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BACKGROUND: Evidence on the (long-term) safety of systemic immunomodulating therapies in atopic dermatitis (AD) generated by real-world data is sparse. OBJECTIVES: To describe real-world reported adverse drug reactions (AEs) related to systemic immunomodulating therapy in patients with AD and to compare the incidence rates of AEs with the Summaries of Product Characteristics (SmPCs). METHODS: We conducted an observational prospective multi-centre cohort study, using the TREAT NL registry. All severe AEs, AEs of special interest and serious AEs in adult and paediatric patients on systemic immunomodulating treatment (ciclosporin, methotrexate, azathioprine, mycophenolic acid, dupilumab, tralokinumab, baricitinib and upadacitinib) were assessed. Incidences rates of all (potentially) drug-related AEs were standardized in patient years and compared to the cumulative incidences in the associated SmPCs. RESULTS: We collected 422 patient years of safety data from 266 patients, of whom 129 (48.5%) reported a total of 224 (potentially) drug-related AEs. Compared to dupilumab's SmPC, higher incidence rates were found for four AEs (reported ≥5 times): eosinophilia, blepharitis, dry eyes and head and neck erythema (i.e. dupilumab facial redness). A higher incidence rate of fatigue was found in patients on oral methotrexate in our cohort compared to the SmPC. Two new drug-related AEs (reported ≥5 times) were found in patients on dupilumab, including non-infectious conjunctivitis and meibomian gland dysfunction. CONCLUSIONS: Real-world reported AEs captured in AD patient registries can add information on the estimated incidence of AEs and benefit clinical decision aids. Future studies using data derived from the TREAT NL registry combined with data from other registries within the TREAT Registry Taskforce will provide more information on (rare) AEs associated with immunomodulating therapy in AD patients.
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Dermatite Atópica , Adulto , Humanos , Criança , Países Baixos/epidemiologia , Estudos de Coortes , Dermatite Atópica/tratamento farmacológico , Metotrexato/efeitos adversos , Estudos ProspectivosAssuntos
Ictiose Lamelar , Humanos , Aciltransferases , Genes Recessivos , Ictiose Lamelar/genética , Mutação , FosfolipasesRESUMO
Background: Atopic dermatitis (AD or eczema) is a most common chronic skin disease. Designing personalised treatment strategies for AD based on patient stratification is of high clinical relevance, given a considerable variation in the clinical phenotype and responses to treatments among patients. It has been hypothesised that the measurement of biomarkers could help predict therapeutic responses for individual patients. Objective: We aim to assess whether serum biomarkers can predict the outcome of systemic immunosuppressive therapy in adult AD patients. Methods: We developed a statistical machine learning model using the data of an already published longitudinal study of 42 patients who received azathioprine or methotrexate for over 24 weeks. The data contained 26 serum cytokines and chemokines measured before the therapy. The model described the dynamic evolution of the latent disease severity and measurement errors to predict AD severity scores (Eczema Area and Severity Index, (o)SCORing of AD and Patient Oriented Eczema Measure) two-weeks ahead. We conducted feature selection to identify the most important biomarkers for the prediction of AD severity scores. Results: We validated our model in a forward chaining setting and confirmed that it outperformed standard time-series forecasting models. Adding biomarkers did not improve predictive performance. Conclusions: In this study, biomarkers had a negligible and non-significant effect for predicting the future AD severity scores and the outcome of the systemic therapy.
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Atopic dermatitis is a heterogeneous disease, accompanied by a wide variation in disease presentation and the potential to identify many phenotypes that may be relevant for prognosis and treatment. We aimed to systematically review previously reported phenotypes of atopic dermatitis and any characteristics associated with them. Ovid EMBASE, Ovid MEDLINE and Web of Science were searched from inception till 12 February 2021 for studies attempting to classify atopic dermatitis. Primary outcomes are atopic dermatitis phenotypes and characteristics associated with them in subsequent analyses. A secondary outcome is the methodological approach used to derive them. In total, 8511 records were found. By focussing only on certain clinical phenotypes, 186 studies were eligible for inclusion. The majority of studies were hospital-based (59%, 109/186) and cross-sectional (76%, 141/186). The number of included patients ranged from seven to 526 808. Data-driven approaches to identify phenotypes were only used in a minority of studies (7%, 13/186). Ninety-one studies (49%) investigated a phenotype based on disease severity. A phenotype based on disease trajectory, morphology and eczema herpeticum was investigated in 56 (30%), 22 (12%) and 11 (6%) studies respectively. Thirty-six studies (19%) investigated morphological characteristics in other phenotypes. Investigated associated characteristics differed between studies. In conclusion, we present an overview of phenotype definitions used in literature for severity, trajectory, morphology and eczema herpeticum, including associated characteristics. There is a lack of uniform and consistent use of atopic dermatitis phenotypes across studies.
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Dermatite Atópica , Eczema , Erupção Variceliforme de Kaposi , Estudos Transversais , Dermatite Atópica/terapia , Humanos , Fenótipo , Índice de Gravidade de DoençaAssuntos
Dermatite Atópica , Eczema , Psoríase , Biomarcadores , Estudos de Coortes , Dermatite Atópica/diagnóstico , Humanos , Psoríase/diagnósticoRESUMO
Dupilumab is a relatively new treatment option for patients with moderate to severe atopic dermatitis. There is a lack of knowledge about the effects of treatment with dupilumab during conception for both men and women, as well as during pregnancy and lactation in women. We report four patients (two men, two women) who expressed a wish to conceive during treatment with dupilumab in daily practice. Both men conceived during dupilumab treatment, while the two women discontinued dupilumab because of anticipated pregnancy. Apart from disease flares in both of the patients who discontinued treatment, no complications were reported concerning the ability to conceive, the course of the pregnancy or the fetal outcome. We present an overview of the current available literature on dupilumab during conception, pregnancy and lactation, which can guide considerations for patients on dupilumab wishing to conceive a child. Until more data are available, preference should be given to treatment with topical corticosteroids, phototherapy, systemic corticosteroids and ciclosporin.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Fertilização , Adulto , Feminino , Humanos , Lactação , Masculino , Gravidez , Resultado da Gravidez , Suspensão de TratamentoRESUMO
BACKGROUND: Biomarkers to objectively measure disease severity and predict therapeutic responses are needed in atopic dermatitis (AD). OBJECTIVE: Primary aim: To identify biomarkers reflecting therapeutic response in patients with AD treated systemically. Secondary aims: (i) To identify a biomarker pattern predicting responsiveness to systemic treatment. (ii) To identify differences in expression of biomarker in filaggrin gene (FLG) mutation carriers vs. non-FLG mutations carriers. METHODS: Thirty-eight severe AD patients treated with methotrexate or azathioprine participated. Serum levels of a proliferation-inducing ligand, B-cell activating factor of the TNF family, thymus and activation-regulated chemokine (chemokine (C-C motif) ligand 17) (TARC (CCl-17)), interleukin-1 receptor antagonist (IL-1RA), interleukin-1 bèta, IL-4, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-18, IL-31, interferon gamma, tumour necrosis factor alpha, vascular endothelial growth factor (VEGF), monokine induced by interferon gamma (chemokine (C-X-C motif) ligand 9), interferon gamma-induced protein 10 (C-X-C motif chemokine Ligand 10), monocyte chemoattractant protein-1 (chemokine (C-C Motif) ligand 2), macrophage inflammatory protein-1 beta (chemokine (C-C motif) ligand 4), regulated on activation, normal T cell expressed and secreted (chemokine (C-C motif) ligand 5), Cutaneous T-cell-attracting chemokine (chemokine (C-C motif) ligand 27) (CTACK (CCL-27)), thymic stromal lymphopoietin, IL-5, interleukin-1 alpha and granulocyte-colony stimulating factor were analysed by ELISA and Luminex. The primary outcomes were differences in mean absolute change of SCORing Atopic Dermatitis (SCORAD) between groups after 12 weeks compared with baseline. Responders to treatment were defined by a SCORAD reduction in ≥50%. Buccal mucosa swabs were collected to determine FLG genotype status. RESULTS: Thymus and activation-regulated chemokine, CTACK, IL-13 and VEGF showed a significant decrease after treatment with methotrexate or azathioprine. However, no decrease in individual cytokine levels was significantly correlated with a change in any of the outcome parameters. In addition, baseline biomarker levels were not significantly different between responders and non-responders, and FLG and non-FLG mutants showed similar biomarker profiles. CONCLUSION: Thymus and activation-regulated chemokine and CTACK were confirmed as potential biomarkers. VEGF and IL-13 have a potential value as well. Biomarkers could not be used to discriminate at baseline between responders and non-responders, or FLG genotype status.
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Dermatite Atópica , Terapia de Imunossupressão , Adulto , Biomarcadores , Quimiocina CCL17/genética , Quimiocinas , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/genética , Proteínas Filagrinas , Humanos , Fator A de Crescimento do Endotélio VascularRESUMO
BACKGROUND: Dupilumab is the first biologic registered for the treatment of moderate-to-severe atopic dermatitis (AD), and efficacy was shown in phase III clinical trials (primary outcome at week 16 was reached in 38% of patients). Currently, there are limited daily practice data available for dupilumab, especially when it is combined with systemic immunosuppressants. OBJECTIVES: To evaluate dupilumab treatment in daily practice in patients with AD. METHODS: In this observational cohort study, we prospectively included all adult patients with AD who had been treated with dupilumab in two university hospitals in the Netherlands. Concomitant systemic immunosuppressive treatment was monitored. Physician-reported outcome measures and patient-reported outcome measures (PROMs) after ≥ 12 weeks of follow-up were analysed. We used a linear mixed-effects model to determine changes in scores during follow-up. RESULTS: Ninety-five patients were included. Of these, 62 patients were using systemic immunosuppressants at baseline; the use of systemic immunosuppressants was continued during dupilumab treatment in 43 patients. From baseline to 16 weeks of treatment, the estimated mean Eczema Area and Severity Index score (0-72) decreased from 18·6 [95% confidence interval (CI) 16·0-21·4)] to 7·3 (95% CI 5·4-10·0), and the estimated mean PROMs showed a decrease of 41-66%. Investigator's Global Assessment 0 or 1 (clear/almost clear) was reached in 38% of the patients. Five patients discontinued dupilumab treatment due to side-effects or ineffectiveness. Eye symptoms and orofacial (nonocular) herpes simplex virus (HSV) reactivation were reported in 62% and 8% of the patients, respectively. CONCLUSIONS: Dupilumab treatment in daily practice shows a clinically relevant improvement of physician-reported outcome measures and PROMs, which is in line with efficacy data from clinical trials. Besides frequently reported eye symptoms and orofacial (nonocular) HSV reactivation, there were no apparent safety concerns. What's already known about this topic? Dupilumab has been shown to be an efficacious treatment for atopic dermatitis in several clinical trials. However, it is known that there may be considerable differences in patient characteristics and treatment responses between clinical trials and daily practice. What does this study add? This study presents the first experience with dupilumab treatment in 95 patients with atopic dermatitis in daily practice in two Dutch university hospitals. Less stringent inclusion and exclusion criteria and follow-up schedules, in contrast to those used in clinical trials, might better represent daily practice. Dupilumab treatment shows a clinically relevant improvement of physician- and patient-reported outcome measures; besides patient-reported eye symptoms (in 59 of 95 patients; 62%) and an apparent increase in orofacial (nonocular) herpes simplex virus reactivation (eight of 95 patients; 8%), there were no other safety concerns during follow-up up to 16 weeks of dupilumab treatment.
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Dermatite Atópica , Eczema , Adulto , Anticorpos Monoclonais Humanizados , Dermatite Atópica/tratamento farmacológico , Humanos , Países Baixos , Resultado do TratamentoRESUMO
BACKGROUND: A long-term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset. OBJECTIVES: To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate-to-severe atopic eczema, to assess the long-term safety risk of these therapies in a routine clinical care setting. METHODS: We describe a registry-embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia. CONCLUSIONS: This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting. What's already known about this topic? There is a need for long-term data on the safety of systemic immunomodulating therapies in patients with atopic eczema. Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long-term safety profile against established therapies. Large numbers of patients with a long duration of follow-up are necessary in order to detect rare events like malignancies. What does this study add? The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries. We present a protocol for an investigator-initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate-to-severe atopic eczema. This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations.
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Dermatite Atópica , Eczema , Adolescente , Adulto , Anticorpos Monoclonais Humanizados , Criança , Dermatite Atópica/tratamento farmacológico , Humanos , Estudos Observacionais como Assunto , Estudos Prospectivos , Sistema de Registros , Resultado do TratamentoRESUMO
BACKGROUND: Comparative, real-life and long-term evidence on the effectiveness and safety of phototherapy and systemic therapy in moderate-to-severe atopic eczema (AE) is limited. Such data must come from well-designed prospective patient registries. Standardization of data collection is needed for direct comparisons and data pooling. OBJECTIVES: To reach a consensus on how and when to measure the previously defined domain items of the TREatment of ATopic eczema (TREAT) Registry Taskforce core dataset for research registries for paediatric and adult patients with AE. METHODS: Proposals for the measurement instruments were based on recommendations of the Harmonising Outcome Measures for Eczema (HOME) initiative, the existing AE database of TREATgermany, systematic reviews of the literature and expert opinions. The proposals were discussed at three face-to-face consensus meetings, one teleconference and via e-mail. The frequency of follow-up visits was determined by an expert survey. RESULTS: A total of 16 experts from seven countries participated in the 'how to measure' consensus process and 12 external experts were consulted. A consensus was reached for all domain items on how they should be measured by assigning measurement instruments. A minimum follow-up frequency of initially 4 weeks after commencing treatment, then every 3 months while on treatment and every 6 months while off treatment was defined. CONCLUSIONS: This core dataset for national AE research registries will aid in the comparability and pooling of data across centres and country borders, and enables international collaboration to assess the long-term effectiveness and safety of phototherapy and systemic therapy used in patients with AE. What's already known about this topic? Comparable, real-life and long-term data on the effectiveness and safety of phototherapy and systemic therapy in patients with atopic eczema (AE) are needed. There is a high diversity of outcomes and instruments used in AE research, which require harmonization to enhance comparability and allow data pooling. What does this study add? Our taskforce has reached international consensus on how and when to measure core domain items for national AE research registries. This core dataset is now available for use by researchers worldwide and will aid in the collection of unified data. What are the clinical implications of this work? The data collected through this core dataset will help to gain better insights into the long-term effectiveness and safety of phototherapy and systemic therapy in AE and will provide important information for clinical practice. Standardization of such data collection at the national level will also allow direct data comparisons and pooling across country borders (e.g. in the analysis of treatment-related adverse events that require large patient numbers).
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Comitês Consultivos/normas , Consenso , Dermatite Atópica/terapia , Sistema de Registros/normas , Adulto , Assistência ao Convalescente/normas , Criança , Conjuntos de Dados como Assunto , Fármacos Dermatológicos/uso terapêutico , Humanos , Fototerapia/estatística & dados numéricos , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Evidence of immunomodulatory therapies to guide clinical management of atopic eczema (AE) is scarce, despite frequent and often off-label use. Patient registries provide valuable evidence for the effects of treatments under real-world conditions that can inform treatment guidelines, give the opportunity for health economic evaluation and the evaluation of quality of care, as well as pharmacogenetic and dynamic research, which cannot be adequately addressed in clinical trials. OBJECTIVES: The TREatment of ATopic eczema (TREAT) Registry Taskforce aims to seek international consensus on a core set of domains and items ('what to measure') for AE research registries, using a Delphi approach. METHODS: Participants from six stakeholder groups were included: doctors, nurses, nonclinical researchers, patients, industry and regulatory body representatives. The eDelphi comprised three sequential online rounds, requesting participants to rate the importance of each proposed domain item. Participants could add domain items to the proposed list in round 1. A final consensus meeting was held to ratify the core set. RESULTS: Participants (n = 479) from 36 countries accessed the eDelphi platform, of whom 86%, 79% and 74% completed rounds 1, 2 and 3, respectively. At the face-to-face consensus meeting attended by 42 participants the final core set was established containing 19 domains with 69 domain items (49 baseline and 20 follow-up items). CONCLUSIONS: This core set of domains and items to be captured by national AE systemic therapy registries will standardize data collection and thereby allow direct comparability across registries and facilitate data pooling between countries. Ultimately, it will provide greater insight into the effectiveness, safety and cost-effectiveness of photo- and systemic immunomodulatory therapies.
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Comitês Consultivos , Dermatite Atópica/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Cooperação Internacional , Fotoquimioterapia/normas , Consenso , Técnica Delphi , Dermatite Atópica/imunologia , Humanos , Fatores Imunológicos/normas , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Sistema de Registros/normas , Participação dos Interessados , Resultado do TratamentoRESUMO
BACKGROUND: Atopic dermatitis (AD) affects children of all skin types. Most research has focused on light skin types. Studies investigating biomarkers in people with AD with dark skin types are lacking. OBJECTIVES: To explore skin barrier and immune response biomarkers in stratum corneum (SC) tape strips from children with AD with different skin types. METHODS: Tape strips were collected from lesional and nonlesional forearm skin of 53 children with AD and 50 controls. We analysed 28 immunomodulatory mediators, and natural moisturizing factors (NMF) and corneocyte morphology. RESULTS: Interleukin (IL)-1ß, IL-18, C-X-C motif chemokine (CXCL) 8 (CXCL8), C-C motif chemokine ligand (CCL) 22 (CCL22), CCL17, CXCL10 and CCL2 were significantly higher (P < 0·05) in lesional AD skin compared with nonlesional AD skin; the opposite trend was seen for IL-1α. CXCL8, CCL2 and CCL17 showed an association with objective SCORing Atopic Dermatitis score. NMF levels showed a gradual decrease from healthy skin to nonlesional and lesional AD skin. This gradual decreasing pattern was observed in skin type II but not in skin type VI. Skin type VI showed higher NMF levels in both nonlesional and lesional AD skin than skin type II. Corneocyte morphology was significantly different in lesional AD skin compared with nonlesional AD and healthy skin. CONCLUSIONS: Minimally invasive tape-stripping is suitable for the determination of many inflammatory mediators and skin barrier biomarkers in children with AD. This study shows differences between children with AD with skin type II and skin type VI in NMF levels, suggesting that some aspects of pathophysiological mechanisms may differ in AD children with light versus dark skin types.
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Quimiocinas/análise , Dermatite Atópica/diagnóstico , Epiderme/patologia , Biomarcadores/análise , Estudos de Casos e Controles , Quimiocinas/imunologia , Quimiocinas/metabolismo , Criança , Pré-Escolar , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Epiderme/imunologia , Epiderme/metabolismo , Estudos de Viabilidade , Feminino , Proteínas Filagrinas , Humanos , Lactente , Masculino , Mutação , Permeabilidade , Proteínas S100/genética , Pigmentação da Pele/imunologiaRESUMO
BACKGROUND: Concomitant allergic contact dermatitis (ACD) has been described as a possible cause of atopic dermatitis (AD) becoming difficult-to-treat. However, contact sensitization in this patient group has barely been studied. OBJECTIVE: To study the occurrence of ACD in a population of difficult-to-treat AD children and adults. METHODS: Clinical and patch test information of 48 patients with difficult-to-treat AD unresponsive to conventional outpatient treatments was gathered retrospectively. We studied prevalence and relevance of common allergens, performed dynamic patch test analysis and assessed occurrence of polysensitization. RESULTS: In 48 patients with difficult-to-treat AD, 75% (n = 36/48) had a concomitant contact allergy, and 39% (n = 14/36) of these patients were polysensitized. ACD and polysensitization prevalences were equal amongst children and adults. The most frequent and relevant reactions were seen against wool alcohols, surfactants cocamidopropyl betaine and dimethylaminopropylamine, bichromate and fragrance mix I. Dynamic pattern analysis showed these reactions to be mostly allergic and not irritative of nature. CONCLUSION: Difficult-to-treat AD patients frequently suffer from concomitant (multiple) contact allergies, and this may be a reason why the AD turns into a difficult-to-treat disease. Awareness of this phenomenon is necessary, as pragmatic implementation of allergen avoidance strategies may be helpful in getting disease control in this population.
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Dermatite Alérgica de Contato/epidemiologia , Dermatite Atópica/epidemiologia , Adolescente , Adulto , Álcoois/efeitos adversos , Criança , Comorbidade , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Dermatite Atópica/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes do Emplastro , Perfumes/efeitos adversos , Prevalência , Estudos Retrospectivos , Tensoativos/efeitos adversos , Adulto JovemRESUMO
An eight-month-old girl was referred to the dermatologist with a progressive desquamative and purulent eruption on the scalp. Laboratory tests confirmed the diagnosis kerion celsi and the girl was successfully treated with an antimycoticum. Kerion celsi is a deep inflammatory fungal infection on the scalp. Early diagnosis is essential to prevent irreversible hair loss.
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Antifúngicos/uso terapêutico , Tinha do Couro Cabeludo/diagnóstico , Alopecia , Exantema , Feminino , Humanos , Lactente , Couro Cabeludo/patologia , Tinha do Couro Cabeludo/tratamento farmacológicoAssuntos
Azatioprina/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Imunossupressores/uso terapêutico , Proteínas de Filamentos Intermediários/genética , Mutação com Perda de Função/genética , Metotrexato/uso terapêutico , Adulto , Dermatite Atópica/genética , Feminino , Proteínas Filagrinas , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: The in vivo levels of inflammatory mediators in chronic atopic dermatitis (AD) skin are not well-defined due to the lack of a non-invasive or minimally invasive sampling technique. OBJECTIVES: To investigate the cytokine milieu in interstitial fluid (ISF) collected from chronic lesional AD skin as compared to ISF from non-lesional AD skin and/or healthy donor skin. METHODS: ISF was obtained using a minimally invasive technique of creating micropores in the skin by a laser, and harvesting ISF through aspiration. We determined the levels of 33 cytokines by Luminex and ELISA in ISF and plasma from sixteen AD patients and twelve healthy individuals. In seven AD patients, we analysed the IL-13, IL-31, IL-17, IL-22 and IFN-γ production by T cells isolated from lesional skin. AD patients were genotyped for the filaggrin gene (FLG)-null mutations 2282del4, R501X, R2447X and S3247X. RESULTS: Twenty-five of 33 examined mediators were detected in the ISF. The levels of IL-1α, IL-1ß, IL-18, IL-1RA, IL-5, IL-13, IL-6, IL-8, TNF-α, RANTES(CCL-5), MIG(CXCL-9), IP-10(CXCL-10), TARC(CCL-17), VEGF and G-CSF showed significant differences between either lesional, non-lesional and/or healthy skin. IP-10 levels in ISF from lesional and non-lesional AD skin showed significant correlation with IP-10 blood levels. IP-10 also showed a significant correlation with clinical severity (SCORAD), as did IL-13. Levels of both IP-10 and IL-13 were more pronounced in patients with FLG-null mutations. Furthermore, FLG-null mutation carriers had more severe AD. CONCLUSION: The presented minimally invasive technique is a valuable tool to determine the in vivo cytokine profile of AD skin.
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Citocinas/metabolismo , Dermatite Atópica/metabolismo , Líquido Extracelular/metabolismo , Pele/metabolismo , Estudos de Casos e Controles , Quimiocina CXCL10/metabolismo , Doença Crônica , Dermatite Atópica/genética , Proteínas Filagrinas , Genótipo , Humanos , Interleucina-13/metabolismo , Proteínas de Filamentos Intermediários/genética , Mutação , Índice de Gravidade de Doença , Manejo de Espécimes/instrumentação , Manejo de Espécimes/métodosRESUMO
BACKGROUND: There is a paucity of evidence for the use of systemic agents in children with atopic eczema refractory to conventional therapy, resulting in considerable variation in patient management. OBJECTIVES: The European TREatment of severe Atopic eczema in children Taskforce (TREAT) survey was established to collect data on current prescribing practice, to identify factors influencing the use of specific systemic agents, and to inform the design of a clinically relevant intervention study. METHODS: Consultant physician members of the paediatric dermatology societies and interest groups of eight European countries were invited to participate in a web-based survey. The multiple-response format questionnaire collated data on clinical practice in general, as well as detailed information on the use of systemic agents in refractory paediatric atopic eczema. RESULTS: In total, 343/765 members (44·8%) responded to the invitational emails; 89·2% were dermatologists and 71% initiate systemic immunosuppression for children with severe atopic eczema. The first-line drugs of choice were ciclosporin (43·0%), oral corticosteroids (30·7%) and azathioprine (21·7%). Ciclosporin was also the most commonly used second-line medication (33·6%), with methotrexate ranked as most popular third choice (26·2%). Around half of the respondents (53·7%) replied that they routinely test and treat reservoirs of cutaneous infection prior to starting systemic treatment. Across the eight countries, penicillins were the first-line antibiotic of choice (78·3%). CONCLUSIONS: In the absence of a clear evidence base, the European TREAT survey confirms the wide variation in prescribing practice of systemic immunosuppression in refractory paediatric atopic eczema. The results will be used to inform the design of a randomized controlled trial relevant to patient management across Europe.
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Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Dermatologia/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Corticosteroides/uso terapêutico , Adulto , Idoso , Antibacterianos/uso terapêutico , Criança , Europa (Continente) , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Infecções Cutâneas Estafilocócicas/diagnóstico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Adulto JovemRESUMO
BACKGROUND: The first choice treatment for vitiligo vulgaris is narrow-band UVB (NB-UVB), but no satisfactory treatment exists. OBJECTIVES: To investigate if Polypodium leucotomos, an antioxidative and immunomodulatory plant extract, improves NB-UVB-induced repigmentation. METHODS: Fifty patients with vitiligo vulgaris randomly received 250 mg oral P. leucotomos or placebo three times daily, combined with NB-UVB twice weekly for 25-26 weeks. RESULTS: Repigmentation was higher in the P. leucotomos group vs. placebo in the head and neck area (44% vs. 27%, P = 0.06). Small repigmentation increases (P = n.s.) were observed for the trunk (6% increased repigmentation), extremities (4%), and hands and feet (5%) in the P. leucotomos group vs. placebo. Patients attending more than 80% of required NB-UVB sessions showed increased repigmentation in the head and neck area in the P. leucotomos group vs. placebo (50% vs. 19%, P < 0.002); no significant differences were seen in the other body areas. Patients with skin types 2 and 3 showed more repigmentation in the head and neck area in the P. leucotomos group vs. placebo (47% vs. 21%, P = 0.01), and no significant differences were seen in the other body areas. No conclusions could be drawn on skin types 4 and 5 due to low patient numbers. CONCLUSION: There is a clear trend towards an increase in repigmentation of vitiligo vulgaris affecting the head and neck area when NB-UVB phototherapy is combined with oral P. leucotomos. This effect may be more pronounced in light skin types.
Assuntos
Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Polypodium , Terapia Ultravioleta/métodos , Vitiligo/tratamento farmacológico , Vitiligo/radioterapia , Administração Oral , Adulto , Idoso , Terapia Combinada , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/administração & dosagem , Estudos Prospectivos , Índice de Gravidade de Doença , Pigmentação da Pele/efeitos dos fármacos , Pigmentação da Pele/efeitos da radiação , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
OBJECTIVE: To compare the incidence, symptomatology and course of mastocytosis with onset in childhood and in adults. DESIGN: Retrospective study of 101 patients with mastocytosis who were referred from 1980 to 1998. PATIENTS: Medical records of 65 cases of mastocytosis with onset in childhood and 36 in adulthood were analysed. The clinical course was assessed in a subgroup consisting of 33 subjects with childhood onset who were followed up until at least adolescence and 12 subjects with adult onset who were followed up for at least 10 years. RESULTS: The onset of the disease occurred before the age of 2 years in 50% and between the ages of 2 and 15 years in 14% of cases (childhood onset). In 36% of patients onset occurred at the age of 16 years and older (adult onset). An incidence peak of 60% was noted in the first year of life. Mast cell-mediated symptoms were not experienced by 21 of 36 adult onset mastocytosis patients nor by 27 of 65 childhood onset mastocytosis patients. Complete resolution was observed in five of 33 children. The majority of childhood onset cases (21 of 33) showed some improvement. Complete resolution was achieved in three of 12 adults. The majority of the remaining adults (eight of 12) showed no improvement. CONCLUSIONS: We confirm the incidence of onset of mastocytosis previously reported in the literature. We conclude that childhood onset mastocytosis is much less transitory than generally is assumed, although improvement occurs in the majority of cases. Symptomatology and clinical course of adult onset mastocytosis is less severe than suggested in the literature.
Assuntos
Idade de Início , Mastocitose Cutânea/diagnóstico , Mastocitose Cutânea/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Probabilidade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Distribuição por SexoRESUMO
There are still many controversies in defining and evaluating mastocytosis. One of the aspects that is missing is a system for clinical evaluation of mastocytosis of the skin. A calculation based on a semi-quantitative analysis of three aspects of mastocytosis was designed. The method is called the scoring index of mastocytosis (SCORMA). The clinical use of SCORMA is advocated.