Asunto(s)
Control de Enfermedades Transmisibles , Infecciones por Coronavirus , Dermatología/educación , Educación de Postgrado en Medicina/organización & administración , Internado y Residencia , Pandemias , Neumonía Viral , Betacoronavirus , COVID-19 , Control de Enfermedades Transmisibles/métodos , Control de Enfermedades Transmisibles/organización & administración , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Educación de Postgrado en Medicina/tendencias , Humanos , Internado y Residencia/métodos , Internado y Residencia/organización & administración , Innovación Organizacional , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , SARS-CoV-2 , Criterios de Admisión Escolar , Facultades de MedicinaAsunto(s)
Infecciones por Coronavirus/prevención & control , Dermatología/educación , Control de Infecciones/normas , Internado y Residencia/normas , Solicitud de Empleo , Pandemias/prevención & control , Neumonía Viral/prevención & control , Betacoronavirus/patogenicidad , COVID-19 , Consenso , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Humanos , Internado y Residencia/métodos , Selección de Personal/normas , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Neumonía Viral/virología , SARS-CoV-2 , Estudiantes de MedicinaAsunto(s)
Infecciones por Uncinaria/complicaciones , Albendazol/uso terapéutico , Ancylostomatoidea/efectos de los fármacos , Ancylostomatoidea/patogenicidad , Animales , Antiprotozoarios/uso terapéutico , Biopsia con Aguja/métodos , Nalgas/anomalías , Nalgas/patología , Nalgas/fisiopatología , Exantema/etiología , Femenino , Infecciones por Uncinaria/patología , Infecciones por Uncinaria/fisiopatología , Humanos , Martinica , Persona de Mediana Edad , Prurito/etiología , ViajeRESUMEN
OBJECTIVE: To assess the safety and efficacy of treatment with belimumab in patients with early diffuse cutaneous systemic sclerosis (dcSSc) treated with background mycophenolate mofetil (MMF). METHODS: In this 52-week, investigator-initiated, single-center, double-blind, placebo-controlled, pilot study, 20 patients with dcSSc recently started on MMF were randomized 1:1 to additionally receive belimumab at 10 mg/kg intravenously or placebo. We assessed safety, efficacy, and differential gene expression. RESULTS: In the belimumab group, the median modified Rodnan skin thickness score (MRSS) decreased from 27 (interquartile range [IQR] 26.5, 31) to 18 (IQR 11, 23) (P = 0.039). In the placebo group, the median MRSS decreased from 28 (IQR 22, 28) to 21 (IQR 14, 25) (P = 0.023). The median change in MRSS was -10 (IQR -13, -9) in the belimumab group and -3.0 (IQR -15, -1) in the placebo group (P = 0.411). There were no significant differences between the groups in the number of adverse events (AEs). A significant decrease in expression of B cell signaling and profibrotic genes and pathways was observed in patients with improved MRSS in the belimumab group but not in the placebo group. CONCLUSION: Patients in both treatment groups experienced significant improvements in MRSS. The median difference was greater in the belimumab group but did not achieve statistical significance in this small pilot study. AEs were similar between the groups. Changes in gene expression were consistent with mechanism of action and showed that clinical response to treatment with belimumab is associated with a significant decrease in profibrotic genes and pathways. Additional studies are needed to determine the role of belimumab in the treatment of dcSSc.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Inmunosupresores/uso terapéutico , Esclerodermia Difusa/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Método Doble Ciego , Femenino , Expresión Génica/efectos de los fármacos , Humanos , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Proyectos Piloto , Esclerodermia Difusa/genética , Índice de Severidad de la Enfermedad , Piel/patología , Resultado del Tratamiento , Escala Visual AnalógicaAsunto(s)
Enfermedades de la Mama/patología , Mama/patología , Carcinoma/patología , Neoplasias Inflamatorias de la Mama/patología , Dermopatía Fibrosante Nefrogénica/patología , Piel/patología , Biopsia , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Valor Predictivo de las PruebasRESUMEN
Pustular psoriasis occurs rarely in children but can present with acute toxicity requiring inpatient admission. For the best approach, medical providers should have an evidence based and systematic treatment algorithm in their armamentarium. Toillustrate this point, we describe a 13-year-old girl who was admitted with generalized pustular psoriasis and who responded dramatically to "wet wrap" therapy and cyclosporine bridged to etanercept. Using this case example, we highlight the three most important considerations in any patient with new onset pustularpsoriasis: avoidance of disease complications, acute "rescue" therapy, and maintenance therapy.
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Ciclosporina/uso terapéutico , Etanercept/uso terapéutico , Inmunosupresores/uso terapéutico , Apósitos Oclusivos , Psoriasis/tratamiento farmacológico , Adolescente , Baños , Terapia Combinada , Quimioterapia Combinada , Femenino , Humanos , Psoriasis/terapia , Enfermedades Cutáneas Vesiculoampollosas/tratamiento farmacológico , Enfermedades Cutáneas Vesiculoampollosas/terapiaRESUMEN
Metastatic Crohn disease is a rare cutaneous manifestation of Crohn disease characterized by granulomatous lesions discontinuous with the diseased areas of the gastrointestinal tract. We report a case of a 32-year-old woman with history of Crohn disease who was admitted for treatment of cellulitis after presenting with a tender erythematous plaque of the left calf. Microbiological tests including tissue cultures were negative. A skin biopsy revealed granulomatous dermatitis consistent with metastatic cutaneous Crohn disease. Owing to concomitant perianal fistulas and abscesses and prior infusion reaction to infliximab, the patient was treated with certolizumab, a pegylated tumor necrosis factor (TNF) inhibitor combined with methotrexate resulting in complete resolution of the skin lesion. This case emphasizes the importance of recognizing this rare skin manifestation of Crohn disease and adds certolizumab as one of TNF inhibitors useful in the treatment of metastatic cutaneous Crohn disease.
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Certolizumab Pegol/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Enfermedades de la Piel/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Femenino , Humanos , Metotrexato/uso terapéuticoRESUMEN
INTRODUCTION: Tyrosine kinase inhibitors (TKI) are medications of interest in the treatment of Systemic Sclerosis (SSc) because of their ability to inhibit pathways involved in fibrosis. In this open-label pilot trial, our objectives were to assess the safety, efficacy, and molecular change associated with treatment of patients with diffuse cutaneous (dc)SSc with the TKI nilotinib (Tasigna™). METHODS: Ten adult patients with early dcSSc were treated with nilotinib. Primary endpoints were safety and change in modified Rodnan Skin Score (MRSS) after 6 months. Lesional skin biopsies at baseline, 6 and 12 months of treatment were assessed by histopathology, immunohistochemistry, and DNA microarray. RESULTS: Patients had early and active dcSSc with median disease duration of 0.7 years (range 0.5, 1.7) and increasing MRSS in the month prior to baseline (mean +2.9, p=0.02). Seven out of ten patients completed 6 and 12 months of treatment. Seventy-one adverse events (AEs) including 2 serious AEs were observed, and 92 % of AEs were grade 1-2. Two patients discontinued the medication due to mild QTc prolongation. MRSS improved by a mean of 4.2 points (16 %) at 6 months and by 6.3 points (23 %) at 12 months in the 7 completers, p=0.02 and 0.01, respectively. Patients with a decrease in MRSS >20 % from baseline at 12 months (classified as improvers) had significantly higher expression of transforming growth factor beta receptor (TGFBR) and platelet-derived growth factor receptor beta (PDGFRB) signaling genes at baseline than non-improvers, and the expression of these genes significantly decreased in improvers post-treatment. CONCLUSION: Nilotinib was well tolerated by the majority of patients in this study, with tolerability limited primarily by mild QTc-prolongation. Significant MRSS improvement was observed in these early, active patients, but is not conclusive of treatment effect given the open-label study-design and small number of patients in this pilot study. Improvers had higher levels of expression of genes associated with TGFBR and PDGFRB signaling at baseline, and a significant decrease in the expression of these genes occurred only in patients with higher MRSS improvement. The findings of this pilot study warrant more conclusive evaluation. TRIAL REGISTRATION: Clinicaltrials.gov NCT01166139 , July 1, 2010.
Asunto(s)
Pirimidinas/uso terapéutico , Esclerodermia Difusa/tratamiento farmacológico , Piel/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Adolescente , Adulto , Anciano , Anemia/inducido químicamente , Enfermedades Cardiovasculares/inducido químicamente , Femenino , Cefalea/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Análisis de Secuencia por Matrices de Oligonucleótidos , Proyectos Piloto , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/efectos adversos , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Receptores de Factores de Crecimiento Transformadores beta/genética , Esclerodermia Difusa/genética , Esclerodermia Difusa/patología , Transducción de Señal/genética , Piel/metabolismo , Piel/patología , Transcriptoma/genética , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To assess the safety and effectiveness of imatinib mesylate in the treatment of diffuse cutaneous systemic sclerosis (dcSSc). METHODS: In this phase IIa, open-label, single-arm clinical trial, 30 patients with dcSSc were treated with imatinib 400 mg daily. Patients were monitored monthly for safety assessments. Modified Rodnan skin scores (MRSS) were assessed every 3 months. Pulmonary function testing, chest radiography, echocardiography and skin biopsies were performed at baseline and after 12 months of treatment. RESULTS: Twenty-four patients completed 12 months of therapy. 171 adverse events (AE) with possible relation to imatinib were identified; 97.6% were grade 1 or 2. Twenty-four serious AE were identified, two of which were attributed to study medication. MRSS decreased by 6.6 points or 22.4% at 12 months (p=0.001). This change was evident starting at the 6-month time point (Δ=-4.5; p<0.001) and was seen in patients with both early and late-stage disease. Forced vital capacity (FVC) improved by 6.4% predicted (p=0.008), and the diffusion capacity remained stable. The improvement in FVC was significantly greater in patients without interstitial lung disease. Health-related quality of life measures improved or remained stable. Blinded dermatopathological analysis confirmed a significant decrease in skin thickness and improvement in skin morphology. CONCLUSIONS: Treatment with imatinib was tolerated by most patients in this cohort. Although AE were common, most were mild to moderate. In this open-label experience, improvements in skin thickening and FVC were observed. Further investigation of tyrosine kinase inhibition for dcSSc in a double-blind randomised placebo controlled trial is warranted. ClinicalTrials.gov, NCT00555581.