Filaggrin mutations and atopy: consequences for future therapeutics

Abstract

Filaggrin is a key component of the epidermal differentiation complex of the stratum corneum in the epidermal layer of human skin. Loss-of-function mutations in filaggrin have been described in patients with atopic eczema and are associated with an increased risk of atopic sensitization in these individuals. Atopic eczema is the first stage of the atopic march that describes the phenomenon of increased rates of allergic rhinitis and allergic asthma observed in individuals with early atopic dermatitis. The skin barrier disruptions of atopic eczema associated with loss-of-function mutations in filaggrin are thought to provide a nidus for allergic sensitization to food and aeroallergens, which can then lead to increased allergic disease. It is on this foundation that therapies aimed at restoration of barrier function are thought to play a role, not only in the effective treatment of atopic eczema, but also in the prevention of further allergic disease development.

Keywords::

• atopic march
• atopy
• epidermal differentiation complex
• filaggrin
• TSLP

Financial & competing interests disclosure

J Spergel has grant support from the Department of Defense, NIH, Ception, Merck Pharmaceutical and Nutricia. J Spergel is also on the scientific advisory board for DBV. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.