A 26-year-old woman presented to the dermatology clinic for evaluation of yellowish plaques on her neck that had been present since childhood. She believed the lesions were due to irritation from wearing a necklace, as they were asymptomatic and unchanged. Her medical history included sickle cell traits, and she denied having any allergies. Examination revealed grouped yellowish papules and plaques with a cobblestone appearance on the neck (Figure 1), absent elsewhere. Biopsy was done, and histopathologic study showed dermal deposits of calcified elastic fibers with a bramble-bush appearance on hematoxylin and eosin staining. These findings confirmed the diagnosis of pseudoxanthoma elasticum.
Tan-to-yellow coalescing papules on the anterolateral left neck.
Although the patient did not have ophthalmologic symptoms or decreased vision, she was referred to ophthalmology for an examination. The ophthalmologist identified angioid streaks and mottled retinal pigment epithelium (Figure 2), and recommended follow-up every 2 years for screening, as well as home metamorphopsia screening with an Amsler grid.
Angioid streaks (blue arrows) and mottling of the retinal pigment epithelium.
The patient had no cardiac symptoms, and her lipid panel was normal. Arterial calcification was not seen on chest radiography. She was referred to a cardiologist, who recommended no specific workup but advised her to minimize modifiable cardiovascular risk factors.
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.
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REFERENCES
- 1↵Stumpf MJ, Schahab N, Nickenig G, Skowasch D, Schaefer CA. Therapy of pseudoxanthoma elasticum: current knowledge and future perspectives. Biomedicines 2021; 9(12):1895. doi:10.3390/biomedicines9121895
- 2↵Brokamp G, Mori M, Faith EF. Pseudoxanthoma elasticum. JAMA Dermatol 2022; 158(1):100. doi:10.1001/jamadermatol.2021.4059
- 3↵Li Q, Jiang Q, Pfendner E, Váradi A, Uitto J. Pseudoxanthoma elasticum: clinical phenotypes, molecular genetics and putative pathomechanisms. Exp Dermatol 2009; 18(1):1–11. doi:10.1111/j.1600-0625.2008.00795.x
- 4↵Gliem M, Finger RP, Fimmers R, Brinkmann CK, Holz FG, Charbel Issa P. Treatment of choroidal neovascularization due to angioid streaks: a comprehensive review. Retina 2013; 33(7):1300–1314. doi:10.1097/IAE.0b013e3182914d2b
- 5↵Aerts C, De Keyser C, Leys A. Visual loss and presumed pseudoxanthoma elasticum confirmed with genetic analysis but not with skin examination and biopsies. GMS Ophthalmol Cases 2011; 1:Doc03. Published 2011 Sep 15. doi:10.3205/oc000003
- 6↵Prunier F, Terrien G, Le Corre Y, et al. Pseudoxanthoma elasticum: cardiac findings in patients and ABCC6-deficient mouse model. PLoS One 2013; 8(7):e68700. doi:10.1371/journal.pone.0068700
- 7↵Burrows NP, Ringpfeil F, Uitto J. Heritable disorders of connective tissue. In: Bolognia JL, Schaffer JV, Cerroni L, eds. Dermatology. 5th ed. Elsevier; 2024:1714–1729.
- 8↵Li Q, Török L, Kocsis L, Uitto J. Mutation analysis (ABCC6) in a family with pseudoxanthoma elasticum: presymptomatic testing with prognostic implications. Br J Dermatol 2010; 163(3):641–643. doi:10.1111/j.1365-2133.2010.09856.x
