Insights into atopic dermatitis – from pathogenesis to therapy

Authors

  • K. Papadakis Department of Physiology and Pathophysiology, Medical Faculty, Medical University – Sofia, Bulgaria Author
  • T. Handjieva-Darlenska Department of Pharmacology and Toxicology, Medical Faculty, Medical University – Sofia, Bulgaria Author
  • R. Tafradjiiska-Hadjiolova Department of Physiology and Pathophysiology, Medical Faculty, Medical University – Sofia, Bulgaria Author
  • H. Nocheva Department of Physiology and Pathophysiology, Medical Faculty, Medical University – Sofia, Bulgaria Author

DOI:

https://doi.org/10.2478/AMB-2023-0022

Keywords:

atopic dermatitis, pathogenesis, genetics, environment, skin barrier

Abstract

Atopic dermatitis (AD), or eczema, is a common skin disease that is often associated with other atopic disorders, such as allergic rhinitis and asthma. The disease can develop both in infancy and adulthood, and characterizes with recurrent episodes impairing the quality of life. The review аnalyzes the genetical, immunological, and environmental factors in the pathogenesis of AD. The role of the skin barrier function is also considered in regard of the main hypotheses for AD development. Further elucidation of the mechanisms involved in the pathogenesis of AD could give interesting and useful clues for therapeutic protocols and prophylactic approaches.

References

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. J Allergy Clin Immunol, 2006, 118:152-169.

Illi S, von Mutius E, Lau S, et al. The natural course of atopic dermatitis from birth to age 7 years and the association with asthma. J Allergy Clin Immunol, 2004, 113:925-931.

Silverberg JI. Atopic Dermatitis in Adults. Med Clin North Am. 2020 Jan; 104(1):157-176. doi: 10.1016/j.mcna.2019.08.009).

Bieber T. Atopic Dermatitis. N Engl J Med, 2008, 358:1483-1494.

Bhattacharya N, Sato WJ, Kelly A, et al. Epidermal Lipids: Key Mediators of Atopic Dermatitis Pathogenesis. Trends Mol Med, 2019, 25(6):551-562. https://doi.org/10.1016/j.molmed.2019.04.001

Schultz LF. Atopic dermatitis: a genetic-epidemiologic study in a population-based twin sample. J Am Acad Dermatol, 1993, 28(5 Pt 1):719–723.

Rawlings AV, Harding CR. Moisturization and skin barrier function. Dermatol Ther, 2004, 17(Suppl 1):43–48.

Kezic S, O’Regan GM, Lutter R, et al. Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of fi laggrin defi ciency. J Allergy Clin Immunol, 2012, 129:1031-1039.

Brauweiler AM, Bin L, Kim BE, et al. Filaggrin dependent secretion of sphingomyelinase protects against Staphylococcal alphatoxin-induced keratinocyte death. J Allergy Clin Immunol, 2013, 131:421-427.

Silverberg JI. Atopic Dermatitis in Adults. Med Clin N Am, 2020, 104:157-176. https://doi.org/10.1016/j.mcna.2019.08.009

Mohiuddin M, Ramamoorthy P, Reynolds PR, et al. Increased compound heterozygous fi laggrin mutations in severe atopic dermatitis in the United States. J Allergy Clin Immunol Pract, 2013, 1:534-536.

Heine G, Hoefer N, Franke A, et al. Association of vitamin D receptor gene polymorphisms with severe atopic dermatitis in adults. Br J Dermatol, 2013, 168(4):855–858.

Berker T, Visscher D, Gooris GS, et al. Topically applied ceramides interact with the stratum corneum lipid matrix in compromised ex vivo skin. Pharm Res, 2018, 35(3):48. doi: 10.1007/s11095-017-2288-y

Schmid-Wendtner MH, Korting HC. The pH of the skin surface and its impact on the barrier function. Skin Pharmacol Physiol, 2006, 19:296-302.

Schafer L, Kragballe K. Abnormalities in epidermal lipid metabolism in patients with atopic dermatitis. J Invest Dermatol, 1991, 96:10–15.

McGirt LY, Beck LA. Innate immune defects in atopic dermatitis. J Allergy Clin Immunol, 2006, 118:202-208.

Howell MD, Wollenberg A, Gallo RL, et al. Cathelicidin defi - ciency predisposes to eczema herpeticum. J Allergy Clin Immunol 2006;117: 836-41.

Butcher EC, Picker LJ. Lymphocyte homing and homeostasis. Science, 1996, 272:60-66.

Picker LJ, Martin RJ, Trumble A, et al. Diff erential expression of lymphocyte homing receptors by human memory/eff ector T cells in pulmonary versus cutaneous immune eff ector sites. Eur J Immunol, 1994, 24:1269-1277.

Novak N, Bieber T. Allergic and nonallergic forms of atopic diseases. J Allergy Clin Immunol, 2003, 112:252-262.

Kerschenlohr K, Darsow U, Burgdorf WH, et al. Lessons from atopy patch testing in atopic dermatitis. Curr Allergy Asthma Rep, 2004, 4:285-289.

Spergel JM, Mizoguchi E, Brewer JP, et al. Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice. J Clin Invest, 1998, 101:1614-1622.

Traidl-Hoff mann C, Mariani V, Hochrein H, et al. Pollen-associated phytoprostanes inhibit dendritic cell interleukin-12 production and augment T helper type 2 cell polarization. J Exp Med, 2005, 201:627-636.

Clark RA, Chong B, Mirchandani N, et al. The vast majority of CLA+ T cells are resident in normal skin. J Immunol, 2006, 176:4431-4439.

Soumelis V, Reche PA, Kanzler H, et al. Human epithelial cells trigger dendritic cell mediated allergic infl ammation by producing TSLP. Nat Immunol, 2002, 3:673-680.

Grewe M, Walther S, Gyufko K, et al. Analysis of the cytokine pattern expressed in situ in inhalant allergen patch test reactions of atopic dermatitis patients. J Invest Dermatol, 1995, 105:407-410.

Tazawa T, Sugiura H, Sugiura Y, et al. Relative importance of IL-4 and IL-13 in lesional skin of atopic dermatitis. Arch Dermatol Res, 2004, 295(11):459–464.

Trautmann A, Akdis M, Kleemann D, et al. T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis. J Clin Invest, 2000, 106:25-35.

Esaki H, Brunner PM, Renert-Yuval Y, et al. Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin. J Allergy Clin Immunol, 2016, 138(6):1639–1651.

Aichberger KJ, Mittermann I, Reininger R, et al. Hom s 4, an IgE-reactive autoantigen belonging to a new subfamily of calcium-binding proteins, can induce Th cell type 1-mediated autoreactivity. J Immunol, 2005, 175:1286-1294.

Leung DYM. Pathogenesis of atopic dermatitis. J Allergy Clin Immunol, 1999, 104 (Suppl):S99-108.

Kramer MS, Kakuma R. Maternal dietary antigen avoidance during pregnancy or lactation, or both, for preventing or treating atopic disease in the child. Evid Based Child Health, 2014, 9:447–483.

Khan A, Adalsteinsson J, Whitaker-Worth DL. Atopic dermatitis and nutrition. Clin Dermatol, 2022, 40(2):135-144. https://doi.org/10.1016/j.clindermatol.2021.10.006

Leung DYM, Guttman-Yassky E. Deciphering the complexities of atopic dermatitis: Shifting paradigms in treatment approaches. J Allergy Clin Immunol, 2014, 134(4):769-779. doi:10.1016/j.jaci.2014.08.008

Lever R, Hadley K, Downey D, et al. Staphylococcal colonization in atopic dermatitis and the eff ect of topical mupirocin therapy. Br J Dermatol, 1988, 119:189-198.

Bunikowski R, Mielke M, Skarabis H, et al. Prevalence and role of serum IgE antibodies to the Staphylococcus aureus–derived superantigens SEA and SEB in children with atopic dermatitis. J Allergy Clin Immunol, 1999, 103:119-124.

Nickoloff BJ, Naidu Y. Perturbation of epidermal barrier function correlates with initiation of cytokine cascade in human skin. J Am Acad Dermatol, 1994, 30:535-546.

Nakajima S, Igyarto BZ, Honda T, et al. Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling. J Allergy Clin Immunol, 2012, 129:1048-1055.

Ghoreschi K, Laurence A, O’Shea JJ. Janus kinases in immune cell signaling. Immunol Rev, 2009, 228(1):273-287.

Suga H, Sato S. Novel topical and systemic therapies in atopic dermatitis. Immunol Med, 2019, 42(2):84-93.

Jimenez JL, Punzon C, Navarro J, et al. Phosphodiesterase 4 inhibitors prevent cytokine secretion by T lymphocytes by inhibiting nuclear factor-kappa B and nuclear factor of activated T cells activation. J Pharmacol Exp Ther, 2001, 299(2):753-759.

Grewe SR, Chan SC, Hanifi n JM. Elevated leukocyte cyclic AMP-phosphodiesterase in atopic disease: a possible mechanism for cyclic AMP-agonist hyporesponsiveness. J Allergy Clin Immunol, 1982, 70(6):452-457.

Nakajima S, Igyarto BZ, Honda T, et al. Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling. J Allergy Clin Immunol, 2012, 129:1048-1055.

Dominguez O, Plaza AM, Alvaro M. Relationship Between Atopic Dermatitis and Food Allergy. Curr Pediatr Rev. 2020;16(2):115-22.

Kajosaari M. Atopy prophylaxis in high-risk infants. Prospective 5-year follow-up study of children with six months exclusive breastfeeding and solid food elimination. Adv Exp Med Biol, 1991, 310:453–458.

Bergmann RL, Diepgen TL, Kuss O, et al. Breastfeeding duration is a risk factor for atopic eczema. Clin Exp Allergy, 2002; 32:205–209.

Khan A, Adalsteinsson J, Whitaker-Worth DL. Atopic dermatitis and nutrition. Clin Dermatol, 2022, 40(2): 135-144. https://doi.org/10.1016/j.clindermatol.2021.10.006

Zhao M, Shen C, Ma L. Treatment effi cacy of probiotics on atopic dermatitis, zooming in on infants: a systematic review and meta-analysis. Int J Dermatol, 2018, 57 :635–641.

Pessi T, Sütas Y, Hurme M, et al. Interleukin-10 generation in atopic children following oral lactobacillus rhamnosus GG. Clin Exp Allergy, 2000, 30:1804–1808.

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Published

30.06.2023

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Section

SCIENTIFIC REVIEW

How to Cite

Papadakis, K., Handjieva-Darlenska, T., Tafradjiiska-Hadjiolova, R., & Nocheva, H. (2023). Insights into atopic dermatitis – from pathogenesis to therapy. Acta Medica Bulgarica, 50(2), 73-80. https://doi.org/10.2478/AMB-2023-0022