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A Review of its Pharmacological Properties and Clinical Efficacy in the Topical Treatment of Photodamaged Skin



Tretinoin (all-trans-retinoic acid) is a retinol (vitamin A) derivative which has been evaluated as a topical treatment for the symptoms of photodamaged skin. In several well-controlled clinical trials, the proportion of patients showing improvement was significantly higher with 0.01 or 0.05% tretinoin cream than with placebo for criteria such as global assessment, fine and coarse wrinkling, pigmentation and roughness. Improvements in the overall severity of photodamage were also significantly greater with tretinoin than with placebo. The extent of clinical improvement with tretinoin has generally been moderate, but cytological and histological studies have shown that extensive changes in the epidermis and dermis occur during treatment. However, the permanency and clinical significance of these changes has yet to be fully evaluated.

Topical tretinoin has also demonstrated potential for the treatment and eradication of premalignant skin growths such as actinic keratoses, and may be useful as combination therapy with fluorouracil in this indication.

Dermatitis (the retinoid skin reaction) is the most common adverse event experienced by patients receiving topical tretinoin; this condition may persist for up to 3 months, but is usually mild or moderate in nature.

Thus, topical tretinoin has been shown to be an effective form of treatment for the characteristic signs of photodamaged skin. Its ability to produce significant, albeit moderate, clinical improvements in symptoms such as fine wrinkling, roughness and pigmentation, together with its relatively mild or moderate adverse event profile, suggests that it is likely to be of considerable value in this indication. The treatment and eradication of potentially malignant growths such as actinic keratoses may also prove to be an important application for topical tretinoin.

Pharmacodynamic Properties

The effects of topical tretinoin on photodamaged skin have been described in numerous animal and human studies; they include thickening of the epidermis, compaction of the stratum corneum, increased collagen synthesis in the dermis, beneficial effects on melanocyte differentiation and distribution, promotion of epidermal hyperplasia and angiogenesis. Increases in epidermal thickening, a primary measure of the effects of tretinoin, ranged from 24 to 40% with 0.01 or 0.05% tretinoin, compared with 2 to 14% for placebo, in several well-controlled investigations involving patients with photodamaged skin. Most of the relevant pharmacodynamic data for tretinoin have been obtained during studies of 6 months’ duration or less. Preliminary evidence suggests that some effects are reduced after 12 months whereas others that are not evident at 6 months become apparent only with continued treatment; these findings and their clinical significance require clarification.

Data from several animal studies suggest that tretinoin may prevent the formation of skin tumours, although contradictory results suggesting enhancement of photocarcinogenesis have also been reported. The clinical significance of these results remains to be determined.

Pharmacokinetic Properties

Systemic tretinoin absorption from human skin after topical administration is low. Excretion of 3H-tretinoin in the urine and faeces accounted for 1.1 to 4.3% of a single topical dose given to healthy volunteers, and plasma concentrations were minimal compared with endogenous levels of tretinoin (8.5 to 34ng equivalents/L vs 1000 to 7000ng equivalents/L). In a separate study, tretinoin was not detected in plasma using a chromatographic/spectrometric assay (detection limit 2 μg/L) following single or multiple applications.3H-tretinoin was found in urine within 1 hour of topical application in healthy volunteers, with peak plasma levels recorded after 10 hours. Urinary excretion of tretinoin has been estimated to be between 0.1 and 5.9% of a single topical dose.

Clinical Efficacy

Several placebo-controlled clinical studies have demonstrated that topical tretinoin has significant efficacy in the treatment of photodamaged skin. Improvements in subjective global assessment scores were recorded in 49 to 100% of patients using once-daily 0.01% tretinoin, 68 to 100% of patients using 0.05% tretinoin and 0 to 44% of patients using placebo.

In 2 randomised, double-blind multicentre studies (n = 296 and 251), patient improvement rates for skin pigmentation, roughness and fine wrinkling were significantly better with 0.05% tretinoin than with placebo (total range 42 to 68% vs 22 to 47% and 59 to 86% vs 39 to 48%, respectively), as were reductions in the overall severity of photodamage (16.5 vs 6.9% and 27 vs 16.8%, respectively). Changes from baseline for several photodamage parameters were significantly greater with 0.05% tretinoin (11.9 to 37% reduction) than with placebo (3.2% increase to 20% reduction) in 251 patients with mild to moderate photodamage. Subjective improvements with tretinoin in these studies were supported by optical analysis of silicone impression skin replicas. Significant improvements in several periorbital and cheek parameters were noted with 0.01 and 0.05% tretinoin (≤20%) when compared with placebo (⪯5%).

Although topical tretinoin has been effective in the treatment or eradication of premalignant skin lesions (such as actinic keratoses, lentigines and dysplastic naevi), mainly in small numbers of patients, definitive efficacy data from well-controlled studies of large patient populations are lacking. Combination therapy with tretinoin and fluorouracil may be useful for the treatment of actinic keratoses.


Topical administration of tretinoin is frequently associated with a mild or moderate dermatitis-like condition which is characterised by dry, scaly, itchy skin and erythema (the retinoid skin reaction). These symptoms are generally transient, appearing from about a week to a few months after treatment initiation and lasting for up to 3 months, before declining despite continued application of the drug. The incidence of this condition in well-controlled clinical trials has ranged from 78 to 82% with 0.01% tretinoin and from 49 to 94% with 0.05% tretinoin. Additional effects experienced by patients receiving topical tretinoin include increased pinkness of the skin and inflammation of subclinical actinic keratoses.

Retinoids have been shown to be potent teratogens when given systemically but the potential for birth abnormalities after topical tretinoin use during pregnancy remains to be fully established. Although no increased incidence of birth defects has been reported during 2 decades of topical tretinoin use for acne, several reports of abnormalities have appeared more recently.

Dosage and Administration

Topical therapy with tretinoin is usually started with a cream formulation of between 0.025 and 0.1%, which is applied nightly to the face or forearm. Self-assessment of tolerance to tretinoin, and hence of the optimal administration regimen, is encouraged via patient monitoring of the irritation caused by the retinoid skin reaction. A slight peeling of the skin and erythema indicate an appropriate dose. The best clinical results are obtained when tretinoin is applied for several months or more. Topical tretinoin should not be used during pregnancy.

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  1. 1.

    Kligman AM, Grove GL, Hirose R, et al. Topical tretinoin for photoaged skin. J Am Acad Dermatol 1986; 15(4 Pt 2): 836–59

    PubMed  CAS  Google Scholar 

  2. 2.

    Carruthers R. Ichthyosis. New Ethicals 1993; 30: 33–9

    Google Scholar 

  3. 3.

    Gano SE, Garcia RL. Topical tretinoin, hydroquinone, and beta-methasone valerate in the therapy of melasma. Cutis 1979; 23: 239–41

    PubMed  CAS  Google Scholar 

  4. 4.

    Kligman AM, Dogadkina D, Lavker RM. Effects of topical tretinoin on non-sun-exposed protected skin of the elderly. J Am Acad Dermatol 1993; 29: 25–33

    PubMed  CAS  Google Scholar 

  5. 5.

    Ertl GA, Levine N, Kligman AM. A comparison of the efficacy of topical tretinoin and low-dose oral isotretinoin in rosacea. Arch Dermatol 1994; 130: 319–24

    PubMed  CAS  Google Scholar 

  6. 6.

    Elson ML. Topical tretinoin in the treatment of striae distensae and in the promotion of wound healing: a review. J Dermatol Treat 1994; 5: 163–5

    Google Scholar 

  7. 7.

    Kligman AM. The treatment of photoaged human skin by topical tretinoin. Drugs 1989; 38: 1–8

    PubMed  CAS  Google Scholar 

  8. 8.

    Kligman LH. Prevention and repair of photoaging: sunscreens and retinoids. Cutis 1989; 43: 458–65

    PubMed  CAS  Google Scholar 

  9. 9.

    Kligman AM. Guidelines for the use of topical tretinoin (Retin-A) for photoaged skin. J Am Acad Dermatol 1989; 21(3 Pt 2): 650–4

    PubMed  CAS  Google Scholar 

  10. 10.

    Kligman LH. The ultraviolet-irradiated hairless mouse: a model for photoaging. J Am Acad Dermatol 1989; 21: 623–31

    PubMed  CAS  Google Scholar 

  11. 11.

    Kligman LH, Duo CH, Kligman AM. Topical retinoic acid enhances the repair of ultraviolet damaged dermal connective tissue. Connect Tissue Res 1984; 12: 139–50

    PubMed  CAS  Google Scholar 

  12. 12.

    Bryce GF, Bogdan NJ, Brown CC. Retinoic acids promote the repair of the dermal damage and the effacement of wrinkles in the UVB-irradiated hairless mouse. J Invest Dermatol 1988; 91: 175–80

    PubMed  CAS  Google Scholar 

  13. 13.

    Bryce GF, Shapiro SS. Retinoid effects on photodamaged skin. Methods Enzymol 1990; 190: 352–60

    PubMed  CAS  Google Scholar 

  14. 14.

    Kligman LH. Retinoid effects on photodamaged skin. Methods Enzymol 1990; 190: 372–82

    PubMed  CAS  Google Scholar 

  15. 15.

    Kligman LH, Mezick JA, Capetola RJ, et al. Lifetime topical application of tretinoin to hairless mice. Acta Derm Venereol 1992; 72: 418–22

    PubMed  CAS  Google Scholar 

  16. 16.

    Chen S, Kiss I, Tramposch KM. The priming effect of ultraviolet B radiation on retinoic acid-stimulated collagen synthesis in the mouse photodamage model. Photodermatol Photoimmunol Photomed 1992; 9: 104–8

    PubMed  CAS  Google Scholar 

  17. 17.

    Weiss JS, Ellis CN, Headington JT, et al. Topical tretinoin improves photoaged skin. A double-blind vehicle-controlled study [published errata appear in JAMA 1988 Jun 10; 259 (22): 3274 and 1988 Aug 19; 260(7): 926]. JAMA 1988; 259: 527–32

    PubMed  CAS  Google Scholar 

  18. 18.

    Lever L, Kumar P, Marks R. Topical retinoic acid for treatment of solar damage. Br J Dermatol 1990; 122: 91–8

    PubMed  CAS  Google Scholar 

  19. 19.

    Rosenthal DS, Roop DR, Huff CA, et al. Changes in photo-aged human skin following topical application of all-trans retinoic acid. J Invest Dermatol 1990; 95: 510–5

    PubMed  CAS  Google Scholar 

  20. 20.

    Weinstein GD, Nigra TP, Pochi PE, et al. Topical tretinoin for treatment of photodamaged skin. A multicenter study. Arch Dermatol 1991; 127:659–65

    PubMed  CAS  Google Scholar 

  21. 21.

    Bhawan J, Gonzalez-Serva A, Nehal K, et al. Effects of tretinoin on photodamaged skin. A histologic study. Arch Dermatol 1991; 127: 666–72

    PubMed  CAS  Google Scholar 

  22. 22.

    Strigini E, Ryan TJ. Assessment of the effects of topical all-trans retinoic acid on the microvasculature of the dermis, using laser Doppler imagery, videomicroscopy, and histology [abstract]. Br J Dermatol 1993 Jul; 129 Suppl. 42: 43

    Google Scholar 

  23. 23.

    Tur E, Hohl D, Panizzon R. Late epidermal differentiation in photoaged skin is changed by long- term topical retinoic acid treatment [abstract]. Dermatology 1994; 189(3): 336

    Google Scholar 

  24. 24.

    Finkel LJ, Rafal ES, Griffiths CEM, et al. Topical retinoic acid: a histologic and clinical analysis of its effects on hyper-pigmented macules of photoaged skin [abstract]. Clin Res 1992; 40: 477A

    Google Scholar 

  25. 25.

    Lowe PM, Woods J, Lewis A, et al. Topical tretinoin improves the appearance of photo damaged skin. Australas J Dermatol 1994; 35(1): 1–9

    PubMed  CAS  Google Scholar 

  26. 26.

    Griffiths CEM, Russman AN, Majmudar G, et al. Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid). N Engl J Med 1993; 329: 530–5

    PubMed  CAS  Google Scholar 

  27. 27.

    Panizzon RG, Bruckner-Tuderman L, Mindek G, et al. The influence of tretinoin on photodamaged human skin: a biochemical, cytogenetic and histological evaluation over nine months [abstract]. Dermatology 1994; 189(3): 336

    Google Scholar 

  28. 28.

    Woodley DT, Zelickson AS, Briggaman RA, et al. Increased anchoring fibrils in photoaged skin after treatment with tretinoin [abstract]. Clin Res 1990; 38: 227A

    Google Scholar 

  29. 29.

    Berardesca E, Gabba P, Farinelli N, et al. In vivo tretinoin-induced changes in skin mechanical properties. Br J Dermatol 1990; 122: 525–9

    PubMed  CAS  Google Scholar 

  30. 30.

    Olsen EA, Katz HI, Levine N, et al. Tretinoin emollient cream: a new therapy for photodamaged skin. J Am Acad Dermatol 1992; 26: 215–24

    PubMed  CAS  Google Scholar 

  31. 31.

    Yamamoto O, Bhawan J, Solares G, et al. Ultrastructural effects of topical tretinoin on dermo-epidermal junction and papillary dermis in photodamaged skin:a controlled study. Exp Dermatol. In press

  32. 32.

    Bhawan J, Palko MJ, Lee J, et al. Reversible histologic effects of tretinoin on photodamaged skin. J Geriatr Dermatol. In press

  33. 33.

    Yamamoto O, Bhawan J, Hara M, et al. Keratinocyte degeneration in human facial skin: documentation of new ultrastructural markers for photodamage and their improvement during topical tretinoin treatment. Exp Dermatol 1995; 4: 9–19

    PubMed  CAS  Google Scholar 

  34. 34.

    Petkovich M, Brand NJ, Krust A, et al. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature 1987; 330: 444–50

    PubMed  CAS  Google Scholar 

  35. 35.

    Li X-Y, Åström A, Qin L, et al. Retinoic acid antagonizes gluco-corticoid induced cytochrome P450IAI gene expression in human skin [abstract]. Clin Res 1993; 41: 442A

    Google Scholar 

  36. 36.

    Mao Y, Ruhl KK, Pomidor M, et al. Retinoic acid regulates human ornithine decarboxylase gene expression at the transcriptional level [abstract]. Clin Res 1993; 41: 443A

    Google Scholar 

  37. 37.

    Kang S, Griffiths CEM, Elder JT, et al. Topical retinol induces CRABP-II mRNA expression and epidermal hyperplasia, but only trace erythema in human skin in vivo [abstract]. Clin Res 1993; 41: 496A

    Google Scholar 

  38. 38.

    Larsen FG, Voorhees JJ, Åström A. Retinoic acid induces expression of an early growth response gene (EGR-1) in human skin in vivo and in cultured human skin fibroblasts [abstract]. Clin Res 1993; 41: 441A

    Google Scholar 

  39. 39.

    Reddy AP, Fisher GJ, Datta S, et al. Topical retinoic acid in human skin in vivo induces expression of cellular retinol binding protein I but not alcohol dehydrogenase-3, although the promoters of both genes contain consensus retinoic acid response elements [abstract]. Clin Res 1993; 41: 443A

    Google Scholar 

  40. 40.

    Lützow-Holm C, Heyden A, Huitfeldt HS, et al. Differential effects of topical retinoic acid application on keratin K1 and filaggrin expression in mouse epidermis. Differentiation 1994; 57: 179–85

    PubMed  Google Scholar 

  41. 41.

    Kim H-J, Bogdan NJ, D’Agostaro LJ, et al. Effect of topical retinoic acids on the levels of collagen mRNA during the repair of UVB-induced dermal damage in the hairless mouse and the possible role of TGF-β as a mediator. J Invest Dermatol 1992; 98: 359–63

    PubMed  CAS  Google Scholar 

  42. 42.

    Fisher GJ, Elder JT, Eisen D, et al. Immunoreactive transforming growth factor-β1 but not its mRNA is increased in human epidermis following topical retinoic acid treatment in vivo [abstract]. Dermatologica 1990; 181: 348

    Google Scholar 

  43. 43.

    Verma AK, Shapas BG, Rice HM, et al. Correlation of the inhibition by retinoids of tumor promoter-induced mouse epidermal ornithine decarboxylase activity and of skin tumor promotion. Cancer Res 1979; 39(2 Pt 1): 419–25

    PubMed  CAS  Google Scholar 

  44. 44.

    Epstein JH, Grekin DA. Inhibition of ultraviolet-induced carcinogenesis by all-trans retinoic acid. J Invest Dermatol 1981; 76: 178–80

    PubMed  CAS  Google Scholar 

  45. 45.

    Kligman LH, Kligman AM. Lack of enhancement of experimental photocarcinogenesis by topical retinoic acid. Arch Dermatol Res 1981; 270: 453–62

    PubMed  CAS  Google Scholar 

  46. 46.

    Connor MJ, Lowe NJ, Breeding JH, et al. Inhibition of ultraviolet-B skin carcinogenesis by all-trans-retinoic acid regimens that inhibit ornithine decarboxylase induction. Cancer Res 1983; 43: 171–4

    PubMed  CAS  Google Scholar 

  47. 47.

    Verma AK. Inhibition of both stage I and stage II mouse skin tumour promotion by retinoic acid and the dependence of inhibition of tumor promotion on the duration of retinoic acid treatment. Cancer Res 1987; 47: 5097–101

    PubMed  CAS  Google Scholar 

  48. 48.

    Verma AK. Inhibition of tumor promoter 12-O-tetradecanoylphorbol-13-acetate-induced synthesis of epidermal ornithine decarboxylase messenger RNA and diacylglycerol-promoted mouse skin tumor formation by retinoic acid. Cancer Res 1988; 48: 2168–73

    PubMed  CAS  Google Scholar 

  49. 49.

    Athar M, Agarwal R, Wang ZY, et al. All-trans retinoic acid protects against conversion of chemically induced and ultraviolet B-radiation-induced skin papillomas to carcinomas. Carcinogenesis 1991; 12: 2325–9

    PubMed  CAS  Google Scholar 

  50. 50.

    Forbes PD, Urbach F, Davies RE. Enhancement of experimental photocarcinogenesis by topical retinoic acid. Cancer Lett 1979; 7: 85–90

    PubMed  CAS  Google Scholar 

  51. 51.

    Epstein JH. Effects of retinoids on ultraviolet-induced carcinogenesis. J Invest Dermatol 1981; 77: 144–6

    PubMed  CAS  Google Scholar 

  52. 52.

    McCormick DL, Bagg BJ, Hultin TA. Comparative activity of dietary or topical exposure to three retinoids in the promotion of skin tumor induction in mice. Cancer Res 1987; 47: 5989–93

    PubMed  CAS  Google Scholar 

  53. 53.

    Kripke ML, Glassman HN. Retinoic acid and photocarcinogenesis workshop. J Am Acad Dermatol 1980; 2: 439–42

    PubMed  CAS  Google Scholar 

  54. 54.

    Kligman LH. Retinoic acid and photocarcinogenesis — a controversy. Photodermatol 1987; 4: 88–101

    PubMed  CAS  Google Scholar 

  55. 55.

    Franz TJ, Lehman PA, Franz SF. Topical use of retinoic acid gel is not teratogenic [abstract]. Clin Res 1993; 41: 495A

    Google Scholar 

  56. 56.

    Franz TJ, Lehman PA, Franz SF. Percutaneous absorption of 3H-retinoic acid from 0.1% retin-A cream [abstract PDD 7030]. Pharm Res 1994; 11(10) Suppl.: S–182

    Google Scholar 

  57. 57.

    Kemper C, Holland ML, Thome EG, et al. Percutaneous absorption of 3H-tretinoin following long-term administration of topical tretinoin [abstract]. Dermatologica 1990; 181: 351

    Google Scholar 

  58. 58.

    Worobec SM, Wong FA, Tolman EL, et al. Percutaneous absorption of3H-tretinoin in normal volunteers [abstract]. Clin Res 1990; 38(3): 786A

    Google Scholar 

  59. 59.

    Brode VE, Kühne J, Kummer H. Zur pharmakokinetik von tretinoin nach lokaler applikation. Arzneimittel Forschung 1974; 24: 1188–92

    PubMed  CAS  Google Scholar 

  60. 60.

    Schaefer H, Zesch A. Penetration of vitamin A acid into human skin. Acta Derm Venereol 1975; Suppl. 74: 50–5

    CAS  Google Scholar 

  61. 61.

    Buchan P, Eckhoff C, Caron D, et al. Repeated administration of all-trans-retinoic acid and plasma levels of retinoic acids in humans. J Am Acad Dermatol 1994; 30: 428–34

    PubMed  CAS  Google Scholar 

  62. 62.

    Chiang T-C. Gas chromatographic-mass spectrometric assay for low levels of retinoic acid in human blood. J Chromatogr 1980; 182: 335–40

    PubMed  CAS  Google Scholar 

  63. 63.

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

    PubMed  CAS  Google Scholar 

  64. 64.

    Duell EA, Åström A, Griffiths CEM, et al. Human skin levels of retinoic acid and cytochrome P-450-derived 4-hydroxyretinoic acid after topical application of retinoic acid in vivo compared to concentrations required to stimulate retinoic acid receptor-mediated transcription in vitro. J Clin Invest 1992; 90: 1269–74

    PubMed  CAS  Google Scholar 

  65. 65.

    Duell EA, Fishman A, Grenier L, et al. Retinoic acid but not sodium lauryl sulfate treated skin or psoriasis metabolizes retinoic acid to 4-hydroxy retinoic acid [abstract]. Clin Res 1992; 40: 533A

    Google Scholar 

  66. 66.

    Kotrajaras R, Kligman AM. The effect of topical tretinoin on photodamaged facial skin: the Thai experience. Br J Dermatol 1993; 129: 302–9

    PubMed  CAS  Google Scholar 

  67. 67.

    Monti M, Caputo R. Clinical efficacy and patient tolerance of topical tretinoin therapy in photo-ageing. J Int Med Res 1990; 18 Suppl. 3: 35C–40C

    PubMed  Google Scholar 

  68. 68.

    Caputo R, Monti M, Rigoni C, et al. Experience with tretinoin therapy in temperate regions. Br J Dermatol 1992 Sep; 127 Suppl. 41: 51–3

    PubMed  Google Scholar 

  69. 69.

    Voorhees JJ, Fisher G, Elder JT, et al. Clinical, cellular and molecular aspects of retinoic acid therapy for aging skin [abstract]. Dermatologica 1990; 181: 347

    Google Scholar 

  70. 70.

    Andreano JM, Bergfeld WF, Medendorp SV. Tretinoin emollient cream 0.01% for the treatment of photoaged skin [see comments]. Cleve Clin J Med 1993; 60: 49–55

    PubMed  CAS  Google Scholar 

  71. 71.

    Leyden JJ, Grove GL, Grove MJ, et al. Treatment of photodamaged facial skin with topical tretinoin. J Am Acad Dermatol 1989; 21(3 Pt 2): 638–44

    PubMed  CAS  Google Scholar 

  72. 72.

    Grove GL, Grove MJ, Leyden JJ, et al. Skin replica analysis of photodamaged skin after therapy with tretinoin emollient cream. J Am Acad Dermatol 1991; 25(2 Pt 1): 231–7

    PubMed  CAS  Google Scholar 

  73. 73.

    Ellis CN, Weiss JS, Hamilton TA, et al. Sustained improvement with prolonged topical tretinoin (retinoic acid) for photoaged skin. J Am Acad Dermatol 1990; 23: 629–37

    PubMed  CAS  Google Scholar 

  74. 74.

    Bollag W, Ott F. Retinoic acid: topical treatment of senile or actinic keratoses and basal cell carcinomas. Agents Actions 1970; 1(4): 172–5

    PubMed  CAS  Google Scholar 

  75. 75.

    Belisario JC. Recent advances in topical cytotoxic therapy of skin cancer and precancer. In: Melanoma and skin cancer. Proceedings of an International Cancer Conference, Sydney, Australia, 1972: 349–65

    Google Scholar 

  76. 76.

    Barranco VP, Olsen RL, Everett MA. Response of actinic keratoses to topical vitamin A acid. Cutis 1970; 6: 681–5

    Google Scholar 

  77. 77.

    Papa CM. Tretinoin therapy for precancerous skin. N J Med 1989; 86: 361–5

    PubMed  CAS  Google Scholar 

  78. 78.

    Kligman AM, Thorne EG. Topical therapy of actinic keratoses with tretinoin. In: Marks R, editor. Retinoids in cutaneous malignancy. Oxford: Blackwell Scientific Publications, 1991: 66–73

    Google Scholar 

  79. 79.

    Rufli T, Büchner SA, Sendagorta E, et al. Arotinoid-methylsulfone and tretinoin in the treatment of solar lentigines [abstract]. Dermatologica 1990; 181: 351

    Google Scholar 

  80. 80.

    Meyskens Jr FL, Edwards L, Levine NS. Role of topical tretinoin in melanoma and dysplastic nevi. J Am Acad Dermatol 1986; 15(4 Pt 2): 822–5

    PubMed  Google Scholar 

  81. 81.

    Halpern AC, Schuchter LM, Elder DE, et al. Effects of topical tretinoin on dysplastic nevi. J Clin Oncol 1994; 12: 1028–35

    PubMed  CAS  Google Scholar 

  82. 82.

    Levine N, Meyskens FL. Topical vitamin-A-acid therapy for cutaneous metastatic melanoma. Lancet 1980; 2: 224–6

    PubMed  CAS  Google Scholar 

  83. 83.

    Rivers JK, McCarthy WH. No effect of topical tretinoin on lentigo maligna [letter]. Arch Dermatol 1991; 127: 129

    PubMed  CAS  Google Scholar 

  84. 84.

    Robinson TA, Kligman AM. Treatment of solar keratoses of the extremities with retinoic acid and 5-fluorouracil. Br J Dermatol 1975; 92: 703–6

    PubMed  CAS  Google Scholar 

  85. 85.

    Bercovitch L. Topical chemotherapy of actinic keratoses of the upper extremity with tretinoin and 5-fluorouracil: a double-blind controlled study. Br J Dermatol 1987; 116: 549–52

    PubMed  CAS  Google Scholar 

  86. 86.

    Goldfarb MT, Ellis CN, Weiss JS, et al. Topical tretinoin therapy: its use in photoaged skin. J Am Acad Dermatol 1989; 21(3 Pt 2): 645–50

    PubMed  CAS  Google Scholar 

  87. 87.

    Weiss JS, Ellis CN, Goldfarb MT, et al. Tretinoin therapy: practical aspects of evaluation and treatment. J Int Med Res 1990; 18 Suppl. 3: 41C–8C

    PubMed  Google Scholar 

  88. 88.

    Kligman AM. Tretinoin (Retin-A) therapy of photoaged skin. Compr Ther 1992; 18: 10–3

    PubMed  CAS  Google Scholar 

  89. 89.

    Teknetzis A, Vakali G, Lefaki I, et al. Pyogenic granuloma developed on a dermatofibroma after treatment with topical tretinoin. In: International Meeting Skin Therapy Update 94, 1994: 255

    Google Scholar 

  90. 90.

    Hogan DJ. Scarring following inappropriate use of 0.05% tretinoin gel [letter]. J Am Acad Dermatol 1987; 17: 1056–7

    PubMed  CAS  Google Scholar 

  91. 91.

    Tosti A, Guerra L, Morelli R, et al. Contact dermatitis due to topical retinoic acid. Contact Dermatitis 1992; 26: 276–7

    PubMed  CAS  Google Scholar 

  92. 92.

    Tomb R, Dolfus A, Couppie P. Allergic contact dermatitis from tretinoin [in French]. Ann Dermatol Venereol 1992; 119(10): 761–4

    PubMed  CAS  Google Scholar 

  93. 93.

    Orfanos CE, Ehlert R, Gollnick H. The retinoids: a review of their clinical pharmacology and therapeutic use. Drugs 1987; 34: 459–503

    PubMed  CAS  Google Scholar 

  94. 94.

    Retinoids have a major role in dermatology but are limited by teratogenicity. Drug Ther Perspect 1993 Jul 5; 1 12: 7-10

  95. 95.

    Medicines in pregnancy. Aust Adv Drug React Bull 1993; 12: 14-6

    Google Scholar 

  96. 96.

    Jick SS, Terris BZ, Jick H. First trimester topical tretinoin and congenital disorders. Lancet 1993; 341: 1181–2

    PubMed  CAS  Google Scholar 

  97. 97.

    Lipson AH, Collins F, Webster WS. Multiple congenital defects associated with maternal use of topical tretinoin [letter]. Lancet 1993; 341: 1352–3

    PubMed  CAS  Google Scholar 

  98. 98.

    Camera G, Pregliasco P. Ear malformation in baby born to mother using tretinoin cream [letter]. Lancet 1992; 339: 687

    PubMed  CAS  Google Scholar 

  99. 99.

    Gardner SS, Weiss JS. Clinical features of photodamage and treatment with topical tretinoin. J Dermatol Surg Oncol 1990; 16: 925–31

    PubMed  CAS  Google Scholar 

  100. 100.

    Weiss JS, Ellis CN, Goldfarb MT, et al. Tretinoin treatment of photodamaged skin. Cosmesis through medical therapy. Dermatol Clin 1991; 9: 123–9

    PubMed  CAS  Google Scholar 

  101. 101.

    Green LJ, McCormick A, Weinstein GD. Photoaging and the skin. The effects of tretinoin. Dermatol Clin 1993; 11: 97–105

    PubMed  CAS  Google Scholar 

  102. 102.

    Farnes SW, Setness PA. Retinoid therapy for aging skin and acne. Postgrad Med 1992; 92: 191–6,199-200

    PubMed  CAS  Google Scholar 

  103. 103.

    Goldfarb MT, Ellis CN, Voorhees JJ. Topical tretinoin: its use in daily practice to reverse photoageing. Br J Dermatol 1990 Apr; 122 Suppl. 35: 87–91

    PubMed  Google Scholar 

  104. 104.

    Raab WP. Photodamaged skin: a medical or cosmetic concern. J Int Med Res 1990; 18 Suppl. 3: 2C–7C

    PubMed  Google Scholar 

  105. 105.

    Leyden JJ. Topical tretinoin no panacea for photodamaged skin. Cleve Clin J Med 1993; 60: 88–9

    PubMed  CAS  Google Scholar 

  106. 106.

    Goh SH. The treatment of visible signs of senescence: the Asian experience. Br J Dermatol 1990 Apr; 122 Suppl. 35: 105–9

    PubMed  Google Scholar 

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Correspondence to Stuart Noble.

Additional information

Various sections of the manuscript reviewed by: J. Bhawan, Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts, USA; P. Buchan, CIRD Galderma, Sophia Antipolis, France; R. Caputo, Istituto di Scienze Dermatologiche, Universitá di Milano, Milan, Italy; J.M. Dayer, Division of Immunology & Allergy, Hôpital Cantonal Universitaire de Genéve, Geneva, Switzerland; S.H. Goh, International Skin Centre, Singapore; J.L.M. Hawk, St John’s Institute of Dermatology, St Thomas’ Hospital, London, England; A.M. Kligman, Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA; G.L. Peck, Department of Dermatology, Washington Hospital Center, Washington, DC, USA; W.P. Raab, Allergy Clinic ‘City’, Vienna, Austria; H. Tagami, Department of Dermatology, Tohoku University School of Medicine, Sendai, Japan.

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Noble, S., Wagstaff, A.J. Tretinoin. Drugs & Aging 6, 479–496 (1995).

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  • Retinoic Acid
  • Dermatol
  • Tretinoin
  • Actinic Keratose
  • Topical Tretinoin