A key epidermal component implicated in dry skin conditions is the protein filaggrin. This promotes the barrier effect by aggregating keratins and by being cross-linked to corneocyte surfaces. Filaggrin disturbances, including gene mutations, are strongly associated with atopic dermatitis.15,16

Proflaggrin is the precursor to filaggrin, which in turn is broken down into usually 10-12 different hygroscopic amino acid monomers which contribute to natural moisturising factors (NMF). Other NMF components include sodium ions, lactate and urea.16

As potent humectants, these molecules retain moisture in the stratum corneum as well as modifying the pH, helping the enzymes involved in ceramide metabolism and the epidermal cell maturation process. The skin surface is normally acidic giving it antimicrobial properties, too. Filaggrin breakdown products may also play a role in UV protection.

If levels of filaggrin or its breakdown products fall, NMF protection decreases with a number of effects:16

·       decreased stratum corneum hydration

·       decreased trans-epidermal water loss (water evaporation from the skin surface)

·       fewer amino acids with increased skin pH.

An increased skin surface pH can lead to:

·       increased serine protease activity

·       early breakdown of the membrane-junction corneodesmosomes

·       increased levels of cytokines with pro-inflammatory activity

·       increased risk of bacterial colonisation.

Filaggrin pathway inhibition also causes:

·       disturbed ceramide production

·       a breakdown in the keratin filaments and lipid distribution affecting corneocyte’s internal and external structures.

Skin barrier function will be lost with an increased likelihood of dry skin, infection, allergen penetration and inflammation.