Psoriasis: Röcken M

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.

Heidenreich R, Röcken M, Ghoreschi K. · Department of Dermatology, University of Tübingen, University Medical Center, Tübingen, Germany. · Drug News Perspect. · Pubmed #18389101 No free full text.

Abstract: Angiogenesis is a hallmark of chronic inflammation such as psoriasis. Unraveling the pathogenesis of psoriasis shows that several proangiogenic mediators are activated and highly expressed during psoriasis. Vascular endothelial growth factor, hypoxia- inducible factor, tumor necrosis factor, interleukin-8 and angiopoietins are considered to be the main players responsible for the strong vessel formation in psoriasis. The proangiogenic milieu in the skin seems to result from a proinflammatory immune response initiated by T helper cells. Interestingly, several small molecules as well as modern biologics used for systemic therapy of psoriasis have been shown to provide not only immune regulatory effects but also influence endothelial cell biology. Thus, direct targeting of angiogenesis may not only help to understand psoriasis pathogenesis but also to develop new strategies to treat psoriasis with therapeutics that halt the angiogenesis required for the inflammatory disease.

Ghoreschi K, Weigert C, Röcken M. · Department of Dermatology, Eberhard Karls University Tübingen, 72076 Tübingen, Germany. · Clin Dermatol. · Pubmed #18021895 No free full text.

Abstract: Psoriasis is a T cell-dependent autoimmune disease of the skin and joints. Disease manifestation is orchestrated by proinflammatory CD4-positive T helper cells producing either interferon-gamma (Th1) or interleukin (IL)-17 (Th17). These Th1 and Th17 cells interact with dermal dendritic cells, macrophages, mast cells, and neutrophils. Together, they cause an inflammation that mainly involves interferon-gamma, tumor necrosis factor, IL-8, IL-12, IL-17, IL-19, and IL-23. New therapeutics either are directed against T cells, tumor necrosis factor, and IL-12/IL-23 or deviate immune responses into a protective IL-4-dominated Th2 phenotype.

Weischer M, Röcken M, Berneburg M. · Department of Dermatology and Venerology, Eberhard Karls University, Liebermeisterstrasse 25, D-72076 Tuebingen, Germany. · Exp Dermatol. · Pubmed #17437481 No free full text.

Abstract: Since the introduction of cyclosporin A (CsA) in the early 1980s, the use of immunosuppressants has markedly increased. Already established drugs have proved effective in the treatment of a wide range of diseases outside transplantation medicine and new immunosuppressants have been developed for more specific indications such as psoriasis and atopic dermatitis. Patients in transplantation medicine as well as in dermatology have benefited significantly from systemic and topical application of both new and established drugs. But are these drugs without risks? Cancer-protecting effects have been reported for some of the available immunosuppressants. Conversely, other publications and the issue of a black box warning by the US Food and Drug Administration have increased concerns about cancer-promoting effects. Knowledge of the specific effects as well as adverse effects is paramount to ensure an application that is safe and beneficial for the patient. Here we review the mechanisms of action and therapeutic potential, and critically review recent literature with respect to possible carcinogenic side effects of systemic and topical CsA, tacrolimus, pimecrolimus and rapamycin.

Berneburg M, Brod C, Benedix F, Röcken M. · Universitäts-Hautklinik, Eberhard-Karls-Universität Tübingen, Liebermeisterstrasse 25, D-72076 Tübingen, Germany. · J Dtsch Dermatol Ges. · Pubmed #16232274 No free full text.

Abstract: Phototherapy with ultraviolet (UV) irradiation of wavelengths between 280 and 320 nm (UV-B) is a safe and effective treatment for a variety of inflammatory skin diseases. In addition to standard broad band UVB, narrow band phototherapy with fluorescent bulbs emitting near monochromatic UV between 310-315 nm has become an important treatment for diseases such as psoriasis, atopic dermatitis or vitiligo. Other diseases respond favorably to narrow band UV-B phototherapy, the number of potential indications for such phototherapy is continuously growing. The differential effects of narrow band UV-B phototherapy in comparison to other UV phototherapies, as well as new and established indications for this treatment modality are reviewed.

Berneburg M, Röcken M, Benedix F. · Department of Dermatology, Eberhard Karls University, DE-72076 Tuebingen, Germany. · Acta Derm Venereol. · Pubmed #15823900 No free full text.

Abstract: Phototherapy with ultraviolet (UV) radiation of wavelengths between 280 and 320 nm (UVB) is a safe and effective treatment for a variety of diseases. In addition to standard broadband UVB (bUVB), narrowband phototherapy with fluorescent bulbs emitting near monochromatic UV around 311 nm (nUVB) has become an important treatment for diseases such as psoriasis, atopic dermatitis and vitiligo. In addition to these indications, the number of diseases for which nUVB phototherapy is reported to be effective is continuously growing. The differential effects of nUVB phototherapy in comparison to other UV wavelengths as well as established and new indications for this treatment modality are reviewed.

Ghoreschi K, Röcken M. · Department of Dermatology, University Medical Center, Eberhard Karls University Tübingen, Germany. · Curr Drug Targets Inflamm Allergy. · Pubmed #15180473 No free full text.

Abstract: The experience with biologicals in currently available animal models suggest that inflammatory autoimmune disease depend on IFN-gamma-producing T helper (Th) cells. Deletion of T cells improves most of these autoimmune diseases but bears the risks of general immunosuppression. Alternatively, selective deviation of the inflammatory, disease-inducing Th cells into an anti-inflammatory Th cell phenotype may be a promising strategy to treat inflammatory autoimmune diseases, such as psoriasis, rheumatoid arthritis, multiple sclerosis or autoimmune diabetes. The common feature of these organ-specific autoimmune diseases is the close association with IFN-gamma-producing Th1 cells, which recognize organ-specific antigens and orchestrate the cells and mediators that ultimately cause the tissue damage. Even though the autoantigens recognized in psoriasis remain enigmatic, it has been the first Th1-mediated autoimmune disease successfully treated in humans by immune deviation. The basis of such an immune intervention therapy has been established in experimental mice with model diseases of multiple sclerosis, rheumatoid arthritis or autoimmune diabetes. In all these autoimmune diseases clinical improvement was associated with the skewing of IFN-gamma producing autoantigen-specific Th1 cells into an IL-4 dominated Th2 phenotype. Such Th2 cells are still reactive to the autoantigen but provide a different cytokine pattern. The most powerful cytokines capable of inducing anti-inflammatory Th2 cells are IL-4 itself or IL-11. Interestingly, another agent that has been used for decades in the therapy of psoriasis in some European countries, fumaric acid esters (FAE), seems also to induce immune deviation. This review focuses on the potential immune deviating strategies based on the use of IL-4, IL-11 or FAE in the therapy of psoriasis, the effects of these agents on the immune system, potential risks and future perspectives for therapeutic intervention by immune deviation replacing immunosuppression.

Biedermann T, Röcken M, Carballido JM. · Novartis Research Institute, Vienna, Austria. · J Investig Dermatol Symp Proc. · Pubmed #14870978 No free full text.

Abstract: Since the first description of the subpopulations of TH1 and TH2 cells, insights into the development and control of these cells as two polarized and physiologically balanced subsets have been generated. In particular, implications of the TH1-TH2 concept for TH cell-mediated skin disorders have been discovered. This article will review the basic factors that control the development of TH1 and TH2 cells, such as the cytokines IL-12 and IL-4 and transcription factors, the possible role of costimulatory molecules, and specialized dendritic cell populations. These regulatory mechanisms will be discussed in the context of polarized TH1 or TH2 skin disorders such as psoriasis and atopic dermatitis. Also presented are the principles that govern how chemokines and chemokine receptors recruit TH1 and TH2 cells to inflammatory sites and how they amplify these polarized TH cell responses. All of these concepts, including a novel role for IL-4-inducing TH1 responses, can contribute to the design of better therapeutic strategies to modulate TH cell-mediated immune responses.

Ghoreschi K, Mrowietz U, Röcken M. · Department of Dermatology, University of Tübingen, Liebermeisterstrasse 25, 72076 Tübingen, Germany. · J Mol Med. · Pubmed #12879154 No free full text.

Abstract: Psoriasis is an autoimmune disease affecting 2-4% of the Caucasian population. Inflammatory processes induce the migration of interferon (IFN) gamma producing Th1 lymphocytes into the skin. These play a key role in the pathogenesis of psoriasis. These Th1 lymphocytes are responsible for the pathological reactions in psoriatic skin leading to keratinocyte hyperproliferation, small vessel proliferation and neutrophilic infiltration. Antigen-presenting cells activate dermal CD4+ T lymphocytes, and various signals can support the polarization of Th1 responses. The main signal for Th1 development is interleukin (IL) 12. After binding to their receptors both IL-12 and IFN-gamma promote intracellular IFN-gamma production by activating signal transducer and activator of transcription (STAT) 4 or 1. STAT1 activation by IFN-gamma is followed by T-bet activation, a master transcription factor for Th1 lymphocytes. In experimental models of Th1-mediated autoimmune diseases immune deviation of polarized autoreactive Th1 into anti-inflammatory Th2 responses generally improves the disease. Therefore new therapeutic approaches based on immunomodulating molecules have been developed for psoriasis, a prototypical Th1-mediated autoimmune disorder. Recently IL-4, the most effective Th2-inducing cytokine, has been shown to be safe and efficient for treating psoriasis. Improvement was associated with the induction of a Th2 phenotype of skin infiltrating lymphocytes. This review summarizes the IL-4 inducing potential of various conventional and newer systemic therapies for psoriasis. Many of these were thought to be primarily immunosuppressive. A review of the literature reveals that most of them can induce IL-4 and Th2, and that Th2 induction may be an underestimated mode of action in the therapy of Th1-mediated autoimmune disease. Further studies are needed to determine the central role of IL-4 in the control of Th1-induced autoimmune disease, namely psoriasis.

Messer G, Degitz K, Plewig G, Röcken M. · No affiliation provided · Br J Dermatol. · Pubmed #11260031 No free full text.

This publication has no abstract.

Heidenreich R, Röcken M, Ghoreschi K. · Department of Dermatology, University Medical Center, University of Tübingen, Tübingen, Germany. · Int J Exp Pathol. · Pubmed #19563608 No free full text.

Abstract: Psoriasis pathogenesis is closely associated with disease-inducing Th1 and Th17 cells. Yet, several studies suggest that aberrant keratinocyte or endothelial cell signalling significantly contributes to disease manifestation. Histological hallmarks of psoriatic skin include the infiltration of multiple immune cells, keratinocyte proliferation and increased dermal vascularity. Formation of new blood vessels starts with early psoriatic changes and disappears with disease clearance. Several angiogenic mediators like vascular endothelial growth factor, hypoxia-inducible factors, angiopoietins and pro-angiogenic cytokines, such as tumour necrosis factor (TNF), interleukin (IL)-8 and IL-17, are up-regulated in psoriasis development. Contact- and mediator-dependent factors derived from keratinocytes, mast cells and immune cells may contribute to the strong blood vessel formation of psoriasis. New technologies and experimental models provide new insights into the role of angiogenesis in psoriasis pathogenesis. Interestingly, many therapies target not only immune cells, but also protein structures of endothelial cells. Here we summarize the role of pro-angiogenic factors in psoriasis development and discuss angiogenesis as a potential target of novel therapies.

Weber HO, Borelli C, Röcken M, Schaller M. · Department of Dermatology, Eberhard-Karls-University, Munich, Germany. · Acta Derm Venereol. · Pubmed #19479130 No free full text.

Abstract: While localized variants of granuloma annulare are typically self-limited, disseminated granuloma annulare tends to be chronic and often therapy-resistant. Treatment with fumaric acid esters is effective for severe forms of psoriasis. Disseminated granuloma annulare has also been reported to respond to fumaric acid esters. We treated 8 patients (mean age 64.2 years; 4 men, 4 women) with low-dose fumaric acid esters for 1-18 months. One patient showed complete clearance, 4 marked improvement, one slight to moderate improvement and one no response. One patient discontinued treatment due to nausea after one month and another stopped it after 18 months. Five out of 8 patients tolerated the treatment well. Six patients developed transient, mild leucopaenia and one eosinophilia. None of these blood abnormalities necessitated discontinuation of therapy. Low-dose fumaric acid esters significantly improve disseminated granuloma annulare in approximately 63% of patients. Larger, controlled, prospective studies are needed to evaluate its efficacy and safety in this setting.

Kneilling M, Röcken M. · Department of Dermatology, Eberhard Karls University, Tübingen, Germany. · Exp Dermatol. · Pubmed #19382316 No free full text.

Abstract: Mast cells are still generally viewed as mediators of type I allergic or pseudoallergic reactions. Research over the past 10 years revealed that our view was too small and that mast cells are of key importance in innate immunity and also types II, III and IV adaptive immune reactions. Understanding their role in modulating and amplifying of inflammatory responses provides important insights into the pathogenesis of skin diseases such as psoriasis, atopic dermatitis, bullous pemphigoid or the control of infections. This helps us to understand the course of these diseases, their trigger mechanisms, and, the new role of agents, which can modulate the function of mast cells. These insights will help to develop new therapeutic approaches.

Lichte V, Ghoreschi K, Metzler G, Möhrle M, Geyer A, Röcken M, Schaller M. · Department of Dermatology, Clinic of the University of Tübingen, Germany. · J Dtsch Dermatol Ges. · Pubmed #19054422 No free full text.

Abstract: Pagetoid reticulosis (Woringer-Kolopp disease) is a rare subtype of cutaneous CD8-positive T-cell lymphoma. A 41-year-old man presented with a 7-year history with a slowly progressive erythematous plaque on his right buttocks. With the working diagnosis of psoriasis, he was treated with topical corticosteroids which produced no improvement. Histological examination showed an epidermotropic T-cell lymphoma with predominance of CD8- vs.CD4-positive lymphocytes. Based on the clinical picture and the histological findings, we diagnosed pagetoid reticulosis. Excision of the plaque and cream PUVA photo-chemotherapy produced long-term remission.

Ghoreschi K, Röcken M. · Universitäts-Hautklinik, Eberhard Karls Universität Tübingen. · J Dtsch Dermatol Ges. · Pubmed #16295038 No free full text.

Abstract: Psoriasis is a chronic inflammatory disease of the skin and the joints. Multiple factors contribute to the initiation of psoriasis. They include specific genetic characteristics such as major histocompatibility antigens and psoriasis susceptibility genes, as well as trigger factors, namely streptococcal infections. Today, psoriasis is considered as a T-lymphocyte mediated autoimmune disease, even though the putative autoantigen remains unknown. Bacterial proteins with similarity to structural proteins of keratinocytes are potential target antigens. As in other autoimmune diseases, inflammatory cytokines of the innate immune system initiate a cascade that activates inflammation locally in the skin, in the circulation and most likely also in lymph nodes. IFN-gamma-producing CD4+ Th1-lymphocytes seem to be of central importance in the pathogenesis of psoriasis as they critically influence differentiation and functioning of antigen presenting cells, mast cells, neutrophils and endothelial cells. This inflammatory cascade simultaneously provokes neoangiogenesis in the dermis and proliferation of keratinocytes. Based on this hypothesis, cytokines or anticytokine antibodies that either inhibit T-cell mediated inflammation or transform disease-inducing, pro-inflammatory Th1-lymphocytes into a phenotype with anti-inflammatory properties were tested in psoriasis. As both approaches improved psoriasis, they strongly support the current concept that views psoriasis as a Th1-lymphocyte mediated disease.

Herzinger T, Degitz K, Plewig G, Röcken M. · Department of Dermatology, University of Munich, Germany. · Clin Exp Dermatol. · Pubmed #15953075 No free full text.

Abstract: Narrow band (311 nm) ultraviolet B (NB-UVB) has been shown to be a safe and effective treatment for psoriasis and other inflammatory skin diseases. We have therefore employed NB-UVB in the treatment of small plaque parapsoriasis (SPP) since 1996. All patients (16/16) responded with complete remission of the disease after a mean number of 32.8 exposures and a mean total dose of 35.4 J/cm2. Unwanted side-effects were rare (3.3%) and always mild. Relapse of the disease occurred after an average of 29 weeks in those patients who came for follow-up visits. Therefore, NB-UVB is an effective, comparably safe and convenient alternative to psoralen and ultraviolet A therapy or other treatment modalities in the suppression of SPP.

Weischer M, Blum A, Eberhard F, Röcken M, Berneburg M. · Department of Dermatology, Eberhard Karls University, Tuebingen, Germany. · Acta Derm Venereol. · Pubmed #15370703 No free full text.

Abstract: Phototherapy of skin diseases such as psoriasis is an effective and safe treatment modality. However, increasing the risk of skin cancer by phototherapy is a serious concern. An increased skin cancer risk occurs after prolonged photochemotherapy (PUVA). In contrast, the role of broadband UVB or narrowband UVB therapy in skin carcinogenesis of humans with psoriasis is less clear. Therefore, we investigated the incidence of skin tumours in a total of 195 psoriasis patients, receiving broadband (n=69) or narrowband (n=126) UVB from 1994 to 2000 with follow-up until 2003. Data were raised from the regional interdisciplinary cancer centre of the University of Tuebingen, Germany and compared with the tumour incidences given for the German population. In this study, with 80% statistical power to detect a 6-7-fold increase in skin cancer with broadband UVB and 83% power to detect a 5-6-fold increase with narrow band UVB at p=0.05, only one patient developed skin cancer - an in situ melanoma. The tumour occurred within the same year that phototherapy was initiated. Thus, the present study does not provide evidence for an increased skin cancer risk for patients treated with either broadband or narrowband UVB phototherapy

Ghoreschi K, Thomas P, Breit S, Dugas M, Mailhammer R, van Eden W, van der Zee R, Biedermann T, Prinz J, Mack M, Mrowietz U, Christophers E, Schlöndorff D, Plewig G, Sander CA, Röcken M. · Department of Dermatology and Allergology, Ludwig-Maximilians University Munich, Munich, Germany. · Nat Med. · Pubmed #12461524 No free full text.

Abstract: Selective skewing of autoreactive interferon-gamma (IFN-gamma)-producing T helper cells (Th1) toward an interleukin-4 (IL-4)-producing (Th2) phenotype can in experimental animals alleviate autoimmune disease without inducing general immunosuppression. In a prospective dose escalation study, we assessed treatment with human IL-4 (rhuIL-4) in 20 patients with severe psoriasis. The therapy was well tolerated, and within six weeks all patients showed decreased clinical scores and 15 improved more than 68%. Stable reduction of clinical scores was significantly better at 0.2-0.5 microg rhuIL-4 than at < or =0.1 microg rhuIL-4 (P = 0.009). In psoriatic lesions, treatment with 0.2-0.5 microg/kg rhuIL-4 reduced the concentrations of IL-8 and IL-19, two cytokines directly involved in psoriasis; the number of chemokine receptor CCR5+ Th1 cells; and the IFN-gamma/IL-4 ratio. In the circulation, 0.2-0.5 microg/kg rhuIL-4 increased the number of IL-4+CD4+ T cells two- to three-fold. Thus, IL-4 therapy can induce Th2 differentiation in human CD4+ T cells and has promise as a potential treatment for psoriasis, a prototypic Th1-associated autoimmune disease.

Ulmer A, Wölbing F, Metzler G, Schanz S, Fierlbeck G, Röcken M. · No affiliation provided · Br J Dermatol. · Pubmed #18284393 No free full text.

This publication has no abstract.