PXE_1013 Derm Dx
A patient experiencing progressive vision loss is referred by his ophthalmologist to the dermatologist. The ophthalmologist noted angiod streaks of the retina. The patient also has a history of hypertension. On total body skin exam, subtle yellow plaques are noted in the inguinal folds.
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Pseudoxanthoma elasticum (PXE) is an inherited condition associated with mutations in the ABC-cassette transporter gene ABCC6 or the gamma-glutamyl carboxylase gene GGCX.
Although the precise mechanism by which these gene defects precipitate disease is unknown, decreased clearance of serum calcium by defective anti-mineralization activity is thought to be the culprit. Calcification of elastic tissues in the dermis, arteries and eyes are characteristic symptoms.
There is significant variability in clinical PXE presentation. The classic skin findings typically manifest in early childhood or adolescence and consist of thin yellow papules or plaques distributed over flexural surfaces, most commonly on the lateral neck.
The primary lesions resemble xanthomas but can be distinguished based on the young age of the patient at presentation and by the flexural distribution. Over time, the plaques may take on a cobblestoned appearance leading to what is commonly referred to as “plucked chicken skin.” Skin laxity may also be present due to underlying disruption of elastic fibers.
Calcification of the elastic tissue in Bruch’s membrane of the eye and the media of medium-sized arteries produces the complications associated with PXE. Although not pathognomonic, angioid streaks occur in nearly all patients with PXE secondary to small fractures in Bruch’s membrane following calcium deposition, and are associated with vision loss. Peau d’orange changes in the retinal-pigmented epithelium can also occur.
Arterial calcification causes accelerated atherosclerosis in patients with PXE, leading to cardiovascular complications and a higher incidence of gastrointestinal hemorrhage from fragile mesenteric vessels.
Other answer choices:
Cutis laxa, an inherited disorder of elastin that causes generalized elastolysis, is also a condition associated with abnormal connective tissue. It is characterized by loose redundant skin, though laxity typically involves all cutaneous surfaces. The clinical presentation varies significantly depending on the specific mutation and inheritance pattern. It may encompass systemic disruption in elastin, affording a poor prognosis, or presentation may be confined to the skin, with concern limited to the cosmetic appearance.
Marfan syndrome, an autosomal dominant disorder due to mutations in fibrillin-1, is characterized by connective tissue abnormalities in the skin, eyes, and cardiovascular and musculoskeletal systems. Skin manifestations may include striae and elastosis perforans serpiginosa. Other complications include ectopia lenis, mitral valve prolapse and aneurysms of the ascending aorta.
Ehlers-Danlos syndrome comprises a diverse group of inheritable connective tissue defects caused by abnormalities in collagen. Skin findings, including laxity and fragility, and joint hyper-extensibility are the most universal manifestations. Skeletal, dental and vascular involvement may also occur in varying degrees based on the clinical and genetic subtype.
Diagnosis & Treatment
Biopsy of the skin in patients with PXE reveals abnormal elastic fibers in the mid-to-deep dermis that are fragmented to give a “raveled wool” appearance. Overlying calcium deposits may be visible with standard hemotoxylin and eosin preparations, or may require special stains for visualization, such as the von Kossa stain.
In patients that do not have overt cutaneous manifestations, biopsy of a pre-existing scar may yield the characteristic pathology.
Though there is no existing therapy for the cutaneous lesions of PXE, management of this disorder should be aimed at reducing the ocular and cardiovascular complications.
Patients should be advised to receive ophthalmologic evaluation every six months and to avoid frequent ocular exposure to UV light. Cardiac evaluation by an internal medicine physician or cardiologist should occur on an annual basis, and patients should be instructed to maintain healthy lifestyle practices.
Kassandra E. Holzem is a senior medical student at Northwestern University Feinberg School of Medicine.
Adam Rees, MD, is a graduate of the University of California Los Angeles School of Medicine and a resident in the Department of Dermatology at Baylor College of Medicine also in Houston.
- Bolognia J, Jorizzo JL, Rapini RP. “Chapter 95: Biology of the Extracellular Matrix.” Dermatology. St. Louis: Mosby/Elsevier, 2008.
- Bolognia J, Jorizzo JL, Rapini RP. “Chapter 97: Heritable Disorders of Connective Tissue.” Dermatology. St. Louis: Mosby/Elsevier, 2008.
- James WD, Berger TD, Elston DM. “Chapter 25: Abnormalities of Dermal Fibrous and Elastic Tissue.” Andrews’ Diseases of the Skin: Clinical Dermatology. Philadelphia: Saunders Elsevier, 2006.