RESUMEN
Tyrosine kinase inhibitors (TKIs) have emerged as a new frontier of cancer therapy. These agents include inhibitors of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), BRAF, mitogenactivated protein kinase kinase (also referred to as MEK), bcrabl, cKIT, plateletderived growth factor (PDGFR), fibroblast growth factor receptor (FGFR), anaplastic lymphoma kinase (ALK) and vascular endothelial growth factor (VEGF). Along with the evolving applications of TKIs, there has been an increased recognition of the breadth of potential cutaneous toxicities to these agents. In this review, we provide an overview of potentially lifethreatening severe cutaneous adverse reactions (SCARs) that may occur during therapy with TKIs. These toxicities include StevensJohnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP).
Asunto(s)
Erupciones por Medicamentos/etiología , Inhibidores de Proteínas Quinasas/efectos adversos , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Erupciones por Medicamentos/diagnóstico , Erupciones por Medicamentos/mortalidad , Erupciones por Medicamentos/patología , Eosinofilia/inducido químicamente , Eosinofilia/diagnóstico , Eosinofilia/mortalidad , Eosinofilia/patología , HumanosAsunto(s)
Antagonistas Adrenérgicos beta/administración & dosificación , Hiperplasia Angiolinfoide con Eosinofilia/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Paroniquia/terapia , Timolol/administración & dosificación , Administración Tópica , Anciano , Hiperplasia Angiolinfoide con Eosinofilia/inducido químicamente , Hiperplasia Angiolinfoide con Eosinofilia/complicaciones , Hiperplasia Angiolinfoide con Eosinofilia/diagnóstico , Antibacterianos/administración & dosificación , Terapia Combinada/métodos , Crioterapia/métodos , Receptores ErbB/antagonistas & inhibidores , Femenino , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Paroniquia/inducido químicamente , Paroniquia/complicaciones , Paroniquia/diagnóstico , Inhibidores de Proteínas Quinasas/efectos adversos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Nitrato de Plata/administración & dosificación , Resultado del TratamientoRESUMEN
Immune checkpoint inhibitors (ICPi) have emerged as a new frontier of cancer therapy. Although monoclonal antibodies to cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) have revolutionized oncologic management, these agents may result in a spectrum of immune-related adverse events (irAE) of which dermatologic toxicities are among the most frequent. Prompt recognition and management of irAE is essential for dermatologists caring for the expanding population of cancer patients exposed to these drugs. Cutaneous toxicities range from mild cases to severe and life-threatening presentations that may cause significant morbidity and mortality. This review provides an overview of severe cutaneous adverse reactions (SCARs) that may develop during ICPi therapy, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). In addition, immunobullous disorders, erythroderma, neutrophilic dermatoses, and cutaneous eruptions associated with systemic manifestations are discussed.
Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/patología , Pustulosis Exantematosa Generalizada Aguda/etiología , Pustulosis Exantematosa Generalizada Aguda/patología , Antígeno B7-H1/inmunología , Antígeno CTLA-4/inmunología , Humanos , Receptor de Muerte Celular Programada 1 , Síndrome de Stevens-Johnson/etiología , Síndrome de Stevens-Johnson/patologíaAsunto(s)
Poliposis Adenomatosa del Colon/tratamiento farmacológico , Antineoplásicos/efectos adversos , Neoplasias Duodenales/tratamiento farmacológico , Eritema Nudoso/inducido químicamente , Fibroma/tratamiento farmacológico , Neoplasias Primarias Múltiples/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Sorafenib/efectos adversos , Anciano , Eritema Nudoso/diagnóstico , Eritema Nudoso/patología , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Triggers of the autoimmune response that leads to type 1 diabetes (T1D) remain poorly understood. A possibility is that parallel changes in both T cells and target cells provoke autoimmune attack. We previously documented greater Ca2+ transients in fibroblasts from T1D subjects than non-T1D after exposure to fatty acids (FA) and tumor necrosis factor α (TNFα). These data indicate that metabolic and signal transduction defects present in T1D can be elicited ex vivo in isolated cells. Changes that precede T1D, including inflammation, may activate atypical responses in people that are genetically predisposed to T1D. To identify such cellular differences in T1D, we quantified a panel of metabolic responses in fibroblasts and peripheral blood cells (PBMCs) from age-matched T1D and non-T1D subjects, as models for non-immune and immune cells, respectively. Fibroblasts from T1D subjects accumulated more lipid, had higher LC-CoA levels and converted more FA to CO2, with less mitochondrial proton leak in response to oleate alone or with TNFα, using the latter as a model of inflammation. T1D-PBMCs contained and also accumulated more lipid following FA exposure. In addition, they formed more peroxidized lipid than controls following FA exposure. We conclude that both immune and non-immune cells in T1D subjects differ from controls in terms of responses to FA and TNFα. Our results suggest a differential sensitivity to inflammatory insults and FA that may precede and contribute to T1D by priming both immune cells and their targets for autoimmune reactions.