Janus Kinase Inhibitors for Treatment of Palmoplantar Pustulosis, Generalized Pustular Psoriasis, and Palmoplantar Pustular Psoriasis: A Systematic Review of the Literature

ABSTRACT Introduction Palmoplantar pustulosis (PPP) is a chronic, recurrent, inflammatory disease and assumed to be a subtype of psoriasis. Pustular psoriasis (PP) is a chronic inflammatory disease that is further subclassified into various entities with different presentations including generalized pustular psoriasis (GPP) and palmoplantar pustular psoriasis (PPPP). Given the central role of the JAK–STAT pathway in cytokine signaling, this systematic review evaluated the effectiveness and safety of Janus kinase inhibitors (JAK‐I) in these PP subtypes. Methods Following PRISMA 2020 guidelines, a systematic search was conducted across PubMed/Medline, Scopus, Web of Science, and Embase up to November 13, 2025. Eligible studies included assessing JAK‐I in PPP, GPP, or PPPP. Exclusion criteria were reviews, articles without full‐text, SAPHO syndrome, and animal/in vitro studies. Risk of bias was assessed using the NHLBI quality assessment tool for clinical studies and Murad et al.'s checklist for case reports/series. Results Thirty‐seven studies were included (29 case reports, 4 case series, and 4 clinical studies), encompassing 157 patients (60.5% female; mean age 46.8 years). Treatments involved tofacitinib, upadacitinib, baricitinib, abrocitinib, and topical ruxolitinib. In PPP, pooled meta‐analysis demonstrated a PPPASI‐50 response rate of 85.5% (95% CI, 71.3–93.3), with upadacitinib achieving 90.9% (95% CI, 81.7–95.7). Case reports and series showed 88.1% clearance or near‐clearance within a mean of 2.5 months. GPP patients ( n = 5) achieved rapid clearance or marked improvement within 2–12 weeks. Adverse events (18.7%) were generally mild, most commonly acneiform eruptions, headache, and transient liver enzyme elevations, with no severe events reported. Conclusion JAK‐I demonstrate high response rates and rapid improvement with manageable safety profiles. However, the current evidence is limited by small sample sizes, short follow‐up durations, and reliance on case‐based data. They represent a promising therapeutic option and warrant further evaluation in larger controlled studies to establish long‐term efficacy and safety.