Efficacy and safety of Janus kinase and TYK2 inhibitors in the treatment of generalized pustular psoriasis and palmoplantar pustulosis: a systematic review.

Pustular psoriasis (PP), including generalized pustular psoriasis (GPP) and palmoplantar pustulosis (PPP), is a rare and severe inflammatory dermatosis distinct from plaque psoriasis and associated with significant unmet therapeutic needs. Although advances in immunopathogenesis have identified key cytokine and signaling pathways, evidence-based treatment options remain limited. This systematic review evaluates the efficacy and safety of emerging Janus kinase (JAK) and tyrosine kinase (TYK) inhibitors in the management of PP. This systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed/Medline, Ovid-Embase, and Web of Science were searched from inception to November 15th, 2025, to identify all English-language clinical studies evaluating JAK or TYK inhibitors in patients with GPP or PPP. Methodological quality and risk of bias were independently assessed using National Institutes of Health quality assessment tools and the Murad et al. criteria. Of 2,259 records identified, 33 clinical studies (177 patients with GPP or PPP) met the predefined eligibility criteria. TYK inhibitors were evaluated in three studies of deucravacitinib (n = 11), which showed variable efficacy across reports: improvements in PASI/PPPASI, symptoms, and quality of life in some patients, and discontinuation due to insufficient response in others, with no serious adverse events reported. JAK inhibitors were evaluated in 30 studies involving 166 patients and were associated with improvements in disease severity, quality of life, and physician-assessed outcomes. Favorable responses were reported in observational studies, while rapid clinical improvement was frequently described in case-based evidence. Overall, treatment was generally well tolerated, although interpretation is limited by the predominance of uncontrolled studies and heterogeneous data. Available evidence indicates that JAK and TYK inhibitors may provide clinical benefit in GPP and PPP, particularly in refractory cases, with generally acceptable safety profiles. However, conclusions are limited by small, heterogeneous studies, and well-designed randomized controlled trials with longer follow-up are needed to establish long-term efficacy and safety.