Pseudoxanthoma elasticum: genetics, clinical manifestations and therapeutic approaches

Pseudoxanthoma elasticum (PXE) is an inherited disorder that is associated with accumulation of mineralized and fragmented elastic fibers in the skin, vascular walls, and Bruch's membrane in the eye. Clinically, patients exhibit characteristic lesions of the posterior segment of the eye including peau d'orange, angioid streaks, and choroidal neovascularisations, of the skin including soft, ivory-colored papules in a reticular pattern that predominantly affect the neck and large flexor surfaces, and of the cardiovascular system with peripheral and coronary arterial occlusive disease as well as gastrointestinal bleedings. There is yet no definitive therapy. Recent studies suggest that PXE is inherited almost exclusively as an autosomal recessive trait. Its prevalence has been estimated to be 1:25,000-100,000. Very recently, the ABCC6 gene on chromosome 16p13.1 was found to be associated with the disease. Mutations within ABCC6 cause reduced or absent transmembraneous transport that leads to accumulation of extracellular material. Presumably, this mechanism causes calcification of elastic fibers. Despite the characteristic clinical features, the variability in phenotypic expressions, and the low prevalence may be responsible for the disease being underdiagnosed. This review compiles and summarizes current knowledge of PXE pathogenesis and clinical findings. Furthermore, different therapeutic strategies to treat retinal manifestations are discussed, including thermal laser coagulation, photodynamic therapy, and intravitreal injections of drugs inhibiting vascular endothelial growth factor.