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BACKGROUND: Dermatologic conditions are estimated to account worldwide for approximately 8% of all visits at emergency departments (EDs). Although rarely life-threatening, several dermatologic emergencies may have a high morbidity. Little is known about ED consultations of patients with dermatological emergencies and their subsequent hospital disposal. OBJECTIVE: We explore determinants and clinical variables affecting patients' disposal and hospitalization of people attending the ED at a Swiss University Hospital, over a 56-month observational period, for a dermatological problem. METHODS: De-identified patients' information was extracted from the hospital electronic medical record system. Generalized estimating equations were used to explore determinants of patient's disposition. RESULTS: Out of 5096 consecutive patients with a dermatological main problem evaluated at the ED, 79% of patients were hospitalized after initial assessment. In multivariable analyses, factors which were significantly associated with an increased admission rate included length of ED stay, age ≥ 45 years, male sex, distinct vital signs, high body mass index, low oxygen saturation, admission time in the ED and number and type of dermatological diagnoses. Only 2.2% of the hospitalized patients were admitted to a dermatology ward, despite the fact that they had dermatological diagnoses critically determining the diagnostic related group (DRG) payment. The number of patients managed by dermatologists during in-patient treatment significantly decreased over the study period. CONCLUSIONS: Our study identifies a number of independent predictors affecting the risk of hospital admission for patients with dermatological conditions, which may be useful to improve patients' disposal in EDs. The results indicate that the dermatological specialty is becoming increasingly marginalized in the management of patients in the Swiss hospital setting. This trend may have significant implications for the delivery of adequate medical care, outcomes and cost-effectiveness. Dermatologists should be more engaged to better position their specialty and to effectively collaborate with nondermatologists to enhance patient care.
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BACKGROUND AND OBJECTIVE: Topical tacrolimus has been shown to be beneficial in the treatment of oral lichen planus (OLP). However, long-term effects and its optimal application protocol with gradual reduction have not been studied. Accordingly, we analysed the clinical response of OLP to tacrolimus in our daily clinical practice with a focus on the optimal long-term therapeutic scheme. METHODS: Retrospective analysis of all consecutive patients diagnosed with OLP and treated with topical tacrolimus (0.03% oral rinse) in a clinical setting between 2015 and 2020. The objective clinical response was measured by a 4-point scale (complete remission, major remission, partial remission and no response), and subjective impairment by a 3-point scale (severe, moderate and none). RESULTS: Fifty-seven patients (74% women; median age: 66 years) were included. Fifty-six (98%) patients had prior treatment with topical steroids. After introduction of tacrolimus, objective remission (major or complete) was reached by 28%, 62%, 87% and 97% of patients after 3, 6, 12 and 24 months respectively. Subjective remission was reported by 16%, 48%, 69% and 83% after 3, 6, 12 and 24 months of treatment respectively. The treatment frequency could be gradually reduced from initially twice daily to once daily or less in 28%, 61%, 78% and 87% after 3, 6, 12 and 24 months respectively; 41% of patients completely suspended the treatment at one point, but 67% of them experienced a relapse after a median time of 3.3 months. Four patients (7%) developed a squamous cell carcinoma (SCC) during the observation period. Otherwise, there were only few and minor side-effects. CONCLUSION: Topical tacrolimus can be an effective second-line therapy for OLP refractory to potent topical corticosteroids. The therapy frequency can often be reduced during the maintenance period. Both signs of clinical activity and subjective impairment should guide therapy. Regular follow-up is necessary to recognize possible SCC.
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Carcinoma de Células Escamosas , Liquen Plano Oral , Humanos , Femenino , Anciano , Masculino , Tacrolimus , Liquen Plano Oral/tratamiento farmacológico , Liquen Plano Oral/patología , Estudios Retrospectivos , Inmunosupresores/uso terapéutico , Administración Tópica , Resultado del Tratamiento , Recurrencia Local de Neoplasia/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Protocolos ClínicosRESUMEN
BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo-like lesions, and eczematous and/or urticarial erythematous lesions. The disease, which is significantly associated with neurological disorders, has high morbidity and severely impacts the quality of life. OBJECTIVES AND METHODOLOGY: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology sought to update the guidelines for the management of BP based on new clinical information, and new evidence on diagnostic tools and interventions. The recommendations are either evidence-based or rely on expert opinion. The degree of consent among all task force members was included. RESULTS: Treatment depends on the severity of BP and patients' comorbidities. High-potency topical corticosteroids are recommended as the mainstay of treatment whenever possible. Oral prednisone at a dose of 0.5 mg/kg/day is a recommended alternative. In case of contraindications or resistance to corticosteroids, immunosuppressive therapies, such as methotrexate, azathioprine, mycophenolate mofetil or mycophenolate acid, may be recommended. The use of doxycycline and dapsone is controversial. They may be recommended, in particular, in patients with contraindications to oral corticosteroids. B-cell-depleting therapy and intravenous immunoglobulins may be considered in treatment-resistant cases. Omalizumab and dupilumab have recently shown promising results. The final version of the guideline was consented to by several patient organizations. CONCLUSIONS: The guidelines for the management of BP were updated. They summarize evidence- and expert-based recommendations useful in clinical practice.
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Dermatología , Penfigoide Ampolloso , Venereología , Corticoesteroides/uso terapéutico , Anciano , Vesícula/tratamiento farmacológico , Humanos , Penfigoide Ampolloso/diagnóstico , Penfigoide Ampolloso/tratamiento farmacológico , Calidad de VidaRESUMEN
This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue-bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10-25% of patients laminin 332 is recognized. In 25-30% of MMP patients with anti-laminin 332 reactivity, malignancies have been associated. As first-line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first-line regimens. Additional recommendations are given, tailored to treatment of single-site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high-quality randomized controlled trials.
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Dermatología , Penfigoide Benigno de la Membrana Mucosa , Penfigoide Ampolloso , Venereología , Autoanticuerpos , Autoantígenos , Humanos , Membrana Mucosa , Penfigoide Benigno de la Membrana Mucosa/diagnóstico , Penfigoide Benigno de la Membrana Mucosa/tratamiento farmacológicoRESUMEN
This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients' autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the 'Cicatrising Conjunctivitis Assessment Tool' and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course.
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Dermatología , Penfigoide Benigno de la Membrana Mucosa , Penfigoide Ampolloso , Venereología , Autoanticuerpos , Autoantígenos , Humanos , Membrana Mucosa , Penfigoide Benigno de la Membrana Mucosa/diagnóstico , Penfigoide Benigno de la Membrana Mucosa/terapia , Calidad de Vida , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: The incidence of skin cancers has been increasing steadily over the last decades. Although there have been significant breakthroughs in the management of skin cancers with the introduction of novel diagnostic tools and innovative therapies, skin cancer mortality, morbidity and costs heavily burden the society. OBJECTIVE: Members of the European Association of Dermato-Oncology, European Academy of Dermatology and Venereology, International Dermoscopy Society, European Dermatology Forum, European Board of Dermatovenereology of the European Union of Medical Specialists and EORTC Cutaneous Lymphoma Task Force have joined this effort to emphasize the fundamental role that the specialist in Dermatology-Venereology has in the diagnosis and management of different types of skin cancer. We review the role of dermatologists in the prevention, diagnosis, treatment and follow-up of patients with melanoma, non-melanoma skin cancers and cutaneous lymphomas, and discuss approaches to optimize their involvement in effectively addressing the current needs and priorities of dermato-oncology. DISCUSSION: Dermatologists play a crucial role in virtually all aspects of skin cancer management including the implementation of primary and secondary prevention, the formation of standardized pathways of care for patients, the establishment of specialized skin cancer treatment centres, the coordination of an efficient multidisciplinary team and the setting up of specific follow-up plans for patients. CONCLUSION: Skin cancers represent an important health issue for modern societies. The role of dermatologists is central to improving patient care and outcomes. In view of the emerging diagnostic methods and treatments for early and advanced skin cancer, and considering the increasingly diverse skills, knowledge and expertise needed for managing this heterogeneous group of diseases, dermato-oncology should be considered as a specific subspecialty of Dermatology-Venereology.
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Dermatología , Melanoma , Enfermedades de la Piel , Neoplasias Cutáneas , Venereología , Dermatólogos , Humanos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapiaRESUMEN
BACKGROUND: Pemphigus encompasses a group of life-threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin. Before the era of immunosuppressive treatment, pemphigus was almost always fatal. Due to its rarity, only few randomized controlled therapeutic trials are available. Recently, rituximab has been approved as first-line treatment for moderate and severe pemphigus vulgaris in Europe and the United States. OBJECTIVES: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology (EADV) has initiated a throughout update of the guideline for the management of patients with pemphigus. RESULTS: The guidelines for the management of pemphigus were updated, and the degree of consent among all task force members was included. The final version of the guideline was consented by the European Dermatology Forum (EDF) and several patient organizations.
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Dermatología , Guías como Asunto , Pénfigo , Venereología , Academias e Institutos , Europa (Continente) , Humanos , Pénfigo/diagnóstico , Pénfigo/tratamiento farmacológicoRESUMEN
BACKGROUND: Most clinical guidelines in dermatology are encyclopaedic, covering a disease and its aetiology, diagnosis, treatment and prevention in their entirety. The usability and uptake of guideline recommendations might be improved by guidelines that are more concise and address specific questions ranked by users according to their perceived importance. OBJECTIVE: To survey the largest association of dermatologists in Europe, identify which questions in their everyday practice they felt would benefit from short, evidence-based guidance and rank these systematically. METHODS: A two-phase online survey using a structured ranking approach and the members directory of the European Academy of Dermatology and Venereology (EADV). RESULTS: The first survey yielded 265 suggestions, indicating a response rate of 3.7%. We grouped all responses according to themes and subsequently combined these into a list of 35 broader topics. These were presented to all members of the EADV in the second survey (response rate: 9.7%), which yielded a list of the top 10 topics participants felt were most in need of guidance. The first three were 'Systemic drug treatment in dermatology during pregnancy and for women wishing to have children in the near future', 'alopecia areata' and 'interpretation of laboratory results in connective tissue diseases'. CONCLUSION: Our two-phase survey of EADV members and a structured ranking process were practical to implement and yielded a list of the top 10 topics in dermatology and venereology for guideline development. Guideline dissemination needs to be improved, and practical, more concise guidelines may facilitate efforts to do so.
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Actitud del Personal de Salud , Dermatología , Guías de Práctica Clínica como Asunto , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/terapia , Europa (Continente) , Medicina Basada en la Evidencia , Femenino , Humanos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Though patient needs are key drivers of treatment decisions, they are rarely systematically investigated in routine care. OBJECTIVE: This study aimed at analysing needs and expectations from the patient perspective in the German and Swiss psoriasis registries PsoBest and Swiss Dermatology Network of Targeted Therapies (SDNTT) with respect to treatment choice, age and gender. METHODS: The German and Swiss psoriasis registries observe patients recruited at first-time use of systemic drugs. Within 10 years, clinical [Psoriasis Area Severity Index (PASI), Body Surface Area (BSA)] and patient-reported outcomes are documented, including the Dermatology Quality of Life Index (DLQI) and the Patient Benefit Index (PBI), characterizing patient needs for treatment. The analysis data set includes n = 4894 patients from PsoBest and n = 449 from SDNTT with mean follow-up time of 7.5 months. RESULTS: A total of 5343 patients registered between 2008 and 2016 were included in the analyses (at baseline: 59.6% male, mean age 47.6 years ± 14.5, PASI 14.2 ± 9.7, BSA 22.7 ± 19.7, DLQI 11.3 ± 7.2). The most important patient needs were to 'get better skin quickly' and to 'be healed of all skin defects'. Subgroup analyses by age revealed significant differences in needs, especially higher needs regarding social impairments in patients younger than 65 years. Patients 65 years or older attributed more importance to sleep quality, less dependency on medical visits, fewer side-effects and confidence in the therapy. Out of 25 items reflecting patient needs, 20 items were rated significantly more important by women than men, with the greatest differences regarding feeling of depression, sleep quality and everyday productivity. Divided by treatment, needs were rated differently, recommending individualized and targeted choice of therapy. CONCLUSION: Age and gender stratify patient needs. Women showed higher expectations and rated specific needs in psoriasis treatment higher than men. Analysing the patient needs on an individual level will facilitate shared decisions by patient and physician in finding the optimal personalized treatment.
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Fármacos Dermatológicos/uso terapéutico , Necesidades y Demandas de Servicios de Salud , Planificación de Atención al Paciente , Prioridad del Paciente , Psoriasis/tratamiento farmacológico , Adulto , Factores de Edad , Depresión/etiología , Fármacos Dermatológicos/efectos adversos , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Necesidades , Psoriasis/psicología , Sistema de Registros , Factores Sexuales , Sueño , Participación Social , SuizaRESUMEN
BACKGROUND: Several treatment options are currently available for the treatment of psoriasis. OBJECTIVE: To explore the main associations between patients' characteristics and systemic treatments prescribed for psoriasis in a large group of patients observed in real-life clinical practice. METHODS: This was a retrospective analysis of baseline data collected within the Swiss Dermatology Network for Targeted Therapies registry in Switzerland between March 2011 and December 2017. Semantic map analysis was used in order to capture the best associations between variables taking into account other covariates in the system. RESULTS: A total of 549 patients (mean age 46.7 ± 14.7 years) were included in the analysis. Conventional therapies such as retinoids and methotrexate were associated with no previous systemic therapies for psoriasis, a moderate quality of life (QoL) at therapy onset and older age (≥60 years). Fumaric acid derivatives were associated with mild psoriasis (psoriasis area severity index < 10) and long disease duration (≥20 years). On the other side, cyclosporine and psoralen and ultraviolet A/ultraviolet B treatments were linked to a more severe condition, including impaired QoL, hospitalization and inability to work. Regarding biological therapies, both infliximab and adalimumab were connected to the presence of psoriatic arthritis, severe disease condition and other comorbidities, including chronic liver or kidney diseases and tuberculosis. Etanercept, ustekinumab and secukinumab were all connected to a complex history of previous systemic treatments for psoriasis, moderate disease condition, overweight and university education. CONCLUSIONS: The analysis shows multifaceted associations between patients' characteristics, comorbidities, disease severity and systemic treatments prescribed for psoriasis. In particular, our semantic map indicates that comorbidities play a central role in decision-making of systemic treatments usage for psoriasis. Future studies should further investigate specific connections emerging from our data.
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Fármacos Dermatológicos/uso terapéutico , Psoriasis/tratamiento farmacológico , Adulto , Algoritmos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psoriasis/fisiopatología , Sistema de Registros , SuizaRESUMEN
BACKGROUND: Lesions of bullous pemphigoid (BP), an autoimmune subepidermal blistering disease characterized by the presence of tissue-bound and circulating autoantibodies to hemidesmosomal antigens, harbor a mixed inflammatory cellular infiltrate. In various models, neutrophils, eosinophils, mast cells, monocytes as well as B and T cells have been shown to be involved in the pathogenesis of BP. However, their interactions with and effective role in blister formation remain uncertain. This study was aimed at investigating the effect of monocyte/neutrophil interaction on blister formation in an ex vivo BP model. METHODS: Skin cryosections were incubated with purified human neutrophils and monocytes, in the presence or absence of BP autoantibodies. Production of reactive oxygen species (ROS), degranulation, mediator release (neutrophil elastase [NE], myeloperoxidase [MPO], matrix metalloproteinase-9 [MMP-9]), binding of Fcγ receptor (CD16, CD32, CD64), and cell adhesion (CD18, ICAM-1) was investigated using appropriate inhibitors. Dermal-epidermal separation (DES) was assessed by light microscopy and quantified by Fiji software. RESULTS: Monocytes and neutrophils synergistically interact resulting in a significantly higher DES compared to either monocytes or neutrophils separately (P < .0001). Monocyte/neutrophil-induced DES was associated with increased ROS production and was dependent on adhesion and FcγRIII binding. Upon stimulation by the granule-poor fraction of monocyte supernatants, neutrophils increased their release of MMP-9, thereby also DES at the dermal-epidermal junction of skin cryosections. CONCLUSION: Our observations suggest that the interaction of cells, as shown here for monocytes and neutrophils, enhances mediator release resulting in an increased subepidermal blister formation. Thus, blocking intercellular cross talk promises a new therapeutic approach for blocking tissue damage in BP.
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Monocitos/inmunología , Neutrófilos/inmunología , Penfigoide Ampolloso/inmunología , Penfigoide Ampolloso/patología , Animales , Vesícula/inmunología , Vesícula/patología , Humanos , RatonesRESUMEN
BACKGROUND: Hand eczema has a high incidence and prevalence and has a negative impact on both physical and psychological well-being, with the risk of persistence as a chronic condition. Epidemiological studies on hand eczema provided mainly descriptive and risk analyses, but pattern analyses of variables associated with hand eczema, in particular chronic hand eczema, have not been explored to date. OBJECTIVES: To investigate and display the semantics of associations between variables of hand eczema obtained from the Swiss and German registries of chronic hand eczema (CARPE) to dissect patterns and novel links. METHODS: This was a cross-sectional study on selected variables from the CARPE registries. Associations between variables were analysed by means of an autoassociative system. A semantic connectivity map was generated by using a maximum spanning tree algorithm. RESULTS: Baseline datasets of 1466 patients with chronic hand eczema (Switzerland: 199; Germany: 1267) were analysed. Occupational exposure had the highest impact in the total and country cohorts. We identified two areas of exposure linked to corresponding occupations that clearly demarcated the sexes. CONCLUSIONS: This study, using semantic connectivity as a novel method of data analysis, reveals the complexity of features characterizing chronic hand eczema as well as novel association patterns that deserve further investigation.
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Dermatitis Profesional/epidemiología , Eccema/epidemiología , Dermatosis de la Mano/epidemiología , Corticoesteroides/uso terapéutico , Actitud Frente a la Salud , Enfermedad Crónica , Estudios Transversales , Dermatitis Profesional/tratamiento farmacológico , Eccema/tratamiento farmacológico , Femenino , Alemania/epidemiología , Dermatosis de la Mano/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Exposición Profesional/efectos adversos , Exposición Profesional/estadística & datos numéricos , Calidad de Vida , Sistema de Registros , Factores de Riesgo , Semántica , Distribución por Sexo , Suiza/epidemiologíaRESUMEN
BACKGROUND: The variables affecting participants' satisfaction with a scientific conference in dermatology have not been systematically assessed. The European Academy of Dermatology and Venereology (EADV) has collected a huge number of questionnaires related to sessions' and speakers' evaluation over the years. The critical analysis of satisfaction's score is important and helpful for continuous improvement of the scientific programming. OBJECTIVE: To identify factors that positively or negatively affect sessions' and speakers' scoring in the largest European congress of dermatology. METHODS: This was a retrospective analysis of all sessions' evaluation forms collected between 2009 and 2015 during seven consecutive EADV congresses. A predictive model for sessions' and another for speakers' score evaluation were built based on multivariate linear regression. RESULTS: Overall, 4964 speakers and 1022 sessions were evaluated. Topics more positively associated with total sessions' scoring were as follows: dermoscopy, neutrophilic diseases and hidradenitis suppurativa. Conversely, types of sessions which considerably negatively associated with total sessions' scoring included short thematic presentations and free communications. Furthermore, types of sessions which were more positively associated with high total speakers' scoring consisted of focus sessions and plenary lectures, whereas the most appreciated topics encompassed dermoscopy, screening programs, melanocytic naevi, panniculitis, organ transplanted and immunosuppressed patients, neutrophilic diseases, dermatopathology and history of dermatology. Finally, short thematic presentations, free communications and guidelines session showed overall poor scores. CONCLUSION: Focused and specialized topics are more prone to capture attention of participants when compared to sessions of heterogeneous content. Quite surprisingly, a practice-oriented topics such as guidelines, did not achieve a high score. Our findings provide new knowledge about components, which increase the level of satisfaction of participants and should facilitate the programming of attractive scientific congresses associated with increased training satisfaction.
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Congresos como Asunto/estadística & datos numéricos , Congresos como Asunto/normas , Comportamiento del Consumidor/estadística & datos numéricos , Dermatología , Sociedades Médicas , Venereología , Investigación Biomédica , Congresos como Asunto/tendencias , Educación Médica Continua/normas , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: Bullous pemphigoid (BP) is an autoimmune bullous disease of the skin characterized by subepidermal blister formation due to tissue-bound and circulating autoantibodies to the hemidesmosomal antigens BP180 and BP230. Although eosinophils and their toxic mediators are found abundantly in BP lesions, their role in blister formation has remained unclear. OBJECTIVE: To investigate the role of eosinophils in the pathogenesis of BP with a specific focus on blister formation and to define conditions inducing dermal-epidermal separation (DES). METHODS: In an ex vivo human model of BP, normal human skin cryosections were incubated with purified human peripheral blood eosinophils with or without activation in the presence or absence of BP autoantibodies, brefeldin A, diphenyleneiodonium, DNase or blocking F(ab')2 fragments to CD16, CD18, CD32 and CD64. Dermal-epidermal separation was assessed by light microscopy studies and quantified using Fiji software. RESULTS: Following activation with IL-5 and in the presence of BP autoantibodies, eosinophils induced separation along the dermal-epidermal junction of ex vivo skin. Dermal-epidermal separation was significantly reduced by blocking any of the following: Fcγ receptor binding (P = 0.048), eosinophil adhesion (P = 0.046), reactive oxygen species (ROS) production (P = 0.002), degranulation (P < 0.0001) or eosinophil extracellular trap (EET) formation (P = 0.048). CONCLUSIONS: Our results provide evidence that IL-5-activated eosinophils directly contribute to BP blister formation in the presence of BP autoantibodies. Dermal-epidermal separation by IL-5-activated eosinophils depends on adhesion and Fcγ receptor activation, requires elevated ROS production and degranulation and involves EET formation. Thus, targeting eosinophils may be a promising therapeutic approach for BP.
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Vesícula/etiología , Vesícula/patología , Eosinófilos/inmunología , Eosinófilos/patología , Penfigoide Ampolloso/inmunología , Penfigoide Ampolloso/patología , Autoanticuerpos/inmunología , Biomarcadores , Antígenos CD18/metabolismo , Adhesión Celular/efectos de los fármacos , Adhesión Celular/inmunología , Degranulación de la Célula/inmunología , Citocinas/metabolismo , Eosinófilos/efectos de los fármacos , Eosinófilos/metabolismo , Humanos , Interleucina-5/metabolismo , Penfigoide Ampolloso/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptores de IgG/metabolismo , Piel/efectos de los fármacos , Piel/inmunología , Piel/metabolismo , Piel/patologíaRESUMEN
BACKGROUND: Port-wine stains (PWS) are relatively common and often cause cosmetic and psychological concerns. The pulsed dye laser is currently the treatment of choice for PWS. OBJECTIVE: To assess the effectiveness of the pulsed sequential dual wavelength 595 and 1064 nm laser as first-line treatment for PWS and to identify prognostic factors for treatment outcome in a retrospective series of 17 consecutive previously untreated patients. METHODS: The response to treatment was evaluated 2 months after treatment utilizing comparative photographs and a standard physician global assessment (PGA) grading system. Furthermore, measurement of the normalized erythema index (NEI) reduction (ΔNEI%) was carried out using an image analysis system. The subjective improvement was assessed using a patient's satisfaction questionnaire. Multiple linear regression models were finally used to identify factors associated with ΔNEI% and patients' satisfaction. RESULTS: Seventeen patients, with PWS, including 12 children were included. The average PGA assessment was 2.5 ± 1.3 corresponding to an amelioration of 50% with a high intraclass correlation coefficient among the experts. The before-after NEI showed a statistically significant mean reduction of 3.5 ± 2.6 units, corresponding to a relative reduction of 31%. Questionnaires showed that the satisfaction was very good with an average score of 6.1 points on a scale ranging from -10 to 10 points. Multiple regression analysis revealed that location in the frontotemporal area was associated with a significant reduction in ΔNEI% (38.4%; 95% CI 4.3, 72.6). Presence of PWS on the neck was associated with a lower patient satisfaction (-3.7 points; 95% CI -6.5, -0.9). There were no significant side-effects, except for transient discomfort and purpura. CONCLUSIONS: Based on the results obtained in the largest reported series so far, the pulsed sequential dual wavelength 595 and 1064 nm laser represents an effective and safe first-line therapeutic option for the treatment of PWS.
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Láseres de Colorantes/uso terapéutico , Satisfacción del Paciente , Mancha Vino de Oporto/cirugía , Adolescente , Adulto , Niño , Preescolar , Femenino , Frente , Humanos , Terapia por Láser/efectos adversos , Terapia por Láser/métodos , Láseres de Colorantes/efectos adversos , Masculino , Cuello , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Cutaneous (CLP) and oral lichen planus (OLP) as the main subtypes of lichen planus (LP) present with different clinical manifestation and disease course, although their histopathologic features such as the band-like lymphocyte infiltrate and keratinocyte apoptosis are similar. So far, the underlying cellular and molecular mechanisms remain poorly understood. OBJECTIVE: The aim of this study was to characterize and compare the in situ cellular infiltrates, cytokine expression profiles and apoptosis markers in CLP and OLP. METHODS: Using immunofluorescence staining and laser scanning microscopy, we evaluated the cellular infiltrate (CD1a, CD3, CD4, CD8, CD21, CD57, CD123), cytokine expression (interleukin (IL)-1, IL-6, IL-9, IL-10, IL-17, IL-22, IL-23, tumour necrosis factor-α, transforming growth factor-ß, interferon (IFN)-γ), and apoptosis markers (Fas, Fas ligand, cleaved caspase-3, TUNEL) of 21 anonymized biopsy specimens of LP (11 CLP, 10 OLP). RESULTS: Among infiltrating cells mainly T cells and natural killer (NK) cells as well as plasmacytoid dendritic cells (DC) were observed. A predominance of CD8+ T cells was noted in OLP. In both CLP and OLP, T helper (Th)1, Th9, Th17, and Th22-type cytokines were expressed. The expression of IL-9, IFN-γ and IL-22 was higher in CLP compared to that of OLP (P = 0.0165; P = 0.0016; P = 0.052 respectively). Expression of Fas and Fas ligand as well as cleaved caspase-3-positive cells was observed in the epithelium of all LP samples. CONCLUSIONS: The cell and cytokine patterns of CLP and OLP were partially distinct and generally resembled those reported for autoimmune diseases. The presence of CD8+ and NK cells as well as Fas/Fas ligand expression suggested that various pathways involved in keratinocyte apoptosis are relevant for LP. These results might help to establish targeted therapies for LP.
Asunto(s)
Interferón gamma/metabolismo , Interleucina-9/metabolismo , Liquen Plano Oral/metabolismo , Liquen Plano/metabolismo , Apoptosis , Biomarcadores , Linfocitos T CD4-Positivos/patología , Humanos , Liquen Plano/patología , Liquen Plano Oral/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: Direct immunofluorescence microscopy (DIF) studies constitute the gold standard for diagnosis of bullous pemphigoid (BP) but depend on the availability of specialized laboratories and often on an additional skin biopsy specimen. OBJECTIVES: To assess the value of immunohistochemical analyses (IHCA) in the diagnosis of BP using formalin-fixed, paraffin-embedded skin biopsy specimens as an alternative to DIF; and to study the correlation between the results of IHCA and the presence of histological subepidermal blister formation and of circulating autoantibodies by indirect immunofluorescence studies using split skin or by enzyme-linked immunosorbent assays. METHODS: We included all patients newly diagnosed with BP evaluated between 2008 and 2010. There were 51 consecutive skin biopsy specimens obtained from 38 patients with BP with positive DIF. RESULTS: By IHCA, deposits of immunoreactants were found in 45% of all tested cases. Deposits of C3d, IgG, IgM, IgE and IgA were found in 37%, 23%, 2%, 0% and 0% of cases, respectively. Deposits of C3d and/or IgG were found in 79% of the 24 cases with a blister and in 83% of the 12 cases with subepidermal blistering and positive immunoserological analyses, respectively. CONCLUSIONS: In contrast to previous studies, our findings in an unselected patient cohort indicate that IHCA are not sufficiently sensitive to replace DIF studies for confirming the diagnosis of BP. IHCA sensitivity significantly increases in the presence of histological blistering and/or of circulating autoantibodies. IHCA represents a potential rescue diagnostic technique only if specialized laboratories and/or a second biopsy specimen for DIF are unavailable.