Skip to main content

Advertisement

SpringerLink
Log in

Topical Macrolide Immunomodulators

A Role in the Treatment of Vitiligo?

  • Current Opinion
  • Published:
American Journal of Clinical Dermatology Aims and scope Submit manuscript

Abstract

Recently, topical macrolide immunomodulators have been successfully introduced in the treatment of atopic dermatitis. With the growing interest in this new line of topical immunosuppressants, research into the efficacy of these medicines in other T-cell-mediated skin diseases, such as psoriasis, lichen planus, and even vitiligo, is expanding rapidly. It is generally accepted that autoimmune factors play an important role in vitiligo. In this article, the possible use and mechanism of topical macrolide immunomodulators in the treatment of vitiligo are discussed, together with the current state of clinical studies and case reports. These limited reports indicate that topical macrolide immunomodulators may play a role in the treatment of vitiligo, particularly in areas where use of potent corticosteroids is contraindicated.

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

Fig. 1
Table I

Similar content being viewed by others

References

  1. Le Poole C, van den Wijngaard RM, Westerhof W, et al. Presence of T cells and macrophages in inflammatory vitiligo skin parallels melanocyte disappearance. Am J Pathol. 1996; 148 (4): 1219–28

    PubMed  CAS  Google Scholar 

  2. Tobin DJ, Swanson NN, Pittelkow MR, et al. Melanocytes are not absent in lesional skin of long duration vitiligo. J Pathol. 2000; 191 (4): 407–16

    Article  PubMed  CAS  Google Scholar 

  3. Jacobson DL, Gange SJ, Rose NR, et al. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol. 1997; 84 (3): 223–43

    Article  PubMed  CAS  Google Scholar 

  4. Nath SK, Majumder PP, Nordlund JJ. Genetic epidemiology of vitiligo: multilocus recessivity cross-validated. Am J Hum Genet. 1994; 55 (5): 981–90

    PubMed  CAS  Google Scholar 

  5. Njoo MD, Westerhof W. Vitiligo: pathogenesis and treatment. Am J Clin Dermatol. 2001; 2 (3): 167–81

    Article  PubMed  CAS  Google Scholar 

  6. van den Wijngaard R, Wankowicz-Kalinska A, Le Poole C, et al. Local immune response in skin of generalized vitiligo patients: destruction of melanocytes is associated with the prominent presence of CLA+ T cells at the perilesional site. Lab Invest. 2000; 80 (8): 1299–309

    Article  PubMed  Google Scholar 

  7. van den Wijngaard R, Wankowicz-Kalinska A, Pals S, et al. Autoimmune melanocyte destruction in vitiligo. Lab Invest. 2001; 81 (8): 1061–7

    PubMed  Google Scholar 

  8. Montes LF, Abulafia J, Wilbom WH, et al. Value of histopathology in vitiligo. Int J Dermatol. 2003; 42 (1): 57–61

    Article  PubMed  Google Scholar 

  9. Lemer AB. Vitiligo. J Invest Dermatol. 1959; 32 (2 Pt 2): 285-310

    Google Scholar 

  10. Schallreuter KU, Wood JM, Berger J. Low catalase levels in the epidermis of patients with vitiligo. J Invest Dermatol. 1991; 97 (6): 1081–5

    Article  PubMed  CAS  Google Scholar 

  11. Schallreuter KU. Effectiveness of pseudocatalase formulations in vitiligo. Clin Exp Dermatol. 2003; 28 (5): 562–3

    Article  PubMed  CAS  Google Scholar 

  12. Moellmann G, Klein-Angerer S, Scollay DA, et al. Extracellular granular material and degeneration of keratinocytes in the normally pigmented epidermis of patients with vitiligo. J Invest Dermatol. 1982; 79 (5): 321–30

    Article  PubMed  CAS  Google Scholar 

  13. Hafez M, Sharaf L, Abd et-Nabi SM. The genetics of vitiligo. Acta Derm Venereol. 1983; 63 (3): 249–51

    PubMed  CAS  Google Scholar 

  14. Kim SM, Chung HS, Hann SK. The genetics of vitiligo in Korean patients. Int J Dermatol. 1998; 37 (12): 908–10

    Article  PubMed  CAS  Google Scholar 

  15. Le Poole IC, Das PK, van den Wijngaard RM, et al. Review of the etiopathomechanism of vitiligo: a convergence theory. Exp Dermatol. 1993; 2 (4): 145–53

    Article  PubMed  CAS  Google Scholar 

  16. Tjioe M, Gerritsen MJ, Juhlin L, et al. Treatment of vitiligo vulgaris with narrow band UVB (311 nm) for one year and the effect of addition of folic acid and vitamin B12. Acta Derm Venereol. 2002; 82 (5): 369–72

    Article  PubMed  CAS  Google Scholar 

  17. Njoo MD, Spuls PI, Bos JD, et al. Nonsurgical repigmentation therapies in vitiligo: meta-analysis of the literature. Arch Dermatol. 1998; 134 (12): 1532–40

    Article  PubMed  CAS  Google Scholar 

  18. British Photodermatology Group guidelines for PUVA. Br J Dermatol J 1994; 130 (2): 246–55

    Article  Google Scholar 

  19. Stern RS, Laird N. The carcinogenic risk of treatments for severe psoriasis: photochemotherapy follow-up study. Cancer. 1994; 73 (11): 2759–64

    Article  PubMed  CAS  Google Scholar 

  20. Stern RS. The risk of melanoma in association with long-term exposure to PUVA. J Am Acad Dermatol. 2001; 44 (5): 755–61

    Article  PubMed  CAS  Google Scholar 

  21. Westerhof W, Nieuweboer-Krobotova L. Treatment of vitiligo with UV-B radiation vs topical psoralen plus UV-A. Arch Dermatol. 1997; 133 (12): 1525–8

    Article  PubMed  CAS  Google Scholar 

  22. Tjice M, Smits T, Van De Kerkhof PCM, et al. The differential effect of broad band versus narrow band UVB with respect to photodamage and cutaneous inflammation. Exp Dermatol. 2003; 12 (6): 729–33

    Article  Google Scholar 

  23. Njoo MD, Westerhof W, Bos JD, et al. A systematic review of autologous transplantation methods in vitiligo. Arch Dermatol. 1998; 134 (12): 1543–9

    Article  PubMed  CAS  Google Scholar 

  24. Eichenfield LF, Lucky AW, Boguniewicz M, et al. Safety and efficacy of pimecrolimus (ASM 981) cream 1% in the treatment of mild and moderate atopic dermatitis in children and adolescents. J Am Acad Dermatol. 2002; 46 (4): 495–504

    Article  PubMed  Google Scholar 

  25. Mrowietz U, Graeber M, Brautigam M, et al. The novel ascomycin derivative SDZ ASM 981 is effective for psoriasis when used topically under occlusion. Br J Dermatol. 1998; 139 (6): 992–6

    Article  PubMed  CAS  Google Scholar 

  26. Rappersberger K, Meingassner JG, Fialla R, et al. Clearing of psoriasis by a novel immunosuppressive macrolide. J Invest Dermatol. 1996; 106 (4): 701–10

    Article  PubMed  CAS  Google Scholar 

  27. Lener EV, Brieva J, Schachter M, et al. Successful treatment of erosive lichen planus with topical tacrolimus. Arch Dermatol. 2001; 137 (4): 419–22

    PubMed  CAS  Google Scholar 

  28. Vente C, Reich K, Rupprecht R, et al. Erosive mucosal lichen planus: response to topical treatment with tacrolimus. Br J Dermatol. 1999; 140 (2): 338–42

    Article  PubMed  CAS  Google Scholar 

  29. Richter-Hintz D, Schuppe HC, Homey B, et al. Topical tacrolimus (FK 506) is effective in the treatment of pyoderma gangrenosum. J Am Acad Dermatol. 2000; 42 (2 Pt 1): 304–5

    Article  PubMed  CAS  Google Scholar 

  30. Reich K, Vente C, Neumann C. Topical tacrolimus for pyoderma gangrenosum. Br J Dermatol. 1998; 139 (4): 755–7

    Article  PubMed  CAS  Google Scholar 

  31. Grimes PE, Soriano T, Dytoc MT. Topical tacrolimus for repigmentation of vitiligo. J Am Acad Dermatol. 2002; 47 (5): 789–91

    Article  PubMed  Google Scholar 

  32. Reynolds NJ, Al Daraji WI. Calcineurin inhibitors and sirolimus: mechanisms of action and applications in dermatology. Clin Exp Dermatol. 2002; 27 (7): 555–61

    Article  PubMed  CAS  Google Scholar 

  33. Assmann T, Homey B, Ruzicka T. Applications of tacrolimus for the treatment of skin disorders. Immunopharmacology. 2000; 47 (2-3): 203–13

    Article  PubMed  CAS  Google Scholar 

  34. Bornhovd EC, Schuller E, Bieber T, et al. Immunosuppressive macrolides and their use in dermatology [in German]. Hautarzt. 2000; 51 (9): 646–54

    Article  PubMed  CAS  Google Scholar 

  35. Nghiem P, Pearson G, Langley RG. Tacrolimus and pimecrolimus: from clever prokaryotes to inhibiting calcineurin and treating atopic dermatitis. J Am Acad Dermatol. 2002; 46 (2): 228–41

    Article  PubMed  Google Scholar 

  36. Castanet J, Ortonne JP. Pathophysiology of vitiligo. Clin Dermatol. 1997; 15 (6): 845–51

    Article  Google Scholar 

  37. Ogg GS, Rod Dunbar P, Romero P, et al. High frequency of skin-homing melanocyte-specific cytotoxic T lymphocytes in autoimmune vitiligo. J Exp Med. 1998; 188 (6): 1203–8

    Article  PubMed  CAS  Google Scholar 

  38. Yeo UC, Yang YS, Park KB, et al. Serum concentration of the soluble interleukin-2 receptor in vitiligo patients. J Dermatol Sci. 1999; 19 (3): 182–8

    Article  PubMed  CAS  Google Scholar 

  39. Caixia T, Hongwen F, Xiran L. Levels of soluble interleukin-2 receptor in the sera and skin tissue fluids of patients with vitiligo. J Dermatol Sci. 1999; 21 (1): 59–62

    Article  PubMed  CAS  Google Scholar 

  40. Grimes PE, Morris R, Avaniss-Aghajani E, et al. Topical tacrolimus therapy for vitiligo: therapeutic responses and skin messenger RNA expression of proinflammatory cytokines. J Am Acad Dermatol. 2004; 51 (1): 52–61

    Article  PubMed  Google Scholar 

  41. Lepe V, Moncada B, Castanedo-Cazares JP, et al. A double-blind randomized trial of 0.1% tacrolimus vs 0.05% clobetasol for the treatment of childhood vitiligo. Arch Dermatol. 2003; 139 (5): 581–5

    Article  PubMed  CAS  Google Scholar 

  42. Tanghetti EA. Tacrolimus ointment 0.1 % produces repigmentation in patients with vitiligo: results of a prospective patient series. Cutis. 2003; 71 (2): 158–62

    PubMed  Google Scholar 

  43. Travis LB, Weinberg JM, Silverberg NB. Successful treatment of vitiligo with 0.1% tacrolimus ointment. Arch Dermatol. 2003; 139 (5): 571–4

    Article  PubMed  Google Scholar 

  44. Castanedo-Cazares JP, Lepe V, Moncada B. Repigmentation of chronic vitiligo lesions by following tacrolimus plus ultraviolet-B-narrow-band. Photodermatol Photoimmunol Photomed. 2003; 19 (1): 35–6

    Article  PubMed  CAS  Google Scholar 

  45. Smith DA, Tofte SJ, Hanifin JM. Repigmentation of vitiligo with topical tacrolimus. Dermatology. 2002; 205 (3): 301–3

    Article  PubMed  CAS  Google Scholar 

  46. Mayoral FA, Gonzalez C, Shah NS, et al. Repigmentation of vitiligo with pimecrolimus cream: a case report. Dermatology. 2003; 207 (3): 322–3

    Article  PubMed  Google Scholar 

  47. Reitamo S, Rissanen J, Remitz A, et al. Tacrolimus ointment does not affect collagen synthesis: results of a single-center randomized trial. J Invest Dermatol. 1998; 111 (3): 396–8

    Article  PubMed  CAS  Google Scholar 

  48. Bos JD. Topical tacrolimus and pimecrolimus are not associated with skin atrophy [letter]. Br J Dermatol. 2002; 146 (2): 342

    Article  PubMed  CAS  Google Scholar 

  49. Queille-Roussel C, Paul C, Duteil L, et al. The new topical ascomycin derivative SDZ ASM 981 does not induce skin atrophy when applied to normal skin for 4 weeks: a randomized, double-blind controlled study. Br J Dermatol. 2001; 144 (3): 50–13

    Article  Google Scholar 

  50. Boguniewicz M, Fiedler VC, Rainier S, et al. A randomized, vehicle-controlled trial of tacrolimus ointment for treatment of atopic dermatitis in children. Pediatric Tacrolimus Study Group. J Allergy Clin Immunol. 1998; 102 (4 Pt 1): 637–44

    Article  PubMed  CAS  Google Scholar 

  51. Hanifin JM, Ling MR, Langley R, et al. Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part I, efficacy. J Am Acad Dermatol. 2001; 44 (1 Suppl.): S28–38

    Article  PubMed  CAS  Google Scholar 

  52. Reitamo S, Wollenberg A, Schopf E, et al. Safety and efficacy of 1 year of tacrolimus ointment monotherapy in adults with atopic dermatitis. The European Tacrolimus Ointment Study Group. Arch Dermatol. 2000; 136 (8): 999–1006

    Article  PubMed  CAS  Google Scholar 

  53. Kawalek AZ, Spencer JM, Phelps RG. Combined excimer laser and topical tacrolimus for the treatment of vitiligo: a pilot study. Dermatol Surg. 2004; 30 (2 Pt 1): 130–5

    Article  PubMed  Google Scholar 

  54. Passeron T, Ostovari N, Zakaria W, et al. Topical tacrolimus and the 308-nm excimer laser: a synergistic combination for the treatment of vitiligo. Arch Dermatol. 2004; 140 (9): 1065–9

    Article  PubMed  CAS  Google Scholar 

  55. Bos JD, Meinardi MM. The 500 Dalton rule for the skin penetration of chemical compounds and drugs. Exp Dermatol. 2000; 9 (3): 165–9

    Article  PubMed  CAS  Google Scholar 

  56. Wester RC, Maibach HI. In vivo percutaneous absorption. In: Marzulli FN, Maibach HI, editors. Dermatoxicology. 2nd ed. Washington, DC: Hemisphere Publishing Corporation, 1983: 131–46

    Google Scholar 

  57. Gutzmer R, Volker B, Kapp A, et al. Successful topical treatment of cutaneous sarcoidosis with tacrolimus [in German]. Hautarzt. 2003; 54 (12): 1193–7

    Article  PubMed  CAS  Google Scholar 

  58. Katoh N, Mihara H, Yasuno H. Cutaneous sarcoidosis successfully treated with topical tacrolimus. Br J Dermatol. 2002; 147 (1): 154–6

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Department of Dermatology, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen, 6500 HB, The Netherlands

    Milan Tjioe & Wynand H.P.M. Vissers

Authors
  1. Milan Tjioe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wynand H.P.M. Vissers
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marie-Jeanne P. Gerritsen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Milan Tjioe.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tjioe, M., Vissers, W.H. & Gerritsen, MJ.P. Topical Macrolide Immunomodulators. Am J Clin Dermatol 7, 7–12 (2006). https://doi.org/10.2165/00128071-200607010-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00128071-200607010-00002

Keywords

Search

Navigation