Pseudoxanthoma elasticum (PXE) is an autosomal recessive condition that causes progressive calcification within the elastic tissue of the skin, retina of the eye, and blood vessels. While this condition is most often associated with skin findings, the main risk of complications occurs in the visual and cardiovascular systems (Plomp et al., 2010). Severe visual impairment and peripheral artery disease often occurs. Gastrointestinal bleeding has also been reported (Tsang and Sharma, 2018).
PXE is due to homozygous or compound heterozygous pathogenic/likely pathogenic (P/LP) variants in the ABCC6 gene. Sequence variants account for the majority of P/LP variants (~90%). Depending upon ancestry, recurrent deletions within exons 23-29 and other exonic or whole gene deletions have been reported to occur for 5-30% of individuals suspected to have PXE. Increased chance for PXE is seen in few populations, such as the Afrikaners of South Africa, for whom a founder mutation is known (Terry and Uitto, 2001).
The minimal criteria for a clinical diagnosis of PXE includes the presence of angioid streaks in the retina and the presence of the characteristic skin lesions showing diagnostic histopathologic findings of calcified dystrophic elastic fibers. Additionally, the presence of two known PXE-causing gene P/LP variants with either of the above clinical features would establish the diagnosis of PXE (Terry and Uitto, 2001).
Treatment for PXE requires coordinated care by a multidisciplinary team typically including dermatology, ophthalmology, cardiology, vascular surgery, genetics, primary care, and nutrition support. Treatments are typically symptom-based, but also preventative surveillance by routine eye examination and physical examinations are recommended (Terry and Uitto, 2001; Legrand et al., 2018). Clinical trials have shown some benefit with the use of bisphosphonates such as alendronate and etidronate to reduce arterial calcification and subretinal neovascularization events (Luo et al., 2020; Kranenburg et al., 2018; Li and Uitto, 2018). Additionally, data has shown that treatment with Aflibercept has been helpful with managing the choroidal neovascularizations seen with PXE (Gliem, et al., 2020). Investigation is ongoing in the development of therapeutics such as dietary magnesium supplementation, enzyme replacement therapy, and gene therapy (Luo et al., 2020).
There are also other PXE-like cutaneous conditions with significant phenotypic overlap that may be included with a differential diagnosis. P/LP variants in ENPP1 have been associated with a phenotype including cutaneous and ocular symptoms similar to PXE, and often also includes generalized arterial calcification of infancy (Uitto et al., 2014). P/LP variants in the GGCX gene may produce a phenotype that includes the cutaneous features of PXE, but also includes deficiency of vitamin K- dependent clotting factors (Terry and Uitto, 2001).