<p>Inflammatory dermatoses like psoriasis and atopic dermatitis are prevalent autoimmune disorders whose management is challenged not only by inflammatory lesions but, more significantly, by persistent pruritus and frequent relapse following treatment discontinuation. The pathogenic progression of these dermatoses is critically influenced by an imbalance between pro-inflammatory adenosine triphosphate (ATP) and anti-inflammatory cyclic adenosine monophosphate (cAMP), alongside reactive oxygen species (ROS) accumulation. To address this imbalance and effectively scavenge ROS, we have developed AC@Mg/Ce-UiO, integrating adenylate cyclase (AC) with a defect-engineered Mg/Ce-UiO nanozyme, for inflammatory dermatosis treatment and recurrence prevention. Mg/Ce-UiO nanozyme, synthesized through a metal-substitution strategy, demonstrates enhanced superoxide dismutase-like and catalase-like activities, facilitating efficient ROS scavenging. Concurrently, the encapsulated AC enzyme catalyzes the conversion of ATP into cAMP. Both in vitro and in vivo studies demonstrate that AC@Mg/Ce-UiO markedly downregulates the expression of inflammatory cytokines and pruritogens, inhibits keratinocyte hyperproliferation, and diminishes the infiltration of immune memory T cells. Consequently, this nanozyme not only alleviates psoriatic symptoms (e.g., lesions and pruritus), but also decreases the likelihood of recurrence. This study introduces a safe and potent dual-catalytic therapy that targets the fundamental pathogenesis of inflammatory dermatoses, providing a promising strategy for achieving long-term remission and preventing recurrence.</p> Graphical abstract <p></p>