Therapy of Pseudoxanthoma Elasticum: Current Knowledge and Future Perspectives

Abstract

Pseudoxanthoma elasticum (PXE) is a rare, genetic, metabolic disease with an estimated prevalence of between 1 per 25,000 and 56,000. Its main hallmarks are characteristic skin lesions, development of choroidal neovascularization, and early-onset arterial calcification accompanied by a severe reduction in quality-of-life. Underlying the pathology are recessively transmitted pathogenic variants of the ABCC6 gene, which results in a deficiency of ABCC6 protein. This results in reduced levels of peripheral pyrophosphate, a strong inhibitor of peripheral calcification, but also dysregulation of blood lipids. Although various treatment options have emerged during the last 20 years, many are either already outdated or not yet ready to be applied generally. Clinical physicians often are left stranded while patients suffer from the consequences of outdated therapies, or feel unrecognized by their attending doctors who may feel uncertain about using new therapeutic approaches or not even know about them. In this review, we summarize the broad spectrum of treatment options for PXE, focusing on currently available clinical options, the latest research and development, and future perspectives.

Targeting ABCC6 in Mesenchymal Stem Cells: Impairment of Mature Adipocyte Lipid Homeostasis

“…The elucidation of the pathomechanism behind ABCC6 causing PXE is a critical step in providing adequate therapy to patients. The application of statins, such as atorvastatin, is currently state-of-the-art medication due to the high risk of coronary artery disease and altered serum lipid profile in patients [ 29 , 30 ]. Positive effects of atorvastatin on abnormal cholesterol biosynthesis and partial improvement of the inflammatory phenotype in the periphery represented by PXE fibroblasts underline the systemic impact of ABCC6 [ 14 , 31 ].…”

Pseudoxanthoma elasticum: Die Lotsenfunktion des Dermatologen

“…Das PXE wird charakterisiert durch eine Kalzifikation der elastischen Fasern in verschiedensten Organen, symptomatisch werden diese jedoch nur in der Haut, arteriellen Gefäßen und der okulären Bruch-Membran [ 2 , 5 ]. Die Prävalenz in der Allgemeinbevölkerung liegt zwischen 1:25.000 und 1:56.000 [ 8 ].…”

“…Durch den gestörten Efflux eines bislang unbekannten Substrates wird die ATP-Ausscheidung in der Leber vermindert [ 3 ], was zu einer reduzierten Menge an Pyrophosphat (PPi), einem starken Inhibitor der ektopen Mineralisation [ 5 , 8 ], führt.…”

“…Bezüglich der dermatologischen Therapie finden sich in der Literatur nur wenige Berichte über kosmetische Operationen, Kollageninjektionen und Skin-Resurfacing mit einem fraktionierten CO 2 -Laser. Insgesamt waren die erzielten Verbesserungen mit einer hohen Rezidivrate oder Komplikationen assoziiert, sodass die Therapieindikation zurückhaltend gestellt werden sollte [ 8 ].…”

“…Eine hoch dosierte Einnahme von Magnesium kann einen leicht positiven Effekt haben [ 4 , 7 ]. Des Weiteren zeigten Bisphosphonate einen unterstützenden Effekt und konnten vaskuläre Kalzifikationen außerhalb der Koronararterien reduzieren [ 8 ].…”