COMPREHENSIVE REVIEW OF PSEUDOXANTHOMA ELASTICUM: PATHOGENESIS, CLINICAL MANIFESTATIONS, AND THERAPEUTIC STRATEGIES

ABSTRACT Pseudoxanthoma elasticum is a rare, autosomal recessive metabolic disorder marked by progressive ectopic mineralization and fragmentation of elastic fibers, primarily affecting the skin, eyes, and vasculature. Pathogenic ABCC6 mutations reduce ATP release from hepatocytes, causing systemic inorganic pyrophosphate deficiency and promoting soft tissue calcification. Clinically, PXE presents with yellowish, lax skin papules, retinal angioid streaks, choroidal neovascularization, and vascular complications including peripheral artery disease and gastrointestinal haemorrhage. Diagnosis combines dermatologic, ophthalmologic, histopathologic, and molecular assessments, with genetic testing confirming ABCC6 variants. Management is largely preventive and supportive, with intravitreal anti-VEGF therapy improving ocular outcomes, cosmetic and surgical interventions addressing skin lesions, and lifestyle modification minimizing cardiovascular risk. Emerging systemic therapies targeting mineralization pathways and genetic counselling offer promise for disease modification, underscoring the importance of multidisciplinary care. Keywords: Pseudoxanthoma elasticum; ABCC6; Ectopic mineralization; Genetic counselling; Rare disease