Ixekizumab-induced urticaria is associated with the short duration of remission in psoriasis by activation of mast cells

Mast cell degranulation plays a pivotal role in urticaria and is also an early histological characteristic of psoriasis. However, whether the activation of mast cells contributes to psoriasis recurrence after discontinuation of IL-17A blockers remains unclear.To investigate the role of mast cells in ixekizumab treatment-associated urticaria (ITAUR) and assess the effect of urticaria eruption on psoriasis relapse.A retrospective analysis was performed on biopsies of patients who experienced psoriasis relapse after discontinuation of ixekizumab. Transcriptomic and histopathological features were assessed. Patterns were compared between patients with ITAUR and non-urticaria (NUR) as well as psoriasis-like mice with mast cell activation or inactivation.Patients with ITAUR experienced early relapse compared to NUR group after treatment withdrawal. Transcriptomic and histopathological analyses revealed that patients with ITAUR had an elevated proportion of mast cells in resolved skin. Especially, the proportion of IL-17A-positive mast cells was inversely correlated with the duration of remission.The mechanism of mast cell activation in ITAUR has not been precisely elucidated.Ixekizumab treatment increases IL-17A-positive mast cells in lesions of ITAUR, which is associated with early psoriasis relapse after ixekizumab withdrawal.