8% has been reported in India. It is caused by various pathogenic factors like genetic predisposition, hyperimmune activation, increased oxidative stress, and alteration in neuropeptides level. Genetic research has revealed a multi- genetic inheritance that exhibits an overlap with other autoimmune disorders. However, melanocytes specific genes are also affected (such as DDR1, XBP1, NLRP1, PTPN22, COMT, FOXP3, ACE, APE, GSTP1, TLR, SOD, and CTLA-4). A number of therapeutic options are employed for the treatment of vitiligo. The topical corticosteroids and immunomodulators are currently in practice for the management of vitiligo. Phototherapies alone and in combinations with other approaches are used in those patients who do not respond to the topical treatment. The main focus of this review is on the etiopathological factors, pharmacological management (phototherapy, topical, systemic, and surgical therapy), and herbal drugs used to treat vitiligo., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Amyloidosis cutis dyschromica (ACD) is a rare form of primary cutaneous amyloidosis featured by reticulate dotted hypo- and hyperpigmentation. Recently, loss-of-function mutations in GPNMB, encoding glycoprotein (transmembrane) nonmetastatic melanoma protein B, were found in autosomal-recessive or semi-dominant ACD., Objective: This study aims to detect the genetic defect underlying ACD in nine separate cases and to investigate the functional consequences of the mutants., Methods: Nine ACD cases were collected including eight with autosomal-recessive pattern and one with autosomal-dominant pattern. Whole-exome sequencing or Sanger sequencing of the GPNMB gene was performed to detect the pathogenic mutations. Haplotype analysis was employed to determine the origin of mutation c.565C > T using adjacent highly polymorphic SNPs. Immunoblotting and subcellular localization assessments were performed to evaluate the expression of the mutants using HEK293 cells transfected with the GPNMB constructs., Results: We detected four recurrent mutations (c.393 T > G, p.Y131*; c.565C > T, p.R189*; c.1056delT, p.P353Lfs*20; c.1238 G > C, p.C413S) and two novel mutations (c.935delA, p.N312Tfs*4; c.969 T > A, p.C323*) in GPNMB. Mutation c.565C > T found in six separate ACD cases shared a common haplotype. The two novel mutations caused a decreased abundance of truncated proteins. The c.1238 G > C mutation, which was detected in the autosomal-dominant case, caused abnormal reticular subcellular localization of the protein. A major percentage of wildtype changed its expression pattern when co-expressed with this mutant., Conclusions: Our findings proved that the recurrent mutation c.565C > T originated from a founder effect. The autosomal-dominant ACD associated mutation p.C413S played its pathogenic role through a dominant-negative effect on wild-type GPNMB. This study expands the genotype and inherited modes of ACD and improves our understanding of the pathogenesis of this disorder., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Hereditary leukonychia (HL) is a rare nail dystrophy disease, and several different clinical manifestations and mutations in the phospholipase C δ 1 ( PLCD1 ) gene have been reported. The present study reports on one Chinese family and one sporadic case of with HL. The family members exhibited an autosomal dominant pattern of inheritance with the involvement of all the fingers and toenails in all the patients. Of interest, most of the affected members had koilonychia during their childhood. Thus, the present study first used gene mapping with an aim to identify the pathogenic gene underlying koilonychia. Through genome‑wide linkage analysis, the pathogenic area of koilonychia was identified on chromosome 3 with multipoint Log of Odds scores >2. A novel pathogenic mutation c.1384G>A (p.E462K) was identified in the PLCD1 gene in all the patients in the family, which confirmed the diagnosis of hereditary leukonychia. A novel mutation c.770G>A (p.R257H) was also detected in one sporadic case of leukonychia. On the basis of these findings and of previous studies, it is suggested that hereditary leukonychia may initially present as koilonychia, whereas hereditary koilonychia does not progress to leukonychia. Moreover, the present study identified two pathogenic variants of the PLCD1 associated with hereditary leukonychia, and highlights the significance of genetic diagnosis.

Background: Hypopigmented mycosis fungoides (HMF) is an uncommon variant of mycosis fungoides., Aims: To study the clinical and histopathology presentation in children with HMF., Method: We reviewed 9 children diagnosed with HMF. The clinical data were collected and analyzed., Result: Eight boys and 1 girl were included, with a median onset age of 7.4 year old and median age of diagnosis of 10.5 year old. Multiple hypopigmented patches were observed in all patients, and 5 patients exhibited multiple scaly erythema at the center of hypopigmented patches. Histopathology showed atypical lymphocytes with hyperchromatic, irregular, and cerebriform nuclei, infiltrated in the epidermis and dermis. Pautrier's microabscesses was noted in 6 of 9 patients, and papillary dermal fibroplasia was noted in 6 of 9 patients. CD8 predominance was detected in 4 of 6 patients. Four patients were simultaneously subjected to skin biopsy on hypopigmented patches and scaly erythema simultaneously. Compared with hypopigmented specimens, erythema biopsy detected deeper and denser infiltration of atypical lymphoid cells in 3 of 4 patients, higher CD4+/CD8+ ratio in 4 of 4 patients, more CD5 loss in 2 of 4 patients, and more CD7 loss in 2 of 4 patients. TCR gene monoclonal rearrangement was detected in 2 of 5 patients. Narrowband ultraviolet B phototherapy was applied in 7 patients. One of 7 patients achieved complete response, and 6 of 7 patients achieved partial response. No recurrence was noted with the median follow-up period of 6 months., Conclusion: HMF could occur in young patients, with indolent and benign course. HMF could gradually seem as scaly erythema based on hypopigmented patches. The histopathology indicated a more advanced stage of the scaly erythema lesions than hypopigmented patches., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

There are limited treatments for dyschromia in burn hypertrophic scars (HTSs). Initial work in Duroc pig models showed that regions of scar that are light or dark have equal numbers of melanocytes. This study aims to confirm melanocyte presence in regions of hypo- and hyper-pigmentation in an animal model and patient samples. In a Duroc pig model, melanocyte presence was confirmed using en face staining. Patients with dyschromic HTSs had demographic, injury details, and melanin indices collected. Punch biopsies were taken of regions of hyper-, hypo-, or normally pigmented scar and skin. Biopsies were processed to obtain epidermal sheets (ESs). A subset of ESs were en face stained with melanocyte marker, S100β. Melanocytes were isolated from a different subset. Melanocytes were treated with NDP α-MSH, a pigmentation stimulator. mRNA was isolated from cells, and was used to evaluate gene expression of melanin-synthetic genes. In patient and pig scars, regions of hyper-, hypo-, and normal pigmentation had significantly different melanin indices. S100β en face staining showed that regions of hyper- and hypo-pigmentation contained the same number of melanocytes, but these cells had different dendricity/activity. Treatment of hypo-pigmented melanocytes with NDP α-MSH produced melanin by microscopy. Melanin-synthetic genes were upregulated in treated cells over controls. While traditionally it may be thought that hypopigmented regions of burn HTS display this phenotype because of the absence of pigment-producing cells, these data show that inactive melanocytes are present in these scar regions. By treating with a pigment stimulator, cells can be induced to re-pigment., Competing Interests: The authors declare no conflicts of interest.

Abstract: Hypopigmented mycosis fungoides (HMF) is a clinical variant of MF with a presentation similar to other hypopigmented diseases, especially vitiligo. In this article, we report an adult case of HMF mimicking vitiligo. A 53-year-old man presented with an asymptomatic well-defined focal and hypopigmented patch with erythematous to brownish macules on the flank which had been developing over several months without other cutaneous findings. He had no past medical or trauma history. Skin biopsy from the hypopigmented patch indicated a slightly band-like, superficial dermal infiltrate of lymphocytes with mild cytologic atypia and epidermotropism. Fontana-Masson and Mart-1 stains showed a decrease in the epidermal pigment and the number of basal melanocytes. In addition, CD4 and CD8 stains were positive, predominantly the CD8 stain, and loss of CD7 stain was noted in the epidermal atypical lymphocytes. A T-cell receptor gene rearrangement study from the hyperpigmented area showed monoclonality. Finally, we diagnosed the patient with HMF. After about 17 months of treatment with narrow-band ultraviolet B, the hypopigmented lesion had notably improved in both the clinical and histological aspects. The clinical appearance of our case was similar to vitiligo while clinical improvement was also exceptionally similar to the skin findings from follicular repigmentation after narrow-band ultraviolet B treatment in vitiligo. Therefore, dermatologists should consider the clinical differential diagnosis of HMF in patients with an asymptomatic hypopigmentation, especially in dark-skinned Asian patients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hypopigmented macules are seen in a variety of disorders and the diagnosis rests on clinicopathological correlation. However, some cases are difficult to classify and pose a diagnostic challenge., Aim: To describe the clinical and histopathological features of patients with hypopigmented macules and follicular spongiosis on histopathology., Materials and Methods: We undertook a retrospective analysis of clinical and histopathological findings in 12 patients who presented with clinically nondiagnostic hypopigmented macules and showed follicular spongiosis on skin biopsy, at All India Institute of Medical Sciences, New Delhi, India between January 2015 and October 2016. The findings were compared with 12 patients with "unclassified" hypopigmented macules, who did not show follicular spongiosis on skin biopsy., Results: A total of 12 patients with hypopigmented macules showed spongiosis affecting the follicular epithelium on histopathology. There were eight men and four women, most in their second decade (mean age 19.1 ± 8.05 years), presenting with hypopigmented macules most commonly on the upper limbs, for a mean duration of 6.33 ± 5.10 months. Clinically evident lesional hair loss was seen in all patients, and follicular prominences in seven (58%) patients. Histological features suggestive of other diagnosis, namely leprosy, mycosis fungoides or sarcoidosis were not seen in any biopsy. Alcian blue stain revealed an minimal amount of mucin in one biopsy. Clinically apparent hair loss and follicular prominences were found to be statistically significantly associated with histological evidence of follicular spongiosis (P < 0.001 and 0.003, respectively)., Limitations: Our study is limited by its retrospective design and small sample size., Conclusions: Patients with hypopigmented macules and follicular spongiosis on histopathology may represent a distinct clinicopathological entity that is associated with lesional hair loss and follicular prominences. It is probably a variant of an endogenous dermatitis similar to pityriasis alba., Competing Interests: None

We herein report a novel mutation in familial progressive hyper- and hypopigmentation (FPHH). The KITLG gene encoding the KIT ligand protein is a disease-causing gene for FPHH. Various disease-causing gain-of-function mutations, which reside within or adjacent to the conserved VTNN motif of this gene, have been described to date. We have now identified a novel KITLG mutation, c.337G>A (p.Glu113Lys), in FPHH which is located within another ligand-receptor interaction site., (© 2020 Japanese Dermatological Association.)