Generalized Pustular Psoriasis Confers Increased Risk of Pyoderma Gangrenosum: First Population-Based Evidence.

INTRODUCTION: Generalized pustular psoriasis (GPP) and pyoderma gangrenosum (PG) are rare, severe neutrophilic dermatoses with overlapping autoinflammatory pathways. Although case reports suggest a link between GPP and PG, no population-based studies have quantified this risk. METHODS: We performed a retrospective cohort study using the TriNetX federated electronic health record network. Adults (≥18 years) with ICD-10 codes for GPP (L40.1) or non-GPP (L40.0-L40.9 excluding L40.1) from 2018 to 2023 were identified. Controls had no psoriasis diagnosis. Cohorts were 1:1 propensity score matched for age, sex, race, ulcerative colitis, Crohn's disease, systemic lupus erythematosus, and rheumatoid arthritis. The primary outcome was new PG diagnosis (L88) post-index. Hazard ratios (HRs) for PG were estimated via matched survival analysis. RESULTS: After matching, the GPP cohort (n = 44,187) had a significantly higher risk of PG than controls (n = 44,187; HR 5.14; 95% CI 2.77-9.53). Non-GPP patients (n = 393,833) also showed elevated PG risk versus controls (n = 393,833; HR 3.83; 95% CI 3.00-4.90). In direct comparison (n = 193,208 each), GPP had greater PG risk than non-GPP (HR 2.33; 95% CI 1.46-3.71). Median follow-up ranged from 687 to 886 days across comparisons. CONCLUSION: This first population-based evidence demonstrates that GPP confers a markedly increased risk of PG compared to both controls and other psoriasis subtypes. These findings underscore the need for heightened clinical vigilance for PG in GPP patients and may inform targeted surveillance strategies.