Eczema Pathogenesis — SCE Dermatology MCQ

Correct answer: D — The primary defect is epidermal barrier dysfunction (e.g., FLG mutations) leading to allergen/irritant penetration, immune activation, and subsequent inflammation

The 'outside-in' hypothesis proposes that atopic eczema begins with a primary defect in the epidermal barrier (epithelial barrier dysfunction) — most notably filaggrin (FLG) loss-of-function mutations — which leads to increased transepidermal water loss, enhanced penetration of allergens/irritants/microbes, and subsequent activation of the immune system (epicutaneous sensitisation). The 'inside-out' hypothesis proposes that primary immune dysregulation (Th2 skewing) drives the inflammation which secondarily damages the barrier. Current understanding supports both mechanisms operating simultaneously, with genetic predisposition (FLG mutations) and immune dysregulation (Th2/IL-4/IL-13) creating a vicious cycle. This dual pathogenesis informs therapeutic approaches: barrier repair (emollients) + immune modulation (anti-inflammatory therapy).

Reference: BAD 2020 AD; JACI Eczema Pathogenesis