RESUMEN
Cases of new-onset pernio and recurrences in our cohort align tightly with trends in mean 7-day COVID-19 positivity in Wisconsin and mean temperature in Madison, Wisconsin by month.
Asunto(s)
COVID-19 , Eritema Pernio , Antivirales , Eritema Pernio/diagnóstico , Eritema Pernio/epidemiología , Eritema Pernio/genética , Humanos , Interferones , Estudios Prospectivos , SARS-CoV-2/genéticaRESUMEN
Mosaic KRAS variants and other RASopathy genes cause oculoectodermal, encephalo-cranio-cutaneous lipomatosis, and Schimmelpenning-Feuerstein-Mims syndromes, and a spectrum of vascular malformations, overgrowth and other associated anomalies, the latter of which are only recently being characterized. We describe eight individuals in total (six unreported cases and two previously reported cases) with somatic KRAS variants and variably associated features. Given the findings of somatic overgrowth (in seven individuals) and vascular or lymphatic malformations (in eight individuals), we suggest mosaic RASopathies (mosaic KRAS variants) be considered in the differential diagnosis for individuals presenting with asymmetric overgrowth and lymphatic or vascular anomalies. We expand the association with embryonal tumors, including the third report of embryonal rhabdomyosarcoma, as well as novel findings of Wilms tumor and nephroblastomatosis in two individuals. Rare or novel findings in our series include the presence of epilepsy, polycystic kidneys, and T-cell deficiency in one individual, and multifocal lytic bone lesions in two individuals. Finally, we describe the first use of targeted therapy with a MEK inhibitor for an individual with a mosaic KRAS variant. The purposes of this report are to expand the phenotypic spectrum of mosaic KRAS-related disorders, and to propose possible mechanisms of pathogenesis, and surveillance of its associated findings.
Asunto(s)
Anomalías Múltiples/patología , Neoplasias Renales/patología , Mosaicismo , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Malformaciones Vasculares/patología , Tumor de Wilms/patología , Anomalías Múltiples/genética , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Neoplasias Renales/genética , Masculino , Fenotipo , Malformaciones Vasculares/genética , Tumor de Wilms/genéticaRESUMEN
Port-wine birthmarks (PWBs) are progressive vascular malformations with significant disfigurement and psychosocial morbidity; early light-based treatment has shown improved outcomes in the pediatric population. Somatic mosaic mutations underly the progressive nature of PWBs and explain the significant differences in response and heterogeneity of vessel architecture in the pediatric population when compared to the adult cohort. Here, we summarize a review of pediatric specific literature on the various light-based treatment modalities, including pulsed dye laser, near-infrared lasers, and intense pulsed light, providing the various indications, tips, advantages, and disadvantages for the pediatric dermatologist.
Asunto(s)
Láseres de Colorantes , Terapia por Luz de Baja Intensidad , Mancha Vino de Oporto , Adulto , Niño , Estudios de Cohortes , Humanos , Láseres de Colorantes/uso terapéutico , Mancha Vino de Oporto/terapia , Resultado del TratamientoRESUMEN
Melanoma is often managed outside hospital settings, creating the potential for underreporting to cancer registries. To our knowledge, completeness of melanoma capture in cancer registries has not been assessed using external data sources since the 1980s. We evaluated the melanoma capture rate from 1993 to 2009 in a provincial cancer registry. We identified all melanoma diagnoses in pathology reports from a major community laboratory in Ontario, Canada. Pathologically confirmed diagnoses were linked to Ontario Cancer Registry (OCR) records using health insurance numbers. We calculated capture rates as the proportion of patients with melanoma confirmed by a pathology report, with a corresponding melanoma diagnosis in OCR. OCR captured 3,798 of 4,275 (88.8, 95 % confidence interval: 87.9, 89.8 %) invasive melanoma diagnoses over the 17-year period. Annual capture rates of 94 % or higher were found for over half the study period. Among all 29,133 melanoma diagnoses in OCR, 27.6 % were registered based on a pathology report alone, compared with 3.4 % for non-cutaneous malignancies. This suggests that comprehensive capture of melanoma cases by a provincial cancer registry is achievable using source data from community laboratories. There is a need for ongoing validation to ensure data remain accurate and complete to reliably inform clinical care, research, and policy.
Asunto(s)
Melanoma/epidemiología , Sistema de Registros , Hospitales , Humanos , Incidencia , Melanoma/patología , Ontario/epidemiología , Características de la Residencia , Neoplasias Cutáneas , Melanoma Cutáneo MalignoAsunto(s)
Competencia Clínica/estadística & datos numéricos , Cirugía de Mohs/métodos , Percepción , Técnicas de Sutura , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cirugía de Mohs/psicología , Cirujanos/estadística & datos numéricos , Encuestas y Cuestionarios/estadística & datos numéricos , Adulto JovenAsunto(s)
Alérgenos/análisis , Inhibidores de la Calcineurina/efectos adversos , Dermatitis Alérgica por Contacto/etiología , Glucocorticoides/efectos adversos , Inhibidores de Fosfodiesterasa 4/efectos adversos , Administración Tópica , Alérgenos/efectos adversos , Inhibidores de la Calcineurina/química , Glucocorticoides/química , Humanos , Inhibidores de Fosfodiesterasa 4/químicaRESUMEN
HIV testing is mandatory for individuals wishing to immigrate to Canada. Since the Designated Medical Practitioners (DMPs) who perform these tests may have varying experience in HIV and time constraints in their clinical practices, there may be variability in the quality of pre- and posttest counseling provided. We surveyed DMPs regarding HIV testing, counseling, and immigration inadmissibility. A 16-item survey was mailed to all DMPs across Canada (N = 203). The survey inquired about DMP characteristics, knowledge of HIV, attitudes and practices regarding inadmissibility and counseling, and interest in continuing medical education. There were a total of 83 respondents (41%). Participants frequently rated their knowledge of HIV diagnostics, cultural competency, and HIV/AIDS service organizations as "fair" (40%, 43%, and 44%, respectively). About 25%, 46%, and 11% of the respondents agreed/strongly agreed with the statements "HIV infected individuals pose a danger to public health and safety," "HIV-positive immigrants cause excessive demand on the healthcare system," and "HIV seropositivity is a reasonable ground for denial into Canada," respectively. Language was cited as a barrier to counseling, which focused on transmission risks (46% discussed this as "always" or "often") more than coping and social support (37%). There was a high level of interest (47%) in continuing medical education in this area. There are areas for improvement regarding DMPs' knowledge, attitudes, and practices about HIV infection, counseling, and immigration criteria. Continuing medical education and support for DMPs to facilitate practice changes could benefit newcomers who test positive through the immigration process.
Asunto(s)
Emigración e Inmigración , Médicos Generales , Infecciones por VIH/diagnóstico , Infecciones por VIH/prevención & control , Encuestas Epidemiológicas , Examen Físico , Adulto , Canadá , Atención a la Salud , Emigración e Inmigración/estadística & datos numéricos , Femenino , Infecciones por VIH/epidemiología , Seropositividad para VIH/diagnóstico , Humanos , Masculino , Tamizaje MasivoRESUMEN
Elevated pernio incidence was observed during the COVID-19 pandemic. This prospective study enrolled subjects with pandemic-associated pernio in Wisconsin and Switzerland. Because pernio is a cutaneous manifestation of the interferonopathies, and type I interferon (IFN-I) immunity is critical to COVID-19 recovery, we tested the hypothesis that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated IFN-I signaling might underlie some pernio cases. Tissue-level IFN-I activity and plasmacytoid dendritic cell infiltrates were demonstrated in 100% of the Wisconsin cases. Across both cohorts, sparse SARS-CoV-2 RNA was captured in 25% (6/22) of biopsies, all with high inflammation. Affected patients lacked adaptive immunity to SARS-CoV-2. A hamster model of intranasal SARS-CoV-2 infection was used as a proof-of-principle experiment: RNA was detected in lungs and toes with IFN-I activity at both the sites, while replicating virus was found only in the lung. These data support a viral trigger for some pernio cases, where sustained local IFN-I activity can be triggered in the absence of seroconversion.
RESUMEN
BACKGROUND: Consumers seek "clean" and "natural" products based on their perception of safety. However, there is no standard, scientific basis, or regulatory oversight in the marketing or ingredient use for "clean" products. OBJECTIVE: The aim of this study was to determine the prevalence of allergenic ingredients in "clean" products. METHODS: Target and Walgreens Web sites were queried for "clean" products with inclusion of 1470 products. Ingredient lists were analyzed for potential allergens. Analysis included descriptive statistics and χ2 test. RESULTS: The most common allergens were fragrances/botanicals (1218/1470, 82.9%), phenoxyethanol (591/1470, 40.2%), tocopherol (545/1470, 40.2%), benzoic acid and benzoates (434/1470, 29.5%), propylene glycol (369/1470, 25.1%), alkyl glucosides (305/1470, 20.7%), ethylhexylglycerin (304/1470, 20.7%), cetyl alcohol (282/1470, 19.2%), cocamidopropyl betaine (258/1470, 17.6%), and benzyl alcohol (232/1470, 15.8%). Among fragrances/botanicals, the most common ingredients found were fragrance/perfume/aroma (911/1470, 68.2%), citrus derivatives (375/1470, 25.5%), linalool (305/1470, 20.7%), limonene (279/1470, 19.0%), and benzyl alcohol (231/1470, 15.7%). A total of 93.8% of the products (1379/1470) contained at least 1 potential allergen. CONCLUSIONS: Most "clean" products contain a potential allergen, predominately fragrances and botanicals.
Asunto(s)
Dermatitis Alérgica por Contacto , Perfumes , Alérgenos/efectos adversos , Belleza , Alcoholes Bencílicos , Dermatitis Alérgica por Contacto/epidemiología , Dermatitis Alérgica por Contacto/etiología , Humanos , Perfumes/efectos adversos , PrevalenciaRESUMEN
Despite thousands of reported patients with pandemic-associated pernio, low rates of seroconversion and PCR positivity have defied causative linkage to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pernio in uninfected children is associated with monogenic disorders of excessive IFN-1 immunity, whereas severe COVID-19 pneumonia can result from insufficient IFN-1. Moreover, SARS-CoV-2 spike protein and robust IFN-1 response are seen in the skin of patients with pandemic-associated pernio, suggesting an excessive innate immune skin response to SARS-CoV-2. Understanding the pathophysiology of this phenomenon may elucidate the host mechanisms that drive a resilient immune response to SARS-CoV-2 and could produce relevant therapeutic targets.
Asunto(s)
COVID-19/inmunología , Eritema Pernio/inmunología , SARS-CoV-2/fisiología , Animales , COVID-19/complicaciones , Eritema Pernio/complicaciones , Humanos , Inmunidad Innata , Interferón Tipo I/metabolismoAsunto(s)
Erupciones por Medicamentos , Liquen Plano , Erupciones Liquenoides , Prostaglandinas F Sintéticas , Humanos , Latanoprost/efectos adversos , Ojo , Erupciones por Medicamentos/diagnóstico , Erupciones por Medicamentos/etiología , Soluciones Oftálmicas/efectos adversos , Erupciones Liquenoides/inducido químicamente , Erupciones Liquenoides/diagnóstico , Antihipertensivos/efectos adversos , Prostaglandinas F Sintéticas/efectos adversosRESUMEN
Importance: Keratinocyte carcinoma (nonmelanoma skin cancer) accounts for substantial burden in terms of high incidence and health care costs but is excluded by most cancer registries in North America. Administrative health insurance claims databases offer an opportunity to identify these cancers using diagnosis and procedural codes submitted for reimbursement purposes. Objective: To apply recursive partitioning to derive and validate a claims-based algorithm for identifying keratinocyte carcinoma with high sensitivity and specificity. Design, Setting, and Participants: Retrospective study using population-based administrative databases linked to 602â¯371 pathology episodes from a community laboratory for adults residing in Ontario, Canada, from January 1, 1992, to December 31, 2009. The final analysis was completed in January 2016. We used recursive partitioning (classification trees) to derive an algorithm based on health insurance claims. The performance of the derived algorithm was compared with 5 prespecified algorithms and validated using an independent academic hospital clinic data set of 2082 patients seen in May and June 2011. Main Outcomes and Measures: Sensitivity, specificity, positive predictive value, and negative predictive value using the histopathological diagnosis as the criterion standard. We aimed to achieve maximal specificity, while maintaining greater than 80% sensitivity. Results: Among 602â¯371 pathology episodes, 131â¯562 (21.8%) had a diagnosis of keratinocyte carcinoma. Our final derived algorithm outperformed the 5 simple prespecified algorithms and performed well in both community and hospital data sets in terms of sensitivity (82.6% and 84.9%, respectively), specificity (93.0% and 99.0%, respectively), positive predictive value (76.7% and 69.2%, respectively), and negative predictive value (95.0% and 99.6%, respectively). Algorithm performance did not vary substantially during the 18-year period. Conclusions and Relevance: This algorithm offers a reliable mechanism for ascertaining keratinocyte carcinoma for epidemiological research in the absence of cancer registry data. Our findings also demonstrate the value of recursive partitioning in deriving valid claims-based algorithms.