RESUMEN
BACKGROUND: Impaired immunity may drive the increased incidence and aggression of cutaneous squamous cell carcinoma (cSCC) in patients with hematologic malignancy; however, precise mechanisms and prognostic biomarkers remain undefined. CD73 maintains elevated immunosuppressive adenosine levels and is associated with poor prognosis in several tumor microenvironments. OBJECTIVE: Identify poor outcome biomarkers in patients with cSCC and hematologic malignancy. MATERIALS AND METHODS: Differentially expressed genes in tumors from patients with hematologic malignancy experiencing good (n = 8) versus poor (n = 7) outcomes were identified by NanoString analysis. Results were validated at the protein level using CD73 immunohistochemistry in cSCC patients with (n = 38) and without (n = 29) hematologic malignancy. RESULTS: Forty-eight genes were differentially expressed in tumors from patients with hematologic malignancy experiencing good versus poor outcomes. CD73 gene expression was >2-fold higher in patients with poor versus good outcomes or normal skin. Significantly increased CD73 protein levels were observed in cSCC tumors with poor versus good outcomes from patients with hematologic malignancies (p < .01), whereas no differences were noted in tumors with poor versus good outcomes from patients without hematologic malignancies (p = .49). CONCLUSION: CD73 is highly expressed in poor prognosis cSCC from patients with hematologic malignancy and may represent a useful biomarker and potential therapeutic target.
Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Melanoma/diagnóstico , Autoexamen/psicología , Neoplasias Cutáneas/diagnóstico , Piel/patología , Factores de Edad , Anciano , Detección Precoz del Cáncer/psicología , Detección Precoz del Cáncer/estadística & datos numéricos , Femenino , Humanos , Masculino , Melanoma/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Aceptación de la Atención de Salud/estadística & datos numéricos , Factores de Riesgo , Neoplasias Cutáneas/patología , Factores de TiempoRESUMEN
BACKGROUND: Atopic dermatitis (AD) is a common, chronic type 2 inflammatory skin disease, typically starting in infancy, with increased risk for subsequent extracutaneous atopic morbidities. Dupilumab is the first biologic agent targeting type 2 inflammation approved by the U.S. Food and Drug Administration (USFDA); it was licensed in 2017 for adults with moderate to severe AD and 2 years later for adolescents. Systemic treatment for pediatric AD remains a significant unmet medical need. OBJECTIVE: To analyze off-label use of dupilumab in children with AD. METHODS: Multicenter retrospective review that evaluated children who were prescribed dupilumab for moderate to severe AD. RESULTS: One hundred eleven of 124 patients (89.5%) gained access to dupilumab after a mean of 9 weeks. The dosing range was 4 to 15.5 mg/kg for the loading dose and 2.0 to 15.3 mg/kg every other week for maintenance. The range was widest for 6- to 11-year-olds and was related to use of either full or half of adult dosing. Associated morbidities, treatment response, and adverse events were comparable to those in previous adolescent and adult trials. LIMITATIONS: The retrospective design of the study limited uniform data collection. CONCLUSION: Access to dupilumab was achievable for the majority of children after a mean 9-week delay because of insurance payment denial. This review supports dupilumab response and tolerability in children. Optimal dosing for patients younger than 12 years has not been defined. Availability of the drug in 2 different concentrations is an important safety issue.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Uso Fuera de lo Indicado/estadística & datos numéricos , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
New-onset psoriasis in patients receiving tumor necrosis factor inhibitors is well recognized in children and adults. We describe three children who underwent cardiac transplantation and developed an analogous form of paradoxic eczema occurring 2-48 months after starting systemic tacrolimus, a drug widely used topically to treat eczema. Anecdotal reports and our experience suggest that tacrolimus taper with alternative systemic antirejection immunosuppressant may lead to skin clearance. Pending additional insight, treatment should include optimizing skin barrier function, minimizing microbial and allergic triggers, and coordinating care to choose the best-tolerated systemic immunosuppressant regimen at the lowest effective dose.
