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Autoimmune connective tissue disorders, including systemic lupus erythematosus, systemic sclerosis (SSc) and dermatomyositis (DM), often manifest with debilitating cutaneous lesions and can result in systemic organ damage that may be life-threatening. Despite recent therapeutic advancements, many patients still experience low rates of sustained remission and significant treatment toxicity. While genetic predisposition plays a role in these connective tissue disorders, the relatively low concordance rates among monozygotic twins (ranging from approximately 4% for SSc to about 11%-50% for SLE) have prompted increased scrutiny of the epigenetic factors contributing to these diseases. In this review, we explore some seminal studies and key findings to provide a comprehensive understanding of how dysregulated epigenetic mechanisms can contribute to the development of SLE, SSc and DM.
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Doenças Autoimunes , Doenças do Tecido Conjuntivo , Dermatomiosite , Lúpus Eritematoso Sistêmico , Escleroderma Sistêmico , Humanos , Dermatomiosite/genética , Esclerose , Lúpus Eritematoso Sistêmico/genética , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/tratamento farmacológico , Doenças do Tecido Conjuntivo/genética , Epigênese GenéticaRESUMO
Limited studies explore the role social determinants of health have on urban-rural health disparities, particularly for Skin of Color. To further evaluate this relationship, a cross-sectional study was conducted on data from five states using the 2018 to 2021 Behavior Risk Factor Surveillance Survey, a national state-run health survey. Prevalence of skin cancer history and urban/rural status were evaluated across these social determinants of health: sex, age, race, insurance status, number of personal healthcare providers, and household income. Overall, rural counterparts were significantly more likely to have a positive skin cancer history across most social determinants of health. Rural populations had a higher prevalence of skin cancer history across all races (P<.001). Rural non-Hispanic Whites had greater odds than their urban counterparts (OR=1.40; 95% CI 1.34 - 1.46). The odds were approximately twice as high for rural Black (OR=1.74; 95% CI 1.14 - 2.65), Hispanic (OR=2.31; 95% CI 1.56 - 3.41), and Other Race, non-Hispanic (OR=1.99; 95% CI 1.51 - 2.61), and twenty times higher for Asians (OR=20.46; 95% CI 8.63 - 48.54), although no significant difference was seen for American Indian/Alaskan Native (OR=1.5; 95% CI 0.99 - 2.28). However, when household income exceeded $100,000 no significant difference in prevalence or odds was seen between urban and rural settings. Despite increasing awareness of metropolitan-based health inequity, urban-rural disparities in skin cancer prevalence continue to persist and may be magnified by social determinants such as income and race. J Drugs Dermatol. 2024;23(6):480-484. doi:10.36849/JDD.8094.
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Disparidades nos Níveis de Saúde , População Rural , Neoplasias Cutâneas , Determinantes Sociais da Saúde , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Estudos Transversais , Disparidades em Assistência à Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Prevalência , Saúde da População Rural/estatística & dados numéricos , População Rural/estatística & dados numéricos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etnologia , Estados Unidos/epidemiologia , População Urbana/estatística & dados numéricos , Negro ou Afro-Americano , Hispânico ou Latino , BrancosRESUMO
Dysesthesia is an abnormal sensation in the skin that occurs in the absence of any extraordinary stimulus or other primary cutaneous disorders, excluding any delusions or tactile hallucinations. Clinicians have characterized dysesthesias to include sensations such as burning, tingling, pruritus, allodynia, hyperesthesia, or anesthesia. The etiology and pathogenesis of various generalized dysesthesias is largely unknown, though many dysesthesias have been associated with systemic pathologies including malignancy, infection, autoimmune disorders, and neuropathies. Dermatologists are often the first-line clinicians for patients presenting with such cutaneous findings, thus it is crucial for these physicians to be able to methodically work-up generalized dysesthesias to build a working differential diagnosis, follow up with key labs and/or imaging, and offer patients evidence-based treatment to relieve their symptoms. This broad literature review is an attempt to centralize key studies, cases, and series to help guide dermatologists in their assessment and evaluation of complaints of abnormal cutaneous sensations.
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Doenças do Sistema Nervoso Periférico , Dermatopatias , Humanos , Parestesia/diagnóstico , Parestesia/etiologia , Parestesia/terapia , Pele , Prurido/diagnóstico , Prurido/etiologia , Prurido/terapia , Doenças do Sistema Nervoso Periférico/complicações , Dermatopatias/complicaçõesRESUMO
Non-biologic immunosuppressive therapies are a mainstay in the treatment of various dermatologic conditions. However, the use of these therapies has been scrutinized for potentially increasing risk of haematologic or solid-organ malignancies. Currently, there are no evidence-based guidelines stratifying the risk of malignancy in patients receiving these immunosuppressive agents for the treatment of dermatologic disease. In our review, we evaluate the risk of solid organ and haematologic malignancies in patients receiving non-biologic immunosuppressant therapy for dermatologic indications. A literature search was conducted on PubMed/MEDLINE. Search terms included commonly prescribed non-biologic immunosuppressants and common dermatologic conditions for which non-biologic immunosuppressants are typically prescribed. Levels of evidence and grades of recommendation were used for guidelines. All immunosuppressants evaluated, with the exception of cyclophosphamide, demonstrated low solid-organ or haematologic malignancy potential. Co-morbidities may play a role in malignancy risk in the context of immunosuppressant treatment, including autoimmune disease, which have been associated with increased risk of malignancy and confound overall risk. Duration and/or dosage of treatment may influence this risk as well. Limitations of the review include that the majority of studies were of small sample size, retrospective in nature, and there was lack of direct comparison trials.
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Imunossupressores , Neoplasias , Humanos , Estudos Retrospectivos , Risco , Terapia de ImunossupressãoRESUMO
Febrile neutropaenia (FNP) is a common cause of morbidity and mortality in immunocompromised patients. Although most infections are caused by bacterial pathogens, fungal infections are becoming increasingly more common. Due to its rarity, the diagnosis of fungal infections in febrile neutropenic patients is often delayed. To provide current clinical features, epidemiology, aetiology, diagnosis and treatment of cutaneous involvement of fungal infection in patients with FNP. A retrospective literature review of PubMed was performed, with no language or publishing data restrictions, yielding 116 results. We queried each case for cutaneous lesions associated with fungal pathogens in FNP. We found 54 publications with 215 reported cases of cutaneous manifestations of fungal injury in patients with FNP. This study is limited in that it is a literature review of a disease that is likely underreported. Cutaneous lesions caused by yeasts such as Candida and Trichosporon manifest as diffuse erythematous papules and usually do not develop central necrosis or eschar, while moulds will present as tender nodules that subsequently develop eschar and necrosis. Recognising the cutaneous manifestations of fungal disease can assist in the diagnosis and management of these infections.
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Neutropenia Febril/complicações , Fungos/patogenicidade , Micoses/complicações , Dermatopatias/microbiologia , Antifúngicos/uso terapêutico , Gerenciamento Clínico , Fungos/isolamento & purificação , Humanos , Hospedeiro Imunocomprometido , Micoses/microbiologia , Necrose/microbiologia , Estudos Retrospectivos , Pele/microbiologia , Pele/patologiaRESUMO
Desquamative gingivitis is a clinical finding with several potential etiologies. Among the most common are oral lichen planus, cicatricial pemphigoid, and pemphigus vulgaris, though various other differential diagnoses exist. The presence of desquamative gingivitis often results in poor oral hygiene, which can have downstream consequences, including periodontitis and tooth loss. Though certain mucosal findings may be suggestive of a particular diagnosis, a thorough history, physical examination, and appropriate dermato- and immunopathologic assessment is necessary for narrowing this broad differential diagnosis. This article offers a comprehensive review on the subject, including how to differentiate between the different underlying causes and the best methods for diagnosis (eg, how best to obtain mucosal biopsy specimens). In addition, there is minimal information in the dermatology literature on evaluation of oral hygiene and the consequences of poor oral hygiene not only on disease activity but also overall health. Knowledge on appropriate oral cavity inspection and evaluation of dental hygiene is lacking, and this continuing medical education series discusses methods to evaluate for these consequences so that the dermatologist can be better equipped in managing these patients and recognizing complications early on.
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Gengivite/patologia , Líquen Plano Bucal/patologia , Penfigoide Mucomembranoso Benigno/patologia , Pênfigo/patologia , Biópsia por Agulha/métodos , Diagnóstico Diferencial , Progressão da Doença , Feminino , Gengivite/etiologia , Humanos , Líquen Plano Bucal/complicações , Líquen Plano Bucal/diagnóstico , Masculino , Penfigoide Mucomembranoso Benigno/complicações , Penfigoide Mucomembranoso Benigno/diagnóstico , Pênfigo/complicações , Pênfigo/diagnóstico , Exame Físico/métodos , Prognóstico , Medição de RiscoRESUMO
Desquamative gingivitis is a clinical finding with several potential etiologies, and therefore histologic examination should be performed to confirm the diagnosis before the implementation of systemic therapy. The best methods for obtaining a mucosal biopsy specimen are discussed to aid the dermatologist in approaching these patients, and indications for additional testing, such as immunofluorescence studies, are reviewed. Desquamative gingivitis is uncommon, and there are no systematic guidelines to assist the physician in treatment, producing a practice gap in management. As such, this article focuses on treatment for individual conditions, with emphasis on levels of evidence. An emphasis is also placed on the role of dental care in disease control and the best methods for achieving good oral hygiene.
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Inibidores de Calcineurina/administração & dosagem , Gengivite/patologia , Líquen Plano Bucal/patologia , Penfigoide Mucomembranoso Benigno/patologia , Pênfigo/patologia , Administração Tópica , Biópsia por Agulha , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Gengivite/diagnóstico , Gengivite/tratamento farmacológico , Gengivite/etiologia , Humanos , Imuno-Histoquímica , Líquen Plano Bucal/diagnóstico , Líquen Plano Bucal/tratamento farmacológico , Masculino , Penfigoide Mucomembranoso Benigno/diagnóstico , Penfigoide Mucomembranoso Benigno/tratamento farmacológico , Pênfigo/diagnóstico , Pênfigo/tratamento farmacológicoRESUMO
INTRODUCTION: Clinical models are invaluable in studying wound healing. Challenges in studying human wounds include heterogeneity of patients and wounds, as well as prolonged study time, resulting in high costs. Animal models are an efficient method to study wound healing, but often lack correlation with human acute wound healing. Human wound models can be created using sharp instruments, suction, acids, heat and cold. In this observational study, we propose a practical human acute wound model where partial thickness wounds are induced by cryosurgery to create wounds that could facilitate wound healing research and development. METHODS: On forearms of 8 healthy adult volunteers, freeze injuries were induced using liquid nitrogen spray delivered onto a target area of a 1 cm circular opening at a distance from the cryo-device to the skin of 0.5-1 cm. Several freeze-thaw time cycles were implemented by administering pulses ranging from 3 to 12 seconds. Clinical evaluation was performed at a 24-hour follow-up period. Blister roofs were histologically analyzed by a blinded dermatophathologist. Clinical assessment of time to heal was determined. RESULTS: Freeze-times greater than 5 seconds caused a majority of subjects to develop blisters, and freeze-times greater than 8 seconds resulted in uniform blister formation. Consistent histology of full thickness necrotic epidermis with intact detached basement membrane with minimal acute neutrophilic inflammatory infiltrate was observed in all blister specimens examined. The 8-second freeze-time group had a time to heal of 13-14 days, while the 12-second freeze-time group required 3 weeks to heal. After healing, an area of hypopigmented skin and slightly hypertrophic scarring remained. DISCUSSION: This novel cryo-induced wound model is a potential simple, efficient and reliable model for studying the dynamic processes involved in acute wound healing and to aid in the development of new wound healing therapies. Clinicaltrials.gov identifier: NCT01253135.
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Criocirurgia/métodos , Pele/lesões , Adulto , Vesícula/etiologia , Vesícula/patologia , Humanos , Pele/patologia , CicatrizaçãoRESUMO
Treatment of chronic wounds can present a challenge, with many patients remaining refractory to available advanced therapies. As such, there is a strong need for the development of new products. Unfortunately, despite this demand, few new wound-related drugs have been approved over the past decade. This is in part due to unsuccessful clinical trials and subsequent lack of Food and Drug Administration (FDA) approval. In this article, we discuss the FDA approval process, how it relates to chronic wound trials, common issues that arise, and how best to manage them. Additionally, problems encountered specific to diabetic foot ulcers (DFU) and venous leg ulcers (VLU) are addressed. Careful construction of a clinical trial is necessary in order to achieve the best possible efficacy outcomes and thereby, gain FDA approval. How to design an optimal trial is outlined.
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Pé Diabético/terapia , Drogas em Investigação/uso terapêutico , Projetos de Pesquisa , Úlcera Cutânea/terapia , United States Food and Drug Administration , Úlcera Varicosa/terapia , Doença Crônica , Ensaios Clínicos como Assunto , Pé Diabético/patologia , Aprovação de Drogas , Drogas em Investigação/farmacologia , Humanos , Seleção de Pacientes , Úlcera Cutânea/patologia , Resultado do Tratamento , Estados Unidos , Úlcera Varicosa/patologia , Cicatrização/efeitos dos fármacosRESUMO
Background: Environmental exposures profoundly impact cutaneous physiology, with hair follicles (HFs) being particularly vulnerable due to their high levels of proliferation and perfusion. HFs are exposed directly to contaminants that are absorbed transcutaneously and exposed indirectly to ingested and inhaled pollutants via the bloodstream. Summary: Some pollutants, such as particulate matter, trigger inflammatory responses and have been associated with alopecia areata. Others, like tobacco smoke and phthalates, exert endocrine effects with unclear ramifications for HF function. Pesticides and heavy metals have both been linked to alopecia areata and acute anagen effluvium, while polyaromatic hydrocarbons - ligands of aryl hydrocarbon receptors - are linked to androgenetic alopecia. Finally, UV exposure, which has increased due to anthropogenic ozone depletion, causes oxidative damage and perifollicular mast cell degranulation. Key Messages: Pollutants have far-reaching consequences for hair pathology, which remain incompletely characterized. The effects of environmental exposures on HFs are an active area of research that deserve further attention.
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BACKGROUND: Tucatinib is a tyrosine kinase inhibitor currently used in salvage therapy for human epidermal growth factor receptor 2 (HER2)-positive breast and colorectal cancer. The use of tucatinib alone or in combination with ado-trastuzumab emtansine (T-DM1) in the treatment of advanced HER2-positive cancers is rapidly expanding. OBJECTIVE/METHODS: We report the case of a 66-year-old female who presented to the dermatology clinic with a one-year history of widespread telangiectasias that began after initiation of combination chemotherapy with tucatinib and T-DM1 for metastatic HER2-positive invasive ductal carcinoma. RESULTS: The patient's lesions regressed upon cessation of combination therapy and reappeared in the setting of tucatinib re-initiation, with gradual improvement over the following four months following electrocautery to the affected regions. CONCLUSIONS: We postulate that telangiectasias may be a previously unreported dermatologic side effect of combination treatment with tucatinib and T-DM1. Electrocautery is a safe and effective procedure to reduce the appearance of telangiectasias and improve patient satisfaction during chemotherapy.
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Neoplasias da Mama , Oxazóis , Piridinas , Feminino , Humanos , Idoso , Ado-Trastuzumab Emtansina/uso terapêutico , Neoplasias da Mama/patologia , Trastuzumab/efeitos adversos , Quinazolinas/uso terapêutico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Environmental dermatology is the study of how environmental factors affect the integumentary system. The environment includes natural and built habitats, encompassing ambient exposure, occupational exposures, and lifestyle exposures secondary to dietary and personal care choices. This review explores common toxins found in personal care products and packaging, such as bisphenols, parabens, phthalates, per- and poly-fluoroalkyl substances, p-phenylenediamine, and formaldehyde. Exposure to these toxins has been associated with carcinogenic, obesogenic, or proinflammatory effects that can potentiate disease. In addition, these compounds have been implicated as endocrine-disrupting chemicals that can worsen dermatological conditions such as acne vulgaris, or dermatitis. Certain pollutants found in personal care products are not biodegradable and have the potential to bioaccumulate in humans. Therefore, even short-term exposure can cause long-lasting issues for communities. The skin is often the first point of contact for environmental exposures and serves as the conduit between environmental toxins and the human body. Therefore, it is important for dermatologists to understand common pollutants and their acute, subacute, and chronic impact on dermatological conditions to better diagnose and manage disease.
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Cosméticos , Poluentes Ambientais , Exposição Ocupacional , Humanos , Cosméticos/efeitos adversos , Cosméticos/química , Exposição Ambiental/efeitos adversos , Exposição Ocupacional/efeitos adversos , Parabenos/análiseRESUMO
Hidradenoma papilliferum (HP) is a benign adnexal tumor, commonly affecting the anogenital region of middle-aged women. Clinically, HP typically presents as a slow-growing, unilateral, well-circumscribed, smooth skin-colored cystic dermal nodule, usually growing less than 1 cm in size. Reports of ectopic HP are exceedingly rare but have been identified in areas containing modified apocrine gland structures, most commonly on the head and neck, and have included ceruminous glands of the external ear canal, the Moll glands of the eyelid, mammary glands of the breast, maxillofacial region and areas on the scalp. To the best of our knowledge, there is only one case of ectopic HP located on the external ear canal reported in English literature. We present a second case of draining ectopic HP located on the conchal bowl of the external ear canal.
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Immune checkpoint inhibitor (ICI) therapies carry the risk of major immune-related adverse events (irAEs). Among the most severe irAEs is epidermal necrosis that may clinically mimic Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN). The aim of this study was to provide a summary of the clinical and histological features of ICI-associated epidermal necrosis, with a special focus on factors associated with fatal outcomes in cases of extensive disease. A total of 98 cases, 2 new cases and 96 reported on PubMed and in the literature, of ICI-associated epidermal necrosis were assessed. Development of epidermal necrosis occurred between 1 day and 3 years after starting ICI therapy, with an average onset of 13.8 weeks for patients with limited (< 30% BSA) and 11.3 weeks for those with extensive (≥ 30% BSA) involvement, and a median onset of 5.8 weeks and 4 weeks respectively. A preceding rash was seen in 52 cases and was more common in extensive cases. Mucosal involvement was only reported in 65% of extensive cases but was significantly associated with fatal reactions. Co-administration of cytotoxic chemotherapy was associated with more extensive disease. Recovery was observed in 96% and 65% of those with limited and extensive involvement respectively and no specific therapy was associated with improved survival. Young age was significantly associated with poor outcomes in extensive disease, the average age of surviving patients was 64.5 years old versus 55.1 years old for deceased patients, p < 0.01. Both superficial perivascular and interface/lichenoid inflammatory infiltrates were commonly seen. These findings suggest that ICI-associated epidermal necrosis should be considered a distinct clinical entity from drug-induced SJS/TEN.
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Inibidores de Checkpoint Imunológico , Necrose , Síndrome de Stevens-Johnson , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Síndrome de Stevens-Johnson/patologia , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/imunologia , Síndrome de Stevens-Johnson/diagnóstico , Necrose/induzido quimicamente , Epiderme/patologia , Epiderme/efeitos dos fármacos , Epiderme/imunologia , Pessoa de Meia-Idade , Feminino , Masculino , Idoso , AdultoRESUMO
Diabetic foot ulcers (DFUs) represent an important clinical problem resulting in significant morbidity and mortality. Ongoing translational research studies strive to better understand molecular/cellular basis of DFU pathology that may lead to identification of novel treatment protocols. Tissue at the non-healing wound edge has been identified as one of major contributors to the DFU pathophysiology that provides important tool for translational and clinical investigations. To evaluate quality of tissue specimens and their potential use, we obtained 81 DFU specimens from 25 patients and performed histological analyses, immunohistochemistry and RNA quality assessments. We found that depth of the collected specimen is important determinant of research utility, and only specimens containing a full-thickness epidermis could be utilized for immunohistochemistry and RNA isolation. We showed that only two-thirds of collected specimens could be utilized in translational studies. This attrition rate is important for designs of future studies involving tissue specimen collection from DFU.
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Desbridamento/métodos , Complicações do Diabetes , Pé Diabético/cirurgia , Pele/patologia , Manejo de Espécimes/normas , Pesquisa Translacional Biomédica/normas , Adulto , Biomarcadores/metabolismo , Derme/metabolismo , Derme/patologia , Pé Diabético/metabolismo , Pé Diabético/patologia , Epiderme/metabolismo , Epiderme/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-myc/metabolismo , Pele/metabolismoRESUMO
Chronic lower extremity ulcers are a significant burden on patients and health care systems worldwide. Although relatively common, these wounds can be difficult to treat and present a challenge to physicians. Treatment has often been based on anecdotal accounts; however, there is a growing emphasis on using evidence-based conclusions to guide clinical decisions. In this review article, the standard of care and adjuvant therapies of venous leg ulcers and diabetic foot ulcers are presented from an evidence-based perspective.
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Prática Clínica Baseada em Evidências , Úlcera da Perna/terapia , Antibacterianos/uso terapêutico , Bandagens , Doença Crônica , Desbridamento , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Oxigenoterapia Hiperbárica , Controle de Infecções , Tratamento de Ferimentos com Pressão NegativaAssuntos
Epiderme/transplante , Piebaldismo/cirurgia , Transplante de Pele/métodos , Adolescente , Feminino , HumanosRESUMO
Limited information is available on the drug-drug interactions of natural supplements in dermatology. Many natural supplements are available over the counter, but drug-drug interactions can occur. This study reviews the clinical use and drug interactions of six natural supplements commonly recommended in dermatology: nicotinic acid (nicotinamide), polypodium leucotomos (heliocare), turmeric, horse chestnut seed extract, zinc, and N-acetylcysteine. We reviewed the drug-drug interactions of each supplement using the PubMed database and IBM Micromedex. For nicotinic acid, zinc, horse chestnut, and N-acetylcysteine, IBM Micromedex generated 11, 23, one, and two results, respectively. Further review of literature from PubMed identified two drug interactions with polypodium leucotomos, two with turmeric, and two more with zinc. Notable interactions included an increased risk of myopathy and rhabdomyolysis when nicotinic acid is taken by patients using statins, an increased risk of bleeding associated with horse chestnut seed, especially when used in combination with warfarin, and reduced plasma concentration in many drugs when taken with zinc. Furthermore, N-acetylcysteine may interfere with concentrations of other medications used in the psychiatric setting, and polypodium leucotomos and turmeric may interfere with the CYP metabolic pathway, which may affect drugs metabolized by this pathway. Prior to recommending a treatment, dermatologists should foster awareness of these interactions. In order to advance the practice as a whole, research should continue to evaluate the drug interactions of these natural supplements.