ImmunologyTier 1Medical Sciences concept

Skin barrier dysfunction in atopic dermatitis (filaggrin)

Core concept

Filaggrin (filament-aggregating protein) cross-links keratin filaments in the stratum corneum and its breakdown products form part of the natural moisturising factor -- essential for skin barrier integrity and hydration
Loss-of-function filaggrin gene mutations are the strongest known genetic risk factor for atopic dermatitis -- present in a substantial proportion of moderate-severe cases
Barrier defect -> increased transepidermal water loss and increased allergen/microbial penetration -> downstream Th2-skewed inflammatory response

Filaggrin deficiency is not itself sufficient to cause eczema -- interacts with environmental factors (soap/detergent exposure, climate, microbiome) and other immune susceptibility genes
Same defective barrier -> facilitates cutaneous sensitisation to food and environmental allergens -- underpins the "atopic march" (eczema -> food allergy -> allergic rhinitis -> asthma), with sensitisation occurring through the skin rather than the gut
Filaggrin mutations also associate with ichthyosis vulgaris (dry, scaly skin) -- often co-exists with atopic dermatitis in the same patient/family

Explains the rationale for early, proactive emollient use in high-risk infants -- restoring barrier function to reduce transcutaneous allergen sensitisation (though trial evidence for eczema/food-allergy prevention has been mixed)
Staphylococcus aureus colonisation exploits the same barrier defect -- colonises non-lesional skin and drives disease flares via superantigen-mediated inflammation
Trap: treating atopic dermatitis as a purely "immune" disease -- barrier repair (emollients, avoiding irritants) is foundational therapy alongside anti-inflammatory treatment, not an afterthought

Directly underlies the atopic march concept -- links atopic dermatitis to subsequent IgE-mediated food allergy and asthma risk
Contrast with primary immunodeficiency-associated eczema (e.g. Wiskott-Aldrich syndrome, hyper-IgE/Job syndrome) -- eczema there arises from immune dysregulation, not a primary structural barrier gene defect
Same transepidermal water loss/barrier concept applies to neonatal skin immaturity and preterm infant fluid losses, albeit a different mechanism

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