Description and therapy of palmoplantar pustular psoriasis under IL-17A or dual IL-17A/F inhibition

Background: Interleukin (IL)-17 inhibitors are effective in treating psoriatic disease, but paradoxical inflammatory reactions can occasionally occur. Palmoplantar pustular psoriasis (PPP) onset or flares have been rarely reported with anti-IL-17A but not dual IL-17A/F inhibition (bimekizumab). Methods: Retrospective study: patients developing PPP while on anti-IL-17 were retrieved from hospital databases. Results: Ten new PPP cases occurred during treatment with anti-IL-17: median age 46 years (range 33-59), females 40%. Six patients were obese, five smokers. Different IL-17 inhibitors were implicated, including secukinumab (n = 4), ixekizumab (n = 4), and for the first reported time bimekizumab (n = 2). PPP occurred after a median of 3 months (range 1-60) from anti-IL-17 initiation, earlier in those who did not respond in the primary disease domain (2 months, range 1-3) compared to responders (median 10 months, 1-60). Management of PPP included anti-IL-17 retention with topical agents, ciclosporin or colchicine, switching within class, or swapping to other mechanisms of action (IL-23, TNF, and JAK inhibition). Clinical benefit was reported with all approaches on available follow-up. Conclusions: PPP is rare during IL-17 inhibition but can occur under dual IL-17A/F inhibition. The underlying immunological mechanisms may involve neutrophil inflammation that independent from type-17 immune response.