T Bieber

University of Bonn, Bonn, North Rhine-Westphalia, Germany

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Publications (251)1056.22 Total impact

  • Thomas Bieber
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    ABSTRACT: This editorial links to: 10.1046/j.1365-3164.2001.00230.x
    Veterinary Dermatology 08/2014; 25(4). · 2.02 Impact Factor
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    Allergy 08/2014; 69(8):978-82. · 5.88 Impact Factor
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    Thomas Bieber, Burkhard Straeter
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    ABSTRACT: Moderate to severe forms of atopic dermatitis (AD) have a substantial impact on the quality of life of patients and their relatives, carrying a significant socio-economic burden. They often require a systemic therapy and ciclosporine A (CsA) is the only medicinal product approved for this indication in a limited number of European countries. However, due to the safety profile of CsA and its approval conditions, this treatment can only be prescribed for a limited period of time. Thus, moderate to severe forms of AD represent a significant unmet medical need and are subject to off-label prescriptions. Besides giving some insights into the approval procedures for medicinal products in the European Union, this short review is aimed to provide some relevant background information for off-label prescription in AD. It also provides a clinical algorithm for the off-label prescription of systemic immunosuppressants in AD, discusses the apparent dilemma between approval and guidelines, and finally suggests practical rules to be considered in the context of off-label prescription.This article is protected by copyright. All rights reserved.
    Allergy 07/2014; · 5.88 Impact Factor
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    D Simon, T Bieber
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    ABSTRACT: Systemic therapy for atopic dermatitis (AD) is indicated in patients with severe disease refractory to adequate topical treatment. Currently available drugs aim to decrease inflammation by suppressing and/or modulating immune responses and thus may indirectly improve skin barrier function, resulting in a decrease in clinical signs and symptoms in particular pruritus. Before considering systemic treatment, patient adherence to topical treatment including skin care has to be ensured. The selection of the drug depends on the disease severity, localization, complications, concomitant diseases, and age of the patient, but also on their availability and costs as well as the doctor's experience. Bearing in mind the potential risk of resistance, systemic therapy with antibiotics should be exclusively considered in clinically manifest infections such as in children. Here, we review recently published clinical trials and case reports on systemic therapy of pediatric and adult patients with AD to draw conclusions for clinical practice. Although AD is a common disease, controlled clinical studies investigating the efficacy of systemic drugs are scarce, except for cyclosporine, which has been approved for the therapy of severe AD.
    Allergy 12/2013; · 5.88 Impact Factor
  • T Bieber, K Broich
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    ABSTRACT: Personalised medicine will address the clinical and pathophysiologic complexity of many diseases with the aim of developing therapeutic strategies more adapted for selected individuals or patient subgroups in order to improve efficacy and safety of medicinal products. This biomarker-based approach will potentially allow identification of populations at risk for chronic and life-threatening diseases and to design early intervention strategies. Personalised medicine will lead to a substantial move from costly and often inefficient health care to a hopefully more cost effective, more targeted and more preventive approach addressing participative patients with increased health literacy. Thus, it provides the basement for an ultimate paradigm shift of modern medicine, away from a "reactive" medicine to a more "proactive" and personalised health care, so-called "P4 medicine".
    Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 11/2013; 56(11):1468-72. · 0.72 Impact Factor
  • S Vieths, T Bieber
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    ABSTRACT: Immunoglobulin E (IgE) mediated allergic diseases are characterised by heterogeneous clinical phenotypes and a large variety of different sensitisation patterns. Apart from genetic predisposition several environmental factors play a role in sensitisation and elicitation of symptoms. Since the majority of clinically relevant allergens are now available as purified recombinant allergens component-resolved in vitro diagnosis allows the sensitization profile of allergic patients to be determined at the molecular level. Such data may allow physicians to draw conclusions on the severity and persistence of a given allergic disease and to predict the outcome of allergen-specific immunotherapy (SIT) However, the potential of this approach needs to be demonstrated in controlled clinical trials. Moreover, in the context of atopic dermatitis, allergic rhinitis, allergic bronchial asthma as well as the atopic march several screening-biomarkers, diagnostic and prognostic biomarkers, biomarkers of severity and predictive biomarkers are presented and discussed in this article. Traditionally a relevant proportion of allergen-specific immunotherapies is performed in a personalised manner using named patient products manufactured on the basis of an individual prescription. Such named patient products are often mixtures containing several allergen extracts from different sources. However, there is no proven evidence for the safety and efficacy of this approach. In Germany the Therapy Allergen Ordinance ("Therapieallergene-Verordnung", TAV) regulates that in the future allergen products for SIT of insect venom allergies, allergies to pollen of early flowering trees and grass pollen and house dust mite allergies cannot be marketed as named patient products, but always require a marketing authorisation. Thus personalised SIT with named patient products is restricted to the treatment of less prevalent allergies, for which the generation of state-of-the-art clinical data is more difficult. Several recombinant allergens are currently evaluated in phase III clinical trials. In contrast to allergen extracts recombinant allergens offer the possibility to treat patients with a precisely adjusted mixture of the disease-eliciting allergen molecules. However, the implementation of this personalised approach to SIT within the given regulatory framework represents a challenge to regulators.
    Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 11/2013; 56(11):1531-7. · 0.72 Impact Factor
  • K Broich, T Bieber
    Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 11/2013; 56(11):1465-7. · 0.72 Impact Factor
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    ABSTRACT: Phlebologic diseases have become extremely common and have major socio-economic impact. However, the percentage of dermatologists working in phlebology appears to be decreasing according to the data of the German Society of Phlebology (DGP). To investigate the reasons for this development, we-on behalf of the DGP-sent a questionnaire to 120 German Departments of Dermatology in autumn 2012. In 76 returned questionnaires, the number of physicians with additional fellowship training in phlebology averaged 1.5; the average number of those who fulfill the criteria for training fellows in phlebology was 0.9. In 71.1 % of the departments there was a phlebologist. A special phlebologic outpatient clinic existed in 73.7 % of the departments. Sonography with Doppler (89.5 %) and duplex (86.8 %) was used as the most frequent diagnostic tool. For therapy, compression (94.7 %), sclerotherapy (liquid 78.9 %, foam 63.2 %, catheter 18.4 %), endoluminal thermic procedures (radio wave 28.9 %, laser 17.1 %) and surgery (especially crossectomy and stripping 67.1 %, phlebectomy of tributaries 75 %) were used. The average number of treatments was very heterogenous in the different departments. Phlebology definitely plays an important role in dermatology. Most departments fulfill the formal criteria for the license to conduct advanced training in phlebology. A wide spectrum of phlebological diagnostic and therapeutic procedures is available.
    Der Hautarzt 09/2013; 64(9):685-94. · 0.50 Impact Factor
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    T Bieber
    Allergy 08/2013; 68(8):957-8. · 5.88 Impact Factor
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    ABSTRACT: BACKGROUND: A unique type of CD11c(pos) dendritic cells (DC) is abundant in inflamed tissue, for example, in chronic inflammatory skin diseases. Due to their remarkable production of tumor necrosis factor (TNF)-α and inducible NO synthase (iNOS), these cells have been referred to as TNF and iNOS-producing DC (Tip-DC). While Tip-DC have been mainly characterized in murine models of infection, functional data about their human counterpart are lacking. OBJECTIVES: We sought to generate human Tip-DC in vitro und thus provide a new model for the investigation of their phenotype and function. METHODS: We generated human Tip-DC from monocytic precursor cells of healthy individuals, atopic and psoriatic patients using human serum. Resting and stimulated cells were analyzed by flow cytometry, real-time PCR, and by ELISA. INOS activity was measured by fluorometric detection of NO. RESULTS: Tip-DC closely resembled their in vivo counterparts by expressing CD11c, CD86, and CD40 while lacking CD1a, CD1c, or CD207/Langerin. Bacterial stimulation of Tip-DC from healthy donors, atopic dermatitis, or psoriasis patients resulted in a similar increase in iNOS activity and TNF-α production. In kinetic experiments, TNF-α, a putative activator of Tip-DC, could not induce NOS2. Upon bacterial stimulation, TNFA, IL6, IL12B, and IL23A mRNA appeared in a first wave, while IL12A and NOS2 mRNA were up-regulated later on but not blocked by anti-TNF-α agents, implying a biphasic pro-inflammatory response. CONCLUSIONS: We developed a new model for the study of human Tip-DC and provide the first evidence of their pro-inflammatory capacity.
    Allergy 06/2013; · 5.88 Impact Factor
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    ABSTRACT: BACKGROUND: Epidermal Langerhans cells (LC) expressing the high-affinity receptor for IgE (FcεRI) play a key role in atopic dermatitis (AD). AD skin is highly colonized with Staphylococcus aureus (S.a.), which are sensed by Toll-like receptor 2 (TLR2). We hypothesized that TLR2 may impact on the expression of FcεRI on LC. OBJECTIVES: To study a putative impact of TLR2 signaling on FcεRI, we analyzed FcεRI and known transcription factors of the receptor after ligand binding to TLR2. METHODS: We generated LC from CD34(+) progenitors in vitro (CD34LC) expressing FcεRI and TLR2 as well as its partners TLR1 and TLR6. The expression of FcεRI and known transcription factors of the receptor was analyzed on the protein and RNA level by flow cytometry, Western blotting, and real-time PCR. RESULTS: For CD34LC from 123 donors, we observed a high heterogeneity in FcεRI surface expression correlating with mRNA level of its α-chain. Stimulation of TLR1/2 or TLR2/6 dramatically down-regulated FcεRI on protein and mRNA level of both α- and γ-chain. Further analysis of putative transcription factors for FCER1A revealed the lack of GATA1 in CD34LC, weak expression of ELF1 and YY1, and high expression of PU.1. While ELF1 and YY1 appeared to be little affected by TLR2 engagement, PU.1 was significantly down-regulated. CONCLUSIONS: Taken together, our findings show that in human, LC ligation of TLR2 by S.a.-derived products down-regulates FcεRI and its transcription factor PU.1, thus suggesting that FcεRI is controlled by PU.1 in these cells.
    Allergy 03/2013; · 5.88 Impact Factor
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    ABSTRACT: BACKGROUND: Atopic dermatitis (AD) starts most often during the first years of life and goes into remission in a high proportion of cases during childhood. However, in severe cases, AD persists until adulthood or starts and relapses later in life. So far, studies investigating the natural course of AD during adolescence and adulthood are rare. The aim of our study was to classify different courses of AD and to correlate these with specific risk factors for severe variants of AD. METHODS: A detailed clinical examination and retrospective evaluation of the history of the disease were performed in a collective of 725 adolescent and adult patients with AD. Laboratory data including total and specific IgE were evaluated. RESULTS: Six hundred and seven patients of 725 patients could be classified into course types. Of these 607 patients 85.7% could be classified into five main different course types of all 31 course types recorded. The highest differences in the number of sensitizations, total immunoglobulin E serum levels and predilection of the skin lesions were observed between patients with an early type of onset of AD and a chronic persisting course until adulthood and patients with a late type of onset of AD, that is, after the 20th year of life. CONCLUSION: Our data show that the natural course of AD can be divided into subgroups that display different clinical features. The data support the assumption of a broad heterogeneity of AD in adolescence and adulthood and emphasize the future need for careful stratification of patients with AD.
    Allergy 03/2013; · 5.88 Impact Factor
  • N Novak, W M Peng, T Bieber, C Akdis
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    ABSTRACT: BACKGROUND: Monocyte differentiation into dendritic cells or macrophages and recruitment to peripheral organs in chronic inflammatory diseases are directed by allergen challenge via FcεRI as well as the nature of soluble factors in the microenvironment. High-affinity receptor for IgE stimulation of effector cells results in the release of histamine, which acts on various histamine receptors (HR) 1-4, expressed by immune cells. METHODS: We examined the effect of FcεRI stimulation of human monocytes on H1R expression and function of differentiating cells. The mRNA levels of H1R, H2R and histidine decarboxylase of differentiating cells were detected by quantitative real-time PCR. Expression of CD1c, CD11c, CD68 and CD163 was detected by flow cytometry. Amount of histamine, IL-6 and IL-12p70 in the cell culture was measured with the help of cytometric bead arrays or ELISA assays. Numbers of H1R-expressing macrophages were evaluated by immunofluorescence double staining of CD68 and H1R on human skin sections. RESULTS: We demonstrated that FcεRI stimulation promotes the generation of H1R-expressing macrophage-like cells with enhanced histamine biosynthesis and H1R-mediated proinflammatory properties. Supporting our in vitro findings, high numbers of H1R-expressing CD68(pos) macrophages were detected in the dermis of atopic dermatitis (AD) skin lesions. CONCLUSION: Our observations point to a close histamine-/HR-mediated activation of dermal macrophages, leading to modified cell differentiation and responsiveness via H1R, which might contribute to the aggravation of allergic skin inflammation in AD.
    Allergy 02/2013; · 5.88 Impact Factor
  • K. Broich, T. Bieber
    Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 01/2013; 56(11). · 0.72 Impact Factor
  • T. Bieber, K. Broich
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    ABSTRACT: Die personalisierte Medizin soll der bedeutsamen klinischen und pathophysiologischen Heterogenität vieler Erkrankungen Rechnung tragen und mehr auf die individuellen Bedürfnisse von Patienten bzw. Patientengruppen im Sinne der besseren Wirksamkeit von Arzneimitteln und/oder verminderter unerwünschter Arzneimittelnebenwirkungen eingehen. Die Möglichkeiten der personalisierten Medizin verstärken auch die Hoffnung auf neuartige Präventionsstrategien, die auf dem frühzeitigen Erkennen von Risikopopulationen anhand genomischer und endophänotypischer Biomarker basieren. Die personalisierte Medizin verspricht also einen Paradigmenwechsel in der Medizin, d. h. weg von der derzeitigen teuren, reaktiven und des Öfteren ineffizienten Gesundheitsversorgung, hin zu einer mehr präventiven Versorgung mit verstärkter Partizipation der Patienten. Sie bildet die Grundlage des Paradigmenwechsel in der modernen Medizin, weg von einer ,,reaktiven Medizin“, hin zu einer mehr proaktiven und personalisierten Medizin, der sog. ,,P4-Medizin“.
    Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 01/2013; 56(11). · 0.72 Impact Factor
  • S. Vieths, T. Bieber
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    ABSTRACT: Immunglobulin-E (IgE)-vermittelte allergische Erkrankungen zeichnen sich durch einen heterogenen klinischen Phänotyp und sehr unterschiedliche Sensibilisierungsprofile aus. Sie weisen somit einen ausgesprochen individuellen Charakter auf. Neben einer genetischen Prädisposition spielen in der Sensibilisierungsphase und bei der Auslösung von Symptomen die verschiedensten Umweltfaktoren eine Rolle. Da die wichtigsten klinisch relevanten Allergene inzwischen in gereinigter Form als rekombinante Allergene zur Verfügung stehen, kann das Sensibilisierungsmuster der betroffenen Allergiker mittels Komponenten-aufgelöster In-vitro-Diagnostik auf molekularer Ebene erfasst werden. Solche Daten erlauben möglicherweise Aussagen über den Schwergrad und die Persistenz der allergischen Erkrankung sowie zur Prognose einer spezifischen Immuntherapie (SIT). Das Potenzial dieses Ansatzes ist noch in kontrollierten klinischen Studien zu prüfen. Weiterhin werden im vorliegenden Beitrag im Kontext der atopischen Dermatitis (AD), der allergischen Rhinitis, des allergischen Asthmas und des atopischen Marsches verschiedene weitere Screening-Biomarker, diagnostische und prognostische Biomarker, Biomarker für den Schweregrad der Erkrankungen und prädiktive Biomarker vorgestellt und diskutiert. Ein erheblicher Anteil der Immuntherapien allergischer Erkrankungen wird traditionell in personalisierter Weise mit Individualrezepturen durchgeführt, die häufig aus Mischungen zahlreicher Allergenextrakte bestehen. Eine gesicherte Evidenz zur Wirksamkeit und Sicherheit dieses Ansatzes liegt nicht vor. In Deutschland wurde durch die Therapieallergene-Verordnung (TAV) festgelegt, dass Allergenprodukte für die SIT von Insektengiftallergien, gegen Pollen früh blühender Bäume und Gräserpollen sowie gegen Hausstaubmilben zukünftig ausschließlich als zugelassene Arzneimittel in den Verkehr gebracht werden dürfen. Die personalisierte SIT mit Individualrezepturen wird somit auf seltenere allergische Erkrankungen eingeschränkt, für die Generierung umfassender klinischer Daten aufgrund der geringen Patientenzahlen problematisch ist. Verschiedene rekombinante Allergene werden inzwischen in klinischen Prüfungen der Phase III untersucht. Im Gegensatz zu Allergenextrakten bieten rekombinante Allergene die Möglichkeit, den Patienten mit einer Mischung exakt derjenigen Moleküle zu behandeln, gegen die eine Sensibilisierung besteht. Die Umsetzung dieses personalisierten, innovativen Immuntherapieansatzes innerhalb des bestehenden regulatorischen Rahmens stellt allerdings eine Herausforderung dar.
    Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 01/2013; 56(11). · 0.72 Impact Factor
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    Journal of Allergy and Clinical Immunology 11/2012; 130(5):1049-62. · 12.05 Impact Factor
  • Clinical and Experimental Dermatology 10/2012; · 1.33 Impact Factor
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    ABSTRACT: Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.
    The Journal of allergy and clinical immunology 10/2012; · 12.05 Impact Factor
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    ABSTRACT: The existing evidence for treatment of atopic eczema (atopic dermatitis, AE) is evaluated using the national standard Appraisal of Guidelines Research and Evaluation. The consensus process consisted of a nominal group process and a DELPHI procedure. Management of AE must consider the individual symptomatic variability of the disease. Basic therapy is focused on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment based on topical glucocorticosteroids and topical calcineurin inhibitors (TCI) is used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, but the TCI tacrolimus and pimecrolimus are preferred in certain locations. Systemic immune-suppressive treatment is an option for severe refractory cases. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial treatment. Adjuvant therapy includes UV irradiation preferably with UVA1 wavelength or UVB 311 nm. Dietary recommendations should be specific and given only in diagnosed individual food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Stress-induced exacerbations may make psychosomatic counselling recommendable. 'Eczema school' educational programs have been proven to be helpful. Pruritus is targeted with the majority of the recommended therapies, but some patients need additional antipruritic therapies.
    Journal of the European Academy of Dermatology and Venereology 09/2012; 26(9):1176-93. · 2.69 Impact Factor

Publication Stats

5k Citations
1,056.22 Total Impact Points

Institutions

  • 1998–2014
    • University of Bonn
      • Klinik und Poliklinik für Dermatologie und Allergologie
      Bonn, North Rhine-Westphalia, Germany
  • 2013
    • Paul-Ehrlich-Institut
      Langen, Hesse, Germany
    • Bundesinstitut für Arzneimittel und Medizinprodukte
      Bonn, North Rhine-Westphalia, Germany
  • 2012
    • Centre Hospitalier Universitaire de Montpellier
      Montpelhièr, Languedoc-Roussillon, France
  • 2011
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2006–2011
    • University of Bonn - Medical Center
      Bonn, North Rhine-Westphalia, Germany
    • Sigmund-Freud-Institut
      Frankfurt, Hesse, Germany
    • Centre Hospitalier Universitaire de Reims
      Rheims, Champagne-Ardenne, France
  • 1986–2001
    • Ludwig-Maximilian-University of Munich
      • Department of Dermatology and Allergology
      München, Bavaria, Germany
  • 1994
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 1987–1992
    • Technische Universität München
      München, Bavaria, Germany
  • 1989
    • University of Vienna
      Wien, Vienna, Austria
  • 1985
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France