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Background Atopic dermatitis (AD) is a heterogeneous, chronic inflammatory skin disease linked to skin microbiome dysbiosis with reduced bacterial diversity and elevated relative abundance of Staphylococcus aureus (S. aureus). Objectives We aimed to characterize the yet incompletely understood association between the skin microbiome and patients' demographic and clinical cofactors in relation to AD severity. Methods The skin microbiome in 48 adult moderate-to-severe AD patients was investigated using next-generation deep sequencing (16S rRNA gene, V1–V3 region) followed by denoising (DADA2) to obtain amplicon sequence variant (ASV) composition. Results In lesional skin, AD severity was associated with S. aureus relative abundance (rS = 0.53, p

Akute oder chronische Rötungen der Unterschenkel sind ein häufiger Vorstellungsgrund in Kliniken und Praxen und stellen oftmals eine differenzialdiagnostische Herausforderung dar. Ziel dieser Leitlinie ist es, Kriterien und Vorgehensweisen für die Differenzialdiagnose akuter oder chronischer, uni- oder bilateraler Rötungen der Unterschenkel festzulegen. Eine korrekte Diagnosestellung ist essenziell, um die adäquate Therapie auszuwählen und den nicht indizierten Einsatz von Antibiotika zu reduzieren. Von der Leitliniengruppe wurden die relevantesten Differenzialdiagnosen identifiziert: (1.) Erysipel, (2.) Stauungsdermatitis, (3.) hypererge Ictusreaktion, (4.) oberflächliche und tiefe Beinvenenthrombose, (5.) Gicht, (6.) chronisch allergisches Kontaktekzem und (7.) akutes toxisches beziehungsweise allergisches Kontaktekzem. Für diese sieben Diagnosen wurden Algorithmen beziehungsweise Diagnosepfade zum diagnostischen Vorgehen, die jeweils in Anamnese, klinische Untersuchung und apparative Diagnostik aufgegliedert sind, entwickelt. Darüber hinaus hat die Leitliniengruppe mindestens 40 weitere Differenzialdiagnosen gesammelt und spezifische Charakteristika zur differenzialdiagnostischen Abgrenzung tabellarisch gegenübergestellt.

Background Limited number of studies have focused on the impact of pollen exposure on asthma. As a part of the EAACI Guidelines on Environment Science, this first systematic review on the relationship of pollen exposure to asthma exacerbations aimed to bridge this knowledge gap in view of implementing recommendations of prevention. Methods We searched electronic iPubMed, Embase, and Web of Science databases using a set of MeSH terms and related synonyms and identified 73 eligible studies that were included for systemic review. When possible, meta-analyses were conducted. Results Overall meta-analysis suggests that outdoor pollen exposure may have an effect on asthma exacerbation but caution is needed due to the low number of studies and their heterogeneity. The strongest associations were found between asthma attacks, asthma-related ED admissions or hospitalizations and an increase of grass pollen concentration in the previous 2 days overall in children aged less than 18 years of age. Tree pollen may increase asthma-related ED visits or admissions lagged up to 7 days overall in individuals younger than 18 years. Rare data show that among subjects under 18 years of age an exposure to grass pollen lagged up to 3 days may lower lung function. Conclusions Further research considering effect modifiers of pollen sensitization, hay fever, asthma, air pollution, green spaces and pre-existing medications is urgently warranted to better evaluate the impacts of pollen on asthma exacerbation. Preventive measures in relation to pollen exposure should be integrated in asthma control as pollen increase continues due to climate change.

Atopic eczema (AE) is an inflammatory skin disease with involvement of genetic, immunological, and environmental factors. One hallmark of AE is a skin barrier disruption on multiple, highly interconnected levels: filaggrin mutations, increased skin pH, and a microbiome dysbiosis towards Staphylococcus aureus overgrowth are observed in addition to an abnormal type 2 immune response. Extrinsic factors seem to play a major role in the development of AE. As AE is a first step in the atopic march, its prevention and appropriate treatment is essential. Although standard therapy remains topical treatment, powerful systemic treatment options emerged in the last years. However, thorough endotyping of the individual patients is still required for ideal precision medicine approaches in the future. Therefore, novel microbial and immunological biomarkers were described recently for the prediction of disease development and treatment response. This review summarizes the current state of the art in AE research.

Social and psychosocial factors are thought to have an effect on the course of atopic eczema. The aim of this scoping review was to search for and summarize observational studies that investigated the effects of (psycho-)social factors on symptoms in atopic eczema and to identify research gaps. We searched PubMed and PsycINFO for literature published between 1 January 1989 and 31 December 2019 using a systematic search strategy. We included observational studies that analysed the effect of (psycho-)social factors on symptom severity in atopic eczema patients. Reviews and non-observational studies, articles with research on animals, and articles with languages other than English or German were excluded. We identified 17 observational studies that met the inclusion criteria. Several studies found significant results for an exacerbating effect of stress on atopic eczema severity. Although coping and social support does not seem to moderate the effect of stress, coping strategies might mediate the impact that stress has on symptoms. Depression is associated with atopic eczema severity. The effect of depression as a consequence of atopic eczema severity is stronger than the effect as an exacerbating factor. Illness identity, anger, frustration and psychosomatic states have been found to affect atopic eczema symptoms. For attachment security, anxiety and social status, contradictory results were found. Statistically non-significant results were reported for personality, being in a partnership, satisfaction with the partnership, childhood experiences and body consciousness. Only the association between psychosocial stress and atopic eczema symptom severity seems robust. To date, other (psycho-)social factors, especially protective and health-promoting factors, were analysed only in a few studies, mostly with low sample sizes and cross-sectional design. Biopsychosocial interactions between stress, protective factors and the course of atopic eczema as well as the psycho-neuroimmunological mechanisms underlying those interactions are considered fields for future research contributions.

Background: Morbidity and mortality from COVID-19 caused by novel coronavirus SARS-CoV-2 is accelerating worldwide, and novel clinical presentations of COVID-19 are often reported. The range of human cells and tissues targeted by SARS-CoV-2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS-CoV-2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID-19. Methods: We performed RNA sequencing and explored available RNA-Seq databases to study gene expression and co-expression of ACE2, CD147 (BSG), and CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4+ and CD8+ T cells, B cells, and plasmablasts. We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID-19 risk factor status. Results: ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA andPPIB), CD26 (DPP4), and related molecules were expressed in both epithelium and in immune cells. We also observed a distinct age-related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2- and CD147-related genes in the bronchial biopsy, BAL, or blood. Additionally, CD147-related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of CD147-related genes in the lesional skin of patients with atopic dermatitis. Conclusions: Our data suggest different receptor repertoire potentially involved in the SARS-CoV-2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related to age, gender, obesity and smoking, as well as with the disease status, might contribute to COVID-19 morbidity and severity patterns. Keywords: COPD; COVID-19; COVID-19 children; SARS receptor; asthma; hypertension; obesity.

Zusammenfassung Die durch das Coronavirus SARS-CoV-2 verursachte Krankheit COVID-19 hat sich zu einer Pandemie entwickelt. Bei der Betrachtung von dermatologischen und allergologischen Krankheiten, die potenziell von COVID-19 betroffen sind, stehen wir vor komplexen Herausforderungen, die Pathogenese und Beeinflussung verschiedener immunologischer Signalwege einschlie ss en. Medizinische Behandlungen mussen daher im Zusammenhang mit dieser Infektion oft neu bewertet und in Frage gestellt werden. Dieser ubersichtsartikel fasst den aktuellen Wissensstand zu COVID-19 hinsichtlich der wichtigsten dermatologischen und allergologischen Erkrankungen zusammen. Es werden aber auch die medizinischen Bereiche beschrieben, fur die keine ausreichenden Daten vorliegen. Unter Zusammenfassung der publizierten Daten und grundsatzlicher pathophysiologischer uberlegungen werden hier Schlussfolgerungen fur das Management unserer Patienten wahrend der Pandemie gezogen. Wir konzentrieren uns auf haufige Hauterkrankungen mit komplexer immunologischer Pathogenese: Psoriasis, Ekzeme einschlie ss lich atopischer Dermatitis, Typ-I-Allergien, blasenbildende Autoimmundermatosen, Kollagenosen, Vaskulitiden und Hautkrebserkrankung. Da viele weitere Hauterkrankungen verwandte oder vergleichbare immunologische Reaktionsmuster aufweisen, konnen pathophysiologisch ahnliche entzundliche Dermatosen moglicherweise auch mit ahnlichen therapeutischen uberlegungen und Schlussfolgerungen wahrend der Pandemie behandelt werden. Daher soll diese ubersicht Behandlungsempfehlungen auf der Basis bisher publizierter Daten und Empfehlungen zu Therapieentscheidungen auch uber die hier diskutierten, haufigsten Erkrankungen hinaus liefern.

Since the introduction of allergen immunotherapy (AIT) over 100 years ago, focus has been on standardization of allergen extracts, with reliable molecular composition of allergens receiving the highest attention. While adjuvants play a major role in European AIT, they have been less well studied. In this Position Paper, we summarize current unmet needs of adjuvants in AIT citing current evidence. Four adjuvants are used in products marketed in Europe: aluminium hydroxide (Al(OH)(3)) is the most frequently used adjuvant, with microcrystalline tyrosine (MCT), monophosphoryl lipid A (MPLA) and calcium phosphate (CaP) used less frequently. Recent studies on humans, and using mouse models, have characterized in part the mechanisms of action of adjuvants on pre-existing immune responses. AIT differs from prophylactic vaccines that provoke immunity to infectious agents, as in allergy the patient is presensitized to the antigen. The intended mode of action of adjuvants is to simultaneously enhance the immunogenicity of the allergen, while precipitating the allergen at the injection site to reduce the risk of anaphylaxis. Contrasting immune effects are seen with different adjuvants. Aluminium hydroxide initially boosts Th2 responses, while the other adjuvants utilized in AIT redirect the Th2 immune response towards Th1 immunity. After varying lengths of time, each of the adjuvants supports tolerance. Further studies of the mechanisms of action of adjuvants may advise shorter treatment periods than the current three-to-five-year regimens, enhancing patient adherence. Improved lead compounds from the adjuvant pipeline are under development and are explored for their capacity to fill this unmet need.

Multiple Chemikaliensensibilitat (MCS) ist eine subjektiv erlebte, erhohte Empfindlichkeit gegenuber Chemikalien aus der Umwelt. Betroffene reagieren mit vielfaltigen, unspezifischen Beschwerden. Symptome an Haut und Schleimhauten werden von Personen mit MCS haufig auf eine Exposition gegenuber Chemikalien zuruckgefuhrt. Auch Dermatologen sollten sich deshalb mit dieser Gesundheitsstorung auseinandersetzen. Multiple Chemikaliensensibilitat ist eine Ausschlussdiagnose. Durch Basisdiagnostik, Allergiediagnostik oder Umweltdiagnostik sollen andere mogliche Ursachen fur Symptome ausgeschlossen werden. Die Dermatologie sollte in erster Linie Hauterkrankungen und Allergien als mogliche Ursachen fur Beschwerden abklaren. Interdisziplinare Betreuung der Betroffenen ist insbesondere bei schweren Verlaufen von Relevanz, beispielsweise, wenn Betroffene in Ihrer Alltagsbewaltigung eingeschrankt sind. Wichtige Disziplinen sind dabei unter anderen Umweltmedizin, Psychosomatik, Arbeits- und Sozialmedizin. Hautbeschwerden werden durch die Dermatologie symptomatisch, zum Beispiel mit Hautbasispflege, behandelt. Evidenzbasierte Therapieempfehlungen zur Behandlung von MCS gibt es bislang nicht. Menschen mit MCS sollen vor uberflussigen Behandlungen und damit vor psychischen, sozialen und finanziellen Belastungen geschutzt werden. Fur den Umgang mit Betroffenen sind neben fachlichen, naturwissenschaftlichen Kompetenzen vor allem auch kommunikative und psychosoziale Kompetenzen relevant. Psychotherapeutische Weiterbildung fur behandelnde Personen ist hilfreich. Unabhangig von den Mechanismen, die zu MCS fuhren, ist eine aktiv unterstutzende Grundhaltung behandelnder Personen, eine gute Arzt-Patient-Beziehung sowie interdisziplinare Zusammenarbeit bei Diagnostik und Therapie notig.

Author(s): Thyssen, JP; de Bruin-Weller, MS; Paller, AS; Leshem, YA; Vestergaard, C; Deleuran, M; Drucker, AM; Foelster-Holst, R; Traidl-Hoffmann, C; Eyerich, K; Taieb, A; Su, JC; Bieber, T; Cork, MJ; Eichenfield, LF; Guttman-Yassky, E; Wollenberg, A | Abstract: BackgroundConjunctivitis is common in patients with atopic dermatitis (AD) in general and a commonly reported adverse event in AD clinical trials with dupilumab.ObjectiveTo survey opinions and experience about conjunctivitis occurring in AD, including those during dupilumab treatment in a group of AD experts from the International Eczema Council (IEC).MethodsElectronic survey and in-person discussion of management strategies.ResultsForty-six (53.5%) IEC members from 19 countries responded to the survey. Consensus was reached for several statements regarding diagnostic workup, referral and treatment. IEC members suggest that patients with AD should (i) routinely be asked about ocular complaints or symptoms, (ii) obtain information about the potential for conjunctivitis before starting dupilumab therapy and (iii) if indicated, be treated with dupilumab despite previous or current conjunctivitis. In cases of new-onset conjunctivitis, there was consensus that dupilumab treatment should be continued when possible, with appropriate referral to an ophthalmologist.LimitationsThe study relies on expert opinion from dermatologists. Responses from few dermatologists without dupilumab access were not excluded from the survey.ConclusionThe IEC recommends that dermatologists address conjunctivitis in patients with AD, especially during treatment with dupilumab.

BACKGROUND Common ragweed has been spreading as a neophyte in Europe. Elevated CO2 levels, a hallmark of global climate change, have been shown to increase ragweed pollen production, but their effects on pollen allergenicity remain to be elucidated. METHODS Ragweed was grown in climate-controlled chambers under normal (380 ppm, control) or elevated (700 ppm, based on RCP4.5 scenario) CO2 levels. Aqueous pollen extracts (RWE) from control- or CO2 -pollen were administered in vivo in a mouse model for allergic disease (daily for 3-11 days, n = 5) and employed in human in vitro systems of nasal epithelial cells (HNECs), monocyte-derived dendritic cells (DCs), and HNEC-DC co-cultures. Additionally, adjuvant factors and metabolites in control- and CO2 -RWE were investigated using ELISA and untargeted metabolomics. RESULTS In vivo, CO2 -RWE induced stronger allergic lung inflammation compared to control-RWE, as indicated by lung inflammatory cell infiltrate and mediators, mucus hypersecretion, and serum total IgE. In vitro, HNECs stimulated with RWE increased indistinctively the production of pro-inflammatory cytokines (IL-8, IL-1β, and IL-6). In contrast, supernatants from CO2 -RWE-stimulated HNECs, compared to control-RWE-stimulated HNECS, significantly increased TNF and decreased IL-10 production in DCs. Comparable results were obtained by stimulating DCs directly with RWEs. The metabolome analysis revealed differential expression of secondary plant metabolites in control- vs CO2 -RWE. Mixes of these metabolites elicited similar responses in DCs as compared to respective RWEs. CONCLUSION Our results indicate that elevated ambient CO2 levels elicit a stronger RWE-induced allergic response in vivo and in vitro and that RWE increased allergenicity depends on the interplay of multiple metabolites.

COVID-19, caused by the coronavirus SARS-CoV-2, has become pandemic. A further level of complexity opens up as soon as we look at diseases whose pathogenesis and therapy involve different immunological signaling pathways, which are potentially affected by COVID-19. Medical treatments must often be reassessed and questioned in connection with this infection. This article summarizes the current knowledge of COVID-19 in the light of major dermatological and allergological diseases. It identifies medical areas lacking sufficient data and draws conclusions for the management of our patients during the pandemic. We focus on common chronic inflammatory skin diseases with complex immunological pathogenesis: psoriasis, eczema including atopic dermatitis, type I allergies, autoimmune blistering and inflammatory connective tissue diseases, vasculitis, and skin cancers. Since several other inflammatory skin diseases display related or comparable immunological reactions, clustering of the various inflammatory dermatoses into different disease patterns may help with therapeutic decisions. Thus, following these patterns of skin inflammation, our review may supply treatment recommendations and thoughtful considerations for disease management even beyond the most frequent diseases discussed here.

Although genetic factors play a role in the etiology of atopic disease, the rapid increases in the prevalence of these diseases over the last few decades suggest that environmental, rather than genetic factors are the driving force behind the increasing prevalence. In modern societies, there is increased time spent indoors, use of antibiotics, and consumption of processed foods and decreased contact with farm animals and pets, which limit exposure to environmental allergens, infectious parasitic worms, and microbes. The lack of exposure to these factors is thought to prevent proper education and training of the immune system. Increased industrialization and urbanization have brought about increases in organic and inorganic pollutants. In addition, Caesarian birth, birth order, increased use of soaps and detergents, tobacco smoke exposure and psychosomatic factors are other factors that have been associated with increased rate of allergic diseases. Here, we review current knowledge on the environmental factors that have been shown to affect the development of allergic diseases and the recent developments in the field.

Modern health care requires a proactive and individualized response to diseases, combining precision diagnosis and personalized treatment. Accordingly, the approach to patients with allergic diseases encompasses novel developments in the area of personalized medicine, disease phenotyping and endotyping, and the development and application of reliable biomarkers. A detailed clinical history and physical examination followed by the detection of IgE immunoreactivity against specific allergens still represents the state of the art. However, nowadays, further emphasis focuses on the optimization of diagnostic and therapeutic standards and a large number of studies have been investigating the biomarkers of allergic diseases, including asthma, atopic dermatitis, allergic rhinitis, food allergy, urticaria and anaphylaxis. Various biomarkers have been developed by omics technologies, some of which lead to a better classification of distinct phenotypes or endotypes. The introduction of biologicals to clinical practice increases the need for biomarkers for patient selection, prediction of outcomes and monitoring, to allow for an adequate choice of the duration of these costly and long‐lasting therapies. Escalating healthcare costs together with questions about the efficacy of the current management of allergic diseases require further development of a biomarker‐driven approach. Here, we review biomarkers in diagnosis and treatment of asthma, atopic dermatitis, allergic rhinitis, viral infections, chronic rhinosinusitis, food allergy, drug hypersensitivity and allergen immunotherapy with a special emphasis on specific IgE, the microbiome and the epithelial barrier. In addition, EAACI guidelines on biologicals are discussed within the perspective of biomarkers.

Background Atopic eczema (atopic dermatitis, AD) is characterized by disrupted skin barrier associated with elevated skin pH and skin microbiome dysbiosis, due to high Staphylococcus aureus loads, especially during flares. Since S aureus shows optimal growth at neutral pH, we investigated the longitudinal interplay between these factors and AD severity in a pilot study. Method Emollient (with either basic pH 8.5 or pH 5.5) was applied double-blinded twice daily to 6 AD patients and 6 healthy (HE) controls for 8 weeks. Weekly, skin swabs for microbiome analysis (deep sequencing) were taken, AD severity was assessed, and skin physiology (pH, hydration, transepidermal water loss) was measured. Results Physiological, microbiome, and clinical results were not robustly related to the pH of applied emollient. In contrast to longitudinally stable microbiome in HE, S aureus frequency significantly increased in AD over 8 weeks. High S aureus abundance was associated with skin pH 5.7-6.2. High baseline S aureus frequency predicted both increase in S aureus and in AD severity (EASI and local SCORAD) after 8 weeks. Conclusion Skin pH is tightly regulated by intrinsic factors and limits the abundance of S aureus. High baseline S aureus abundance in turn predicts an increase in AD severity over the study period. This underlines the importance and potential of sustained intervention regarding the skin pH and urges for larger studies linking skin pH and skin S aureus abundance to understand driving factors of disease progression.

Ze339, an herbal extract from Petasites hybridus leaves is effective in treatment of allergic rhinitis by inhibition of a local production of IL-8 and eicosanoid LTB4 in allergen-challenged patients. However, the mechanism of action and anti-inflammatory potential in virally induced exacerbation of the upper airways is unknown. This study investigates the anti-inflammatory mechanisms of Ze339 on primary human nasal epithelial cells (HNECs) upon viral, bacterial and pro-inflammatory triggers. To investigate the influence of viral and bacterial infections on the airways, HNECs were stimulated with viral mimics, bacterial toll-like-receptor (TLR)-ligands or cytokines, in presence or absence of Ze339. The study uncovers Ze339 modulated changes in pro-inflammatory mediators and decreased neutrophil chemotaxis as well as a reduction of the nuclear translocation and phosphorylation of STAT molecules. Taken together, this study suggests that phyto drug Ze339 specifically targets STAT-signalling pathways in HNECs and has high potential as a broad anti-inflammatory drug that exceeds current indication. © 2016 BioFactors, 43(3):388-399, 2017.

BACKGROUND: Besides allergens, pollen release bioactive, low molecular weight compounds that modulate and stimulate allergic reactions. Clinical relevance of these substances hasn't been investigated to date. OBJECTIVE: To elucidate the effect of a non-allergenic, low molecular weight factors from aqueous birch pollen extracts (Bet-APE

Ragweed pollen is the main cause of allergenic diseases in Northern America, and the weed has become a spreading neophyte in Europe. Climate change and air pollution are speculated to affect the allergenic potential of pollen. The objective of this study was to investigate the effects of NO2 , a major air pollutant, under controlled conditions, on the allergenicity of ragweed pollen. Ragweed was exposed to different levels of NO2 throughout the entire growing season, and its pollen further analysed. Spectroscopic analysis showed increased outer cell wall polymers and decreased amounts of pectin. Proteome studies using two-dimensional difference gel electrophoresis and liquid chromatography-tandem mass spectrometry indicated increased amounts of several Amb a 1 isoforms and of another allergen with great homology to enolase Hev b 9 from rubber tree. Analysis of protein S-nitrosylation identified nitrosylated proteins in pollen from both conditions, including Amb a 1 isoforms. However, elevated NO2 significantly enhanced the overall nitrosylation. Finally, we demonstrated increased overall pollen allergenicity by immunoblotting using ragweed antisera, showing a significantly higher allergenicity for Amb a 1. The data highlight a direct influence of elevated NO2 on the increased allergenicity of ragweed pollen and a direct correlation with an increased risk for human health.

Zusammenfassung Der Genuss von grunem Tee hat in asiatischen Landern – vor allem in China – eine lange Tradition. Die epidemiologisch und experimentell beobachteten antikarzinogenen und antiinflammatorischen Effekte von grunem Tee haben zum Einsatz von Gruntee-Extrakten bei verschiedenen therapeutischen Anwendungen gefuhrt – sowohl in dermatologischen als auch in kosmetischen Praparaten, wobei die umfangreichsten Untersuchungen fur die antikarzinogene und chemopraventive Wirkung von grunem Tee bzw. seines Hauptbestandteils Epigallocatechin-3-gallat vorliegen. Fast ebenso gut nachgewiesen ist die Wirkung bei Infektionskrankheiten wie kutanen Virusinfektionen. Zur topischen Behandlung von Genitalwarzen wurde eine Salbe mit Gruntee-Extrakten 2010 in den USA und kurzlich auch in Europa zugelassen. Experimentelle Daten, die auf eine Blockade zentraler Signaltransduktionsfaktoren hinweisen, haben zur Untersuchung von Catechinen bei entzundlichen Erkrankungen wie atopischer Dermatitis gefuhrt. Die Ansicht, gruner Tee sei eine „Wunderwaffe“ gegen Krankheiten, ist bereits Tausende von Jahren alt. Einer chinesischen Legende zufolge bemerkte der antike Kaiser Shen Nung ein herrliches Aroma, nachdem einige Blatter eines in der Nahe stehenden Baumes in kochendes Wasser gefallen waren. Sofort erklarte er das neue „Getrank“ zu einem „Geschenk des Himmels“, was den Ursprung der – bis heute bestehenden – Uberzeugung bildete, gruner Tee sei ein Arzneimittel aus der Natur und gegen viele verschiedene Krankheiten wirksam. Dieser Ubersichtsartikel fasst die biologischen und klinischen Effekte von grunem Tee zusammen.

Green tea consumption has a long tradition in Asian countries--especially China. The epidemiologically and experimentally observed anticarcinogenic and antiinflammatory effects of green tea have led to the implementation of green tea extracts in multiple therapeutic applications - both in dermatological and cosmeceutical preparations. The most abundant evidence exists for the anticarcinogenic and chemopreventive effect of green tea or its major constituent epigallocatechin-3-gallate. Almost equally evident is the effect in infectious diseases such as cutaneous viral infections. For external genital warts, a topical ointment with green tea extracts was licensed in the USA in 2010, and recently also in Europe. Experimental evidence pinpointing the block of central signal transduction factors in inflammatory mechanisms has led to the evaluation of catechins in inflammatory disorders such as atopic dermatitis. The belief of green tea as a "wonder weapon" against diseases dates back thousands of years. According to a Chinese legend, ancient Emperor Shen Nung noted a delightful aroma after some leaves of a nearby tree had fallen into boiling water. He immediately proclaimed the new "drink" as "heaven-sent", starting the belief - persisting until today - of green tea as a medication from nature against many different diseases. This review summarizes biological effects and clinical implications of green tea.

Allergies and autoimmune diseases are spreading worldwide. Control of infections, on the other hand, remains an issue, even in the post-antibiotic era. Chronic or poorly controlled infections occur in immune compromised individuals such as HIV patients, hospitalized patients exposed to multi-resistant bacteria, or patients on immunosuppressive treatment. They may become an even more emerging issue in an ageing population. At the same time, profound environmental changes such as global warming, urbanization, increasing environmental pollution and novel food engineering technologies may alter the abundance or aggressiveness of allergens/allergen carriers in our environment. Likewise, changes in dietary habits - and possibly also use of antibiotics - have an impact on the composition of our natural microbial flora in the gut, airways and skin, which may alter susceptibility for common diseases, among them allergies, asthma and atopic eczema. At the recently founded Institute of Environmental Medicine of the Technische Universitat Munich, located in Augsburg at the UNIKA-T, experimental, clinical and translational research is focused on the complex interactions of environment, pathogen and host in expression or control of communicable and non-communicable diseases. We present our research concept and recent findings in environment - host interactions.

Item does not contain fulltext Recurrent fever can be the sole or leading manifestation of a variety of diseases including malignancies, autoimmune diseases and infections. Because the differential diagnoses are manifold, no formal guidelines for the approach of patients with recurrent fever exists. The newly recognized group of autoinflammatory diseases are often accompanied by repetitive fever attacks. As these episodes are frequently associated by a variety of divergent presentations, the differentiation of other causes for febrile illnesses can be difficult. In this article, we first review disease entities, which frequently present with the symptom of recurrent fever. In a next step, we summarize their characteristic pattern of disease presentation. Finally, we analyse key features of autoinflammatory diseases, which are helpful to distinguish this group of diseases from the other causes of recurrent fever. Recognizing these symptom patterns can provide the crucial clues and, thus, lead to the initiation of targeted specific diagnostic tests and therapies.

T cells exercise their full impact on target cells through a combination of secreted cytokines. The recently described T helper cell subset Th22 is characterized by a combinatorial secretion of IL-22 and TNF-α. Here, we demonstrate that IL-22 increases the TNF-α-dependent induction and secretion of several immune-modulatory molecules such as initial complement factors C1r and C1s, antimicrobial peptides S100A7 and HBD-2 (human β defensin 2), and antimicrobial chemokines CXCL-9/-10/-11 in primary human keratinocytes. The synergism of IL-22 and TNF-α is transmitted intracellularly by MAP kinases and downstream by transcription factors of the AP-1 family. The induction of innate immunity is relevant in an in vitro infection model, where keratinocytes stimulated with Th22 supernatants or recombinant IL-22 plus TNF-α effectively inhibit the growth of Candida albicans and maintain survival of epithelia. Accordingly, the combinatorial stimulation of keratinocytes with IL-22 and TNF-α most efficiently conserves the integrity of the epidermal barrier in a three-dimensional skin infection model as compared with IFN-γ, IL-17, IL-22 or TNF-α alone. In summary, we demonstrate that IL-22 and TNF-α represent a potent, synergistic cytokine combination for cutaneous immunity.

Please cite this paper as: Comparative in situ topoproteome analysis reveals differences in patch test-induced eczema: cytotoxicity-dominated nickel versus pleiotrope pollen reaction. Experimental Dermatology 2010; 19: 511–517. Abstract: A subgroup of patients with atopic eczema develops acute eczematous reactions to type I allergy-inducing agents such as pollen that clinically resemble type IV allergies induced by haptens like metal ions. To clarify the underlying immunologic mechanisms, this study was designed to map the inflammatory in situ topoproteome of eczematous responses to grass/birch pollen and nickel by using atopy patch test (APT) and nickel patch test (NPT) as an appropriate clinical model, respectively. Biopsies from NPT (n = 6) and APT (n = 6) with positive reactions at 72 h were analysed by multiple epitope ligand cartography (MELC), which enabled to investigate coexpression of 49 different epitopes immunohistochemically in a single given tissue section. Colocalisation of IgE and FceRI was investigated by confocal microscopy. Compared with APT responses, NPT reactions were dominated by cytotoxic TIA-1 + and CD8 + T cells. In contrast, the immune response in APT reactions appeared more pleiotrope – as detected by colocalisation analysis. Multiple combinatorial molecular phenotype (CMP) motifs containing naive, early maturation and memory T cell (CD45RA, CD7, CD44, CD45R0), and general activation markers (CLA, HLA-DR, CD13, CD29, CD58, CD71, CD138) were significantly higher expressed in APT when compared with NPT reactions. APT response was confirmed to be accompanied by IgE bound to FceRI. In summary, our results demonstrate that the NPT reaction is clearly dominated by cytotoxic events, while the APT reaction to pollen grains is more heterogeneous and elicits a combined humoral and cellular immune reaction.