Background: Topical retinoic acid (RA) causes irritation of the skin. To prevent this side effect, natural precursors of RA have been proposed. The aim of the present study was to compare the local tolerance profiles of retinol (ROL), retinaldehyde (RAL) and RA. Methods: ROL, RAL and RA were studied using repeated insult patch tests for 14 days (n = 6). Similarly, RAL and RA were assessed in long-term clinical use for 44 weeks (n = 355). Clinical scoring on irritation, measurement of transepidermal water loss (barrier function) and laser Doppler blood flow perfusion units (irritation) were performed. Results: Under maximized conditions, an equally low irritation potential for ROL and RAL and a more pronounced irritant effect with RA could be demonstrated clinically (p < 0.05 in the intergroup analysis). Furthermore, RAL and RA induced more scaling than ROL (p < 0.05), and ROL and RA tended to induce more burning/pruritus than RAL (nonsignificant). The TEWL values were low with ROL and high with RAL and RA (nonsignificant, intergroup analysis). The laser Doppler measurements confirmed pro-irritating effects of RA and the nonirritating effects of ROL and RAL (p = 0.001, intergroup analysis). The long-term clinical study showed that the study population developed a high frequency of erythema (44% of the population), scaling (35%) and burning/pruritus (29%) with RA in the first 4 weeks of treatment, whereas these 3 parameters were significantly less frequent with RAL (p < 0.0001 in the intergroup analysis). Conclusion: The natural retinoids ROL and RAL do have a good tolerance profile, in contrast with the irritating potential of RA.

Keywords:
Patch-testing, Local tolerance, Irritation, Retinol, Retinaldehyde, Retinoic acid
1.
Lehmann L, Clemens M, Gloor M, Fluhr J: Über die Effektivität von Tretinoin in Lokaltherapeutika: Lösungs- versus Suspensionszubereitungen – Wechselwirkungen mit Erythromycin. Akt Dermatol 1998;24:51–55.
2.
Kang S, Duell EA, Fisher GJ, Datta SC, Wang ZQ, Reddy AP, Tavakkol A, Yi JY, Griffiths CEM, Elder JT, Voorhees JJ: Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation. J Invest Dermatol 1995;105:549–556.
3.
Saurat JH, Didierjean L, Masgrau E, Piletta PA, Jaconi S, Châtellard-Gruaz D, Masouyé I, Salomon D, Sigenthaler G: Topical retinaldehyde on human skin: Biologic effects and tolerance. J Invest Dermatol 1994;103:770–774.
4.
Pinnagoda J, Tupker RA, Agner T, Serup J: Guidelines for transepidermal water loss (TEWL) measurement. Contact Dermatitis 1990;22:164–178.
5.
Fullerton A, Fischer T, Lahti A, Wilhelm KP, Takiwaki H, Serup J: Guidelines for measurement of skin color and erythema. Contact Dermatitis 1996;35:1–10.
6.
Kligman AM: Current status of topical tretinoin in the treatment of photoaged skin. Drugs Aging 1992;2:7–13.
7.
Creaven NM, Voorhees JJ, Griffiths CEM: Topical retinoic acid for photoaged skin: Therapeutic effects and mechanisms. J Dermatol Treat 1996;7(suppl 2):23–27.
8.
Olsen EA, Katz HI, Levine N, Nigra TP, Pochi PE, Savin RC, Shupack J, Weinstein GD, Lufrano L, Perry BH: Tretinoin emollient cream for photodamaged skin: Results of 48-week, multicenter, double-blind studies. J Am Acad Dermatol 1997;37:217–226.
9.
Gilchrest BA: Treatment of photodamage with topical tretinoin: An overview. J Am Acad Dermatol 1997;36(suppl):27–36.
10.
Kligman AM, Fulton JE, Plewig G: Topical vitamin A acid in acne vulgaris. Arch Dermatol 1969;99:469–476.
11.
Duell EA, Kang S, Voorhees JJ: Occluded retinol penetrates human skin in vivo more effectively than unoccluded retinyl palmitate or retinoic acid. J Invest Dermatol 1997;109: 301–305.
12.
Siegenthaler G, Gumowki-Sunek D, Saurat JH: Metabolism of natural retinoids in psoriatic epidermis. J Invest Dermatol 1990;95:47–48.
13.
Didierjean L, Carraux P, Grand D, Sass JO, Nau H, Saurat JH: Topical retinaldehyde increases skin content of retinoic acid and exerts biologic activity in mouse skin. J Invest Dermatol 1996; 107:714–719.
1999
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.