Fernández VJM, Armario HJC

Language: Spanish
References: 187
Page: 271-294
PDF size: 389.62 Kb.

ABSTRACT

Since its introduction in Dermatalogy 60 years ago, retinoids have acquired the condition of an essential drug in our specialty. This fact is due to the effective results in a large number of cutaneous processes as well as to the innovations undertaken in both its structure and its formula. Today its effectiveness and security have been well established in the topic and systemic formulations, in acne, psoriasis and photoaging. Over the last years new indications have been described of retinoids in dermatology among which we highlight their use in the treatment of cutaneous cancer, or in cosmetic uses with good results in the cicatrization of wounds, cutaneous striae in initial phases or androgenetic alopecia. Pharmacological advances have permitted more effective vitamin A derivatives and with less adverse effects. Tretinoin, although being of the most irritant activity, continues to be the most effective topica drug in photoaging and cutaneous cancer. Isotretinoin is the drug to choose for severe chronic acne, adapalene is the topica formulation best tolerated by acne, tazarotene is the first topica retinoid with effectiveness in psoriasis, etretinate and acitretino are considered the ones for the systemic treatment of psoriasis. In recent years new molecules have been described that have broadened the indications of the retinoids in dermatology, these are alitretinoin for Kaposi’s sarcoma associated to AIDS and bexarotene for the cutaneous lymphoma of T cells.

REFERENCES

1. Fernández Vozmediano JM, Galiana Martínez J, Casas Gómez VE. Retinoids. Basel (Switzerland): Ediciones Roche, 1991.

2. Fernández Vozmediano JM, Alonso Blasi N, Romero Cabrera MA, Fernández García JR, Cañizares Molle JC. Pitiriasis rubra pilaris infantil. Tratamiento con etretinato. Actas Dermo-Sif 1988;79:697-700.

3. Fernández Vozmediano JM, Puerto Castrillon M. Terapéutica con Ácido Retinoico: indicación en la ictiosis, dosis y efectos secundarios. Antol Dermatol 1984;14:29-31.

4. Fernández Vozmediano JM, Calap Calatayud J. Ictiosis Vulgar: tratamiento con Etretinato. Gaceta Dermatológica 1984;5:123-126.

5. Fernández Vozmediano JM, Calap Calatayud J. Ictiosis lamelar: Tratamiento con etretinato. Gaceta Dermatológica 1984;5:123-126.

6. Fernández Vozmediano JM, Rico de Cos S, Fernández Gómez E, Calap Calatayud J. Colodión Baby con evolución a ictiosis lamelar. Tratamiento con ácido retinóico. Actas Dermo-Sif 1985;76:503-507.

7. Pfahl M. The molecular mechanism of retinoid action. Retinoids today and tomorrow. Retinoid Dermatol 1996;44:2-6.

8. Pektovich M. Regulation of gene expression by vitamin A: the role of nuclear retinoic acid receptors. Annu Rev Nutr 1992;12:443-447.

9. Orfanos C, Zouboulis CC, Almond-Roesler B, Geilen CC. Current use and future potential role of retinoids in dermatology. Drugs 1997;53:358-388.

10. Bouclier M, Chatelus A, Ferracin J, Delain C, Shroot B, Hensby CN. Quantification of epidermal histological changes induced by topical retinoids and CD271 in the rhino mouse model using a standardized image analysis technique. Skin Pharmacol 1991;4:65-69.

11. Krust A, Kastner P, Petrovich M, Zelent A, Chambon P. A third human retinoic acid receptor h-RAR-gamma. Proc Natl Acad Sci USA 1989;86:5310-5314.

12. Chytil F, Stump DG. Cellular retinoic acid and retinol binding proteins. In Saurat JH (ed). Retinoids: 10 years on. Basel: Karger, 1991;38.

13. Brand NJ, Petrovich M, Krust A, Chambon P, de The H, Marchio A, Tiollais P, Dejean A. Identification of a second human retinoic acid receptor. Nature 1988;332:850-853.

14. Mangelsdorf DJ, Ong ES, Dyck JA, Evans RM. Nuclear receptor that identifies a novel retinoic acid response pathway. Nature 1990;345:224-226.

15. Zelent A, Krust A, Petrovich M, Kastner P, Chambon P. Cloning of a murine alfa and beta retinoic acid receptor and a novel receptor gamma predominantly expressed in skin. Nature 1989;339:714-717.

16. Mangelsdorf DJ, Borgmeyer U, Heyman RA, Zhou JY, Ong ES, Oro AE, Kakizuka A, Evans RM. Characterization of three RXR genes that mediate the actioin of 9-cis-retinoic acid. Genes Dev 1992;6:329-344.

17. Leid M, Kastner P, Lyons R, Nakshatri H, Saunders M, Zacharewski T, Chen JY, Staub A, Garnier JM, Mader S. Purification, cloning and RXR identity of the HeLa cell factor with which RAR or TR heterodimirizes to bind target sequences efficiently. Cell 1992;68:377-395.

18. Klingman AM. The growing importance of topical retionids in clinical dermatology: a retrospective and prospective analysis. J Am Acad Dermatol 1998;39:S2-S7.

19. Sfavi K. Serum vitamin A levels in psoriasis: results from the first national health and nutrition examination survey. Arch Dermatol 1992;128:1130-1131.

20. Shapiro SS, Latriano L. Pharmacokinetic and pharmacodynamic considerations of retinoids: tretinoin. J Am Acad Dermatol 1998;39:S13-S16.

21. Thomas JR, Doyle JP.l The therapeutic uses of topical vitamin A acid. J Am Acad Dermatol 1981;4:505-515.

22. Gollnick HPM. The treatment of acne. Drugs Today 1992;5:353-361.

23. Boudou P, Soliman H, Chivot M, Villete JM, Vexiau P, Belanger A, Fiet J. Effect of oral isotretinoin treatment on skin androgen receptor level in male acneic patients. J Clin Endocrinol Metab 1995;80:1158-1161.

24. Goulden V, Layton AM, Cunliffe WJ. Current indications for isotretinoin as a treatment for acne vulgaris. Dermatology 1995;190:284-287.

25. Gottardis MM, Lamph WW, Shalinsky DR, Wellstein A, Heyman RA. The efficacy of 9-cis-retinoic acid in experimental models of cancer. Breast Cancer Res Treat 1996;38:85-96.

26. Brodowicz T, Wiltschke C, Kandioler-Eckersberger D, Grunt TW, Rudas M, Schneider SM, Hejna M, Budinsky A, Zielinski CC. Inhibition of proliferation and induction of apoptosis in soft tissue sarcoma cell by interferon- and retinoids. Br J Cancer 1999;80:1350-1358.

27. Lovat PE, Irving H, Annicchiarico-Petruzzelli M, Bernassola F, Malcolm AJ, Pearson AD, Melino G, Redfern CP. Retinoids in neuroblastoma therapy: distinct biological propierties of 9-cis and all-trans-retinoic acid. Eur J Cancer 1997;33:2075-2080.

28. Lucek RW, Colburn WA. Clinical pharmacokinetics of the retinoids. Clin Pharmacokinet 1985;10:38-62.

29. Wiegand UW, DeBersaques J, de la Brassinne M. Etretinate concentrations in plasma and subcutis of acitretin-treated female patients. J Eur Acad Dermatol Venereol 1995;5:S86.

30. Wiegand UW, Jensen BK. Pharmacokinetics of acitretin in humans. In Saurat JH (ed). Retinoids: 10 years on. Basel: Karger, 1991:192-203.

31. Chou RC, Wyss R, Huselton CA, Wiegand UW. A potentially new metabolic pathway: ethyl esterification of acitretin. Xenobiotica 1992;22:993-1002.

32. Larsen FG, Steinkjer B, Jakobsen P, Hjorter A, Brockhoff PB, Nielsen-Kudsk F. Acitretin is converted to etretinate only during concomitant alcohol intake. Br J Dermatol 2000;143:1164-1169.

33. Wiegand UW, Chou RC. Pharmacokinetics of acitretin and etretinate. J Am Acad Dermatol 1998;39:S25-S33.

34. Bernard BA. Adapalene, a new chemical entity with retinoid activity. Skin Pharmacol 1993;6 (Suppl 1):61-69.

35. Millikan LE. Adapalene: an update on newer comparative studies between the various retinoids. Int J Dermatol 2000;39:784-788.

36. Napgal S, Patel S, Asano AT, Johnson AT, Duvic M, Chandraratna RA. Tazarotene induced gene 1 (TIG-1), a novel retinoic acid receptor-responsive gene in skin. J Invest Dermatol 1996;106:269-274.

37. Napgal S, Patel S, Jacobe S, Disepio D, Ghosn C, Malhota M, Teng M, Duvic M, Chandraratna RAS. Tazarotene induced gene 2 (TIG-2), a novel retinoic acid receptor-responsive gene in skin. J Invest Dermatol 1997;109:91-95.

38. Bernard F, Ortonne JP, Boucliler M. The rhino mouse model: the effects of topically applied all-trans retinoic acid and CD271 on the fine structure of the epidermis and utricle wall of pseudocomedones. Arch Derm Res 1991;283:100-107.

39. Chandraratna RAS. Tazarotene: the first receptor-selective topical retinoid for the treatment of psoriasis. J Am Acad Dermatol 1997;37:48-55.

40. Lowe MN, Plosker GL. Bexarotene. Am J Clin Dermatol 2000;1:245-250.

41. Sun SY, Lotan R. Retinoids as chemopreventive and therapeutic agents. Drug Future 1998;23:621-634.

42. Kizaki M, Dawson MI, Heyman R, Elster E, Morosetti R, Pakkala S, Chen DL, Ueno H, Chao W, Morikawa M, Ikeda Y, Heber D, Pfahl M, Koeffler HP. Effects of novel retinoid X receptor-selective ligands on myeloid leukemic differentiation and proliferation in vitro. Blood 1996;87:1977-1984.

43. Plewig G, Ruhfus A, Klovexorn W. Sebum suppression after topical application of retionid (Arotinoid and isotretinoin). J Invest Dermatol 1993;80:357.

44. Kligman AM, Fulton JE, Plewig G. Topical vitamin A acid in acne vulgaris. Arch Dermatol 1969;99:469-476.

45. Verschoore M, Langner A, Wolska H, Jablonska S, Czernielewski J, Schaefer H. Efficacy and safety of CD271 alcoholic gels in the topical treatment of acne vulgaris. Br J Dermatol 1991;124:368-371.

46. Webster GF. Topical tretinoin in acne therapy. J Am Acad Dermatol 1998;39:S38-S44.

47. Selcen D, Seidman S, Nigro MA. Otocerebral anomalies associated with topical tretinoin use. Brain Dev 2000;22:218-220.

48. Amblard P, Bazex A. L’association tretinoine-erythromycine base: nouveau traitment local de l’acné. Sem Hosp Paris 1980;56:17.

49. Kligman AM. The compatibility of combinations of glicolic acid and tretinoin in acne and in photoaged facial skin. J Geriatr Dermatol 1995;3:25A-28A.

50. Chalker DK, Lesher JL, Smith JG Klauda HC, Pochi PE, Jacoby WS, Yonkosky DM, Voorhees JJ, Ellis CN, Matsuda-John S. Efficacy of topical isotretinoin 0.05% gel in acne vulgaris: results of a multicenter, double-blind investigation. J Am Acad Dermatol 1987;17:251-254.

51. Hughes BR, Norris JFB, Cunliffe WJ. A double-blind evaluation of topical isotretinoin, benzoyl peroxide and placebo in patients with acne. Br J Dermatol 1989;121 (Suppl 34):42-44.

52. Santana D, Bun H, Joachim J, Durand A, Reynier JP. Plasma concentrations after different doses of topical isotretinoin. Skin Pharmacol 1994;7:140-144.

53. Fernández Vozmediano JM, Romero MA, Casas VE, Alonso N. Empeoramiento eventual durante el tratamiento con isotretinoino. Retinoides al día 1989;4:10-11.

54. Fernández Vozmediano JM, Casas Gómez V, Alonso Blasi N, Galiana Martínez FJ, Luque Barea MA. Resistencia terapéutica al isotretinoin en un caso de acné conglobata en tratamiento anticomicial. Actas Derm-Sif 1990;81:185-187.

55. Casas Gómez V, Alonso Trujillo F, Alonso Blasi N, Romero Cabrera MA, Fernández Vozmediano JM, Almenara Barrios J, Galiana Martínez FJ. Farmacovigilancia de pacientes tratados con isotretinoino. Actas Dermo-Sif 1990;81:247-251.

56. Bernerd F, Verschoore M, Bouclier M. Comparison of the comedolytic action of adapalene in the rhino mouse and human acne. J Eur Acad Dermatol Venereol 1996;7(Suppl 2):S184-S186.

57. Shalita A, Weiss JL, Chalker DK, Ellis CN, Greenspan A, Katz HI, Kantor I, Millikan LE, Swinehart T, Swinyer L, Whitmore C, Baker M, Czermieslewski J. A comparison of the efficacy and safety of adapalene gel 0.1% and tretinoin gel 0.025% in the treatment of acne vulgaris. A multicentric trial. J Am Acad Dermatol 1996;34:482-485.

58. Hensby CN, Cavey D, Bouclier M, Chatelus A, Algate D, Eustache J, Shroot B. The in vivo and in vitro anti-inflammatory activity of CD 271, a new retinoid-like modulator of cell differentiation. Pharmacol Skin. 1989;3:160-162.

59. Verschoore M, Bouclier PhD, Czernielewki J, Hensby C. Topical retinoids. Dermatol Clin 1993;11:107-115.

60. Guerra Tapia A. Los retinoides en el tratamiento del acné. En Fernández Vozmediano JM (ed). Acné. Aula Médica, Madrid, 2000;177-217.

61. Philips P, Steinberg M, Maibach HI, Askers WA. A comparison of rabbit and human skin responses to certain irritants. Toxicol Applic Pharmacol 1972;21:369-372.

62. Marzulli FN, Maibach HI. Contact allergy: predictive testing in humans. Advances in modern toxicology 1977;4:353-372.

63. Kaidbey KH, Kligman AM. Identification of topical photosensitizing agents in humans. J Invest Dermatol 1978;70:149-151.

64. Guy R, Green M, Kealey T. Modeling of acne in vitro. J Invest Dermatol 1996;106:176-182.

65. Weiss JS, Shavin JS. Adapalene for the treatment of acne vulgaris. J Am Acad Dermatol 1998;39:S50-S54.

66. Shalita A, Chalker D, Griffith R. Double-blind study of AGN 190168, a new retinoid gel, in the topical treatment of acne vulgaris. J Invest Dermatol 1993;100:542-547.

67. Weinstein GD. Safety, efficacy and duration of therapeutic effect of tazarotene used in the treatment of plaque psoriasis. Br J Dermatol 1996;135(Suppl 49):32-36.

68. Leyden JJ. Topical treatment of acne vulgaris: retinoids and cutaneous irritation. J Am Acad Dermatol 1998;38:S1-S4.

69. Layton AM, Henderson CA, Cunliffe WJ. A clinical evaluation of acne scarring and its incidence. Clin Exp Dermatol 1994;19:303-308.

70. Leyden JJ. The role of isotretinoin in the treatment of acne: personal observations. J Am Acad Dermatol 1998;39:S45-S49.

71. Azón-Mansoliver A, Grau C. Acute appendicitis and isotretinoin. A coincidence? J Eur Acad Dermatol Venereol 2000;14:222-236.

72. Layton AM, Cunliffe WJ. Guidelines for optimal use of isotretinoin in acne. J Am Acad Dermatol 1992;27:S2-S7.

73. Wiegand UW, Chou RC. Pharmacokinetics of oral isotretinoin. J Am Acad Dermatol 1998;39:S8-S12.

74. Kellet SC, Gawkrodger DJ. The psychological and emotional impact of acne and the effect of treatment with isotretinoin. Br J Dermatol 1999;140:273-282.

75. Strauss JS, Gottlieb AB, Jones T, Koo JYM, Leyden JJ, Lucky A, Pappas AA, McLane J, Leach EE. Concomitant administration of vitamin E does not change the side effects of isotretinoin as used in acne vulgaris: A randomized trial. J Am Acad Dermatol 2000;43:777-784.

76. Gollnick HPM, Bonnekoh B. Topical and Systemic Retinoids. In: van de Kerkhof (ed). Textbook of psoriasis. Blackwell Science, Oxford 1999,pp.233-256.

77. Saurat JH. Retinoids and psoriasis: novel issues in retinoid pharmacology and implications for psoriasis treatment. J Am Acad Dermatol 1999;41:S2-S6.

78. Harper RA. Specificity in the synergism between retinoic acid and EGF on the growth of adult human skin fibroblasts. Exp Cell Res 1988;178:254-263.

79. Imcke E, Ruszczak ZB, Mayer-da-Silva A, Detmar M, Orfanos CE. Cultivation of human dermal microvascular endothelial cells in vitro: Immunocytochemical and ultrastructural characterization and effect of treatment with three synthetic retinoids. Arch Dermatol Res 1991;283:149-157.

80. Bauer R, Orfanos CE. Effects of synthetic retinoids on human peripheral blood lymphocytes and polymorphonuclears in vitro. In: Cunliffe WJ (ed). Retinoid Therapy: A review of Clinical and Laboratory Research. MTP Press, Boston 1984,pp.101-118.

81. Struy H, Bohne M, Morenz J. Effects of retinoids on human neutrophil-derived free radicals. Eur J Haematol 1996;59(Suppl 57):52.

82. Dupuy P, Bagot M, Heslan M, Dubertret L. Synthetic retinoids inhibit the antigen presenting properties of epidermal cells in vitro. J Invest Dermatol 1989;93:455-459.

83. DiSepio D, Malhotra M, Chandaratna AS, Nagpal S. Retinoic acid receptor-nuclear factor-interleukin 6 antagonism. J Biol Chem 1997;41:25555-25559.

84. Gollnick H, Zaun H, Ruzicka T. Relapse rate of severe generalised psoriasis after treatment with acitretin or etretinate. Results of the first randomised double-blind multicenter half-year follow up study. Eur J Dermatol 1993;3:442-446.

85. Casas Gómez V, Alonso Trujillo F, Alonso Blasi N, Romero Cabrera MA, Fernández Vozmediano JM, Almenara Barrios J, Galiana Martínez FJ. Seguimiento de los pacientes tratados con etretinato. Actas Derm-Sif 1990;81:243-246.

86. Kragballe K, Jansen CT, Geiger JM, Bjerke JR, Falk ES, Gip L, Hjorth N, Lauharanta J, Mork NJ, Reunala T. A double-blind comparison of acitretin and etretinate in the treatment of severe psoriasis. Acta Derm Venereol 1989;69:35-40.

87. Armario Hita JC, Fernández Vozmediano JM. Actualización en el tratamiento de la psoriasis (VII). Retinoides. Act Dermatolog 2001;40:231-238.

88. Katz HI, Waalen J, Leach EE. Acitretin in psoriasis: an overview of adverse effects. J Am Acad Dermatol 1999;41:S7-S12.

89. van de Kerkhof PC, Cambazard F, Hutchinson PE, Haneke E, Wong E, Souteyrand P, Damstra RJ, Combemale P, Neumann MH, Chalmers RJ, Olsen L, Revuz J. The effect of addition of calcipotriol ointment (50micrograms/g) to acitretin therapy in psoriasis. Br J Dermatol 1998;138:84-89.

90. Carlberg C, Saurat JH. Vitamin D-retinoid association: molecular basis and clinical applications. J Invest Dermatol Symp Proc 1996;1:82-86.

91. Rosenbaum MM, Roegnik HH. Treatment of generalized pustular psoriasis with etretinate (RO-10-9359) and methotrexate. J Am Acad Dermatol 1984;10:357-361.

92. Armario Hita JC, Fernández Vozmediano JM. Actualización en el tratamiento de la psoriasis (X). Tratamientos combinados para la psoriasis. Act Dermatolog 2001;40:541-547.

93. Sommerburg C, Kietzmann H, Eichelberg D. Acitretin in combination with PUVA: a randomized double-blind placebo-controlled study in severe psoriasis. J Eur Acad Derm Venereol 1993;2:308-317.

94. Lowe NJ, Prystowsky JH, Bourget T, Edelstein J, Nychay s, Armstrong R. Acitretin plus UVB therapy for psoriasis. J Am Acad Dermatol 1991;24:591-594.

95. Esgleyes-Ribot T, Chandraratna RA, Lew-Kaya DA, Sefton J, Duvic M. Response of psoriasis to a new topical retinoid ADN 190168. J Am Acad Dermatol 1994;30:581-590.

96. Duvic M, Nagpal S, Asano AT, Chandraratna RAS. Molecular mechanisms of tazarotene action in psoriasis. J Am Acad Dermatol 1997;37:S18-S24.

97. Persaud A, Bershad S, Lamba S, Lebwohl M. Short-contact tazarotene therapy for psoriasis[abstract & poster P510]. 59th Annual Meeting of the American Academy of Dermatology, 2001 Mar 2-5, Washington DC.

98. Marks R. Pharmacokinetics and safety review of tazarotene. J Am Acad Dermatol 1998;39:S134-S138.

99. Lebwohl M, Poulin Y. Tazarotene in combination with topical corticosteroids. J Am Acad Dermatol 1998;39:S139-S143.

100. Koo JY. Tazarotene in combination with phototherapy. J Am Acad Dermatol 1998;39:S144-S148.

101. Koo JYM, Lowe J, Lew-Kaya DA, Vasilopoulos AI, Lue JC, Sefton J, Gibson JR. Tazarotene plus UVB phototherapy in the treatment of psoriasis. J Am Acad Dermatol 2000;43:821-828.

102. Gilchrest BA, Yaar M. Aging and photoaging of the skin: observations at the cellular and molecular level. Br J Dermatol 1992; 127(Suppl 41):25-30.

103. Fisher GJ, Datta SC, Talwar HS, Wan ZQ, Varani J, Kang S, Voorhees JJ. Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature 1996;379:335-339.

104. Bhawan J. Short- and long-term histologic effects of topical tretinoin on photodamaged skin. Int J Dermatol 1998;37:286-292.

105. Wang Z, Boudjelal M, Kang S, Voorhees JJ, Fisher GJ. Ultraviolet irradiation of human skin causes functional vitamin A deficiency, preventable by all-trans-retinoic acid pre-treatment. Nat Med 1999;5:418-422.

106. Cordero A Jr. La vitamina A acida en la piel senil. Act Ter Dermatol 1983;6:49-54.

107. Kligman AM, Grove GL, Hirose R, Leyden JJ. Topical tretinoin for photoaged skin. J Am Acad Dermatol 1986;15:836-859.

108. Weiss JS, Ellis CN, Headington JT, Tincoff T, Hamilton TA, Voorhees JJ. Topical tretinoin improves photoaged skin: a double-blind, vehicle controlled study. JAMA 1988;259:527-532.

109. Kang S, Voorhess JJ. Photoaging therapy with topical tretinoin: an evidence-based analysis. J Am Acad Dermatol 1998;39:S55-S61.

110. Fernández Vozmediano JM, Alonso Trujillo F, Carbajo Espejo J, Espejo Posada ML. Estudio del efecto del Ácido Retinoico en el tratamiento del envejecimiento cutáneo. Dermatología Cosmética 1990;2:38-44.

111. Rafal ES, Griffiths CEM, Ditre CM, Finkel LJ, Hamilton TA, Ellis CN, Voorhees JJ. Topical tretinoin (retinoic acid) treatment for liver spots associated with photodamage. N Engl J Med 1992;326:368-374.

112. Fleischer AB, Schwartzel EH, Colby SI, Altman DJ. The combination of 2% 4-hydroxyanisole (Mequinol) and 0.01% tretinoin is effective in improving the appearance of solar lentigines and related hyperpigmented lesions in two double-blind multicenter clinical studies. J Am Acad Dermatol 2000;42:459-467.

113. Griffiths CEM, Kang S, Ellis CN Kim KJ, Finkel LJ, Ortiz-Ferrer LC, White GM, Hamilton TA, Voorhees JJ. Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation: a double-blind, vehicle-controlled comparison of 0.1% and 0.025% tretinoin creams. Arch Dermatol 1995;131:1037-1044.

114. Griffiths CEM. The role of retinoids in the prevention and repair of aged and photoaged skin. Clin Dermatol 2001;26:613-618.

115. Olsen EA, katz HI, Levine N, Nigra TP, Pochi PE, Savin RC, Shupack J, Weinstein GD, Lufrano L, Jou HC. Sustained improvement in photodamaged skin with reduced tretinoin emollient cream treatment regimen: effect of once-weekly and three-times-weekly applications. J Am Acad Dermatol 1997;37:227-230.

116. Griffiths CEM, Russman AN, Majmudar G, Singer RS, Hamilton TA, Voorhees JJ. Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid). N Engl J Med 1993;329:530-535.

117. Kim JJ, Chang MW, Shwayder T. Topical tretinoin and 5-fluoruracil in the treatment of linear verrucous epidermal nevus. J Am Acad Dermatol 2000;43:129-132.

118. Biesalski HK. All-trans-retinoic acid modulates ultraviolet-induced lipid peroxidation and suppresses ornithine decarboxylase in human skin fibroblasts. Retinoids 1999;15:118-120.

119. Fisher GJ, Datta SC, Talwar HS, Wang ZQ, Varani J, Kang S, Voorhees JJ. Molecular basis of sun-induced premature skin aging and retinoid antagonism. Nature 1996;379:335-339.

120. Diffey BL, Spiro JG, Hindson TC. Photosensitivity studies and isotretinoin therapy. J Am Acad Dermatol 1985;12:119-120

121. Robinson TA, Kligman AM. Treatment of solar keratoses of extremities with retinoic acid and 5-fluoruracil. Br J Dermatol 1975;92:703-706.

122. Maddin S, Lauharanta J, Agache P, Burrows L, Zultak M, Bulger L. Isotretinoin improves the appearance of photodamaged skin: results of a 36-week, multicenter, double-blind, placebo-controlled trial. J Am Acad Dermatol 2000;42:56-63.

123. Hernández-Pérez E, Khawaja HA, Alvarez TY. Oral isotretinoin as part of the treatment of cutaneous aging. Dermatol Surg 2000;26:649-652.

124. Humphreys TR, Werth V, Dzubow L, Kligman A. Treatment of photodamaged skin with trichloroacetic acid and topical tretinoin. J Am Acad Dermatol 1996;34:638-344.

125. Pierard-Franchimont C, Castelli D, Cromphaut IV. Tensile properties and contours of aging facial skin. A controlled double-blind comparative study of the effects of retinol, melibose-lactose and their association. Skin Res Technol 1998;4:237-243.

126. Duell EA, Derguini F, Kang S, Elder JT, Voorhees JJ. Extraction of human epidermis treated with retinol yields retro-retinoids in to free retinol and retinyl esters. J Invest Dermatol 1996;107:178-182.

127. Goldfarb M, Kang S, Griffiths CEM. Photographic assessment of the effects of adapalene 0.1% and 0.3% gels and vehicle on photodamaged skin. J Eur Acad Dermatol Venereol 2000;14:S315

128. Sefton J, Kligman AM, Kooper SC, Lue JC, Gibson JR. Photodamage pilot study: a double-blind, vehicle-controlled study to assess the efficacy and safety of tazarotene 0.1% gel. J Am Acad Dermatol 2000;43:656-663.

129. Casas Gómez V, Fernández Vozmediano JM. Retinoides y cancer. Piel 1990;5:151-153.

130. Hong WK, Itri LM. Retinoids and human cancer. In: Sporn MB, Roberts AB, Goodman DS (eds). The retinoids. New york: Raven Press;1994:597-658.

131. Levine N. Role of retinoids in skin cancer treatment and prevention. J Am Acad Dermatol 1998;39:S62-S66.

132. Cristofolini M, Zumiani G, Scappini P, Piscioli F. Aromatic retinoid in the chemoprevention of the progression of nevoid basal-cell carcinoma syndrome. J Dermatol Sur Oncol 1984;10:778-781.

133. Fernandez Vozmediano JM. Investigación en Cirugía Dermatológica. Retinoides. En: Camacho F, de Dulanto F (eds.): Cirugía Dermatológica. Aula Médica: Madrid, 1995:717-726.

134. Moriarty M, Dunn J, Darragh A, Lambe R, Brick I. Etretinate in treatment of actinic keratoses. Lancet 1982;1:364-365.

135. Kligman AM, Thorne EG. Topical therapy of actinic keratoses with tretinoin. In: Marks R (ed). Retinoids in cutaneous malignancy. Oxford, UK: Blackwell Scientific Publications;1991:66-73.

136. Hughes BR, Marks R, Pearse AD, Gaskell SA. Clinical response and tissue effects of etretinate treatment of patients with solar keratoses and basal cell carcinoma. J Am Acad Dermatol 1988;18:522-529.

137. Thorne EG. Long-term clinical experience with a topical retinoid. Br J Dermatol 1992;127(Suppl):31-36.

138. Odom R. Managing actinic keratoses with retinoids. J Am Acad Dermatol 1998;39:S74-S78.

139. Bercovitch L. Topical chemotherapy of actinic keratoses of the upper extremity with tretinoin and 5-fluoruracil: a double-blind controlled study. Br J Dermatol 1987;116:549-552.

140. Sander Ca, Pfeiffer C, Kligman AM, Plewig G. Chemotherapy for disseminated actinic keratoses with 5-fluoruracil and isotretinoin. J Am Acad Dermatol 1997;36:236-243.

141. Sankaranarayanan R, Mathew B, Nair PP, Somanathan T, Varghese C, Jyothirmayi R, Krishnan Nair M. Chemoprevention of cancer of the oral cavity and the head and neck. IARC Sci Publ 1996;136:13-25.

142. Hong WK, Endicott J, Itri LM, Doos W, Batsakis JG, Bell R, Forfonoff S, Byers R, Atkinson EN, Vaughan C. 13-cis-retinoic acid in the treatment of oral leukoplasia. N Engl J Med 1986;315:1501-1505.

143. Lippman SM, Batsakis JG, Toth BB, Webers RS, Lee JJ, Martin JW, Hays GL, Goepfert H, Hong WK. Comparison of low dose isotretinoin with beta carotene to prevent oral carcinogenesis. N Engl J Med 1993;328:15-20.

144. Moon TE, Levine N, Cartmel B, Bangert J, Rodney S, Schreiber M, Peng YM, Ritenbaugh C, Meyskens F, Alberts D. Design and recruitment for retinoid skin cancer prevention (SKI-CAP) trials. Cancer Epidemiol Biomarkers Prev 1995;4:661-669.

145. Kraemer KH, DiGiovanna JJ, Moshell AN, Tarone RE, Peck GL. Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med 1988;318:1633-1637.

146. DiGiovanna JJ. Retinoid chemoprevention in the high-risk patient. J Am Acad Dermatol 1998;39:S82-S85.

147. Peris K, Fargnoli MC, Chimenti S. Preliminary observations on the use of topical tazarotene to treat basal-cell carcinoma. N Engl J Med 1999;341:1767-1768.

148. Kelly JW, Sabto J, Gurr FW, Bruce F. Retinoids to prevent skin cancer in organ transplant recipients. Lancet 1991;338:1407.

149. Bavinck JN, Tieben LM, Van der Woude FJ, Tegzess AM, Hermans J, ter Schegget J, Vermeer BJ. Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant recipients: a double-blind, placebo-controlled study. J Clin Oncol 1995;13:1933-1938.

150. McKenna DB, Murphy GM. Skin cancer chemoprophylaxis in renal transplant recipients: 5 years of experience using low-dose acitretin. Br J Dermatol 1999;140:656-660.

151. Rook AH, Jaworsky C, Nguyen T, Grossman RA, Wolfe JT, Witmer WK, Kligman AM. Beneficial effect of low-dose systemic retinoid in combination with topical tretinoin for the treatment and prophylaxis of premalignant and malignant skin lesions in renal transplant recipients. Transplantation 1995;59:714-719

152. Lupo MP. Antioxidants and vitamins in cosmetics. Clin Dermatol 2001;19:467-473.

153. Boerman MHEM, Napoli JL. Cellular retinol-binding protein-supported retinoid acid synthesis. J Biol Chem 1996;271:5610-5616.

154. Duell EA, Kang S, Voorhees JJ. Unoccluded retinol penetrates human skin in vivo more effectively than unoccluded retinyl palmitate or retinoic acid. J Invest Dermatol 1997;109:301-309.

155. Counts DF, Skreko F, McBee J. The effects of retinyl palmitate on skin composition and morphometry. J Soc Cosmet Chem 1988;39:235-240.

156. Saurat JH, Didierjena L, Masgruve E, Piletta PA, Jaconi S, Chatellard-Gruaz D, Gumowski D, Masouye I, Salomon D, Siegenthaler G. Topical retinaldehyde on human skin: Biologic effects and tolerance. J Invest Dermatol 1994;103:770-774.

157. Kang S, Duell EA, Fisher GJ, Datta SC, Wang ZQ, Reddy AP, Tavakkol A, Yi JY, Griffiths CE, Elder JT. Application of retinol to human skin in vivo induces epidermal hyperplasia and celllular retinoid-binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation. J Invest Dermatol 1995;105:549-556.

158. Kennedy MC, Shin LM, Labermeir U. Modulation of rabbit keratinocyte production of collagen, sulfated glycosaminoglycans and fibronectin by retinol and retinoic acid. Biochem Biophys Acta 1991;889:156.

159. Kligman LH. Effects of all transretinoic acid on the dermis of hairless mice. J Am Acad Dermatol 1986;15:779-785.

160. Lee KH, Tong TG. Mechanism of action of retinyl compounds on wound healing. J Pharm Sci 1970;59:1195.-1197.

161. Gajdusek CM, Luo Z, Myberg MR. Basic fibroblast growth factor and transforming growth factor beta-1 synergistic mediators of angiogenesis in vitro. J Cell Physiol 1993;157:133-144.

162. Elson ML. The role of retinoids in wound healing. J Am Acad Dermatol 1998;39:S79-S81.

163. Popp C, Kligman AM, Stoudemayer TJ. Pretreatment of photoaged forearm skin with topical tretinoin accelerates healing of full-thickness wounds. Br J Dermatol 1995;132:46-53.

164. Mandy S. Tretinoin in the preoperative and postoperative management of dermabrasion. J Am Acad Dermatol 1986;15:848-879.

165. Apfelberg DB. Ultrapulse carbon dioxide laser with CPG scanner for full-face resurfacing for rhytids, photoaging, and acne scars. Plast Reconstr Surg 1997;99:1817-1825.

166. Hevia O, Nemeth AJ, Taylor JR. Tretinoin accelerates healing after trichloroacetic acid chemical peel. Arch Dermatol 1991;127:678-682.

167. Paquette D, Badiavas E, Falanga V. Short-contact topical tretinoin therapy to stimulate granulation tissue in chronic wounds. J Am Acad Dermatol 2001;45:382-386.

168. Kang S. Topical tretinoin therapy for management of early striae. J Am Acad Dermatol 1998;39:S90-S92.

169. Bergfeld WF. Retinoids and hair growth. J Am Acad Dermatol 1998;39:S86-S89.

170. Arechalde A, Saurat JH. Retinoids: unapproved uses or indications. Clin Dermatol 2000;18:63-76.

171. Hail NJr, Lotan R. Synthetic retinoid Cd437 promotes rapid apoptosis in malignant human epidermal keratinocytes and G1 arrest in their normal counterparts. J Cell Physiol 2001;186:24-32.

172. Duvic M, Friedman-Kien AE, Looney DJ, Miles SA, Myskowski PL, Scadden DT, von Roenn J, Galpin JE, Groopman J, Loewen G, Stevens V, Truglia JA, Yocum RC. Topical treatment of cutaneous lesions of acquired immunodeficiency syndrome-related Kaposi sarcoma using alitretinoin gel: results of phase 1 and 2 trials. Arch Dermatol 2000;136:1461-1469.

173. Walmsley S, Northfelt DW, Melosky B, Conant M, Friedman-Kien AE, Wagner B. Treatment of AIDS-related cutaneous Kaposi’s sarcoma with topical alitretinoin (9-cis-retinoic acid) gel. J Acquir Immune Defic Syndr 1999;22:235-246.

174. Bodsworth N, International Alitretinoina® Gel KS Study Group. Topical 9-cis-retinoic acid (Alitretinoina®) gel as treatment of cutaneous AIDS-related Kaposi’s sarcoma: interim results of an international, placebo-controlled trial (ALRT 1057-503)[abstract-poster presentation]. 12th World AIDS Conference; 1998 Jun 28-Jul 3; Geneva, 317-318.

175. Duvic M, Friedman-Kien AE, Miles SA. Phase I-II evaluation of PanretinTM (ALRT1057; LGD1057; AGN192013; 9-cis retinoic acid) topical gel for AIDS-related cutaneous Kaposi’s sarcoma[abstract no. 160]. 33rd Annual Meeting Am Soc Clin Oncol; 1997 May 17-20; Denver, 46.

176. Morganroth GS. Successful treatment of classical Kaposi’s sarcoma with alitretinoin gel 0.1%[abstract & poster P465]. 59th Annual Meeting of the American Academy of Dermatology; 2001 Mar 2-5; Washington DC.

177. Cheer SM, Foster RH. Alitretinoin. Am J Clin Dermatol 2000;1:307-314.

178. Miles S, Dezube B, Lee J, Krown S, Fletcher MA, Saville MW, Kaplan L, Groopman J, Scadden DT, Cooley T, von Roenn J, Friedman-Kien A. Antitumor activity of oral 9-cis-retinoic acid in HIV-associated Kaposi’s sarcoma. AIDS 2002;16:421-429.

179. Duvic M, Martin AG, Kim Y, Olsen E, Woods GS, Crowley CA, Yocum, and the Worldwide Bexarotene Study Group. Phase 2 and 3 clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistant early-stage cutaneous T-cell lymphoma. Arch Dermatol 2001;137:649-652.

180. Duvic M, Hymes K, Heald P, Breneman D, Martin AG, Myskowski P, Crowley C, Yocum RC, Bexarotene Worlwide Study Group. Bexarotene is efective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol 2001;19:2456-2471.

181. Miller VA, Benedetti FM, Rigas JR, Verret AL, Pfister DG, Straus D, Kris MG, Crisp M, Heyman R, Loewen GR, Truglia JA, Warrell RP. Initial clinicall trial of a selective retinoid X reeceptor ligand, LGD1069. J Clin Oncol 1997;15:790-795.

182. Hymes KB, Washenik K, Duvic M. Oral bexarotene in CTCL patients by TNM stages of disease[abstract no. 53]. 36th Annual Meeting of the American Society of Clinical Oncology; 2000 May 20-23; New Orleans, 16ª.

183. Heald PW, Duvic M. Palliation and remission of erythrodermic cutaneous T-cell lymphoma with a novel oral RXR-selective retinoid[abstract no. 484% poster]. 41st Annual Meeting and Exposition of the American Society of Hematology; 1999 Dec 3-7; New Orleans, 98.

184. Heald P, Mehlmauer M, Martin A. the benefits of topical bexarotene (Targretin®) in patients with refractary or persistant early stage CTCL.[abstract no. 545]. J Invest Dermatol 2000;114:840.

185. Prince HM, McCormack C, Ryan G, Baker C, Rotstein H, Davidson J, Yocum R. Bexarotene capsules and gel for previously treated patients with cutaneous T-cell lymphoma: results of the Australian patients treated on phase II trials. Australas J Dermatol 2001;42:91-97.

186. Kuzel T, Breneman D, Duvic M. Phase I-II trial of Targretin® gel in the topical treatment of patients with cutaneous T-cell lymphoma[abstract no. 532]. J Invest Dermatol 2000;114:839.

187. Duvic M, Martin AG, Kim Y, Olsen E, Wood GS, Crowley CA, Yocum RC. Phase 2 and 3 Clinical Trial of Oral Bexarotene (Targretin Capsules) for the Treatment of Refractory or Persistent Early-Stage Cutaneous T-Cell Lymphoma. Arch Dermatol 2001;137:581-593.