title: New treatment modalities for vitiligo: focus on topical immunomodulators.
abstract: The development of effective treatment modalities for vitiligo is dependent on an understanding of the events leading to depigmentation. However, the exact pathogenesis of vitiligo is still mostly unknown. Abnormalities in both humoral and cell-mediated immunity have been documented in vitiligo patients and they present a basis for using immunomodulating agents, such as corticosteroids and macrolide immunomodulators, in the treatment of vitiligo. Macrolide immunomodulators, such as tacrolimus and pimecrolimus, which can be used topically, are known as topical immunomodulators (TIMs). TIMs inhibit the action of calcineurin, and consequently inhibit T-cell activation and the production of various cytokines; this is considered the working mechanism of action of TIMs in vitiligo. Several small studies and case reports on the use of TIMs in vitiligo have been published so far. Tacrolimus achieves better results on the face and neck than on other body areas. Particular advantages of TIMs are safety in treating these areas because of lack of skin atrophy and good tolerability. The incidence of application site adverse events in vitiligo seems to be lower than in the treatment of atopic dermatitis. On the face and neck, TIMs may become a useful tool in the treatment of adults and children with vitiligo despite possibly lower efficacy than topical corticosteroids. Further, larger, controlled clinical studies are warranted to determine the definite role of TIMs as monotherapy or in combination with other modalities in the treatment of vitiligo.
authors.affiliation: Department of Dermatology and Venerology, Zagreb University Hospital Center, Salata 4, Zagreb, HR-100000, Croatia. kreso.kostovic@zg.htnet.hr
authors.forename: Kresimir
authors.initials: K
authors.lastname: Kostovic
authors.forename: Aida
authors.initials: A
authors.lastname: Pasic
mesh_terms: D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011701:PUVA Therapy; D014820:Vitiligo / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents
references.citation: Am J Ophthalmol. 2003 Mar;135(3):297-302
references.pmid: 12614745
references.citation: J Dermatol Sci. 1999 Apr;19(3):182-8
references.pmid: 10215190
references.citation: Dermatol Surg. 2004 Feb;30(2 Pt 1):130-5
references.pmid: 14756638
references.citation: J Am Acad Dermatol. 2002 Feb;46(2):228-41
references.pmid: 11807435
references.citation: Clin Exp Dermatol. 2002 Nov;27(8):641-4
references.pmid: 12472535
references.citation: Arch Dermatol Res. 1988;280(3):137-9
references.pmid: 3377526
references.citation: Br J Dermatol. 1998 Nov;139(5):798-805
references.pmid: 9892944
references.citation: Ann Intern Med. 1990 Oct 15;113(8):619-27
references.pmid: 2205142
references.citation: Dermatology. 2002;205(3):301-3
references.pmid: 12399684
references.citation: Cutis. 1985 Oct;36(4):317-8, 322
references.pmid: 2998703
references.citation: J Am Acad Dermatol. 1986 Nov;15(5 Pt 1):978-81
references.pmid: 3782537
references.citation: Pediatrics. 2002 Jul;110(1 Pt 1):e2
references.pmid: 12093983
references.citation: Photodermatol Photoimmunol Photomed. 2003 Feb;19(1):35-6
references.pmid: 12713553
references.citation: Lancet. 1994 Oct 15;344(8929):1049-52
references.pmid: 7934446
references.citation: Biochim Biophys Acta. 1994 May 25;1226(2):181-92
references.pmid: 8204666
references.citation: Curr Opin Investig Drugs. 2002 May;3(5):708-12
references.pmid: 12090543
references.citation: J Am Acad Dermatol. 1998 May;38(5 Pt 1):647-66; quiz 667-8
references.pmid: 9591808
references.citation: J Am Acad Dermatol. 2002 May;46(5):727-31
references.pmid: 12004315
references.citation: Cutis. 2004 Apr;73(4):267-71
references.pmid: 15134327
references.citation: J Am Acad Dermatol. 2001 Apr;44(4):634-7
references.pmid: 11260538
references.citation: J Am Acad Dermatol. 2002 Oct;47(4):562-70
references.pmid: 12271302
references.citation: Arch Dermatol. 2003 May;139(5):581-5
references.pmid: 12756094
references.citation: Clin Exp Immunol. 1996 Jul;105(1):84-8
references.pmid: 8697641
references.citation: J Am Acad Dermatol. 2001 Jan;44(1 Suppl):S58-64
references.pmid: 11145796
references.citation: Am J Clin Dermatol. 2001;2(3):167-81
references.pmid: 11705094
references.citation: Dermatology. 1995;190(2):109-15
references.pmid: 7727831
references.citation: Arch Dermatol. 1998 Dec;134(12):1532-40
references.pmid: 9875190
references.citation: J Dermatol. 1998 Oct;25(10):637-40
references.pmid: 9830261
references.citation: Dermatology. 1998;197(2):167-70
references.pmid: 9732168
references.citation: Acta Derm Venereol Suppl (Stockh). 1989;151:26-30; discussion 47-52
references.pmid: 2624063
references.citation: Arch Dermatol. 1993 Aug;129(8):994-8
references.pmid: 8352624
references.citation: Int J Dermatol. 1995 Dec;34(12):837-40
references.pmid: 8647660
references.citation: Acta Derm Venereol. 1994 Mar;74(2):120-3
references.pmid: 7911617
references.citation: Thyroidology. 1991 May;3(2):89-91
references.pmid: 1726907
references.citation: Expert Opin Investig Drugs. 2000 Jan;9(1):69-77
references.pmid: 11060661
references.citation: Acta Derm Venereol. 1983;63(3):249-51
references.pmid: 6192645
references.citation: Lancet. 1971 Jun 26;1(7713):1331-4
references.pmid: 4103398
references.citation: J Pathol. 1993 Jun;170(2):149-55
references.pmid: 8345407
references.citation: Yonsei Med J. 1994 Dec;35(4):404-10
references.pmid: 7871844
references.citation: Skin Pharmacol Appl Skin Physiol. 1999 May-Jun;12(3):132-8
references.pmid: 10393521
references.citation: J Am Acad Dermatol. 1992 May;26(5 Pt 1):693-700
references.pmid: 1316387
references.citation: J Dermatol Sci. 1999 Sep;21(1):59-62
references.pmid: 10468193
references.citation: J Invest Dermatol. 1991 Dec;97(6):1081-5
references.pmid: 1748819
references.citation: J Allergy Clin Immunol. 2002 Aug;110(2):277-84
references.pmid: 12170269
references.citation: Eur J Dermatol. 2002 Nov-Dec;12(6):618-22
references.pmid: 12459545
references.citation: Int J Dermatol. 1992 May;31(5):321-6
references.pmid: 1587659
references.citation: West J Med. 1995 Feb;162(2):123-6
references.pmid: 7794369
references.citation: Arch Dermatol. 1983 Apr;119(4):300-3
references.pmid: 6601472
references.citation: Am J Pathol. 1996 Apr;148(4):1219-28
references.pmid: 8644862
references.citation: J Dermatol Sci. 2001 May;26(1):62-6
references.pmid: 11323222
references.citation: Br J Dermatol. 2001 Sep;145(3):472-5
references.pmid: 11531839
references.citation: Int J Dermatol. 1983 Oct;22(8):477-80
references.pmid: 6642834
references.citation: Acta Genet Med Gemellol (Roma). 1953 May;2(2):118-25
references.pmid: 13057537
references.citation: J Allergy Clin Immunol. 1998 Oct;102(4 Pt 1):637-44
references.pmid: 9802373
references.citation: Dermatol Online J. 2003 Dec;9(5):4
references.pmid: 14996377
references.citation: J Invest Dermatol. 1991 Dec;97(6):1078-80
references.pmid: 1748818
references.citation: Dermatology. 1994;188(4):269-75
references.pmid: 8193398
references.citation: Pigment Cell Res. 1994 Feb;7(1):1-8
references.pmid: 8072943
references.citation: Am J Clin Dermatol. 2001;2(6):389-406
references.pmid: 11770393
references.citation: Int J Dermatol. 2002 Sep;41(9):616-8
references.pmid: 12358838
references.citation: J Invest Dermatol. 1998 Dec;111(6):1034-9
references.pmid: 9856813
references.citation: Dermatology. 2003;207(3):322-3
references.pmid: 14571079
references.citation: Pigment Cell Res. 1992 Mar;5(2):65-9
references.pmid: 1321419
references.citation: Br J Dermatol. 1985 Aug;113(2):153-5
references.pmid: 4027182
references.citation: Curr Probl Dermatol. 1995;22:124-31
references.pmid: 7587313
references.citation: J Am Acad Dermatol. 2004 Jul;51(1):52-61
references.pmid: 15243524
references.citation: J Am Acad Dermatol. 2002 Nov;47(5):789-91
references.pmid: 12399778
references.citation: Pigment Cell Res. 2003 Apr;16(2):90-100
references.pmid: 12622785
references.citation: J Eur Acad Dermatol Venereol. 2003 Sep;17(5):493-503
references.pmid: 12941081
references.citation: J Cell Physiol. 1988 Aug;136(2):273-80
references.pmid: 2842346
references.citation: Arch Dermatol. 1997 Dec;133(12):1525-8
references.pmid: 9420536
references.citation: Arch Dermatol Res. 1996 Oct;288(11):670-5
references.pmid: 8931869
references.citation: J Am Acad Dermatol. 2001 Jan;44(1 Suppl):S47-57
references.pmid: 11145795
references.citation: Arch Dermatol. 2004 Sep;140(9):1065-9
references.pmid: 15381545
references.citation: J Invest Dermatol. 1989 Apr;92(4 Suppl):53S-60S
references.pmid: 2649615
references.citation: Am J Hum Genet. 1988 Aug;43(2):119-25
references.pmid: 3400640
references.citation: Arch Dermatol. 2003 May;139(5):571-4; discussion 573
references.pmid: 12756092
references.citation: J Eur Acad Dermatol Venereol. 2002 Mar;16(2):137-8
references.pmid: 12046816
references.citation: J Allergy Clin Immunol. 2001 Aug;108(2):275-80
references.pmid: 11496246
references.citation: J Invest Dermatol. 1992 Feb;98(2):162-5
references.pmid: 1370675
references.citation: J Invest Dermatol. 1993 Jun;100(6):816-22
references.pmid: 7684427
references.citation: Arch Dermatol. 1998 Jul;134(7):805-9
references.pmid: 9681343
references.citation: J Invest Dermatol. 1993 Jun;100(6):823-8
references.pmid: 8496622
references.citation: J Exp Med. 1998 Sep 21;188(6):1203-8
references.pmid: 9743539
references.citation: Drugs. 2004;64(1):89-107
references.pmid: 14723560
references.citation: Am J Hum Genet. 1994 Nov;55(5):981-90
references.pmid: 7977362
references.citation: Lab Invest. 2000 Aug;80(8):1299-309
references.pmid: 10950121
references.citation: Br J Dermatol. 2001 Mar;144(3):507-13
references.pmid: 11260007
references.citation: Acta Genet Stat Med. 1951;2(3):252-5
references.pmid: 14868352
references.citation: J Dermatol. 2002 Feb;29(2):68-73
references.pmid: 11890298
references.citation: J Pathol. 1993 Feb;169(2):203-6
references.pmid: 8095298
references.citation: J Invest Dermatol. 1992 Dec;99(6):723-8
references.pmid: 1281861
references.citation: J Exp Med. 1996 Oct 1;184(4):1385-95
references.pmid: 8879211
references.citation: Pigment Cell Res. 2003 Apr;16(2):111-6
references.pmid: 12622787
references.citation: Science. 1994 Mar 11;263(5152):1444-6
references.pmid: 8128228
references.citation: J Dermatol. 1997 Sep;24(9):561-3
references.pmid: 9350100
references.citation: J Dermatolog Treat. 2002 Mar;13(1):19-25
references.pmid: 12006134
references.citation: J Invest Dermatol. 1990 Aug;95(2):233-7
references.pmid: 1974278
references.citation: Acta Dermatovenerol Croat. 2003;11(3):163-70
references.pmid: 12967509
references.citation: Br J Dermatol. 2001 Apr;144(4):788-94
references.pmid: 11298538
references.citation: J Am Acad Dermatol. 2001 Jan;44(1 Suppl):S28-38
references.pmid: 11145793
references.citation: Pigment Cell Res. 1995 Feb;8(1):53-9
references.pmid: 7792255
references.citation: Drugs. 2002;62(5):817-40
references.pmid: 11929333
references.citation: Curr Opin Ophthalmol. 2000 Dec;11(6):478-83
references.pmid: 11141645
references.citation: J Dermatol. 1993 Jul;20(7):418-23
references.pmid: 8408923
references.citation: Exp Dermatol. 2000 Jun;9(3):165-9
references.pmid: 10839713
references.citation: J Allergy Clin Immunol. 2001 Mar;107(3):519-25
references.pmid: 11240954
references.citation: N Engl J Med. 1977 Sep 22;297(12):634-7
references.pmid: 331108
references.citation: J Am Acad Dermatol. 2000 Feb;42(2 Pt 1):245-53
references.pmid: 10642680
references.citation: J Invest Dermatol. 1998 Sep;111(3):396-8
references.pmid: 9740230
references.citation: Am J Clin Dermatol. 2002;3(6):381-8
references.pmid: 12113647
references.citation: Cutis. 2003 Feb;71(2):158-62
references.pmid: 12635898
references.citation: Int J Dermatol. 1992 Apr;31(4):229-36
references.pmid: 1634286
references.citation: Dermatology. 1995;190(3):223-9
references.pmid: 7599386
references.citation: N Engl J Med. 1997 Sep 18;337(12):816-21
references.pmid: 9295241
references.citation: Br J Dermatol. 1994 Aug;131(2):160-5
references.pmid: 7522512