Impact of topical anti-inflammatory therapy on morpho-functional characteristics of epidermal barrier. Optimization of atopic dermatitis treatment schedules

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In this literature review data regarding impact of topical therapy with topical corticosteroids (TCS) and tacrolimus ointment on morpho-functional characteristics of epidermal barrier is analyzed. Whereas TCS has profound negative impact on nearly all epidermal barrier parameters, including epidermal structure and thickness, integrity and cohesion of stratum corneum, protease activity, hydration, pH, differentiation, lipid lamellae structure etc., tacrolimus ointment (Protopic®) exerts positive effect on the majority of the aforementioned parameters, thus allowing to compensate deleterious effect of TCS. These data allow defining recommendations upon optimization of topical therapy of atopic dermatitis with stepwise switching from TCS to Protopic® ointment.

About the authors

L. S. Kruglova

Central State Medical Academy of A ffairs Management Depar tment of President of Russian Federation

Author for correspondence.

Dr. Sci. (Med.), Prof., Departmental Head, Department of the Dermatovenereology and Cosmetology

Marshala Timoshenko str., 19, building 1А, Moscow, 121359, Russian Federation

Russian Federation

D. D. Petrunin

LEO Pharmaсeutical Products, LLC


Cand. Sci. (Med.), Manager for Scientific and Medical Issues

Leningradsky prospect, 72, korpus 2, Moscow, 125315, Russian Federation

Russian Federation


  1. Хлебникова А. Н., Петрунин Д. Д., Молочков А. В. Липиды человеческого эпидермиса (фундаментальные сведения и клиническая имплементация): Учебно-методическое пособие. М.: МОНИКИ, 2015;
  2. [Khlebnikova A. N., Petrunin D. D., Molochkov A. V. Lipids of human epidermis. Fundamental data and clinical implementation: Study guide. Moscow: MONIKI, 2015: 71. (In Russ.)]
  3. Bieber T. Atopic Dermatitis. Ann Dermatol. 2010;22(2):125–137.
  4. Dharmage S. C., Lowe A. J., Matheson M., Burgess J. A., Allen K. J., Abramson M. J. Atopic dermatitis and the atopic march revisited. Allergy. 2014;69:17–27.
  5. Jungersted J. M., Scheer H., Mempel M., Baurecht H., Cifuentes L., Høgh J. K. et al. Stratum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema. Allergy. 2010;65:911–918.
  6. Elias P. M., Steinhoff M. “Outside-to-Inside” (and Now Back to “Outside”) Pathogenic Mechanisms in Atopic Dermatitis. J Invest Dermatol. 2008;128:1067–1070.
  7. Sugarman J. L., Fluhr J. W., Fowler A. J., Bruckner T., Diepgen T. L., Williams M. L. The objective severity assessment of atopic dermatitis score: an objective measure using permeability barrier function and stratum corneum hydration with computer-assisted estimates for extent of disease. Arch Dermatol. 2003;139:1417–1422.
  8. Proksch E., Folster-Holst R., Jensen J. M. Skin barrier function, epidermal proliferation and differentiation in eczema. J Dermatol Sci. 2006;43:159–169.
  9. Chamlin S. L., Kao J., Frieden I. J., Sheu M. Y., Fowler A. J., Fluhr J. W. et al. Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis: changes in barrier function provide a sensitive indicator of disease activity. J Am Acad Dermatol. 2002;47:198–208.
  10. Grimalt R., Mengeaud V., Cambazard F. The steroid-sparing effect of an emollient therapy in infants with atopic dermatitis: a randomized controlled study. Dermatology. 2007;214:61–67.
  11. КР211. Клинические рекомендации — дерматит атопический. Российское общество дерматовенерологов и косметологов, 2016. [КР211 Clinical recommendations. Atopic dermatitis. Russian Society of Dermatologists and Cosmetologists, 2016. (In Russ.)]
  12. Eichenfield L. F., Tom W. L., Berger T. G., Krol A., Paller A. S., Schwarzenberger Ketal. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116–132.
  13. Wollenberg A., Oranje A., Deleuran M., Simon D., Szalai Z., Kunz B. et al. ETFAD/EADV Eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients. J Eur Acad Dermatol Venereol. 2016;30(5):729–747.
  14. Kao J. S., Fluhr J. W., Man M. Q., Fowler A. J., Hachem J. P., Crumrine D. et al. Short-term glucocorticoid treatment compromises both permeability barrier homeostasis and stratum corneum integrity: inhibition of epidermal lipid synthesis accounts for functional abnormalities. J Invest Dermatol. 2003;120(3):456–464.
  15. Tadicherla S., Ross K., Shenefelt P. D., Fenske N. A. Topical corticosteroids in dermatology. J Drugs Dermatol. 2009;8(12):1093–1105.
  16. Kolbe L., Kligman A. M., Schreiner V., Stoudemayer T. Corticosteroid-induced atrophy and barrier impairment measured by non-invasive methods in human skin. Skin Res Technol. 2001;7:73–77.
  17. Sheu H. M., Lee J. Y., Chai C. Y., Kuo K. W. Depletion of stratum corneum intercellular lipid lamellae and barrier function abnormalities after long-term topical corticosteroids. Br J Dermatol. 1997;136(6):884–890.
  18. Haapasaari K. M., Risteli J., Koivukangas V., Oikarinen A. Comparison of the effect of hydrocortisone, hydrocortisone-17-butyrate and betamethasone on collagen synthesis in human skin in vivo. Acta Derm Venereol. 1995;75(4):269–271.
  19. Gebhardt C., Averbeck M., Diedenhofen N., Willenberg A., Anderegg U., Sleeman J. P., Simon J. C. Dermal hyaluronan is rapidly reduced by topical treatment with glucocorticoids. J Invest Dermatol. 2010;130(1):141–149.
  20. Zhang W., Watson C. E., Liu C., Williams K. J., Werth V. P. Glucocorticoids induce a near-total suppression of hyaluronan synthase mRNA in dermal fibroblasts and in osteoblasts: a molecular mechanism contributing to organ atrophy. Biochem J. 2001;349(Pt 1):91–97.
  21. Saarni H., Hopsu-Havu V. K. Inhibition of acid mucopolys accharide synthesis by hydrocortisone, hydrocortisone 17-butyrate and betamethasone 17-valerate. Br J Dermatol. 1977;97(5):505–507.
  22. Carr W. W. Topical calcineurin inhibitors for atopic dermatitis: review and treatment recommendations. Pediatr Drugs. 2013;15:303–310.
  23. Kyllonen H., Remitz A., Mandelin J. M., Elg P., Reitamo S. Effects of 1-year intermittent treatment with topical tacrolimus monotherapy on skin collagen synthesis in patients with atopic dermatitis. Br J Dermatol. 2004;150:1174–1181.
  24. Бакулев А. Л., Кравченя С. С. Эффективность топической терапии такролимусом при атопическом дерматите у взрослых. Вестник дерматологиии и венерологии. 2012;5:106–111. [Bakulev A. L., Kravchenya S. S. Efficacy of the topical therapy with tacrolimus in case of atopic dermatit is in adults. Vestn Dermatol Venerol. 2012;5:106–111. (In Russ.)]
  25. Jiráková A., Rob F., Sečníková Z., Koblová K., Džambová M., Rajská L. Topical corticosteroids but not calcineurin inhibitors induced atrophy after four weeks. J Biol Regul Homeost Agents. 2015;29(3):701–706.
  26. Chittock J., Brown K., Cork M. J., Danby S. G. Comparing the effect of a twice-weekly tacrolimus and betamethasone valerate dose on the subclinical epidermal barrier defect in atopic dermatitis. Acta Derm Venereol. 2015;95:653–658.
  27. Hachem J. P., Man M. Q., Crumrine D., Uchida Y., Brown B. E., Rogiers V. et al. Sustained serine proteases activity by prolonged increasein pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity. J Invest Dermatol. 2005;125:510–520.
  28. Hachem J. P., Houben E., Crumrine D., Man M. Q., Schurer N., Roelandt T. et al. Serine protease signaling of epidermal permeability barrier homeostasis. J Invest Dermatol. 2006;126:2074–2086.
  29. Dähnhardt-Pfeiffer S., Dähnhardt D., Buchner M., Walter K., Proksch E., Fölster-Holst R. Comparison of effects of tacrolimus ointment and mometasone furoate cream on the epidermal barrier of patients with atopic dermatitis. J Dtsch Dermatol Ges. 2013;11(5):437–443.
  30. Lee S.E., Choi Y., Kim S. E., Noh E. B., Kim S. C. Differential effects of topical corticosteroid and calcineurin inhibitor on the epidermal tight junction. Exp Dermatol. 2013;22(1):59–61.
  31. Reitamo S., Rissanen J., Remitz A., Granlund H., Erkko P., Elg P. et al. Tacrolimus ointment does not affect collagen synthesis: results of a single-center randomized trial. J Invest Dermatol. 1998;111:396–398.
  32. Danby S. G., Chittock J., Brown K., Albenali L. H., Cork M. J. The effect of tacrolimus compared with betamethasone valerate on the skin barrier in volunteers with quiescent atopic dermatitis. Br J Dermatol. 2014;170(4):914–921.
  33. Raab W., Kindl U., Daniels R. Pflegekosmetik. Ein Leitfaden. 3rd ed. Stuttgart: Wissenschaftliche Verlagsgesellschaft, 1999.
  34. Wilhelm K. P., Cua A. B., Wolff H. H., Maibach H. I. Surfactant-induced stratum corneum hydration in vivo: prediction of the irritation potential of anionic surfactants. J Invest Dermatol. 1993;101(3):310–315.
  35. Effendy I., Maibach H. I. Surfactants and experimental irritant contact dermatitis. Contact Dermatitis. 1995;33(4):217–225.
  36. Mandelin J., Remitz A., Reitamo S. Effect of oral acetylsalicylic acid on burning caused by tacrolimus ointment in patients with atopic dermatitis. Arch Dermatol. 201;146(10):1178–1180.

Copyright (c) 2018 Kruglova L.S., Petrunin D.D.

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