RESUMO
BACKGROUND: Lipid metabolism plays essential roles in skin barrier formation and the regulation of skin inflammation. Moreover, lipid homeostasis regulates skin melanogenesis, although the underlying mechanism remains largely unknown. Sterol regulatory element binding protein 1 (SREBP-1) is a key transcription factor essential for cellular lipid metabolism. Loss-of-function variants in SREBF1 are responsible for autosomal-dominant ichthyosis follicularis, alopecia, and photophobia syndrome, emphasizing the significance of lipid homeostasis in skin keratinization. OBJECTIVES: To identify the genetic basis of a new entity featuring diffuse skin hyperpigmentation with congenital cataracts, and to unravel the underlying mechanism for the pathogenesis of the SREBF1 variant. METHODS: Whole-exome sequencing was performed to identify the underlying genetic variants. Quantitative PCR, western blot, and immunofluorescent staining were employed to assess the expression and the subcellular localization of the SREBF1 variant. The transcriptional activity of the mutant SREBP-1 was determined by luciferase reporter assay. A transgenic zebrafish model was constructed. RESULTS: Two patients of different ethnicities presented with generalized skin hyperpigmentation with skin xerosis, congenital cataracts, and extracutaneous symptoms. We identified a de novo nonsense variant c.1289C>A (p.Ser430*) in the SREBF1 gene in both patients. The variant encoded a truncated protein which showed preferential nucleus localization, in contrast to wild-type SREBP-1 which is mainly localized in cytoplasm in sterol-sufficient conditions. Luciferase reporter assay revealed that the Ser430* mutant exhibited an enhanced transcriptional activity. The primary cultured melanocytes from the patient showed increased melanin synthesis compared to those from normal controls. The Ser430* transgenic zebrafish model exhibited more black spots, along with upregulated expression of melanogenic genes at 35 days post-fertilization. CONCLUSIONS: We demonstrated that a gain-of-function variant in SREBF1 caused a previously undescribed disorder characterized by generalized skin hyperpigmentation and congenital cataracts. Our study reveals the involvement of SREBP-1 in melanogenesis and lens development and paves the way for developing novel therapeutic targets for skin dyspigmentation or cataracts.
RESUMO
BACKGROUND: MEK inhibitors cause a wide spectrum of mucocutaneous toxicities which can delay or interrupt life-saving therapy. PURPOSE: To summarize the morphology, incidence, and clinical presentation of mucocutaneous toxicities from MEK inhibitors via a scoping review of the literature. METHODS: We conducted a scoping review of the published literature, including clinical trials, retrospective and prospective studies, reviews, and case reports and series. All included literature was analyzed by a panel of pediatric and adult oncodermatologists. RESULTS: Of 1626 initial citations, 227 articles met final inclusion criteria. Our review identified follicular reactions, ocular toxicities, xerosis, eczematous dermatitis, edema, and paronychia as the most common mucocutaneous side effects from MEK inhibitor therapy. Grade 1 and 2 reactions were the most prevalent and were typically managed while continuing treatment; however, grade 3 toxicities requiring dose reductions or treatment interruptions were also reported. CONCLUSION: Mucocutaneous toxicities to MEK inhibitor therapy are common and most often mild in severity. Early recognition and treatment can mitigate disruptions in oncologic therapy.
Assuntos
Inibidores de Proteínas Quinases , Humanos , Inibidores de Proteínas Quinases/efeitos adversos , Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Índice de Gravidade de Doença , Toxidermias/etiologiaRESUMO
Dermatologists routinely see patients with inflammatory skin conditions and aesthetic concerns that involve substantial psychological comorbidity. However, most dermatologists do not receive formal training in this area, and many are unsure how to best help treat certain patients holistically. Body dysmorphic disorder (BDD) is a common and distressing psychiatric condition that disproportionately impacts dermatology patients, including patients living with chronic inflammatory skin conditions such as acne and atopic dermatitis. BDD is characterized by preoccupation with nonexistent or minimally noticeable flaws in physical appearance that cause clinically significant distress or impairment in functioning. Adolescent populations may be particularly vulnerable to clinically significant body image dissatisfaction, including BDD, due to the high prevalence of acne and the pervasive role of social media platforms. The rise of social media may exacerbate body image issues through repetitive exposure to idealized and often unrealistic beauty standards. Though screening questionnaires can assist dermatologists in recognizing BDD, dermatologists must collaborate with mental health providers to provide comprehensive care to vulnerable patients, including adolescents.J Drugs Dermatol. 2024;23(7):545-550. doi:10.36849/JDD.8156.
Assuntos
Transtornos Dismórficos Corporais , Humanos , Transtornos Dismórficos Corporais/psicologia , Transtornos Dismórficos Corporais/diagnóstico , Transtornos Dismórficos Corporais/terapia , Transtornos Dismórficos Corporais/epidemiologia , Adolescente , Imagem Corporal/psicologia , Acne Vulgar/psicologia , Acne Vulgar/diagnóstico , Acne Vulgar/terapia , Insatisfação Corporal/psicologia , Dermatologia/métodos , Mídias Sociais , Dermatite Atópica/psicologia , Dermatite Atópica/diagnóstico , Dermatite Atópica/terapia , Dermatologistas/psicologiaRESUMO
Poliosis is defined as the absence of melanin in hair, and hair graying typically occurs with hair melanin reduction. Poliosis can occur at any age but presents in childhood in certain genetic and acquired conditions, with many families seeking evaluation from a pediatric dermatologist. Poliosis presents as white hair typically restricted to a certain location of the scalp. Children may also present with a reduction of expected hair pigmentation, referred to as pigment dilution, or the development of hair graying. This review aims to provide a streamlined diagnostic approach for pediatric dermatologists when presented with these hair findings. Poliosis should be recognized as a potential diagnostic feature or initial sign in many syndromes and thus can guide clinicians in diagnosing and managing conditions earlier in a patient's care. Since many of the genetic and acquired conditions that present with poliosis or hair pigment dilution have extracutaneous manifestations, early diagnosis is vital in establishing multidisciplinary care.
Assuntos
Doenças do Cabelo , Hipopigmentação , Transtornos da Pigmentação , Humanos , Criança , Melaninas , Cabelo , Transtornos da Pigmentação/diagnóstico , Doenças do Cabelo/diagnóstico , Cor de CabeloRESUMO
Across the world, there are varied cultural practices applied in the newborn period that pediatric dermatologists need to be familiar with. This report details a 9-day-old girl who presented with black, spike-like hairs across the back after her mother had been rubbing breast milk on her back in a circular motion for the first 7 days of life. On dermatoscopic exam, these lesions were found to be tight bundles of lanugo hairs, consistent with a diagnosis of knotted lanugo. Improved understanding of cultural practices and newborn skin care routines is critical for diagnosis, treatment, and counseling.
Assuntos
Cabelo , Pele , Feminino , Recém-Nascido , Humanos , Criança , Cabelo/patologia , Mães , Dermoscopia , Higiene da PeleRESUMO
The rate of pediatric hospitalization for cutaneous pathology has been increasing in recent years, often requiring the expertise of consulting pediatric dermatologists; however, the infrastructure of inpatient pediatric dermatology consultative services remains poorly characterized. We sought to assess the structure, consult volume, physician compensation, and utilization of teledermatology in pediatric dermatology inpatient services to better understand the current care model. Our survey of 118 pediatric dermatologists revealed that 89% of respondents see between 1 and 10 new consults per week, 39% perform all inpatient consults including evening and weekends without assistance from other providers, 71% do not have protected time during the week to provide inpatient consultations, and only 10% receive financial compensation via stipend. By highlighting both the high demand for pediatric consultative dermatology as well as the significant burden placed on these providers by existing practice models, we hope to encourage a reappraisal of the current infrastructure of pediatric inpatient dermatology to increase structural and financial support for this vital service.
Assuntos
Dermatologia , Humanos , Criança , Estados Unidos , Pele , Inquéritos e Questionários , Recursos Humanos , Encaminhamento e ConsultaRESUMO
Monogenic diseases of immune dysregulation should be considered in the evaluation of children presenting with recurrent neutrophilic dermatoses in association with systemic signs of inflammation, autoimmune disease, hematologic abnormalities, and opportunistic or recurrent infections. We report the case of a 2-year-old boy presenting with a neutrophilic dermatosis, found to have a novel likely pathogenic germline variant of the IKAROS Family Zinc Finger 1 (IKZF1) gene; the mutation likely results in a loss of function dimerization defective protein based on reports and studies of similar variants. IKZF1 variants could potentially lead to aberrant neutrophil chemotaxis and development of neutrophilic dermatoses. Long-term surveillance is required to monitor the development of hematologic malignancy, autoimmunity, immunodeficiency, and infection in patients with pathogenic IKZF1 germline variants.
Assuntos
Fator de Transcrição Ikaros , Humanos , Masculino , Pré-Escolar , Fator de Transcrição Ikaros/genética , Síndrome de Sweet/genética , Síndrome de Sweet/diagnóstico , Neutrófilos , Doenças Hereditárias Autoinflamatórias/genética , Doenças Hereditárias Autoinflamatórias/diagnóstico , Mutação em Linhagem GerminativaRESUMO
PURPOSE OF REVIEW: This review provides updates in the evaluation and management of key dermatologic diseases encountered in the hospitalized child. RECENT FINDINGS: Our understanding of dermatologic disorders in children continues to evolve. Staphylococcal scalded skin syndrome (SSSS) is a potentially severe blistering disorder typically seen in children under the age of 4 with an incidence that is increasing in the United States. Recent research has highlighted that the majority of cases are due to methicillin-sensitive Staphylococcus aureus (MSSA) and most patients can be adequately managed with beta-lactams. Toxic epidermal necrolysis (TEN) is one of the most feared dermatologic disorders. Currently, there is a lack of consensus on the most efficacious first-line systemic therapy. Etanercept is increasingly being used based on studies showing a shorter time to re-epithelization and decreased mortality. Lastly, the COVID-19 pandemic introduced the novel inflammatory condition multisystem inflammatory syndrome in children (MIS-C) in which approximately three out of four children present with a mucocutaneous eruption. Early recognition of the dermatologic features of MIS-C is important in potentially establishing a diagnosis and differentiating it from the many other causes of childhood fever and rash. SUMMARY: There are no clear universal treatment guidelines for these rare diagnoses, and therefore, clinicians must remain informed of the latest findings in diagnosis and therapeutics.
Assuntos
COVID-19 , Dermatologia , Criança , Humanos , Estados Unidos/epidemiologia , Pacientes Internados , Pandemias , COVID-19/epidemiologiaRESUMO
Pediatric oncologists are increasingly involved in the management of benign vascular tumors and their associated life-threatening complications. Hemangiomas are the most common referring diagnosis to multidisciplinary vascular anomalies clinics. However, as contemporary research has revealed, hemangiomas are not a single, easily defined entity but rather a diverse set of related vascular tumors, each having a unique natural history, growth pattern, and response to therapy. This manuscript seeks to illustrate how we evaluate and manage these complex tumors, their complications, and associated syndromes, while remaining ever vigilant for malignant hemangioma mimickers such as soft tissue sarcomas and congenital leukemia.
Assuntos
Hemangioma , Neoplasias de Tecidos Moles , Neoplasias Vasculares , Criança , Hemangioma/complicações , Hemangioma/diagnóstico , Hemangioma/terapia , Humanos , Lactente , Neoplasias de Tecidos Moles/complicações , SíndromeRESUMO
PURPOSE OF REVIEW: Photograph-based social media use among children and adolescents has skyrocketed over the past decade, raising concerns about the implications for self-confidence and behavior in this population. Social media 'challenges' encourage participants to complete potentially dangerous tasks while sharing their completion of the tasks on social media. Many of these challenges affect the skin and lead to recognizable findings on physical examination. This review discusses the history of prominent social media challenges and their effects on the skin. Attention is also given to the effects of social media trends on self-confidence and body image in children and adolescents. RECENT FINDINGS: Over the past several years, there have been several notable social media trends that can harm the skin. These include the Kylie Jenner lip challenge, salt and ice challenge, deodorant challenge, eraser challenge, fire challenge, and hot water challenge. Participation in these challenges can cause morbidity in children and adolescent that should be recognized by clinicians. SUMMARY: Social media has become an important platform for communication and self-expression among children and adolescents. Pediatricians should remain aware of social trends in this age group and look out for cutaneous findings that may signal dangerous behavior on social media.
Assuntos
Comportamento do Adolescente , Dermatopatias , Mídias Sociais , Adolescente , Criança , Humanos , Polissorbatos , Pele , Dermatopatias/diagnóstico , Dermatopatias/epidemiologiaRESUMO
BACKGROUND/OBJECTIVES: To investigate the evaluation and management of atopic dermatitis (AD) in the pediatric emergency department (PED). METHODS: This retrospective chart review was performed at the PED of a single institution and examined data from 2012 to 2017. Of 335 visits from patients 18 years and younger coded for AD, 167 visits with documented findings that supported a diagnosis of AD according to guidelines from the American Academy of Dermatology were included. RESULTS: The mean age of presentation was 6.3 years (standard deviation [SD]: 5.9). Of 11 patients with multiple visits, the mean between-visit interval was 31 days (SD: 41). Topical corticosteroids (TCSs) were not prescribed or recommended in 63/167 visits. In an additional 46/167 visits, over-the-counter topical hydrocortisone was recommended. Of prescribed TCS, the mean TCS class was 5.5 (SD: 1.9). 61/104 recommended or prescribed TCSs were weak (Class 7), the most likely used class (P < .001). Dermatology consultation was requested in 14/167 visits and was associated with higher rates of TCS prescriptions (13/14 vs 91/153, P = .018), a higher mean class of TCS prescribed (3.1 vs 5.9, P < .001), higher prescription rates of systemic antibiotics (8/14 vs 10/153, P < .001), and higher recommendation rates for emollient usage (10/14 vs 46/153, P = .005). CONCLUSIONS: Most patients presenting to the PED for AD were either not prescribed a TCS or were prescribed a weak TCS, often one that is over-the-counter. While there may be a variety of explanations for these findings, it is possible they reveal a practice gap regarding AD management in the PED.
Assuntos
Dermatite Atópica , Corticosteroides/uso terapêutico , Criança , Dermatite Atópica/tratamento farmacológico , Serviço Hospitalar de Emergência , Emolientes/uso terapêutico , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND/OBJECTIVE: Papular scars are a recently described clinical phenotype of acne scarring characterized by papules occurring on the nose and chin. We have observed a similar presentation of nasal papules among patients seen in our clinic for acne and sought to further characterize the clinical and histopathological characteristics of this entity. METHODS: In this single-site case series, a retrospective review of electronic medical records of patients with nasal papules in association with acne vulgaris between April 2018 and April 2019 was performed. Clinical and histopathologic findings were recorded. RESULTS: We identified 20 patients who presented with a similar clinical phenotype of predominantly skin-colored, dome-shaped papules concentrated on the nose and chin in association with a history of more classic facial acne vulgaris. Papular lesions were seen predominately in adolescent Hispanic males. Concomitant acne on other areas of the face was identified in 18 patients at presentation while two patients had a history of adolescent acne. Biopsies were performed for five patients. Histopathologic examination demonstrated features of fibrosis and dilated thin-walled blood vessels, typical of angiofibromas. CONCLUSION: We present a series of adolescent patients with large, flesh-colored to erythematous papules seen predominantly on the nose. These lesions are histologically indistinguishable from angiofibromas and may represent an under-recognized yet disfiguring sequela of acne that may disproportionately affect adolescents with skin of color.
Assuntos
Acne Vulgar , Angiofibroma , Acne Vulgar/diagnóstico , Adolescente , Angiofibroma/diagnóstico , Humanos , Masculino , Nariz , Estudos Retrospectivos , PeleRESUMO
Nevus psiloliparus is a rare fatty tissue nevus that is a marker for encephalocraniocutaneous lipomatosis, a neurocutaneous syndrome with ocular and central nervous system anomalies. Clinically, nevus psiloliparus is often described as a congenital alopecia and appears as an irregularly shaped, circumscribed area of alopecia on the scalp. Histopathology demonstrates a near-complete absence of mature hair follicles with preservation of arrector pili muscles and mature adipocytes within the dermis. The pathogenesis of nevus psiloliparus may be related to mosaic mutations in fibroblast growth factor receptor 1. Herein we report the histopathological features of a nevus psiloliparus in an 11-year-old girl diagnosed from transverse sections, which show "shadow" follicular units characterized by columns of loosely arranged collagen and a relative paucity of elastic fibers.
Assuntos
Alopecia/patologia , Lipomatose/patologia , Dermatoses do Couro Cabeludo/patologia , Criança , Feminino , HumanosRESUMO
Photograph editing has been present for centuries, but the past decade has seen an unprecedented rise in the practice, particularly on social media platforms. Common filters are able to soften complexion, remove blemishes, and even reshape facial features. Children and adolescents with skin conditions may find solace in using these applications to mask their disease online, but there is increasing concern about negative overall body image among those who filter their photographs. Pediatric dermatologists should remain aware of the practice of photograph editing among young people and consider asking patients about their social media presence.
Assuntos
Dermatopatias , Adolescente , Criança , Dedos , Humanos , Pele , Mídias SociaisRESUMO
BRAF inhibitor-induced neutrophilic panniculitis is a rare event that is well-characterized in adults undergoing therapy for metastatic melanoma. To date, there are very few reports of this event in children undergoing BRAF inhibitor therapy for low-grade gliomas, all of which were seen with vemurafenib. We report a case of dabrafenib-induced neutrophilic panniculitis in a 9-year-old girl that manifested within several weeks of initiating dual BRAF-MEK inhibitor therapy for glioblastoma multiforme. This case highlights neutrophilic panniculitis as a side effect of dabrafenib in children and serves as a reminder to consider cutaneous side effects of BRAF inhibitors as they are increasingly used to treat children with primary brain tumors.
Assuntos
Glioblastoma , Paniculite , Neoplasias Cutâneas , Protocolos de Quimioterapia Combinada Antineoplásica , Criança , Feminino , Glioblastoma/tratamento farmacológico , Humanos , Imidazóis , Quinases de Proteína Quinase Ativadas por Mitógeno/uso terapêutico , Oximas/efeitos adversos , Paniculite/induzido quimicamente , Paniculite/diagnóstico , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
Infectious panniculitis from hematogenous spread is uncommon and usually occurs in immunocompromised patients. Dissemination of gram-positive organisms to the subcutaneous tissue is rare with only several reports of disseminated panniculitis caused by Streptococcal species. We report a case of an immunocompetent 2-year-old boy presenting with diffuse neutrophilic panniculitis arising from methicillin-resistant Staphylococcus aureus septicemia. This case represents a highly atypical manifestation of severe MRSA infection and serves as a reminder to consider MRSA as a cause of disseminated neutrophilic panniculitis, particularly in high-risk populations.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Paniculite , Dermatopatias Infecciosas , Infecções Estafilocócicas , Antibacterianos , Pré-Escolar , Humanos , Hospedeiro Imunocomprometido , Masculino , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológicoRESUMO
BACKGROUND/OBJECTIVES: The COVID-19 pandemic has raised questions about the approach to management of systemic immunosuppressive therapies for dermatologic indications in children. Change to: Given the absence of data to address concerns related to SARS-CoV-2 infection and systemic immunosuppressive therapies in an evidence-based manner, a Pediatric Dermatology COVID-19 Response Task Force (PDCRTF) was assembled to offer time-sensitive guidance for clinicians. METHODS: A survey was distributed to an expert panel of 37 pediatric dermatologists on the PDCRTF to assess expert opinion and current practice related to three primary domains of systemic therapy: initiation, continuation, and laboratory monitoring. RESULTS: Nearly all respondents (97%) reported that the COVID-19 pandemic had impacted their decision to initiate immunosuppressive medications. The majority of pediatric dermatologists (87%) reported that they were pausing or reducing the frequency of laboratory monitoring for certain immunosuppressive medications. In asymptomatic patients, continuing therapy was the most popular choice across all medications queried. The majority agreed that patients on immunosuppressive medications who have a household exposure to COVID-19 or test positive for new infection should temporarily discontinue systemic and biologic medications, with the exception of systemic steroids, which may require tapering. CONCLUSIONS: The ultimate decision regarding initiation, continuation, and laboratory monitoring of immunosuppressive therapy during the pandemic requires careful deliberation, consideration of the little evidence available, and discussion with families. Consideration of an individual's adherence to COVID-19 preventive measures, risk of exposure, and the potential severity if infected must be weighed against the dermatological disease, medication, and risks to the patient of tapering or discontinuing therapies.
Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Terapia de Imunossupressão , Pneumonia Viral/epidemiologia , Dermatopatias/terapia , COVID-19 , Criança , Tomada de Decisão Clínica , Consenso , Humanos , Imunossupressores/uso terapêutico , Pandemias , SARS-CoV-2 , Dermatopatias/etiologiaRESUMO
Vogt-Koyanagi-Harada (VKH) disease is uncommon in the pediatric population and can have an aggressive course with serious visual sequelae. A 12-year-old Han Chinese American female, who presented with mild headaches and panuveitis with diffuse serous retinal detachments, was diagnosed with VKH. Despite treatment with a combination of high-dose systemic corticosteroids, intravitreal triamcinolone injection, and mycophenolate mofetil, ocular inflammation was inadequately controlled. Addition of adalimumab allowed for inflammation remission, improvement of vision, and tapering of systemic corticosteroids. Escalation of immunosuppression until remission appears to be critical in this population. Further research is needed to understand the complex pathophysiology of VKH and investigation for similar efficacy of other anti-tumor necrosis factor-alpha agents will need to be performed.
Assuntos
Adalimumab/administração & dosagem , Pan-Uveíte/tratamento farmacológico , Síndrome Uveomeningoencefálica/diagnóstico , Síndrome Uveomeningoencefálica/tratamento farmacológico , Criança , Quimioterapia Combinada , Feminino , Angiofluoresceinografia , Cefaleia/etiologia , Humanos , Ácido Micofenólico/administração & dosagem , Pan-Uveíte/etiologia , Indução de Remissão , Tomografia de Coerência Óptica , Triancinolona/administração & dosagem , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Acuidade VisualRESUMO
This report describes a case of chronic neutrophilic urticarial dermatosis as a presenting feature of systemic juvenile idiopathic arthritis. When encountered in children, neutrophilic urticarial dermatosis should raise suspicion of autoimmune or autoinflammatory disease.