Vitamin A and the Skin

Chapter

Core Messages

  • Vitamin A (vit. A) is essential for normal differentiation and maintenance of epithelial tissues in skin and mucous membranes, vision (retinaldhyde), reproduction (retinol), and embryonic morphogenesis.

  • Retinoids (compounds with biological activities similar to those of vit. A) are used as therapeutic agents for hyperkeratotic and parakeratotic skin diseases, acne and acne-related disorders, and hand eczema. They are also used as prophylaxis for epithelial skin tumors in immune-suppressed patients and as therapy for nonmelanoma skin cancers and cutaneous T-cell lymphoma.

  • Regular monitoring is essential for the avoidance and management of a wide range of adverse effects.

Keywords

Nicotine PGE2 Hypothyroidism Myopathy Ceramides 

References

  1. Abbott RA, Whittaker SJ, Morris SL, Russell-Jones R, Hung T, Bashir SJ, et al. Bexarotene therapy for mycosis fungoides and Sézary syndrome. Br J Dermatol. 2009;160:1299–307.PubMedCrossRefGoogle Scholar
  2. Abdel Naser MB, Zouboulis CC. Retinoids in the management of non melanoma skin cancer. In: Jemec GBE, Kemény L, Mieh D, editors. Non-surgical treatment of keratinocyte skin cancer. Berlin/Heidelberg: Springer; 2010. p. 187–95.CrossRefGoogle Scholar
  3. Adams J, Kiss E, Arroyo AB, Bonrouhi M, Sun Q, Li Z, Gretz N, Schnitger A, Zouboulis CC, Wiesel M, Wagner J, Nelson PJ, Gröne HJ. 13-cis retinoic acid inhibits development and progression of chronic allograft nephropathy. Am J Pathol. 2005;167:285–98.PubMedGoogle Scholar
  4. Avis I, Mathias A, Unsworth EJ, Miller MJ, Cuttitta F, Mulshine JL, et al. Analysis of small cell lung cancer cell growth inhibition by 13-cis-retinoic acid: importance of bioavailability. Cell Growth Differ. 1995;6:485–92.PubMedGoogle Scholar
  5. Ayer DE, Lawrence QA, Eisenman RN. Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3. Cell. 1995;80:767–76.PubMedCrossRefGoogle Scholar
  6. Barth JH, MacDonald-Hull SP, Mark J, et al. Isotretinoin therapy for acne vulgaris: a re-evaluation of the need for measurements of plasma lipids and liver function tests. Br J Dermatol. 1993;129:704–7.PubMedCrossRefGoogle Scholar
  7. Benifla JL, Ville Y, Imbert MC, Frydman R, Thomas A, Pons JC. Fetal tissue dosages of retinoids: experimental study concerning a case of isotretinoin (Roaccutan) administration and pregnancy. Fetal Diagn Ther. 1995;10:189–91.PubMedCrossRefGoogle Scholar
  8. Biesalski HK. Comparative assessment of the toxicology of vitamin A and retinoids in man. Toxicology. 1989;57:117–61.PubMedGoogle Scholar
  9. Bikowski JB. Mechanisms of the comedolytic and anti-inflammatory properties of topical retinoids. J Drugs Dermatol. 2005;4:41–7.PubMedGoogle Scholar
  10. Bollag W, Ott F. Successful treatment of chronic hand eczema with oral 9-cis-retinoic acid. Dermatology. 1999;199:308–12.PubMedCrossRefGoogle Scholar
  11. Brewster AM, Lee JJ, Clayman GL, Clifford JL, Reyes MJ, Zhou X, et al. Randomized trial of adjuvant 13-cis-retinoic acid and interferon alfa for patients with aggressive skin squamous cell carcinoma. J Clin Oncol. 2007;25:1974–8.PubMedCrossRefGoogle Scholar
  12. Chen WC, Sass JO, Seltmann H, Nau H, Orfanos CE, Zouboulis CC. Biological effects and metabolism of 9-cis-retinoic acid and its metabolite 9,13-di-cis-retinoic acid in HaCaT keratinocytes in vitro: comparison with all-trans-retinoic acid. Arch Dermatol Res. 2000;292:612–20.PubMedGoogle Scholar
  13. Chroni E, Monastirli A, Tsambaos D. Neuromuscular adverse effects associated with systemic retinoid dermatotherapy: monitoring and treatment algorithm for clinicians. Drug Saf. 2010;33:25–34.PubMedCrossRefGoogle Scholar
  14. Cunliffe WJ, Poncet M, Loesche C, Verschoore M. A comparison of the efficacy and tolerability of adapalene 0.1% gel versus tretinoin 0.025% gel in patients with acne vulgaris: a metaanalysis of five randomized trials. Br J Dermatol. 1998;139 Suppl 52:48–56.PubMedCrossRefGoogle Scholar
  15. Del Rosso JQ. Study results of benzoyl peroxide 5%/clindamycin 1% topical gel, adapalene 0.1% gel, and use in combination for acne vulgaris. J Drugs Dermatol. 2007;6:616–22.PubMedGoogle Scholar
  16. Downie MM, Sanders DA, Kealey T. Modelling the remission of individual acne lesions in vitro. Br J Dermatol. 2002;147:869–78.PubMedGoogle Scholar
  17. Duvic M. Bexarotene and DAB(389)IL-2 (denileukin diftitox, ONTAK) in treatment of cutaneous T-cell lymphomas: algorithms. Clin Lymphoma. 2000;1 Suppl 1:S51–5.PubMedCrossRefGoogle Scholar
  18. Duvic M, Hymes K, Heald P, Breneman D, Martin AG, Myskowski P, et al. Bexarotene is effective and safe for treatment of refractory, advanced-stage cutaneous T-cell lymphoma: multinational phase II-m trial results. J Clin Oncol. 2001a;19:2456–71.PubMedGoogle Scholar
  19. Duvic M, Martin AG, Kim Y, et al. 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. 2001b;137:581–93.PubMedGoogle Scholar
  20. Enders SI, Enders IM. Isotretinoin and psychiatric iIInessin adolescents and young adults. Ann Pharmacother. 2003;37:1124–7.PubMedCrossRefGoogle Scholar
  21. Estival JL, Dupin M, Kanitakis J, Combemale P. Capillary leak syndrome induced by acitretin. Br J Dermatol. 2004;150:150–2.PubMedCrossRefGoogle Scholar
  22. Ethan-Quan, Wolverton. Ligand Pharmaceuticals. Targretin (bexarotene) capsules prescribing information. San Diego, CA. 2003.PubMedCrossRefGoogle Scholar
  23. Fanjul A, Dawson MI, Hobbs PD, Jong L, Cameron JF, Harlev E, et al. A new class of retinoids with selective inhibition of AP-1 inhibits proliferation. Nature. 1994;372:107–11.PubMedCrossRefGoogle Scholar
  24. Ganceviciene R, Zouboulis CC. Isotretinoin: state of the art treatment for acne vulgaris. Expert Rev Dermatol. 2007;2:693–706.CrossRefGoogle Scholar
  25. Gold JA, Schupack JL, Nemel MA. Ocular side effects of retinoids. Int J Dermatol. 1989;28:218–25.PubMedCrossRefGoogle Scholar
  26. Goldberg LH, Hsu SH, Alcalay J. Effectiveness of isotretinoin in preventing the appearance of basal cell carcinomas in basal cell nevus syndrome. J Am Acad Dermatol. 1989;21:144–5.PubMedCrossRefGoogle Scholar
  27. Gollnick H, Cunliffe W, Berson D, Dreno B, Finlay A, Leyden JJ, et al. Management of acne: a report from a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol. 2003;49:S1–37.PubMedCrossRefGoogle Scholar
  28. Gupta AK, Goldfarb MT, Ellis CN, Voorhees JJ. Side-effect profile of acitretin therapy in psoriasis. J Am Acad Dermatol. 1989;20:1088–93.PubMedCrossRefGoogle Scholar
  29. Guy R, Ridden C, Kealey T. The improved organ maintenance of the human sebaceous gland: modeling in vitro the effects of epidermal growth factor, androgens, estrogens, 13-cis retinoic acid, and phenol red. J Invest Dermatol. 1996;106:454–60.PubMedGoogle Scholar
  30. Hanifi JM, Stevens V, Sheth P, et al. Novel treatment of severe chronic hand dermatitis with bexarotene gel. Br J Dermatol. 2004;150:545–53.CrossRefGoogle Scholar
  31. Hassig CA, Fleischer TC, Billin AN, Schreiber SL, Ayer DE. Histone deacetylase activity is required for full transcriptional repression by mSin3A. Cell. 1997;89:341–7.PubMedCrossRefGoogle Scholar
  32. Haugen BR. Drugs that suppress TSH or cause central hypothyroidism. Best Pract Res Clin Endocrinol Metab. 2009;23:793–800.PubMedCrossRefGoogle Scholar
  33. Imam A, Hoyos B, Swenson C, Levi E, Chua R, Viriya E, et al. Retinoids as ligands and coactivators of protein kinase C alpha. FASEB J. 2001;15:28–30.PubMedGoogle Scholar
  34. Jones DA. The potential immunomodulatory effects of topical retinoids. Dermatol Online J. 2005;11:3.PubMedGoogle Scholar
  35. Kanekura T, Higashi Y, Kanzaki T. Inhibitory effects of 9-cis-retinoic acid and pyrrolidinedithiocarbamate on cyclooxygenase (COX)-2 expression and cell growth in human skin squamous carcinoma cells. Cancer Lett. 2000;161:177–83.PubMedCrossRefGoogle Scholar
  36. Karlsson T, Vahlquist A, Kedishvili N, Törmä H. 13-cis-retinoic acid competitively inhibits 3 alpha-hydroxysteroid oxidation by retinol dehydrogenase RoDH-4: a mechanism for its anti-androgenic effects in sebaceous glands? Biochem Biophys Res Commun. 2003;303:273–8.PubMedCrossRefGoogle Scholar
  37. King K, Jones DH, Daltrey DC, Cunliffe WJ. A double-blind study of the effects of 13-cis-retinoic acid on acne, sebum excretion rate and microbial population. Br J Dermatol. 1982;107:583–90.PubMedGoogle Scholar
  38. Korting HC, Braun-Falco O. Efficacy and tolerability of combined topical treatment of acne vulgaris with tretinoin and erythromycin in general practice. Drugs Exp Clin Res. 1989;15:447–51.PubMedGoogle Scholar
  39. Kovach BT, Murphy G, Otley CC, Shumack S, Ulrich C, Stasko T. Oral retinoids for chemoprevention of skin cancers in organ transplant recipients: results of a survey. Transplant Proc. 2006;38:1366–8.PubMedCrossRefGoogle Scholar
  40. 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;318:1633–7.PubMedCrossRefGoogle Scholar
  41. Lavker RM, Leyden JJ, Thorne EG. An ultrastructural study of the effects of topical tretinoin on microcomedones. Clin Ther. 1992;14:773–80.PubMedGoogle Scholar
  42. Layton AM, Dreno B, Gollnick HP, Zouboulis CC. A review of the European Directive for prescribing systemic isotretinoin for acne vulgaris. J Eur Acad Dermatol Venereol. 2006;20:773–6.PubMedGoogle Scholar
  43. Lippman SM, Kesseier JF, Meyskens FL Jr. Retinoids as preventive and therapeutic anticancer agents (Part 11). Cancer Treat Rep. 1987;21:493–515.Google Scholar
  44. Marazzi P, Boorman GC, Donald AE, Davies HD. Clinical evaluation of double strength isotrexin versus benzamycin in the topical treatment of mild to moderate acne vulgaris. J Dermatol Treat. 2002;13:111–7.CrossRefGoogle Scholar
  45. Mills OH Jr, Kligman AM. Treatment of acne vulgaris with topically applied erythromycin and tretinoin. Acta Derm Venereol. 1978;58:555–7.PubMedGoogle Scholar
  46. Nelson AM, Gilliland KL, Cong Z, Thiboutot DM. 13-cis Retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes. J Invest Dermatol. 2006;126:2178–89.PubMedCrossRefGoogle Scholar
  47. Nguyen EH, Wolverton SE. Systemic retinoids. In: Wolverton SE, Wilkin JK, editors. Systemic drugs for skin diseases. Philadelphia: WB Saunders; 2000. p. 269–310.Google Scholar
  48. Olsen EA, Weed WW, Meyer CJ, Cobo LM. A double-blind, placebo-controlled trial of acitretin for the treatment of psoriasis. J Am Acad Dermatol. 1989;21:681–6.PubMedCrossRefGoogle Scholar
  49. Orfanos CE, Zouboulis CC. Oral retinoids in the treatment of seborrhoea and acne. Dermatology. 1998;196:140–7.PubMedCrossRefGoogle Scholar
  50. Orfanos CE, Zouboulis CC, Almond-Roesler B, Geilen C. Current use and future potential role of retinoids in dermatology. Drugs. 1997;53:358–88.PubMedCrossRefGoogle Scholar
  51. Otley CC, Stasko T, Tope WD, Lebwohl M. Chemoprevention of nonmelanoma skin cancer with systemic retinoids: practical dosing and management of adverse effects. Dermatol Surg. 2006;32:562–8.PubMedCrossRefGoogle Scholar
  52. Papakonstantinou E, Aletras AJ, Glass E, Tsogas P, Dionyssopoulos A, Adjaye J, et al. Matrix metalloproteinases of epithelial origin in facial sebum of patients with acne and their regulation by isotretinoin. J Invest Dermatol. 2005;125:673–84.PubMedCrossRefGoogle Scholar
  53. Rollman O, Vahlquist A. Oral isotretinoin (13-cis-retinoic acid) therapy in severe acne: drug and vitamin A concentrations in serum and skin. J Invest Dermatol. 1986;86:384–9.CrossRefGoogle Scholar
  54. Rook AH, Jaworsky C, Nguyen T, Grossman RA, Wolfe JT, Witmer WK, et al. 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;59:714–9.PubMedCrossRefGoogle Scholar
  55. Ruzicka T, Larsen FG, Galewicz D, Horváth A, Coenraads PJ, Thestrup-Pedersen K, et al. Oral alitretinoin (9-cis-retinoic acid) therapy for chronic hand dermatitis in patients refractory to standard therapy: results of a randomized, double-blind, placebo-controlled, multicenter trial. Arch Dermatol. 2004;140:1453–9.PubMedCrossRefGoogle Scholar
  56. Scheinfeld N, Bangalore S. Facial edema induced by isotretinoin use: a case and a review of the side effects of isotretinoin. J Drugs Dermatol. 2006;5:467–8.PubMedGoogle Scholar
  57. Shuttleworth D, Marks R, Griftin PJ, Salaman JR. Treatment of cutaneous neoplasia with etretinate in renal transplant recipients. Q J Med. 1988;68:717–25.PubMedGoogle Scholar
  58. Smit JW, Stokkel MP, Pereira AM, Romijn JA, Visser TJ. Bexarotene-induced hypothyroidism: bexarotene stimulates the peripheral metabolism of thyroid hormones. J Clin Endocrinol Metab. 2007;92:2496–9.PubMedCrossRefGoogle Scholar
  59. Stephensen CB, Rasooly R, Jiang X, Ceddia MA, Weaver CT, Chandraratna RA, et al. Vitamin A enhances in vitro Th2 development via retinoid X receptor pathway. J Immunol. 2002;168:4495–503.PubMedGoogle Scholar
  60. Sun SY, Yue P, Mao L, Dawson MI, Shroot B, Lamph WW, et al. Identification of receptor-selective retinoids that are potent inhibitors of the growth of human head and neck squamous cell carcinoma cells. Clin Cancer Res. 2000;6:1563–73.PubMedGoogle Scholar
  61. Tanghetti E, Abramovits W, Solomon B, Loven K, Shalita A. Tazarotene versus tazarotene plus clindamycin/ benzoyl peroxide in the treatment of acne vulgaris: a multicenter, doubleblind, randomized parallel-group trial. J Drugs Dermatol. 2006;5:256–61.PubMedGoogle Scholar
  62. Thiboutot DM, Shalita AR, Yamauchi PS, Dawson C, Arsonnaud S, Kang S. Combination therapy with adapalene gel 0.1% and doxycycline for severe acne vulgaris: a multicenter, investigator- blind, randomized, controlled study. Skinmed. 2005;4:138–46.PubMedCrossRefGoogle Scholar
  63. Thiboutot DM, Weiss J, Bucko A, Eichenfield L, Jones T, Clark S, et al. Adapalene-benzoyl peroxide, a fixed-dose combination for the treatment of acne vulgaris: results of a multicenter, randomized double-blind, controlled study. J Am Acad Dermatol. 2007;57:791–9.PubMedCrossRefGoogle Scholar
  64. Thielitz A, Sidou F, Gollnick H. Control of microcomedone formation throughout a maintenance treatment with adapalene gel, 0.1%. J Eur Acad Dermatol Venereol. 2007;21:747–53.PubMedCrossRefGoogle Scholar
  65. Thomas X, Anglaret B, Thiebaut A, Belhabri A, Treille-Ritouet D, Fiere D, Archimbaud E. Improvement of prognosis in refractory and relapsed acute promyelocytic leukemia over recent years: the role of all-trans retinoic acid therapy. Ann Hematol. 1997;75:195–200.PubMedGoogle Scholar
  66. Tsukada M, Schröder M, Roos TC, Chandraratna RA, Reichert U, Merk HF, Orfanos CE, Zouboulis CC. 13-cis retinoic acid exerts its specific activity on human sebocytes through selective intracellular isomerization to all-trans retinoic acid and binding to retinoid acid receptors. J Invest Dermatol. 2000;115:321–7.PubMedGoogle Scholar
  67. Tsukada M, Schröder M, Seltmann H, Orfanos CE, Zouboulis CC. High albumin levels restrict the kinetics of 13-cis retinoic acid uptake and intracellular isomerization to all-trans retinoic acid and inhibit its anti-proliferative effect on SZ95 sebocytes. J Invest Dermatol. 2002;119: 182–5.PubMedCrossRefGoogle Scholar
  68. Vane FM, Bugge CJL, Rodriguez LC, Rosenberger M, Doran TI. Human biliary metabolites of isotretinoin: identification, quantification, synthesis, and biological activity. Xenobiotica. 1990;20:193–207.PubMedCrossRefGoogle Scholar
  69. 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. Panretin Gel North American Study Group. J Acquir Immune Defic Syndr. 1999;22:235–46.PubMedCrossRefGoogle Scholar
  70. Webster GF, Guenther L, Poulin YP, Solomon BA, Loven K, Lee J. A multicenter, double-blind, randomized comparison study of the efficacy and tolerability of once-daily tazarotene 0.1% gel and adapalene 0.1% gel for the treatment of facial acne vulgaris. Cutis. 2002;69:4–11.PubMedGoogle Scholar
  71. Wiegand UW, Chou RC. Pharmacokinetics of acitretin and etretinate. J Am Acad Dermatol. 1998;39:S25–33.PubMedCrossRefGoogle Scholar
  72. Zane LT, Leyden WA, Marqueling AL, Manos MM. A population-based analysis of laboratory abnormalities during isotretinoin therapy for acne vulgaris. Arch Dermatol. 2006;142:1016–22.PubMedCrossRefGoogle Scholar
  73. Zhang JZ, Li LF, Tu YT, Zheng J. A successful maintenance approach in inflammatory acne with adapalene gel 0.1% after an initial treatment in combination with clindamycin topical solution 1% or after monotherapy with clindamycin topical solution 1%. J Dermatol Treat. 2004;15:372–8.CrossRefGoogle Scholar
  74. Zouboulis CC, Korge BP, Mischke D, Orfanos CE. Altered proliferation, synthetic activity, and differentiation of cultured human sebocytes in the absence of vitamin A and their modulation by synthetic retinoids. J Invest Dermatol. 1993;101:628–33.PubMedGoogle Scholar
  75. Zouboulis CC, Orfanos CE. Retinoids. In: Millikan LE, editor. Drug therapy in dermatology. New York/Basel: Marcel Dekker; 2000. p. 171–233.Google Scholar
  76. Zouboulis CC, Chen WC, Sass JO, Seltmann H, Nau H, Orfanos CE. Biological effects and metabolism of 9-cis-retinoic acid and its metabolite 9,13-di-cis-retinoic acid in HaCaT keratinocytes in vitro: comparison with all-trans-retinoic acid. Arch Dermatol Res. 2000;292:612–20.PubMedGoogle Scholar
  77. Zouboulis CC. Retinoids – which dermatological indications will benefit in the near future? Skin Pharmacol Appl Skin Physiol. 2001;14:303–15.PubMedGoogle Scholar
  78. Zouboulis CC, Piquero-Martin J. Update and future of systemic acne treatment. Dermatology. 2003;206:37–53.PubMedCrossRefGoogle Scholar
  79. Zouboulis CC. Isotretinoin revisited: pluripotent effects on human sebaceous gland cells. J Invest Dermatol. 2006a;126:2154–6.PubMedCrossRefGoogle Scholar
  80. Zouboulis CC. The truth behind this undeniable efficacy – recurrence rates and relapse risk factors of acne treatment with oral isotretinoin. Dermatology. 2006b;212:99–100.PubMedCrossRefGoogle Scholar
  81. Zouboulis CC, Rabe T. Hormonal antiandrogens in acne treatment. J Dtsch Dermatol Ges. 2010;8 Suppl 1:S60–74.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Departments of Dermatology, Venereology, Allergology, and ImmunologyDessau Medical CenterDessauGermany
  2. 2.Departments of Dermatology, Venereology, Allergology, and ImmunologyDessau Medical CenterDessauGermany

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