-
Journal der Deutschen Dermatologischen Gesellschaft 05/2013; 11(5):429-36. · 1.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Safety and efficacy of fumaric acid esters (FAE) in patients with psoriasis requiring treated comorbidit condition were investigated. PATIENTS AND METHODS: Data collected from 7 dermatology centers were used for a retrospective analysis of patients treated continuously with FAE for at least 6 weeks who required at least one medication for a comorbid condition. The records were analyzed at baseline and after 1, 3, 6, 12 and 24 months of therapy. Safety parameters were monitored and the severity of skin symptoms was assessed by 'Physician's Global Assessment' (PGA). RESULTS: A total of 69 patients with moderate to severe psoriasis and a mean duration of 27.4 months of continuous treatment were included in the study. In less than 5% were interactions between FAE and co-medications observed. Changes of hepatic, renal or hematological laboratory parameters were usually insignificant and required a modification of FAE treatment in less than 12% of the cases. The percentage of patients documented as markedly improved or clear was 61% after 6 months, 77% after 12 months, and 75% after 24 months of therapy. CONCLUSIONS: In patients with moderate to severe psoriasis on co-medications, FAE were effective and safe without any noteworthy drug interactions.
Journal der Deutschen Dermatologischen Gesellschaft 02/2013; · 1.47 Impact Factor
-
Alexander Nast,
Wolf-Henning Boehncke,
Ulrich Mrowietz,
Hans-Michael Ockenfels, Sandra Philipp,
Kristian Reich,
Thomas Rosenbach,
Adel Sammain,
Martin Schlaeger,
Michael Sebastian, [......],
Matthias Augustin,
Ricardo Erdmann,
Joachim Klaus,
Joachim Koza,
Siegrid Muller,
Hans-Dieter Orzechowski,
Stefanie Rosumeck,
Gerhard Schmid-Ott,
Tobias Weberschock,
Berthold Rzany
[show abstract]
[hide abstract]
ABSTRACT: Psoriasis vulgaris is a common and often chronic inflammatory skin disease. The incidence of psoriasis in Western industrialized countries ranges from 1.5% to 2%. Patients afflicted with severe psoriasis vulgaris may experience a significant reduction in quality of life. Despite the large variety of treatment options available, surveys have shown that patients still do not received optimal treatments. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologi sche Gesellschaft (DDG) and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. They were first published in 2006 and updated in 2011. The Guidelines focus on induction therapy in cases of mild, moderate and severe plaque-type psoriasis in adults including systemic therapy, UV therapy and topical therapies. The therapeutic recommendations were developed based on the results of a systematic literature search and were finalized during a consensus meeting using structured consensus methods (nominal group process).
Journal der Deutschen Dermatologischen Gesellschaft 03/2012; 10 Suppl 2:S1-95. · 1.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Acne inversa (AI; also designated as Hidradenitis suppurativa) is a common chronic inflammatory skin disease, localized in the axillary, inguinal and perianal skin areas that causes painful, fistulating sinuses with malodorous purulence and scars. Several chronic inflammatory diseases are associated with the metabolic syndrome and its consequences including arteriosclerosis, coronary heart disease, myocardial infraction, and stroke. So far, the association of AI with systemic metabolic alterations is largely unexplored.
A hospital-based case-control study in 80 AI patients and 100 age- and sex-matched control participants was carried out. The prevalence of central obesity (odds ratio 5.88), hypertriglyceridemia (odds ratio 2.24), hypo-HDL-cholesterolemia (odds ratio 4.56), and hyperglycemia (odds ratio 4.09) in AI patients was significantly higher than in controls. Furthermore, the metabolic syndrome, previously defined as the presence of at least three of the five alterations listed above, was more common in those patients compared to controls (40.0% versus 13.0%; odds ratio 4.46, 95% confidence interval 2.02 to 9.96; P<0.001). AI patients with metabolic syndrome also had more pronounced metabolic alterations than controls with metabolic syndrome. Interestingly, there was no correlation between the severity or duration of the disease and the levels of respective parameters or the number of criteria defining the metabolic syndrome. Rather, the metabolic syndrome was observed in a disproportionately high percentage of young AI patients.
This study shows for the first time that AI patients have a high prevalence of the metabolic syndrome and all of its criteria. It further suggests that the inflammation present in AI patients does not have a major impact on the development of metabolic alterations. Instead, evidence is given for a role of metabolic alterations in the development of AI. We recommend monitoring of AI patients in order to correct their modifiable cardiovascular risk factors.
PLoS ONE 01/2012; 7(2):e31810. · 4.09 Impact Factor
-
Alexander Nast,
Wolf-Henning Boehncke,
Ulrich Mrowietz,
Hans-Michael Ockenfels, Sandra Philipp,
Kristian Reich,
Thomas Rosenbach,
Adel Sammain,
Martin Schlaeger,
Michael Sebastian, [......],
Matthias Augustin,
Ricardo Erdmann,
Joachim Klaus,
Joachim Koza,
Siegrid Müller,
Hans-Dieter Orzechowski,
Stefanie Rosumeck,
Gerhard Schmid-Ott,
Tobias Weberschock,
Berthold Rzany
Journal der Deutschen Dermatologischen Gesellschaft 06/2011; 9 Suppl 2:S1-104. · 1.47 Impact Factor
-
Alexander Nast,
Wolf-Henning Boehncke,
Ulrich Mrowietz,
Hans-Michael Ockenfels, Sandra Philipp,
Kristian Reich,
Thomas Rosenbach,
Adel Sammain,
Martin Schlaeger,
Michael Sebastian, [......],
Matthias Augustin,
Ricardo Erdmann,
Joachim Klaus,
Joachim Koza,
Siegrid Müller,
Hans-Dieter Orzechowski,
Stefanie Rosumeck,
Gerhard Schmid-Ott,
Tobias Weberschock,
Berthold Rzany
Journal der Deutschen Dermatologischen Gesellschaft 05/2011; 9(s2):S1 - S104. · 1.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The monoclonal anti tumor necrosis factor (TNF) antibody adalimumab has recently been approved for Crohn's disease (CD) and evaluated for ulcerative colitis (UC). Cutaneous lesions associated with its administration have not been prospectively studied in inflammatory bowel disease (IBD).
We evaluated the first 50 consecutive patients (female n = 30, median age 32½ years, interquartile range [IQR 27-46]) with CD (n = 46) and UC (n = 4) who received adalimumab (82% induction with 160/80 and 94% maintenance with 40 mg subcutaneously biweekly) at our center and were followed up for a median of 17 months [IQR 12-21]. The Kaplan-Meier method was used to estimate skin reaction free survival (SRFS) and Fisher's exact test to examine contingency between demographic variables and outcomes.
Sixty-two percent of all patients developed a dermatological reaction (eczema [n = 9], acne-like dermatitis [n = 9], psoriasis-like lesions [n = 6], localized erythema and swelling at injection site [n = 1], dermatitis sicca [n = 1], rosacea [n = 1], prurigo simplex [n = 1], tinea [n = 1], localized herpes simplex [n = 1], and candida [n = 1] infections) that resolved in 12% at follow-up. SRFS was 12 months [IQR 30-5]. Adalimumab was discontinued in 22% of all patients. Longer disease duration, a lower dose induction schedule, as well as concomitant use of steroids or immunosuppressants were more often associated with an unfavorable skin outcome. Skin outcomes differed significantly between patients who saw a dermatologist (P = 0.022) and/or had a dermatological intervention (P = 0.012).
A broad spectrum of adverse cutaneous reactions occurs more frequently and later in adalimumab therapy for IBD compared with other indications. Consultation with a dermatologist is highly recommended.
Inflammatory Bowel Diseases 02/2011; 17(12):2512-20. · 4.86 Impact Factor
-
Alexander Nast,
Matthias Augustin,
Wolf-Henning Boehncke,
Joachim Klaus,
Ulrich Mrowietz,
Hans-Michael Ockenfels, Sandra Philipp,
Kristian Reich,
Thomas Rosenbach,
Martin Schlaeger,
Michael Sebastian,
Wolfram Sterry,
Volker Streit,
Peter Weisenseel,
Berthold Rzany
[show abstract]
[hide abstract]
ABSTRACT: Summary In February 2009, the European Medicines Agency's (EMEA) Committee for Medicinal Products for Human Use (CHMP) had recommended the suspension of efalizumab's (Raptiva((R))) marketing authorization, because its benefits in the treatment of psoriasis were modest, while there was a risk of serious side effects in patients receiving the medicine, including the occurrence of progressive multifocal leukoencephalopathy (PML). The guideline group has changed the guideline accordingly.
Journal der Deutschen Dermatologischen Gesellschaft 11/2009; · 1.47 Impact Factor
-
Kerstin Wolk,
Ellen Witte,
Katarzyna Warszawska,
Gundula Schulze-Tanzil,
Katrin Witte, Sandra Philipp,
Stefanie Kunz,
Wolf-Dietrich Döcke,
Khusru Asadullah,
Hans-Dieter Volk,
Wolfram Sterry,
Robert Sabat
[show abstract]
[hide abstract]
ABSTRACT: Psoriasis is a common chronic skin disease. Recent studies demonstrated that IL-20 and IL-22, cytokines produced by keratinocytes and T cells, respectively, both inhibit keratinocyte terminal differentiation and induce psoriasis-like epidermis alterations. Here, we investigated the relationship between these mediators. Although IL-20 was not able to regulate IL-22 production, IL-22 induced IL-20 mRNA and protein in human keratinocytes. However, IL-22 had only a minimal effect, if any, on IL-19 and IL-26. Cutaneous IL-20 was also elevated in mice following IL-22 application. Accordingly, some of IL-22's effects on differentiation-regulating genes were partially mediated by an endogenous, secreted protein and attenuated by anti-IL-20 Ab. Like IL-22, IL-17A and TNF-alpha induced IL-20 in keratinocytes, whereas IFN-gamma and IL-20 itself did not. Furthermore, IL-17A and TNF-alpha individually strengthened the IL-22-induced IL-20 production. In lesional skin of psoriasis patients, highly elevated IL-20 levels strongly correlated with IL-22, and to a lesser extent, with IL-17A and TNF-alpha. As previously shown for IL-22, IL-20 blood levels correlated with the disease severity, although with a lower significance. This study demonstrates that a T-cell mediator induces a tissue cell mediator with similar effects to its own and therefore suggests the existence of a novel type of pathogenetic cascade.
European Journal of Immunology 10/2009; 39(12):3570-81. · 5.10 Impact Factor
-
Kathrin Keeren,
Markus Friedrich,
Inga Gebuhr, Sandra Philipp,
Robert Sabat,
Wolfram Sterry,
Christine Brandt,
Christian Meisel,
Gerald Grütz,
Hans-Dieter Volk,
Birgit Sawitzki
[show abstract]
[hide abstract]
ABSTRACT: Immune modulating therapies gain increasing importance in treatment of patients with autoimmune diseases such as psoriasis. None of the currently applied biologics achieves significant clinical improvement in all treated patients. Because the therapy with biologics is cost intensive and sometimes associated with side effects, noninvasive diagnostic tools for early prediction of responders are of major interest. We studied the effects of Alefacept (LFA3Ig), an approved drug for treatment of psoriasis, on leukocytes in vitro and in vivo to identify gene markers predictive for treatment response and to further investigate its molecular mechanisms of action. In an open-label study, 20 psoriasis patients were treated weekly with 15 mg Alefacept over 12 wk. We demonstrate that transcription of the tolerance-associated gene (TOAG-1) is significantly up-regulated whereas receptor for hyaluronic acid mediated migration (RHAMM) transcription is down-regulated in PBMCs of responding patients before clinical improvement. TOAG-1 is exclusively localized within mitochondria. Overexpression of TOAG-1 in murine T cells leads to increased susceptibility to apoptosis. Addition of Alefacept to stimulated human T cells in vitro resulted in reduced frequencies of activated CD137(+) cells, increased TOAG-1 but reduced RHAMM expression. This was accompanied by reduced proliferation and enhanced apoptosis. Inhibition of proliferation was dependent on enhanced PDL1 expression of APCs. Thus, peripheral changes of TOAG-1 and RHAMM expression can be used to predict clinical response to Alefacept treatment in psoriasis patients. In the presence of APCs Alefacept can inhibit T cell activation and survival by increasing expression of TOAG-1 on T cells and PDL1 on APCs.
The Journal of Immunology 09/2009; 183(6):4077-87. · 5.79 Impact Factor
-
Kerstin Wolk,
Harald S Haugen,
Wenfeng Xu,
Ellen Witte,
Kim Waggie,
Monica Anderson,
Elmar Vom Baur,
Katrin Witte,
Katarzyna Warszawska, Sandra Philipp,
Caroline Johnson-Leger,
Hans-Dieter Volk,
Wolfram Sterry,
Robert Sabat
[show abstract]
[hide abstract]
ABSTRACT: Psoriasis is a common chronic skin disease with a largely unknown pathogenesis. We demonstrate here that transgenic over-expression of interleukin (IL)-22 in mice resulted in neonatal mortality and psoriasis-like skin alterations including acanthosis and hypogranularity. This cutaneous phenotype may be caused by the direct influence of IL-22 on keratinocytes, since this cytokine did not affect skin fibroblasts, endothelial cells, melanocytes, or adipocytes. The comparison of cytokines with hypothesized roles in psoriasis pathogenesis determined that neither interferon (IFN)-gamma nor IL-17, but only IL-22 and, with lower potency, IL-20 caused psoriasis-like morphological changes in a three-dimensional human epidermis model. These changes were associated with inhibited keratinocyte terminal differentiation and with STAT3 upregulation. The IL-22 effect on differentiation-regulating genes was STAT3-dependent. In contrast to IL-22 and IL-20, IFN-gamma and IL-17 strongly induced T-cell and neutrophilic granulocyte-attracting chemokines, respectively. Tumor necrosis factor-alpha potently induced diverse chemokines and additionally enhanced the expression of IL-22 receptor pathway elements and amplified some IL-22 effects. This study suggests that different cytokines are players in the psoriasis pathogenesis although only the IL-10 family members IL-22 and IL-20 directly cause the characteristic epidermal alterations.
Journal of Molecular Medicine 04/2009; 87(5):523-36. · 4.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Psoriasis is a chronic skin disease that affects about 1.5% of the Caucasian population and is characterized by typical macroscopic and microscopic skin alterations. Psoriatic lesions are sharply demarcated, red and slightly raised lesions with silver-whitish scales. The microscopic alterations of psoriatic plaques include an infiltration of immune cells in the dermis and epidermis, a dilatation and an increase in the number of blood vessels in the upper dermis, and a massively thickened epidermis with atypical keratinocyte differentiation. It is considered a fact that the immune system plays an important role in the pathogenesis of psoriasis. Since the early 1990s, it has been assumed that T1 cells play the dominant role in the initiation and maintenance of psoriasis. However, the profound success of anti-tumor necrosis factor-alpha therapy, when compared with T-cell depletion therapies, should provoke us to critically re-evaluate the current hypothesis for psoriasis pathogenesis. Recently made discoveries regarding other T-cell populations such as Th17 and regulatory T cells, dendritic cells, macrophages, the keratinocyte signal transduction and novel cytokines including interleukin (IL)-22, IL-23 and IL-20, let us postulate that the pathogenesis of psoriasis consists of distinct subsequent stages, in each of them different cell types playing a dominant role. Our model helps to explain the varied effectiveness of the currently tested immune modulating therapies and may enable the prediction of the success of future therapies.
Experimental Dermatology 11/2007; 16(10):779-98. · 3.54 Impact Factor
-
Journal of Allergy and Clinical Immunology 04/2007; 119(3):752-4. · 11.00 Impact Factor
-
Contact Dermatitis 04/2007; 56(3):177-8. · 3.51 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Psoriasis is a common chronic, recurring skin disease that is characterised by typical macroscopic and microscopic skin alterations. It is widely accepted that the immune system plays an important role in the pathogenesis of this disorder. Since the early 1990s, the dominant role of a subpopulation of T cells, so-called T1 cells, and their prominent cytokine IFN-gamma has been assumed in the pathogenesis of psoriasis. Surprisingly, the comparison of the therapeutic success of treatments with recombinant proteins directed against defined immunological structures shows that those that directly affect T cells (alefacept, efalizumab, Hu-max-CD4, OKTcdr4a) were clearly less effective than those targeting TNF-alpha (etanercept, adalimumab, infliximab). For this reason, the authors critically re-evaluated the view of psoriasis pathogenesis and postulate that in the majority of patients the T1 cells do not play a dominant role in the clinical, visible stage of this disease.
Expert opinion on therapeutic targets 01/2007; 10(6):817-31. · 3.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Psoriasis is a systemic chronic inflammatory disorder. One of the major characteristics is an excess of infiltration of inflammatory cells, mainly lymphocytes, into the skin. Because the adhesion family of selectins is suggested to play a relevant role in this process, selectins have emerged as an interesting target for drug discovery and development in psoriasis. Different strategies targeting selectins have been described. This review discusses these approaches and summarises the current development of selectin antagonists for the treatment of psoriasis. An expert opinion will give the authors' personal opinion about selectin antagonism in psoriasis and which approach might be preferable.
Expert Opinion on Investigational Drugs 09/2006; 15(8):963-79. · 5.27 Impact Factor
-
Markus Friedrich,
Daniel Bock, Sandra Philipp,
Nina Ludwig,
Robert Sabat,
Kerstin Wolk,
Sabine Schroeter-Maas,
Ewald Aydt,
Sewon Kang,
Tomas Norman Dam,
Rainer Zahlten,
Wolfram Sterry,
Gerhard Wolff
[show abstract]
[hide abstract]
ABSTRACT: The selectin family of vascular cell adhesion molecules is comprised of structurally related carbohydrate binding proteins, which mediate the initial rolling of leukocytes on the activated vascular endothelium. Because this process is one of the crucial events in initiating and maintaining inflammation, selectins are proposed to be an attractive target for the development of new antiinflammatory therapeutics. Here, we demonstrate that the synthetic pan-selectin antagonist bimosiamose is effective in pre-clinical models of psoriasis as well as in psoriatic patients. In vitro bimosiamose proved to be inhibitory to E- or P-selectin dependent lymphocyte adhesion under flow conditions. Using xenogeneic transplantation models, bimosiamose reduced disease severity as well as development of psoriatic plaques in symptomless psoriatic skin. The administration of bimosiamose in patients suffering from psoriasis resulted in a reduction of epidermal thickness and lymphocyte infiltration. The clinical improvement was statistically significant (P=0.02) as analyzed by comparison of psoriasis area and severity index before and after treatment. Assessment of safety parameters showed no abnormal findings. These data suggest that pan-selectin antagonism may be a promising strategy for the treatment of psoriasis and other inflammatory diseases.
Archives for Dermatological Research 03/2006; 297(8):345-51. · 2.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The ability of interleukin-10 therapy to reduce the severity of exacerbated psoriasis has been demonstrated recently. Considering the immunobiologic properties of this cytokine we investigated the effects of long-term interleukin-10 application on the immune system and duration of psoriasis remission. We performed a placebo-controlled, double-blind, phase II trial using interleukin-10 in patients with chronic plaque psoriasis in remission. Patients received subcutaneous injections with either interleukin-10 (10 microg per kg body weight; n = 7) or placebo (n = 10) three times per week until relapse or study termination after 4 months. The treatment was well tolerated. In the placebo group almost all patients (90%) showed a relapse during the observation period. In contrast to this, only two of seven patients (28.6%) relapsed in the interleukin-10-treated group. Kaplan-Meier analysis revealed a significantly lower relapse incidence in the interleukin-10 than in the placebo group (p = 0.02). The mean relapse-free interval time was 101.6 +/- 12.6 d in the interleukin-10 group in comparison with 66.4 +/- 10.4 d in the placebo group. Immunologic activity of interleukin-10 application was indicated by an increase in soluble interleukin-2 receptor plasma levels and higher ex vivo interleukin-4 secretion capacities. Remarkably, a significant negative correlation was demonstrated between the interleukin-4 secretion capacity and Psoriasis Area and Severity Index score (r = -0.36, p < 0.01). Our data suggest that interleukin-10 therapy is immunologic effective, decreases the incidence of relapse and prolongs the disease-free interval in psoriasis. Its value should be further determined in larger trials and for the prevention of re-exacerbation of other inflammatory disorders with a similar immunologic profile.
Journal of Investigative Dermatology 05/2002; 118(4):672-7. · 6.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Psoriasis is a common chronic skin disease. Its pathogenesis has intensively been investigated in the last 3 decades. In the 1970s, the observed increased proliferation of keratinocytes and their altered differentiation were considered to be the most important signs and causes of psoriatic skin lesions. Since the early 1980s, T cells slid into the focus of psoriasis research. It was then postulated that a subpopulation of T cells, so-called T1 cells, and their prominent cytokine interferon-gamma, had a dominant role in the pathogenesis of psoriasis. In the last decade, new data regarding macrophages and dendritic cells and the high therapeutic success of anti-tumor necrosis factor alpha biologics led to the assumption that antigen-presenting cells are important not only in the induction of psoriasis but also in its maintenance. The knowledge gained over the past 3 decades let us postulate that psoriasis is an immunologically induced, overshot, regeneration-like reaction of the skin in which various cells play a dominant role at different stages. This hypothesis is also supported by the very recent discoveries about interleukin (IL)-22, IL-20, and IL-23.
Clinics in Dermatology 25(6):504-9. · 2.33 Impact Factor
