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BACKGROUND: Abrocitinib efficacy by comorbidity status in patients with moderate-to-severe atopic dermatitis (AD) has not been previously assessed. This post hoc analysis evaluated the efficacy and safety of abrocitinib in patients with AD and allergic comorbidities. METHODS: Data were pooled from patients who received abrocitinib 200 mg, 100 mg, or placebo in phase 2b (NCT02780167) and phase 3 (NCT03349060, NCT03575871) monotherapy trials. Patients with and without allergic comorbidities (allergic asthma, rhinitis, conjunctivitis, or food allergy) were evaluated for Investigator's Global Assessment (IGA) response (clear [0] or almost clear [1]), ≥75% improvement in the Eczema Area and Severity Index (EASI-75), ≥4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4), and Dermatology Life Quality Index (DLQI) response (<2 with baseline score ≥2). Other outcomes were Patient-Oriented Eczema Measure (POEM), SCORing Atopic Dermatitis (SCORAD), Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD), and treatment-emergent adverse events (TEAEs). RESULTS: Of 942 patients, 498 (53%) reported at least one allergic comorbidity (asthma only, 33%; conjunctivitis only or rhinitis only or both, 17%; food allergies only, 15%; >1 allergic comorbidity, 34%). Regardless of comorbidity status, from Week 2 to Week 12, higher percentages of patients treated with either abrocitinib dose achieved IGA 0/1, EASI-75, PP-NRS4, or DLQI 0/1 versus placebo-treated patients. Changes from baseline in POEM, SCORAD, and PSAAD were greater with abrocitinib than with placebo in patients with and without allergic comorbidities. Most TEAEs were mild or moderate. CONCLUSIONS: Efficacy and safety data support abrocitinib use to manage AD in patients with or without allergic comorbidities.
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Asma , Conjuntivite , Dermatite Atópica , Eczema , Rinite , Humanos , Comorbidade , Dermatite Atópica/complicações , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Imunoglobulina A , Prurido , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
INTRODUCTION: Dupilumab has emerged as a promising treatment option for bullous pemphigoid (BP). Rapid identification of responders could avoid the need for additional immunosuppressive treatments that are associated with increased morbidity and mortality. METHODS: To investigate the course of itch as an early indicator of treatment response, data of 12 BP patients treated with dupilumab at the University Hospital of Zurich were retrospectively evaluated. Disease severity was assessed by bullous pemphigoid disease area index (BPDAI) and pruritus by a numeric rating scale (NRS, 0-10) at baseline; days 1, 3, 14; months 1, 2; and the last follow-up. RESULTS: A total of 8/12 patients (67%) had complete response, and 4/12 patients (33%) had partial response during dupilumab treatment. Notably, a highly significant reduction of pruritus (p < 0.0001) was observed already on day 1 with further improvement at later time points. Moreover, fast relief of itch could predict treatment response with a significant correlation to clinical response on day 14 (Spearman correlation R 0.70, p value 0.025), with a positive but non-significant trend on day 3 (R 0.63, p value 0.091). Additionally, 92% (11/12 patients) were on dupilumab monotherapy at the last follow-up without any concomitant systemic or topical treatment for BP. CONCLUSIONS: The rapid and significant decline in BP-associated pruritus observed with dupilumab correlated significantly with disease remission. Early evaluation of pruritus response could change how BP is treated in the future and avoid additional immunosuppressive treatment in BP.
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The International Society of AD (ISAD) organized a roundtable on global aspects of AD at the WCD 2023 in Singapore. According to the Global Burden of Disease (GBD) consortium, at least 171 million individuals were affected with AD in 2019, corresponding to 2.23% of the world population, with age-standardized prevalence and incidence rates that were relatively stable from 1990 to 2019. Based on the panel experience, most AD cases are mild-to-moderate. Without parallel data on disease prevalence and severity, the GBD data are difficult to interpret in many regions. This gap is particularly important in countries with limited medical infrastructure, but indirect evidence suggests a significant burden of AD in low-and-medium resource settings, especially urban areas. The Singapore roundtable was an opportunity to compare experiences in World Bank category 1 (Madagascar and Mali), 3 (Brazil, China) and 4 (Australia, Germany, Qatar, USA, Singapore, Japan) countries. The panel concluded that current AD guidelines are not adapted for low resource settings and a more pragmatic approach, as developed by WHO for skin NTDs, would be advisable for minimal access to moisturizers and topical corticosteroids. The panel also recommended prioritizing prevention studies, regardless of the level of existing resources. For disease long-term control in World Bank category 3 and most category 4 countries, the main problem is not access to drugs for most mild-to-moderate cases, but rather poor compliance due to insufficient time at visits. Collaboration with WHO, patient advocacy groups and industry may promote global change, improve capacity training and fight current inequalities. Finally, optimizing management of AD and its comorbidities needs more action at the primary care level, because reaching specialist care is merely aspirational in most settings. Primary care empowerment with store and forward telemedicine and algorithms based on augmented intelligence is a future goal.
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Dermatite Atópica , Saúde Global , Humanos , Dermatite Atópica/epidemiologia , Dermatite Atópica/terapia , Prevalência , Carga Global da Doença , Singapura/epidemiologiaRESUMO
Atopic dermatitis (AD) is a common disease that is associated with atopic and nonatopic comorbidities. There has been a growing interest in this area of AD, because presence or risk of comorbidities can in many ways impact the management of patients with AD. Thus, some treatments for AD may improve its comorbidities as well, whereas others may increase their risk. In this review article, we discuss various comorbidities of AD mostly on the basis of the results of recent multiple systematic reviews and meta-analyses to update readers about this rapidly developing area of dermatology. We emphasize the important information provided by studies presenting both relative risk and absolute risk, and show that AD is associated with, among others, atopic comorbidities such as asthma, rhinitis, and food allergy, nonatopic comorbidities such as ocular, psychiatric, infectious, endocrine, autoimmune, and cardiovascular diseases, and certain cancers. Clinicians need to be aware of these and be cognizant about positive and negative effects of existing and new treatments for AD.
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Asma , Dermatite Atópica , Hipersensibilidade Alimentar , Rinite , Humanos , Dermatite Atópica/epidemiologia , Dermatite Atópica/complicações , Comorbidade , Asma/epidemiologia , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/complicações , Rinite/complicaçõesRESUMO
This S3 guideline was created based on the European S3 guideline, with special consideration of the medical conditions in the German-speaking region and incorporating additions from the previous German-language version. The interdisciplinary guideline commission consisted of representatives from the German Dermatological Society, the Professional Association of German Dermatologists, the Austrian Society of Dermatology and Venereology, the Swiss Society of Dermatology and Venereology, the German Society for Allergology and Clinical Immunology, the German Society for Pediatric and Adolescent Medicine, the Professional Association of Pediatricians and Adolescent Medicine, the Society for Pediatric Allergology and Environmental Medicine, the German Society for Pediatric Rehabilitation and Prevention, the German Society for Psychosomatic Medicine and Medical Psychotherapy, the German Network for Health Services Research, the German Eczema Association and the German Allergy and Asthma Association. This first part of the guideline focuses on the definition and diagnostic aspects of atopic dermatitis (AD), addressing topical therapy as well as non-pharmacological treatment approaches such as UV therapy, psychoeducational therapy, dietary interventions for AD, allergen immunotherapy for AD, and complementary medicine. This part of the guideline also covers specific aspects of AD in children and adolescents, during pregnancy and lactation, and in the context of family planning. Additionally, it addresses occupational aspects of AD and highlights the perspective of the patients. The second part of the guideline, published separately, addresses the systemic therapy of AD.
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Asma , Dermatite Atópica , Adolescente , Feminino , Gravidez , Humanos , Criança , Dermatite Atópica/terapia , Dermatite Atópica/tratamento farmacológicoRESUMO
The present S3 guideline was created based on the European English-language S3 guideline, with special consideration given to the medical conditions in the German-speaking region, and with additions from the previous German-language version, in accordance with the criteria of the AWMF. This second part of the guideline addresses the systemic therapy of atopic dermatitis (AD). It covers topics such as the indication for systemic therapy in children, adolescents, and adult patients with AD. Furthermore, it addresses all medications approved for AD, such as the biologics dupilumab and tralokinumab, the Janus kinase inhibitors abrocitinib, baricitinib, and upadacitinib, as well as conventional immunosuppressive therapies with systemic glucocorticosteroids and ciclosporin. Additionally, it discusses systemic off-label therapies. The first part of the guideline, published separately, includes the definition and diagnostic aspects of AD, describes topical therapy, non-drug therapy approaches, and addresses aspects related to special patient groups.
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Produtos Biológicos , Dermatite Atópica , Adolescente , Adulto , Criança , Humanos , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Administração Cutânea , Ciclosporina , Terapia de Imunossupressão , Resultado do TratamentoRESUMO
BACKGROUND: Chronic rhinosinusitis with a type 2 inflammatory pattern (T2CRS) is believed to be restricted to the nose and sinuses and associated with polyps, without clear serologic markers. Dupilumab is a promising new therapy in difficult to treat T2CRS. No factors are known to predict dupilumab treatment outcome. METHODS: Patients undergoing dupilumab treatment were assessed clinically to report ultra-short- and short-term outcome up to 90 days. Serum samples were taken on day 0 and 30 days of treatment, and proteomic analyses were performed using Olink®. The results were compared with healthy controls (HC). The aim was to identify clinical and serological markers associated with a treatment response to dupilumab. Confirmation of predictive parameters was evaluated in a prospective cohort of 20 T2CRS patients. RESULTS: Thirty patients were included, 80% of which were treatment responders. SinoNasalOutcomeTest-20 (SNOT-20) scores and the total nasal polyp score improved significantly (p < .05) on Day 7. An improvement of 2.5 points at the first visit was associated with a favorable outcome with a sensitivity of 86%. Proteomic analyses revealed significant changes compared with HC. Furthermore, we could identify OPG in the serum of dupilumab-treated patients that may serve as a predictor of the clinical outcome of dupilumab treatment. The predictive value of OPG was confirmed in the second cohort. CONCLUSION: Clinical response after 1 week of treatment with dupilumab is highly associated with a favorable outcome. High sensitivity proteomic analyses can identify T2CRS-specific dysregulated proteins in serum. Serum OPG may serve as a predictor for dupilumab treatment outcome before the initiation of any therapy.
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Pólipos Nasais , Rinite , Sinusite , Humanos , Estudos Prospectivos , Proteômica , Rinite/tratamento farmacológico , Rinite/complicações , Sinusite/tratamento farmacológico , Sinusite/complicações , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/complicações , Resultado do Tratamento , Doença CrônicaRESUMO
BACKGROUND: Atopic dermatitis (AD) has long been regarded as a primarily pediatric disease. However, there is growing evidence for a high rate of adult-onset AD. We aimed to characterize factors associated with adult-onset versus childhood-onset AD and controls. METHODS: We analyzed cross-sectional data of the CK-CARE-ProRaD cohorts Bonn, Augsburg, Davos, Zürich of 736 adult patients stratified by age of AD onset (childhood-onset <18 years: 76.4% (subsets: 0 to 2; ≥2 to 6; ≥7 to 11; ≥12 to 18); adult-onset ≥18 years: 23.6% (subsets: ≥18 to 40; ≥41 to 60; ≥61) and 167 controls (91 atopic, 76 non-atopic)). RESULTS: We identified active smoking to be associated with adult-onset AD versus controls (adjusted Odds Ratio (aOR) = 5.54 [95% Confidence Interval: 1.06-29.01] vs. controlsnon-atopic , aOR = 4.03 [1.20-13.45] vs. controlsatopic ). Conjunctivitis showed a negative association versus controlsatopic (aOR = 0.36 [0.14-0.91]). Food allergy (aOR = 2.93 [1.44-5.96]), maternal food allergy (aOR = 9.43 [1.10-80.95]), palmar hyperlinearity (aOR = 2.11 [1.05-4.25]), and academic background (aOR = 2.14 [1.00-4.54]) increased the odds of childhood-onset AD versus controlsatopic . Shared AD-associated factors were maternal AD (4-34x), increased IgE (2-20x), atopic stigmata (2-3x) with varying effect sizes depending on AD onset and control group. Patients with adult-compared to childhood-onset had doubled odds of allergic rhinitis (aOR = 2.15 [1.12-4.13]), but reduced odds to feature multiple (3-4) atopic comorbidities (aOR = 0.34 [0.14-0.84]). Adult-onset AD, particularly onset ≥61 years, grouped mainly in clusters with low contributions of personal and familial atopy and high frequencies of physical inactivity, childhood-onset AD, particularly infant-onset, mainly in "high-atopic"-clusters. CONCLUSIONS: The identified associated factors suggest partly varying endo- and exogeneous mechanisms underlying adult-onset versus childhood-onset AD. Our findings might contribute to better assessment of the individual risk to develop AD throughout life and encourage prevention by non-smoking and physical activity as modifiable lifestyle factors.
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Dermatite Atópica , Hipersensibilidade Alimentar , Lactente , Criança , Adulto , Humanos , Adolescente , Dermatite Atópica/etiologia , Dermatite Atópica/complicações , Idade de Início , Estudos Transversais , Fatores de Risco , Hipersensibilidade Alimentar/complicaçõesRESUMO
INTRODUCTION: IgE-mediated bee venom allergy can be treated with allergen-specific immunotherapy (AIT). Subcutaneous immunotherapy (SCIT) is time and cost intensive due to the repeated consultations, but the costs are justified by the high risk of potentially life-threatening allergic reactions, including anaphylaxis. However, intralymphatic immunotherapy (ILIT) offers potential to reduce treatment costs due to a significant reduction in injections and a shorter duration of therapy. Therefore, we calculated the cost savings that arise when switching from SCIT to ILIT. METHODS: Treatment protocols for ILIT were based on previous ILIT studies. Treatment protocols for SCIT were based on routine treatment at the University Hospital Zurich (USZ). The treatment costs were calculated based on the internal hospital information system (KISIM). RESULTS: The calculations revealed a potential two-fold reduction in treatment costs if ILIT is used instead of SCIT in patients with bee venom allergy. The costs could be reduced from EUR 11,612.59 with SCIT to EUR 5,942.15 with ILIT over 5 years. CONCLUSIONS: This study shows that bee venom ILIT has a cost-benefit potential for health insurances and patients, which should encourage further ILIT studies and which should be taken into account when considering future implementation of ILIT in the standard care of venom allergy.
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BACKGROUND: Chronic prurigo (CPG) is a pruritic skin disease, characterized by an itch-scratch cycle and scarring. It reduces patients' quality of life (QoL). Dupilumab is a monoclonal human IgG antibody that inhibits signaling of the interleukin 4 (IL-4) and interleukin 13 (IL-13) pathways through blockade of the IL-4 receptor. Patients with CPG who receive dupilumab often report great improvement in itch and overall QoL. We therefore reviewed our experience in order to follow up on QoL, safety, and treatment response in patients with CPG who received dupilumab. METHODS: We conducted a real-world retrospective single-center case series. Outcomes were assessed by phone interviews and photographs using validated questionnaires and scores. Demographic data were obtained from the hospital files. Follow-up was up to 2 years. We assessed QoL with the Dermatology Life Quality Index (DLQI) and the Itchy quality of life questionnaire (ItchyQoL). Numerical Rating Scale (NRS) was used to assess itch. Prurigo lesions were documented with the Prurigo activity and severity score (PAS). RESULTS: Ten patients were included in this study. Results were reported up to 2 years after treatment with dupilumab. The response variables for DLQI, ItchyQoL, NRS, and PAS analyses showed a statistically significant decrease over time (DLQI: p ≤ 0.0001 [-0.84; -1.27], ItchyQoL: p ≤ 0.0001 [-9.89; -18.69], NRS maximum and average: p ≤ 0.0001 [-0.52; -0.86] and p ≤ 0.0001 [-0.55; -0.94], and PAS number of lesions: p = 0.0005 [-1.70; -5.28]). The percent decrease after 1 year of treatment (this estimate is based on model estimates) ranges from -42% to -82%. Four (40%) patients reported mild side effects. No serious side effects were reported. CONCLUSION: Dupilumab treatment of CGP for up to 2 years is associated with improved QoL and less itching.
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Dermatite Atópica , Prurigo , Humanos , Prurigo/tratamento farmacológico , Qualidade de Vida , Dermatite Atópica/tratamento farmacológico , Estudos Retrospectivos , Prurido/induzido quimicamente , Prurido/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Interleucina-13 , Resultado do Tratamento , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Earlier studies have suggested that the leukocyte redistribution can be considered as an immunological marker of the clinical response to corticosteroids (CS), representing an easy measurable potential biomarker in severe asthma. OBJECTIVE: The aim of this study was to determinate the utility of the leukocyte redistribution as a biomarker of disease heterogeneity in patients with severe asthma and as a bioindicator of potential CS resistance. METHODS: We developed an unbiased clustering approach based on the clinical data and the flow cytometry results of peripheral blood leukocyte phenotypes of 142 patients with severe asthma before and after systemic CS administration. RESULTS: Based on the differences in the blood count eosinophils, neutrophils and lymphocytes, together with the flow cytometry measurements of basic T cell, B cell and NK cell subpopulations before and after systemic CS administration, we identified two severe asthma clusters, which differed in the cell frequencies, response to CS and atopy status. Patients in cluster 1 had higher frequency of blood eosinophils at baseline, were sensitized to less allergens and had better steroid responsiveness, measured as the pronounced leukocyte redistribution after the administration of systemic CS. Patients in cluster 2 were determined by the higher frequency of B-cells and stronger IgE sensitization status to the multiple allergens. They also displayed higher steroid resistance, as the clinical correlate for the lower leukocyte redistribution after administration of systemic CS. CONCLUSION: The flow cytometry-based profiling of the basic populations of immune cells in the blood and its analysis before and after systemic corticosteroid administration could improve personalized treatment approaches in patients with severe asthma.
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Asma , Biomarcadores Ambientais , Corticosteroides/uso terapêutico , Alérgenos , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/genética , Biomarcadores , Eosinófilos , Humanos , Imunoglobulina E , Contagem de Leucócitos , LeucócitosRESUMO
BACKGROUND: Coronavirus disease-2019 (COVID-19) has been associated with cutaneous findings, some being the result of drug hypersensitivity reactions such as maculopapular drug rashes (MDR). The aim of this study was to investigate whether COVID-19 may impact the development of the MDR. METHODS: Blood and skin samples from COVID-19 patients (based on a positive nasopharyngeal PCR) suffering from MDR (COVID-MDR), healthy controls, non-COVID-19-related patients with drug rash with eosinophilia and systemic symptoms (DRESS), and MDR were analyzed. We utilized imaging mass cytometry (IMC) to characterize the cellular infiltrate in skin biopsies. Furthermore, RNA sequencing transcriptome of skin biopsy samples and high-throughput multiplexed proteomic profiling of serum were performed. RESULTS: IMC revealed by clustering analyses a more prominent, phenotypically shifted cytotoxic CD8+ T cell population and highly activated monocyte/macrophage (Mo/Mac) clusters in COVID-MDR. The RNA sequencing transcriptome demonstrated a more robust cytotoxic response in COVID-MDR skin. However, severe acute respiratory syndrome coronavirus 2 was not detected in skin biopsies at the time point of MDR diagnosis. Serum proteomic profiling of COVID-MDR patients revealed upregulation of various inflammatory mediators (IL-4, IL-5, IL-6, TNF, and IFN-γ), eosinophil and Mo/Mac -attracting chemokines (MCP-2, MCP-3, MCP-4 and CCL11). Proteomics analyses demonstrated a massive systemic cytokine storm in COVID-MDR compared with the relatively milder cytokine storm observed in DRESS, while MDR did not exhibit such features. CONCLUSION: A systemic cytokine storm may promote activation of Mo/Mac and cytotoxic CD8+ T cells in severe COVID-19 patients, which in turn may impact the development of MDR.
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COVID-19 , Exantema , Preparações Farmacêuticas , Linfócitos T CD8-Positivos , Humanos , Proteômica , SARS-CoV-2RESUMO
Allergic diseases are characterized by a complex complex chronic pathophysiology. Therapeutic patient education (TPE) programs are an important part of health care for allergic patients. These programs aim to increase the patient's adherence to evidence-based treatment and improve their ability to cope with the disease. TPE led by a multiprofessional team covers the complex pathogenesis of the disease, trigger factors, nursing and dietary issues, and the broad variety of treatment options available including psychological and behavioral aspects.Regarding atopic dermatitis (AD), randomized, controlled studies have demonstrated the beneficial effects of delivering structured group training to children, their caregivers, and adult patients with AD. Such intervention achieved substantial improvements in quality of life and objective clinical disease parameters. Besides AD, training programs have also been developed and evaluated for patients with anaphylaxis and asthma. This article provides an overview of the multitude of TPE concepts and their impact on subjective and objective outcomes. It focuses on AD but also sheds light on other allergic diseases such as anaphylaxis and asthma.
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Asma , Dermatite Atópica , Adulto , Criança , Dermatite Atópica/terapia , Humanos , Educação de Pacientes como Assunto , Qualidade de Vida , Projetos de PesquisaRESUMO
BACKGROUND: Use of Janus kinase 1 inhibitors in moderate-to-severe atopic dermatitis (AD) is associated with incident acne in adolescent and adults that is mostly mild, transient and treatable. There is a need for more knowledge about the risk and severity of acne in patients with AD. OBJECTIVES: To examine the prevalence, incidence and risk of acne in adolescents and adults with AD using nationwide prescription data. METHODS: A matched cohort study of 6600 adults with AD and 66 000 controls was conducted using routinely and prospectively collected nationwide administrative data. Adjusted hazard ratios (HR) are reported with 95% confidence intervals (CIs). RESULTS: The 12-month prevalence of acne was 3.7% in the general population and 3.9% among AD patients. The incidence rate of acne was highest among 12- to 18-year-old AD patients, and overall slightly higher in women with AD compared with males. The overall risk in patients with AD was similar with that of the general population (HR 0.96; 95% CI 0.88-1.06), whereas the risk of being treated for severe acne was reduced in AD patients (HR 0.59; 95% CI 0.47-0.73) and mainly among adolescents and young adults. The HR of acne increased with age reaching 1.41 (95% CI 1.07-1.87) for ages 30-39 years, and 2.07 (95% CI 1.42-3.03) for patients ≥40 years compared with controls. CONCLUSIONS: The risk and severity of acne in AD patients change with age and sex, which may be used for the risk assessment of acne following treatment with Janus kinase 1 inhibitors.
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Acne Vulgar , Dermatite Atópica , Inibidores de Janus Quinases , Acne Vulgar/complicações , Acne Vulgar/tratamento farmacológico , Acne Vulgar/epidemiologia , Adolescente , Adulto , Criança , Estudos de Coortes , Dermatite Atópica/complicações , Dermatite Atópica/epidemiologia , Feminino , Humanos , Incidência , Janus Quinase 1 , Masculino , Prevalência , Adulto JovemRESUMO
Sub-Saharan Africa (SSA) is currently undergoing a transformation process of unprecedented magnitude owing to economic development and urbanization. This process is paralleled by a dramatic increase in prevalence and incidence of noncommunicable diseases. In this article we analyze the current situation with regard to 1 group of the earliest noncommunicable diseases in a person's life, namely, allergies and asthma. This article provides an update on the epidemiology, availability, and access to management strategies by patients experiencing bronchial asthma or atopic dermatitis in SSA. Despite all of the progress, there is still a tremendous need to support education and training, transfer of resources, and cooperation with pharmaceutical and diagnostic companies to achieve adequate treatment and sustainability in SSA with regard to allergy, asthma, and eczema management.
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Asma/epidemiologia , Dermatite Atópica/epidemiologia , África Subsaariana/epidemiologia , Animais , Asma/diagnóstico , Asma/terapia , Dermatite Atópica/diagnóstico , Dermatite Atópica/terapia , Desenvolvimento Econômico , Educação Médica , Humanos , Incidência , Prevalência , UrbanizaçãoRESUMO
STUDY OBJECTIVES: Obstructive sleep apnea (OSA) might lead to oxidative stress, inflammation and elevated circulating copeptin, proANP and proADM levels. We aimed to evaluate whether the levels of these prohormones are higher in patients with OSA and whether they might change under continuous positive airway pressure (CPAP) therapy, serving as potential proxies for the diagnosis and therapy-response in OSA. METHODS: A total of 310 patients with suspicion of OSA were recruited. Screening for OSA was performed using overnight pulse oximetry followed by polygraphy and a venous puncture in the morning. All patients diagnosed with OSA underwent CPAP adaptation. A venous puncture was conducted in the night before CPAP and in the following morning. At 1 and 6 months of treatment, polygraphy was performed, followed by a venous puncture in the morning. In the acquired blood, copeptin, proANP and proADM levels were measured. RESULTS: We analyzed 232 patients with OSA and 30 patients without OSA. Our results indicated that only copeptin levels differed significantly among patients with and without OSA at baseline. In OSA patients, the levels of proADM significantly changed after 1 and 6 months on CPAP therapy, when compared to baseline (p < 0.001 and p = 0.020). Additionally, proANP levels significantly decreased after 12 h on CPAP therapy, as compared to baseline levels (p < 0.001). CONCLUSIONS: Copeptin is significantly associated with the presence of OSA. ProANP levels might serve as a potential proxy for the acute response to non-invasive ventilation (12 h), while proADM reflects the long-term response (1 and 6 months).
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Adrenomedulina/sangue , Fator Natriurético Atrial/sangue , Glicopeptídeos/sangue , Hipóxia/sangue , Precursores de Proteínas/sangue , Apneia Obstrutiva do Sono/sangue , Adulto , Idoso , Biomarcadores/sangue , Pressão Positiva Contínua nas Vias Aéreas , Feminino , Humanos , Hipóxia/diagnóstico , Hipóxia/terapia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapia , Fatores de Tempo , Resultado do Tratamento , Regulação para CimaRESUMO
BACKGROUND: Transbronchial cryobiopsy in the evaluation of patients with interstitial lung diseases (ILD) is expected to reduce the need for surgical lung biopsy (SLB). OBJECTIVE: To evaluate the diagnostic value of cryobiopsy in combination with bronchoalveolar lavage (BAL), radiologic and clinical data in patients with ILD. METHODS: Between 08/15 and 01/20 patients with ILD underwent cryobiopsy if they: did not have (i) an usual interstitial pneumonia (UIP)-pattern on CT, (ii) predominant ground-glass opacities suggesting alveolitis, (iii) findings suggestive of sarcoidosis on CT, or if they had (i) a CT showing UIP-pattern, but had findings suggesting alternative diagnosis than idiopathic pulmonary fibrosis (IPF), or (ii) had previous non-diagnostic conventional transbronchial forceps biopsy. Histological findings were integrated into the multidisciplinary team discussion (MDTD) and a diagnostic consensus was sought. RESULTS: One hundred patients underwent cryobiopsy. In 88/100 patients, cryobiopsy was representative with diagnostic findings in 45/88 and non-specific histological findings in 43/88 patients. In 25/43 with non-specific findings, a consensus diagnosis was reached after MDTD integrating BAL, radiologic and clinical data; eight of the remaining 18 patients with non-specific findings were referred to SLB. In 12/100 patients cryobiopsy was not representative and three of these patients were also referred to SLB. In 7/11 patients (64%) SLB was diagnostic. Complications of cryobiopsy included pneumothorax (14%) and locally controlled bleeding (24%). CONCLUSIONS: The diagnostic yield of cryobiopsy was 70%:45% of cryobiopsies were diagnostic based on histology alone and an additional 25% provided non-specific, but valuable findings allowing a consensus diagnosis after MDTD. Our data demonstrate that the diagnostic value of cryobiopsy is high if combined with BAL, radiologic and clinical data.
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Lavagem Broncoalveolar/métodos , Broncoscopia/métodos , Criocirurgia/métodos , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/cirurgia , Equipe de Assistência ao Paciente , Idoso , Biópsia/métodos , Feminino , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Masculino , Pessoa de Meia-IdadeRESUMO
The pandemic condition coronavirus disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can take asymptomatic, mild, moderate, and severe courses. COVID-19 affects primarily the respiratory airways leading to dry cough, fever, myalgia, headache, fatigue, and diarrhea and can end up in interstitial pneumonia and severe respiratory failure. Reports about the manifestation of various skin lesions and lesions of the vascular system in some subgroups of SARS-CoV-2-positive patients as such features outside the respiratory sphere, are rapidly emerging. Vesicular, urticarial, and maculopapular eruptions and livedo, necrosis, and other vasculitis forms have been reported most frequently in association with SARS-CoV-2 infection. In order to update information gained, we provide a systematic overview of the skin lesions described in COVID-19 patients, discuss potential causative factors, and describe differential diagnostic evaluations. Moreover, we summarize current knowledge about immunologic, clinical, and histologic features of virus- and drug-induced lesions of the skin and changes to the vascular system in order to transfer this knowledge to potential mechanisms induced by SARS-CoV-2.
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COVID-19/complicações , SARS-CoV-2 , Dermatopatias/etiologia , Enzima de Conversão de Angiotensina 2/análise , COVID-19/imunologia , COVID-19/patologia , COVID-19/transmissão , Feminino , Humanos , Masculino , Pele/patologia , Dermatopatias/patologiaRESUMO
BACKGROUND: Allergic disorders such as atopic dermatitis (AD) are strongly associated with an impairment of the epithelial barrier, in which tight junctions and/or filaggrin expression can be defective. Skin barrier assessment shows potential to be clinically useful for prediction of disease development, improved and earlier diagnosis, lesion follow-up, and therapy evaluation. This study aimed to establish a method to directly assess the in vivo status of epithelial barrier using electrical impedance spectroscopy (EIS). METHODS: Thirty-six patients with AD were followed during their 3-week hospitalization and compared with 28 controls. EIS and transepidermal water loss (TEWL) were measured in lesional and non-lesional skin. Targeted proteomics by proximity extension assay in serum and whole-genome sequence were performed. RESULTS: Electrical impedance spectroscopy was able to assess epithelial barrier integrity, differentiate between patients and controls without AD, and characterize lesional and non-lesional skin of patients. It showed a significant negative correlation with TEWL, but a higher sensitivity to discriminate non-lesional atopic skin from controls. During hospitalization, lesions reported a significant increase in EIS that correlated with healing, decreased SCORAD and itch scores. Additionally, EIS showed a significant inverse correlation with serum biomarkers associated with inflammatory pathways that may affect the epithelial barrier, particularly chemokines such as CCL13, CCL3, CCL7, and CXCL8 and other cytokines, such as IRAK1, IRAK4, and FG2, which were significantly high at admission. Furthermore, filaggrin copy numbers significantly correlated with EIS on non-lesional skin of patients. CONCLUSIONS: Electrical impedance spectroscopy can be a useful tool to detect skin barrier dysfunction in vivo, valuable for the assessment of AD severity, progression, and therapy efficacy.
Assuntos
Dermatite Atópica , Eczema , Citocinas , Dermatite Atópica/diagnóstico , Espectroscopia Dielétrica , Proteínas Filagrinas , Humanos , Prurido , PeleRESUMO
BACKGROUND: As an evidence resource for the currently planned European Academy of Allergy and Clinical Immunology (EAACI) clinical practice guideline "systemic treatment of atopic dermatitis (AD)," we critically appraised evidence on systemic treatments for moderate-to-severe AD. METHODS: We systematically identified randomized controlled trials (RCTs) investigating the safety and efficacy of systemic treatments for AD up to February 2020. Primary efficacy outcomes were clinical signs, AD symptoms and health-related quality of life. Primary safety outcomes included cumulative incidence rates for (serious) adverse events. Trial quality was assessed applying the Cochrane Risk of Bias Tool 2.0. Meta-analyses were conducted where appropriate. RESULTS: 50 RCTs totalling 6681 patients were included. Trial evidence was identified for apremilast, azathioprine (AZA), baricitinib, ciclosporin A (CSA), corticosteroids, dupilumab, interferon-gamma, intravenous immunoglobulins (IVIG), mepolizumab, methotrexate (MTX), omalizumab, upadacitinib and ustekinumab. Meta-analyses were indicated for the efficacy of baricitinib [EASI75 RD 0.16, 95% CI (0.10;0.23)] and dupilumab [EASI75, RD 0.37, 95% CI (0.32;0.42)] indicating short-term (ie 16-week treatment) superiority over placebo. Furthermore, efficacy analyses of AZA and CSA indicated short-term superiority over placebo; however, nonvalidated scores were used and can therefore not be compared to EASI. CONCLUSION: The most robust, replicated high-quality trial evidence is present for the efficacy and safety of dupilumab for up to 1 year in adults. Robust trial evidence was further revealed for AZA, baricitinib and CSA. Methodological restrictions led to limited evidence-based conclusions for all other systemic treatments. Head-to-head trials with novel systemic treatments are required to clarify the future role of conventional therapies.