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Topical calcineurin inhibitors in cutaneous lupus erythematosus

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Abstract

Calcineurin inhibitors are immunomodulator macrolides that block T cell activation in the skin. These molecules bind to macrophilin 12 to form a complex capable of blocking calcineurin, a protein that dephosphorylates, and thereby activates, the cytoplasmic subunit of nuclear factor of activated T cells (NF-AT). Thus, in the presence of calcineurin inhibitors, NF-AT cannot enter the nucleus and interact with the promoter regions of many cytokine genes. In addition to T cells, calcineurin inhibitors have also been shown to inhibit the activation of a number of other cell types in the skin immune system, including eosinophils, basophils, and Langerhans cells. These drugs are highly effective in treating atopic dermatitis, even in monotherapy, and they result in rapid, progressive, and sustained improvement. Additionally, calcineurin inhibitors are well tolerated for long-term treatment, and there are virtually no contraindications when using these medications on the face, eyelids, flexural skin, or mucous membranes. Although calcineurin inhibitors are immunomodulators, no significantly increased incidence of infections can be detected during therapy. Cutaneous lupus erythematosus is a chronic, autoimmune, inflammatory skin condition with a wide spectrum of skin manifestations, which presents a therapeutic challenge for dermatologists. In this review, the current treatment options for the different clinical subtypes of this disease are discussed. Therapy with topical calcineurin inhibitors is emphasized, and advantages and drawbacks, effects and side effects, treatment protocols, dosage, and expected outcome are described in detail.

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References

  1. Bacman D, Tanbajewa A, Megahed M, Ruzicka T, Kuhn A (2003) Topical treatment with tacrolimus in lupus erythematosus tumidus. Hautarzt 54:977–979. doi:10.1007/s00105-003-0593-3

    Article  PubMed  CAS  Google Scholar 

  2. Böhm M, Gaubitz M, Luger TA, Metze D, Bonsmann G (2003) Topical tacrolimus as a therapeutic adjunct in patients with cutaneous lupus erythematosus. A report of three cases. Dermatology 207:381–385. doi:10.1159/000074119

    Article  PubMed  CAS  Google Scholar 

  3. Breneman D, Fleischer AB Jr, Abramovits W, Zeichner J, Gold MH, Kirsner RS, Tacrolimus Ointment Study Group et al (2008) Intermittent therapy for flare prevention and long-term disease control in stabilized atopic dermatitis: a randomized comparison of 3-times-weekly applications of tacrolimus ointment versus vehicle. J Am Acad Dermatol 58:990–999. doi:10.1016/j.jaad.2008.02.008

    Article  PubMed  Google Scholar 

  4. de la Rosa Carrillo D, Christensen OB (2004) Treatment of chronic discoid lupus erythematosus with topical tacrolimus. Acta Derm Venereol 84:233–234. doi:10.1080/00015550310007698

    Article  PubMed  CAS  Google Scholar 

  5. de Prost Y (2004) Clinical experience in children. In: Ruzicka T, Reitamo S (eds) Tacrolimus ointment. A topical immunomodulator for atopic dermatitis. Springer, Heidelberg, pp 161–183

    Google Scholar 

  6. Draelos ZD (2008) Use of topical corticosteroids and topical calcineurin inhibitors for the treatment of atopic dermatitis in thin and sensitive skin areas. Curr Med Res Opin 24:985–994. doi:10.1185/030079908X280419

    Article  PubMed  CAS  Google Scholar 

  7. Drüke A, Gambichler T, Altmeyer P, Freitag M, Kreuter A (2004) 0.1% Tacrolimus ointment in a patient with subacute cutaneous lupus erythematosus. J Dermatolog Treat 15:63–64. doi:10.1080/09546630310017852

    Article  PubMed  Google Scholar 

  8. Gilliam JN, Sontheimer RD (1981) Distinctive cutaneous subsets in the spectrum of lupus erythematosus. J Am Acad Dermatol 4:471–475

    PubMed  CAS  Google Scholar 

  9. Goto T, Nakagawa H (2004) Development of tacrolimus ointment. In: Ruzicka T, Reitamo S (eds) Tacrolimus ointment. A topical immunomodulator for atopic dermatitis. Springer, Heidelberg, pp 81–98

    Google Scholar 

  10. Gupta AK, Chow M (2003) Pimecrolimus: a review. J Eur Acad Dermatol Venereol 17:493–503. doi:10.1046/j.1468-3083.2003.00692.x

    Article  PubMed  CAS  Google Scholar 

  11. Heffernan MP, Nelson MM, Smith DI, Chung JH (2005) 0.1% tacrolimus ointment in the treatment of discoid lupus erythematosus. Arch Dermatol 141:1170–1171. doi:10.1001/archderm.141.9.1170

    Article  PubMed  Google Scholar 

  12. Ho S, Clipstone N, Timmermann L, Northrop J, Graef I, Fiorentino D et al (1996) The mechanism of action of cyclosporin A and FK506. Clin Immunol Immunopathol 80(3 Pt 2):S40–S45. doi:10.1006/clin.1996.0140

    Article  PubMed  CAS  Google Scholar 

  13. Kanekura T, Yoshii N, Terasaki K, Miyoshi H, Kanzaki T (2003) Efficacy of topical tacrolimus for treating the malar rash of systemic lupus erythematosus. Br J Dermatol 148:353–356. doi:10.1046/j.1365-2133.2003.05186.x

    Article  PubMed  CAS  Google Scholar 

  14. Kreuter A, Gambichler T, Breuckmann F, Pawlak FM, Stücker M, Bader A et al (2004) Pimecrolimus 1% cream for cutaneous lupus erythematosus. J Am Acad Dermatol 51:407–410. doi:10.1016/j.jaad.2004.01.044

    Article  PubMed  Google Scholar 

  15. Kuhn A, Beissert S (2005) Photosensitivity in lupus erythematosus. Autoimmunity 38:519–529. doi:10.1080/08916930500285626

    Article  PubMed  CAS  Google Scholar 

  16. Kuhn A, Ruzicka T (2005) Classification of cutaneous lupus erythematosus. In: Kuhn A, Lehmann P, Ruzicka T (eds) Cutaneous lupus erythematosus. Springer, Heidelberg, pp 53–57

    Chapter  Google Scholar 

  17. Kuhn A, Sontheimer R, Ruzicka T (2005) Clinical manifestations of cutaneous lupus erythematosus. In: Kuhn A, Lehmann P, Ruzicka T (eds) Cutaneous lupus erythematosus. Springer, Heidelberg, pp 59–92

    Chapter  Google Scholar 

  18. Kuhn A, Sticherling M, Bonsmann G (2007) Clinical manifestations of cutaneous lupus erythematosus. J Dtsch Dermatol Ges 5:1124–1137. doi:10.1111/j.1610-0387.2007.06554.x

    Article  PubMed  Google Scholar 

  19. Lampropoulos CE, Sangle S, Harrison P, Hughes GR, D’Cruz DP (2004) Topical tacrolimus therapy of resistant cutaneous lesions in lupus erythematosus: a possible alternative. Rheumatology (Oxford) 43:1383–1385. doi:10.1093/rheumatology/keh325

    Article  CAS  Google Scholar 

  20. Lee LA (2007) Lupus erythematosus. In: Bolognia JL, Jorizzo JL, Rapini RP (eds) Dermatology, 2nd edn. Elsevier Ltd, Oxford, pp 561–569

    Google Scholar 

  21. Lehmann P (2005) Topical treatment of cutaneous lupus erythematosus. In: Kuhn A, Lehmann P, Ruzicka T (eds) Cutaneous lupus erythematosus. Springer, Heidelberg, pp 337–345

    Chapter  Google Scholar 

  22. Meller S, Bruch-Gerharz D, Ruzicka T, Homey B (2005) Topische Behandlung des subakut-kutanen Lupus erythematodes mit Tacrolimus. Hautarzt 56:368–369. doi:10.1007/s00105-005-0921-x

    Article  PubMed  CAS  Google Scholar 

  23. Reitamo S (2004) Clinical experience in adults. In: Ruzicka T, Reitamo S (eds) Tacrolimus ointment. A topical immunomodulator for atopic dermatitis. Springer, Heidelberg, pp 129–160

    Google Scholar 

  24. Ring J, Abraham A, de Cuyper C, Kim K, Langeland T, Parra V et al (2008) Control of atopic eczema with pimecrolimus cream 1% under daily practice conditions: results of a >2000 patient study. J Eur Acad Dermatol Venereol 22:195–203

    PubMed  CAS  Google Scholar 

  25. Ring J, Möhrenschlager M, Henkel V (2008) The US FDA ‘black box’ warning for topical calcineurin inhibitors: an ongoing controversy. Drug Saf 31:185–198

    Article  PubMed  CAS  Google Scholar 

  26. Sticherling M, Bonsmann G, Kuhn A (2008) Diagnostic approach and treatment of cutaneous lupus erythematosus. J Dtsch Dermatol Ges 6:48–59

    PubMed  Google Scholar 

  27. Sugano M, Shintani Y, Kobayashi K, Sakakibara N, Isomura I, Morita A (2006) Successful treatment with topical tacrolimus in four cases of discoid lupus erythematosus. J Dermatol 33:887–891. doi:10.1111/j.1346-8138.2006.00203.x

    Article  PubMed  Google Scholar 

  28. Ting WW, Sontheimer RD (2001) Local therapy for cutaneous and systemic lupus erythematosus: practical and theoretical considerations. Lupus 10:171–184. doi:10.1191/096120301667674688

    Article  PubMed  CAS  Google Scholar 

  29. Tlacuilo-Parra A, Guevara-Gutiérrez E, Gutiérrez-Murillo F, Soto-Ortiz A, Barba-Gómez F, Hernández-Torres M et al (2005) Pimecrolimus 1% cream for the treatment of discoid lupus erythematosus. Rheumatology (Oxford) 44:1564–1568. doi:10.1093/rheumatology/kei093

    Article  CAS  Google Scholar 

  30. Tzung TY, Liu YS, Chang HW (2007) Tacrolimus vs. clobetasol propionate in the treatment of facial cutaneous lupus erythematosus: a randomized, double-blind, bilateral comparison study. Br J Dermatol 156:191–192. doi:10.1111/j.1365-2133.2006.07595.x

    Article  PubMed  CAS  Google Scholar 

  31. von Pelchrzim R, Schmook T, Friedrich M, Worm M (2006) Efficacy of topical tacrolimus in the treatment of various cutaneous manifestations of lupus erythematosus. Int J Dermatol 45:84–85. doi:10.1111/j.1365-4632.2004.02539.x

    Article  Google Scholar 

  32. Walker SL, Kirby B, Chalmers RJ (2002) The effect of topical tacrolimus on severe recalcitrant chronic discoid lupus erythematosus. Br J Dermatol 147:405–406. doi:10.1046/j.1365-2133.2002.488616.x

    Article  PubMed  CAS  Google Scholar 

  33. Wollenberg A, Reitamo S, Atzori F, Lahfa M, Ruzicka T, Healy E and others for the European Tacrolimus Ointment Study Group (2008) Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment. Allergy 63:742–750. doi:10.1111/j.1398-9995.2008.01683.x

    Google Scholar 

  34. Wollina U, Hansel G (2008) The use of topical calcineurin inhibitors in lupus erythematosus: an overview. J Eur Acad Dermatol Venereol 22:1–6

    PubMed  CAS  Google Scholar 

  35. Woo DK, James WD (2005) Topical tacrolimus: a review of its uses in dermatology. Dermatitis 16:6–21. doi:10.2310/6620.2005.04045

    PubMed  Google Scholar 

  36. Wooltorton E (2005) Eczema drugs tacrolimus (Protopic) and pimecrolimus (Elidel): cancer concerns. CMAJ 172:1179–1180. doi:10.1503/cmaj.050373

    PubMed  Google Scholar 

  37. Yoshimasu T, Ohtani T, Sakamoto T, Oshima A, Furukawa F (2002) Topical FK506 (tacrolimus) therapy for facial erythematous lesions of cutaneous lupus erythematosus and dermatomyositis. Eur J Dermatol 12:50–52

    PubMed  Google Scholar 

  38. Zabawski E (2002) Treatment of cutaneous lupus with Elidel. Dermatol Online J 8:25

    PubMed  Google Scholar 

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Acknowledgments

This work was supported by a Heisenberg Scholarship from the German Research Foundation to A. K. (KU 1559/1-2). We thank Vincent Ruland for help in preparation of Table 1. The pictures were kindly provided by the Department of Dermatology of the University of Münster (with special thanks to P. Wissel, J. Bueckmann, and Prof. Dr. T. A. Luger).

Conflict of interest statement

The authors have no potential conflict of interest.

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Authors and Affiliations

  1. Department of Dermatology and Allergology, Ludwig-Maximilians University, Frauenlobstr. 9-11, 80337, Munich, Germany

    Miklós Sárdy & Thomas Ruzicka

  2. Department of Dermatology, Westfälische Wilhelms-University Münster, Von-Esmarch-Str. 58, 48149, Münster, Germany

    Annegret Kuhn

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  1. Miklós Sárdy
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Correspondence to Miklós Sárdy.

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Sárdy, M., Ruzicka, T. & Kuhn, A. Topical calcineurin inhibitors in cutaneous lupus erythematosus. Arch Dermatol Res 301, 93–98 (2009). https://doi.org/10.1007/s00403-008-0894-6

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