Pseudoxanthoma elasticum

doi:10.1016/B978-0-444-62702-5.00015-9

Handbook of Clinical Neurology

Volume 132, 2015, Pages 215-221

https://doi.org/10.1016/B978-0-444-62702-5.00015-9 Get rights and content

Abstract

Pseudoxanthoma elasticum (PXE) is characterized by elastic tissue fragmentation and calcification. The deterioration of elastic fibers leads to characteristic yellowish papules and plaques (pseudoxanthomas) and retinal angioid streaks. Although these findings may begin in childhood, the diagnosis is typically not made until the second or third decade after the skin and retinal findings become more prominent. Cerebrovascular complications include brain infarction due to narrowing and occlusion of cerebral arteries and aneurysm formation. Intracranial hemorrhage can occur in the absence of aneurysm, and gastrointestinal hemorrhage is common. Peripheral arterial vascular disease can lead to intermittent leg claudication. A skin biopsy often demonstrates calcified elastic fibers, even in a mildly affected area of skin. The inheritance is autosomal recessive, although heterozygotes may exhibit some features of the disease. PXE is due to mutation of the ABCC6 gene on chromosome 16. There is no treatment, but certain lifestyle modifications may limit the complications. The potential for retinal hemorrhage has led to recommendations for limitations of contact sports or other activities that might facilitate eye trauma. Other recommendations include maintaining a normal lipid profile, avoidance of aspirin and nonsteroidal anti-inflammatory agents, and limiting dietary calcium intake.

Introduction

Pseudoxanthoma elasticum (PXE; OMIM #264800) is an autosomal recessive connective tissue disease that is characterized by fragmentation (“elastorrhexia”) and calcification of elastic fibers. The deterioration of the elastic fibers leads to dermatologic, ophthalmologic, and vascular dysfunction. The clinical presentation, manifestations, and rate of progression vary considerably, even among affected members of the same family, and heterozygous individuals can also exhibit some features of the disorder.

PXE results from a mutation of the ABCC6 gene on chromosome 16p13.1 that codes for a transmembrane transporter protein of the ATP binding ABC family (Chassaing et al., 2005). The prevalence of PXE is around 1 in 25 000 people, but some individuals with milder phenotypes probably remain undiagnosed (Chassaing et al., 2005).

Section snippets

History

Balzer provided the first clinical description of pseudoxanthoma elasticum in 1884, but he mistakenly suggested that the lesions represent a form of xanthoma and failed to appreciate the distinctive elastic fiber mineralization (Balzer, 1884). Darier (1896) soon discovered the mineralization of the skin elastic fibers in these lesions. To emphasize the absence of a xanthomatous lesion, Darier devised the term “pseudoxanthoma” and added “elasticum” to identify the specific anatomic site of the

Dermatologic features

Although the diagnosis of PXE is most often made late in the second or third decade, characteristic yellowish papules or plaque-like skin lesions often appear even in children (Naouri et al., 2009). The lesions often appear first on the lateral neck (Fig. 15.1). Other common lesion sites are the antecubital fossae, axillae, popliteal spaces, periumbilical area, and groin (Neldner, 1988). Similar plaque-like lesions have been documented in the mucous membranes. The skin lesions advance most

Pathology of pseudoxanthoma elasticum

Apart from the highly characteristic clinical appearance and location of the skin lesions, a skin biopsy showing calcified elastic fibers is diagnostic. The initial calcification occurs within the central core of the elastic fiber (Fig. 15.3), gradually becoming more pronounced and eventually leading to rupture of the fiber. Calcified elastic fibers are demonstrable even in early, barely visible, skin lesions. Increased concentrations of mucopolysaccharide (glycosaminoglycans) in the affected

Genetics of pseudoxanthoma elasticum

Pseudoxanthoma elasticum is best characterized as an autosomal recessive trait, although heterozygous individuals occasionally exhibit some signs of the disease. The chromosomal localization of the PXE gene to 16p 13.1 was demonstrated in 1997 (Struk et al., 1997), and the 31 exon gene (ABCC6) was identified simultaneously in 2000 by four separate groups (Bergen et al., 2000, Le Saux et al., 2000, Ringpfeil et al., 2000, Struk et al., 2000). A mutation in both ABCC6 alleles can be demonstrated

Management of pseudoxanthoma elasticum

There is no fully effective treatment for PXE. Many of the serious manifestations of PXE represent vascular dysfunction, so it is prudent to develop habits that facilitate lifelong general health and cardiovascular fitness. Affected individuals should avoid the use of tobacco, optimize the diet, and develop a lifelong fitness regimen. They should also maintain a normal lipid profile by whatever method is required.

It has been suggested that a high calcium diet early in life may facilitate

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