Pseudoxanthoma elasticum

PSEUDOXANTHOMA ELASTICUM: PRESENTATION, COMPLICATIONS, AND DIAGNOSIS

Pseudoxanthoma elasticum is a rare autosomal recessive genetic disorder caused by mutations in ABCC6, resulting in low levels of the ectopic calcification inhibitor pyrophosphate and leading to elastic fiber fragmentation and calcification in the skin, eyes, and vascular system. It affects 1 in 25,000 to 56,000 individuals.¹ While skin lesions might start during childhood, dermatologic manifestations are found most often during the second or third decade.² The characteristic skin manifestations are yellowish papules that coalesce into plaques with a cobblestone appearance, most commonly seen on the lateral neck. Although not present in this patient, plaques in axillary folds are also a frequent finding.² A negative family history does not rule out pseudoxanthoma elasticum due to its variable presentation.³

Ophthalmologic complications of pseudoxanthoma elasticum include mottling of the retinal pigment epithelium and angioid streaks (representing breaks in a calcified Bruch membrane), which may progress to choroidal neovascularization and vision loss.⁴ Angioid streaks are observed in at least 85% of patients with pseudoxanthoma elasticum.⁵ Vision loss typically does not occur until the fourth decade. Intravitreal inhibitors of vascular endothelial growth factor remain the most effective treatment for choroidal neovascularization associated with angioid streaks, helping to limit scar formation and preserve vision.⁴

A person with pseudoxanthoma elasticum may also have cardiac issues, including arterial calcifications. In a prospective cohort study of 47 individuals with pseudoxanthoma elasticum, the prevalence of coronary artery disease was about 6%.⁶

Diagnosis of pseudoxanthoma elasticum is confirmed with clinical and histologic findings.² Differential diagnoses for neck papules and plaques include acanthosis nigricans, cutis laxa, elastosis perforans serpiginosa, tuberous xanthoma, cutaneous sclerosis, and amyloidosis.⁷ Elastosis perforans serpiginosa has more of a red color than pseudoxanthoma elasticum, and the papules have a more serpiginous or annular pattern than the clusters of pseudoxanthoma elasticum. Ultimately, histopathology demonstrating the bramble-bush appearance of calcifications of elastic fibers is diagnostic.

Genetic testing was not needed for diagnosis in this patient but could be considered for presymptomatic family members or family planning.⁸ In our case, the patient was referred to genetics but did not follow up.

TAKE-HOME MESSAGE

This case highlights the importance of awareness among primary care clinicians of pseudoxanthoma elasticum’s subtle skin manifestations. Yellowish papules and plaques, especially on the neck, may seem insignificant or be misattributed to irritation or cosmetic concerns. However, they can be an early clue to an underlying systemic disorder. Early recognition of subtle dermatologic signs allows for timely referrals and multidisciplinary management to mitigate systemic risks.

DISCLOSURES

The authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.