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target IL-23, including guselkumab, a fully human immunoglobulin G1 monoclonal antibody that binds to the p19 subunit of IL-23. Interleukin 23 is thought to be a potent inhibitor of psoriasis disease activity through its disruption of the IL-23/T H 17 disease axis. Specifically, T H 17 cells depend on IL-23 for their continued maintenance. T helper 17 cells interact with keratinocytes, endothelial cells, and other immune cells, all central to psoriasis pathophysiology. Reactivation of memory T H 17 cells is thought to underlie psoriasis chronicity. 2 The cytokine profile of ACD involves the IL-12/T H 1 cell axis. 3,4 Multiple immune signaling pathways, such as nuclear factor κB and interferon regulatory factor 1, cooperate in allergen-stimulated dendritic cells to result in IL-12 production. Interleukin 12 supports STAT4-mediated interferon γ release by immune cells and is thus crucial to T H 1 pathway activation and differentiation. Neutralization of IL-12 has been found to suppress the response to sensitizing allergens in vivo. 3 Interleukin 23 may be able to modulate T H 1 polarization through disruption of lymphocyte response to IL-12. 5 Thus, inhibition of IL-23 with guselkumab could enrich T H 1 activation and shift the cytokine milieu in favor of ACD development (Fig. 2), similar to the reported mechanism in the case of other dermatologic adverse events. 6 Theoretically, dual IL-12/IL-23 inhibitors, such as ustekinumab, should pose a lower risk in comparison because they block both T H 1 and T H 17 axes.Although we were unable to find a previous report of ACD occurring in the setting of IL-23 blockade for psoriasis, it is noteworthy that the Food and Drug Administration's multidisciplinary review of guselkumab does state that ACD occurs more frequently in patients in treatment arms compared with controls. 7 Notably, adverse events, such as ACD, take time to develop and thus are not likely to have been fully captured during the monitoring period of anti-IL-23 clinical trials, which were designed to evaluate efficacy. In addition, given the overlap in clinical presentation of ACD and psoriasis, it is possible that ACD is an underreported adverse event associated with IL-23 blockade. ZEBRAGiven the overlap in clinical presentation of ACD and psoriasis, it is possible that ACD is an underreported adverse event associated with IL-23 blockade.