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Latest Paper:
PLoS One. 2012 ;7 (5):e35778
22590513
Linus Grabenhenrich,
Stephanie Hompes,
Hannah Gough,
Franziska Ruëff,
Kathrin Scherer,
Claudia Pföhler,
Regina Treudler,
Vera Mahler,
Thomas Hawranek,
Katja Nemat,
Alice Koehli,
Thomas Keil,
Margitta Worm
Institute of Social Medicine, Epidemiology and Health Economics, Charité University Medical Centre Berlin, Berlin, Germany.
BACKGROUND Anaphylaxis management guidelines recommend the use of intramuscular adrenaline in severe reactions, complemented by antihistamines and corticoids; secondary prevention includes allergen avoidance and provision of self-applicable first aid drugs. Gaps between recommendations and their implementation have been reported, but only in confined settings. Hence, we analysed nation-wide data on the management of anaphylaxis, evaluating the implementation of guidelines. METHODS Within the anaphylaxis registry, allergy referral centres across Germany, Austria and Switzerland provided data on severe anaphylaxis cases. Based on patient records, details on reaction circumstances, diagnostic workup and treatment were collected via online questionnaire. Report of anaphylaxis through emergency physicians allowed for validation of registry data. RESULTS 2114 severe anaphylaxis patients from 58 centres were included. 8% received adrenaline intravenously, 4% intramuscularly; 50% antihistamines, and 51% corticoids. Validation data indicated moderate underreporting of first aid drugs in the Registry. 20% received specific instructions at the time of the reaction; 81% were provided with prophylactic first aid drugs at any time. CONCLUSION There is a distinct discrepancy between current anaphylaxis management guidelines and their implementation. To improve patient care, a revised approach for medical education and training on the management of severe anaphylaxis is warranted.
Contact Dermatitis. 2012 Apr 15;:
22500724
Wolfgang Uter,
Aberer Werner,
José Carlos Armario-Hita,
José M Fernandez-Vozmediano,
Fabio Ayala,
Anna Balato,
Andrea Bauer,
Barbara Ballmer-Weber,
Aiste Beliauskiene,
Anna Belloni Fortina,
Andreas Bircher,
Jochen Brasch,
Mahbub M U Chowdhury,
Pieter-Jan Coenraads,
Marie-Louise Schuttelaar,
Sue Cooper,
Magda Czarnecka-Operacz,
Maria Zmudzinska,
Peter Elsner,
John S C English,
Peter J Frosch,
Thomas Fuchs,
Juan García-Gavín,
Virginia Fernández-Redondo,
David J Gawkrodger,
Ana Giménez-Arnau,
Cathy M Green,
Helen L Horne,
Jeanne Duus Johansen,
Riitta Jolanki,
Maria Pesonen,
Clodagh M King,
Beata Krêcisz,
Dorota Chomiczewska,
Marta Kiec-Swierczynska,
Francesca Larese,
Vera Mahler,
Anthony D Ormerod,
Andrea Peserico,
Tapio Rantanen,
Thomas Rustemeyer,
Javier Sánchez-Pérez,
Jane E Sansom,
Juan Fco Silvestre,
Dagmar Simon,
Radoslaw Spiewak,
Barry N Statham,
Natalie Stone,
Mark Wilkinson,
Axel Schnuch
Department of Medical Informatics, Biometry and Epidemiology, University of Erlangen-Nürnberg, D-91054 Erlangen, Germany Department of Dermatology, Medical University of Graz, A-8036 Graz, Austria Department of Dermatology, University Hospital of Puerto Real, ES-11500 Cadiz, Spain Deptartment of Dermatology, University of Naples Federico II, IT-80125 Napoli, Italy Department of Dermatology, University Hospital Carl Gustav Carus, Technical University of Dresden, D-01307 Dresden, Germany Department of Dermatology, University Hospital Zürich, CH-8091 Zürich, Switzerland Department of Skin and Venereal Diseases, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania Dermatology Unit, Department of Paediatrics, University of Padova, IT-35137 Padova, Italy Allergy Unit, Department of Dermatology, University Hospital Basel, CH-4031 Basel, Switzerland Department of Dermatology, University of Schleswig-Holstein, D-24105 Kiel, Germany The Welsh Institute of Dermatology, University Hospital of Wales, Cardiff CF14 4XN, U.K. Department of Dermatology, University Medical Centre Groningen, University of Groningen, NL-9700 RB Groningen, The Netherlands Churchill Hospital, Oxford OX3 7LJ, U.K. Dermatology Department, University of Medical Sciences, PL- 60-355 Poznan, Poland Department of Dermatology and Allergology, Friedrich Schiller University, D-07740 Jena, Germany Department of Dermatology, The Queens Medical Centre, Nottingham NG7 2UH, U.K. Department of Dermatology, Dortmund and University of Witten/Herdecke, D-44137 Dortmund, Germany Department of Dermatology, University Medicine, D-37075 Göttingen, Germany Department of Dermatology, University Hospital Complex, ES- 15782 Santiago de Compostela , Spain Department of Dermatology, Royal Hallamshire Hospital, Sheffield S10 2JF, U.K. Department of Dermatology, Hospital del Mar, Universitat Autònoma, ES- 08003 Barcelona, Spain Department of Dermatology, Ninewells Hospital and Medical School, Dundee DD2 1UB, U.K. James Cook University Hospital, Middlesbrough TS4 3BW, U.K. Department of Derma-allergology, Gentofte Hospital, University of Copenhagen, DK-2900 Hellerup, Denmark Control of Hypersensitivity Diseases, Finnish Institute of Occupational Health (FIOH), FI-00250 Helsinki, Finland The Royal Liverpool University Hospitals, Liverpool L7 8XP, U.K. Department of Dermatology, Nofer Institute of Occupational Medicine, PL-90-950 Lodz, Poland Department of Public Health, Occupational Medicine, University of Trieste, IT-34129 Trieste, Italy Department of Dermatology, University of Erlangen-Nürnberg, D-91054 Erlangen, Germany Department of Dermatology, Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, U.K. Department of Dermatology, University of Padova, IT-35100 Padova, Italy Department of Dermatology, Päijät-Häme Central Hospital, FI-15850 Lahti, Finland Department of Dermatology, Free University of Amsterdam, NL-1081 HV Amsterdam, The Netherlands Department of Dermatology, Hospital Universitario la Princesa, ES- 28006 Madrid, Spain Department of Dermatology, Bristol Royal Infirmary, Bristol BS2 8ED, U.K. Department of Dermatology, Hospital General Universitario de Alicante, ES-03010 Alicante, Spain Department of Dermatology, Inselspital, Bern University Hospital, CH-3010 Bern, Switzerland Department of Experimental Dermatology and Cosmetology, Jagiellonian University Medical College, PL-31-008 Krakow, Poland Department of Dermatology, Abertawe Bromorgannwg University NHS Trust, Swansea SA2 8QA, U.K. Aneurin Bevin Health Board, Newport, Gwent NP23 6HA, U.K. Department of Dermatology, the General Infirmary at Leeds, Leeds LS1 3EX, U.K. Information Network of Departments of Dermatology (IVDK), University Medicine, D-37075 Göttingen, Germany.
Background. The pattern of contact sensitization to the supposedly most important allergens assembled in the baseline series differs between countries, presumably at least partly because of exposure differences. Objectives. To describe the prevalence of contact sensitization to allergens tested in consecutive patients in the years 2007 and 2008, and to discuss possible differences. Methods. Data from the 39 departments in 11 European countries comprising the European Surveillance System on Contact Allergy network (www.essca-dc.org) in this period have been pooled and analysed according to common standards. Results. Patch test results with the European baseline series, and country-specific or department-specific additions to it, obtained in 25 181 patients, showed marked international variation. Metals and fragrances are still the most frequent allergens across Europe. Some allergens tested nationally may be useful future additions to the European baseline series, for example methylisothiazolinone, whereas a few long-term components of the European baseline series, namely primin and clioquinol, no longer warrant routine testing. Conclusions. The present analysis points to 'excess' prevalences of specific contact sensitization in some countries, although interpretation must be cautious if only few, and possibly specialized, centres are representing one country. A comparison as presented may help to target in-depth research into possible causes of 'excess' exposure, and/or consideration of methodological issues, including modifications to the baseline series.
Allergy. 2012 May ;67 (5):691-8
22335765
M Worm,
G Edenharter,
F Ruëff,
K Scherer,
C Pföhler,
V Mahler,
R Treudler,
R Lang,
K Nemat,
A Koehli,
B Niggemann,
S Hompes
Department of Dermatology and Allergy, University Hospital Charité, Berlin, Germany.
BACKGROUND Anaphylaxis is the most severe manifestation of an IgE-dependent allergy. Standardized acquired clinical data from large cohorts of well-defined cases are not available. The aim of this study was to analyse the symptom profile and risk factors of anaphylaxis in a large Central European cohort. METHODS We acquired data from patients in Germany, Austria and Switzerland who experienced a severe allergic reaction defined by the onset of severe pulmonary and/or severe cardiovascular symptoms. The data were gained via an online questionnaire from 83 medical centres specialized in allergy. Data were collected from 2006 to 2010 and analysed by using a multinomial regression model. RESULTS A total of 2012 paediatric and adult patients were included into the present analysis. The skin (84%) was the most frequently affected organ followed by the cardiovascular (72%) and the respiratory (68%) system. The regression model analysing the onset of cardiovascular versus respiratory symptoms revealed a strong impact of age (adjusted OR = 6.08; 95% CI, 3.35-11.01; P < 0.001). Furthermore, the elicitor food (adjusted OR = 0.29; 95% CI, 0.21-0.41, P < 0.001) and the presence of atopic diseases (adjusted OR = 0.54; 95% CI, 0.40-0.73, P < 0.001) were significantly associated with the onset of respiratory symptoms. CONCLUSION Data from individuals who experienced anaphylaxis can support the identification of risk factors. The present study indicates that age, the elicitor itself and the presence of atopic diseases have an impact on the symptom profile of anaphylaxis. Identifying further risk factors of anaphylaxis is of significant importance for clinical practice in the future.
A Wangorsch,
D Weigand,
S Peters,
V Mahler,
K Fötisch,
A Reuter,
J Imani,
A M Dewitt,
K-H Kogel,
J Lidholm,
S Vieths,
S Scheurer
Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
BACKGROUND Up to 25% of food allergic subjects in central Europe suffer from carrot allergy. Until now, two isoforms of the major carrot (Daucus carota) allergen Dau c 1 have been described: Dau c 1.01, comprising five variants (Dau c 1.0101-Dau c 1.0105) and Dau c 1.02. OBJECTIVE To investigate potential allergenic properties of a Dau c PRPlike protein, a novel isoform of the PR-10 protein family in carrot. METHODS Dau c PRPlike cDNA from carrot roots (cv Rodelika) was cloned after RT-PCR and 5'RACE. Dau c PRPlike protein was expressed in E. coli, purified under native conditions by Ni-NTA chromatography and analysed by CD spectroscopy. Immuno-reactivity of the rDau c PRPlike protein was compared with rDau c 1.0104 and rDau c 1.0201 in terms of IgE binding (immunoblotting, ImmunoCAP), IgE cross-reactivity (ELISA inhibition) and in vitro mediator release with sera from carrot allergic patients. mRNA expression of Dau c PRPlike protein in wild-type and transgenic carrot roots was analysed by qRT-PCR. RESULTS The Dau c PRPlike protein was identified as a new allergenic isoform, Dau c 1.03, in carrot roots. 68% of carrot allergic patients were sensitized to rDau c 1.03. The IgE-reactivity of rDau c 1.03 strongly correlated with reactivity to rDau c 1.0104, but not to rDau c 1.0201. The extent of IgE cross-reactivity and allergenic potency of Dau c 1 isoforms varied between the individual sera tested. Dau c 1.03 mRNA transcripts were up-regulated in Dau c 1.01 and Dau c 1.02 gene-silenced carrot roots. CONCLUSION AND CLINICAL RELEVANCE Dau c 1 isoforms display distinct IgE epitope heterogeneity. Dau c 1.03 appears to contribute to the allergenicity of carrots and the manifestation of carrot allergy. The epitope diversity of different Dau c 1 isoforms should be considered for component-resolved diagnosis and gene silencing of carrot allergens.
Marcus Maurer,
Sabine Altrichter,
Thomas Bieber,
Tilo Biedermann,
Matthias Bräutigam,
Stefan Seyfried,
Randolf Brehler,
Jürgen Grabbe,
Nicolas Hunzelmann,
Thilo Jakob,
Andreas Jung,
Jörg Kleine-Tebbe,
Martin Mempel,
Michael Meurer,
Kristian Reich,
Franziska Ruëff,
Knut Schäkel,
Kaushik Sengupta,
Christian Sieder,
Jan C Simon,
Bettina Wedi,
Torsten Zuberbier,
Vera Mahler,
Petra Staubach
Charité-Universitätsmedizin Berlin, Allergie-Centrum-Charité, Klinik für Dermatologie, Venerologie und Allergologie, Berlin, Germany. marcus.maurer@charite.de
BACKGROUND A subgroup of patients with chronic spontaneous urticaria (CU) exhibits IgE antibodies directed against autoantigens, such as thyroperoxidase (TPO). We conducted this study to investigate whether such patients with CU with IgE against TPO benefit from treatment with omalizumab, a humanized anti-IgE mAb licensed for the treatment of severe persistent allergic (IgE-mediated) asthma. OBJECTIVES We sought to assess the efficacy of omalizumab treatment in patients with CU with IgE autoantibodies against TPO. METHODS In this multicenter, randomized, double-blind, placebo-controlled study patients with CU (male/female, 18-70 years of age) with IgE autoantibodies against TPO who had persistent symptoms (wheals and pruritus) despite standard antihistamine therapy were randomized to receive either omalizumab (75-375 mg, dose determined by using the approved asthma dosing table) or placebo subcutaneously once every 2 or 4 weeks for 24 weeks. The primary end point was the change from baseline in mean weekly urticaria activity score after 24 weeks of treatment, as calculated from patients' diaries. The safety and tolerability of omalizumab were also assessed. RESULTS Of the 49 randomized patients (omalizumab, n = 27; placebo, n = 22), 42 completed the study. At week 24, patients demonstrated a mean reduction in the weekly urticaria activity score from baseline of 17.8 with omalizumab and 7.9 with placebo (P =.0089). Complete protection from wheal development was observed in 19 (70.4%) patients in the omalizumab group compared with only 1 (4.5%) patient in the placebo group. The rate of adverse events was similar in both groups. CONCLUSIONS The results of this study indicate that omalizumab is an effective treatment option for patients with CU with IgE autoantibodies against TPO who are refractory to conventional treatment.
Christian Joachim Apfelbacher,
Wilhelm Akst,
Sonja Molin,
Jochen Schmitt,
Andrea Bauer,
Elke Weisshaar,
Vera Mahler,
Sabine Treichel,
Thomas Ruzicka,
Thomas Luger,
Peter Elsner,
Thomas Ludwig Diepgen
Division of Clinical Social Medicine, University of Heidelberg, Germany.
BACKGROUND The aim of the CARPE (German acronym: Chronisches Handekzem-Register zum Patienten-Langzeitmanagement; meaning: chronic hand eczema registry on long-term patient management) registry is to investigate characteristics and treatment modalities in patients affected by chronic hand eczema in Germany. METHODS The registry was built up under the auspices of the German Dermatological Society (Deutsche Dermatologische Gesellschaft, DDG). Patients with chronic hand eczema are prospectively assessed by dermatological examination and patient questionnaire. Socio-economic data and data on diagnostics, skin status, severity and treatment of chronic hand eczema and atopy criteria are repeatedly assessed. Here, we present baseline characteristics of the first 515 patients. RESULTS 53.8 % of the patients were female, mean age was 47.3 years. The average duration of CHE was 7.7 years. 30.4 % had already received inpatient care, 31.2 % had been on sick leave in the past 12 months. 94.5 % had received topical corticosteroids prior to inclusion in the registry, 31.9 % topical calcineurin inhibitors, 38.3 % UV therapy, 28.6 % systemic antihistamines, 36.5 % systemic treatments, 14.9 % systemic corticosteroids, 25.8 % systemic retinoids. CONCLUSIONS The CARPE project demonstrates the high medical burden and therapeutic challenge of chronic hand eczema and presents first data for health care research. Furthermore, the designed follow-up study will present important data about the natural history and prognosis of this chronic skin disease.
Uwe Hillen,
Heinrich Dickel,
Harald Löffler,
Wolfgang Pfützner,
Vera Mahler,
Detlef Becker,
Jochen Brasch,
Margitta Worm,
Thomas Fuchs,
Sven M John,
Johannes Geier
Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, Essen, Germany. uwe.hillen@uk-essen.de
BACKGROUND p-Phenylenediamine (PPD) 1% in petrolatum has been shown in a prospective study to elicit late reactions in 1.5% of routine patch tests, which may be indicative of patch test sensitization. OBJECTIVES To assess the frequency of late reactions to reduced PPD patch test concentrations. METHODS In 1838 patients, PPD was tested at three concentrations (0.5% pet., group I; 0.4% pet., group II; and 0.35% pet., group III). Patch tests were read on D1 (D2) to D3 (D4); additional late readings were performed on D7, D14, and D21. Patients who were not able to return for all scheduled late readings were telephoned on D7, D14, and D21, and questioned about a reaction at the patch test sites. RESULTS Data of 1666 patients (1069 women and 597 men) were eligible. Late reactions were observed in 9 patients, 3 in group I (0.49%) and 5 in group II (0.63%). In 7 of 8 of the patients with late reactions, patch tests were applied for 48 hr. On retesting, 4 of 5 patients became positive at D2 or D3. CONCLUSIONS The occurrence of late reactions to PPD may be influenced by patch test concentration and duration. PPD 0.4-0.5% pet. may cause late reactions indicative of active sensitization.
FASEB J. 2010 Dec ;24 (12):4939-47
20709910
Cit:1
Lien Q Le,
Vera Mahler,
Stephan Scheurer,
Kay Foetisch,
Yvonne Braun,
Daniela Weigand,
Ernesto Enrique,
Jonas Lidholm,
Kathrin E Paulus,
Sophia Sonnewald,
Stefan Vieths,
Uwe Sonnewald
Department of Biology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Gene silencing of Lyc e 1 leads to reduced allergenicity of tomato fruits but impaired growth of transgenic tomato plants. The aim of the study was to restore growth of Lyc e 1-deficient tomato plants while retaining reduced allergenicity by simultaneous complementation of profilin deficiency by expression of nonallergenic yeast profilin. Transgenic plants were generated and tested by RT-PCR and immunoblotting; allergenicity of yeast profilin and transgenic fruits was investigated by IgE binding, basophil activation, and skin-prick tests. Lyc e 1 content of transgenic tomato fruits was <5% of that of wild-type plants, causing significantly reduced IgE antibody binding. Simultaneous coexpression of yeast profilin restored growth and biomass production almost to wild-type levels. Yeast profilin, sharing 32.6% amino acid sequence identity with Lyc e 1, displayed low IgE-binding capacity and allergenic potency. Among 16 tomato-allergic patients preselected for sensitization to Lyc e 1, none showed significant reactivity to yeast profilin. Yeast profilin did not induce mediator release, and coexpression of yeast profilin did not enhance the allergenicity of Lyc e 1-reduced fruits. Simultanous coexpression of yeast profilin allows silencing of tomato profilin and generation of viable plants with Lyc e 1-deficient tomato fruits. Therefore, a novel approach to allergen avoidance, genetically modified foods with reduced allergen accumulation, can be generated even if the allergen fulfills an essential cellular function in the plant. In summary, our findings of efficiently complementing profilin-deficient tomato plants by coexpression of low allergenic yeast profilin demonstrate the feasibility of creating low-allergenic food even if the allergen fulfills essential cellular functions.
Annice Heratizadeh,
Claudia Killig,
Margitta Worm,
Stephanie Soost,
Dagmar Simon,
Andrea Bauer,
Vera Mahler,
Christian Schuster,
Christiane Szliska,
Yvonne Frambach,
Ricarda Eben,
Thomas Werfel,
Wolfgang Uter,
Axel Schnuch
Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hanover, Germany. heratizadeh.annice@mh-hannover.de
HASH(0x1ad48190)
Department of Dermatology and Allergology, University Hospital Aachen, Aachen, Germany. hagen.ott@post.rwth-aachen.de
BACKGROUND: Component-resolved diagnosis using microarray technology has recently been introduced in clinical allergology, but its applicability in patients with natural rubber latex (NRL) allergy has not been investigated. OBJECTIVES: To evaluate the utility of microarray-based immunoglobulin (Ig) E detection in the diagnostic workup of NRL allergy and to compare this new diagnostic tool with established methods of NRL-specific IgE detection. METHODS: We investigated 52 adults with immediate-type NRL allergy and 50 control patients. Determination of specific serum IgE against 8 recombinant Hevea brasiliensis allergen components was performed using a customized allergen microarray and a conventional fluorescence enzyme immunoassay (FEIA). RESULTS: The panel of microarrayed allergen components was shown to represent a comprehensive repertoire of clinically relevant NRL proteins. NRL-specific IgE recognition patterns and sensitization rates determined by microarray analysis were similar to those obtained by conventional FEIA. The diagnostic sensitivity rates of combined single-component data were not significantly different for the respective recombinant test system, whereas the sensitivity level of extract-based FEIA analysis was markedly higher. CONCLUSION: The current study provides evidence that microarrays of recombinant NRL allergen components are a suitable new tool for the diagnosis of NRL-specific sensitization.They show performance characteristics comparable to those of current diagnostic tests and could be indicated in small children in whom only limited blood volumes are obtainable. Further large-scale studies in unselected patient populations and in high-risk groups are warranted before the microarray can be introduced into routine management of patients with NRL allergy.
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