Skip to main content
SpringerLink
Log in

Neue Immunsuppressiva in der Therapie der Psoriasis

  • Leitthema
  • Published:
Der Hautarzt Aims and scope Submit manuscript

Zusammenfassung

Die Psoriasis ist eine genetisch determinierte, immunologisch mediierte, chronische Erkrankung der Haut. Im Mittelpunkt des Entzündungsgeschehens stehen T-Lymphozyten, die durch Produktion und Ausschüttung verschiedener proinflammatorischer Zytokine den Entzündungsvorgang initiieren und unterhalten und dabei Keratinozyten zur überschießenden Proliferation anregen. Die stimulierten Keratinozyten treten in eine beschleunigte, aber unvollständige Differenzierung. Dabei exprimieren sie Rezeptoren, die sie für Entzündungssignale empfindlich machen und setzen zusätzlich selbst Entzündungsmediatoren frei. So wird die psoriatische Entzündung durch eine gegenseitige Stimulation zwischen Leukozyten und Keratinozyten unterhalten. Dieser komplexe Ablauf auto- und parakriner Stimulationsmechanismen kann durch Immunsuppressiva recht gut unspezifisch unterdrückt werden, insbesondere am T-Zell-Schenkel. Im Folgenden werden Wirkmechanismen, Effizienz und Nebenwirkungen wichtiger Immunsuppressiva wie Methotrexat, Ciclosporin A, Tacrolimus, Pimecrolimus dargestellt und der Stellenwert der Therapie mit Mycophenolat Mofetil und Fumarsäureester diskutiert.

Abstract

Accumulative evidence suggests that psoriasis may be a genetically determined immunologenic inflammatory disorder based on an ongoing autoreactive Th-1 response. Various cytokines (e.g. IL-2, interferon-gamma etc.) are released and exert proliferative signals on to keratinocytes, which start proliferation that finally results in an incomplete differentiation. During this pathobiological process keratinocytes themselves express receptors that make them sensitive for growth inducing stimulation and also start the production of a set of cytokines that contribute to and maintain inflammation. Immunosuppressive agents, mostly by affecting T-cells may interfere with or even disrupt by rather unspecific mechanisms, this complex process of mutual stimulation of leucocytes and keratinocytes. In this manuscript we show mode of action, efficacy and side effects of Methotrexate, Ciclosporin A, Tacrolimus and Pimecrolimus, and discuss therapeutic options with mycophenolate mofetil and fumaric acid esters.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Al-Daraji WI, Grant KR, Ryan K et al. (2002) Localization of calcineurin/NFAT in human skin and psoriasis and inhibition of calcineurin/NFAT activation in human keratinocytes by cyclosporin A. J Invest Dermatol 118:779–788

    Google Scholar 

  2. Ali H, Ahamed J, Hernandez-Munain C et al. (2000) Chemokine production by G-protein-coupled receptoractivation in a human mast cell line: roles of extracellular signal-regulated kinase and NFAT. J Immunol 165:7215–7232

    Google Scholar 

  3. Bornhövdt EC, Schuller E, Bieber T, Wollenberg A (2000) Immunsuppressive Makrolide und ihr Einsatz in der Dermatologie. Hautarzt 51:646–654

    Google Scholar 

  4. Chen J, Fangy (2002) A novel pathway regulating the mammalian target of rapamycin (mTOR) signaling. Bloch Pharmacol 64:1071–1077

  5. Erdogan M, Wright JR Jr, McAlister VC (2002) Liposomal tacrolimus lotion as a novel agent for the treatment of immune mediated skin disorders:experimental studies in a murine model. Br J Dermatol 146:964–967

    Google Scholar 

  6. Evans WE, Christensen ML (1985) Drug interactions with methotrexate. J Rheumatol 12 [Suppl 12]:15–20

    Google Scholar 

  7. Geilen CC, Arnold M, Orfanos CE (2001) Mycophenolate mofetil as a systemic antipsoriatic agent: positive experience in 11 patients. Br J Dermatol 144:583–58G

    Google Scholar 

  8. Griffiths CE, Vorhees JJ (1996) Psoriasis, T cells and autoimmunity. J R Soc Med 89:315–319

    Google Scholar 

  9. Hackstein H, Taner T, Zahorchak AF et al. (2003) Rapamycin inhibits IL-4-induced dendritic cell maturation in vitro and dendritic cell mobilization and function in vivo. Blood, epub ahead of print

  10. Jegasothy BV, Ackerman CD, Fung JJ et al. (1992) Tacrolimus (FK506): a new therapeutic agentfor severe recalcitrant psoriasis. Arch Dermatol 128:781–785

    Google Scholar 

  11. Kalthoff FS, Chung J, Stuetz A (2002) Pimecrolimus inhibits up-regulation of OX40 and synthesis of inflammatory cytokines upon secondary T cell activation by allogeneic dendritic cells. Clin Exp Immunol 130:85–92

    Google Scholar 

  12. MacDonald AS, The Rapamune Global Study Group (2001) A worldwide, phase III, randomized, controlled, safety and efficacy study of a sirolimus/cyclosporine regimen for prevention of acute rejection in recipients of primaly mismatched renal allografts. Transplantation 71:271–280

    Google Scholar 

  13. Marinari R, Fleischmajer R, Schragger AH, Rosenthal AL (1977) Mycophenolic acid in the treatment of psoriasis: long-term administration. Arch Denmatol 113:930–1032

    Google Scholar 

  14. Mihatsch MJ, Wolff K (1992) Consensus conference on cyclosprin A for psoriasis February 1992. Br J Dermatol126:621–623

    Google Scholar 

  15. Mrowietz U, Gräber M, Bräutigam M et al. (1998) The novel ascomycin derivative SDZ ASM 981 is effective for psoriasis when used topically under occlusion. Br J Dermatol 139:992–996

    Google Scholar 

  16. Mrowietz U, Christophers E, Altmeyer P, for the German fumaric acid ester consensus conference (1999) Treatment of severe psoriasis with fumaric acid esters: scientific background and guidelines for therapeutic use. Br J Dermatol 141:424–429

    Google Scholar 

  17. Prens EP, van Joost T, Hegmans JP et al. (1995) Effects of cyclosporine on cytokines and cytokine receptors in psoriasis. J Am Acad Dermatol 33:947–953

    Google Scholar 

  18. Rappersberger K, Meingassner JG, Fialla R et al. (1996) Clearing of psoriasis by a novel immunosuppressive Macrolide. J Invest Dermatol 106:701–771

    Google Scholar 

  19. Rappersberger K, Komar M, Ebelin ME et al. (2002) Pimecrolimus identifies a common genomic anti-inflammatory profile, is clinically highly effective in psoriasis and is well tolerated. J Invest Dermatol 119:876–887

    Google Scholar 

  20. Reich K, Hummel KM, Beckmann I et al. (2002) Treatment of severe psoriasis and psoriatic arthritis with leflunomide. Br J Dermatol 146:335–336

    Google Scholar 

  21. Reitamo S, Spuls P, Sassolas B et al. (for the sirolimus european psoriasis study group) (2001) Efficacy of sirolimus (rapamycin) administered concomitantly with a subtherapeutic dose of cyclosporin in the treatment of severe psoriasis: a randomized controlled trial. Br J Dermatol 145:438–445

    Google Scholar 

  22. Reynolds NJ, Al-Daraji (2002) Calcineurin inhibitors and sirolimus: mechanisms of action and applications in dermatology. Clin Exp Dermatol 127:555–561

  23. Roenigk HH Jr, Auerbach R, Maibach H et al. (1998) Methotrexate in psoriasis: consensus conference. J Am Acad Dermatol 38:487–498

    Google Scholar 

  24. Schulz BS, Michel G, Wagner S et al. (1993) Increased expression of epidermal IL-8 expression in psoriasis. Downregulation by FK506 in vitro. J Immunol 151:4399–4406

    Google Scholar 

  25. Shaw AS, Dustin ML (199997) Making the T-cell receptor go the distance. A topological view of T-cell activation. Immunity 6:361–369

    Google Scholar 

  26. Stepkowski SM, Tian L, Napoli KL et al. (1997) Synergistic mechanisms by which sirolimus and cyclosporin inhibit rat heart and kidney allograft rejection. Clin Exp Immunol 198:63–68

    Google Scholar 

  27. Stuetz A, Grassberger M, Meingassner JG (2001) Pimecrolimus (Elidel, SDZ ASM 981)-preclinical pharmacologic profile ans skin selectivity. Sem Cut Med Surg 20:233–241

    Google Scholar 

  28. The European FK-506 multicenter psoriasis study group (1996) Systemic Tacrolimus (FK-506) is effective for the treatment of psoriasis in a double blind, placebo controlled study. Arch Dermatol 132:419–423

    Google Scholar 

  29. Wohlrab J, Jahn K, Plätzer M et al. (2001) Topical application of mycophenolate mofetil in plaque-type psoriasis. Br J Dermatol 144:1263–1264

    Google Scholar 

  30. Wollenberg A, Sharma S, von Bubnoff D et al. (2001) Topical tacrolimus (FK506) leads to profound phenotypic and functional alterations of epidermal antigen-presenting dendritic cells in atopic dermatitis. J Allergy Clin Immunol 107:519–525

    Google Scholar 

  31. Wozel G, Pfeiffer C (2002) Leflunomide a new drug for pharmacological immunomodulation. Hautarzt 53:309–315

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dermatologische Abteilung Krankenanstalt Rudolfstiftung, Wien

    K. Rappersberger

  2. Department of Dermatology, Stanford Medical School, Stanford

    S. Ortiz-Urda

  3. Krankenanstalt Rudolfstiftung, Juchgasse 25, 1030 , Wien, Österreich

    K. Rappersberger

Authors
  1. S. Ortiz-Urda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Rappersberger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. Rappersberger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ortiz-Urda, S., Rappersberger, K. Neue Immunsuppressiva in der Therapie der Psoriasis. Hautarzt 54, 230–236 (2003). https://doi.org/10.1007/s00105-003-0499-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00105-003-0499-0

Schlüsselwörter

Keywords

Search

Navigation