RESUMEN
Aero-allergens, such as house dust mite (HDM), have been suggested to play a role in the initiation of atopic dermatitis (AD)-related skin inflammation. Here, we analysed the proliferation and the cytokine expression of blood-derived T cells from AD and healthy individuals upon HDM-allergen stimulation. The proliferating cells from healthy individuals and AD patients had a significantly different, distinct cytokine profile: in AD blood, we found increased frequencies of HDM-reactive IL-31-producing T cells, as well as a decreased Th1/Th2 and Tc1/Tc2 ratio, suggesting that allergen-specific T cells in blood of chronic AD patients are subject to pre-existent Th2-Tc2 and "Th31-Tc31" programming.
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Antígenos Dermatofagoides/farmacología , Linfocitos T CD8-positivos/metabolismo , Dermatitis Atópica/sangre , Interleucinas/metabolismo , Células TH1/metabolismo , Células Th2/metabolismo , Adulto , Animales , Recuento de Linfocito CD4 , Linfocitos T CD8-positivos/inmunología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Dermatitis Atópica/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pyroglyphidae , Células TH1/inmunología , Células Th2/inmunología , Adulto JovenRESUMEN
BACKGROUND /OBJECTIVES: Environmental exposure and personal susceptibility both contribute to the development of hand eczema. Here, we report an investigation on wet work exposure and its influence on the risk of developing hand eczema in apprentice nurses. METHODS: A prospective cohort study was performed among 721 Dutch apprentice nurses. Participants recorded wet work exposure and symptoms of hand eczema using specially designed diary cards. RESULTS: For 533 apprentice nurses, a follow-up time of 1-3 years was completed. Diary cards were supplied by 383 students. The 1-year period prevalence of hand eczema was 23% in the first year, 25% in the second year and 31% in the third year of follow-up. Eighty-one new cases of hand eczema developed, most of which occurred during the first year of follow-up. In approximately one-third of the participants, wet work exposure exceeded the national guidelines. Frequent hand washing during traineeships [odds ratio (OR) 1.5; 90% confidence interval (CI) 1.0-2.3], frequent hand washing at home (OR 2.3; 90% CI 1.5-3.7) and having a side job involving wet work (OR 1.6; 90% CI 1.0-2.4) were independent risk factors for hand eczema. CONCLUSION: As a considerable number of apprentice nurses had already developed hand eczema during traineeships, more attention should be paid to skin protection in vocational education.
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Dermatitis Profesional/etiología , Dermatosis de la Mano/etiología , Desinfección de las Manos , Exposición Profesional/efectos adversos , Estudiantes de Enfermería , Adulto , Dermatitis Alérgica por Contacto/epidemiología , Dermatitis Alérgica por Contacto/etiología , Dermatitis Atópica/epidemiología , Dermatitis Atópica/etiología , Dermatitis Irritante/epidemiología , Dermatitis Irritante/etiología , Dermatitis Profesional/epidemiología , Femenino , Estudios de Seguimiento , Dermatosis de la Mano/epidemiología , Humanos , Masculino , Modelos Estadísticos , Países Bajos/epidemiología , Exposición Profesional/estadística & datos numéricos , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
BACKGROUND/OBJECTIVES: Environmental exposure and personal susceptibility both contribute to the development of hand eczema. In this study, we investigated the effect of loss-of-function mutations in the filaggrin gene (FLG), atopic dermatitis and wet work exposure on the development of hand eczema in apprentice nurses. METHODS: Dutch apprentice nurses were genotyped for the four most common FLG mutations; atopic dermatitis and hand eczema history were assessed by questionnaire. Exposure and hand eczema during traineeships were assessed with diary cards. RESULTS: The prevalence of hand eczema during traineeships was higher among subjects with a history of hand eczema reported at inclusion. Hand washing during traineeships and at home increased the risk of hand eczema. After adjustment for the effects of exposure and FLG mutations, an odds ratio of 2.5 (90% confidence interval 1.7-3.7) was found for a history of atopic dermatitis. In this study, an increased risk of hand eczema conferred by FLG mutations could not be shown, but subjects with concomitant FLG mutations and atopic dermatitis showed the highest risk of hand eczema during traineeships. CONCLUSION: A history of atopic dermatitis, a history of hand eczema and wet work exposure were the most important factors increasing the risk of hand eczema during traineeships.
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Dermatitis Atópica/genética , Dermatitis Profesional/genética , Dermatosis de la Mano/genética , Proteínas de Filamentos Intermediarios/genética , Mutación , Dermatitis Irritante/genética , Proteínas Filagrina , Predisposición Genética a la Enfermedad , Desinfección de las Manos , Humanos , Enfermeras y Enfermeros , Permeabilidad , Estudios Prospectivos , Factores de Riesgo , Piel/metabolismo , Crema para la Piel/uso terapéuticoRESUMEN
BACKGROUND/AIMS: Vitiligo is considered to be an autoimmune disease and is known to be associated with other autoimmune diseases, particularly affecting the thyroid. In children and adolescents this association has been reported in only a few studies, with varying results. The aim of this study was to examine thyroid function and prevalence of thyroid autoimmunity in children and adolescents with vitiligo and to investigate the utility of screening. METHODS: Two hundred and sixty patients with vitiligo were enrolled. Plasma TSH, FT4 and anti-thyroid peroxidase (TPO) antibody concentrations were measured. The prevalence of thyroid dysfunction and autoimmunity were compared to the general healthy paediatric population. RESULTS: Autoimmune thyroiditis (AIT) with thyroid hormone disturbances was diagnosed in 16 patients (6.2%). This is significantly higher than the prevalence reported in the general healthy paediatric population. Increased levels of anti-TPO antibodies (= 30 kU/l), without thyroid hormone disturbances, were found in 27 patients (10.5%). CONCLUSION: The prevalence of AIT in children and adolescents with vitiligo is significantly higher than in the general population. It may be advantageous to screen thyroid function and antibody levels in all paediatric patients with non-segmental vitiligo. To strengthen recommendations on screening, research on the burden for patients and cost-effectiveness is needed.
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Tiroiditis Autoinmune/complicaciones , Tiroiditis Autoinmune/epidemiología , Vitíligo/complicaciones , Adolescente , Enfermedades Autoinmunes/complicaciones , Niño , Femenino , Humanos , Yoduro Peroxidasa/inmunología , Masculino , Países Bajos/epidemiología , Prevalencia , Enfermedades de la Tiroides/inmunología , Tirotropina/sangre , Tiroxina/sangre , Vitíligo/epidemiologíaRESUMEN
The mechanisms preventing detrimental T-cell responses against commensal skin bacteria remain elusive. Using monocyte-derived and skin-derived dendritic cells (DCs), we demonstrate that epidermal Langerhans cells (LCs), the DCs in the most superficial layer of the skin, have a poor capacity to internalize bacteria because of low expression of FcγRIIa. Furthermore, LCs show deficiency in processing and major histocompatibility complex II (MHC-II)-restricted presentation of bacterial antigens, as a result of a decreased expression of molecules involved in these functionalities. The reduced capacity to take up, process, and present bacterial antigens cannot be restored by LC activation by ectopically expressed Toll-like receptors or by cytokines. Consequently, bacteria-primed LCs poorly restimulate antibacterial memory CD4(+) T cells and inefficiently induce bacteria-specific effector CD4(+) T cells from naive T cells; however, they initiate the development of regulatory Foxp3(+)CD4(+) T cells, which are able to suppress the proliferation of autologous bystander T cells specific for the same bacteria. In contrast, dermal DCs that reside in the deeper dermal layer of the skin efficiently present bacterial antigens and provoke robust antibacterial naive and memory CD4(+) T-cell responses. In conclusion, LCs form a unique DC subset that is adapted at multiple levels for the maintenance of tolerance to bacterial skin flora.
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Antígenos Bacterianos/metabolismo , Proliferación Celular , Tolerancia Inmunológica/fisiología , Células de Langerhans/patología , Piel/microbiología , Linfocitos T Reguladores/patología , Antígenos CD4/metabolismo , Células Cultivadas , Factores de Transcripción Forkhead/metabolismo , Humanos , Inmunidad Celular , Células de Langerhans/inmunología , Células de Langerhans/metabolismo , Receptores de IgG/metabolismo , Piel/inmunología , Piel/patología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Receptores Toll-Like/metabolismoRESUMEN
BACKGROUND: There is a need for biomarkers to screen the effectiveness of (novel) therapeutic agents for psoriasis at an early stage. OBJECTIVE: We aimed to determine which of the changes in psoriatic skin correlates best with clinical improvement 4 weeks after effective adalimumab therapy. METHODS: Twenty-two psoriatic arthritis patients were randomized to receive adalimumab or placebo. T cell numbers and markers of innate immunity were estimated in lesional and nonlesional skin biopsies at baseline and after 4 weeks of treatment. RESULTS: CD161+ and elastase+ dermal cells in lesional skin were significantly reduced upon 4 weeks of successful adalimumab treatment compared with placebo. CONCLUSION: Early improvement of psoriasis lesions during adalimumab therapy is associated with a marked reduction of infiltrated dermal CD161+ T cells and elastase+ neutrophils, suggesting that these parameters could be used as biomarkers to monitor early changes after active treatment in small proof-of-concept studies of short duration.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Piel/efectos de los fármacos , Adalimumab , Adulto , Anciano , Artritis Psoriásica/metabolismo , Biomarcadores/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Psoriasis/metabolismo , Linfocitos T/metabolismo , Adulto JovenRESUMEN
INTRODUCTION: Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis. Alefacept (a lymphocyte function-associated antigen (LFA)-3 Ig fusion protein that binds to CD2 and functions as an antagonist to T-cell activation) has been shown to result in improvement in psoriasis but has limited effectiveness in PsA. Interleukin-20 (IL-20) is a key proinflammatory cytokine involved in the pathogenesis of psoriasis. The effects of alefacept treatment on IL-20 expression in the synovium of patients with psoriasis and PsA are currently unknown. METHODS: Eleven patients with active PsA and chronic plaque psoriasis were treated with alefacept (7.5 mg per week for 12 weeks) in an open-label study. Skin biopsies were taken before and after 1 and 6 weeks, whereas synovial biopsies were obtained before and 4 and 12 weeks after treatment. Synovial biopsies from patients with rheumatoid arthritis (RA) (n = 10) were used as disease controls. Immunohistochemical analysis was performed to detect IL-20 expression, and stained synovial tissue sections were evaluated with digital image analysis. Double staining was performed with IL-20 and CD68 (macrophages), and conversely with CD55 (fibroblast-like synoviocytes, FLSs) to determine the phenotype of IL-20-positive cells in PsA synovium. IL-20 expression in skin sections (n = 6) was analyzed semiquantitatively. RESULTS: IL-20 was abundantly expressed in both PsA and RA synovial tissues. In inflamed PsA synovium, CD68+ macrophages and CD55+ FLSs coexpressed IL-20, and its expression correlated with the numbers of FLSs. IL-20 expression in lesional skin of PsA patients decreased significantly (P = 0.04) 6 weeks after treatment and correlated positively with the Psoriasis Area and Severity Index (PASI). IL-20 expression in PsA synovium was not affected by alefacept. CONCLUSIONS: Conceivably, the relatively limited effectiveness of alefacept in PsA patients (compared with anti-tumor necrosis factor (TNF) therapy) might be explained in part by persistent FLS-derived IL-20 expression.
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Artritis Psoriásica/tratamiento farmacológico , Fármacos Dermatológicos/uso terapéutico , Interleucinas/metabolismo , Proteínas Recombinantes de Fusión/uso terapéutico , Piel/metabolismo , Membrana Sinovial/metabolismo , Adulto , Alefacept , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Artritis Psoriásica/metabolismo , Artritis Psoriásica/patología , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Biopsia , Antígenos CD55/metabolismo , Fármacos Dermatológicos/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Recombinantes de Fusión/farmacología , Piel/efectos de los fármacos , Piel/patología , Membrana Sinovial/efectos de los fármacos , Membrana Sinovial/patología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Interleukin (IL)-31 has been associated with pruritus, a characteristic feature of atopic dermatitis (AD). Local T cell responses may be responsible for the increased level of IL-31 mRNA observed in AD. We investigated the frequency of IL-31-producing T cells in AD lesions, as well as their cytokine profile. T cells were isolated from chronic AD lesions, autologous blood and healthy donor skin. Intracellular expression of IL-31, IFN-γ, IL-13, IL-17 and IL-22 was measured using flow cytometry. T cells from AD lesions contained significantly higher percentages of IL-31-producing T cells compared to autologous blood and donor skin. Many IL-31-producing T cells co-produced IL-13 and to lesser extent IL-22, but rarely IFN-γ or IL-17. A substantial part of the IL-31-producing T cells did not co-produce any of the other cytokines and could therefore not be linked to any of the known functionally different T cell subsets. The T cell infiltrates were also relatively enriched for Th2/Tc2 and Th22/Tc22 cells, while frequencies of Th1/Tc1 and Th17 cells were decreased. This is the first report describing the detection of IL-31 at protein level in skin-infiltrating T cells. We show here that T cells in chronic AD skin produce IL-31 and that AD lesions contain increased levels of these IL-31-producing T cells. This suggests that a substantial part of previously reported increased IL-31 mRNA levels in AD skin is T cell derived and that these cells may be involved in the pathogenesis of AD.
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Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Dermatitis Atópica/inmunología , Interleucinas/sangre , Adulto , Anciano , Dermatitis Atópica/metabolismo , Femenino , Humanos , Interferón gamma/metabolismo , Interleucinas/metabolismo , Masculino , Persona de Mediana Edad , Piel/inmunología , Adulto JovenRESUMEN
BACKGROUND: Erythema dyschromicum perstans and postinflammatory hyperpigmentation (PIH) are characterized by papillary dermal pigmentation or pigment incontinence. To date, no standard treatment is available. Fractional laser therapy (FLT) was recently reported to improve different pigment disorders. OBJECTIVES: To assess the efficacy and safety of non-ablative FLT in the treatment of erythema dyschromicum perstans and PIH. METHODS: Eight patients with erythema dyschromicum perstans and six patients with PIH were included. In each patient, two similar test regions were randomized to receive either five fractional laser treatments in combination with intermittent daily topical bleaching or the same intermittent regimen of topical bleaching alone. Three months after the last treatment, improvement of hyperpigmentation was assessed by melanin index, reflectance spectroscopy, physician's assessment, patient's assessment and patient's satisfaction. In addition, a biopsy of both laser treated and control site was evaluated by an independent blinded pathologist. RESULTS: No clinical improvement of hyperpigmentation was observed. Reflectance spectroscopy, melanin index, number of melanocytes and amount of dermal melanin did not significantly differ. Patients considered FLT unsatisfactory. Moreover, three patients developed laser-induced PIH. CONCLUSIONS: With these specific laser settings, non-ablative FLT was not effective for the treatment of erythema dyschromicum perstans and PIH.
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Eritema/radioterapia , Hiperpigmentación/radioterapia , Terapia por Láser , Adulto , Eritema/patología , Femenino , Humanos , Hiperpigmentación/etiología , Hiperpigmentación/patología , Inflamación/complicaciones , Terapia por Láser/efectos adversos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Método Simple Ciego , Adulto JovenRESUMEN
BACKGROUND: Fractional laser therapy (FLT) has become a widely accepted modality for skin rejuvenation and has also been used in various other skin diseases. OBJECTIVE: To observe long-term histologic effects of nonablative and ablative FLT in the treatment of pigment disorders. METHODS: A randomized controlled observer-blinded study was performed in 18 patients with pigment disorders. Two similar test regions were randomized to receive FLT with intermittent topical bleaching or topical bleaching alone. Patients with ashy dermatosis (AD) and postinflammatory hyperpigmentation (PIH) were treated using nonablative 1,550-nm FLT (15 mJ/microbeam, 14-20% coverage), whereas patients with Becker's nevus (BN) were treated with ablative 10,600-nm FLT (10 mJ/microbeam, 35-45% coverage) for three to five sessions. Biopsies were obtained 3 months after the last treatment. RESULTS: At follow-up, dermal fibrosis was observed in four of eight patients treated using ablative FLT and no patients treated using nonablative FLT (p < .05). CONCLUSIONS: Assuming that the dermal response is comparable in AD, PIH, and BN, at the given settings, ablative FLT may induce fibrosis, whereas treatment with nonablative FLT does not. Whether formation of fibrosis has to be regarded as dermal remodeling or a subtle subclinical form of scarring should be investigated in future research.
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Fibrosis/etiología , Terapia por Luz de Baja Intensidad/métodos , Trastornos de la Pigmentación/radioterapia , Adulto , Biopsia , Femenino , Humanos , Masculino , Resultado del TratamientoRESUMEN
PURPOSE: To predict the potential antitumor effect of antigen-specific T cells in melanoma patients, we investigated T-cell effector function in relation to tumor-escape mechanisms. EXPERIMENTAL DESIGN: CD8(+) T cells isolated from tumor, adjacent normal skin, and peripheral blood of 17 HLA-A2(+) patients with advanced-stage melanoma were analyzed for their antigen specificity and effector function against melanocyte differentiation antigens MART-1, gp100, and tyrosinase by using HLA-A2/peptide tetramers and functional assays. In addition, the presence of tumor-escape mechanisms PD-L1/PD-1 pathway, FoxP3 and loss of HLA or melanocyte differentiation antigens, both required for tumor cell recognition and killing, were studied. RESULTS: Higher percentages of melanocyte antigen-specific CD8(+) T cells were found in the melanoma tissues as compared with adjacent normal skin and peripheral blood. Functional analysis revealed 2 important findings: (i) in 5 of 17 patients, we found cytokine production after specific peptide stimulation by tumor-infiltrating lymphocytes (TIL), not by autologous peripheral blood lymphocytes (PBL); (ii) CD8(+) T cells from 7 of 17 patients did not produce cytokines after specific stimulation, which corresponded with significant loss of tumor HLA-A2 expression. The presence of other tumor-escape mechanisms did not correlate to T-cell function. CONCLUSIONS: Our data show that functional T-cell responses could be missed when only PBL and not TIL are evaluated, emphasizing the importance of TIL analysis for immunomonitoring. Furthermore, loss of tumor HLA-A2 may explain the lack of T-cell functionality. These findings have important implications for selecting melanoma patients who may benefit from immunotherapy.
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Linfocitos T CD8-positivos/inmunología , Inmunoterapia , Linfocitos Infiltrantes de Tumor/inmunología , Melanoma/inmunología , Piel/inmunología , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/biosíntesis , Linfocitos T CD4-Positivos , Células Cultivadas , Citocinas/biosíntesis , Citotoxicidad Inmunológica , Femenino , Factores de Transcripción Forkhead/biosíntesis , Antígeno HLA-A2/biosíntesis , Antígeno HLA-A2/inmunología , Humanos , Activación de Linfocitos , Antígeno MART-1/inmunología , Masculino , Melanoma/sangre , Melanoma/patología , Melanoma/terapia , Persona de Mediana Edad , Monofenol Monooxigenasa/inmunología , Escape del Tumor , Antígeno gp100 del Melanoma/inmunologíaRESUMEN
BACKGROUND: Becker nevus (BN) is an uncommon pigment disorder characterized by hyperpigmentation and sometimes hypertrichosis. To date, no effective treatment has been available. OBJECTIVES: We sought to assess efficacy and safety of ablative 10,600-nm fractional laser therapy (FLT) in the treatment of BN. METHODS: Eleven patients with BN, older than 18 years, were included in a prospective randomized controlled, observer-blinded split-lesion trial. In each patient two similar square test regions were randomized to either ablative FLT at 10 mJ/microbeam, coverage 35% to 45%, and topical bleaching (to prevent laser-induced postinflammatory hyperpigmentation), or topical bleaching alone (to allow comparison of the regions). At 3- and 6-month follow-up, clearance of hyperpigmentation was assessed by physician global assessment, reflectance spectroscopy, melanin index, patient global assessment, patient satisfaction, and histology. RESULTS: At 6-month follow-up, physician global assessment improved in the FLT region (P < .05). Reflectance spectroscopy, melanin index, number of melanocytes, and amount of dermal melanin did not significantly differ between the regions. Patient global assessment and patient satisfaction were 5.0 and 5.9 (visual analog scale score, 0-10), respectively. Side effects were postinflammatory hyperpigmentation (n = 3), erythema (n = 3), burning sensation (n = 3), crusting (n = 3), edema (n = 2), and blistering (n = 2). LIMITATIONS: Limitations include the small number of patients, treatment in spring, possibly suboptimal laser settings, and the combined usage of FLT and a bleaching agent. CONCLUSION: Ablative FLT was moderately effective in some patients with BN. However, postinflammatory hyperpigmentation and relatively negative patient-reported outcomes still preclude ablative FLT from being a standard therapy. Larger studies with different laser settings will be required to optimize this treatment modality.
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Terapia por Láser , Nevo/cirugía , Neoplasias Cutáneas/cirugía , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Método Simple Ciego , Adulto JovenRESUMEN
There is no gold standard for a definite diagnosis of atopic dermatitis. For the time being, several lists of diagnostic criteria have been proposed, some of them in actual use. The Millennium Criteria have been proposed to diagnose atopic dermatitis and to differentiate it from atopiform dermatitis. Our aim was to further refine the Millennium Criteria into a manageable set that can differentiate between atopic and atopiform dermatitis and other entities. The hereby refined Millennium Criteria will be compared with the UK Working Party Criteria and the Hanifin & Rajka Criteria. Data of 210 included patients were used. After multiple logistic regression, a minimum set of five criteria was identified as best discriminators: (i) typical morphology; (ii) early age of onset; (iii) Dennie-Morgan fold; (iv) historical and (v) actual flexural involvement. The refined Millennium Criteria were constituted from these criteria. When comparing the different list for validity in diagnosing atopic dermatitis, the refined Millennium Criteria showed a sensitivity of 81.8% and a specificity of 98.8% compared to a sensitivity of 97.7% and specificity of 72.9% of the UK Criteria and a sensitivity of 100% and specificity of 48.8% of the Hanifin & Rajka Criteria. This refinement and validity study shows that the refined Millennium Criteria are a valid tool to diagnose atopic and atopiform dermatitis in a hospital-based setting and therefore could be incorporated in clinical practice and trials.
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Dermatitis Atópica/diagnóstico , Adolescente , Adulto , Alérgenos , Especificidad de Anticuerpos , Niño , Preescolar , Dermatitis Atópica/inmunología , Diagnóstico Diferencial , Femenino , Humanos , Inmunoglobulina E/sangre , Lactante , Masculino , Persona de Mediana Edad , Países Bajos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
In this study, we report the previously unknown mechanism of inducing robust anti-melanoma immunity by the vitiligo-inducing compound monobenzone. We show monobenzone to increase melanocyte and melanoma cell immunogenicity by forming quinone-haptens to the tyrosinase protein and by inducing the release of tyrosinase- and melanoma antigen recognized by T cells-1 (MART-1)-containing CD63+ exosomes following melanosome oxidative stress induction. Monobenzone further augments the processing and shedding of melanocyte-differentiation antigens by inducing melanosome autophagy and enhanced tyrosinase ubiquitination, ultimately activating dendritic cells, which induced cytotoxic human melanoma-reactive T cells. These T cells effectively eradicate melanoma in vivo, as we have reported previously. Monobenzone thereby represents a promising and readily applicable compound for immunotherapy in melanoma patients.
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Autoinmunidad/efectos de los fármacos , Autofagia/efectos de los fármacos , Haptenos/metabolismo , Hidroquinonas/farmacología , Melanocitos/efectos de los fármacos , Melanosomas/efectos de los fármacos , Monofenol Monooxigenasa/metabolismo , Linfocitos T/efectos de los fármacos , Células Dendríticas/inmunología , Antígenos HLA-DR/análisis , Humanos , Lisosomas/metabolismo , Melaninas/biosíntesis , Melanocitos/inmunología , Melanoma/inmunología , Melanoma/terapia , Melanosomas/fisiología , Monofenol Monooxigenasa/inmunología , Especies Reactivas de Oxígeno/metabolismo , Pigmentación de la Piel/efectos de los fármacos , Linfocitos T/inmunología , UbiquitinaciónRESUMEN
OBJECTIVES: To provide a comprehensive overview of dermatologic adverse events of etanercept described in the literature (including all study types, case reports, and surveys) and to present information on the occurrence, severity, treatment, and course of these adverse events. DATA SOURCES: MEDLINE and EMBASE. STUDY SELECTION: All reports on individual patients who developed a dermatologic adverse event associated with systemic etanercept treatment for any indication in any type of original article were included. DATA EXTRACTION: All data were independently extracted by 2 reviewers. Disagreements were resolved by consensus. All articles included (except for case reports/case series) were assessed regarding level of evidence. DATA SYNTHESIS: In 126 included study reports, a total of 72 separate specific dermatologic adverse events of etanercept were mentioned. In 101 case reports/case series, 153 individual patients with approximately 65 different specific diagnoses (eg, not rash) were reported. CONCLUSIONS: Etanercept is associated with a wide variety of dermatologic adverse events, many of which were described in study reports, but case reports also described numerous exceptional cases. Although the adverse events are usually mild, some reactions are serious and even potentially life threatening. Therefore, all drug-associated cutaneous abnormalities should be carefully evaluated. Diagnostic steps do not deviate from the norm in these patients, but management of the dermatologic adverse events may need special attention.
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Erupciones por Medicamentos/etiología , Inmunoglobulina G/efectos adversos , Factores Inmunológicos/efectos adversos , Animales , Erupciones por Medicamentos/diagnóstico , Erupciones por Medicamentos/patología , Etanercept , Humanos , Receptores del Factor de Necrosis Tumoral , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Various treatments are currently available for melasma. However, results are often disappointing. OBJECTIVE: We sought to assess the efficacy and safety of nonablative 1550-nm fractional laser therapy and compare results with those obtained with triple topical therapy (the gold standard). METHODS: Twenty female patients with moderate to severe melasma and Fitzpatrick skin types II to V were treated either with nonablative fractional laser therapy or triple topical therapy (hydroquinone 5%, tretinoin 0.05%, and triamcinolone acetonide 0.1% cream) once daily for 8 weeks in a randomized controlled observer-blinded study. Laser treatment was performed every 2 weeks for a total of 4 times. Physician Global Assessment was assessed at 3 weeks, 3 months, and 6 months after the last treatment. RESULTS: Physician Global Assessment improved (P < .001) in both groups at 3 weeks. There was no difference in Physician Global Assessment between the two groups. Mean treatment satisfaction and recommendation were significantly higher in the laser group at 3 weeks (P < .05). However, melasma recurred in 5 patients in both groups after 6 months. Side effects in the laser group were erythema, burning sensation, facial edema, and pain; in the triple group side effects were erythema, burning, and scaling. LIMITATIONS: Limitations were: small number of patients; only one set of laser parameters; and a possible difference in motivation between groups. CONCLUSIONS: Nonablative fractional laser therapy is safe and comparable in efficacy and recurrence rate with triple topical therapy. It may be a useful alternative treatment option for melasma when topical bleaching is ineffective or not tolerated. Different laser settings and long-term maintenance treatment should be tested in future studies.
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Terapia por Láser/métodos , Melanosis/terapia , Administración Tópica , Adulto , Femenino , Humanos , Hidroquinonas/uso terapéutico , Terapia por Láser/efectos adversos , Melanosis/tratamiento farmacológico , Persona de Mediana Edad , Proyectos Piloto , Recurrencia , Resultado del Tratamiento , Tretinoina/uso terapéutico , Triamcinolona Acetonida/uso terapéuticoAsunto(s)
Permeabilidad de la Membrana Celular/fisiología , Dermatitis Atópica/fisiopatología , Proteínas de Filamentos Intermediarios/genética , Mutación/genética , Fenómenos Fisiológicos de la Piel , Piel/fisiopatología , Adulto , Estudios de Casos y Controles , Permeabilidad de la Membrana Celular/genética , Dermatitis Atópica/genética , Femenino , Proteínas Filagrina , Genotipo , Humanos , Membrana Dobles de Lípidos , Masculino , Persona de Mediana Edad , Polietilenglicoles/farmacocinética , Pérdida Insensible de Agua/fisiologíaRESUMEN
BACKGROUND: Although recent studies indicate a crucial role for IL-17A and IL-22 producing T cells in the pathogenesis of psoriasis, limited information is available on their frequency and heterogeneity and their distribution in skin in situ. METHODOLOGY/PRINCIPAL FINDINGS: By spectral imaging analysis of double-stained skin sections we demonstrated that IL-17 was mainly expressed by mast cells and neutrophils and IL-22 by macrophages and dendritic cells. Only an occasional IL-17(pos), but no IL-22(pos) T cell could be detected in psoriatic skin, whereas neither of these cytokines was expressed by T cells in normal skin. However, examination of in vitro-activated T cells by flow cytometry revealed that substantial percentages of skin-derived CD4 and CD8 T cells were able to produce IL-17A alone or together with IL-22 (i.e. Th17 and Tc17, respectively) or to produce IL-22 in absence of IL-17A and IFN-γ (i.e. Th22 and Tc22, respectively). Remarkably, a significant proportional rise in Tc17 and Tc22 cells, but not in Th17 and Th22 cells, was found in T cells isolated from psoriatic versus normal skin. Interestingly, we found IL-22 single-producers in many skin-derived IL-17A(pos) CD4 and CD8 T cell clones, suggesting that in vivo IL-22 single-producers may arise from IL-17A(pos) T cells as well. CONCLUSIONS/SIGNIFICANCE: The increased presence of Tc17 and Tc22 cells in lesional psoriatic skin suggests that these types of CD8 T cells play a significant role in the pathogenesis of psoriasis. As part of the skin-derived IL-17A(pos) CD4 and CD8 T clones developed into IL-22 single-producers, this demonstrates plasticity in their cytokine production profile and suggests a developmental relationship between Th17 and Th22 cells and between Tc17 and Tc22 cells.
Asunto(s)
Linfocitos T CD8-positivos/metabolismo , Interleucina-17/metabolismo , Interleucinas/metabolismo , Psoriasis/metabolismo , Piel/metabolismo , Adulto , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/patología , Células Dendríticas/metabolismo , Citometría de Flujo , Humanos , Inmunohistoquímica , Macrófagos/metabolismo , Masculino , Mastocitos/metabolismo , Persona de Mediana Edad , Neutrófilos/metabolismo , Psoriasis/patología , Piel/patología , Interleucina-22RESUMEN
Tertiary teledermatology (TTD), where a general dermatologist consults a specialized dermatologist on difficult cases, is a relatively new telemedicine service. We evaluated TTD in a Dutch university hospital, where 13 general dermatologists used TTD to consult 11 specialized dermatologists and two residents at the university medical centre. We measured the avoided referrals to the university centre, the usability of the system and the user acceptance of it. During a three-month study, general dermatologists consulted via TTD 28 times. In 17 of the consultations (61%), the general dermatologists would have referred their patients to the university centre if teledermatology had not been available. Referral was not necessary after teledermatology for 12 of these 17 consultations (71%). The mean usability score (0-100) of all the users was 80. All dermatologists were satisfied with TTD (mean satisfaction of 7.6 on a 10-point scale) and acceptance was high. The baseline measurements showed that half of tertiary referrals were suitable for TTD. These results suggest that TTD reduces unnecessary physical referrals and that users are satisfied with it. A large-scale evaluation is now required.