Scientific and Practical Innovations in Restoring Skin Barrier Properties in Children with Atopic Dermatitis

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease. Its pathogenetic basis is epidermal barrier dysfunction, immune system dysregulation, as well as skin microbiome diversity decrease that occurs due to genetic predisposition. Considering these factors, the skin of patients with AD requires constant care and use of medications with active regenerative properties. The inclusion of anti-inflammatory components in the composition of modern emollients (zinc sulfate and sucralfate) is crucial for restoring the microbiome and immune mechanisms controlling the skin. This article presents data on pathogenetic applicability and clinical efficacy of emollients with anti-inflammatory compounds in patients with AD.

1. Drucker AM, Wang AR, Li WQ, et al. The Burden of Atopic Dermatitis: Summary of a Report for the National Eczema Asso ciation. J Investig Dermatol. 2017;137(1):26–30. doi: https://doi.org/10.1016/j.jid.2016.07.012

2. Maliyar K, Sibbald C, Pope E, et al. Diagnosis and Management of Atopic Dermatitis. Adv Skin Wound Care. 2018;31(12):538–550. doi: https://doi.org/10.1097/01.asw.0000547414.38888.8d

3. Xu X, van Galen LS, Koh MJ, et al. Factors influencing quality of life in children with atopic dermatitis and their caregivers: A cross-sectional study. Sci Rep. 2019;9(1):15990. doi: https://doi.org/10.1038/s41598-019-51129-5

4. Akdis CA, Akdis M, Bieber T, et al. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL consensus report. Allergy. 2006;61(8):969–987. doi: https://doi.org/10.1111/j.1398-9995.2006.01153.x

5. Abu-Dayyeh I, Abu-Kwaik J, Weimann A, Abdelnour A. Prevalence of IgE-mediated sensitization in patients with suspected food allergic reactions in Jordan. Immun Inflamm Dis. 2020;8(3): 384–392. doi: https://doi.org/10.1002/iid3.320

6. Kim J, Kim BE, Leung DYM. Pathophysiology of atopic dermatitis: Clinical implications. Allergy Asthma Proc. 2019;40(2):84–92. doi: https://doi.org/10.2500/aap.2019.40.4202

7. Elias PM, Steinhoff M. “Outside-to-inside” (and now back to “outside”) pathogenic mechanisms in atopic dermatitis. J Invest Dermatol. 2008;128(5):1067–1070. doi: https://doi.org/10.1038/jid.2008.88

8. Elias PM, Schmuth M. Abnormal skin barrier in the etiopathogenesis of atopic dermatitis. Curr Opin Allergy Clin Immunol. 2009;9(5):437–446. doi: https://doi.org/10.1097/ACI.0b013e32832e7d36

9. Kubo A, Nagao K, Amagai M. Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases. J Clin Invest. 2012; 122(2):440–447. doi: https://doi.org/10.1172/JCI57416

10. Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med. 2011;365(14): 1315–1327. doi: https://doi.org/10.1056/NEJMra1011040

11. Kaufman BP, Guttman-Yassky E, Alexis AF. Atopic dermatitis in diverse racial and ethnic groups-Variations in epidemiology, genetics, clinical presentation and treatment. Exp Dermatol. 2018;27(4):340–357. doi: https://doi.org/10.1111/exd.13514

12. Bin L, Leung DY. Genetic and epigenetic studies of atopic dermatitis. Allergy Asthma Clin Immunol. 2016;12:52. doi: https://doi.org/10.1186/s13223-016-0158-5

13. Peng W, Novak N. Pathogenesis of atopic dermatitis. Clin Exp Allergy. 2015;45(3):566–574. doi: https://doi.org/10.1111/cea.12495

14. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) — a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994;19(3):210–216. doi: https://doi.org/10.1111/j.1365-2230.1994.tb01167.x

15. Altrichter S, Kriehuber E, Moser J, et al. Serum IgE Autoantibodies Target Keratinocytes in Patients with Atopic Dermatitis. J Invest Dermatol. 2008;128(9):2232–2239. doi: https://doi.org/10.1038/jid.2008.80

16. Tan BB, Weald D, Strickland I, Friedmann PS. Double-blind controlled trial of effect of housedust-mite allergen avoidance on atopic dermatitis. Lancet. 1996;347(8993):15–18. doi: https://doi.org/10.1016/s0140-6736(96)91556-1

17. McGirt LY, Beck LA. Innate immune defects in atopic dermatitis. J Allergy Clin Immunol. 2006;118(1):202–208. doi: https://doi.org/10.1016/j.jaci.2006.04.033

18. Nakatsuji T, Chen TH, Two AM, et al. Staphylococcus aureus Exploits Epidermal Barrier Defects in Atopic Dermatitis to Trigger Cytokine Expression. J Invest Dermatol. 2016;136(11):2192–2200. doi: https://doi.org/10.1016/j.jid.2016.05.127

19. Leung DY, Harbeck R, Bina P, et al. Presence of IgE antibod ies to staphylococcal exotoxins on the skin of patients with atopic dermatitis. Evidence for a new group of allergens. J Clin Invest. 1993;92(3):1374–1380. doi: https://doi.org/10.1172/JCI1167

20. Hauk PJ, Hamid QA, Chrousos GP, et al. Induction of corticosteroid insensitivity in human PBMCs by microbial superantigens. J Allergy Clin Immunol. 2000;105(4):782–787. doi: https://doi.org/10.1067/mai.2000.105807

21. Egawa G, Weninger W. Pathogenesis of atopic dermatitis: A short review. Cogent Biology. 2015;1(1):1103459. doi: https://doi.org/10.1080/23312025.2015.1103459

22. Kezic S, Novak N, Jakasa I, et al. Skin barrier in atopic dermatitis. Fron Biosci (Landmark Ed). 2014;19(3):542–556. doi: https://doi.org/10.2741/4225

23. Adhikary PP, Tan Z, Page BDG, Hedtrich S. TSLP as druggable target — a silver-lining for atopic diseases? Pharmacol Ther. 2021;217: 107648. doi: https://doi.org/10.1016/j.pharmthera.2020.107648

24. Kubo A, Nagao K, Yokouchi M, et al. External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers. J Exp Med. 2009;206(13):2937–2946. doi: https://doi.org/10.1084/jem.20091527

25. Rutz S, Ouyang W. Regulation of Interleukin-10 Expression. In: Regulation of Cytokine Gene Expression in Immunity and Diseases. Ma X, ed. Springer Dordrecht; 2016. pp. 89–116. doi: https://doi.org/10.1007/978-94-024-0921-5_5

26. Rinaldi G. The Itch-Scratch Cycle: A Review of the Mechanisms. Dermatol Pract Concept. 2019;9(2):90–97. doi: https://doi.org/10.5826/dpc.0902a03

27. Davidson WF, Leung DYM, Beck LA, et al. Report from the National Institute of Allergy and Infectious Diseases workshop on “Atopic dermatitis and the atopic march: Mechanisms and interventions”. J Allergy Clin Immunol. 2019;143(3):894–913. doi: https://doi.org/10.1016/j.jaci.2019.01.003

28. Szczepanowska J, Reich A, Szepietowski JC. Emollients improve treatment results with topical corticosteroids in childhood atopic dermatitis: a randomized comparative study. Pediatr Allergy Immunol. 2008;19(7):614–618. doi: https://doi.org/10.1111/j.1399-3038.2007.00706.x

29. Eckert RL, Rorke EA. Molecular biology of keratinocyte differentiation. Environ Health Perspect. 1989;80:109–116. doi: https://doi.org/10.1289/ehp.8980109

30. Siddiqi KS, ur Rahman A, Tajuddin, Husen A. Properties of Zinc Oxide Nanoparticles and Their Activity Against Microbes. Nanoscale Res Lett. 2018;13(1):141. doi: https://doi.org/10.1186/s11671-018-2532-3

31. Chew SWT, Zeng Y, Cui M, et al. In Situ Generation of Zinc Oxide Nanobushes on Microneedles as Antibacterial Coating. SLAS Technol. 2018;24(2):181–187. doi: https://doi.org/10.1177/2472630318812350

32. Clement JL, Jarrett PS. Antibacterial Silver. Met Based Drugs. 1994;1(5-6):467–482. doi: https://doi.org/10.1155/MBD.1994.467

33. Wisniewski JA, Agrawal R, Minnicozzi S, et al. Sensitization to food and inhalant allergens in relation to age and wheeze among children with atopic dermatitis. Clin Exp Allergy. 2013;43(10): 1160–1170. doi: https://doi.org/10.1111/cea.12169