Skip to main content
Log in

Influence of oral isotretinoin treatment on the composition of comedonal lipids. Implications for comedogenesis in acne vulgaris

  • Original Contributions
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

One of the primary events in the pathogenesis of acne vulgaris is abnormal follicular keratinization. Since oral isotretinoin therapy reduces follicular hyperkeratinization in acne, our study has been designed to determine whether epidermal lipid composition of the epithelium of sebaceous follicles is affected by isotretinoin treatment.

Noninflamed early comedones obtained from ten patients with nodulocystic acne before and after the 6th week of isotretinoin therapy (mean daily dose 0.7 mg/kg b.wt.) were used as probes of the hyperkeratinizing follicular epithelium. Comedonal lipids were analyzed by high-performance thin-layer chromatography. Oral isotretinoin caused a decrease of the comedonal glyceride fraction by 36% (P<0.01), whereas free sterols and total ceramides increased by 34% (P<0.10) and 19%, respectively. The changes of comedonal lipids were associated with a significant elevation of the free sterols/cholesterol sulfate ratio of 86% from pretreatment levels (P<0.05). The isotretinoin-induced changes of the comedonal lipid composition in direction to a pattern of epidermal lipids of normal desquamating stratum corneum are discussed as a possible comedolytic mechanism of oral isotretinoin treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Downing DT, Strauss JS, Pochi PE (1969) Variability in the chemical composition of human surface lipids. J Invest Dermatol 53:322–327

    Google Scholar 

  2. Downing DT, Stewart ME, Wertz PW, Strauss JS (1986) Essential fatty acids and acne. J Am Acad Dermatol 14:221–225

    Google Scholar 

  3. Downing DT, Stewart ME, Strauss JS (1987) Biology of sebaceous glands. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF (eds) Dermatology in general medicine, 3rd edn. McGraw-Hill, New York, pp 185–190

    Google Scholar 

  4. Elias PM (1983) Epidermal lipids, barrier function, and desquamation. J Invest Dermatol 80:44s-49s

    Google Scholar 

  5. Elias PM, Fritsch PO, Lampe M, Williams ML, Brown BE, Nemanic M, Grayson S (1981) Retinoid effects on epidermal structure, differentiation, and permeability. Lab Invest 44:531–540

    Google Scholar 

  6. Elias PM, Grayson S, Lampe MA, Williams ML, Brown BE (1983) The intercorneocyte space. In: Marks R, Plewig G (eds) Stratum corneum. Springer, Berlin Heidelberg New York, 53–67

    Google Scholar 

  7. Elias PM, Williams M, Maloney ME, Bonifas JA, Brown BE, Grayson S, Epstein Jr EH (1984) Stratum corneum lipids in disorders of cornification. II. Steroid sulfatase and cholesterol sulfate in normal desquamation and the pathogenesis of recessive x-linked ichthyosis. J Clin Invest 74:1414–1421

    Google Scholar 

  8. Elias PM, Williams ML, Maloney ME, Fritsch PO, Chung J-C (1986) Applications of the diazacholesterol animal model of ichthyosis. In: Marks R, Plewig G (eds) Skin models. Springer, Berlin Heidelberg New York, pp 122–135

    Google Scholar 

  9. Epstein Jr EH, Williams ML, Elias PM (1981) Steroid sulfatase, x-linked ichthyosis, and stratum corneum cell cohesion. Arch Dermatol 117:761–763

    Google Scholar 

  10. Epstein Jr EH, Williams ML, Elias PM (1984) The epidermal cholesterol sulfate cycle. J Am Acad Dermatol 10:866–868

    Google Scholar 

  11. Farrell LN, Strauss JS, Stranieri AM (1980) The treatment of severe cystic acne with 13-cis-retinoic acid. J Am Acad Dermatol 3:602–611

    Google Scholar 

  12. Folch J, Lees M, Sloane Stanley GH (1956) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509

    Google Scholar 

  13. Geiger J-M, Hartmann H-R (1986) Diazacholesterol-induced ichthyosiform changes in hairless mice: effects of oral etretinate and isotretinoin. Arch Dermatol Res 278:426–428

    Google Scholar 

  14. Gershbein LL, Haeberlin JB, Singh EJ (1970) Composition of human comedone lipids. Dermatologica 140:264–274

    Google Scholar 

  15. Gomez EC (1982) Actions of isotretinoin and etretinate on the pilosebaceous unit. J Am Acad Dermatol 6:746–750

    Google Scholar 

  16. Holland DB, Gowland G, Cunliffe W (1984) Inflammatory responses in acne patients treated with 13-cis-retinoic acid [isotretinoin] Br J Dermatol 110:343–345

    Google Scholar 

  17. Kligman AM (1974) An overview of acne. J Invest Dermatol 62:268–287

    Google Scholar 

  18. Landthaler M, Kummermehr J, Wagner A, Plewig G (1980) Inhibitory effects of 13-cis-retinoic acid on human sebaceous glands. Arch Dermatol Res 269:297–309

    Google Scholar 

  19. Lavker RM, Leyden JJ, McGinley KJ (1981) The relationship between bacteria and the abnormal follicular keratinization in acne vulgaris. J Invest Dermatol 77:325–330

    Google Scholar 

  20. Lester RS, Schachter GD, Light MJ (1985) Isotretinoin and tetracycline in the management of severe nodulocystic acne. Int J Dermatol 24:252–257

    Google Scholar 

  21. Long SA, Wertz PW, Strauss JS, Downing DT (1985) Human stratum corneum polar lipids and desquamation. Arch Dermatol Res 277:284–287

    Google Scholar 

  22. maloney ME, Williams ML, Epstein Jr EH, Law MYL, Fritsch PO, Elias PM (1984) Lipids in the pathogenesis of ichthyosis: topical cholesterol sulfate-induced scaling in hairless mice. J Invest Dermatol 83:252–256

    Google Scholar 

  23. Melnik B, Verhoeven B, Plewig G (1986) Microanalysis of stratum corneum lipids by high-performance thin-layer chromatography. J Invest Dermatol 87:155

    Google Scholar 

  24. Nicolaides N, Ansari MNA, Fu HC, Lindsay DG (1970) Lipid composition of comedones compared with that of human skin surface in acne patients. J Invest Dermatol 54:487–495

    Google Scholar 

  25. Peck GL, Olsen TG, Yoder FW, Strauss JS, Downing DT Pandya M, Butkus D, Arnaud-Battandier J (1979) Prolonged remissions of cystic and conglobate acne with 13-cisretinoic acid. N Engl J Med 300:329–333

    Google Scholar 

  26. Plewig G, Kligman AM (1975) Ache: morphogenesis and treatment. Springer, Berlin Heidelberg New York

    Google Scholar 

  27. Plewig G, Gollnick H, Meigel W, Wokalek H et al (1981) 13-cis-Retinsäure zur oralen Behandlung der Acne conglobata. Hautarzt 32:634–646

    Google Scholar 

  28. Plewig G, Wagner A, Nikolowski J, Landthaler M (1981) Effects of two retinoids in animal experiments and after clinical application in acne patients: 13-cis-retinoic acid Ro 4-3780 and aromatic retinoid Ro 10-9359. In: Orfanos CE, Braun-Falco O, Farber EM, Grupper C, Polano MR (eds) Retinoids — advances in basic research and therapy. Springer, Berlin Heidelberg New York, pp 219–235

    Google Scholar 

  29. Plewig G, Nikolowski J, Wolff HH (1982) Action of isotretinoin in acne, rosacea and gram-negative folliculitis. J Am Acad Dermatol 6:766–785

    Google Scholar 

  30. Ranasinghe AW, Wertz PW, Downing DT, MacKenzie IC (1986) Lipid composition of cohestive and desquamated corneocytes from mouse ear skin. J Invest Dermatol 86:187–190

    Google Scholar 

  31. Shapiro LJ, Weiss R, Webster D, France JT (1978) Enzymatic basis of typical x-linked ichthyosis. Lancet 1:70–72

    Google Scholar 

  32. Smith WP, Christensen MS, Nacht S, Gans EH (1982) Effect of lipids on the aggregation and permeability of human stratum corneum. J Invest Dermatol 78:7–11

    Google Scholar 

  33. Stewart ME, Benoit AM, Downing DT, Strauss JS (1984) Suppression of sebum secretion with 13-cis-retinoic acid: effect on individual skin surface lipids and implications for their anatomic origin. J Invest Dermatol 82:74–78

    Google Scholar 

  34. Stewart ME, Grahek MO, Cambier LS, Wertz PW, Downing DT (1986) Dilutional effect of increased sebaceous gland activity on the proportion of linoleic acid in sebaceous wax esters and in epidermal acylceramides. J Invest Dermatol 87:733–736

    Google Scholar 

  35. Strauss JS, Stranieri M (1982) Changes in long-term sebum production from isotretinoin therapy. J Am Acad Dermatol 6:751–755

    Google Scholar 

  36. Strauss JS, Peck GL, Olson TG, Downing DT, Windhorst DB (1978) Alteration of skin lipid composition by oral 13-cis retinoic acid: comparison of pretreatment and treatment values. J Invest Dermatol 70:223

    Google Scholar 

  37. Strauss JS, Peck GL, Olsen TG, Downing DT, Windhorst DB (1978) Sebum composition during oral 13-cis retinoic acid administration. J Invest Dermatol 70:228

    Google Scholar 

  38. Wertz PW (1986) Lipids of keratinizing tissues. In: Bereiter-Hahn J, Matoltsy AG, Richards KS (eds) Biology of the integument, vol 21, chap 42. Springer, Berlin Heidelberg New York, pp 815–823

    Google Scholar 

  39. Wertz PW, Miethke MC, Long SA, Strauss JS, Downing DT (1985) The composition of the ceramides from human stratum corneum and from comedones. J Invest Dermatol 84:410–412

    Google Scholar 

  40. Williams ML, Elias PM (1981) Stratum corneum lipids in disorders of cornification. Increased cholesterol sulfate content of stratum corneum in recessive x-linked ichthyosis. J Clin Invest 68:1404–1410

    Google Scholar 

  41. Williams ML, Elias PM (1986) The ichthyoses. In: Thiers BH, Dobson RL (eds) Pathogenesis of skin disease. Churchill Livingstone, New York, pp 519–551

    Google Scholar 

  42. Yao JK, Rastetter GM (1985) Microanalysis of complex tissue lipids by high-performance thin-layer chromatography. Anal Biochem 150:111–116

    Google Scholar 

  43. Zelickson AS, Strauss JS, Mottaz J (1985) Ultrastructural changes in open comedones following treatment of cystic acne with isotretinoin. Am J Dermatopathol 7:241–244

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Melnik, B., Kinner, T. & Plewig, G. Influence of oral isotretinoin treatment on the composition of comedonal lipids. Implications for comedogenesis in acne vulgaris. Arch Dermatol Res 280, 97–102 (1988). https://doi.org/10.1007/BF00417712

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00417712

Key words

Navigation