Skip to main content

Advertisement

SpringerLink
Log in

Time-kinetic study of repigmentation in vitiligo patients by tacrolimus or pimecrolimus

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

New topical immunomodulators have been reported to cause repigmentation of vitiligo lesions. However, time-kinetics of such repigmentation in different anatomic locations is not well known. We performed a randomized double-blind placebo control study with tacrolimus versus the vehicle and a nonrandomized control study with pimecrolimus to evaluate the time to reach significant pigmentation, its duration and extent in treated areas. Antioxidant status of serum was also assessed. Twenty patients, in the tacrolimus study, had one pair of lesions on different localizations, and 20 on face and/or upper limbs for pimecrolimus. The extent of repigmentation was evaluated by slides and mapmakings at baseline and every 4 weeks during 7 months. Adverse events were recorded. The derivatives of oxygen metabolites, the ferric reducing ability of serum and vitamin E were assessed. Three groups of patients were identified with the tacrolimus study. Eight had no significant change in response characterized by a parallel increase of repigmentation or none in treated and control areas. Nine had a better repigmentation to tacrolimus at fifth month of treatment. Three had a marked repigmentation in control areas at the end of treatment. Repigmentation was significant on the face compared to upper-limbs with pimecrolimus from fourth to seventh month. A significant reduction of oxidative stress and an increase in antioxidant capacity in serum of patients treated with topical tacrolimus was observed, while those treated with pimecrolimus did not show any significant changes but an increase in vitamin E. Our work defines three periods in repigmentation, triggering during the first 4 months, increase in pigmentation with tacrolimus and a plateau or a sustained repigmentation. The continuity of the treatment seems necessary to ensure a prolonged repigmenting effect and even an enhanced one, such as the one we observed on the face with pimecrolimus. The extent of repigmentation was more significant on the face compared to other locations probably due to differences in melanocyte density. Furthermore, we did not find any relationship between repigmentation and the duration of vitiligo. Tacrolimus was able to reduce the systemic oxidative stress independently from its repigmenting capacity. Both drugs were well tolerated.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Agrawal D, Shajil EM, Marfatia YS, Begum R (2004) Study on the antioxidant status of vitiligo patients of different age groups in Baroda. Pigment Cell Res 17:289–294

    Article  PubMed  Google Scholar 

  2. Akyol M, Celik VK, Ozcelik S, Polat M, Marufihah M, Atalay A (2002) The effects of vitamin E on the skin lipid peroxidation and the clinical improvement in vitiligo patients treated with PUVA. Eur J Dermatol 12:24–26

    CAS  PubMed  Google Scholar 

  3. Alaiti S, Kang S, Fiedler VC et al (1998) Tacrolimus (FK506) ointment for atopic dermatitis: a phase I study in adults and children. J Am Acad Dermatol 38:69–76

    Article  CAS  PubMed  Google Scholar 

  4. Alomar A, Berth-Jones J, Bos JD et al (2004) The role of topical calcineurin inhibitors in atopic dermatitis. Br J Dermatol 151(Suppl 70):3–27

    Article  CAS  PubMed  Google Scholar 

  5. Benzie IF, Strani JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239:70–76

    Article  CAS  PubMed  Google Scholar 

  6. Billich A, Aschauer H, Aszodi A, Stuetz A (2004) Percutaneous absorption of drugs used in atopic eczema: pimecrolimus permeates less through skin than corticosteroids and tacrolimus. Int J Pharm 269:29–35

    Article  CAS  PubMed  Google Scholar 

  7. Comaish JS, Greener JS (1976) The inhibiting effect of soft paraffin on the Kobner response in psoriasis. Br J Dermatol 94:195–200

    Article  CAS  PubMed  Google Scholar 

  8. Dell’Anna ML, Maresca V, Briganti S, Camera E, Falchi M, Picardo M (2001) Mitochondrial impairment in peripheral blood mononuclear cells during the active phase of vitiligo. J Invest Dermatol 117:908–913

    Article  PubMed  Google Scholar 

  9. Dell’Anna ML, Urbanelli S, Mastrofrancesco A et al (2003) Alterations of mitochondria in peripheral blood mononuclear cells of vitiligo patients. Pigment Cell Res 16:553–559

    Article  PubMed  Google Scholar 

  10. Drake LA, Dinehart SM, Farmer ER et al (1996) Guidelines of care for vitiligo. J Am Acad Dermatol 35:620–626

    Article  CAS  PubMed  Google Scholar 

  11. Gabryel B, Chalimoniuk M, Stolecka A, Waniek K, Langfort J, Malecki A (2006) Inhibition of arachidonic acid release by cytosolic phospholipase A2 is involved in the antiapoptotic effect of FK506 and cyclosporin a on astrocytes exposed to simulated ischemia in vitro. J Pharmacol Sci 102:77–87

    Article  CAS  PubMed  Google Scholar 

  12. Grimes PE, Soriano T, Dytoc MT (2002) Topical tacrolimus for repigmentation of vitiligo. J Am Acad Dermatol 47:789–791

    Article  PubMed  Google Scholar 

  13. Iamele L, Fiocchi R, Vernocchi A (2002) Evaluation of an automated spectrophotometric assay for reactive oxygen metabolites in serum. Clin Chem Lab Med 40:673–676

    Article  CAS  PubMed  Google Scholar 

  14. Kanwar AJ, Dogra S, Parsad D (2004) Topical tacrolimus for the treatment of childhood vitiligo in Asians. Clin Exp Dermatol 29:589–592

    Article  CAS  PubMed  Google Scholar 

  15. Kato S, Nishio H, Ogura M, Takeuchi K (2007) Tacrolimus (FK506), an immunosuppressive agent, prevents indomethacin induced small intestinal ulceration in the rat: inhibition of inducible nitric oxide synthase expression. J Pharmacol Sci 103(1):40–47

    Article  CAS  PubMed  Google Scholar 

  16. Koca R, Armutcu F, Altinyazar HC, Gurel A (2004) Oxidant-antioxidant enzymes and lipid peroxidation in generalized vitiligo. Clin Exp Dermatol 29:406–409

    Article  CAS  PubMed  Google Scholar 

  17. Lan C-CE, Chen G-S, Chiou M-H, Wu C-S, Chang C-H, Yu H-S (2005) FK506 promotes melanocyte and melanoblast growth and creates a favourable milieu for cell migration via keratinocytes: possible mechanisms of how tacrolimus ointment induces repigmentation in patients with vitiligo. Br J Dermatol 153:498–505

    Article  CAS  PubMed  Google Scholar 

  18. Lee AY, Kim NH, Choi WI, Youm YH (2005) Less keratinocyte-derived factors related to more keratinocyte apoptosis in depigmented than normally pigmented suction-blistered epidermis may cause passive melanocyte death in vitiligo. J Invest Dermatol 124:976–983

    Article  CAS  PubMed  Google Scholar 

  19. Marsland AM, Griffiths CEM (2002) The macrolide immunosuppressants in dermatology: mechanisms of action. Eur J Dermatol 12:618–622

    CAS  PubMed  Google Scholar 

  20. Mayoral FA, Gonzalez C, Shah NS, Arciniegas C (2003) Repigmentation of vitiligo with pimecrolimus cream: a case report. Dermatology 207:322–323

    Article  PubMed  Google Scholar 

  21. Nghiem P, Pearson G, Langley RG (2002) Tacrolimus and pimecrolimus: from clever prokaryotes to inhibiting calcineurin, treating atopic dermatitis. J Am Acad Dermatol 46:228–241

    Article  PubMed  Google Scholar 

  22. Njoo MD, Spuls PI, Bos JD, Westerhof W, Bossuyt PM (1998) Nonsurgical repigmentation therapies in vitiligo. Meta-analysis of the literature. Arch Dermatol 134:1532–1540

    Article  CAS  PubMed  Google Scholar 

  23. Nordlund JJ, Ortonne J-P (1998) Vitiligo vulgaris. In: Nordlund JJ, Boissy RE, Hearing VJ, King RA, Ortonne J-P (eds) The pigmentary system. Physiology and pathophysiology, 1st edn. Oxford University Press, Oxford, pp 513–531

  24. Otberg N, Richter H, Schaefer H, Blume-Peytavi U, Sterry W, Lademann J (2004) Variations of hair follicle size and distribution in different body sites. J Invest Dermatol 122:14–19

    Article  CAS  PubMed  Google Scholar 

  25. Paller A, Eichenfield LF, Leung DYM, Appel M (2001) A 12 week study of tacrolimus ointment for the treatment of atopic dermatitis in pediatric patients. J Am Acad Dermatol 44:47–57

    Article  Google Scholar 

  26. Passi S, Morrone A, Picardo M, De Luca C, Ippolito F (1991) Blood level of vitamin E, polyunsatured fatty acids of phospholipids, lipoperoxides and glutathione peroxidase activity in patients with seborrheic dermatitis. J Dermatol Sci 2:171–178

    Article  CAS  PubMed  Google Scholar 

  27. Sakuma S, Higashi Y, Sato N, Sasakawa T, Sengoku T, Ohkubo Y, Amaya T, Goto T (2001) Tacrolimus suppressed the production of cytokines involved in atopic dermatitis by direct stimulation of human PBMC system (comparison with steroids). Int Immunopharmacol 1(6):1219–1226

    Article  CAS  PubMed  Google Scholar 

  28. Sauder DN (2004) Mechanism of action and emerging role of immune response modifier therapy in dermatologic conditions. J Cutan Med Surg 8(Suppl 3):3–12

    Article  PubMed  Google Scholar 

  29. Schallreuter KU, Chiuchiarelli G, Cemeli E et al (2006) Estrogens can contribute to hydrogen peroxide generation and quinone-mediated DNA damage in peripheral blood lymphocytes from patients with vitiligo. J Invest Dermatol 126:1036–1042

    Article  CAS  PubMed  Google Scholar 

  30. Smith DA, Tofte SJ, Hanifin JM (2002) Repigmentation of vitiligo with topical tacrolimus. Dermatology 205:301–303

    Article  CAS  PubMed  Google Scholar 

  31. Tanaka K, Fujita N, Yoshioka M, Ogawa N (2001) Immunosuppressive and non-immunosuppressive immunophilin ligands improve H2O2-induced cell damage by increasing glutathione levels in NG108-15 cells. Brain Res 889:225–228

    Article  CAS  PubMed  Google Scholar 

  32. Tanghetti EA (2003) Tacrolimus ointment 0.1% produces repigmentation in patients with vitiligo: results of a prospective patient series. Cutis 71:158–162

    PubMed  Google Scholar 

  33. Travis LB, Weinberg JM, Silverberg NB (2003) Successful treatment of vitiligo with 0.1% tacrolimus ointment. Arch Dermatol 139:571–574

    Article  PubMed  Google Scholar 

  34. Van Leent EJ, De Vries HJ, Ebelin ME, Burtin P, Scott G, Bos JD (2007) Blood concentrations of pimecrolimus in adult patients with atopic dermatitis following intermittent administration of pimecrolimus cream 1% (Elidel) for up to 1 year. J Dermatol Treat 18(1):19–22

    Article  Google Scholar 

  35. Whiteman DC, Parsons PG, Green AC (1999) Determinants of melanocyte density in adult human skin. Arch Dermatol Res 291:511–516

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to thank Prof M. Dramaix for her valuable help in statistics, Dr. Y. Gauthier for his strong experience in vitiligo which contributed to improving the article, Mrs. M. Debuisseret and F. Flemal for their efficient assistance.

Author information

Authors and Affiliations

  1. Department of Dermatology, Hôpital Erasme, Université Libre de Bruxelles, 808 Route de Lennik, 1070, Brussels, Belgium

    L. J. Lubaki, P. Vereecken, J. Vadoud-Seyedi & M. Heenen

  2. LOCE, Institut J. Bordet, Université Libre de Bruxelles, Brussels, Belgium

    L. J. Lubaki, G. Ghanem & P. Vereecken

  3. Public Health School, Université Libre de Bruxelles, Brussels, Belgium

    E. Fouty

  4. Department of Pharmacy, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium

    L. Benammar

  5. Instituto Dermatologico San Gallicano, Rome, Italy

    M. L. Dell’Anna, S. Briganti & M. Picardo

Authors
  1. L. J. Lubaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Ghanem
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Vereecken
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Fouty
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L. Benammar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. Vadoud-Seyedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. L. Dell’Anna
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S. Briganti
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M. Picardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M. Heenen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. J. Lubaki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lubaki, L.J., Ghanem, G., Vereecken, P. et al. Time-kinetic study of repigmentation in vitiligo patients by tacrolimus or pimecrolimus. Arch Dermatol Res 302, 131–137 (2010). https://doi.org/10.1007/s00403-009-0973-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-009-0973-3

Keywords

Search

Navigation