Assuntos
Hemoptise/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Esclerodermia Difusa/diagnóstico por imagem , Idoso , Diagnóstico Diferencial , Feminino , Hemoptise/sangue , Hemoptise/complicações , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/complicações , Nódulos Pulmonares Múltiplos/sangue , Nódulos Pulmonares Múltiplos/complicações , Esclerodermia Difusa/sangue , Esclerodermia Difusa/complicaçõesRESUMO
BACKGROUND: Toxic epidermal necrolysis (TEN) is a rare systemic allergic drug eruption with high patient mortality. Currently, no established treatments have been shown to be effective for TEN beyond supportive care. Prior studies of systemic corticosteroids have yielded conflicting data, with some showing a possible benefit and others reporting in increased mortality. However, topical steroids have shown promise for treatment of ocular sequelae of TEN, such as scarring and vision loss. We have designed a randomized controlled trial to evaluate topical clobetasol for treatment of the epidermal manifestations of TEN. In addition, we propose genetic studies to characterize the TEN transcriptome and alterations in cutaneous gene expression that might occur following topical steroid treatment. METHODS/DESIGN: This split-body randomized, double-blind, placebo-controlled Phase IIa proof-of-concept trial will evaluate the safety and efficacy of once-daily topical clobetasol applied to the skin of patients with TEN. This multicenter trial will recruit a total of 15 patients between the ages of 12 and 85 from the University of California Davis Medical Center and Shriners Hospital for Children inpatient burn units. Designated treatment areas on opposite sides of the body will be treated with blinded clobetasol 0.05% ointment or control petrolatum ointment daily for 14 days. On day 3 of therapy, a biopsy will be taken from the treated area for genetic studies. The primary study aims will be to establish the safety of topical clobetasol treatment and determine the time to cessation of skin detachment for the control and clobetasol-treated areas. Secondary endpoints will evaluate efficacy using parameters such as time to 90% re-epithelialization and percentage of affected skin at 0, 3, 6, 9, 12 and 15 days. Genomic DNA and RNA will be obtained from biopsy samples, to characterize the TEN transcriptome and identify changes in gene expression after topical steroid treatment. DISCUSSION: Topical steroids have shown promise for treating ocular complications of TEN, but to date have not been evaluated for cutaneous manifestations of the disease. This trial will investigate clinical and molecular outcomes of topical clobetasol application and hopefully provide insight into the disease pathophysiology. TRIAL REGISTRATION: ClinicalTrials.gov NCT02319616. https://clinicaltrials.gov/ct2/show/NCT02351037.
Assuntos
Clobetasol/administração & dosagem , Glucocorticoides/administração & dosagem , Pele/efeitos dos fármacos , Síndrome de Stevens-Johnson/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Administração Cutânea , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , California , Criança , Protocolos Clínicos , Clobetasol/efeitos adversos , Método Duplo-Cego , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Glucocorticoides/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Pomadas , Reepitelização/efeitos dos fármacos , Projetos de Pesquisa , Pele/patologia , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/genética , Fatores de Tempo , Resultado do Tratamento , Cicatrização/genética , Adulto JovemRESUMO
Despite advances in treatment and surveillance, melanoma continues to claim approximately 9,000 lives in the US annually (SEER 2013). The National Comprehensive Cancer Network currently recommends ipilumumab, vemurafenib, dabrafenib, and high-dose IL-2 as first line agents for Stage IV melanoma. Little data exists to guide management of cutaneous and subcutaneous metastases despite the fact that they are relatively common. Existing options include intralesional Bacillus Calmette-Guérin, isolated limb perfusion/infusion, interferon-α, topical imiquimod, cryotherapy, radiation therapy, interferon therapy, and intratumoral interleukin-2 injections. Newly emerging treatments include the anti-programmed cell death 1 receptor agents (nivolumab and pembrolizumab), anti-programmed death-ligand 1 agents, and oncolytic vaccines (talimogene laherparepevec). Available treatments for select sites include adoptive T cell therapies and dendritic cell vaccines. In addition to reviewing the above agents and their mechanisms of action, this review will also focus on combination therapy as these strategies have shown promising results in clinical trials for metastatic melanoma treatment.