Skin and Arterial Wall Deposits of 18F-NaF and Severity of Disease in Patients with Pseudoxanthoma Elasticum.

Antonio Gutierrez-Cardo,Juan Luis Carrillo-Linares,Alejandro Rodriguez-Morata,María García-Fernández,Eugenia Lillo,Isabel Baquero Aranda,Pedro Valdivielso,Francisco García-Argüello,Belén Murcia-Casas,Purificación Sánchez-Sánchez,Miguel Ángel Sánchez-Chaparro

doi:10.3390/jcm9051393

Abstract

Pseudoxanthoma elasticum (PXE) is a genetic disease characterized by the calcification of elastin fibers. Our aim was to quantify vascular calcification in the arteries and the deposition of 18F-sodium-fluoride (18F-NaF) in the skin and vessel walls with positron emission tomography/computed tomography. This was an observational study including 18 patients with PXE. Vascular calcification was measured in Agatston units, and deposition in the skin and vessel walls was shown using target-to-background ratio (TBR). Severity of the disease was scored by Phenodex. We found higher vascular calcification in the popliteal, femoral, and aortic arch vessels compared to other vascular regions; however, the uptake of radiotracer was the highest in the aorta and femoral arteries. In the skin, the highest uptake was observed in the neck and the axillae. There was no significant association between 18F-NaF deposition in the arteries or skin and the global Phenodex score. In contrast, the Phenodex score was significantly associated in univariate analyses with the averaged vascular calcium score (p < 0.01). In the neck, patients with higher skin Phenodex scores exhibited higher radiotracer uptake. As a conclusion, because vascular calcification is physiological, our data suggested that the detection of cutaneous (neck) 18F-NaF deposits might serve to monitor the calcification process in the short-term for patients with PXE.

Highlights

Pseudoxanthoma elasticum (PXE) is a rare disease caused by mutations in the ABCC6 gene, which encodes multidrug resistance-associated protein 6 (MRP6)
All patients with hypertension were under treatment with anti-hypertensive drugs; eight patients were under treatment with statins; and five were under treatment with antiplatelet agents
Our study confirmed that 18F-NaF was deposited in calcified areas of the skin and vessel walls in PXE, but it was only weakly associated with disease severity

Summary

Introduction

Pseudoxanthoma elasticum (PXE) is a rare disease caused by mutations in the ABCC6 gene, which encodes multidrug resistance-associated protein 6 (MRP6). Patients with PXE have less ATP available for conversion into inorganic pyrophosphate (PPi), a physiological inhibitor of calcification [1]. PXE is characterized by progressive calcification of elastic fibers, which undergo fragmentation and deformation. This condition leads to loss of function and damage to Bruch’s membrane in the retina, the skin, and vessel walls. The severity of PXE is evaluated with the Phenodex score [4]. This score rates the signs and symptoms in different systems (skin, eye, gastrointestinal system, vasculature, and the heart), and 12 is the highest score

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