New treatment modalities for vitiligo: focus on topical immunomodulators.
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.
Kostovic
Kresimir
K
Department of Dermatology and Venerology, Zagreb University Hospital Center, Salata 4, Zagreb, HR-100000, Croatia. kreso.kostovic@zg.htnet.hr
Pasic
Aida
A
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
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents
Am J Ophthalmol. 2003 Mar;135(3):297-302
12614745
J Dermatol Sci. 1999 Apr;19(3):182-8
10215190
Dermatol Surg. 2004 Feb;30(2 Pt 1):130-5
14756638
J Am Acad Dermatol. 2002 Feb;46(2):228-41
11807435
Clin Exp Dermatol. 2002 Nov;27(8):641-4
12472535
Arch Dermatol Res. 1988;280(3):137-9
3377526
Br J Dermatol. 1998 Nov;139(5):798-805
9892944
Ann Intern Med. 1990 Oct 15;113(8):619-27
2205142
Dermatology. 2002;205(3):301-3
12399684
Cutis. 1985 Oct;36(4):317-8, 322
2998703
J Am Acad Dermatol. 1986 Nov;15(5 Pt 1):978-81
3782537
Pediatrics. 2002 Jul;110(1 Pt 1):e2
12093983
Photodermatol Photoimmunol Photomed. 2003 Feb;19(1):35-6
12713553
Lancet. 1994 Oct 15;344(8929):1049-52
7934446
Biochim Biophys Acta. 1994 May 25;1226(2):181-92
8204666
Curr Opin Investig Drugs. 2002 May;3(5):708-12
12090543
J Am Acad Dermatol. 1998 May;38(5 Pt 1):647-66; quiz 667-8
9591808
J Am Acad Dermatol. 2002 May;46(5):727-31
12004315
Cutis. 2004 Apr;73(4):267-71
15134327
J Am Acad Dermatol. 2001 Apr;44(4):634-7
11260538
J Am Acad Dermatol. 2002 Oct;47(4):562-70
12271302
Arch Dermatol. 2003 May;139(5):581-5
12756094
Clin Exp Immunol. 1996 Jul;105(1):84-8
8697641
J Am Acad Dermatol. 2001 Jan;44(1 Suppl):S58-64
11145796
Am J Clin Dermatol. 2001;2(3):167-81
11705094
Dermatology. 1995;190(2):109-15
7727831
Arch Dermatol. 1998 Dec;134(12):1532-40
9875190
J Dermatol. 1998 Oct;25(10):637-40
9830261
Dermatology. 1998;197(2):167-70
9732168
Acta Derm Venereol Suppl (Stockh). 1989;151:26-30; discussion 47-52
2624063
Arch Dermatol. 1993 Aug;129(8):994-8
8352624
Int J Dermatol. 1995 Dec;34(12):837-40
8647660
Acta Derm Venereol. 1994 Mar;74(2):120-3
7911617
Thyroidology. 1991 May;3(2):89-91
1726907
Expert Opin Investig Drugs. 2000 Jan;9(1):69-77
11060661
Acta Derm Venereol. 1983;63(3):249-51
6192645
Lancet. 1971 Jun 26;1(7713):1331-4
4103398
J Pathol. 1993 Jun;170(2):149-55
8345407
Yonsei Med J. 1994 Dec;35(4):404-10
7871844
Skin Pharmacol Appl Skin Physiol. 1999 May-Jun;12(3):132-8
10393521
J Am Acad Dermatol. 1992 May;26(5 Pt 1):693-700
1316387
J Dermatol Sci. 1999 Sep;21(1):59-62
10468193
J Invest Dermatol. 1991 Dec;97(6):1081-5
1748819
J Allergy Clin Immunol. 2002 Aug;110(2):277-84
12170269
Eur J Dermatol. 2002 Nov-Dec;12(6):618-22
12459545
Int J Dermatol. 1992 May;31(5):321-6
1587659
West J Med. 1995 Feb;162(2):123-6
7794369
Arch Dermatol. 1983 Apr;119(4):300-3
6601472
Am J Pathol. 1996 Apr;148(4):1219-28
8644862
J Dermatol Sci. 2001 May;26(1):62-6
11323222
Br J Dermatol. 2001 Sep;145(3):472-5
11531839
Int J Dermatol. 1983 Oct;22(8):477-80
6642834
Acta Genet Med Gemellol (Roma). 1953 May;2(2):118-25
13057537
J Allergy Clin Immunol. 1998 Oct;102(4 Pt 1):637-44
9802373
Dermatol Online J. 2003 Dec;9(5):4
14996377
J Invest Dermatol. 1991 Dec;97(6):1078-80
1748818
Dermatology. 1994;188(4):269-75
8193398
Pigment Cell Res. 1994 Feb;7(1):1-8
8072943
Am J Clin Dermatol. 2001;2(6):389-406
11770393
Int J Dermatol. 2002 Sep;41(9):616-8
12358838
J Invest Dermatol. 1998 Dec;111(6):1034-9
9856813
Dermatology. 2003;207(3):322-3
14571079
Pigment Cell Res. 1992 Mar;5(2):65-9
1321419
Br J Dermatol. 1985 Aug;113(2):153-5
4027182
Curr Probl Dermatol. 1995;22:124-31
7587313
J Am Acad Dermatol. 2004 Jul;51(1):52-61
15243524
J Am Acad Dermatol. 2002 Nov;47(5):789-91
12399778
Pigment Cell Res. 2003 Apr;16(2):90-100
12622785
J Eur Acad Dermatol Venereol. 2003 Sep;17(5):493-503
12941081
J Cell Physiol. 1988 Aug;136(2):273-80
2842346
Arch Dermatol. 1997 Dec;133(12):1525-8
9420536
Arch Dermatol Res. 1996 Oct;288(11):670-5
8931869
J Am Acad Dermatol. 2001 Jan;44(1 Suppl):S47-57
11145795
Arch Dermatol. 2004 Sep;140(9):1065-9
15381545
J Invest Dermatol. 1989 Apr;92(4 Suppl):53S-60S
2649615
Am J Hum Genet. 1988 Aug;43(2):119-25
3400640
Arch Dermatol. 2003 May;139(5):571-4; discussion 573
12756092
J Eur Acad Dermatol Venereol. 2002 Mar;16(2):137-8
12046816
J Allergy Clin Immunol. 2001 Aug;108(2):275-80
11496246
J Invest Dermatol. 1992 Feb;98(2):162-5
1370675
J Invest Dermatol. 1993 Jun;100(6):816-22
7684427
Arch Dermatol. 1998 Jul;134(7):805-9
9681343
J Invest Dermatol. 1993 Jun;100(6):823-8
8496622
J Exp Med. 1998 Sep 21;188(6):1203-8
9743539
Drugs. 2004;64(1):89-107
14723560
Am J Hum Genet. 1994 Nov;55(5):981-90
7977362
Lab Invest. 2000 Aug;80(8):1299-309
10950121
Br J Dermatol. 2001 Mar;144(3):507-13
11260007
Acta Genet Stat Med. 1951;2(3):252-5
14868352
J Dermatol. 2002 Feb;29(2):68-73
11890298
J Pathol. 1993 Feb;169(2):203-6
8095298
J Invest Dermatol. 1992 Dec;99(6):723-8
1281861
J Exp Med. 1996 Oct 1;184(4):1385-95
8879211
Pigment Cell Res. 2003 Apr;16(2):111-6
12622787
Science. 1994 Mar 11;263(5152):1444-6
8128228
J Dermatol. 1997 Sep;24(9):561-3
9350100
J Dermatolog Treat. 2002 Mar;13(1):19-25
12006134
J Invest Dermatol. 1990 Aug;95(2):233-7
1974278
Acta Dermatovenerol Croat. 2003;11(3):163-70
12967509
Br J Dermatol. 2001 Apr;144(4):788-94
11298538
J Am Acad Dermatol. 2001 Jan;44(1 Suppl):S28-38
11145793
Pigment Cell Res. 1995 Feb;8(1):53-9
7792255
Drugs. 2002;62(5):817-40
11929333
Curr Opin Ophthalmol. 2000 Dec;11(6):478-83
11141645
J Dermatol. 1993 Jul;20(7):418-23
8408923
Exp Dermatol. 2000 Jun;9(3):165-9
10839713
J Allergy Clin Immunol. 2001 Mar;107(3):519-25
11240954
N Engl J Med. 1977 Sep 22;297(12):634-7
331108
J Am Acad Dermatol. 2000 Feb;42(2 Pt 1):245-53
10642680
J Invest Dermatol. 1998 Sep;111(3):396-8
9740230
Am J Clin Dermatol. 2002;3(6):381-8
12113647
Cutis. 2003 Feb;71(2):158-62
12635898
Int J Dermatol. 1992 Apr;31(4):229-36
1634286
Dermatology. 1995;190(3):223-9
7599386
N Engl J Med. 1997 Sep 18;337(12):816-21
9295241
Br J Dermatol. 1994 Aug;131(2):160-5
7522512