Psoriasis: Bieber T

Mrowietz U, Altmeyer P, Bieber T, Röcken M, Schopf RE, Sterry W. · Psoriasis Center, Department of Dermatology, Venereology and Allergy, University Clinic of Schleswig-Holstein, Campus Kiel, Kiel, Germany. · J Dtsch Dermatol Ges. · Pubmed #17659047 No free full text.

This publication has no abstract.

Wilsmann-Theis D, Hagemann T, Jordan J, Bieber T, Novak N. · Department of Dermatology and Allergy, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. · Eur J Dermatol. · Pubmed #18424378 No free full text.

Abstract: Atopic dermatitis (AD) and psoriasis vulgaris (Pso) represent the most frequent chronic inflammatory skin diseases. It has been assumed for a long time that these diseases have a completely different background. Recent findings about the genetic, epidemiologic and pathophysiologic factors of both diseases have remarkably improved our knowledge about the complex mechanisms underlying AD and Pso. Beyond that, in view of these findings, the question arises, which similarities and differences between AD and Pso exist. In order to address this point, we provide an overview about the current knowledge in the field of AD and Pso.

Bonness S, Bieber T. · Department of Dermatology and Allergy, Rheinische Friedrich-Wilhelms-University Bonn, Germany. · Curr Opin Allergy Clin Immunol. · Pubmed #17873576 No free full text.

Abstract: PURPOSE OF REVIEW: Atopic dermatitis is a common chronic inflammatory skin disease and there are numerous publications on this topic. This review will focus on developments in understanding the molecular basis of atopic dermatitis while considering the genetic background, skin barrier impairment, immune system deviation and microbial superinfections. RECENT FINDINGS: Atopic dermatitis is a complex genetic disease in which gene-gene and gene-environment interactions play a key role. Surprisingly some genetic regions of interest were found to be overlapping with loci identified to play a role in another very common inflammatory skin disease, psoriasis, while no overlap has so far been observed with asthma. Impairment of the skin barrier followed by antigens trespassing seems to play an important role, favouring sensitization via transepidermal penetration which is the focus of current investigations. Superinfections by pathogens such as Staphylococcus aureus due to a weak innate defence seem to be significant in atopic dermatitis as they elicit a strong inflammatory response. SUMMARY: Atopic dermatitis is a chronic inflammatory skin disease with a high incidence in school children and adults. Disease pathogenesis is complex and the background is multifactorial, making the underlying predispositions elusive. Understanding new pathogenic pathways may lead to the development of new drugs with enhanced benefit for the patient.

Wilsmann-Theis D, Hagemann T, Dederer H, Wenzel J, Bieber T, Novak N. · Department of Dermatology, University of Bonn, 53105, Germany. · Br J Dermatol. · Pubmed #15214910 No free full text.

Abstract: Acrodermatitis continua suppurativa of Hallopeau (ACS) is a rare pustular variant of psoriasis in which numerous treatment modalities have been used without any consistent long-term effect. We report for the first time two patients with ACS which was successfully treated with topical tacrolimus 0.1% ointment. Our observations raise hopes that this new treatment strategy for ACS may constitute a novel effective therapeutic option for this recalcitrant condition.

Böhm I, Bieber T, Bauer R. · Klinik und Poliklinik für Dermatologie der Rheinischen Friedrich-Wilhelms Universität Bonn. · Hautarzt. · Pubmed #10591793 No free full text.

Abstract: A 7-year-old otherwise healthy girl presented with a 2-year history of an ILVEN (inflammatory linear verrucous epidermal nevus) located on the inner part of her right upper arm. The diagnosis was histologically confirmed. Different conservative therapeutic strategies with corticosteroids, antibiotics and antimycotics produced little or no improvement. Because of encouraging reports describing the successful use of 0.005% calcipotriol ointment in patients with ILVEN, we treated our patient with this regimen. After 4 weeks we could recognize a impressive improvement and after 8 weeks the ILVEN had nearly completely disappeared. 25 weeks after withdrawal of calcipotriol, no relapse had occurred. The dramatic response to calcipotriol suggests some pathological links between ILVEN and psoriasis.

Scheler M, Wenzel J, Tüting T, Takikawa O, Bieber T, von Bubnoff D. · Department of Dermatology, Friedrich-Wilhelms University, Sigmund Freud-Strasse 25, 53105 Bonn, Germany. · Am J Pathol. · Pubmed #18055547 links to  free full text

Abstract: Recent studies have provided evidence that a type I interferon (IFN)-driven immune response might play an important role in the pathogenesis of lichen planus (LP), an inflammatory disorder of the skin of unclear etiology. Plasmacytoid dendritic cells in affected skin from LP have been proposed to produce IFN-alpha/beta locally, which leads to the expression of IFN-inducible chemokines such as IP10/CXCL10 in the epidermis. This chemokine recruits chemokine receptor CXCR3-expressing T-lymphocytes into the skin via CXCR3/IP10 interactions. Indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan and suppresses T-cell proliferation, is induced by IFNs and other inflammatory cytokines. We show that type I IFN-mediated skin disorders, such as LP, strongly express IDO in lesional skin. This expression closely correlates to the expression of the highly specific type I IFN marker MxA. We further demonstrate that the IDO+ cells in LP are large myeloid CD11c+S100+CD68(-) dendritic cells. Accordingly, CD11c+ antigen-presenting cells significantly up-regulate IDO gene expression and intracellular IDO protein expression after stimulation with IFN-alpha in vitro. These findings reveal that both proinflammatory and counterregulatory mechanisms are operative in cutaneous lesions of LP. We propose that the balance of these mechanisms may be involved in the pathogenesis of this disorder.

Wenzel J, Peters B, Zahn S, Birth M, Hofmann K, Küsters D, Tomiuk S, Baron JM, Merk HF, Mauch C, Krieg T, Bieber T, Tüting T, Bosio A. · Department of Dermatology, University of Bonn, Bonn, Germany. · J Invest Dermatol. · Pubmed #17703176 links to  free full text

Abstract: Here, we present data of a gene expression profiling approach to apply the diagnostic value and pathological significance of this method in different inflammatory skin diseases, using whole skin biopsies. Initially, SAGE was performed to identify frequent tags differentially expressed in various skin diseases. On the basis of these results, a new skin pathology-oriented PIQOR microarray was designed. Lichen planus (LP) was chosen as a model disease to evaluate this system. Controls included healthy skin, atopic dermatitis (AD), and psoriasis (Pso). Gene expression analyses using the topic-defined microarray followed by unclassified clustering was able to discriminate LP from AD and Pso. Genes significantly expressed in LP included type I IFN inducible genes and a specific chemokine expression pattern. The CXCR3 ligand, CXCL9, was the most significant marker for LP. In situ hybridization and immunohistochemistry confirmed the results and revealed that keratinocytes are type I IFN producers in LP skin lesions. Our results show that gene expression profiling using a skin-specific microarray is a reliable method to identify patients with LP in the chosen context and reflect recent models concerning the pathogenesis of this disease. Gene expression profiling might complement the diagnostic spectrum in dermatology and may provide new pathogenetic insights.

Neis MM, Peters B, Dreuw A, Wenzel J, Bieber T, Mauch C, Krieg T, Stanzel S, Heinrich PC, Merk HF, Bosio A, Baron JM, Hermanns HM. · Department of Dermatology and Allergology, University Hospital RWTH Aachen, Germany. · J Allergy Clin Immunol. · Pubmed #17030248 No free full text.

Abstract: BACKGROUND: IL-31 is produced by activated T lymphocytes, preferentially by TH2 cells. Transgenic mice overexpressing IL-31 have a phenotype resembling allergic dermatitis in human subjects. OBJECTIVE: We sought to evaluate the potential importance of IL-31 in the pathogenesis of human T cell-mediated skin diseases. METHODS: We analyzed total RNA taken from 149 skin biopsy specimens from patients with atopic dermatitis (AD), allergic contact dermatitis (ACD), or psoriasis in comparison with specimens taken from patients with healthy skin (n = 13) by using quantitative real-time PCR for the expression of TH1/TH2 cytokines. RESULTS: We found statistically increased mRNA levels of IL-31 in biopsy specimens taken from patients with AD, irrespective of the severity of the disease and serum IgE levels. Moreover, IL-31 mRNA levels were strongly increased in many biopsy specimens taken from patients with ACD. However, no increased transcription of IL-31 could be detected in biopsy specimens taken from psoriatic plaques. A comparison of mRNA levels of IL-31 with TH1 or TH2 cytokines demonstrates a correlation of the expression of IL-31 with IL-4 and IL-13 but not with IFN-gamma. No significant increase of IL-31 receptor mRNA could be detected in any disease, whereas the second receptor subunit of IL-31, the oncostatin M receptor, seems to be enhanced transcribed in patients with psoriasis. CONCLUSION: IL-31 expression is not only increased in patients with AD but also in those with ACD, 2 pruritic skin disorders. In both types of eczema, expression of IL-31 is associated with the expression of the TH2 cytokines IL-4 and IL-13. CLINICAL IMPLICATIONS: IL-31 might contribute not only to the development of AD but also to ACD-provoked skin inflammation.

Howell MD, Boguniewicz M, Pastore S, Novak N, Bieber T, Girolomoni G, Leung DY. · Division of Allergy and Immunology, Department of Pediatrics, The National Jewish Medical and Research Center, Room K926, 1400 Jackson Street, Denver, CO 80206, USA. · Clin Immunol. · Pubmed #17015038 No free full text.

Abstract: Extrinsic atopic dermatitis (EAD) and intrinsic atopic dermatitis (IAD) patients suffer from recurrent bacterial and viral infections. In this study, we demonstrate significantly decreased expression of human beta defensin (HBD)-3, a potent antimicrobial peptide (AMP), in lesional skin of both IAD (p<0.01) and EAD patients (p<0.01), as compared to psoriasis patients. Using primary keratinocytes from EAD and IAD patients, we determined that the deficiency in HBD-3 expression is an acquired rather than a constitutive defect. Furthermore, we demonstrate the down-regulatory effect of IL-4, IL-10, and IL-13 - which are over-expressed in the skin of AD patients - on HBD-3 expression in keratinocytes. Additionally, treatment of EAD skin explants with antibodies against IL-4, IL-10, and IL-13 augmented the expression of HBD-3. These studies suggest that neutralizing the Th2 cytokine milieu in AD skin may augment the innate immune response against bacterial and viral pathogens.

Ortonne JP, van de Kerkhof PC, Prinz JC, Bieber T, Lahfa M, Rubins A, Wozel G, Lorette G, Anonymous00289. · Service de Dermatologie, Hôpital Archet 2, Nice, France. · Acta Derm Venereol. · Pubmed #16585986 No free full text.

Abstract: The efficacy and safety of 0.3% tacrolimus gel and 0.5% tacrolimus cream compared with calcipotriol ointment were evaluated in adults (n = 124) with mild to moderate plaque psoriasis. Treatment was twice daily for a maximum of 12 weeks. Clinical efficacy was assessed by the percentage change in the local psoriasis severity index of a target lesion between baseline and week 12. By week 12, the median percentage changes in local psoriasis severity index of the target lesions in the tacrolimus gel, tacrolimus cream and calcipotriol groups were 55.6%, 50.0% and 58.6%, respectively (no statistically significant differences). Clinical improvement was observed after one week and increased throughout the study. Tacrolimus-treated patients experienced more application site skin burning (tacrolimus gel and cream both 31.0% versus 7.5% for calcipotriol; p = 0.011). Skin burning was mostly mild in intensity and decreased substantially after 1 week of treatment. There were no differences in the nature and incidence of infections and no clinically relevant changes in laboratory values.

Wilsmann-Theis D, Martin S, Reber M, Kwiek B, Bieber T, Novak N. · Department of Dermatology, University of Bonn, Germany. · Curr Pharm Des. · Pubmed #16533166 No free full text.

Abstract: Innovations in biotechnology have made possible the development of several new systemic therapies for psoriasis - the "biologicals", a new group of compounds including monoclonal antibodies, fusion proteins and recombinant proteins. These novel biotechnological advances potentially offer designer drugs, which interfere with specific targets in the pathophysiological network of psoriasis and are thus much safer. The therapeutic strategy of biologicals is based on the knowledge derived from pathogenetic studies, which have focused on targeting disease relevant T-cell- or mediator-systems. Important targets include inactivation of soluble mediators such as tumor-necrosis-factor-alpha, the blockade of receptors for cytokines, adhesion molecules and the interference with T-cell activation by antigen-presenting cells. In addition, recombinant cytokines are able to modulate the immunological balance of this chronic inflammatory skin disease. Currently, up to forty agents are under investigation for the treatment of psoriasis. Four of these agents, alefacept, efalizumab, etanercept and infliximab have already impacted on routine clinical practice. Current developments in the treatment of psoriasis with biologicals are reviewed.

Wenzel J, Philipp-Dormston W, Bieber T, Tüting T. · Klinik und Poliklinik für Dermatologie, Universitätsklinikum Bonn. · J Dtsch Dermatol Ges. · Pubmed #16372815 No free full text.

Abstract: Bullous pemphigoid (BP) is a cutaneous autoimmune disease predominantly affecting older patients which can cause death either due to severe clinical manifestations or due to the side effects of systemic immunosuppressive treatment. Topical treatment with corticosteroids is an established alternative to systemic treatment. However, prolonged application is accompanied by side effects such as skin atrophy. Recently, the immunomodulatory calcineurin antagonists tacrolimus and pimecrolimus have been introduced for topical treatment of skin diseases. Tacrolimus has been reported to be effective in several inflammatory skin disorders such as atopic dermatitis, psoriasis, lichen planus, lupus erythematosus and pyoderma gangraenosum. Efficacy has also been described in the topical treatment of BP in some cases. Here we present the case of a 89 year old patient with BP. He was treated with 0.1% tacrolimus ointment, which was able to control the disease. We briefly review the literature and discuss the potential role of tacrolimus as a novel option for the topical treatment of BP.

Howell MD, Novak N, Bieber T, Pastore S, Girolomoni G, Boguniewicz M, Streib J, Wong C, Gallo RL, Leung DY. · Division of Allergy and Immunology, Department of Pediatrics, The National Jewish Medical and Research Center, Denver, Colorado 80206, USA. · J Invest Dermatol. · Pubmed #16185274 links to  free full text

Abstract: Recurrent skin infections in extrinsic atopic dermatitis (EAD) may be because of the suppression of anti-microbial peptide (AMP) expression by interleukin (IL)-4 and IL-13. Twenty to thirty percent of AD, however, are classified as intrinsic atopic dermatitis (IAD). They exhibit normal serum IgE levels, no allergen-specific sensitization, and lower levels of IL-4 and IL-13 than EAD. Both forms of AD have increased propensity to skin infection, suggesting a novel mechanism for infection in IAD. In this study, we observed significantly decreased human beta-defensin (HBD)-2 gene expression in the skin of both IAD (p = 0.010) and EAD (p = 0.004), as compared with psoriasis patients. Conversely, IAD (p = 0.019) and EAD (p = 0.002) skin lesions exhibited elevated IL-10 gene expression when compared with psoriasis. Using primary keratinocytes, we found that the deficiency in AMP expression is an acquired rather than a constitutive defect. Interestingly, neutralizing antibodies to IL-10 augmented the production of tumor necrosis factor-alpha and interferon-gamma by peripheral blood mononuclear cell from AD patients. Additionally, treatment of AD skin explants with anti-IL-10 augmented the expression of both HBD-2 and LL-37. Thus, increased levels of IL-10 may contribute to the AMP deficiency in both IAD and EAD by reducing cytokines that induce AMP.

Siemes C, Quast T, Klein E, Bieber T, Hooper NM, Herzog V. · Institute of Cell Biology and Bonner Forum Biomedizin, University of Bonn, Ulrich-Haberland-Strasse 61A, 53121 Bonn, Germany. · J Invest Dermatol. · Pubmed #15304096 links to  free full text

Abstract: The soluble form of the beta-amyloid precursor protein (sAPPalpha) is known to function in the autocrine regulation of epidermal growth and repair. Here we show that its proteolytic release by alpha-secretase in normal human keratinocytes is susceptible to hydroxamic-acid-based zinc metalloproteinase inhibitors and suppressed by these inhibitors by 80%-90%. As various other growth factors participate in regulating epidermal growth we investigated whether the inhibitor-induced sAPPalpha-deficiency would affect keratinocyte proliferation. At optimal inhibitor concentrations the suppression of sAPPalpha-release was followed by a decline in proliferation by 50%-60%, indicating that sAPPalpha is a major growth factor that cannot be compensated for by other growth factors. This finding was the basis for the treatment of human lesional psoriatic keratinocytes with these inhibitors, which resulted in the normalization of their increased proliferation rates. The reversibility of these effects and the lack of toxicity underline the value of these inhibitors and suggest their therapeutic application in psoriatic skin diseases.

Novak N, Allam P, Geiger E, Bieber T. · Department of Dermatology, Friedrich-Wilhelms University, D-53105 Bonn. · Allergy. · Pubmed #12269940 No free full text.

Abstract: BACKGROUND: Monocyte (Mo) subsets exhibiting distinct phenotypic and functional properties identified in peripheral blood are assumed to be under the control of soluble factors from their surrounding micromilieu. Atopic eczema/dermatitis syndrome (AEDS) is accompanied by humoral and cellular alterations among which an increased expression of the high-affinity receptor for IgE (Fc epsilon RI) on antigen presenting cells, like Mo, could be found. Therefore we analyzed the assembly of circulating Mo populations and their Fc epsilon RI surface expression during the course of AEDS. METHODS: Blood samples were taken from AEDS patients before and after topical treatment as well as from psoriasis patients and healthy control donors. Detailed analysis of Mo subsets was done by flow cytometry. Meticulous clinical scoring included quantification of the surface damage using the eczema area and severity index (EASI score) as well as evaluation of the serum level of thymus- and activation-regulated chemokine (TARC); this was done before and after 2 weeks of topical treatment with tacrolimus ointment 0.1%. RESULTS: During the exacerbation phase of AEDS, patients harboured a different assembly of Mo subtypes from normal nonatopic individuals and patients with psoriasis with a significant increased population of CD14(+)CD64(-) CD16(+) Mo. Clinical improvement led to a significant decrease of this subpopulation in favor of CD14(+)CD64(+)CD16(-) Mo, leading to a composition of Mo subsets similar to the state found in healthy donors. Interestingly, Fc epsilon RI expression was confined to the CD14(+)CD64(+)CD16(-) Mo subpopulation and the percentage of this Fc epsilon RI(+) Mo subset increased significantly in the peripheral blood after topical treatment. CONCLUSION: Our data provide for the first time clear evidence that fluctuations of Mo subsets in AEDS might reflect qualitatively and quantitatively distinct contributions of Mo subsets to the development of AEDS.

Bornhövd EC, Schuller E, Bieber T, Wollenberg A. · Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians-Universität München. · Hautarzt. · Pubmed #11057390 No free full text.

Abstract: The immunosuppressive macrolides are a novel class of antiinflammatory substances, which could supplant glucocorticosteroids for the topical treatment of some chronic inflammatory skin diseases. Cyclosporine A (CyA), well known from transplantation medicine for years, is licensed in Germany for oral treatment of psoriasis and atopic dermatitis but is not suitable for topical therapy. Tacrolimus (FK506) penetrates the inflamed epidermis and is regarded as the key immunosuppressive macrolide. Clinical trials have demonstrated the efficacy of FK506 ointment for atopic dermatitis, many case reports have been published regarding other inflammatory skin diseases. The ascomycin derivative ASM 981 has many of the properties of FK506 but less data is available at present. Sirolimus (Rapamycin) is structurally related to FK506 but has other biological effects since its molecular actions involve different biochemical pathways. A review of the biochemical and cellular properties, mode of action, therapeutic efficacy and unwanted side effects, as well as data from clinical trials and status of licensing, is given for the respective drugs.

Novak N, Petrow W, Bieber T. · Klinik und Poliklinik für Dermatologie, Rheinischen Friedrich-Wilhelms-Universität Bonn. · Hautarzt. · Pubmed #10907159 No free full text.

Abstract: Benign symmetric lipomatosis of the pseudoathletic type was identified in a woman with a positive family history for the disorder and a past history of alcohol abuse. She had an exceptionally high number of additional diseases such as arthropathy with degenerative osteoporosis, hyperuricemia, hyperlipidemia, psoriasis, neuropathy, muscular atrophy, arteriosclerosis and increased cardiovascular risk factors.

Jordan J, Bieber T, Wilsmann-Theis D. · No affiliation provided · J Eur Acad Dermatol Venereol. · Pubmed #18761550 No free full text.

This publication has no abstract.

Jordan J, Mey U, Bieber T, Wilsmann-Theis D. · No affiliation provided · Eur J Dermatol. · Pubmed #18474491 No free full text.

This publication has no abstract.

Wenzel J, Bieber T. · No affiliation provided · J Rheumatol. · Pubmed #11550990 links to  free full text

This publication has no abstract.