Asymptomatic yellow papules on the neck and axillae in an elderly man

Question

What is your diagnosis?

Answer

Diagnosis: Pseudoxanthoma elasticum

Discussion

Pseudoxanthoma elasticum (PXE) is a heritable disorder characterised by progressive fragmentation and calcification of elastic fibres, primarily affecting the skin, eyes, and cardiovascular system.¹ PXE is an autosomal recessive condition caused by mutations in the ABCC6 gene, leading to reduced plasma levels of inorganic pyrophosphate and consequent mineralisation of medium- and small-sized arteries.² PXE exhibits considerable phenotypic variability, often resulting in delayed recognition and diagnosis. Cutaneous manifestations typically present as yellowish papules that gradually coalesce into cobblestone-like plaques on flexural areas such as the neck and axillae, which frequently serve as the earliest clinical indicator preceding potentially severe ocular and vascular involvement.³

Histologically, PXE is characterised by irregularly thickened and fragmented elastic fibres in the mid-dermis, highlighted by Verhoeff’s elastic stain, with calcification commonly observed in well-developed lesions, although it may be absent in early stages, as demonstrated by Von Kossa staining.⁴ Differential diagnoses include papular elastorrhexis, typically seen in adolescents with asymptomatic white papules lacking systemic involvement or calcification; mid-dermal elastolysis, characterised by selective loss of elastic fibres resulting in fine wrinkling of the skin; and colloid milium, which presents with amorphous eosinophilic deposits in the upper dermis.

There is currently no definitive treatment for PXE. PXE may also involve medium-sized arteries, predisposing patients to accelerated atherosclerosis and significantly increasing the risk of systemic ischaemic complications, such as intermittent claudication, angina pectoris, myocardial infarction, and cerebrovascular events, including ischaemic strokes. For example, a nationwide Dutch cohort study found cerebral disease in 17% of PXE patients, including ischemic stroke (8%) and transient ischemic attack (TIA) (7%), highlighting the need for vigilant cardiovascular and neurological monitoring in PXE.² Ocular involvement is a hallmark feature of PXE, almost universally affecting the posterior segment with peau d’orange, angioid streaks, and sometimes choroidal neovascularisation, which may lead to retinal haemorrhages and progressive vision loss.⁵

Management focuses on regular monitoring and prevention of systemic complications. Patients are advised to undergo periodic ophthalmologic evaluations to detect early retinal changes and cardiovascular assessments to monitor blood pressure and arterial integrity. Lifestyle modifications, including smoking cessation and strict control of cardiovascular risk factors, are essential. In cases of ocular involvement with choroidal neovascularisation, intravitreal anti-VEGF therapy may be indicated to prevent vision loss.

The present case demonstrated classic cutaneous features of PXE with yellowish papules merging into cobblestone-like plaques on the neck and axillae. Histopathology confirmed the diagnosis by revealing fragmented and calcified elastic fibres in the mid-dermis. Ophthalmologic examination showed characteristic angioid streaks with associated retinal pigment epithelial atrophy and subretinal fibrosis, consistent with ocular involvement of PXE. Interestingly, the patient’s history of macular degeneration, diagnosed nine years prior, may have represented early ocular manifestations of PXE-related choroidal neovascularisation that were initially misattributed. Further systemic evaluation uncovered a history of ischaemic stroke, likely secondary to vascular involvement associated with PXE. Genetic testing was not performed, as the diagnosis was made based on characteristic clinical and histopathologic features, and advanced age made further genetic confirmation clinically unnecessary. This underscores the importance of early dermatologic recognition, as delayed diagnosis remains common due to patients’ unawareness of cutaneous signs and limited recognition by non-dermatologists, ultimately highlighting the need for timely ophthalmologic and cardiovascular screening to mitigate serious systemic complications.