🧴 Filaggrin Skin Barrier Dysfunction Simulator

Filaggrin Gene Mutation Background

FLG loss-of-function variants are the strongest known genetic risk factor for atopic dermatitis.

• FLG: Gene (Chromosome 1q21, EDC locus)
• ~10%: Carrier frequency (European populations, short placeholder)
• ~3x: AD risk increase (Short placeholder estimate)
• Semi-dominant: Inheritance (Short placeholder note)

Profilaggrin to filaggrin processing

Short placeholder: profilaggrin is proteolytically cleaved into filaggrin monomers.

Stratum Corneum Barrier Breakdown

Loss of filaggrin weakens the corneocyte-lipid brick-and-mortar architecture.

• 15-20: Barrier layers (Corneocyte layers, short placeholder)
• Reduced: Lipid loss (Ceramide content, short placeholder)
• Elevated: pH shift (Surface pH, short placeholder)
• Increased: Gap frequency (Short placeholder metric)

Brick and mortar disruption

Short placeholder: corneocytes loosen and lipid mortar becomes discontinuous.

Transepidermal Water Loss Increase

A defective barrier lets water escape far faster than normal skin.

• ~5 g/m²h: Normal TEWL (Short placeholder baseline)
• 2-5x: AD skin TEWL (Short placeholder elevation)
• Marked: NMF reduction (Natural moisturizing factor, placeholder)
• Modulating: Humidity effect (Short placeholder note)

Water gradient escape

Short placeholder: water diffuses outward along the disrupted lipid pathway.

Allergen and Microbe Penetration

Gaps in the barrier allow allergens and microbes to enter and trigger immune activation.

• Elevated: Th2 activation (Short placeholder immune note)
• Increased: S. aureus colonization (Short placeholder metric)
• Higher risk: IgE sensitization (Short placeholder note)
• Accelerated: Atopic march (Short placeholder concept)

Outside-in penetration route

Short placeholder: allergen particles diffuse through fissures into the epidermis.

Barrier Repair Strategy Implications

Restoring lipids and hydration can partially compensate for filaggrin deficiency.

• First-line: Emollient use (Short placeholder therapy note)
• Optimized: Ceramide ratio (Short placeholder formulation note)
• Improved: Flare reduction (Short placeholder outcome)
• Early infancy: Prevention window (Short placeholder timing note)

Restorative barrier therapy

Short placeholder: proactive emollient therapy reduces flare frequency and severity.

Short placeholder: early barrier repair may reduce atopic march progression.