Palmoplantar pustulosis: pathogenesis, differential diagnosis, and treatment

Palmoplantar pustulosis (PPP) is a chronic inflammatory and often painful disease characterized by sterile pustules on the palms and soles, significantly impairing quality of life. Women are more frequently affected than men, and smoking is a major trigger. Under biologic therapies, especially TNF antagonists, a paradoxical PPP may occur. PPP is associated with psoriasis vulgaris and may be accompanied by osteoarticular involvement. Pathogenetically, PPP likely begins around the acrosyringium, with the pustules consisting almost exclusively of infiltrating neutrophilic granulocytes attracted by chemotactic factors secreted by activated keratinocytes. Inflammation is sustained through a self-amplifying cytokine network, including interleukin (IL)-17, IL-19, and related mediators. Treatment options for PPP include topical treatments, UV-phototherapies - particularly topical PUVA (Psoralen plus UVA) therapy- and systemic therapies. Systemic agents comprise conventional treatments such as acitretin, methotrexate, fumaric acid esters, and ciclosporin, newer small molecules like apremilast and Janus kinase inhibitors, as well as biologics. Conventional systemic therapies are often not sufficiently effective in PPP and associated with side effects. Currently, among systemic therapies, only acitretin is approved for PPP. In recent years, placebo-controlled studies have demonstrated a significant effect of apremilast, brodalumab, guselkumab and risankizumab on PPP, and further studies with topical and systemic Janus kinase inhibitors as well as IL-17A/F inhibitors are underway.