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. 1985 May 15;132(10):1129–1136.

Synthetic retinoids in dermatology

Elizabeth H Heller, Norman J Shiffman
PMCID: PMC1345937  PMID: 3158386

Abstract

The potential of vitamin A, or retinol, in the treatment of a variety of skin diseases has long been recognized, but because of serious toxic effects this substance generally could not be used. The recent development and marketing of two relatively nontoxic synthetic analogues, which are known as retinoids, has made it possible to treat some of the diseases that are resistant to standard forms of therapy. Isotretinoin is very effective in cystic and conglobate acne, while etretinate is especially useful in the more severe forms of psoriasis. Good results have also been obtained in other disorders of keratinization. Vitamin A and its derivatives apparently have an antineoplastic effect as well and may come to be used in both the prevention and the treatment of epithelial cancer. In many of these diseases the retinoids act by enhancing the normal differentiation and proliferation of epidermal tissues, but the exact mechanisms are not well understood. Their influence on the intracellular polyamines that control the synthesis of nucleic acids and proteins may be an important factor. Although the retinoids have few serious systemic effects, they are teratogenic, and because they persist in the body their use in women of childbearing potential is limited.

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Selected References

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  1. BERN H. A., ELIAS J. J., PICKETT P. B., POWERS T. R., HARKNESS M. N. The influence of vitamin A on the epidermis. Am J Anat. 1955 May;96(3):419–447. doi: 10.1002/aja.1000960305. [DOI] [PubMed] [Google Scholar]
  2. Benke P. J. The isotretinoin teratogen syndrome. JAMA. 1984 Jun 22;251(24):3267–3269. [PubMed] [Google Scholar]
  3. Bergfeld W. F., Derbes V. J., Elias P. M., Frost P., Greer K. E., Shupack J. L. The treatment of keratosis palmaris et plantaris with isotretinoin. A multicenter study. J Am Acad Dermatol. 1982 Apr;6(4 Pt 2 Suppl):727–731. doi: 10.1016/s0190-9622(82)80053-4. [DOI] [PubMed] [Google Scholar]
  4. Bjelke E. Dietary vitamin A and human lung cancer. Int J Cancer. 1975 Apr 15;15(4):561–565. doi: 10.1002/ijc.2910150405. [DOI] [PubMed] [Google Scholar]
  5. Bollag W. Therapy of chemically induced skin tumors of mice with vitamin A palmitate and vitamin A acid. Experientia. 1971 Jan 15;27(1):90–92. doi: 10.1007/BF02137759. [DOI] [PubMed] [Google Scholar]
  6. Boutwell R. K. Retinoids and inhibition of ornithine decarboxylase activity. J Am Acad Dermatol. 1982 Apr;6(4 Pt 2 Suppl):796–800. doi: 10.1016/s0190-9622(82)80060-1. [DOI] [PubMed] [Google Scholar]
  7. Brazzell R. K., Colburn W. A. Pharmacokinetics of the retinoids isotretinoin and etretinate. A comparative review. J Am Acad Dermatol. 1982 Apr;6(4 Pt 2 Suppl):643–651. doi: 10.1016/s0190-9622(82)70053-2. [DOI] [PubMed] [Google Scholar]
  8. Campbell J. P., Grekin R. C., Ellis C. N., Matsuda-John S. S., Swanson N. A., Voorhees J. J. Retinoid therapy is associated with excess granulation tissue responses. J Am Acad Dermatol. 1983 Nov;9(5):708–713. doi: 10.1016/s0190-9622(83)70184-2. [DOI] [PubMed] [Google Scholar]
  9. Claudy A. L., Rouchouse B., Boucheron S., Le Petit J. C. Treatment of cutaneous lymphoma with etretinate. Br J Dermatol. 1983 Jul;109(1):49–56. doi: 10.1111/j.1365-2133.1983.tb03991.x. [DOI] [PubMed] [Google Scholar]
  10. Cram D. L. Psoriasis: current advances in etiology and treatment. J Am Acad Dermatol. 1981 Jan;4(1):1–14. doi: 10.1016/s0190-9622(81)70001-x. [DOI] [PubMed] [Google Scholar]
  11. De Luca L. M., Sasak W., Adamo S., Bhat P. V., Akalovsky I., Silverman-Jones C. S., Maestri N. Retinoid metabolism and mode of action. Environ Health Perspect. 1980 Apr;35:147–152. doi: 10.1289/ehp.8035147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dicken C. H., Connolly S. M. Eruptive xanthomas associated with isotretinoin (13-cis-retinoic acid). Arch Dermatol. 1980 Aug;116(8):951–952. [PubMed] [Google Scholar]
  13. Dowling J. E., Wald G. VITAMIN A DEFICIENCY AND NIGHT BLINDNESS. Proc Natl Acad Sci U S A. 1958 Jul 15;44(7):648–661. doi: 10.1073/pnas.44.7.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Exner J. H., Dahod S., Pochi P. E. Pyogenic granuloma-like acne lesions during isotretinoin therapy. Arch Dermatol. 1983 Oct;119(10):808–811. [PubMed] [Google Scholar]
  15. Flynn P. J., Miller W. J., Weisdorf D. J., Arthur D. C., Brunning R., Branda R. F. Retinoic acid treatment of acute promyelocytic leukemia: in vitro and in vivo observations. Blood. 1983 Dec;62(6):1211–1217. [PubMed] [Google Scholar]
  16. Folkers E., Tafelkruyer J. Subcorneal pustular dermatosis (Sneddon-Wilkinson disease)--therapeutic problems. Br J Dermatol. 1978 Jun;98(6):681–684. doi: 10.1111/j.1365-2133.1978.tb03588.x. [DOI] [PubMed] [Google Scholar]
  17. Fredriksson T., Pettersson U. Severe psoriasis--oral therapy with a new retinoid. Dermatologica. 1978;157(4):238–244. doi: 10.1159/000250839. [DOI] [PubMed] [Google Scholar]
  18. Fritsch P. Oral retinoids in dermatology. Int J Dermatol. 1981 Jun;20(5):314–329. doi: 10.1111/j.1365-4362.1981.tb00814.x. [DOI] [PubMed] [Google Scholar]
  19. Glazer S. D., Roenigk H. H., Jr, Yokoo H., Sparberg M. A study of potential hepatotoxicity of etretinate used in the treatment of psoriasis. J Am Acad Dermatol. 1982 Apr;6(4 Pt 2 Suppl):683–687. doi: 10.1016/s0190-9622(82)70057-x. [DOI] [PubMed] [Google Scholar]
  20. Goldsmith L. A., Weinrich A. E., Shupack J. Pityriasis rubra pilaris response to 13-cis-retinoic acid (isotretinoin). J Am Acad Dermatol. 1982 Apr;6(4 Pt 2 Suppl):710–715. doi: 10.1016/s0190-9622(82)70061-1. [DOI] [PubMed] [Google Scholar]
  21. Happle R., Kastrup W., Macher E. Systemic retinoid therapy of systematized verrucous epidermal nevus (with 1 colour plate). Dermatologica. 1977;155(4):200–205. doi: 10.1159/000250999. [DOI] [PubMed] [Google Scholar]
  22. Haydey R. P., Reed M. L., Dzubow L. M., Shupack J. L. Treatment of keratoacanthomas with oral 13-cis-retinoic acid. N Engl J Med. 1980 Sep 4;303(10):560–562. doi: 10.1056/NEJM198009043031005. [DOI] [PubMed] [Google Scholar]
  23. Hersle K., Mobacken H., Sloberg K., Thilander H. Severe oral lichen planus: treatment with an aromatic retinoid (etretinate). Br J Dermatol. 1982 Jan;106(1):77–80. doi: 10.1111/j.1365-2133.1982.tb00904.x. [DOI] [PubMed] [Google Scholar]
  24. Jetten A. M., Jetten M. E. Possible role of retinoic acid binding protein in retinoid stimulation of embryonal carcinoma cell differentiation. Nature. 1979 Mar 8;278(5700):180–182. doi: 10.1038/278180a0. [DOI] [PubMed] [Google Scholar]
  25. Kanigsberg N., DesGroseilliers J. P. Use of 13-cis-retinoic acid in cystic acne. Can Med Assoc J. 1983 Aug 1;129(3):224–228. [PMC free article] [PubMed] [Google Scholar]
  26. Kaplan R. P., Russell D. H., Lowe N. J. Etretinate therapy for psoriasis: clinical responses, remission times, epidermal DNA and polyamine responses. J Am Acad Dermatol. 1983 Jan;8(1):95–102. doi: 10.1016/s0190-9622(83)70012-5. [DOI] [PubMed] [Google Scholar]
  27. Kariniemi A. L., Stubb S., Lassus A. Treatment of disseminated superficial actinic porokeratosis with a new aromatic retinoid (Ro 10-9359). Br J Dermatol. 1980 Feb;102(2):213–214. doi: 10.1111/j.1365-2133.1980.tb05694.x. [DOI] [PubMed] [Google Scholar]
  28. Kessler J. F., Meyskens F. L., Jr, Levine N., Lynch P. J., Jones S. E. Treatment of cutaneous T-cell lymphoma (mycosis fungoides) with 13-cis-retinoic acid. Lancet. 1983 Jun 18;1(8338):1345–1347. doi: 10.1016/s0140-6736(83)92136-0. [DOI] [PubMed] [Google Scholar]
  29. Landthaler M., Kummermehr J., Wagner A., Plewig G. Inhibitory effects of 13-cis-retinoic acid on human sebaceous glands. Arch Dermatol Res. 1980;269(3):297–309. doi: 10.1007/BF00406424. [DOI] [PubMed] [Google Scholar]
  30. Lassus A., Lauharanta J., Juvakoski T., Kanerva L. Efficacy of etretinate (Tigason) in clearing and prevention of relapse of palmoplantar pustulosis. Dermatologica. 1983;166(4):215–219. doi: 10.1159/000249871. [DOI] [PubMed] [Google Scholar]
  31. Lassus A. Systemic treatment of psoriasis with an oral retinoic acid derivative (Ro 10-9359). Br J Dermatol. 1980 Feb;102(2):195–202. doi: 10.1111/j.1365-2133.1980.tb05692.x. [DOI] [PubMed] [Google Scholar]
  32. Lotan R. Effects of vitamin A and its analogs (retinoids) on normal and neoplastic cells. Biochim Biophys Acta. 1980 Mar 12;605(1):33–91. doi: 10.1016/0304-419x(80)90021-9. [DOI] [PubMed] [Google Scholar]
  33. Lowe N. J., Kaplan R., Breeding J. Etretinate treatment for psoriasis inhibits epidermal ornithine decarboxylase. J Am Acad Dermatol. 1982 Apr;6(4 Pt 2 Suppl):697–698. doi: 10.1016/s0190-9622(82)70059-3. [DOI] [PubMed] [Google Scholar]
  34. Meyskens F. L. Studies of retinoids in the prevention and treatment of cancer. J Am Acad Dermatol. 1982 Apr;6(4 Pt 2 Suppl):824–827. doi: 10.1016/s0190-9622(82)70072-6. [DOI] [PubMed] [Google Scholar]
  35. Moriarty M., Dunn J., Darragh A., Lambe R., Brick I. Etretinate in treatment of actinic keratosis. A double-blind crossover study. Lancet. 1982 Feb 13;1(8268):364–365. doi: 10.1016/s0140-6736(82)91393-9. [DOI] [PubMed] [Google Scholar]
  36. O'Brien T. G. The induction of ornithine decarboxylase as an early, possibly obligatory, event in mouse skin carcinogenesis. Cancer Res. 1976 Jul;36(7 Pt 2):2644–2653. [PubMed] [Google Scholar]
  37. Ong D. E., Chytil F. Retinoic acid-binding protein in rat tissue. Partial purification and comparison to rat tissue retinol-binding protein. J Biol Chem. 1975 Aug 10;250(15):6113–6117. [PubMed] [Google Scholar]
  38. Orfanos C. E., Goerz G. Orale psoriasis-Therapie mit einem neuen aromatischen Retinoid (Ro 10-9359). Eine multizentrische kontrollierte Studie an 291 Patienten in der Bundesrepublik. Vorläufige Mitteilung. Dtsch Med Wochenschr. 1978 Feb 3;103(5):195–199. doi: 10.1055/s-0028-1104405. [DOI] [PubMed] [Google Scholar]
  39. Orfanos C. E. Oral retinoids--present status. Br J Dermatol. 1980 Nov;103(5):473–481. doi: 10.1111/j.1365-2133.1980.tb01661.x. [DOI] [PubMed] [Google Scholar]
  40. PORTER A. D. Vitamin A in some congenital anomalies of the skin. Br J Dermatol. 1951 Apr;63(4):123–127. doi: 10.1111/j.1365-2133.1951.tb13702.x. [DOI] [PubMed] [Google Scholar]
  41. Peck G. L., Gross E. G., Butkus D., DiGiovanna J. J. Chemoprevention of basal cell carcinoma with isotretinoin. J Am Acad Dermatol. 1982 Apr;6(4 Pt 2 Suppl):815–823. doi: 10.1016/s0190-9622(82)70071-4. [DOI] [PubMed] [Google Scholar]
  42. Peck G. L., Olsen T. G., Butkus D., Pandya M., Arnaud-Battandier J., Gross E. G., Windhorst D. B., Cheripko J. Isotretinoin versus placebo in the treatment of cystic acne. A randomized double-blind study. J Am Acad Dermatol. 1982 Apr;6(4 Pt 2 Suppl):735–745. doi: 10.1016/s0190-9622(82)70063-5. [DOI] [PubMed] [Google Scholar]
  43. Peck G. L., Olsen T. G., Yoder F. W., Strauss J. S., Downing D. T., Pandya M., Butkus D., Arnaud-Battandier J. Prolonged remissions of cystic and conglobate acne with 13-cis-retinoic acid. N Engl J Med. 1979 Feb 15;300(7):329–333. doi: 10.1056/NEJM197902153000701. [DOI] [PubMed] [Google Scholar]
  44. Pettit J. H. Oral retinoid for psoriasis. A report of a double blind study. Acta Derm Venereol Suppl (Stockh) 1979;59(85):133–136. [PubMed] [Google Scholar]
  45. Pittsley R. A., Yoder F. W. Retinoid hyperostosis. Skeletal toxicity associated with long-term administration of 13-cis-retinoic acid for refractory ichthyosis. N Engl J Med. 1983 Apr 28;308(17):1012–1014. doi: 10.1056/NEJM198304283081707. [DOI] [PubMed] [Google Scholar]
  46. Plewig G., Nikolowski J., Wolff H. H. Action of isotretinoin in acne rosacea and gram-negative folliculitis. J Am Acad Dermatol. 1982 Apr;6(4 Pt 2 Suppl):766–785. doi: 10.1016/s0190-9622(82)70067-2. [DOI] [PubMed] [Google Scholar]
  47. Plewig G., Wagner A. Anti-inflammatory effects of 13-Cis-retinoic acid. An in vivo study. Arch Dermatol Res. 1981;270(1):89–94. doi: 10.1007/BF00417154. [DOI] [PubMed] [Google Scholar]
  48. Polano M. K., van der Rhee H. J., van der Schroeff J. G. A three-year follow-up study of psoriasis patients treated with low dosages of etretinate orally and corticosteroids topically. Acta Derm Venereol. 1982;62(4):361–364. [PubMed] [Google Scholar]
  49. Prutkin L. Mucous metaplasia and gap junctions in the vitamin A acid-treated skin tumor, keratoacanthoma. Cancer Res. 1975 Feb;35(2):364–369. [PubMed] [Google Scholar]
  50. Rollman O., Vahlquist A. Retinoid concentrations in skin, serum and adipose tissue of patients treated with etretinate. Br J Dermatol. 1983 Oct;109(4):439–447. doi: 10.1111/j.1365-2133.1983.tb04618.x. [DOI] [PubMed] [Google Scholar]
  51. Russell R. M., Boyer J. L., Bagheri S. A., Hruban Z. Hepatic injury from chronic hypervitaminosis a resulting in portal hypertension and ascites. N Engl J Med. 1974 Aug 29;291(9):435–440. doi: 10.1056/NEJM197408292910903. [DOI] [PubMed] [Google Scholar]
  52. Saffiotti U., Montesano R., Sellakumar A. R., Borg S. A. Experimental cancer of the lung. Inhibition by vitamin A of the induction of tracheobronchial squamous metaplasia and squamous cell tumors. Cancer. 1967 May;20(5):857–864. doi: 10.1002/1097-0142(1967)20:5<857::aid-cncr2820200545>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  53. Stewart M. E., Benoit A. M., Stranieri A. M., Rapini R. P., Strauss J. S., Downing D. T. Effect of oral 13-cis-retinoic acid at three dose levels on sustainable rates of sebum secretion and on acne. J Am Acad Dermatol. 1983 Apr;8(4):532–538. doi: 10.1016/s0190-9622(83)70061-7. [DOI] [PubMed] [Google Scholar]
  54. Stüttgen G. Oral vitamin A acid therapy. Acta Derm Venereol Suppl (Stockh) 1975 Jan 27;74:174–179. [PubMed] [Google Scholar]
  55. THOMPSON J. N., HOWELL J. M., PITT G. A. VITAMIN A AND REPRODUCTION IN RATS. Proc R Soc Lond B Biol Sci. 1964 Feb 18;159:510–535. doi: 10.1098/rspb.1964.0017. [DOI] [PubMed] [Google Scholar]
  56. Windhorst D. B., Nigra T. General clinical toxicology of oral retinoids. J Am Acad Dermatol. 1982 Apr;6(4 Pt 2 Suppl):675–682. doi: 10.1016/s0190-9622(82)70056-8. [DOI] [PubMed] [Google Scholar]
  57. Zarowny D. P. Accutane Roche: risk of teratogenic effects. Can Med Assoc J. 1984 Aug 15;131(4):273–273. [PMC free article] [PubMed] [Google Scholar]
  58. Zech L. A., Gross E. G., Peck G. L., Brewer H. B. Changes in plasma cholesterol and triglyceride levels after treatment with oral isotretinoin. A prospective study. Arch Dermatol. 1983 Dec;119(12):987–993. [PubMed] [Google Scholar]
  59. Zile M., DeLuca H. F. Retinoic acid: some aspects of growth-promoting activity in the albino rat. J Nutr. 1968 Mar;94(3):302–308. doi: 10.1093/jn/94.3.302. [DOI] [PubMed] [Google Scholar]

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