IN ATOPIC DERMATITIS, INFLAMMATION LIES AT THE HEART OF SIGNS & SYMPTOMS

Underlying chronic inflammation is a source of lesions and itch, primary signs and symptoms of atopic dermatitis1-3

Current evidence has shown that nonlesional skin is not normal skin, owing to persistent subclinical inflammation throughout the body.1-4 Chronic skin inflammation can be orchestrated by a mixture of activated immune and epidermal cells and can lead to pruritic lesion development.5-11 The epidermal layer of skin in atopic dermatitis is primed to react to environmental triggers, with signs and symptoms resulting from underlying hyperactivity in the deeper layers.2

  • Nonlesional skin frequently manifests with increased dryness and a greater irritant skin response in patients with atopic dermatitis than with healthy controls2

Experiments in murine models and human cell culture suggest that Th2-mediated inflammation weakens the skin barrier and creates susceptibility to xerosis (i.e., abnormal dryness of the skin) and highly pruritic lesion formation.12-13

  • Xerosis, infection, and/or allergens all contribute to pruritus,14 which can:15
    • Initiate a harmful itch-scratch cycle
    • Damage the skin barrier
    • Exacerbate signs and symptoms
  • Animal studies have shown that damage to the stratum corneum leads to the release of neuromediators by keratinocytes and to nerve-fibre sprouting in the epidermis, which can exacerbate pruritus15

Xerosis and Highly Pruritic Lesion Formation on Skin 

From J Derm Sci, Bieber T, Mechanisms of disease: atopic dermatitis. 2008;358(14):1483-1494. © 2016 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.16

Atopic dermatitis is a chronic, inflammatory skin disease in which the Th2 pathway is involved in the underlying inflammatory process.1,3

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References: 1. Gittler JK, Shemer A, Suárez-Fariñas M, et al. Progressive activation of Th2/Th22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012;130(6):1344-1354. 2. Leung DYM, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest. 2004;113(5):651-657. 3. Suárez-Fariñas M, Tintle SJ, Shemer A, et al. Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalities. J Allergy Clin Immunol. 2011;127(4):954-964. 4. De Benedetto A, Rafaels NM, McGirt LY, et al. Tight junction defects in patients with atopic dermatitis. J Allergy Clin Immunol. 2011;127(3):773-786. 5. Gaffal E, Glodde N, Jakobs M, Bald T, Tüting T. Cannabinoid 1 receptors in keratinocytes attenuate fluorescein isothiocyanate-induced mouse atopic-like dermatitis. Exp Dermatol. 2014;23(6):401-406. 6. Kagami S, Kakinuma T, Saeki H, et al. Significant elevation of serum levels of eotaxin-3/CCL26, but not of eotaxin-2/CCL24, in patients with atopic dermatitis: serum eotaxin-3/CCL26 levels reflect the disease activity of atopic dermatitis. Clin Exp Immunol. 2003;134(2):309-313. 7. Owczarek W, Paplińska M, Targowski T, et al. Analysis of exotoxin 1/CCL11, exotoxin 2/CCL24 and exotoxin 3/CCL26 expression in lesional and non-lesional skin of patients with atopic dermatitis. Cytokine. 2010;50(2):181-185. 8. Akdis M, Akdis CA, Weigl L, Disch R, Blaser K. Skin-homing, CLA+ memory T cells are activated in atopic dermatitis and regulate IgE by an IL-13-dominated cytokine pattern: IgG4 counter-regulation by CLA-memory T cells. J Immunol. 1997;159(9):4611-4619. 9. Akdis M, Simon H-U, Weigl L, Kreyden O, Blaser K, Akdis CA. Skin homing (cutaneous lymphocyte-associated antigen-positive) CD8+ T cells respond to superantigen and contribute to eosinophilia and IgE production in atopic dermatitis. J Immunol. 1999;163(1):466-475. 10. Seneviratne SL, Black AP, Jones L, Bailey AS, Ogg GS. The role of skin-homing T cells in extrinsic atopic dermatitis. Q J Med. 2007;100(1):19-27. 11. Jung T, Moessner R, Neumann C. Naïve CD4+ T cells from patients with atopic dermatitis show an aberrant maturation towards IL-4 producing skin-homing CLA+ cells. Exp Dermatol. 2003;12(5):555-562. 12. Hatano Y Adachi Y, Elias PM, et al. The Th2 cytokine, interleukin-4, abrogates the cohesion of normal stratum corneum in mice: implications for pathogenesis of atopic dermatitis. Exp Dermatol. 2013;22(1):30-35. 13. Kabashima K. New concept of the pathogenesis of atopic dermatitis: interplay among the barrier, allergy, and pruritus as a trinity. J Derm Sci. 2013;70(1):3-11. 14. Brandt EB, Sivaprasad U. Th2 cytokines and atopic dermatitis. J Clin Cell Immunol. 2011;2(3). doi:10.4172/2155-9899.1000110. 15. Yosipovitch G, Papoiu ADP. What causes itch in atopic dermatitis? Curr Allergy Asthma Reports. 2008;8(4):306-311. 16. Bieber T. Mechanisms of disease: atopic dermatitis. N Engl J Med. 2008;358(14):1483-1494.