Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Skin Res Technol ; 30(2): e13602, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38348764

RESUMEN

INTRODUCTION: Software to predict the impact of aging on physical appearance is increasingly popular. But it does not consider the complex interplay of factors that contribute to skin aging. OBJECTIVES: To predict the +15-year progression of clinical signs of skin aging by developing Causal Bayesian Belief Networks (CBBNs) using expert knowledge from dermatologists. MATERIAL AND METHODS: Structures and conditional probability distributions were elicited worldwide from dermatologists with experience of at least 15 years in aesthetics. CBBN models were built for all phototypes and for ages ranging from 18 to 65 years, focusing on wrinkles, pigmentary heterogeneity and facial ptosis. Models were also evaluated by a group of independent dermatologists ensuring the quality of prediction of the cumulative effects of extrinsic and intrinsic skin aging factors, especially the distribution of scores for clinical signs 15 years after the initial assessment. RESULTS: For easiness, only models on African skins are presented in this paper. The forehead wrinkle evolution model has been detailed. Specific atlas and extrinsic factors of facial aging were used for this skin type. But the prediction method has been validated for all phototypes, and for all clinical signs of facial aging. CONCLUSION: This method proposes a skin aging model that predicts the aging process for each clinical sign, considering endogenous and exogenous factors. It simulates aging curves according to lifestyle. It can be used as a preventive tool and could be coupled with a generative AI algorithm to visualize aging and, potentially, other skin conditions, using appropriate images.


Asunto(s)
Envejecimiento de la Piel , Humanos , Teorema de Bayes , Cara , Envejecimiento , Frente
2.
J Eur Acad Dermatol Venereol ; 37(6): 1207-1214, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36802102

RESUMEN

BACKGROUND: Adverse pregnancy outcomes (APO) occur in 35% of patients with pemphigoid gestationis (PG). No biological predictor of APO has been established yet. OBJECTIVES: To assess a potential relationship between the occurrence of APO and the serum value of anti-BP180 antibodies at the time of PG diagnosis. METHODS: Multicentre retrospective study conducted from January 2009 to December 2019 in 35 secondary and tertiary care centres. INCLUSION CRITERIA: (i) diagnosis of PG according to clinical, histological and immunological criteria, (ii) ELISA measurement of anti-BP180 IgG antibodies determined at the time of PG diagnosis with the same commercial kit and (iii) obstetrical data available. RESULTS: Of the 95 patients with PG included, 42 had one or more APO, which mainly corresponded to preterm birth (n = 26), intrauterine growth restriction (IUGR) (n = 18) and small weight for gestational age at birth (n = 16). From a ROC curve, we identified a threshold of 150 IU ELISA value as the most discriminating to differentiate between patients with or without IUGR, with 78% sensitivity, 55% specificity, 30% positive and 91% negative predictive value. The threshold >150 IU was confirmed using a cross-validation based on bootstrap resampling, which showed that the median threshold was 159 IU. Upon adjusting for oral corticosteroid intake and main clinical predictors of APO, an ELISA value of >150 IU was associated with the occurrence of IUGR (OR = 5.11; 95% CI: 1.48-22.30; p = 0.016) but not with any other APO. The combination of blisters and ELISA values higher than 150 IU led to a 2.4-fold higher risk of all-cause APO (OR: 10.90; 95% CI: 2.33-82.3) relative to patients with blisters but lower values of anti-BP180 antibodies (OR of 4.54; 95% CI 0.92-34.2). CONCLUSION: These findings suggest that anti-BP180 antibody ELISA value in combination with clinical markers is helpful in managing the risk of APO, in particular IUGR, in patients with PG.


Asunto(s)
Penfigoide Gestacional , Penfigoide Ampolloso , Nacimiento Prematuro , Embarazo , Femenino , Humanos , Recién Nacido , Penfigoide Gestacional/diagnóstico , Estudios Retrospectivos , Penfigoide Ampolloso/diagnóstico , Vesícula , Resultado del Embarazo , Colágenos no Fibrilares , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina G , Autoantígenos , Autoanticuerpos
3.
J Am Acad Dermatol ; 86(6): 1293-1300, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35091001

RESUMEN

BACKGROUND: A high level of anti-BP180 antibodies on enzyme-linked immunosorbent assay and a persistent positive direct immunofluorescence at the end of treatment (immunologic tests, [ITs]) are predictors of relapse after treatment cessation (TC) in patients with bullous pemphigoid. OBJECTIVE: To evaluate the real-life impact of the immunologic-based decision of TC on the 3- and 6-month relapse rates after TC in bullous pemphigoid. METHODS: Retrospective multicentric study included patients followed almost 6 months after TC. Patients were classified according to whether the TC decision was in accordance with the results of ITs performed during the 3 months before TC, despite the results of ITs or without ITs performed. RESULTS: We included 238 patients. Three months after TC, 36 patients showed relapse: 14 of 95 patients with TC in accordance with IT results (14.7%); 5 of 21 with TC despite ITs (23.8%); and 17 of 122 with TC without ITs (13.9%; P = .5). Six months after TC, the relapse rate was 18.9%, 28.6%, and 18.9% (P = .56), respectively, in the 3 groups. LIMITATIONS: The retrospective design and the limited follow up. CONCLUSION: In real-life practice, in bullous pemphigoid, the 3- and 6-month relapse rates were not significantly reduced with TC decision based on results of ITs as compared with a classic clinical-based decision.


Asunto(s)
Penfigoide Ampolloso , Autoanticuerpos , Autoantígenos , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Pruebas Inmunológicas , Colágenos no Fibrilares , Penfigoide Ampolloso/tratamiento farmacológico , Recurrencia , Estudios Retrospectivos , Privación de Tratamiento
4.
Skin Res Technol ; 26(6): 794-803, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32713074

RESUMEN

BACKGROUND: In vivo multiphoton imaging and automatic 3D image processing tools provide quantitative information on human skin constituents. These multiphoton-based tools allowed evidencing retinoids epidermal effects in the occlusive patch test protocol developed for antiaging products screening. This study aimed at investigating their relevance for non-invasive, time course assessment of retinoids cutaneous effects under real-life conditions for one year. MATERIALS AND METHODS: Thirty women, 55-65 y, applied either retinol (RO 0.3%) or retinoic acid (RA 0.025%) on one forearm dorsal side versus a control product on the other forearm once a day for 1 year. In vivo multiphoton imaging was performed every three months, and biopsies were taken after 1 year. Epidermal thickness and dermal-epidermal junction undulation were estimated in 3D with multiphoton and in 2D with histology, whereas global melanin density and its z-epidermal distribution were estimated using 3D multiphoton image processing tools. RESULTS: Main results after one year were as follows: a) epidermal thickening with RO (+30%); b) slight increase in dermal-epidermal junction undulation with RO; c) slight decrease in 3D melanin density with RA; d) limitation of the melanin ascent observed with seasonality and time within supra-basal layers with both retinoids, using multiphoton 3D-melanin z-epidermal profile. CONCLUSIONS: With a novel 3D descriptor of melanin z-epidermal distribution, in vivo multiphoton imaging allows demonstrating that daily usage of retinoids counteracts aging by acting not only on epidermal morphology, but also on melanin that is shown to accumulate in the supra-basal layers with time.


Asunto(s)
Microscopía de Fluorescencia por Excitación Multifotónica , Retinoides , Piel , Anciano , Femenino , Humanos , Imagenología Tridimensional , Melaninas , Persona de Mediana Edad , Retinoides/uso terapéutico , Piel/diagnóstico por imagen , Piel/efectos de los fármacos
7.
Int J Dermatol ; 63(8): 1081-1088, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38366727

RESUMEN

BACKGROUND: The structure and physiology of skin and hair in people of African ancestry are different from other ethnic categories and studies from other continents cannot necessarily be extrapolated to Sub-Saharan Africa (SSA) due to the differences in genetics, lifestyle, climate, cultures, and hair and skin care practices. The aim of this report is to highlight the recent advances in local skin and hair research in SSA from a grant program. METHODS: African Hair and Skin Research Grants from an industrial sponsor were awarded between 2013 and 2022 on five main topics: acne, hair and scalp, keloid scars, atopic dermatitis, and air pollution. A literature search in Scopus identified publications on these topics in African or black skin in SSA and worldwide to provide insight into the impact of the program. RESULTS: The number of publications from around the world on the skin and hair of people of African ancestry has increased significantly over the past 30 years on all five topics, especially as a result studies conducted in the United States. Fewer studies have been conducted in SSA but there has been an increasing number of publications over the past 10 years, especially from South Africa. CONCLUSIONS: Scientific and clinical partnerships between the industry, academia, and public healthcare sectors have contributed to a steady increase in hair and skin publications from SSA, which may be useful for the development of tailored products and public educational campaigns to raise awareness of the risks of using inappropriate products.


Asunto(s)
Investigación Biomédica , Humanos , África del Sur del Sahara/etnología , Población Negra/estadística & datos numéricos , Dermatología , Cabello , Apoyo a la Investigación como Asunto , Piel , Enfermedades de la Piel/etnología
8.
JAMA Dermatol ; 160(3): 290-296, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38265821

RESUMEN

Importance: The Ritux 3 trial demonstrated the short-term efficacy and safety of first-line treatment with rituximab compared with a standard corticosteroid regimen in pemphigus. No data on the long-term follow-up of patients who received rituximab as first line are available. Objective: To assess the long-term efficacy and safety of the Ritux 3 treatment regimen. Design, Setting, and Participants: This 7-year follow-up study of the Ritux 3 trial included patients with pemphigus from 25 dermatology departments in France from January 1, 2010, to December 31, 2015. Exposure: Patients were initially randomized in the rituximab plus prednisone group or prednisone-alone group. Main outcomes and measures: The primary outcome was the 5- and 7-year disease-free survival (DFS) without corticosteroids, assessed by Kaplan-Meier curves. Secondary outcomes were occurrence of relapse, occurrence of severe adverse events (SAEs), and evolution of antidesmoglein (Dsg) antibody enzyme-linked immunosorbent assay values to predict long-term relapse. Results: Of the 90 patients in the Ritux 3 trial, 83 were evaluated at the end of follow-up study visit (44 in the rituximab plus prednisone group; 39 in the prednisone-alone group) with a median (IQR) follow-up of 87.3 (79.1-97.5) months. Forty-three patients (93%) from the rituximab plus prednisone and 17 patients (39%) from the prednisone-alone group had achieved complete remission without corticosteroids at any time during the follow-up. Patients from the rituximab group had much longer 5- and 7-year DFS without corticosteroids than patients from the prednisone-alone group (76.7% and 72.1% vs 35.3% and 35.3%, respectively; P < .001), and had about half the relapses (42.2% vs 83.7%; P < .001). Patients who received rituximab as second-line treatment had shorter DFS than patients treated as first line (P = .007). Fewer SAEs were reported in the rituximab plus prednisone group compared with the prednisone-alone group, 31 vs 58 respectively, corresponding to 0.67 and 1.32 SAEs per patient, respectively (P = .003). The combination of anti-Dsg1 values of 20 or more IU/mL and/or anti-Dsg3 values of 48 or more IU/mL yielded 0.83 positive predictive value and 0.94 negative predictive value to predict long-term relapse. Conclusions and Relevance: In this secondary analysis of the Ritux 3 trail, first-line treatment of patients with pemphigus with the Ritux 3 regimen was associated with long-term sustained complete remission without corticosteroid therapy without any additional maintenance infusion of rituximab.


Asunto(s)
Pénfigo , Humanos , Rituximab/efectos adversos , Pénfigo/tratamiento farmacológico , Prednisona/efectos adversos , Estudios de Seguimiento , Recurrencia Local de Neoplasia , Corticoesteroides , Recurrencia , Resultado del Tratamiento
9.
Skin Res Technol ; 19(2): 115-24, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23441573

RESUMEN

BACKGROUND/PURPOSE: Multiphoton microscopy has emerged in the past decade as a useful noninvasive imaging technique for in vivo human skin characterization. However, it has not been used until now in evaluation clinical trials, mainly because of the lack of specific image processing tools that would allow the investigator to extract pertinent quantitative three-dimensional (3D) information from the different skin components. METHODS: We propose a 3D automatic segmentation method of multiphoton images which is a key step for epidermis and dermis quantification. This method, based on the morphological watershed and graph cuts algorithms, takes into account the real shape of the skin surface and of the dermal-epidermal junction, and allows separating in 3D the epidermis and the superficial dermis. RESULTS: The automatic segmentation method and the associated quantitative measurements have been developed and validated on a clinical database designed for aging characterization. The segmentation achieves its goals for epidermis-dermis separation and allows quantitative measurements inside the different skin compartments with sufficient relevance. CONCLUSIONS: This study shows that multiphoton microscopy associated with specific image processing tools provides access to new quantitative measurements on the various skin components. The proposed 3D automatic segmentation method will contribute to build a powerful tool for characterizing human skin condition. To our knowledge, this is the first 3D approach to the segmentation and quantification of these original images.


Asunto(s)
Algoritmos , Dermoscopía/métodos , Interpretación de Imagen Asistida por Computador/métodos , Imagenología Tridimensional/métodos , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Reconocimiento de Normas Patrones Automatizadas/métodos , Piel/citología , Adolescente , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto Joven
10.
Sci Rep ; 13(1): 11196, 2023 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-37433822

RESUMEN

Topically applied all-trans-retinoic acid (RA) is a gold-standard anti-aging molecule used in dermatology. As its cosmetic counterpart used in anti-aging, Retinol (ROL) is also a known metabolic precursor of RA. Despite this metabolic link, they haven't been compared exhaustively in vivo at a mechanistic level. Therefore, to highlight the effect of a topical application of both molecules on in vivo skin, we undertook a longitudinal 1-year study and performed an untargeted proteomic analysis to get a more holistic view on the underlying biological mechanisms of action. The generation of the temporal proteomics signatures of retinol and all-trans-retinoic acid reveals the impact of these molecules on biological functions related to the aging of skin. New biological functions impacted by retinoids were discovered: glycan metabolism and protein biosynthesis. In addition, the temporal analysis reveals highest modulations at early time points while the physical measures, such as epidermal thickening, was mostly observed at the latest time point, demonstrating a strong time lapse between molecular and morphological impacts. Finally, these global temporal signatures could be used to identify new cosmetic compounds of interest.


Asunto(s)
Proteoma , Vitamina A , Humanos , Estudios Longitudinales , Proteómica , Tretinoina/farmacología
11.
Sci Rep ; 12(1): 1642, 2022 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-35102172

RESUMEN

Characterizing melanins in situ and determining their 3D z-epidermal distribution is paramount for understanding physiological/pathological processes of melanin neosynthesis, transfer, degradation or modulation with external UV exposure or cosmetic/pharmaceutical products. Multiphoton fluorescence intensity- and lifetime-based approaches have been shown to afford melanin detection, but how can one quantify melanin in vivo in 3D from multiphoton fluorescence lifetime (FLIM) data, especially since FLIM imaging requires long image acquisition times not compatible with 3D imaging in a clinical setup? We propose an approach combining (i) multiphoton FLIM, (ii) fast image acquisition times, and (iii) a melanin detection method called Pseudo-FLIM, based on slope analysis of autofluorescence intensity decays from temporally binned data. We compare Pseudo-FLIM to FLIM bi-exponential and phasor analyses of synthetic melanin, melanocytes/keratinocytes coculture and in vivo human skin. Using parameters of global 3D epidermal melanin density and z-epidermal distribution profile, we provide first insights into the in vivo knowledge of 3D melanin modulations with constitutive pigmentation versus ethnicity, with seasonality over 1 year and with topical application of retinoic acid or retinol on human skin. Applications of Pseudo-FLIM based melanin detection encompass physiological, pathological, or environmental factors-induced pigmentation modulations up to whitening, anti-photoaging, or photoprotection products evaluation.


Asunto(s)
Epidermis/metabolismo , Imagenología Tridimensional , Melaninas/metabolismo , Melanocitos/metabolismo , Microscopía de Fluorescencia por Excitación Multifotónica , Pigmentación de la Piel , Administración Cutánea , Adolescente , Adulto , Anciano , Células Cultivadas , Técnicas de Cocultivo , Fármacos Dermatológicos/administración & dosificación , Epidermis/efectos de los fármacos , Femenino , Humanos , Melanocitos/efectos de los fármacos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pigmentación de la Piel/efectos de los fármacos , Factores de Tiempo , Resultado del Tratamiento , Tretinoina/administración & dosificación , Vitamina A/administración & dosificación , Adulto Joven
12.
Sci Rep ; 12(1): 14863, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-36050338

RESUMEN

Quantifying skin aging changes and characterizing its 3D structure and function in a non-invasive way is still a challenging area of research, constantly evolving with the development of imaging methods and image analysis tools. In vivo multiphoton imaging offers means to assess skin constituents in 3D, however prior skin aging studies mostly focused on 2D analyses of dermal fibers through their signals' intensities or densities. In this work, we designed and implemented multiphoton multiparametric 3D quantification tools for in vivo human skin pigmentation and aging characterization. We first demonstrated that despite the limited field of view of the technic, investigation of 2 regions of interest (ROIs) per zone per volunteer is a good compromise in assessing 3D skin constituents in both epidermis and superficial dermis. We then characterized skin aging on different UV exposed areas-ventral and dorsal forearms, face. The three major facts of aging that are epidermal atrophy, the dermal-epidermal junction (DEJ) flattening and dermal elastosis can be non-invasively quantified and compared. Epidermal morphological changes occur late and were only objectified between extreme age groups. Melanin accumulation in suprabasal layers with age and chronic exposure on ventral and dorsal forearms is less known and appears earlier. Superficial dermal aging changes are mainly elastin density increase, with no obvious change in collagen density, reflected by SHGto2PEF ratio and SAAID index decrease and ImbrN index increase on all skin areas. Analysis of the z-dermal distribution of these parameters highlighted the 2nd 20 µm thickness normalized dermal sub-layer, that follows the DEJ shape, as exhibiting the highest aging differences. Moreover, the 3D ImbrN index allows refining the share of photoaging in global aging on face and the 3D SAAID index on forearm, which elastin or fibrillar collagens densities alone do not allow. Photoaging of the temple area evolves as a function of chronic exposure with a more pronounced increase in elastin density, also structurally modified from thin and straight elastic fibers in young volunteers to dense and compact pattern in older ones. More generally, multiphoton multiparametric 3D skin quantification offers rich spatial information of interest in assessing normal human skin condition and its pathological, external environment or product induced changes.


Asunto(s)
Microscopía de Fluorescencia por Excitación Multifotónica , Envejecimiento de la Piel , Piel , Anciano , Envejecimiento , Elastina/química , Cara , Antebrazo , Humanos , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Piel/diagnóstico por imagen , Enfermedades de la Piel/diagnóstico por imagen
13.
N Engl J Med ; 357(6): 545-52, 2007 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-17687130

RESUMEN

BACKGROUND: The combination of multiple cycles of rituximab and intravenous immune globulins has been reported to be effective in patients with severe pemphigus. The aim of this study was to assess the efficacy of a single cycle of rituximab in severe types of pemphigus. METHODS: We studied 21 patients with pemphigus whose disease had not responded to an 8-week course of 1.5 mg of prednisone per kilogram of body weight per day (corticosteroid-refractory disease), who had had at least two relapses despite doses of prednisone higher than 20 mg per day (corticosteroid-dependent disease), or who had severe contraindications to corticosteroids. The patients were treated with four weekly infusions of 375 mg of rituximab per square meter of body-surface area. The primary end point was complete remission 3 months after the end of rituximab treatment; complete remission was defined as epithelialization of all skin and mucosal lesions. RESULTS: Eighteen of 21 patients (86%; 95% confidence interval, 64 to 97%) had a complete remission at 3 months. The disease relapsed in nine patients after a mean of 18.9+/-7.9 months. After a median follow-up of 34 months, 18 patients (86%) were free of disease, including 8 who were not receiving corticosteroids; the mean prednisone dose decreased from 94.0+/-10.2 to 12.0+/-7.5 mg per day (P=0.04) in patients with corticosteroid-refractory disease and from 29.1+/-12.4 to 10.9+/-16.5 mg per day (P=0.007) in patients with corticosteroid-dependent disease. Pyelonephritis developed in one patient 12 months after rituximab treatment, and one patient died of septicemia 18 months after rituximab treatment. These patients had a profound decrease in the number of circulating B lymphocytes but normal serum levels of IgG. CONCLUSIONS: A single cycle of rituximab is an effective treatment for pemphigus. Because of its potentially severe side effects, its use should be limited to the most severe types of the disease. (ClinicalTrials.gov number, NCT00213512 [ClinicalTrials.gov].).


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Factores Inmunológicos/administración & dosificación , Pénfigo/tratamiento farmacológico , Anciano , Antiinflamatorios/administración & dosificación , Anticuerpos/sangre , Anticuerpos Monoclonales de Origen Murino , Linfocitos B , Desmogleínas/inmunología , Esquema de Medicación , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Isotipos de Inmunoglobulinas/sangre , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Pénfigo/inmunología , Prednisona/administración & dosificación , Inducción de Remisión , Rituximab
14.
J Invest Dermatol ; 139(1): 31-37, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30301637

RESUMEN

The Pemphigus Disease Area Index (PDAI) and Autoimmune Bullous Skin Disorder Intensity-Score (ABSIS) scores have been proposed to provide an objective measure of pemphigus activity. These scores have been evaluated only on already treated patients mainly with mild to moderate activity. The objective was to assess the interrater reliability of ABSIS and PDAI scores and their correlation with other severity markers in a large international study. Consecutive patients with newly diagnosed pemphigus were enrolled in 31 centers. Severity scores were recorded during a 24-month period by the same two blinded investigators. Serum was collected at each visit for ELISA measurement of anti-desmoglein antibodies. The intraclass correlation coefficient (ICC) and Spearman rank correlation coefficient were calculated. A total of 116 patients with pemphigus vulgaris (n = 84) or pemphigus foliaceus (n = 32) were included. At baseline, the ABSIS and PDAI ICCs were 0.90 (95% confidence interval [CI] = 0.85-0.93), and 0.91(95% CI = 0.87-0.94), respectively. The ICCs for PDAI were higher in moderate and extensive pemphigus (ICC = 0.82, 95% CI = 0.63-0.92 and ICC = 0.80, 95% CI = 0.62-0.90, respectively) than in patients with intermediate (significant) extent (ICC = 0.50, 95% CI = 0.27-0.68). Conversely, the ICCs for ABSIS were lower in patients with moderate extent (ICC = 0.44, 95% CI = 0.004-0.74) than in those with intermediate or extensive forms, (ICC = 0.69, 95% CI = 0.51-0.81 and ICC = 0.75, 95% CI = 0.51-0.88, respectively). During patients' follow-up, the ICCs of both ABSIS and PDAI scores remained higher than 0.70. ABSIS and PDAI skin (r = 0.71 and r = 0.75) but not mucosal (r = 0.32 and r = 0.37) subscores were correlated with the evolution of anti-DSG1 and anti-DSG3 ELISA values, respectively. ABSIS and PDAI scores are robust tools to accurately assess pemphigus activity.


Asunto(s)
Autoanticuerpos/inmunología , Autoinmunidad , Desmogleína 1/inmunología , Pénfigo/diagnóstico , Piel/patología , Humanos , Pénfigo/inmunología , Índice de Severidad de la Enfermedad , Estudios de Validación como Asunto
15.
Arch Dermatol ; 141(6): 691-8, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15967914

RESUMEN

OBJECTIVE: To identify the prognostic factors of bullous pemphigoid (BP). DESIGN: Prospective study of patients with BP included in a randomized, controlled trial. SETTING: Twenty dermatology departments in France. Patients One hundred seventy patients with BP initially treated with a 40-g/d dosage of clobetasol propionate cream (testing sample) and 171 patients initially treated with oral corticosteroids at a dosage of 0.5 or of 1.0 mg/kg per day, depending on the extent of BP (validation samples). MAIN OUTCOME MEASURES: The end point was overall survival during the first year after BP diagnosis. From the testing sample, associations of clinical and biological variables with overall survival were assessed using univariate and multivariate analyses. Selected predictors were included in a prognostic model. To verify that these predictors were not dependent on the treatment used, the model was then validated independently on the 2 series of BP patients treated with oral corticosteroids. RESULTS: Median age of the BP patients included in the testing sample was 83 years. The 1-year Kaplan-Meier survival rate was 74%. From univariate analysis, the main deleterious predictors were demographic factors (ie, older age and female sex), associated medical conditions (ie, cardiac insufficiency, history of stroke, and dementia), and low Karnofsky score, which is a measure of the patient's general condition. No factors directly related to BP, in particular extent of cutaneous lesions, were shown to be related to the patients' prognosis. From multivariate analysis, only older age (P = .02) and low Karnofsky score (P<.001) appeared independently predictive of death. From the Cox model including these 2 predictors, the predicted 1-year survival rates were 90% (95% confidence interval [CI], 85%-96%) for patients 83 years or younger with Karnofsky score greater than 40, 79% (95% CI, 69%-90%) for patients older than 83 years with Karnofsky score greater than 40, 65% (95% CI, 50%-86%) for patients 83 years or younger with Karnofsky score of 40 or less, and 38% (95% CI, 26%-57%) for patients older than 83 years with Karnofsky score of 40 or less. Kaplan-Meier survival distributions of patients from the validation samples appeared clearly separated according to these 4 categories and were in close agreement with corresponding predicted 1-year survival rates obtained from the testing sample. CONCLUSIONS: The prognosis of patients with BP is influenced by age and Karnofsky score. These predictors are easy to use and should facilitate the management of BP.


Asunto(s)
Corticoesteroides/uso terapéutico , Causas de Muerte , Clobetasol/uso terapéutico , Penfigoide Ampolloso/diagnóstico , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/mortalidad , Administración Oral , Administración Tópica , Análisis de Varianza , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Masculino , Análisis Multivariante , Valor Predictivo de las Pruebas , Probabilidad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Resultado del Tratamiento
16.
Arch Dermatol ; 140(9): 1057-61, 2004 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15381544

RESUMEN

OBJECTIVE: To investigate the prognostic value of initial characteristics including blood eosinophilia in patients with primary cutaneous T-cell lymphoma. DESIGN: A retrospective inception cohort, patients included from date of diagnosis (1982-1998). SETTING: Two dermatology departments of a university hospital. Patients A total of 104 patients with cutaneous T-cell lymphoma, including patients with mycosis fungoides (n = 69), Sézary syndrome (n = 13), and nonepidermotropic cutaneous lymphoma (n = 22). The following variables were recorded: age, sex, diagnosis according to the European Organization for Research and Treatment of Cancer (EORTC) classification, type of skin involvement at the time of diagnosis, initial eosinophil absolute count, lactate dehydrogenase value, date of disease progression, and cause and date of death or date of last contact. MAIN OUTCOME MEASURES: Time from diagnosis to disease progression and to disease-specific death. RESULTS: The median follow-up was 43 months (range, 7-197 months). Estimated rates of disease progression and disease-specific death for 3 years were 19.5% (95% confidence interval [CI],11.3%-27.6%) and 9.9% (95% CI, 2.8%-13.6%), respectively. Univariable analysis of initial variables possibly influencing disease progression revealed significant prognostic value for diagnosis according to EORTC classification (hazard ratio [HR], 2.77; 95% CI, 1.04-7.41; P =.04), type of skin involvement (HR, 2.70; 95% CI, 1.00-7.25; P =.04), raised blood eosinophil absolute count (HR, 7.33; 95% CI, 2.84-18.91; P<.001), and raised serum level of lactate dehydrogenase (HR, 3.72; 95% CI, 1.58-8.78; P =.001). Concerning disease-specific death, significant prognostic indicators were diagnosis according to the EORTC classification (HR, 6.62; 95% CI, 1.68-26.12; P =.007) and a raised blood eosinophil absolute count (HR, 10.57; 95% CI, 2.28-49.0; P<.001). In multivariable analysis, only blood eosinophilia was associated with disease progression and disease-specific death. CONCLUSION: These results strongly suggest that blood eosinophilia at baseline is a prognostic factor in patients with primary cutaneous T-cell lymphoma.


Asunto(s)
Causas de Muerte , Eosinofilia/diagnóstico , Linfoma Cutáneo de Células T/diagnóstico , Linfoma Cutáneo de Células T/mortalidad , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores/sangre , Biopsia con Aguja , Estudios de Cohortes , Intervalos de Confianza , Eosinofilia/epidemiología , Femenino , Humanos , Inmunohistoquímica , Linfoma Cutáneo de Células T/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Probabilidad , Pronóstico , Estudios Retrospectivos , Sensibilidad y Especificidad , Neoplasias Cutáneas/tratamiento farmacológico , Análisis de Supervivencia , Resultado del Tratamiento
17.
Sci Transl Med ; 5(175): 175ra30, 2013 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-23467561

RESUMEN

Pemphigus is a severe blistering condition of the skin and mucosa caused by autoantibodies directed against desmogleins, which are a type of keratinocyte adhesion protein. B cell depletion by rituximab has short-term efficacy against pemphigus. We aimed to assess the long-term course of pemphigus patients after B cell depletion and to understand the immunological mechanisms that mediate long-lasting remissions. We evaluated the clinical course of 22 pemphigus patients treated with rituximab after a 79-month median follow-up and compared the anti-desmoglein B cell response and B and T lymphocyte subpopulations and repertoire between patients who achieved complete remission (CR) and those who had incomplete remission (IR). Thirteen patients (59%) experienced CR during the study, including 10 patients off treatment and 3 patients with prednisone doses <10 mg/day; 9 patients had IR. A marked increase was observed in the ratio of CD19(+)CD27(-) naïve B cells to CD19(+)CD27(+) memory B cells. Indeed, patients in CR had a fourfold higher number of transitional B cells and interleukin-10-secreting regulatory B cells than those in IR. Furthermore, CR was associated with modification of the initial B cell repertoire and the disappearance of desmoglein-specific circulating immunoglobulin G-positive (IgG(+)) B lymphocytes, whereas a skewed B cell repertoire was observed in patients in IR. Thus, a blockage of B cell maturation, a prolonged repopulation with naïve B cells, and a delayed reappearance of memory B cells, which resulted in the disappearance of circulating desmoglein-specific IgG(+) B lymphocytes, contribute to the long-lasting effectiveness of rituximab for treating pemphigus.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Linfocitos B/inmunología , Desmogleínas/inmunología , Pénfigo/tratamiento farmacológico , Humanos , Inmunofenotipificación , Pénfigo/inmunología , Pénfigo/fisiopatología , Rituximab
18.
J Biomed Opt ; 17(2): 026009, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22463041

RESUMEN

Multiphoton microscopy has emerged in the past decade as a promising tool for noninvasive skin imaging. Our aim was to evaluate the potential of multiphoton microscopy to detect topical corticosteroids side effects within the epidermis and to provide new insights into their dynamics. Healthy volunteers were topically treated with clobetasol propionate on a small region of their forearms under overnight occlusion for three weeks. The treated region of each patient was investigated at D0, D7, D15, D22 (end of the treatment), and D60. Our study shows that multiphoton microscopy allows for the detection of corticoid-induced epidermis modifications: thinning of stratum corneum compactum and epidermis, decrease of keratinocytes size, and changes in their morphology from D7 to D22. We also show that multiphoton microscopy enables in vivo three-dimensional (3-D) quantitative assessment of melanin content. We observe that melanin density decreases during treatment and almost completely disappears at D22. Moreover, these alterations are reversible as they are no longer present at D60. Our study demonstrates that multiphoton microscopy is a convenient and powerful tool for noninvasive 3-D dynamical studies of skin integrity and pigmentation.


Asunto(s)
Corticoesteroides , Epidermis/efectos de los fármacos , Epidermis/patología , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Trastornos de la Pigmentación/inducido químicamente , Trastornos de la Pigmentación/patología , Administración Tópica , Adulto , Atrofia/inducido químicamente , Atrofia/patología , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto Joven
19.
Arch Dermatol ; 145(5): 537-42, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19451497

RESUMEN

OBJECTIVE: To identify prognostic factors for relapse in the first year after cessation of therapy in bullous pemphigoid (BP). DESIGN: Prospective, multicenter, cohort study (January 1, 2000, through December 31, 2006). SETTING: Fifteen French dermatology departments. Patients Patients with BP in remission under low doses of topical or systemic corticosteroids. Interventions Cessation of corticosteroid treatment (day 0) followed by a systematic clinical and immunologic follow-up. MAIN OUTCOME MEASURES: The end point was clinical relapse within the first year after cessation of therapy. Associations of clinical, biological, and immunologic (including direct immunofluorescence, serum anti-basement membrane zone autoantibodies, and serum BP180 autoantibodies by enzyme-linked immunosorbent assay [ELISA] on day 0) variables with clinical relapse were assessed by means of univariate and multivariate analyses. RESULTS: On day 0, 30 of 114 patients (26.3%) still had a positive result of direct immunofluorescence, 63 of 112 (56.3%) had circulating anti-basement membrane zone autoantibodies, and 34 of 57 (60%) had anti-BP180 antibodies by ELISA. At month 12, 22 patients were dead (n = 11) or lost to follow-up (n = 11), 51 were in remission, and 45 had had relapses (mean interval to relapse, 3.2 months). Factors predictive of relapse within 12 months after cessation of therapy were a positive result of direct immunofluorescence microscopy (P = .02), a greater age (P = .01), and high-titer ELISA scores (P = .02) on day 0. In multivariate analysis, the only factor independently predictive of relapse was a high-titer ELISA score on day 0 (odds ratio, 11.00; 95% confidence interval, 1.29-93.76). CONCLUSIONS: High-titer anti-BP180 ELISA score and, to a lesser degree, a positive direct immunofluorescence finding are good indicators of further relapse of BP. At least 1 of these tests should be performed before therapy is discontinued.


Asunto(s)
Autoantígenos/inmunología , Glucocorticoides/administración & dosificación , Colágenos no Fibrilares/inmunología , Penfigoide Ampolloso/epidemiología , Inducción de Remisión/métodos , Medición de Riesgo/métodos , Anciano , Anciano de 80 o más Años , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Autoantígenos/sangre , Intervalos de Confianza , Relación Dosis-Respuesta a Droga , Vías de Administración de Medicamentos , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnica del Anticuerpo Fluorescente Directa , Estudios de Seguimiento , Francia/epidemiología , Humanos , Masculino , Microscopía Fluorescente , Persona de Mediana Edad , Morbilidad/tendencias , Colágenos no Fibrilares/sangre , Oportunidad Relativa , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/inmunología , Pronóstico , Estudios Prospectivos , Recurrencia , Factores de Riesgo , Tasa de Supervivencia/tendencias , Factores de Tiempo , Colágeno Tipo XVII
20.
J Invest Dermatol ; 129(7): 1681-7, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19177141

RESUMEN

Superpotent topical corticosteroids (CS) have been demonstrated to improve bullous pemphigoid (BP) patients' survival. We assessed whether a mild regimen using lower doses of topical CS and a shorter duration could improve the outcome of BP patients even more. Three-hundred and twelve BP patients were included in a multicenter randomized controlled trial and stratified depending on the extent of BP as moderate (n=134) or extensive (n=178). Patients were randomly assigned to the standard regimen (clobetasol propionate cream, 40 g per day initially, with CS tapering over 12 months) or the mild regimen (10-30 g per day), with CS tapering over 4 months. A noninferior rate of BP control was obtained with the mild regimen 156/159 (98%) as compared with the standard regimen 150/150 (100%; P=0.005). Event-free survival, that is, the combined outcome of deaths and life-threatening adverse events did not differ between the two treatment groups (P=0.77). However, upon adjusting through the Cox model for age and Karnofsky score, a strong beneficial effect of the mild regimen was observed in patients with moderate BP, with an almost twofold decrease in the risk of death or life-threatening adverse events relative to the standard regimen (hazard ratio=0.54; 95% confidence interval, 0.30-0.97; P=0.039). This mild regimen allows a 70% reduction of the cumulative doses of CS and improves BP patients' outcome.


Asunto(s)
Clobetasol/administración & dosificación , Glucocorticoides/administración & dosificación , Penfigoide Ampolloso/tratamiento farmacológico , Administración Tópica , Glándulas Suprarrenales/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Clobetasol/efectos adversos , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Glucocorticoides/efectos adversos , Humanos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Masculino , Modelos de Riesgos Proporcionales , Recurrencia , Resultado del Tratamiento
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA