Psoriasis: Prinz JC

Weisenseel P, Kuznetsov AV, Prinz JC. · Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians-Universität, München, Germany. · J Dtsch Dermatol Ges. · Pubmed #17659043 No free full text.

Abstract: The recently published German S3- guidelines for the treatment of psoriasis vulgaris offer an extensive evidence-based documentation and evaluation of currently available treatment modalities. In order to incorporate this detailed information into the actual treatment decisions in individual patients, we have transformed the recommendations regarding phototherapy and systemic therapies into an algorithm. This algorithm should allow a stepwise treatment approach in adult patients with moderate to severe psoriasis, in whom topical therapy is not sufficient. It can also facilitate documentation of treatment. In our hands the treatment algorithm proved to be feasible and reliable in a large number of patients.

Prinz JC. · Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians-Universität, Frauenlobstrasse 9-11, Munich, Germany. · Hautarzt. · Pubmed #19151963 No free full text.

Abstract: Infections with Streptococcus pyogenes are highly relevant among the environmental factors that contribute to first onset or relapses of psoriasis in predisposed individuals. Streptococcal angina or pharyngitis, but also perianal streptococcal dermatitis, vulvovaginitis or balanoposthitis are potential causes. Several mechanisms such as molecular mimicry or superantigens may be involved. Many patients develop a chronic streptococcal infection or colonization that may result from the ability of streptococci for intracellular uptake and persistence in epithelial cells. Whether and under what conditions a curative treatment of streptococcal infection by tonsillectomy or antibiotic treatment may affect the course of psoriasis, as proposed by several observations, needs to be determined in more detail by clinical trials.

Prinz JC. · Klinik und Poliklinik für Dermatologie und Allergologie der Ludwig-Maximilians-Universität. · J Dtsch Dermatol Ges. · Pubmed #16281603 No free full text.

This publication has no abstract.

Prinz JC. · Klinik und Poliklinik für Dermatologie und Allergologie der Ludwig-Maximilians-Universität München. · Hautarzt. · Pubmed #16096737 No free full text.

Abstract: Efalizumab is a humanized monoclonal CD11a-antibody. It inhibits T-cell migration and activation which are essential steps in the immunopathogenesis of psoriasis. Clinical studies have demonstrated that efalizumab is efficient and safe in the treatment of chronic plaque psoriasis. Approximately 30% of patients achieve an improvement in PASI of > or =75% within 12 weeks, with further clinical benefit noted with continued therapy. Efalizumab thus appears as an important option in the long-term management of chronic plaque psoriasis.

Jullien D, Prinz JC, Langley RG, Caro I, Dummer W, Joshi A, Dedrick R, Natta P. · Department of Dermatology and INSERM U346, Hôpital Edouard Herriot, Lyon, France. · Dermatology. · Pubmed #15178911 No free full text.

Abstract: Psoriasis is a chronic, incurable, auto-immune disorder with cutaneous manifestations. New evidence on the central role of the immune system in the pathogenesis of psoriasis increasingly provides insight into pathogenic steps that can be modulated to provide disease control. Numerous biological therapies are in various stages of clinical development, with expectation of providing enhanced safety and efficacy over currently available psoriasis therapies. Efalizumab, a recombinant humanized monoclonal IgG1 antibody, is a novel targeted T-cell modulator that inhibits multiple steps in the immune cascade that result in the production and maintenance of psoriatic plaques, including initial T-cell activation and T-cell trafficking into sites of inflammation, including psoriatic skin, with subsequent reactivation in these sites. This article reviews the pharmacodynamic, pharmacokinetic and clinical effects observed during phase I, II and III efalizumab trials in patients with moderate to severe chronic plaque psoriasis.

Ortonne JP, Prinz JC. · Department of Dermatology, Hôpital L'Archet II, 15 rue de Saint Antoine de Ginestiere, BP 079, Nice, France. · Eur J Dermatol. · Pubmed #14965795 links to  free full text

Abstract: Psoriasis is a chronic immune-mediated disease affecting the skin and sometimes the joints. Approximately 14 million people in Europe have psoriasis and the disease has a profound effect on the quality of life of patients worldwide. Currently available therapies for psoriasis have several shortcomings, including organ-based toxicity, generalized immunosuppression, short duration of response, and inconvenient regimens. Alefacept is a recombinant, fully human fusion protein that selectively targets the memory T cell population implicated in psoriasis pathogenesis. Alefacept is unique among psoriasis treatments because of its selective therapeutic action, ability to induce lengthy disease remissions even in the absence of continued therapy, positive effect on quality of life, and favorable safety profile. Two courses of alefacept confer greater efficacy and duration of clinical improvement versus that observed with a single course. This novel biologic agent is currently approved in the United States and under regulatory review in Europe for moderate to severe chronic plaque psoriasis.

Prinz JC. · Department of Dermatology, Ludwig-Maximilians-University, Frauenlobstr. 9-11, Munich 80337, Germany. · Autoimmun Rev. · Pubmed #14871644 No free full text.

Abstract: Molecular mimicry is considered as a mechanism by which infectious pathogens may break immunological tolerance and cause autoimmune disease. It implicates that peptides shared between pathogen and host may induce cross-reactive immune reactions. According to this hypothesis, the resulting autoimmune response actually represents a secondary immune response. It is mediated by cross-reactive T cells that have been educated in a primary immune response against a particular pathogen. Using psoriasis vulgaris as a model, this article discusses the potential functional consequences molecular mimicry should have for the resulting autoimmune disease. It proposes that due to the functional memory of T cells, which is an integral feature of adaptive immunity, the phenotype of an autoimmune disease induced by molecular mimicry should reflect the immune mechanisms raised in the primary immune response. This process might be called 'disease mimicry'.

Prinz JC. · Department of Dermatology, Ludwig-Maximilians University, Frauenlobstrausse 9-11, D-80337 Munich, Germany. · J Eur Acad Dermatol Venereol. · Pubmed #12702062 No free full text.

Abstract: Evidence for a key role of T cells in the pathogenesis of psoriasis has come from both experimental and clinical data. Initially, generalized immunosuppressants, intended for use in transplant settings, were found to improve clinical signs and symptoms of psoriasis. Their efficacy attracted attention to the activated T cells that are a major component of the inflammatory infiltrate of psoriatic lesions. Further research determined that T cells from patients with psoriasis could transmit disease in animal models. These findings laid the groundwork for characterizing the pathogenesis of psoriasis as immune mediated with skin-directed T cells playing a central role. Once these pathogenic T cells have entered the skin, they become activated and release cytokines and chemokines to attract other immune cells to perpetuate the inflammatory cascade. As the role of the T cell in psoriasis has evolved and understanding of immunopathology has increased, a multitude of biologic targets have been revealed. Newer strategies for the treatment of psoriasis have therefore focused on modifying T cells in this disease through direct elimination of activated T cells, inhibition of T-cell activation, or inhibition of cytokine secretion or activity. The mechanisms by which these new biologic agents act on psoriasis will affect their profile of efficacy and safety. Important selection criteria for optimal antipsoriatic therapies include long-term safety and tolerability, ability to produce long-lasting remissions, and convenient dosing regimens.

Prinz JC. · Department of Dermatology, University of Munich, Frauenlobstr. 9-11, D-80337 Munich, Germany. · Clin Exp Dermatol. · Pubmed #11422184 No free full text.

Abstract: The understanding of the pathogenesis of psoriasis vulgaris has advanced significantly since the therapeutic efficacy of immunosuppressive drugs has drawn attention to the role of immune mechanisms in psoriasis manifestation. Today, the results of many experimental studies provide evidence that psoriasis is largely a T-cell mediated disorder. It may result from antigen-specific activation of T cells in the skin of genetically predisposed individuals. These T cells apparently have a particular functional differentiation and promote the psoriatic skin changes by secreting a certain set of cytokines. Based on the fact that streptococcal throat infections are a trigger of guttate psoriasis, the putative psoriatic antigens are assumed to be in keratinocyte proteins that share structural homologies with streptococcal proteins and thus induce cross-reactive responses of antibacterial T cells against skin components. Together with the particular phenotype of psoriatic skin lesions these findings suggest that psoriasis represents a sterile antibacterial tissue reaction, which is mediated by streptococci-specific T cells that cross-react against epidermal autoantigens.

Prinz JC. · Department of Dermatology, Klinikum Innenstadt, Ludwig-Maximilians-University, Munich, Germany. · Clin Exp Dermatol. · Pubmed #10457134 No free full text.

Abstract: Today, T cells appear to be the main protagonists in the pathogenesis of psoriasis vulgaris. This article summarizes how T cells might contribute to the generation of psoriatic skin lesions. It discusses the preferential T cell receptor usage and the putative mode of T cell activation in psoriatic skin lesions, and how streptococcal throat infections could be involved in disease manifestations. The results are integrated into a pathogenetic concept which considers psoriasis as a T-cell mediated autoimmune disorder.

Campione E, Mazzotta A, Paternò EJ, Diluvio L, Prinz JC, Chimenti S. · Department of Dermatology, University of Rome Tor Vergata Viale Oxford 81, Rome, Italy. · Acta Derm Venereol. · Pubmed #19479128 No free full text.

Abstract: Patients who respond only partially to etanercept may require additional treatments that act synergistically to improve their therapeutic response while at the same time reducing the dose required and the risk of side-effects. The aim of this study was to evaluate the effecti veness of topical calcipotriol in etanercept partial responder patients. We enrolled 120 patients affected by psoriasis vulgaris and psoriatic arthritis. A 50 mg dose of etanercept was administered twice weekly for the first 12 weeks, followed by a 25 mg dose twice weekly for an additional 12 weeks. At week 12, for 45 patients who had not achieved PASI 50, calcipotriol cream was also prescribed twice daily for 4 weeks and then once daily for a further 8 weeks. At week 24, of the 45 patients in the group treated with etanercept plus calcipotriol, 14 (31.1%) had achieved PASI 75, and 23 PASI 50, while 8 (17.7%) had dropped out of therapy; of the 75 patients who continued etanercept in monotherapy with a 25 mg dose twice weekly for another 12 weeks, 71 (94.6%) had achieved PASI 50 and 57 (76.0%) PASI 75. The application of calcipotriol in etanercept partial responder patients had therefore helped 37 out of 120 patients (31%) achieve at least PASI 50. This is the first report about the controlled combination of topical calcipotriol and etanercept in a large group of psoriatic patients. The efficacy and cost-effectiveness of the combined treatment is evidenced by the good response shown at week 24 by a group of etanercept low-responder patients using drugs sparingly and limiting likely toxicity.

Prinz JC. · Klinik und Poliklinik für Dermatologie der Ludwig-Maximilians-Universität München, Frauenlobstrasse 9-11, 80337 München. · Hautarzt. · Pubmed #19319491 No free full text.

This publication has no abstract.

Peric M, Koglin S, Kim SM, Morizane S, Besch R, Prinz JC, Ruzicka T, Gallo RL, Schauber J. · Department of Dermatology and Allergology, Ludwig-Maximilians-University, Munich, Germany. · J Immunol. · Pubmed #19050268 links to  free full text

Abstract: Cathelicidin is strongly expressed in lesional skin in psoriasis and may play an important role as both an antimicrobial peptide and as an autoinflammatory mediator in this chronic skin disease. The mechanism of increased cathelicidin in psoriatic keratinocytes is not known, but recent observations have found that psoriasis has abundant Th17 cells that produce IL-17A and IL-22. We found that human keratinocytes stimulated with supernatants from T cells isolated from lesional psoriatic skin increased expression of cathelicidin when stimulated in the presence of 1,25-dihydroxyvitamin D(3) (1,25D(3)). This increase was signaled through the IL-17RA. In vitro, IL-17A, but not IL-22, enhanced cathelicidin mRNA and peptide expression in keratinocytes dependent on the presence of 1,25D(3). At the same time, coincubation with 1,25D(3) blocked induction of human beta-defensin 2 (HBD2), IL-6, and IL-8, which are other target genes of IL-17A. Act1, an adaptor associated with IL-17RA and essential for IL-17A signaling, mediated cathelicidin induction, as its suppression by small interfering RNA inhibited HBD2 and cathelicidin. Both, 1,25D(3) and IL-17A signaled cathelicidin induction through MEK-ERK. These results suggest that increased IL-17A in psoriatic skin increases cathelicidin through a vitamin D(3)-, Act1-, and MEK-ERK-dependent mechanism. Therapy targeting this cathelicidin-regulating system might be beneficial in patients suffering from psoriasis.

Weisenseel P, Kuznetsov AV, Flaig M, Prinz JC. · Department of Dermatology, Ludwig Maximilian University, Munich, Germany. · Dermatology. · Pubmed #18446030 No free full text.

Abstract: Molluscum contagiosum is a common viral skin infection in children with atopic diathesis and not rare in HIV patients. We report a 45-year-old psoriasis patient who developed eruptive mollusca contagiosa during an antipsoriatic treatment with efalizumab.

Weisenseel P, Prinz JC. · Department of Dermatology, Ludwig-Maximilians-University, Munich, Germany. · Cutis. · Pubmed #17036664 No free full text.

Abstract: Generalized pustular psoriasis is a dramatic potentially life-threatening psoriasis variant and represents a major therapeutic challenge. Tumor necrosis factor alpha (TNF-alpha) inhibitors have been shown to be highly effective in psoriasis vulgaris and psoriasis arthritis. Currently, TNF-alpha can be targeted therapeutically by 2 different approaches. TNF-alpha antibodies show a fast onset of action and a long-lasting activity. Soluble TNF-alpha receptors have a slower onset and a shorter duration of activity, which allows a rapid cessation of the drug's activity in the case of adverse events. Here we report that a remission of generalized pustular psoriasis achieved by the TNF-alpha antibody infliximab was maintained by long-term application of the soluble TNF-alpha receptor etanercept. Sequential therapy with TNF-alpha antibodies and TNF-alpha receptors may represent a novel concept that combines a rapid onset of action in the initiation therapy with a lower risk for severe adverse events in the maintenance treatment of pustular psoriasis.

Boehncke WH, Brasie RA, Barker J, Chimenti S, Daudén E, de Rie M, Dubertret L, Giannetti A, Katsambas A, Kragballe K, Naeyaert JM, Ortonne JP, Peyrí J, Prinz JC, Saurat JH, Strohal R, van de Kerkhof P, Sterry W, Anonymous00010. · Johann Wolfgang Goethe-University, Frankfurt, Germany. · J Eur Acad Dermatol Venereol. · Pubmed #16922950 No free full text.

Abstract: BACKGROUND: Psoriasis is a chronic, inflammatory skin disorder that has a significant impact on quality of life and, particularly in moderate to severe cases, adversely affects the patient's overall health and well-being. Biological treatments, such as etanercept, are being widely adopted across Europe for treatment of moderate to severe psoriasis due to favourable safety and efficacy profiles. The increase in usage, combined with a growing body of clinical evidence, has identified a need to clarify the best use of etanercept within its current treatment label. OBJECTIVE: To prepare a series of recommendations agreed by an expert group of dermatologists, relating to the most effective use of etanercept for psoriasis in Europe, within the product license. METHODS: An expert panel of dermatologists from across Europe completed a Delphi survey to address the current use of etanercept in psoriasis in Europe. In June 2005 the results were presented to the expert panel at their nominal group meeting, and a consensus was agreed. RESULTS: It was recommended that, where possible, patients are initiated on the 50 mg twice-weekly (BIW) dose. Etanercept should be given until remission is achieved (maximum 24 weeks) and retreatment should be initiated according to the physician's judgement. Before commencing treatment, contraindications, such as infection or previous malignancy (within 5 years), should be ruled out. CONCLUSIONS: The consensus presented herein provides valuable clarification of use of etanercept according to the label, which may have wider implications relating to the use of all biological therapies in psoriasis.

Diluvio L, Vollmer S, Besgen P, Ellwart JW, Chimenti S, Prinz JC. · Department of Dermatology, Ludwig-Maximilians-University of Munich, Munich, Germany. · J Immunol. · Pubmed #16709873 links to  free full text

Abstract: Tonsillar infection with Streptococcus pyogenes may induce several nonsuppurative autoimmune sequelae. The precise pathogenetic mechanisms behind this clinically well-established association are still unresolved. Using TCR analysis, we sought to identify a link between streptococcal tonsillitis and the T cell-mediated autoimmune response in psoriasis. Three patients with streptococcal-induced psoriasis underwent tonsillectomy. Using size spectratyping and sequencing of TCR beta-chain variable region gene (TCRBV) rearrangements, we compared the TCR usage of psoriatic skin lesions, blood, tonsils, and tonsillar T cells fractionated according to the expression of the skin address in "cutaneous lymphocyte-associated Ag" (CLA). TCRBV-size spectratype analysis of the blood lymphocytes, tonsils, and the CLA-negative tonsillar T cells revealed largely unselected T cell populations. Instead, TCRBV gene families of the psoriatic lesions and skin-homing CLA-positive tonsillar T cells displayed highly restricted spectratypes. Sequencing of TCRBV cDNA identified various clonal TCRBV rearrangements within the psoriatic lesions that indicated Ag-driven T cell expansion. Several of these clonotypes were also detected within the tonsils and, in one of the patients, within the small subset of CLA-positive tonsillar T cells, suggesting that T cells from the same T cell clones were simultaneously present within skin and tonsillar tissue. Because after tonsillectomy psoriasis cleared in all three patients our observations indicate that T cells may connect psoriatic inflammation to streptococcal angina. They suggest that the chronic streptococcal immune stimulus within the tonsils could act as a source for pathogenic T cells in poststreptococcal disorders, and they may help to explain why eliminating this source with tonsillectomy may improve streptococcal-induced sequelae.

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.

Weisenseel P, Prinz JC. · Department for Dermatology, Ludwig Maximilians-University, Frauenlobstr. 9-11, 80337, Munich, Germany. · Arch Dermatol Res. · Pubmed #15856267 No free full text.

Abstract: Psoriasis vulgaris is a T cell-mediated autoimmune skin disease. First disease onset and disease worsening are often triggered by tonsillar infection with Streptococcus pyogenes. Here we demonstrate the incidental detection of S. pyogenes DNA in samples of different biological origin from patients with chronic plaque-type psoriasis by PCR. These findings may support the model of molecular mimicry in psoriasis pathogenesis.

Prinz JC. · Klinik und Poliklinik für Dermatologie und Allergologie der LMU München, Munich. · Hautarzt. · Pubmed #12634988 No free full text.

Abstract: During recent years the understanding of psoriasis pathogenesis has changed essentially. Psoriasis is now considered as a T cell mediated inflammation of the skin. Genetic predisposition and microbial environment cooperate in the induction of an antigen-specific T cell mediated immune response which may persist lifelong. The phenotype of the psoriatic inflammation is determined by the particular functional differentiation of the pathogenic T cells. The progress in understanding the pathogenesis of psoriasis has identified T cells and T cell-derived cytokines as targets for causal treatment approaches that in the near future will change psoriasis therapy considerably.

Weisenseel P, Laumbacher B, Besgen P, Ludolph-Hauser D, Herzinger T, Roecken M, Wank R, Prinz JC. · No affiliation provided · J Med Genet. · Pubmed #12362037 links to  free full text

This publication has no abstract.

Vollmer S, Menssen A, Prinz JC. · Department of Dermatology, Ludwig Maximilians-University, Munich, Germany. · J Invest Dermatol. · Pubmed #11710947 links to  free full text

Abstract: In a previous study we reported that clonally expanded T cell receptor beta-chain rearrangements characterized the T cell receptor usage in skin lesions of psoriasis vulgaris and indicated antigen-specific T cell selection. To assess the relevance of clonal T cell expansion for disease progression, we now determined if select clonal T cell receptor rearrangements persisted over time and were present in nonlesional skin. Sequential biopsies were taken from psoriatic skin lesions of two patients. V-D-J junctional regions of T cell receptor beta-chain variable region gene families 2, 3, 6, 13S1, and BV17 were cloned and sequenced, as these particular BV gene families are preferentially selected in psoriatic skin lesions. The lesional T cell receptor rearrangements were compared with the T cell receptor usage in nonlesional skin and in blood. Several T cell receptor beta-chain rearrangements with high transcript frequency in the first lesional biopsy were again found in sequential lesional biopsies taken as much as 3 y later from psoriasis relapses. Only T cell receptor beta-chain rearrangements with low transcript abundance showed variability in that several clones appeared for the first time or disappeared. Although nonlesional skin also exhibited a restricted T cell receptor usage with clonal T cell receptor rearrangements, the T cell receptor usage in lesional and nonlesional skin differed nearly completely. The select lesional recurrence of identical T cell receptor rearrangements reveals that inflammation in psoriasis involves the same clonally expanded T cell populations and the same antigens over prolonged periods of time. It hereby suggests that specifically recruited and locally expanded T cell clones are permanently involved in psoriatic inflammation and may play a crucial part in disease perpetuation.

Prinz JC, Vollmer S, Boehncke WH, Menssen A, Laisney I, Trommler P. · Department of Dermatology University of Munich, Munich, Germany. · Eur J Immunol. · Pubmed #10540348 No free full text.

Abstract: Psoriasis vulgaris is a common HLA-associated inflammatory skin disease. Although its etiology is still unknown, it is thought to involve T cell-mediated inflammatory mechanisms. In examining the lesional psoriatic TCR beta chain (TCRB) usage in a pair of identical twins concordant for psoriasis, we observed repetitive TCR VDJ rearrangements which indicated antigen-specific oligoclonal T cell expansion. Several of these TCRB rearrangements were identical or highly homologous in the amino acid composition of the complementarity determining region 3 (CDR3), suggesting that T cells with these TCR might be important for disease manifestation. This conclusion was strengthened by TCR analysis of other psoriasis patients. Several repetitive lesional TCRB rearrangements were found that were similar to the conserved CDR3 seen in the twins. Since TCR antigen specificity is largely determined by the beta chain CDR3, selection of T cells with conserved TCRB CDR3 motifs could indicate the presence of a common antigen as a major target of the lesional psoriatic immune response.

Weisenseel P, Kuznetsov AV, Ruzicka T, Prinz JC. · No affiliation provided · Br J Dermatol. · Pubmed #17535244 No free full text.

This publication has no abstract.