Pyoderma gangrenosum is associated with excess incident major atherothrombotic events

Background and aims Systemic inflammation contributes to atherosclerosis and its thrombotic complications, yet population-level data for neutrophil-predominant dermatoses are limited. Pyoderma gangrenosum (PG) is a prototypical neutrophilic inflammatory dermatosis, we quantified its association with incident atherothrombotic events and MACE over 5 years. Methods Adults with PG were compared with non-PG controls. To limit reverse causation, we excluded individuals with pre-index cardiovascular events and selected vascular procedures. Cohorts were 1:1 propensity-score matched (greedy nearest neighbor; caliper 0.1 SD of logit). Follow-up was up to 5 years. Primary endpoint was MACE (cardiac arrest, cardiogenic shock, acute myocardial infarction [MI], ischemic stroke, all-cause mortality). Secondary endpoints were MI, ischemic stroke, symptomatic peripheral artery disease (PAD), and all-cause mortality. A negative-control outcome and a procedure-anchored PAD sensitivity analysis (lower-extremity revascularization) were prespecified. Results Among 10,669 PG patients and 2,908,830 controls, 10,666 matched pairs were retained with good covariate balance. Over 5 years, PG was associated with higher risk of MACE (HR 1.32; p < 0.001), MI (HR 1.42; p = 0.001), and all-cause mortality (HR 1.44; p < 0.001), while ischemic stroke was neutral (HR 0.94; p = 0.52). Symptomatic PAD showed the largest association (HR 5.48; p < 0.001), confirmed in the procedure-anchored analysis (HR 5.58; p < 0.0001). The negative control was null (HR 1.04; p = 0.82). Conclusions PG is associated with meaningful excess atherothrombotic risk, particularly PAD, supporting PG as a systemic inflammatory risk-enhancing condition requiring intensified cardiovascular prevention.