Multifactorial skin barrier deficiency and atopic dermatitis: Essential topics to prevent the atopic march

J Allergy Clin Immunol. 2016 Aug;138(2):350-358.e1. doi: 10.1016/j.jaci.2016.06.002. Epub 2016 Jun 22.


Atopic dermatitis (AD) is the most common inflammatory skin disease in the industrialized world and has multiple causes. Over the past decade, data from both experimental models and patients have highlighted the primary pathogenic role of skin barrier deficiency in patients with AD. Increased access of environmental agents into the skin results in chronic inflammation and contributes to the systemic "atopic (allergic) march." In addition, persistent skin inflammation further attenuates skin barrier function, resulting in a positive feedback loop between the skin epithelium and the immune system that drives pathology. Understanding the mechanisms of skin barrier maintenance is essential for improving management of AD and limiting downstream atopic manifestations. In this article we review the latest developments in our understanding of the pathomechanisms of skin barrier deficiency, with a particular focus on the formation of the stratum corneum, the outermost layer of the skin, which contributes significantly to skin barrier function.

Keywords: Atopic dermatitis; barrier function; corneocytes; cornified envelope; filaggrin; lipid; stratum corneum; tight junction.

Publication types

  • Review

MeSH terms

  • Animals
  • Dermatitis, Atopic / diagnosis
  • Dermatitis, Atopic / etiology*
  • Dermatitis, Atopic / metabolism*
  • Dermatitis, Atopic / therapy
  • Desmosomes / immunology
  • Desmosomes / metabolism
  • Desmosomes / pathology
  • Disease Management
  • Epidermis / pathology
  • Epidermis / physiology
  • Filaggrin Proteins
  • Humans
  • Hypersensitivity / etiology
  • Hypersensitivity / metabolism
  • Immunomodulation
  • Intermediate Filament Proteins / metabolism
  • Lipid Metabolism
  • Skin / immunology*
  • Skin / metabolism*
  • Skin / pathology
  • Tight Junctions / immunology
  • Tight Junctions / metabolism
  • Tight Junctions / pathology


  • FLG protein, human
  • Filaggrin Proteins
  • Intermediate Filament Proteins