Efficacy of upadacitinib in palmoplantar pustulosis case series highlights the complex immune response patterns

BACKGROUND AND OBJECTIVES: Palmoplantar pustulosis (PPP) is a chronic and refractory inflammatory skin disorder with unclear pathogenesis. PATIENTS AND METHODS: Ten PPP patients treated with upadacitinib were monitored to assess efficacy and safety. Immunofluorescence and immunohistochemistry were employed to evaluate Th1, Th2, and Th17 cell expressions, along with their associated cytokines in lesions on palms or soles from 16 PPP patients, 10 chronic eczema (CE) patients, 10 psoriasis vulgaris (PV) patients, and 7 healthy controls (HC). RESULTS: In PPP patients receiving upadacitinib, the shortest time to achieve PPPASI75 and PPPASI90 was 4 weeks and 8 weeks, respectively. The rates of patients achieving PPPASI90 at week 16, week 24, and week 52 was 70 %, 100 %, and100 %, respectively. Th1 cells and IFN-γ levels in PPP were comparable to CE and PV, and higher than HC. Th2 cells, IL-4, and IL-13 levels in PPP were similar to CE, and greater than HC and PV. Th17 cells, IL-17, and IL-36γ levels in PPP were comparable to PV, and more abundant than HC and CE. CONCLUSIONS: Upadacitinib is a safe and effective option for PPP patients, which may be attributed to the complex Th1, Th2, and Th17 inflammatory responses associated with PPP.