25 results on '"Bieber, T."'
Search Results
2. Why we need a harmonized name for atopic dermatitis/atopic eczema/eczema!
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Bieber, T.
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ATOPIC dermatitis , *BIOLOGICAL nomenclature , *SKIN diseases , *TERMS & phrases , *DATA mining , *SCIENTIFIC community , *DATABASES - Abstract
The author reflects on the need for a harmonized nomenclature for the condition atopic dermatitis, atopic eczema, or eczema to determine the different levels of the most common skin disease. He cites the study by Kantor et al. which established the widespread acceptance of the term atopic dermatitis which is ripe for international agreement. The author believes that the term can impact the data mining of the scientific community in terms of search strategies in databases.
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- 2016
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3. A review of recent journal highlights focusing on atopic dermatitis.
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Allam, J.-P. and Bieber, T.
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ATOPIC dermatitis , *SKIN diseases - Abstract
Discusses various aspects of atopic dermatitis (AD). Identification of the yeast Malassezia sympodialis as factor triggering AD; Level of circulating antibodies to staphylococcal enterotoxin B; Effective topical treatment regimen; Benefit of probiotics; Predominance of a Th2 cytokine profile.
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- 2003
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4. Epigallocatechin‐3‐gallate exhibits anti‐inflammatory effects in a human interface dermatitis model—implications for therapy.
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Braegelmann, C., Niebel, D., Ferring‐Schmitt, S., Fetter, T., Landsberg, J., Hölzel, M., Effern, M., Glodde, N., Steinbuch, S., Bieber, T., and Wenzel, J.
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WARTS , *EPIGALLOCATECHIN gallate , *LICHEN planus , *CHEMOKINES , *SKIN inflammation , *SKIN diseases - Abstract
Background: Epigallocatechin‐3‐gallate (EGCG) has been proven effective in treating viral warts. Since anticarcinogenic as well as anti‐inflammatory properties are ascribed to the substance, its use has been evaluated in the context of different dermatoses. The effect of EGCG on interface dermatitis (ID), however, has not yet been explored. Objectives: In this study, we investigated the effect of EGCG on an epidermal human in vitro model of ID. Methods: Via immunohistochemistry, lesional skin of lichen planus patients and healthy skin were analysed concerning the intensity of interferon‐associated mediators, CXCL10 and MxA. Epidermal equivalents were stained analogously upon ID‐like stimulation and EGCG treatment. Monolayer keratinocytes were treated likewise and supernatants were analysed via ELISA while cells were processed for vitality assay or transcriptomic analysis. Results: CXCL10 and MxA are strongly expressed in lichen planus lesions and induced in keratinocytes upon ID‐like stimulation. EGCG reduces CXCL10 and MxA staining intensity in epidermis equivalents and CXCL10 secretion by keratinocytes upon stimulation. It furthermore minimizes the cytotoxic effect of the stimulus and downregulates a magnitude of typical pro‐inflammatory cytokines that are crucial for the perpetuation of ID. Conclusions: We provide evidence concerning anti‐inflammatory effects of EGCG within a human in vitro model of ID. The capacity to suppress mediators that are centrally involved in disease perpetuation suggests EGCG as a potential topical therapeutic in lichen planus and other autoimmune skin diseases associated with ID. [ABSTRACT FROM AUTHOR]
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- 2022
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5. The mode of topical immunomodulators in the immunological network of atopic dermatitis.
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Novak, N., Kwiek, B., and Bieber, T.
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ATOPIC dermatitis , *SKIN inflammation , *SKIN diseases , *ALLERGIES , *IMMUNOSUPPRESSIVE agents , *THERAPEUTICS , *PATHOLOGICAL physiology , *DERMATOLOGY - Abstract
For a long time, therapeutic strategies of atopic dermatitis (AD) have been dominated by the application of local or systemic steroids or other immunosuppressive agents, which have been limited by their potential for unwanted local or systemic side effects. Recently, the use of a new generation of topical nonsteroidal, immunomodulatory drugs has revolutionized the therapeutic options of this often recalcitrant allergic-inflammatory skin disease. Research work has focused on the identification of the exact mode of action and the immune specificities of the so-called‘topical immunomodulators’ (TIMs) such astacrolimusand pimecrolimusin AD. In addition to the previous findings about the mode of action of TIMs on T cells, other target cells of TIMs such as keratinocytes, mast cells, eosinophils and dendritic cells have been identified recently as potential therapeutic targets. In this overview, we provide a research update about the anti-inflammatory and anti-allergic properties of TIMs on effector cells of AD that may be involved in the complex pathophysiology of AD. [ABSTRACT FROM AUTHOR]
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- 2005
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6. Risk of severe allergic reactions to COVID‐19 vaccines among patients with allergic skin diseases – practical recommendations. A position statement of ETFAD with external experts.
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Ring, J., Worm, M., Wollenberg, A., Thyssen, J.P., Jakob, T., Klimek, L., Bangert, C., Barbarot, S., Bieber, T., Bruin‐Weller, M.S., Chernyshov, P.V., Christen‐Zaech, S., Cork, M., Darsow, U., Flohr, C., Fölster‐Holst, R., Gelmetti, C., Gieler, U., Gutermuth, J., and Heratizadeh, A.
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COVID-19 vaccines , *SKIN diseases , *ALLERGIES , *MEDICAL personnel , *ECZEMA , *PHYSICIANS - Abstract
Dr. Seneschal has been an investigator, speaker, or consultant for Novartis, Abbvie, Sanofi, LeoPharma and Eli Lilly. Dr. De Raeve is a consultant, member of scientific advisory boards and/ or received personal fees and non-financial support from LEO Pharma, Pierre Fabre, Sanofi-Genzyme and Bioderma. Dr. Vestergaard has been investigator, speaker, or consultant for Novartis, Abbvie, Sanofi, LeoPharma and Eli Lilly. [Extracted from the article]
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- 2021
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7. Baricitinib in patients with moderate‐to‐severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase III trials.
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Simpson, E.L., Lacour, J.‐P., Spelman, L., Galimberti, R., Eichenfield, L.F., Bissonnette, R., King, B.A., Thyssen, J.P., Silverberg, J.I., Bieber, T., Kabashima, K., Tsunemi, Y., Costanzo, A., Guttman‐Yassky, E., Beck, L.A., Janes, J.M., DeLozier, A.M., Gamalo, M., Brinker, D.R., and Cardillo, T.
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ATOPIC dermatitis , *PATIENT safety , *CARDIOVASCULAR diseases , *SYMPTOMS , *SKIN diseases , *ITCHING , *BARICITINIB - Abstract
Summary: Background: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced atopic dermatitis (AD) severity in a phase II study with concomitant topical corticosteroids. Objectives: To evaluate the efficacy and safety of baricitinib in patients with moderate‐to‐severe AD who had an inadequate response to topical therapies. Methods: In two independent, multicentre, double‐blind, phase III monotherapy trials, BREEZE‐AD1 and BREEZE‐AD2, adults with moderate‐to‐severe AD were randomized 2 : 1 : 1 : 1 to once‐daily placebo, baricitinib 1 mg, 2 mg, or 4 mg for 16 weeks. Results: At week 16, more patients achieved the primary end point of Validated Investigator's Global Assessment of AD (0, 1) on baricitinib 4 mg and 2 mg compared with placebo in BREEZE‐AD1 [N = 624; baricitinib 4 mg 16·8% (P < 0·001), 2 mg 11·4% (P < 0·05), 1 mg 11·8% (P < 0·05), placebo 4·8%], and BREEZE‐AD2 [N = 615; baricitinib 4 mg 13·8% (P = 0·001), 2 mg 10·6% (P < 0·05), 1 mg 8·8% (P = 0·085), placebo 4·5%]. Improvement in itch was achieved as early as week 1 for 4 mg and week 2 for 2 mg. Improvements in night‐time awakenings, skin pain and quality‐of‐life measures were observed by week 1 for both 4 mg and 2 mg (P ≤ 0·05, all comparisons). The most common adverse events in patients treated with baricitinib were nasopharyngitis and headache. No cardiovascular events, venous thromboembolism, gastrointestinal perforation, significant haematological changes, or death were observed with any baricitinib dosage. Conclusions: Baricitinib improved clinical signs and symptoms in patients with moderate‐to‐severe AD within 16 weeks of treatment and induced rapid reduction of itch. The safety profile remained consistent with prior findings from baricitinib clinical development in AD, with no new safety concerns. What is already known about this topic? Atopic dermatitis (AD) is a chronic heterogeneous inflammatory skin disease with few approved therapies for patients with moderate‐to‐severe disease. What does this study add? These two phase III trials show that baricitinib, an oral inhibitor of Janus kinase 1 and 2, significantly improved clinical signs and symptoms of AD compared with placebo within the first 16 weeks of treatment.Baricitinib may represent a first‐in‐class oral treatment option for adult patients with moderate‐to‐severe AD. Linked Comment: Drucker. Br J Dermatol 2020; 183:199–200. Plain language summary available online [ABSTRACT FROM AUTHOR]
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- 2020
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8. Successful treatment of systemic juvenile xanthogranulomatosis with cytarabine and 2-chlorodeoxyadenosine: case report and review of the literature.
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Maintz, L., Wenzel, J., Irnich, M., Reinhard, H., and Bieber, T.
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GRANULOMA , *CYTARABINE , *SKIN diseases , *PREDNISONE , *VINBLASTINE , *PSYCHOMOTOR disorders - Abstract
The non-Langerhans cell histiocytosis ( LCH) juvenile xanthogranulomatosis ( JXG) is usually a benign disease limited to the skin. Only a few cases of systemic disease with at least two affected organs and lethal outcomes have been reported to date. Treatment is controversial and no standard protocol is available. We report the rare case of a 22-month-old boy presenting multiple erythematous brownish papules of the head, trunk and legs, which had developed starting from his 6th month of life. Additional symptoms were delayed psychomotor development, hydrocephalus and hepatosplenomegaly. Further diagnostics revealed a systemic JXG with involvement of the skin, central nervous system, liver and spleen. The patient did not respond to initial therapy with prednisone and vinblastine according to protocol III for LCH. However, further therapy with cytarabine and 2-chlorodeoxyadenosine followed by a consolidation phase with 2-chlorodeoxyadenosine alone was successful and the patient is in his 4th year of remission. We provide a comprehensive review of the reported cases of systemic JXG to date. [ABSTRACT FROM AUTHOR]
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- 2017
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9. Microbiome in healthy skin, update for dermatologists.
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Dréno, B., Araviiskaia, E., Berardesca, E., Gontijo, G., Sanchez Viera, M., Xiang, L.F., Martin, R., and Bieber, T.
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HUMAN microbiota , *DERMATOLOGISTS , *IMMUNE system , *SKIN diseases , *ALLERGIES , *AUTOIMMUNE diseases - Abstract
The skin is a complex barrier organ made of a symbiotic relationship between microbial communities and host tissue via complex signals provided by the innate and the adaptive immune systems. It is constantly exposed to various endogenous and exogenous factors which impact this balanced system potentially leading to inflammatory skin conditions comprising infections, allergies or autoimmune diseases. Unlike the gut and stool microbiome which has been studied and described for many years, investigations on the skin or scalp microbiome only started recently. Researchers in microbiology and dermatology started using modern methods such as pyrosequencing assays of bacterial 16S rRNA genes to identify and characterize the different microorganisms present on the skin, to evaluate the bacterial diversity and their relative abundance and to understand how microbial diversity may contribute to skin health and dermatological conditions. This article aims to provide an overview on the knowledge about the skin microbiota, the microbiome and their importance in dermatology. [ABSTRACT FROM AUTHOR]
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- 2016
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10. Pyoderma gangrenosum: another cutaneous side-effect of sunitinib?
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ten Freyhaus, K., Homey, B., Bieber, T., and Wilsmann-Theis, D.
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LETTERS to the editor , *SKIN diseases - Abstract
A letter to the editor is presented about the article on pyoderma gangrenosum, which appeared within the issue.
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- 2008
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11. Among the S100 proteins, S100A12 is the most significant marker for psoriasis disease activity.
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Wilsmann ‐ Theis, D., Wagenpfeil, J., Holzinger, D., Roth, J., Koch, S., Schnautz, S., Bieber, T., and Wenzel, J.
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PSORIASIS , *SKIN diseases , *PSORIATIC arthritis , *GENE expression , *BIOMARKERS - Abstract
Background Psoriasis is a chronic skin disease with deregulation of proteins in the immune system. These proteins include members of the heterogeneous S100 family, which have been discussed as potential biomarkers for disease severity. Objective The aim of this study was to evaluate the impact of S100A7, S100A8, S100A9 and S100A12 as possible markers for disease activity in patients with psoriasis skin disease. Patients and Methods S100A7, S100A8, S100A9 and S100A12 mRNA expression was determined in the skin of patients with psoriasis and controls ( N = 341) by gene expression analyses. In addition, S100 serum levels were investigated by ELISA in an independent cohort of psoriasis patients (i) untreated, with different manifestations (skin/joints), (ii) under treatment (etanercept) and (iii) healthy controls, ( N = 55). Results All S100-subtypes included are significantly upregulated in psoriasis skin lesions when compared with atopic dermatitis, lichen ruber and healthy donors. In untreated psoriasis patients, S100A12-serum levels showed the closest association with disease activity ( PASI) ( r = 0.542; P < 0.01). Serum levels decreased under treatment with etanercept ( P < 0.05). Conclusion Among the investigated S100-proteins, S100A12 showed the closest association with disease activity and therapeutic response and might therefore provide a valuable biomarker for psoriasis. [ABSTRACT FROM AUTHOR]
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- 2016
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12. The science of dermocosmetics and its role in dermatology.
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Dreno, B., Araviiskaia, E., Berardesca, E., Bieber, T., Hawk, J., Sanchez ‐ Viera, M., and Wolkenstein, P.
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DERMATOLOGY , *SKIN physiology , *SKIN diseases , *COSMETICS , *SKIN care - Abstract
Our increased knowledge of normal skin physiology has ushered in a subtle revolution in cosmetic science. Originally designed as preparations to enhance personal appearance by direct application on to the skin, cosmetics have now taken on a new role in dermatology, through the support of the management of many skin disorders. This evolving role of cosmetics in skin care is primarily due to scientific and technological advancements that have changed our understanding of normal skin physiology and how cosmetics modify its appearance both physically and biologically. The vast array of techniques currently available to investigate skin responsivity to multiple stimuli has brought about a new era in cosmetic and dermocosmetic development based on a robust understanding of skin physiology and its varied responses to commonly encountered environmental insults. Most cosmetic research is undertaken on reconstructed skin models crucial in dermatological research, given the strict ban imposed by the European Union on animal testing. In addition, the design and conduct of trials evaluating cosmetics now follow rules comparable to those used in the development and evaluation of pharmaceutical products. Cosmetic research should now aim to ensure all trials adhere to strictly reproducible and scientifically sound methodologies. The objective of this review is to provide an overview of the multidisciplinary scientific approach used in formulating dermocosmetics, and to examine the major advances in dermocosmetic development and assessment, the safety and regulatory guidelines governing their production and the exciting future outlook for these dermocosmetic processes following good practice rules. [ABSTRACT FROM AUTHOR]
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- 2014
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13. Management of dermatofibrosarcoma protuberans with fibrosarcomatous transformation: an evidence-based review of the literature.
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Voth, H., Landsberg, J., Hinz, T., Wenzel, J., Bieber, T., Reinhard, G., Höller, T., Wendtner, C.-M., and Schmid-Wendtner, M.-H.
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SARCOMA , *FIBROMAS , *TUMORS , *SKIN diseases , *DERMATOLOGY , *COHORT analysis - Abstract
Fibrosarcomatous transformation represents a rare event in dermatofibrosarcoma protuberans (DFSP) with unpredictable biological behaviour. No guidelines for the adequate treatment of patients with this rare neoplasm have been published. Herein, we present a comprehensive review of the literature comprising 157 patients with transformed DFSP focussing on surgical and adjuvant treatment modalities for this tumour. In the cohort examined, local recurrence occurred in 36% of cases and was significantly lower in patients treated by wide excision with margins ≥2 cm when compared with those treated with local excision without defined margins ( P = 0.01). Consistently, negative margin status was associated with a lower recurrence rate when compared with positive or unknown margin status ( P = 0.01). Distant metastases were detected in 13% of patients, which is significantly higher when compared with ordinary dermatofibrosarcoma protuberans. Systemic dissemination was preceded by local recurrence in 81% of cases, and is therefore strongly associated with tumour recurrence ( P ≤ 0.001). The present data confirm that wide excision with margins ≥2 cm represent the gold standard in the treatment of transformed dermatofibrosarcoma protuberans, and prevents recurrence as well as metastasis. When R0-resection is not feasible, adjuvant radiation should be considered for cases with incomplete resection or unknown surgical margins. Irresectable or metastatic transformed DFSP harbouring the COL1A1-PDGFB fusion gene should be treated with imatinib in the palliative setting or as an adjunctive treatment before surgery, although responses may be short-lasting. [ABSTRACT FROM AUTHOR]
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- 2011
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14. Reduction of relapses of atopic dermatitis with methylprednisolone aceponate cream twice weekly in addition to maintenance treatment with emollient: a multicentre, randomized, double-blind, controlled study.
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Peserico, A., Städtler, G., Sebastian, M., Fernandez, R. Suarez, Vick, K., and Bieber, T.
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SKIN inflammation , *ATOPIC dermatitis , *ITCHING , *ADRENOCORTICAL hormones , *SKIN diseases - Abstract
Background The relapsing nature of atopic dermatitis (AD) presents a challenge for its long-term treatment. Efficacy and safety of corticosteroids have been proven in the acute treatment of active AD, but their long-term efficacy and potential to reduce or prevent relapses have only partially been addressed. Objectives To investigate long-term management (16 weeks) of AD with methylprednisolone aceponate (MPA) 0·1% cream twice weekly in addition to an emollient (Advabase®) after stabilization of an acute severe or very severe flare of AD with MPA cream. Methods Patients ≥ 12 years of age with a ≥ 2-year history of moderate to severe AD were eligible for this multicentre, randomized, double-blind, controlled study if they presented with an acute flare of severe or very severe AD [Investigator’s Global Assessment (IGA) score ≥ 4]. After successful treatment of the flare in an acute phase (AP), patients received either MPA twice weekly plus emollient or emollient alone over a 16-week maintenance phase (MP). The primary study endpoint was time to relapse of AD. Secondary endpoints included relapse rate and disease status, the patient’s assessment of intensity of itch, the Eczema Area and Severity Index, the IGA score, affected body surface area, Dermatology Life Quality Index (DLQI) and children’s DLQI (CDLQI), patient’s and investigator’s global assessment of response and patient’s assessment of quality of sleep. Results Two hundred and forty-nine patients entered the AP and 221 continued into the MP. Time to relapse was longer in the MPA group than in the emollient group. The probability of remaining free from relapse after 16 weeks was 87·1% in the MPA group compared with 65·8% for the emollient. Patients treated with MPA twice weekly had a 3·5-fold lower risk of experiencing a relapse than patients treated with emollient alone (hazard ratio 3·5, 95% confidence interval 1·9–6·4; P < 0·0001). MPA was also superior to emollient for all other efficacy endpoints. Therapy with both treatments was well tolerated. Conclusions MPA twice weekly plus an emollient provides an effective maintenance treatment regimen to control AD. Once stabilized, treatment with MPA significantly reduces the risk of relapse and the intensity of itching, and improves the overall patient status. [ABSTRACT FROM AUTHOR]
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- 2008
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15. The expression pattern of interferon-inducible proteins reflects the characteristic histological distribution of infiltrating immune cells in different cutaneous lupus erythematosus subsets.
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Wenzel, J., Zahn, S., Mikus, S., Wiechert, A., Bieber, T., and Tüting, T.
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GENE expression , *LUPUS erythematosus , *SKIN diseases , *PROTEINS , *INTERFERONS , *HISTOLOGY - Abstract
Background Plasmacytoid dendritic cells and type I interferons (IFNs) are supposed to play a central proinflammatory role in the pathogenesis of cutaneous lupus erythematosus (LE). The IFN-inducible chemokines CXCL9 and CXCL10 are involved in recruiting CXCR3+ effector lymphocytes from the peripheral blood into skin lesions of LE. We hypothesized that the expression pattern of IFN-inducible proteins reflects the characteristic distribution of the inflammatory infiltrate in different subsets of cutaneous LE. Objectives To test this hypothesis in patients with LE. Methods Lesional skin biopsies taken from patients with different subsets of LE [chronic discoid LE (CDLE), n = 12; subacute cutaneous LE (SCLE), n = 5; LE tumidus (LET), n = 4; LE profundus (LEP), n = 6] were investigated by immunohistochemistry using monoclonal antibodies to the lymphocyte surface markers CD3, CD4, CD8, CD20 and CD68, the cytotoxic proteins Tia1 and granzyme B, the chemokine receptor CXCR3, the specifically type I IFN-inducible protein myxovirus protein A (MxA) and the chemokines CXCL9 and CXCL10. Results The expression pattern of MxA followed the distribution of the inflammatory infiltrate typically seen in the investigated cutaneous LE subsets. In CDLE and SCLE, expression was focused in the epidermis and upper dermis, while in LET a perivascular and in LEP a subcutaneous pattern was found. Similar findings were obtained for CXCL9 and CXCL10. Conclusions Our results demonstrate a close morphological association between the expression pattern of IFN-inducible proteins and the distribution of CXCR3+ CD3+ lymphocytes in all investigated subsets of cutaneous LE. This supports the importance of an IFN-driven inflammation in this condition. Infiltrating lymphocytes carrying CXCL10 in their granules might amplify the lesional inflammation and be responsible for the chronic course of this disease. [ABSTRACT FROM AUTHOR]
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- 2007
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16. Type I interferon-associated skin recruitment of CXCR3+ lymphocytes in dermatomyositis.
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Wenzel, J., Schmidt, R., Proelss, J., Zahn, S., Bieber, T., and Tüting, T.
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INTERFERONS , *LYMPHOCYTES , *DERMATOMYOSITIS , *CUTANEOUS manifestations of general diseases , *MYOSITIS , *SKIN diseases - Abstract
Background. Dermatomyositis (DM) is an autoimmune disease of unknown origin affecting skin and muscles. Infiltrating autoreactive T lymphocytes are thought to play an important pathogenetic role, but it is unclear which mechanisms are involved in the recruitment of these cells. Recent studies provided evidence that a type I interferon (IFN)-driven immune response, including the recruitment of T cells via IP10/CXCR3 interactions, might be important for the generation of skin lesions of cutaneous lupus erythematosus (CLE), an autoimmune disease that shares some clinical and histopathological features with DM. We hypothesized that a similar mechanism might also be involved in the pathogenesis of DM skin lesions. Methods. Skin biopsies of 23 donors (11 DM, 5 healthy controls, 7 CLE controls) were analysed by immunohistochemistry using monoclonal antibodies against CD3, CD4, CD8, CD20, CD68, CD123, the chemokine receptor CXCR3 and its ligand IP10/CXCL10, and the myxovirus-resistance protein A (MxA)-protein, which is a specific marker for type I IFNs. Results. We detected strong expression of the MxA protein in all DM skin biopsies, indicating involvement of type I IFNs. Expression of MxA was closely associated with expression of the interferon-inducible protein IP10/CXCL10 and the recruitment of CXCR3+ lymphocytes. Plasmacytoid dendritic cells appear to be an important source of type I IFNs in DM. Discussion. Our results support the hypothesis that lesional type I IFN signalling, induction of IP10 expression, and recruitment of potentially autoreactive T cells via IP10/CXCR3 interaction are involved in the pathogenesis of DM skin lesions. [ABSTRACT FROM AUTHOR]
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- 2006
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17. Absence of CD26 expression on skin-homing CLA+ CD4+ T lymphocytes in peripheral blood is a highly sensitive marker for early diagnosis and therapeutic monitoring of patients with Sézary syndrome.
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Sokolowska-Wojdylo, M., Wenzel, J., Gaffal, E., Steitz, J., Roszkiewicz, J., Bieber, T., and Tüting, T.
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SYNDROMES , *T cells , *SKIN diseases , *DIAGNOSIS , *CYTOMETRY , *THERAPEUTICS , *MYCOSIS fungoides - Abstract
Patients with Sézary syndrome (SS) show clonal expansion in the peripheral blood of skin-homing CD4+ T-helper cells expressing cutaneous lymphocyte antigen (CLA). However, an increase of CLA+ CD4+ T cells can also be observed in various inflammatory dermatoses. To facilitate early diagnosis and therapeutic monitoring of SS using flow cytometry, we evaluated the expression of CD7 and CD26 on the CLA+ CD4+ lymphocyte subset. Peripheral lymphocytes from 7 patients with SS, 16 patients with mycosis fungoides (MF) and 11 healthy controls were analysed by flow cytometry for the expression of CD4, CD7, CD26, CLA and CCR4. In addition, a longitudinal study was performed over 16 months in two patients with SS. Absence of CD7 and CD26 on CLA+ CD4+ T cells was highly specific for SS. Importantly, the absence of CD26 on CLA+ CD4+ T cells was very sensitive for SS, at 100% in our patient cohort. The number of CD26− CLA+ CD4+ T cells closely correlated with therapeutic interventions in the longitudinal analysis of two patients over more than 1 year. We conclude that the absence of CD26 expression on skin-homing CLA+ CD4+ T-helper cells is a very sensitive and highly specific parameter for early diagnosis and therapeutic monitoring of patients with SS. [ABSTRACT FROM AUTHOR]
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- 2005
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18. Scarring skin lesions of discoid lupus erythematosus are characterized by high numbers of skin-homing cytotoxic lymphocytes associated with strong expression of the type I interferon-induced protein MxA.
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Wenzel, J., Uerlich, M., Wörrenkämper, E., Freutel, S., Bieber, T., and Tüting, T.
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SKIN diseases , *AUTOIMMUNE diseases , *T cells , *ANTINEOPLASTIC agents , *IMMUNOHISTOCHEMISTRY , *IMMUNOLOGIC diseases - Abstract
Background Infiltrating T lymphocytes are considered to play a major pathological role in skin lesions of cutaneous lupus erythematosus (CLE), a cutaneous autoimmune disease of unknown aetiology. Earlier histological studies revealed that the inflammatory infiltrate in CLE skin lesions is predominantly composed of T lymphocytes, with a slight predominance of CD4+ over CD8+ T cells, but failed to explain the development of scarring skin lesions, characteristic for chronic discoid lupus erythematosus (CDLE). Because recent investigations have highlighted the relevance of cytotoxic lymphocytes in autoimmune tissue destruction, we hypothesized that the scarring CDLE lesions might be caused by cytotoxic T lymphocytes. Objectives To analyse skin biopsies of 15 patients with CLE [10 female, five male; localized CDLE (lCDLE), n = 5; disseminated CDLE (dCDLE), n = 5, subacute CLE (SCLE), n = 5] and five control biopsies taken from healthy controls and to characterize the inflammatory infiltrate. Methods We used immunohistochemistry, including staining for the cytotoxic molecule granzyme B, the skin-homing molecule cutaneous lymphocyte antigen (CLA) and the protein MxA, which is specifically induced by type I interferons (IFNs). Results We found a strong coexpression of granzyme B and CLA on lesional lymphocytes of patients with scarring lCDLE and dCDLE, which was significantly enhanced when compared with nonscarring SCLE and healthy controls. The increased expression of granzyme B was closely associated with the lesional expression of the type I IFN-induced protein MxA. Conclusions Our results provide evidence that type I IFNs and potentially autoreactive cytotoxic lymphocytes targeting adnexal structures are highly associated with scarring lupus erythematosus lesions and might be responsible for their scarring character. [ABSTRACT FROM AUTHOR]
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- 2005
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19. Efficacy and safety of methotrexate in recalcitrant cutaneous lupus erythematosus: results of a retrospective study in 43 patients.
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Wenzel, J., Brähler, S., Bauer, R., Bieber, T., and Tüting, T.
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DISEASES , *IMMUNOSUPPRESSIVE agents , *ANTINEOPLASTIC agents , *SKIN diseases , *ANTIPARASITIC agents , *ADRENOCORTICAL hormones - Abstract
The therapy of cutaneous lupus erythematosus (CLE) is often challenging, especially in patients resistant to topical treatment and established first-line systemic drugs such as antimalarials. Systemic corticosteroids are effective, but their use is limited due to well-known side-effects, especially in long-term treatment. In recent years several other immunosuppressive agents have been successfully applied in CLE. However, there are no large studies or explicit guidelines on the use of these drugs in CLE. To perform a retrospective investigation of the efficacy of low-dose methotrexate (MTX) in the treatment of CLE. One hundred and thirty-nine patients with CLE were seen at our department between 2001 and 2003, of whom 43 patients required low-dose MTX. All had histologically confirmed CLE lesions. Clinical data including disease activity, additional treatment, laboratory parameters and side-effects were recorded carefully at the time of presentation. Statistical analyses were performed by paired nonparametric Wilcoxon test and Student's t-test using SPSS 11 software. MTX led to a highly significant ( P < 0·01) decline in disease activity. An improvement of the cutaneous lesions was recorded in nearly all patients treated with MTX (42 of 43; 98%). Severe side-effects necessitating discontinuation of MTX treatment were recorded in seven patients (16%), which quickly resolved when MTX was discontinued. Life-threatening complications were not observed. Intravenous application was tolerated better than oral administration. Interestingly, we observed a significant increase in circulating lymphocyte numbers in patients with lymphopenia (< 1·0 × 109 cells L−1) prior to MTX treatment. Our study supports earlier findings reporting the efficacy of low-dose MTX in CLE lesions, particularly in recalcitrant clinical courses. MTX treatment appears to be safe if patients are carefully selected and monitored, with particular attention to side-effects and contraindications. [ABSTRACT FROM AUTHOR]
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- 2005
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20. Circulating clonal CLA+ and CD4+ T cells in Sézary syndrome express the skin-homing chemokine receptors CCR4 and CCR10 as well as the lymph node-homing chemokine receptor CCR7.
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Sokolowska-Wojdylo, M., Wenzel, J., Gaffal, E., Lenz, J., Speuser, P., Erdmann, S., Abuzahra, F., Bowman, E., Roszkiewicz, J., Bieber, T., and Tüting, T.
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CD4 antigen , *T cells , *CHEMOKINES , *LYMPH nodes , *SKIN diseases , *DERMATOLOGY - Abstract
Adhesion molecules and chemokine receptors are involved in tissue-specific homing of T cells to the skin and play an important role in the pathophysiology of cutaneous lymphoma. It has recently been reported that the chemokine CCL27 expressed by keratinocytes attracts lymphocytes bearing the chemokine receptor CCR10.To investigate the expression of CCR4, CCR7 and CCR10 on skin-homing CLA+ and CD4+ T cells in the peripheral blood of patients with Sézary syndrome (SS), a rare leukaemic variant of cutaneous T-cell lymphoma.Lymphocytes from five patients with SS, six patients with mycosis fungoides and four healthy volunteers were isolated and analysed using flow cytometry. Additionally, the T-cell receptor (TCR)-Vβ CDR3 regions were cloned and sequenced in two patients.We found that CCR4 is expressed on almost all CLA+ and CD4+ memory T cells. Using monoclonal antibodies specific for single TCR-Vβ chains we identified malignant T cells in four patients with SS. Importantly, we found that most but not all malignant Sézary cells expressed the skin-homing chemokine receptor CCR10. Additionally, we found that a significant proportion of these cells also expressed the lymph node-homing chemokine receptor CCR7.Our results support the concept that chemokine receptors play an important role in the pathophysiology of SS and suggest that the malignant clone may represent an expansion of skin-homing cutaneous‘central’ memory T cells in the peripheral blood of these patients. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
21. Atopic dermatitis: pathogenetic mechanisms.
- Author
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Wollenberg, A., Kraft, S., Oppel, T., and Bieber, T.
- Subjects
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ATOPIC dermatitis , *SKIN diseases , *ALLERGENS , *PATHOLOGY - Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease with increasing incidence and socio-economical relevance. The diagnosis is made on clinical grounds and different diagnostic criteria sets have been established. The majority of all AD cases is associated with a sensitization to environmental allergens and increased serum IgE (so-called extrinsic AD), but about 10-30% of all cases suffer from the so-called intrinsic AD, which obviously lacks any link to the classical atopic diathesis. The genetic background of AD has been investigated by target gene approach by different groups with mostly contradictory results for each of the genes under study. An imbalance in the spectrum of Th1/Th2 responses, a disturbed prostaglandin metabolism, intrinsic defects in keratinocyte function, delayed eosinophil apoptosis, IgE-mediated facilitated antigen presentation by epidermal dendritic cells, a two phase model of the inflammatory response and staphylococcal superantigen effects are among the currently studied pathogenetical aspects of extrinsic AD, which are reviewed in this paper. [ABSTRACT FROM AUTHOR]
- Published
- 2000
- Full Text
- View/download PDF
22. The value of lymphocytopenia as a marker of systemic involvement in cutaneous lupus erythematosus.
- Author
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Wenzel, J, Bauer, R, Uerlich, M, Bieber, T, and Boehm, I
- Subjects
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LUPUS erythematosus , *SKIN diseases - Abstract
Summary Background Some patients suffering from cutaneous lupus erythematosus (CLE) develop extracutaneous manifestations during the course of the disease: up to 5% of patients with discoid LE (DLE) and up to 30% of subacute cutaneous LE (SCLE) patients show systemic involvement. Recent studies revealed some markers indicating systemic manifestations of CLE patients. However, the significance of diminished peripheral lymphocyte numbers as a marker of systemic involvement in CLE has not been investigated before. Objectives To determine the value of lymphocytopenia (< 1500 cells µL-1 ) as a marker of extracutaneous manifestations in CLE patients. Methods The records of 72 CLE patients (44 DLE; 28 SCLE) were investigated. Systemic involvement was defined in accordance with the criteria of the European Academy of Dermatology and Venereology. Analyses of peripheral lymphocyte numbers were done by fluorescence-activated cell sorter analysis. Results Five CLE patients developed extracutaneous manifestations during the course of disease. All these patients were lymphocytopenic. Differences between peripheral lymphocyte numbers of CLE patients with and without additional systemic involvement were highly significant (P < 0·01). Conclusions Our results suggest that lymphocytopenia in patients with CLE is a high sensitive but low specific marker of systemic involvement. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
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23. Successful topical immunotherapy of bowenoid papulosis with imiquimod.
- Author
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Petrow, W., Gerdsen, R., Uerlich, M., Richter, O., and Bieber, T.
- Subjects
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GENITAL diseases , *SKIN diseases , *DERMATOLOGIC agents , *DRUG efficacy - Abstract
Presents correspondence on the successful topical immunotherapy treatment of bowenoid papulosis with imiquimod. Case example of a 38-year-old woman; Presenting signs and symptoms; Drug background of imiquimod.
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- 2001
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24. Hailey–Hailey disease: exacerbation by scabies.
- Author
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Gerdsen, R., Hartl, C., Christ, S., Uerlich, M., Bauer, R., and Bieber, T.
- Subjects
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SKIN diseases , *STEROIDS , *RADIOTHERAPY - Abstract
Examines the diagnosis of Hailey-Hailey disease in woman with pruritic skin lesions on the trunk and limbs. Predominance of recurrent erosive skin lesions in intertriginous areas; Treatment of the disease with topical steroids and radiotherapy; Development of erythematous papules and erythematous plaques on the back, abdomen and limbs.
- Published
- 2001
- Full Text
- View/download PDF
25. Papular Palmoplantar Hyperkeratosis Following Chronic Medical Exposure to Arsenic: Human Papillomavirus as a Co-factor in the Pathogenesis of Arsenical Keratosis?
- Author
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Gerdsen, R., Stockfleth, E., Uerlich, M., Fartasch, M., Steen, K. H., and Bieber, T.
- Subjects
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SKIN diseases , *PAPILLOMAVIRUSES - Abstract
This study presents the case of a 38-year-old patient from Pakistan with vitiligo, who developed multiple verrucous papules on the palms and soles several years after receiving “herbal treatment” from a travelling Indian doctor for a period of 12 months. Histopathological examination showed changes consistent with the diagnosis of arsenical keratosis. Molecular-biological examination of a skin biopsy detected an atypical human papillomavirus. This observation supports the concept of human papillomavirus as a co-factor in the pathogenesis of premalignant arsenic-induced skin tumours. [ABSTRACT FROM AUTHOR]
- Published
- 2000
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