Calcineurin Inhibitor Topikal Dalam Bidang Dermatologi
Abstrak
Beberapa dermatosis terjadi akibat ketidakseimbangan jalur imunologi. Imunomodulator dapat berfungsi sebagai imunostimulan atau imunosupresan. Pengobatan konvensional kelainan-kelainan inflamasi kulit umumnya menggunakan kortikosteroid topikal, tetapi penggunaan klinis terbatas oleh potensi efek samping lokal dan sistemik. Imunomodulator topikal yang terkini dikembangkan dan telah mendapat lisensi dari Food and Drug Administration (FDA) yaitu salap takrolimus dan krim pimekrolimus. Calcineurin inhibitor topikal dianggap sebagai alternatif pengganti kortikosteroid yang aman dan efektif, meskipun masih digolongkan dalam kategori C. Mekanisme kerja obat topikal tersebut dengan menghambat maturasi dan aktivasi sel T melalui kompleks protein sitolitik. Efek samping yang sering terjadi adalah efek lokal berupa pruritus atau rasa panas, tanpa menimbulkan efek sistemik. Kedua obat tersebut disetujui untuk pengobatan dermatitis atopik, namun dapat juga digunakan untuk kelainan-kelainan inflamasi kulit lainnya seperti psoriasis, vitiligo, dermatitis kontak, dermatitis seboroik, liken planus, reaksi reversal dan pioderma gangrenosum. Obat topikal ini tidak menyebabkan atrofi kulit, telangiektasia, striae ataupun toksisitas sistemik.
Kata Kunci: Calcineurin inhibitor topikal, takrolimus, pimekrolimus
References
1. Burkhart CN, Gottwald L, Nelson L. Tacrolimus and pimecrolimus: revolutionary new topical immunomodulators for skin disorders. Int Pediatr. 2004;19:7-11
2. Vicari-Christensen M, Repper S, Basile S, Young D. Tacrolimus: review of pharmacokinetics, pharmacodynamics, and pharmacogenetics to facilitate practitioners’ understanding and offer strategies for educating patients and promoting adherence. Progress in Transplant. 2009;19:277-84
3. Khandpur S, Sharma VK, Sumanth K. Topical immunomodulators in dermatology. J Postgrad Med. 2004;50:131-9
4. Gupta AK, Chow M. Pimecrolimus: a review. J Eur Acad Dermatol Venereol. 2003;17:493-503
5. Esperaza EM, Sidbury R. Topical immunomodulators. Dalam: Goldsmith LA, Katz SI, Gilchrest BA, Paller As, Leffell DJ, Wolff K, penyunting. Fitzpatrick’s dermatology in general medicine. Edisi ke-8. New York: McGraw Hill; 2008. h.2125-9
6. Berman B, Araujo TD, Lebwohl M. Immunomodulators. Dalam: Bolognia JL, Jorizzo JL, Rapini RP, penyunting. Dermatology. London: Mosby; 2003. h.2033-53
7. Mandelin J, Remitz A, Virtanen H, Reitamo S. One-year treatment with 0,1% tacrolimus ointment versus a corticosteroid regimen in adults with moderate to severe atopic dermatitis: a randomized, double-blind, comparative trial. Acta Derm Venereol. 2010;90:170-4
8. Paul C, Cork M, Rossi AB, Papp KA, Barbier N, Prost Y. Safety and tolerability of 1% pimecrolimus cream among infants: experience with 1133 patients treated for up to 2 years. Pediatrics. 2006;117:e118-28
9. Arguelles AR, Gorbea RM, Zamora MEI, Crelgo JG. Topic tacrolimus, alternative for oral erosive lichen planus resistant to steroids: a case report. Med Oral Patol Oral Cir Bucal. 2006;11:E462-6
10. Bernard LA, Bergman JN, Eichenfield LF. Pimecrolimus 1% cream (Elidel®) for atopic dermatitis. Skin Ther Letter. 2002;7:1-7
11. Buck ML. Topical macrolactam immunomodulators for atopic dermatitis. Pediatr Pharmacother. 2002;8:1-4
12. Reitamo S. Topical calcineurin inhibitors for atopic dermatitis. Eur Pharmacother. 2006;1-3
13. Baldo A, Cafiero M, Caterino PD, Costanzo LD. Tacrolimus ointment in the management of atopic dermatitis. Clin Cosmetic Invest Dermatol. 2009;2:1-7
14. Doss N, Kamoun M-R, Dubertret L, Cambazard F, Remitz A, et al. Efficacy of tacrolimus 0,03% ointment as second-line treatment for children with moderate-to-severe atopic dermatitis: evidence from a randomized, double-blind non-inferiority trial vs. fluticasone 0,005% ointment. Pediatr Allergy Immunol. 2010;21:321-9
15. Gupta AK, Adamiak A, Chow M. Tacrolimus: a review of its use for the management of dermatoses. J Eur Acad Dermatol Venereol. 2002;16:100-14
16. Furue M, Takeuchi S. Topical tacrolimus as treatment of atopic dermatitis. Clin Cosmetic Invest Dermatol. 2009;2:161-6
17. Thaci D, Salgo R. The topical calcineurin inhibitor pimecrolimus in atopic dermatitis: a safety update. Acta Dermatoven APA. 2007;16:58-62
18. Gollnick H, Kaufmann R, Stough D, Heikkila H, Andriano K, dkk. Pimecrolimus cream 1% in the long-term management of adult atopic dermatitis: prevention of flare progression. A randomized controlled trial. Br J Dermatol. 2008;158:1083-93
19. Kirsner RS, Heffernan MP, Antaya R. Safety and efficacy of tacrolimus ointment versus pimecrolimus cream in the treatment of patients with atopic dermatitis previously treated with corticosteroids. Acta Derm Venereol. 2010;90:58-64
20. Norris DA. Mechanisms of action of topical therapies and the rationale for combination therapy. J Am Acad Dermatol. 2005;53:S17-25
21. Brune A, Miller DW, Lin P, Cotrim-Russi D, Paller AS. Tacrolimus ointment is effective for psoriasis on the face and intertriginous areas in pediatric patients. Pediatr Dermatol. 2007;24:76-80
22. Ortonne J-P, Van de Kerkhof PCM, Prinz JC, Bieber T, Lahfa M, dkk. 0,3% tacrolimus gel and 0,5% tacrolimus cream show efficacy in mild to moderate plaque psoriasis: results of a randomized, open-label, observer-blinded study. Acta Derm Venereol. 2006;86:29-33
23. Kroft EBM, Erceg A, Maimets K, Vissers W, Van der Valk PGM, Van de Kerkhof PCM. Tacrolimus ointment for the treatment of severe facial plaque psoriasis. J Eur Acad Dermatol Venereol. 2005;19:249-51
24. Mrowietz U, Wustlich S, Hoexter G, Graeber M, Brautigam M, Luger T. An experimental ointment formulation of pimecrolimus is effective in psoriasis without occlusion. Acta Derm Venereol. 2003;83:351-3
25. Jacobi A, Braeutigam M, Mahler V, Schultz E, Herti M. Pimecrolimus 1% cream in the treatment of facial psoriasis: a 16-week open-label study. Dermatology. 2008;216:133-6
26. Kreuter A, Sommer A, Hyun J, Brautigam M, Brockmeyer NH, dkk. 1% pimecrolimus, 0,005% calcipotriol, and 0,1% betamethasone in the treatment of intertriginous psoriasis. Arch Dermatol. 2006;142:1138-43
27. Boone B, Ongenae K, Van Geel N, Vernijns S, De Keyser S, Naeyaert J-M. Topical pimecrolimus in the treatment of vitiligo. Eur J Dermatol. 2007;17:55-61
28. Radakovic S, Breier-Maly J, Konschitzky R, Kittler H, Sator P, et al. Response of vitiligo to once-vs. twice-daily topical tacrolimus: a controlled prospective, randomized, observer-blinded trial. J Eur Acad Dermatol Venereol. 2009;23:951-3
29. Tamler C, Oliveira PA, Duque-Estrada B, Avelleira JCR. Tacrolimus 0,1% ointment in the treatment of vitiligo: a series of cases. An Bras Dermatol. 2011;86:169-71
30. Falabella R, Barona MI. Update on skin repigmentation therapies in vitiligo. Pigment Cell Melanoma Res. 2008;22:42-65
31. Xu A-E, Zhang D-M, Wei X-D, Huang B, Lu L-J. Efficacy and safety of tacrolimus cream 0,1% in the treatment of vitiligo. Int J Dermatol. 2009;48:86-90
32. Hartmann A, Brocker E-B, Hamm H. Occlusive treatment enhances efficacy of tacrolimus 0,1% ointment in adult patients with vitiligo: results of a placebo controlled 12-month prospective study. Acta Derm Venereol. 2008;88:474-9
33. Kanwar AJ, Dogra S, Parsad D. Topical tacrolimus for treatment of childhood vitiligo in Asians. Clin Exp Dermatol. 2004;29:589-92
34. Fai D, Cassano N, Vena GA. Narrow-band UVB phototherapy combined with tacrolimus ointment in vitiligo: a review of 110 patients. J Eur Acad Dermatol Venereol. 2007;21:916-20
35. Kawalek AZ, Spencer JM, Phelps RG. Combined excimer laser and topical tacrolimus for the treatment of vitiligo: a pilot study. Dermatol Surg. 2004;30:130-5
36. Boone B, Ongenae K, Van Geel N, Vernijns S, De Keyser S, Naeyaert J-M. Topical pimecrolimus in the treatment of vitiligo. Eur J Dermatol. 2007;17:55-61
37. Goweini ME, Sayed NE, Ramly ME. Topical pimecrolimus versus clobetasol in the treatment of vitiligo. Egypt J Derm & Androl. 2006;27:13-8
38. Farajzadeh S, Daraei Z, Esfandiarpour I, Hosseini SH. The efficacy of pimecrolimus 1% cream combined with microdermabrasion in the treatment of nonsegmental childhood vitiligo: a randomized placebo-controlled study. Pediatr Dermatol. 2009;26:286-91
40. Brownell I, Quan LT, Hsu S. Topical pimecrolimus in the treatment of seborrheic dermatitis. Dermatol Online J. 2003;9:13
41. Ozden MG, Tekin NS, Ilter N, Ankarali H. Topical pimecrolimus 1% cream for resistant seborrheic dermatitis of the face. Am J Clin Dermatol. 2010;11:51-4
42. Koc E, Arca E, Kose O, Akar A. An open, randomized, prospective, comparative study of topical pimecrolimus 1% cream and topical ketoconazole 2% cream in the treatment of seborrheic dermatitis. J Dermatol Treat. 2009;20:4-9
43. Sugita T, Tajima M, Tsubuku H, Tsuboi R, Nishikawa A. A new calcineurin inhibitor, pimecrolimus, inhibits the growth of Malassezia spp. Antimicrob Agents Chemother. 2006;50:2897-8
44. Cicek D, Kandi B, Bakar S, Turgut D. Pimecrolimus 1% cream, methylprednisolone aceponate 0,1% cream and metronidazole 0,75% gel in the treatment of seborrhoeic dermatitis: a randomized clinical study. J Dermatol Treat. 2009;20:344-9
45. Tatlican S, Eren C, Oktay B, Eskioglu F, Durmazlar PK. Experience with repetitive use of pimecrolimus: exploring the effective and safe use in the treatment of relapsing seborrheic dermatitis. J Dermatol Treat. 2010;21:83-5
46. Safa G, Darrieux L, Coic A, Tisseau L. Type 1 leprosy reversal reaction treated with topical tacrolimus along with systemic corticosteroids. Indian J Med Sci. 2009;63:359-62
47. Ruzicka T, Assmann T, Lebwohl M. Potential future dermatological indications for tacrolimus ointment. Eur J Dermatol. 2003;13:331-42
48. Edwards PC, Kelsch R. Oral lichen planus: clinical presentation and management. J Can Dental Assoc. 2002;68:494-9
49. Lener EV, Brieva J, Schachter M, West LE, West DP. Successful treatment of erosive lichen planus with topical tacrolimus. Arch Dermatol. 2001;137:419-22
50. Ujiie H, Shibaki A, Akiyama M, Shimizu H. Successful treatment of nail lichen planus with topical tacrolimus. Acta Derm Venereol. 2010:90:218-9
51. Laeijendecker R, Tank B, Dekker SK, Neumann HAM. A comparison of treatment of oral lichen planus with topical tacrolimus and triamcinolone acetonide ointment. Acta Derm Venereol. 2006;86:227-9
52. Becker JC, Houben R, Vetter CS, Brocker EB. The carcinogenic potential of tacrolimus ointment beyond immune suppression: a hypothesis creating case report. BMC Cancer. 2006;6:7
2. Vicari-Christensen M, Repper S, Basile S, Young D. Tacrolimus: review of pharmacokinetics, pharmacodynamics, and pharmacogenetics to facilitate practitioners’ understanding and offer strategies for educating patients and promoting adherence. Progress in Transplant. 2009;19:277-84
3. Khandpur S, Sharma VK, Sumanth K. Topical immunomodulators in dermatology. J Postgrad Med. 2004;50:131-9
4. Gupta AK, Chow M. Pimecrolimus: a review. J Eur Acad Dermatol Venereol. 2003;17:493-503
5. Esperaza EM, Sidbury R. Topical immunomodulators. Dalam: Goldsmith LA, Katz SI, Gilchrest BA, Paller As, Leffell DJ, Wolff K, penyunting. Fitzpatrick’s dermatology in general medicine. Edisi ke-8. New York: McGraw Hill; 2008. h.2125-9
6. Berman B, Araujo TD, Lebwohl M. Immunomodulators. Dalam: Bolognia JL, Jorizzo JL, Rapini RP, penyunting. Dermatology. London: Mosby; 2003. h.2033-53
7. Mandelin J, Remitz A, Virtanen H, Reitamo S. One-year treatment with 0,1% tacrolimus ointment versus a corticosteroid regimen in adults with moderate to severe atopic dermatitis: a randomized, double-blind, comparative trial. Acta Derm Venereol. 2010;90:170-4
8. Paul C, Cork M, Rossi AB, Papp KA, Barbier N, Prost Y. Safety and tolerability of 1% pimecrolimus cream among infants: experience with 1133 patients treated for up to 2 years. Pediatrics. 2006;117:e118-28
9. Arguelles AR, Gorbea RM, Zamora MEI, Crelgo JG. Topic tacrolimus, alternative for oral erosive lichen planus resistant to steroids: a case report. Med Oral Patol Oral Cir Bucal. 2006;11:E462-6
10. Bernard LA, Bergman JN, Eichenfield LF. Pimecrolimus 1% cream (Elidel®) for atopic dermatitis. Skin Ther Letter. 2002;7:1-7
11. Buck ML. Topical macrolactam immunomodulators for atopic dermatitis. Pediatr Pharmacother. 2002;8:1-4
12. Reitamo S. Topical calcineurin inhibitors for atopic dermatitis. Eur Pharmacother. 2006;1-3
13. Baldo A, Cafiero M, Caterino PD, Costanzo LD. Tacrolimus ointment in the management of atopic dermatitis. Clin Cosmetic Invest Dermatol. 2009;2:1-7
14. Doss N, Kamoun M-R, Dubertret L, Cambazard F, Remitz A, et al. Efficacy of tacrolimus 0,03% ointment as second-line treatment for children with moderate-to-severe atopic dermatitis: evidence from a randomized, double-blind non-inferiority trial vs. fluticasone 0,005% ointment. Pediatr Allergy Immunol. 2010;21:321-9
15. Gupta AK, Adamiak A, Chow M. Tacrolimus: a review of its use for the management of dermatoses. J Eur Acad Dermatol Venereol. 2002;16:100-14
16. Furue M, Takeuchi S. Topical tacrolimus as treatment of atopic dermatitis. Clin Cosmetic Invest Dermatol. 2009;2:161-6
17. Thaci D, Salgo R. The topical calcineurin inhibitor pimecrolimus in atopic dermatitis: a safety update. Acta Dermatoven APA. 2007;16:58-62
18. Gollnick H, Kaufmann R, Stough D, Heikkila H, Andriano K, dkk. Pimecrolimus cream 1% in the long-term management of adult atopic dermatitis: prevention of flare progression. A randomized controlled trial. Br J Dermatol. 2008;158:1083-93
19. Kirsner RS, Heffernan MP, Antaya R. Safety and efficacy of tacrolimus ointment versus pimecrolimus cream in the treatment of patients with atopic dermatitis previously treated with corticosteroids. Acta Derm Venereol. 2010;90:58-64
20. Norris DA. Mechanisms of action of topical therapies and the rationale for combination therapy. J Am Acad Dermatol. 2005;53:S17-25
21. Brune A, Miller DW, Lin P, Cotrim-Russi D, Paller AS. Tacrolimus ointment is effective for psoriasis on the face and intertriginous areas in pediatric patients. Pediatr Dermatol. 2007;24:76-80
22. Ortonne J-P, Van de Kerkhof PCM, Prinz JC, Bieber T, Lahfa M, dkk. 0,3% tacrolimus gel and 0,5% tacrolimus cream show efficacy in mild to moderate plaque psoriasis: results of a randomized, open-label, observer-blinded study. Acta Derm Venereol. 2006;86:29-33
23. Kroft EBM, Erceg A, Maimets K, Vissers W, Van der Valk PGM, Van de Kerkhof PCM. Tacrolimus ointment for the treatment of severe facial plaque psoriasis. J Eur Acad Dermatol Venereol. 2005;19:249-51
24. Mrowietz U, Wustlich S, Hoexter G, Graeber M, Brautigam M, Luger T. An experimental ointment formulation of pimecrolimus is effective in psoriasis without occlusion. Acta Derm Venereol. 2003;83:351-3
25. Jacobi A, Braeutigam M, Mahler V, Schultz E, Herti M. Pimecrolimus 1% cream in the treatment of facial psoriasis: a 16-week open-label study. Dermatology. 2008;216:133-6
26. Kreuter A, Sommer A, Hyun J, Brautigam M, Brockmeyer NH, dkk. 1% pimecrolimus, 0,005% calcipotriol, and 0,1% betamethasone in the treatment of intertriginous psoriasis. Arch Dermatol. 2006;142:1138-43
27. Boone B, Ongenae K, Van Geel N, Vernijns S, De Keyser S, Naeyaert J-M. Topical pimecrolimus in the treatment of vitiligo. Eur J Dermatol. 2007;17:55-61
28. Radakovic S, Breier-Maly J, Konschitzky R, Kittler H, Sator P, et al. Response of vitiligo to once-vs. twice-daily topical tacrolimus: a controlled prospective, randomized, observer-blinded trial. J Eur Acad Dermatol Venereol. 2009;23:951-3
29. Tamler C, Oliveira PA, Duque-Estrada B, Avelleira JCR. Tacrolimus 0,1% ointment in the treatment of vitiligo: a series of cases. An Bras Dermatol. 2011;86:169-71
30. Falabella R, Barona MI. Update on skin repigmentation therapies in vitiligo. Pigment Cell Melanoma Res. 2008;22:42-65
31. Xu A-E, Zhang D-M, Wei X-D, Huang B, Lu L-J. Efficacy and safety of tacrolimus cream 0,1% in the treatment of vitiligo. Int J Dermatol. 2009;48:86-90
32. Hartmann A, Brocker E-B, Hamm H. Occlusive treatment enhances efficacy of tacrolimus 0,1% ointment in adult patients with vitiligo: results of a placebo controlled 12-month prospective study. Acta Derm Venereol. 2008;88:474-9
33. Kanwar AJ, Dogra S, Parsad D. Topical tacrolimus for treatment of childhood vitiligo in Asians. Clin Exp Dermatol. 2004;29:589-92
34. Fai D, Cassano N, Vena GA. Narrow-band UVB phototherapy combined with tacrolimus ointment in vitiligo: a review of 110 patients. J Eur Acad Dermatol Venereol. 2007;21:916-20
35. Kawalek AZ, Spencer JM, Phelps RG. Combined excimer laser and topical tacrolimus for the treatment of vitiligo: a pilot study. Dermatol Surg. 2004;30:130-5
36. Boone B, Ongenae K, Van Geel N, Vernijns S, De Keyser S, Naeyaert J-M. Topical pimecrolimus in the treatment of vitiligo. Eur J Dermatol. 2007;17:55-61
37. Goweini ME, Sayed NE, Ramly ME. Topical pimecrolimus versus clobetasol in the treatment of vitiligo. Egypt J Derm & Androl. 2006;27:13-8
38. Farajzadeh S, Daraei Z, Esfandiarpour I, Hosseini SH. The efficacy of pimecrolimus 1% cream combined with microdermabrasion in the treatment of nonsegmental childhood vitiligo: a randomized placebo-controlled study. Pediatr Dermatol. 2009;26:286-91
40. Brownell I, Quan LT, Hsu S. Topical pimecrolimus in the treatment of seborrheic dermatitis. Dermatol Online J. 2003;9:13
41. Ozden MG, Tekin NS, Ilter N, Ankarali H. Topical pimecrolimus 1% cream for resistant seborrheic dermatitis of the face. Am J Clin Dermatol. 2010;11:51-4
42. Koc E, Arca E, Kose O, Akar A. An open, randomized, prospective, comparative study of topical pimecrolimus 1% cream and topical ketoconazole 2% cream in the treatment of seborrheic dermatitis. J Dermatol Treat. 2009;20:4-9
43. Sugita T, Tajima M, Tsubuku H, Tsuboi R, Nishikawa A. A new calcineurin inhibitor, pimecrolimus, inhibits the growth of Malassezia spp. Antimicrob Agents Chemother. 2006;50:2897-8
44. Cicek D, Kandi B, Bakar S, Turgut D. Pimecrolimus 1% cream, methylprednisolone aceponate 0,1% cream and metronidazole 0,75% gel in the treatment of seborrhoeic dermatitis: a randomized clinical study. J Dermatol Treat. 2009;20:344-9
45. Tatlican S, Eren C, Oktay B, Eskioglu F, Durmazlar PK. Experience with repetitive use of pimecrolimus: exploring the effective and safe use in the treatment of relapsing seborrheic dermatitis. J Dermatol Treat. 2010;21:83-5
46. Safa G, Darrieux L, Coic A, Tisseau L. Type 1 leprosy reversal reaction treated with topical tacrolimus along with systemic corticosteroids. Indian J Med Sci. 2009;63:359-62
47. Ruzicka T, Assmann T, Lebwohl M. Potential future dermatological indications for tacrolimus ointment. Eur J Dermatol. 2003;13:331-42
48. Edwards PC, Kelsch R. Oral lichen planus: clinical presentation and management. J Can Dental Assoc. 2002;68:494-9
49. Lener EV, Brieva J, Schachter M, West LE, West DP. Successful treatment of erosive lichen planus with topical tacrolimus. Arch Dermatol. 2001;137:419-22
50. Ujiie H, Shibaki A, Akiyama M, Shimizu H. Successful treatment of nail lichen planus with topical tacrolimus. Acta Derm Venereol. 2010:90:218-9
51. Laeijendecker R, Tank B, Dekker SK, Neumann HAM. A comparison of treatment of oral lichen planus with topical tacrolimus and triamcinolone acetonide ointment. Acta Derm Venereol. 2006;86:227-9
52. Becker JC, Houben R, Vetter CS, Brocker EB. The carcinogenic potential of tacrolimus ointment beyond immune suppression: a hypothesis creating case report. BMC Cancer. 2006;6:7
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