Filaggrin gene (FLG) loss-of-function mutations are the strongest genetic risk factor for atopic dermatitis. Filaggrin deficiency leads to barrier impairment through which mechanism?

• A Deficient natural moisturising factor (NMF) production and impaired lamellar body secretion raising skin pH and enabling protease activation ✓
• B Increased IL-4 receptor expression on keratinocytes
• C Upregulation of Th17 pathway with increased IL-17 in the skin
• D Absence of Langerhans cells from the epidermis

Explanation

Filaggrin is cleaved in the cornified cell envelope to produce natural moisturising factor (NMF) components—pyrrolidone carboxylic acid, urocanic acid and free amino acids—that maintain stratum corneum hydration and acidic pH. FLG mutations reduce NMF, raise skin surface pH (reducing antimicrobial defence), impair lipid lamellar body secretion, and allow serine protease over-activation, collectively disrupting barrier function. This barrier defect allows allergen penetration, skin sensitisation and Th2 skewing, explaining the 'atopic march' (eczema → asthma → rhinitis).

Reference: Neena Khanna Illustrated Synopsis of Dermatology & STD, 6th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.