RESUMO
While vitiligo is primarily caused by melanocyte deficiency or dysfunction, recent studies have revealed a notable prevalence of metabolic syndrome (MetS) among patients with vitiligo. This suggests shared pathogenic features between the two conditions. Individuals with vitiligo often exhibit variations in triglyceride levels, cholesterol, and blood pressure, which are also affected in MetS. Given the similarities in their underlying mechanisms, genetic factors, pro-inflammatory signalling pathways, and increased oxidative stress, this study aims to highlight the common traits between vitiligo and metabolic systemic disorders. Serum analyses confirmed increased low-density lipoprotein (LDL) levels in patients with vitiligo, compared to physiological values. In addition, we reported significant decreases in folate and vitamin D (Vit D) levels. Oxidative stress is one of the underlying causes of the development of metabolic syndromes and is related to the advancement of skin diseases. This study found high levels of inflammatory cytokines, such as interleukin-6 (IL-6) and chemokine 10 (CXCL10), which are markers of inflammation and disease progression. The accumulation of insulin growth factor binding proteins 5 (IGFBP5) and advanced glycation end products (AGEs) entailed in atherosclerosis and diabetes onset, respectively, were also disclosed in vitiligo. In addition, the blood-associated activity of the antioxidant enzymes catalase (Cat) and superoxide dismutase (SOD) was impaired. Moreover, the plasma fatty acid (FAs) profile analysis showed an alteration in composition and specific estimated activities of FAs biosynthetic enzymes resembling MetS development, resulting in an imbalance towards pro-inflammatory n6-series FAs. These results revealed a systemic metabolic alteration in vitiligo patients that could be considered a new target for developing a more effective therapeutic approach.
Assuntos
Biomarcadores , Síndrome Metabólica , Estresse Oxidativo , Vitiligo , Vitiligo/sangue , Vitiligo/metabolismo , Humanos , Biomarcadores/sangue , Masculino , Adulto , Feminino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Vitamina D/sangue , Vitamina D/metabolismo , Lipoproteínas LDL/sangue , Lipoproteínas LDL/metabolismo , Citocinas/sangue , Citocinas/metabolismo , Ácidos Graxos/metabolismo , Ácidos Graxos/sangue , Catalase/sangue , Catalase/metabolismoRESUMO
Aging is a natural intrinsic process associated with the loss of fibrous tissue, a slower cell turnover, and a reduction in immune system competence. In the skin, the continuous exposition of environmental factors superimposes extrinsic damage, mainly due to ultraviolet radiation causing photoaging. Although not usually considered a pathogenic event, photoaging affects cutaneous biology, increasing the risk of skin carcinogenesis. At the cellular level, aging is typified by the rise of senescence cells a condition characterized by reduced or absent capacity to proliferate and aberrant hyper-secretory activity. Senescence has a double-edged sword in cancer biology given that senescence prevents the uncontrolled proliferation of damaged cells and favors their clearance by paracrine secretion. Nevertheless, the cumulative insults and the poor clearance of injured cells in the elderly increase cancer incidence. However, there are not conclusive data proving that aged skin represents a permissive milieu for tumor onset. On the other hand, tumor cells are capable of activating resident fibroblasts onto a pro-tumorigenic phenotype resembling those of senescent fibroblasts suggesting that aged fibroblasts might facilitate cancer progression. This review discusses changes that occur during aging that can prime neoplasm or increase the aggressiveness of melanoma and non-melanoma skin cancer.
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Envelhecimento da Pele , Neoplasias Cutâneas , Idoso , Humanos , Raios Ultravioleta/efeitos adversos , Neoplasias Cutâneas/etiologia , Envelhecimento , Pele , CarcinogêneseRESUMO
Among disorders of pigmentation, vitiligo is the most common, with an estimated prevalence between 0.5% and 1%. The disease has gathered increased attention in the most recent years, leading to a better understanding of the disease's pathophysiology and its implications and to the development of newer therapeutic strategies. A better, more integrated approach is already in use for other chronic inflammatory dermatological diseases such as psoriasis, for which metabolic comorbidities are well-established and part of the routine clinical evaluation. The pathogenesis of these might be linked to cytokines which also play a role in vitiligo pathogenesis, such as IL-1, IL-6, TNF-α, and possibly IL-17. Following the reports of intrinsic metabolic alterations reported by our group, in this brief review, we analyze the available data on metabolic comorbidities in vitiligo, accompanied by our single-center experience. Increased awareness of the metabolic aspects of vitiligo is crucial to improving patient care.
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Doenças Metabólicas/epidemiologia , Vitiligo/epidemiologia , Ensaios Clínicos como Assunto , Comorbidade , Humanos , Doenças Metabólicas/patologia , Vitiligo/patologiaRESUMO
Radiotherapy is frequently associated with a great number of collateral effects, which can affect the skin and its appendages. In addition to more common side effects, like radiodermatitis, other cutaneous conditions are less known and often they are underdiagnosed. Among these, isoradiotopic response is one of the rare radiotherapy-associated phenomena. This term refers to the appearance of a secondary dermatosis in a previously irradiated district. The term was used for the first time by Shurman et al. to describe a case of lichen ruber planus arising in the genital area after radiotherapy for squamous cell carcinoma. The pathologic mechanism is not completely clear, but a few hypotheses have been proposed. Alterations in the local lymphatic drainage, in the nervous system and the immune microenvironment have all been called into play (the immunocompromised district theory). We present the case of a male patient that developed discoid lupus on a previously irradiated cutaneous area and review the literature, highlighting the numerous possible manifestations of this phenomenon.
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Lúpus Eritematoso Discoide/etiologia , Lesões por Radiação/diagnóstico , Humanos , Lúpus Eritematoso Discoide/diagnóstico , Lúpus Eritematoso Discoide/patologia , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/patologia , Neoplasias Cutâneas/radioterapiaRESUMO
Bromoderma is a rare skin disease caused by the ingestion, inhalation, or contact with products containing bromides. We report a case of bromoderma in a 36-year-old farmer, characterized by remission during the spring and exacerbation during the winter. The recognition of the use of products containing bromides during the winter helped us to understand the cause of the clinical condition.
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Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Hidrocarbonetos Bromados/efeitos adversos , Exposição Ocupacional , Praguicidas/efeitos adversos , Estações do Ano , Pele/efeitos dos fármacos , Corticosteroides/uso terapêutico , Adulto , Doenças dos Trabalhadores Agrícolas/diagnóstico , Doenças dos Trabalhadores Agrícolas/tratamento farmacológico , Antibacterianos/uso terapêutico , Biópsia , Luvas Protetoras , Humanos , Masculino , Recidiva , Indução de Remissão , Pele/patologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Androgenetic alopecia (AGA), one of the most common causes of hair loss in men and women, is an infrequent cause of alopecia in children. In AGA, patients generally start noticing hair thinning after the onset of puberty due to progressive miniaturisation of the hair follicle which leads to vellus transformation of terminal hair. However, the occurrence of prepubertal AGA has rarely been reported in the literature. The pathophysiology of AGA is tightly linked to androgen hormones; prepubertal children do not usually produce significant amounts of adrenal or gonadal androgens. When it does occur, an underlying abnormality should be suspected. Secondary causes of AGA must be excluded when evaluating a patient before the appearance of puberty. Premature puberty, polycystic ovarian syndrome and other causes of hyperandrogenism can present with hair loss in an androgenetic pattern. This article reviews the normal physiology of androgen hormones and their role in the pathophysiology of childhood AGA.
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Alopecia/diagnóstico , Alopecia/fisiopatologia , Androgênios/metabolismo , Criança , Feminino , Folículo Piloso/metabolismo , Humanos , Hiperandrogenismo/fisiopatologia , Masculino , Síndrome do Ovário Policístico/fisiopatologia , Puberdade Precoce/fisiopatologia , Fenômenos Fisiológicos da PeleRESUMO
Pseudomyogenic hemangioendothelioma (PMH) is a rare, mostly indolent, endothelial neoplasm of low-grade malignancy, often mimicking myoid and epithelioid tumors histologically. It is more frequent in young adult males and it usually presents with multiple cutaneous nodules, mostly localized at the extremities. It traverses several tissue planes simultaneously and can involve dermis, subcutis, skeletal muscle, and bone. Histologically, it is characterized by plump spindle cells with eosinophilic cytoplasm, often arranged in fascicles and epithelioid cells with "pseudomyogenic" morphology. Immunohistochemically, PMH is positive for Factor VIII, FLI-1, INI-1, vimentin, MDM2, CDK4, CD31, AE1/AE3, EMA, and P63. The efficacy of treatments is only partially known. Because of the frequent multifocal aspect of PMH, which contraindicates surgery, systemic treatments, such as gemcitabine, sirolimus, and everolimus are used. Based on our observation of multifocal PMH of the foot in a 17-year-old male patient, treated with gemcitabine with complete cutaneous response in a 2-year follow-up, we decided to discuss this rare tumor and underline its progression and therapeutic approaches. Thanks to a correct diagnosis, it is possible to avoid aggressive therapeutic approaches, which would be necessary for nonindolent diseases, such as sarcoma, which often needs amputation.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Hemangioendotelioma Epitelioide/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adolescente , Biomarcadores Tumorais/análise , Biópsia , Desoxicitidina/uso terapêutico , Pé , Hemangioendotelioma Epitelioide/química , Hemangioendotelioma Epitelioide/patologia , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Neoplasias de Tecidos Moles/química , Neoplasias de Tecidos Moles/patologia , Resultado do Tratamento , GencitabinaRESUMO
OBJECTIVE: Psychiatric disorders and suicide risk (especially in psoriasis) are frequent and disabling conditions in patients with skin diseases. The aim of this study was to examine the risk of suicide and stressful life events in a sample of patients with skin disease. METHODS: A sample of 242 dermatological patients (142 women and 100 men), 112 of which had psoriasis, 77 had melanoma, and 53 were suffering with chronic allergic diseases. Patients were administered the MINI International Neuropsychiatric Interview (MINI), Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), and the Columbia-Suicide Severity Rating Scale (C-SSRS). Patients were also asked about their experiences with stressful life events. RESULTS: Patients with psoriasis were more likely to have a history of psychiatric disorders (36.6% vs. 13.2% χ2(1) = 9.55; p = 0.002) compared to patients with allergies. Specifically, patients with psoriasis more likely had a diagnosis of a mood disorder (16.1% vs. 3.9% χ2(1) = 6.85; p = 0.009; 16.1% vs. 0% χ2(1) = 9.56; p = 0.002) and reported past suicidal ideation (33.9% vs. 15.6% χ2(1) = 7.89; p = 0.005; 33.9% vs. 18.9% χ2(1) = 3.96; p = 0.047) as compared to those with melanoma and allergy. CONCLUSIONS: The results from this study suggest that patients affected by psoriasis have an increased risk of psychiatric comorbidities and suicidal ideation compared to those who have other dermatological disorders.
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Hipersensibilidade/epidemiologia , Melanoma/epidemiologia , Transtornos Mentais/epidemiologia , Psoríase/epidemiologia , Ideação Suicida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto JovemAssuntos
Alopecia/induzido quimicamente , Alopecia/diagnóstico por imagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cor de Cabelo/efeitos dos fármacos , Ciclofosfamida/administração & dosagem , Dermoscopia , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Taxoides/administração & dosagemRESUMO
The most common cutaneous T-cell lymphoma, mycosis fungoides (MF), is clinically characterized by erythematous-violaceous nodules and erythematous-scaly patches. In the early stages of MF, phototherapy is currently the first line of treatment and plays a significant role. This study aims to review and analyze the various phototherapy options for cutaneous lymphoma.
RESUMO
Skin aging is one of the most evident signs of human aging. Modification of the skin during the life span is characterized by fine lines and wrinkling, loss of elasticity and volume, laxity, rough-textured appearance, and pallor. In contrast, photoaged skin is associated with uneven pigmentation (age spot) and is markedly wrinkled. At the cellular and molecular level, it consists of multiple interconnected processes based on biochemical reactions, genetic programs, and occurrence of external stimulation. The principal cellular perturbation in the skin driving senescence is the alteration of oxidative balance. In chronological aging, reactive oxygen species (ROS) are produced mainly through cellular oxidative metabolism during adenosine triphosphate (ATP) generation from glucose and mitochondrial dysfunction, whereas in extrinsic aging, loss of redox equilibrium is caused by environmental factors, such as ultraviolet radiation, pollution, cigarette smoking, and inadequate nutrition. During the aging process, oxidative stress is attributed to both augmented ROS production and reduced levels of enzymatic and non-enzymatic protectors. Apart from the evident appearance of structural change, throughout aging, the skin gradually loses its natural functional characteristics and regenerative potential. With aging, the skin immune system also undergoes functional senescence manifested as a reduced ability to counteract infections and augmented frequency of autoimmune and neoplastic diseases. This review proposes an update on the role of oxidative stress in the appearance of the clinical manifestation of skin aging, as well as of the molecular mechanisms that underline this natural phenomenon sometimes accelerated by external factors.
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Vitiligo is a complex disease wherein derangements in multiple pathways determine the loss of functional melanocytes. Since its pathogenesis is not yet completely understood, vitiligo lacks a definitive safe and efficacious treatment. At present, different therapies are available; however, each modality has its baggage of disadvantages and side effects. Recently we have described several metabolic abnormalities in cells from pigmented skin of vitiligo patients, including alterations of glucose metabolism. Therefore, we conducted a study to evaluate the effect of Pioglitazone (PGZ), a Peroxisome proliferator-activated receptor-γ (PPARγ) agonist, on cells from pigmented vitiligo skin. We treated vitiligo melanocytes and fibroblasts with low doses of PGZ and evaluated the effects on mitochondrial alterations, previously reported by our and other groups. Treatment with PGZ significantly increased mRNA and protein levels of several anaerobic glycolytic enzymes, without increasing glucose consumption. The PGZ administration fully restored the metabolic network, replacing mitochondrial membrane potential and mitochondrial DNA (mtDNA) copy number. These effects, together with a significant increase in ATP content and a decrease in reactive oxygen species (ROS) production, provide strong evidence of an overall improvement of mitochondria bioenergetics in vitiligo cells. Moreover, the expression of HMGB1, Hsp70, defined as a part of DAMPs, and PD-L1 were significantly reduced. In addition, PGZ likely reverts premature senescence phenotype. In summary, the results outline a novel mode of action of Pioglitazone, which may turn out to be relevant to the development of effective new vitiligo therapeutic strategies.
Assuntos
PPAR gama , Vitiligo , Humanos , PPAR gama/metabolismo , Vitiligo/tratamento farmacológico , Vitiligo/genética , Vitiligo/metabolismo , Pioglitazona/farmacologia , Pioglitazona/uso terapêutico , Hipoglicemiantes , Melanócitos/metabolismoRESUMO
Vitiligo is an acquired skin depigmentation disease involving multiple pathogenetic mechanisms, which ultimately direct cytotoxic CD8+ cells to destroy melanocytes. Abnormalities have been described in several cells even in pigmented skin as an expression of a functional inherited defect. Keratinocytes regulate skin homeostasis by the assembly of a proper skin barrier and releasing and responding to cytokines and growth factors. Alterations in epidermal proliferation, differentiation, and lipid composition as triggers for immune response activation in vitiligo have not yet been investigated. By applying cellular and lipidomic approaches, we revealed a deregulated keratinocyte differentiation with altered lipid composition, associated with impaired energy metabolism and increased glycolytic enzyme expression. Vitiligo keratinocytes secreted inflammatory mediators, which further increased following mild mechanical stress, thus evidencing immune activation. These findings identify intrinsic alterations of the nonlesional epidermis, which can be the prime instigator of the local inflammatory milieu that stimulates immune responses targeting melanocytes.
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Vitiligo, the most common depigmenting disorder of the skin, is undergoing a period of intense advances in both disease understanding and therapeutic possibilities leading the way to the beginning of a new era for the disorder. Its pathophysiology has gathered the attention of researchers for years, and many advances have been made in the clarification of the interaction between different factors that result in depigmented macule formation. The complex interplay between non-immunological and immunological factors in vitiligo is key for the development of the disease, and the participation of cells other than melanocytes, such as keratinocytes, fibroblasts, natural killer cells, and innate lymphoid cells, has been shown. Recent advances have also brought to the understanding of the complex part played by a specific subtype of T cells: T-resident memory cells. This review analyzes some of the most recent insights in vitiligo pathogenesis underlining the interactions between different cell types, which are the basis for the therapeutic approaches under development.
Assuntos
Autoimunidade , Imunidade Inata , Linfócitos T/imunologia , Vitiligo/patologia , Animais , Humanos , Vitiligo/imunologiaRESUMO
Since the introduction of the first chemotherapeutic regimens for the treatment of oncological disease, hundreds of drugs have been approved for cancer treatment and many more are under investigation. The development of newer drugs such as target therapies, immuno-oncotherapies, and hormonal therapies has increased in specificity with the development of smaller molecules and more selective targets. Cutaneous side effects are now well known for both standard chemotherapy and targeted therapies. The correct diagnosis and management of these effects are of vital importance both to optimize therapeutic success rates and to reduce the patient's suffering. In fact, the appearance of a cutaneous adverse event can be responsible for a reduction in drug dosage or worse its suspension. In order to achieve this objective, we propose a management algorithm, based on three different steps, before, during, and after the oncological treatments, respectively. Our proposal underlines the importance of correct skin care measures to limit or reduce the severity of side effects.
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Antineoplásicos , Algoritmos , Antineoplásicos/efeitos adversos , Humanos , PeleRESUMO
BACKGROUND: Chemotherapy-induced alopecia (CIA) is one of the most dramatic side effects of chemotherapy. Currently no guidelines are available for its prevention and treatment. Several devices and drugs are used, but results are often disappointing. AIMS: Our aim is to analyze drugs and devices proposed in the literature for prevention and treatment of CIA induced by cytotoxic drugs and to discuss the evidenced-based opinion. METHODS AND RESULTS: Scalp cooling is the only agent that has been approved by the US Food and Drug Administration for CIA prevention. Minoxidil and bimatoprost should not be used during chemotherapy administration, but they can be used after chemotherapy discontinuation to obtain greater regrowth. CONCLUSIONS: Therapy should always be modulated for the patient and no fixed protocol should be used. Trichoscopy and trichogram could be useful tools in supporting this treatment.
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BACKGROUND AND OBJECTIVES: Female pattern hair loss (FPHL) is a common form of scalp hair loss that occurs in 38% of females. Currently, minoxidil solution is the only therapy approved by the US Food and Drug Administration, but many other treatments are used, including cyproterone acetate, spironolactone, topical 17α-estradiol, and prostaglandin analogs. Systemic finasteride has been considered a treatment option in women even though its teratogenic effects tend to limit its prescription. Recently, topical finasteride has been evaluated to limit the side effect profile of the drug. The objective of the present study is to compare retrospectively the efficacy of topical 0.05% 17α-estradiol solution and a 0.5% finasteride lotion in the treatment of FPHL. PATIENTS AND METHODS: We enrolled 119 postmenopausal female patients. The first group comprised 69 women treated with finasteride 0.5% and minoxidil 2%. The second group included 50 women treated with 17α-estradiol 0.05% and minoxidil 2%. At baseline and at 6- and 12- to 18-month follow-up, global photographs were systematically taken. Three operators blind to the prescribed treatment evaluated photographs using a 7-point scale. One-way analysis of variance and unpaired Student t tests were performed to analyze 7-point scale scores. RESULTS: The improvement was statistically significant from 6 months to 12-18 months, both for finasteride (P < 0.005) and 17α-estradiol (P < 0.05). The efficacy of topical finasteride was significantly greater than that of 17α-estradiol solution, both at the 6-month (P < 0.05) and at the 12- to 18-month follow-up (P < 0.005). In general, the highest improvement was observed after 12-18 months of treatment with topical finasteride therapy. CONCLUSIONS: Topical finasteride 0.5% in combination with minoxidil 2% could represent a valid therapeutic option for the treatment of postmenopausal FPHL, showing higher efficacy than topical 17α-estradiol with minoxidil 2% both at 6-month and 12- to 18-month follow-up.
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Alopecia areata (AA) is an organ-specific autoimmune disorder that targets anagen phase hair follicles. The course is unpredictable and current available treatments have variable efficacy. Nowadays, there is relatively little evidence on treatment of AA from well-designed clinical trials. Moreover, none of the treatments or devices commonly used to treat AA are specifically approved by the Food and Drug Administration. The Italian Study Group for Cutaneous Annexial Disease of the Italian Society of dermatology proposes these Italian guidelines for diagnosis and treatment of Alopecia Areata deeming useful for the daily management of the disease. This article summarizes evidence-based treatment associated with expert-based recommendations.