In this episode of Derms and Conditions, host James Q. Del Rosso, DO, sits down with Jason Hawkes, MD, Chief Scientific Officer at Oregon Medical Research Center, to explore the role of dupilumab in chronic spontaneous urticaria (CSU), a condition historically managed outside dermatology. They begin with the immunologic underpinnings of CSU, explaining the role of IL-4 and IL-13 in driving mast cell activation and the role of IL-31 in itch. Since dupilumab blocks these key cytokines, it can disrupt the disease process at multiple levels, from antibody formation to immune cell recruitment. They discuss the growing comfort among dermatologists in treating CSU now that a familiar and accessible agent like dupilumab is available, especially when compared to omalizumab, which has been limited by concerns over anaphylaxis and practice logistics. They next address real-world considerations, including the time dupilumab takes to work, the use of short-term corticosteroids, and the need for personalized treatment approaches. They caution against over-reliance on corticosteroids and discuss alternative bridging therapies like cyclosporine or methotrexate for severe cases. The episode also covers dosing nuances, patient selection, how to distinguish CSU from other urticaria types, and the importance of setting expectations. Dr Hawkes shares his experience with long-term efficacy, noting minimal loss of response among his patients. Listen to this episode for more clinical insights on dupilumab as a key treatment in managing chronic spontaneous urticaria, including considerations around patient selection, duration of therapy, and long-term disease control.