Severe skin inflammation and filaggrin mutation similarly alter the skin barrier in patients with atopic dermatitis

Br J Dermatol. 2014 Mar;170(3):617-24. doi: 10.1111/bjd.12743.

Abstract

Background: Filaggrin (FLG) deficiency is a well-known predisposing factor for the development of atopic dermatitis (AD). Decreased FLG expression can be the result of haploinsufficiency or severe inflammation, which can cause acquired FLG alterations. FLG mutations are related to several clinical and laboratory parameters of AD; however, some recent data seem to contradict these associations.

Objectives: Our aim was to determine which clinical and biochemical parameters are connected to FLG haploinsufficiency and which ones are also associated with acquired FLG alterations due to severe skin symptoms in patients with AD.

Methods: We introduced a novel classification of patients with AD, based on FLG mutations and SCORAD (SCORing Atopic Dermatitis). Based on these parameters, we created three groups of patients with AD: mild-to-moderate wild-type (A), severe wild-type (B) and severe mutant (C). In all groups, we assessed laboratory and clinical parameters and performed immunohistochemical analyses.

Results: Groups B and C contained patients with equally severe symptoms based on the SCORAD. The two severe groups did not differ significantly with respect to barrier-specific parameters, whereas group A had significantly better results for the barrier function measurements. However, significant differences were detected between groups B and C with respect to the allergic sensitization-specific parameters.

Conclusions: These findings suggest that skin barrier function correlates with the severity of skin inflammation and can be equally impaired in patients with FLG mutant- and wild-type AD with severe symptoms. Nevertheless, our results also suggest that patients with FLG mutant-type AD may have a higher risk of allergic sensitization compared with patients with the wild-type.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cytokines / metabolism
  • Dermatitis, Atopic / genetics*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Filaggrin Proteins
  • Genotype
  • Humans
  • Intermediate Filament Proteins / deficiency
  • Intermediate Filament Proteins / genetics*
  • Male
  • Mutation / genetics*
  • Skin / metabolism
  • Thymic Stromal Lymphopoietin
  • Water Loss, Insensible / genetics
  • Young Adult

Substances

  • Cytokines
  • FLG protein, human
  • Filaggrin Proteins
  • Intermediate Filament Proteins
  • Thymic Stromal Lymphopoietin