Nail Involvement Is a Key Determinant of Treatment Persistence in Palmoplantar Pustulosis

Palmoplantar pustulosis (PPP) is a chronic relapsing inflammatory skin disorder predominantly affecting the palms and soles. Despite the continued use of oral systemic agents, real-world data on their durability and treatment patterns in PPP remain limited. To investigate the treatment patterns, drug survival, and clinical factors associated with treatment persistence in patients with PPP receiving oral systemic therapies. We conducted a retrospective cohort study of patients diagnosed with PPP at a tertiary care referral center in Korea between January 2010 and August 2023. Patients were categorized according to the initial oral agent prescribed-cyclosporine, acitretin, or methotrexate. Treatment trajectories were assessed using predefined criteria, and 12-month drug survival was evaluated. Clinical predictors of treatment non-persistence were identified using Cox proportional hazards regression analysis. Among 374 patients, 192 received oral systemic therapy (cyclosporine, n = 110; acitretin, n = 72; methotrexate, n = 8). Cyclosporine was the most commonly prescribed first-line agent. Median drug survival was the longest for cyclosporine, followed by methotrexate and acitretin (p = 0.15). Nail involvement was associated with greater persistence (HR = 0.617; 95% CI: 0.444-0.857; p = 0.004), whereas baseline hypertension increased discontinuation risk (HR = 1.492; 95% CI: 1.015-2.195; p = 0.042). Discontinuation patterns differed by agent: cyclosporine was often stopped early due to adverse events but remained durable in patients who tolerated it; acitretin was associated with early and persistent adverse events, with well-controlled disease emerging as a later reason for cessation; and methotrexate showed sustained use beyond 6 months, with most discontinuations attributed to well-controlled disease. This study highlights the heterogeneous treatment trajectories and variable drug survival among oral agents for PPP. Nail involvement and hypertension may be key clinical predictors of persistence. These findings support individualized treatment approaches to improve long-term management of PPP.