When topical therapy of atopic dermatitis fails: a guide for the clinician.

INTRODUCTION: While topical medications are the first line of treatment for mild-to-moderate atopic dermatitis, they are ineffective in individuals with diffuse disease and moderate-to-severe atopic itch. For these individuals, as well as those who do not respond to topical treatments, systemic medicines are typically essential and helpful. AREAS COVERED: We conducted a review of the literature to identify established systemic therapies, novel biologic agents, and recent advances in the pathophysiology of atopic dermatitis. The review discusses these data, which show that the majority of atopic itch medications now in development target the type 2 immune axis and brain sensitization, two main etiologies of atopic itch. We emphasize the evidence, efficacy, and side effect profiles of currently available systemic medications for atopic itch, as well as future potential for tailored therapy. EXPERT OPINION: We give our professional opinion on the current state of knowledge about atopic eczema pathogenesis and the innovative targets and therapies for atopic itch that include MRGPRX2, periostin, gabaergic medicines, and JAK/STAT inhibitors. Additionally, we discuss patient populations that stand to benefit the most from targeting these molecules or utilizing these drugs, as well as those who may face a disproportionate weight of adverse effects.