A 6-month-old infant presents with pruritic oozing eczema on the cheeks and extensor surfaces. Serum IgE is elevated. The filaggrin protein (FLG) gene mutation predisposes to atopic dermatitis primarily by:

• A Directly increasing IL-4 and IL-13 secretion from keratinocytes
• B Impairing skin barrier function (reduced NMF, increased TEWL), allowing epicutaneous sensitization to allergens ✓
• C Activating mast cell degranulation via FcεRI receptor upregulation
• D Increasing Th1 cytokine production from dermal dendritic cells

Explanation

Filaggrin (profillagrin is processed to filaggrin, then to natural moisturizing factor/NMF components including urocanic acid and pyrrolidone carboxylic acid) is critical for skin barrier integrity. FLG loss-of-function mutations (R501X, 2282del4) cause reduced NMF, increased transepidermal water loss (TEWL), and elevated skin pH, allowing epicutaneous penetration of allergens, microbes, and irritants. This triggers Th2 sensitization and the atopic march. Dupilumab (anti-IL-4Rα) blocks both IL-4 and IL-13 signalling, which are the key Th2 effectors.

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.