Connecting the Dots of a Rare Connective Tissue Disease: Pseudoxanthoma Elasticum

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Abstract

Pseudoxanthoma elasticum (PXE) is a rare, autosomal recessive connective tissue disease that manifests primarily in the skin, eyes, vasculature, and gastrointestinal tract. Most cases occur in women and are present in the third decade of life. Diagnosis is confirmed via skin biopsy or by genetic testing that reveals a variant ABCC6 gene. We present the case of a 68-year-old woman who came to the clinic to discuss her daughter’s diagnosis of PXE, specifically, what testing she and her family should pursue. A family pedigree revealed a strong family history of abdominal aortic aneurysm (AAA). Although PXE has not been directly related to AAA, this raised concern for familial connective tissue disease. It was recommended that all family members undergo AAA screening with ultrasound, but that not all family members warranted genetic testing. Patients diagnosed with PXE should establish care with specialists to monitor for adverse outcomes.

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Pseudoxanthoma elasticum

Dominique Germain (2017)

Pseudoxanthoma elasticum (PXE) is a genetic metabolic disease with autosomal recessive inheritance caused by mutations in the ABCC6 gene. The lack of functional ABCC6 protein leads to ectopic mineralization that is most apparent in the elastic tissues of the skin, eyes and blood vessels. The clinical prevalence of PXE has been estimated at between 1 per 100,000 and 1 per 25,000, with slight female predominance. The first clinical sign of PXE is almost always small yellow papules on the nape and sides of the neck and in flexural areas. The papules coalesce, and the skin becomes loose and wrinkled. The mid-dermal elastic fibers are short, fragmented, clumped and calcified. Dystrophic calcification of Bruch’s membrane, revealed by angioid streaks, may trigger choroidal neovascularization and, ultimately, loss of central vision and blindness in late-stage disease. Lesions in small and medium-sized artery walls may result in intermittent claudication and peripheral artery disease. Cardiac complications (myocardial infarction, angina pectoris) are thought to be relatively rare but merit thorough investigation. Ischemic strokes have been reported. PXE is a metabolic disease in which circulating levels of an anti-mineralization factor are low. There is good evidence to suggest that the factor is inorganic pyrophosphate (PPi), and that the circulating low levels of PPi and decreased PPi/Pi ratio result from the lack of ATP release by hepatocytes harboring the mutant ABCC6 protein. However, the substrate(s) bound, transported or modulated by the ABCC6 protein remain unknown. More than 300 sequence variants of the ABCC6 gene have been identified. There is no cure for PXE; the main symptomatic treatments are vascular endothelial growth factor inhibitor therapy (for ophthalmic manifestations), lifestyle, lipid-lowering and dietary measures (for reducing vascular risk factors), and vascular surgery (for severe cardiovascular manifestations). Future treatment options may include gene therapy/editing and pharmacologic chaperone therapy.

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Pseudoxanthoma elasticum and skin: Clinical manifestations, histopathology, pathomechanism, perspectives of treatment.

Stefano Racchini, Barbara Marconi, Ivan Bobyr … (2015)

Pseudoxantoma elasticum (PXE), also known as Groenblad-Strandberg syndrome, is a rare heritable disease with an estimated prevalence of 1:50,000 in the general population. PXE is considered a prototype of multisystem ectopic mineralization disorders and it is characterized by aberrant mineralization of soft connective tissue with degeneration of the elastic fibers, involving primarily the eyes, the cardiovascular system, and the skin. Cutaneous lesions consist of small, asymptomatic, yellowish papules or larger coalescent plaques, typically located on the neck and the flexural areas. PXE is caused by mutations in the ABCC6 (ATP-binding cassette subfamily C member 6) gene that encodes a transmembrane ATP binding efflux transporter, normally expressed in the liver and the kidney; however, the exact mechanism of ectopic mineralization remains largely unknown. The histological examination of cutaneous lesions, revealing accumulation of pleomorphic elastic structures in middermis, is essential for the definitive diagnosis of PXE, excluding PXE-like conditions. PXE is currently an intractable disease; although the cutaneous findings primarily present a cosmetic problem, they signify the risk for development of ocular and cardiovascular complications associated with considerable morbidity and mortality. The purpose of this review is to present a comprehensive overview of this rare form of hereditary connective tissue disorders, focus on the pathogenesis, the clinical manifestation, and the differential diagnosis of PXE. Emphasis is also placed on the management of cutaneous lesions and treatment perspectives of PXE.

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Pseudoxanthoma elasticum.

C Moss, S Laube (2005)

Pseudoxanthoma elasticum (PXE) is a rare multisystem disorder characterised by progressive calcification and fragmentation of elastic fibres. Recent genetic advances have identified the underlying defect to the ABCC6 gene on chromosome 16p13.1. Patients typically develop cutaneous, ocular, and cardiovascular manifestations but there is considerable phenotypic variability. The skin changes are usually apparent in adulthood, and rarely observed in childhood. Since the prognosis of PXE largely depends on the extent of extracutaneous organ involvement early recognition, intervention and lifestyle adjustments are important to reduce morbidity. First-degree family members should be carefully examined for any cutaneous or ophthalmologic features of PXE.

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Journal

Journal ID (nlm-ta): Cureus

Journal ID (iso-abbrev): Cureus

Journal ID (issn): 2168-8184

Title: Cureus

Publisher: Cureus (Palo Alto (CA) )

ISSN (Electronic): 2168-8184

Publication date (Electronic, pub): 4 October 2021

Publication date (Electronic, collection): October 2021

Volume: 13

Issue: 10

Electronic Location Identifier: e18481

Affiliations

[1 ] Department of Family Medicine, Mayo Clinic, Jacksonville, USA

[2 ] College of Medicine, Santa Casa de Misericordia de Vitoria, Vitoria, BRA

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Ashley L. Yenior yenior.ashley@ 123456mayo.edu

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DOI: 10.7759/cureus.18481

PMC ID: 8565792

SO-VID: 38058b4e-1932-4eb7-8976-c048ef7ed507

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This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Date accepted : 22 September 2021

Connecting the Dots of a Rare Connective Tissue Disease: Pseudoxanthoma Elasticum

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Pseudoxanthoma elasticum

Pseudoxanthoma elasticum and skin: Clinical manifestations, histopathology, pathomechanism, perspectives of treatment.

Pseudoxanthoma elasticum.

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