Management and Treatment for Pseudoxanthoma Elasticum (PXE)
There is no curative treatment for Pseudoxanthoma Elasticum, but management focuses on monitoring and treating organ-specific complications, particularly ocular, cardiovascular, and dermatological manifestations.
Disease Overview
Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive genetic disorder caused by mutations in the ABCC6 gene, with an estimated prevalence between 1:25,000 and 1:100,000 1. The condition is characterized by:
- Progressive calcification and fragmentation of elastic fibers in the skin, eyes, and blood vessels
- Reduced levels of peripheral pyrophosphate (PPi), a natural inhibitor of calcification
- Dysregulation of blood lipids 2
Diagnostic Approach
Diagnosis is based on the following findings:
- Skin manifestations: Small yellow papules on the neck, flexural areas that coalesce into loose, wrinkled skin
- Ocular findings: Angioid streaks, peau d'orange appearance, and comet tail lesions in the retina
- Vascular involvement: Peripheral artery disease, intermittent claudication
- Genetic testing: Identification of pathogenic variants in the ABCC6 gene
Management by Organ System
1. Ocular Management
Ocular complications represent the most significant threat to quality of life:
- Regular ophthalmologic monitoring: At least twice yearly examinations by specialists 3
- Treatment of choroidal neovascularization (CNV):
- Intravitreal anti-VEGF injections are the first-line treatment for CNV 4
- Photodynamic therapy may be considered as an alternative option
- Thermal laser coagulation for select cases
2. Cardiovascular Management
- Risk factor modification:
- Regular monitoring of blood pressure and lipid profiles
- Smoking cessation
- Healthy diet and regular exercise
- Vascular screening:
- Periodic assessment for peripheral arterial disease
- Evaluation for coronary artery disease in symptomatic patients
- Surgical intervention: For severe cardiovascular manifestations 1
3. Dermatological Management
- Skin care: Moisturizing and protecting affected skin areas
- Cosmetic concerns: Counseling regarding the appearance of skin lesions
- Monitoring: Regular dermatological examinations to assess progression
4. Gastrointestinal Management
- Monitoring for GI bleeding: Patients should be educated about signs of GI bleeding
- Prompt evaluation: Of any symptoms suggesting GI bleeding
Multidisciplinary Approach
Due to the multisystem nature of PXE, management requires:
- Coordination between dermatologists, ophthalmologists, cardiologists, and vascular specialists
- Regular follow-up with appropriate specialists based on organ involvement
- Genetic counseling for patients and families 5
Emerging Therapeutic Approaches
Several promising treatments are under investigation:
- Pyrophosphate supplementation: To address the underlying deficiency
- Gene therapy/editing: Targeting the ABCC6 gene
- Pharmacologic chaperone therapy: To improve function of mutated ABCC6 protein 2, 6
Patient Education and Lifestyle Recommendations
- Avoid trauma to affected skin areas
- Use sun protection to prevent additional skin damage
- Regular eye examinations to detect early signs of CNV
- Maintain a heart-healthy lifestyle to minimize cardiovascular complications
- Genetic counseling for family planning
Prognosis
The disease is slowly progressive with variable expression. Visual impairment from CNV and cardiovascular complications are the main determinants of morbidity and mortality. Early detection and appropriate management of complications can significantly improve quality of life and outcomes.
Follow-up Recommendations
- Ophthalmologic examination: Every 6 months
- Cardiovascular assessment: Annually
- Dermatologic evaluation: Annually
- Genetic counseling: At diagnosis and when planning pregnancy
PXE requires lifelong monitoring and management of complications to maintain quality of life and prevent serious complications.