Enzyme replacement therapy increases skin blood flow in Fabry disease

Background: In Fabry patients, alpha-galactosidase A deficiency with glycosphingolipid deposition in vessel walls and sympathetic vasomotor fibers alters tissue perfusion. Impaired vasomotor control results in excessive post-ischemic hyperemia (Stemper and Hilz, J Neurol., 2003). Enzyme replacement therapy (ERT) with agalsidase beta improves small nerve fiber function (Hilz et al. Neurology. 2004) and very likely improves end-organ perfusion, including skin perfusion.

Objective: To assess ERT effects on the control of post-ischemic superficial skin blood flow (SBF).

Methods: In 22 Fabry patients (29±8 years) we assessed SBF at the index finger after 180 seconds of forearm ischemia using laser Doppler flowmetry (PeriFlux™, Sweden) before and after 23 months of biweekly ERT with 0.9–1.1mg/kg body weight agalsidase beta® (Wilcoxon-test), and compared data to those of 15 healthy controls (30±8 years, U-test). Significance was assumed for p<0.05.

Results: Post-ischemic SBF was higher in untreated patients (555.75±306.28 PU) than in controls (266.1±65.1 PU; p<0.05). After 23 months of ERT, post-ischemic SBF of patients (308.44±116.82 PU) was lower than in untreated patients (p<0.05) and no longer differed from control values (p>0.05).

Conclusions: Ischemic acidosis induces post-ischemic hyperperfusion which is counter-regulated by sympathetic vasomotor activation (Somers et al. J Appl Physiol. 1992). Post-ischemic hyperperfusion in untreated Fabry patients is very likely due to compromised sympathetic activation. Normal post-ischemic hyperperfusion after 23 months of ERT very likely results from re-established vasomotor control due to improved small nerve fiber function (Hilz et al. Neurology. 2004).