Increased Risk of Cerebrovascular Events in Pseudoxanthoma Elasticum

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare, hereditary disease characterized by ectopic calcifications in the skin, eyes, and arteries. It is caused by pathogenic variants in the ABCC6 gene, leading to lower plasma levels of inorganic pyrophosphate (PPi), a natural inhibitor of ectopic calcification. Patients with PXE often have cerebrovascular events, but the incidence and subtypes of these events have yet to be elucidated. AIM: This study aims to compare the incidence of cerebrovascular events in PXE with that in the general population and to assess the underlying subtypes of symptomatic ischemic cerebrovascular events in adult patients with PXE. METHODS: Adult patients with a definitive or probable PXE diagnosis were included from the Dutch Expertise Center for PXE. All ischemic cerebrovascular events were systematically classified by two independent vascular neurologists according to the Trial of Org 10172 in Acute Cerebrovascular Event Treatment criteria. The incidence rate of cerebrovascular events in the PXE cohort was compared by calculating age- and sex-standardized incidence rates using data from Statistics Netherlands. Patient characteristics stratified by subtype according to the TOAST criteria were presented, and differences in patient characteristics were described. RESULTS: In total, 381 patients with PXE (mean age 50 ±14 years, 59% women) were included. During a median follow-up of 8.1 years (IQR 5.3-11.0), 47 incident cerebrovascular events occurred in 34 patients. Of all events, 45 were of ischemic origin, and 2 were intracerebral hemorrhages. Patients with PXE were more likely to develop a cerebrovascular event, compared to the general Dutch population (SIR, 4.8 (95% CI, 3.3-6.7). The most common subtype of ischemic strokes was small vessel disease (SVD) (10/29, 34%). Followed by cardioembolic stroke (5/29, 17%) and large artery atherosclerosis (3/29, 10%). CONCLUSION: Patients with PXE have a 4.8-fold higher risk of cerebrovascular events compared to the general population. Various ischemic cerebrovascular event subtypes occur in patients with PXE, with SVD being the most common subtype.