Pseudoxanthoma Elasticum and the Logic of its Ocular Manifestations

Pseudoxanthoma elasticum (PXE) is a fascinating disease. Its hallmark clinical findings, salient changes in the skin, cardiovascular system, and eyes, seemed at odds with the biology of the causative gene-encoding adenosine-binding cassette protein C6, ABCC6, which is expressed predominantly in the liver and, to a lesser degree, the kidneys. The paradox of gene expression in one organ but disease manifestations in entirely different organs slowed conceptual progress for years. Calcification and fragmentation of elastic fibers in the skin results in yellow papules, cobblestone plaques, and laxity, especially in flexural areas. Blood vessel involvement causes early-onset vascular calcification and atherosclerosis, contributing to complications like claudication, ischemic heart disease, and an increased risk of gastrointestinal bleeding from vascular brittleness and fragility. Ocular involvement often leads to loss of central vision and will be the focus of most of this commentary. The intriguing aspect of PXE was how was the laundry list of disparate pathological findings tied together?