Generalized pustular psoriasis patient with a heterozygous hypomorphic <i>MPO</i> variant refractory to intravenous spesolimab

Generalized pustular psoriasis (GPP) is a recurrent and sometimes life-threatening sterile pustular disease. Because interleukin (IL)-36 is the central cytokine in disease formation, spesolimab, which interferes with IL-36 receptor signaling, is highly effective. Here, we report a patient with GPP with a heterozygous hypomorphic MPO variant refractory to intravenous spesolimab. Although spesolimab showed excellent clinical efficacy in resolving pre-existing pustules and erythema, it did not suppress the emergence of new pustules and erythema, which did not decrease the peripheral blood neutrophil count, therefore bimekizumab, an anti-IL-17A/IL-17F antibody, was administered after the second spesolimab infusion, which resolved the pustules and erythema. We discuss the possible reasons for the resistance mechanism to spesolimab.