Pseudoxanthoma elasticum and skin: Clinical manifestations, histopathology, pathomechanism, perspectives of treatment

Abstract

Pseudoxantoma elasticum (PXE), also known as Groenblad-Strandberg syndrome, is a rare heritable disease with an estimated prevalence of 1:50,000 in the general population. PXE is considered a prototype of multisystem ectopic mineralization disorders and it is characterized by aberrant mineralization of soft connective tissue with degeneration of the elastic fibers, involving primarily the eyes, the cardiovascular system, and the skin. Cutaneous lesions consist of small, asymptomatic, yellowish papules or larger coalescent plaques, typically located on the neck and the flexural areas. PXE is caused by mutations in the ABCC6 (ATP-binding cassette subfamily C member 6) gene that encodes a transmembrane ATP binding efflux transporter, normally expressed in the liver and the kidney; however, the exact mechanism of ectopic mineralization remains largely unknown. The histological examination of cutaneous lesions, revealing accumulation of pleomorphic elastic structures in middermis, is essential for the definitive diagnosis of PXE, excluding PXE-like conditions. PXE is currently an intractable disease; although the cutaneous findings primarily present a cosmetic problem, they signify the risk for development of ocular and cardiovascular complications associated with considerable morbidity and mortality. The purpose of this review is to present a comprehensive overview of this rare form of hereditary connective tissue disorders, focus on the pathogenesis, the clinical manifestation, and the differential diagnosis of PXE. Emphasis is also placed on the management of cutaneous lesions and treatment perspectives of PXE.

Increased vascular occlusion in patients with pseudoxanthoma elasticum

“…These regions show typically a lax, wrinkled, and redundant skin. [3] The ocular manifestations have characteristic funduscopic fi ndings: angioid streaks, peau d'orange, peripheral comet lesions, and choroidal neovascularization [6]. A thickening and calcifi cation of the Bruch's membrane appears to be the primary ophthalmologic pathology of PXE patients.…”

“…PXE is caused by a mutation of the ABCC6 (ATP-binding cassette subfamily C member 6) gene, which encodes a transmembrane transporter expressed primarily in liver and kidney [3]. Using a cellular model, generally, by releasing ATP the carrier leads to an increase of pyrophosphate (PPi), which inhibits ectopic mineralization.…”

Angioid Streaks in Psuedoxanthoma Elasticum

“…A mutation has been found in the ABCC6 gene, which encodes for a membrane transport protein involved in the synthesis of the extracellular matrix [2].…”

“…An early sign in the skin of PXE patients is the appearance of small (1 -5 mm), asymptomatic, soft papules of yellow ivory color, presenting in a reticular pattern. Skin changes commonly start at the neck, affecting flexural areas such as axillae, inguinal region, antecubital and popliteal fossa later during the course [2].…”

“…In the course of time the affected skin can lose elasticity, resulting in redundant skin folds. Skin lesions almost always begin at the lateral side of the neck, together with or followed by the flexural sites of the body [2]. In the posterior segment of the eye, Bruch's membrane, an extracellular matrix between the retinal pigment epithelium (RPE) and the choroid, contains elastic fibers.…”