Palmoplantar pustulosis (PPP) is a rare, chronic, recurrent inflammatory disease that affects the palms and/or the soles with sterile, erupting pustules, which are debilitating and usually resistant to treatment. It has genetic, histopathologic and clinical features that are not present in psoriasis; thus, it can be classified as a variant of psoriasis or as a separate entity. Smoking and upper respiratory infections have been suggested as main triggers of PPP. PPP is a challenging disease to manage, and the treatment approach involves both topical and systemic therapies, as well as phototherapy and targeted molecules. No gold standard therapy has yet been identified, and none of the treatments are curative. In patients with mild disease, control may be achieved with on-demand occlusion of topical agents. In patients with moderate-to-severe PPP, phototherapy or a classical systemic agent (acitretin being the best treatment option, especially in combination with PUVA) may be effective. Refractory patients or those with contraindications to use these therapies may be good candidates for apremilast or biologic therapy, particularly anti-IL-17A and anti-IL-23 agents. Recent PPP trials are focusing on blockage of IL-36 or IL-1 pathways, which play an important role in innate immunity. Indeed, IL-36 isoforms have been strongly implicated in the pathogenesis of psoriasis. Therefore, blockage of the IL-36 pathway has become a new treatment target in PPP, and three studies are currently evaluating the use of monoclonal antibodies that block the IL-36 receptor in PPP: ANB019 and spesolimab (BI 655130). In this review, we explore the diagnosis, screening and treatment of patients with PPP.

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