RESUMO
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).
Assuntos
Dermoscopia , Hipopigmentação , Sensibilidade e Especificidade , Vitiligo , Humanos , Hipopigmentação/diagnóstico , Hipopigmentação/diagnóstico por imagem , Hipopigmentação/patologia , Feminino , Masculino , Adolescente , Adulto , Criança , Vitiligo/diagnóstico , Vitiligo/diagnóstico por imagem , Vitiligo/patologia , Adulto Jovem , Pessoa de Meia-Idade , Pré-Escolar , Pele/patologia , Pele/diagnóstico por imagem , Diagnóstico Diferencial , IdosoAssuntos
Cicatriz Hipertrófica , Hiperpigmentação , Hipopigmentação , Humanos , Cicatriz Hipertrófica/patologia , Cicatriz Hipertrófica/terapia , Cicatriz Hipertrófica/etiologia , Hipopigmentação/etiologia , Hipopigmentação/patologia , Hiperpigmentação/etiologia , Hiperpigmentação/patologia , Feminino , Terapia de Luz Pulsada Intensa/métodos , Masculino , Adulto , Resultado do Tratamento , Criança , Adolescente , InflamaçãoRESUMO
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.
Assuntos
Hiperpigmentação , Hipopigmentação , Humanos , Feminino , Hiperpigmentação/patologia , Hipopigmentação/patologia , Estudos Retrospectivos , Adolescente , Adulto Jovem , Criança , Dermoscopia , AdultoAssuntos
Hipopigmentação , Humanos , Hipopigmentação/patologia , Pigmentação da Pele , Masculino , FemininoRESUMO
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.
Assuntos
Receptores ErbB , Gefitinibe , Hipopigmentação , Queratinócitos , Melaninas , Melanócitos , Inibidores de Proteínas Quinases , Receptores ErbB/metabolismo , Animais , Melaninas/metabolismo , Melaninas/biossíntese , Humanos , Inibidores de Proteínas Quinases/farmacologia , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Melanócitos/patologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/patologia , Hipopigmentação/patologia , Hipopigmentação/tratamento farmacológico , Gefitinibe/farmacologia , Cobaias , Pigmentação da Pele/efeitos dos fármacos , Fator de Células-Tronco/metabolismo , Epiderme/efeitos dos fármacos , Epiderme/patologia , Epiderme/metabolismo , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Endotelina-1/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Fator de Crescimento Epidérmico/farmacologia , QuinazolinasAssuntos
Hipopigmentação , Micose Fungoide , Neoplasias Cutâneas , Humanos , Micose Fungoide/patologia , Micose Fungoide/diagnóstico , Micose Fungoide/complicações , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/complicações , Hipopigmentação/patologia , Hipopigmentação/diagnóstico , Masculino , Pele/patologia , FemininoRESUMO
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.
Assuntos
Hipopigmentação , Vitiligo , Animais , Camundongos , Humanos , Vitiligo/etiologia , Vitiligo/patologia , Camundongos Endogâmicos C57BL , Hipopigmentação/complicações , Hipopigmentação/patologia , Epiderme , Melanócitos/patologiaRESUMO
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.
Assuntos
Hipopigmentação , Transtornos Motores , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/patologia , Substância Negra/metabolismo , Melaninas/metabolismo , Imageamento por Ressonância Magnética/métodos , Hipopigmentação/metabolismo , Hipopigmentação/patologiaRESUMO
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 [CI95%]: 1.16-1.84, pBONF = 0.004), particularly in individuals with cortical AD neuropathology (OR = 1.56, CI95%: 1.15-2.15, pBONF = 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, CI95%: -0.023--0.002, pBONF = 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.
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Doença de Alzheimer , Disfunção Cognitiva , Hipopigmentação , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Locus Cerúleo/patologia , Estudos Retrospectivos , Disfunção Cognitiva/patologia , Hipopigmentação/patologia , Autopsia , Ritmo Circadiano/fisiologiaRESUMO
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.
Assuntos
Doenças Autoimunes , Hipopigmentação , Vitiligo , Humanos , Doenças Autoimunes/patologia , Linfócitos T CD8-Positivos/metabolismo , Citocinas/metabolismo , Hipopigmentação/patologia , Melanócitos/metabolismo , Estresse Oxidativo/fisiologia , Pele/patologia , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Ubiquitinas/metabolismo , Vitiligo/patologiaRESUMO
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.
Assuntos
Hipopigmentação , Micose Fungoide , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Estudos Retrospectivos , Hipopigmentação/diagnóstico , Hipopigmentação/patologia , Micose Fungoide/diagnóstico , Micose Fungoide/patologia , Membrana Basal/patologia , CorantesRESUMO
Skin hypopigmentation and depigmentation disorders are a top concern for patients with skin of color seeking care from a dermatologist. The visual contrast between involved and uninvolved skin in these disorders makes them particularly burdensome for patients with skin of color. These disorders may have a wide differential of diagnosis, as patients with skin of color may present differently or more frequently than White patients for certain conditions. Clues from a comprehensive history and physical examination with standard lighting and a Wood's light are essential for clinching the diagnosis, although a biopsy may be warranted in special cases.
Assuntos
Hipopigmentação , Pigmentação da Pele , Humanos , Diagnóstico Diferencial , Hipopigmentação/diagnóstico , Hipopigmentação/etiologia , Hipopigmentação/patologiaRESUMO
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.
Assuntos
Hipopigmentação , Tatuagem , Adulto , Humanos , Feminino , Tatuagem/efeitos adversos , Fluoruracila/efeitos adversos , Hipopigmentação/induzido quimicamente , Hipopigmentação/patologia , Satisfação do PacienteRESUMO
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.
Assuntos
Hipopigmentação , Transtornos da Pigmentação , Feminino , Humanos , Criança , Pele/patologia , Hipopigmentação/patologia , Transtornos da Pigmentação/patologia , Melanócitos/patologia , BiópsiaRESUMO
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/ß-catenin signalling pathway has been of recent interest in vitiligo. Wnt/ß-catenin signalling pathway is downregulated in vitiligo. Upregulation of Wnt/ß-catenin signalling possibly control vitiligo autoimmune response by protecting melanocyte from OS damage, inhibiting CD8+ T cell effector cell differentiation and enhancing Treg. Wnt/ß-catenin signalling plays a critical role in the melanocyte regeneration by driving the differentiation of melanocyte stem cells (McSCs) into melanocytes. Promoting Wnt/ß-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/ß-catenin signalling. Agents that can enhance the effect of Wnt/ß-catenin signalling may become potential candidates for the development of new drugs for vitiligo treatment.
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Hipopigmentação , Vitiligo , Humanos , Vitiligo/tratamento farmacológico , Vitiligo/metabolismo , beta Catenina/metabolismo , Hipopigmentação/patologia , Melanócitos/patologia , Epiderme/metabolismoRESUMO
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.