Despite a common CD4+ T-cell precursor, helper T (Th) 1 and 2 lymphocytes affect different immunologic responses, including cellular and humoral pathways, respectively. Th1 cells stimulate the activation of type 1 macrophages, IgG/immunoglobulin M production, and cytokine release (eg, interferon gamma [IFN-γ], interleukin 2) to respond to intracellular pathogens. In contrast, Th2 cells target extracellular pathogens, leading to increases in immunoglobulin E and proliferation of eosinophils, basophils, B lymphocytes, type 2 macrophages, and mast cells through the actions of interleukin 4 (IL-4), interleukin 5, interleukin 13 (IL-13), and interleukin 31.1 Th17 cells are important for host defense against extracellular bacteria and fungi, as well as injury, and are thought to be key drivers of autoimmune diseases. Th17 cells produce interleukin 17A, interleukin 17F, interleukin 22, and C-C motif chemokine ligand 20 and are characterized by neutrophil and macrophage recruitment. The Th2 cytokine, IL-4, has been shown to inhibit Th17 development.2 Dupilumab (Dupixent, Regeneron Pharmaceuticals and Sanofi Genzyme), a fully human monoclonal (IgG4) antibody, inhibits the signaling of IL-4/13 by blocking the shared receptor subunit, IL-4 receptor α. Dupilumab is an effective treatment for a number of Th2-driven conditions, including atopic dermatitis (AD), asthma, and chronic rhinosinusitis with nasal polyposis. Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, which is characterized by multifocal demyelination and neuroaxonal degeneration, where the immune system is skewed toward Th1/Th17 axes.3 Interestingly, epidemiologic studies have suggested that a history of allergic diseases may confer some protection from MS.4 We report a temporal association of relapsing-remitting MS flareup and dupilumab treatment for AD. We provide a potential mechanism by which dupilumab leads to Th2 suppression with secondary Th1/17 dysregulation.