A 6-year-old child with severe atopic dermatitis has failed topical steroids and topical tacrolimus. Dupilumab is considered. The mechanism of action of dupilumab in AD is:

• A Blocks IgE binding to FcεRI on mast cells and basophils
• B Monoclonal antibody blocking the IL-4Rα subunit, thereby inhibiting both IL-4 and IL-13 signalling ✓
• C Inhibits Janus kinase 1/2 (JAK1/JAK2) preventing downstream STAT activation
• D Anti-IL-31 antibody reducing pruritus via itch-specific neurons

Explanation

Dupilumab is a fully human monoclonal antibody that blocks the IL-4 receptor alpha (IL-4Rα) subunit, which is shared by the type I (IL-4Rα/γc) and type II (IL-4Rα/IL-13Rα1) receptor complexes. This dual blockade inhibits both IL-4 and IL-13 signalling, which are the dominant Th2 cytokines driving AD pathogenesis — reducing IgE production, barrier dysfunction, and eosinophilic inflammation. Omalizumab (anti-IgE) blocks IgE; JAK inhibitors (abrocitinib, upadacitinib) act intracellularly; nemolizumab targets IL-31Rα.

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

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Written and medically reviewed by the StethoPrep medical team.