A curious case study
Our patient had developed skin folds on her neck, and her vision was deteriorating. Interestingly, her sister had the same complaints.
Importantly, an absence of skin lesions does not exclude the diagnosis of pseudoxanthoma elasticum.4
Ocular changes. Angioid streaks of the fundus are the most common ocular findings and are associated with pseudoxanthoma elasticum 85% of the time.2 They result from a rupture of the elastic tissue in the Bruch’s membrane of the retina. Angioid streaks may become less marked with time or disappear in conjunction with generalized atrophy of the retinal pigmentum epithelium.15 The visual prognosis for patients with angioid streaks is often poor.
Other retinal changes include macular degeneration, altered pigmentation (eg, peau d’orange appearance), subretinal neovascularization, and chorioretinal scarring. Ocular hemorrhage can occur even with minimal trauma. Hu et al described one fundus feature that seems to be typical of pseudoxanthoma elasticum: comet-like tails.1
Cardiovascular involvement. Elastic tissue degeneration and calcification of arterial media within medium-sized arteries results in diminished peripheral pulses, intermittent claudication, coronary insufficiency, premature calcification of peripheral arteries, intracranial aneurysms, cerebral ischemia, and hypertension.16 Twenty-five percent of patients acquire renovascular hypertension secondary to renal blood flow obstruction from calcium deposition in the renal arteries.
Premature cardiovascular disease may begin as early as 4 years of age and may lead to angina or sudden death.2 Consider pseudoxanthoma elasticum in young patients with coronary artery disease and no cardiovascular risk factors.17
Calcification of elastic fibers in the thin-walled arteries directly under the gastric mucosa can cause gastrointestinal bleeding.18 Melena and hematemesis are reported in up to 15% of cases.19 Subarachnoid, nasal, renal, bladder, and joint bleeding are much less common.
Skin biopsy is key
The classic histologic picture with pseudoxanthoma elasticum skin lesions is fragmentation and clumping of elastic tissue evident on Verhoeff-van Gieson stain, and calcification on von Kossa stain.7 Patients who have angioid streaks on funduscopic examination but no visible skin lesions have received a diagnosis of pseudoxanthoma elasticum based on the biopsy results of scars or flexural skin of the neck or axillae.20 Hausser described a specific ultrastructural aberrant pattern in 3 siblings without any clinical symptoms: elastin of elastic fibers regularly contained small foci of calcification resembling those in perilesional skin of the mother and other pseudoxanthoma elasticum patients.21
Another reason for biopsy. Clinically visible pseudoxanthoma elasticum-like skin lesions are not pathognomonic for this disease, because they also occur in late-onset focal dermal elastosis,22 beta-thalassemia,23 adult patients with deforming osteitis (Paget’s disease) or osteoectasia,24 farmers exposed to saltpeter fertilizers,25 pseudoxanthoma elasticum-like papillary dermal elastolysis,26 and patients who have had penicillamine therapy.
Management
Watch out for complications
Management of pseudoxanthoma elasticum focuses on preventing, screening for, and monitoring complications. One study of adolescents with pseudoxanthoma elasticum demonstrated a positive correlation between a high intake of dietary calcium and cardiovascular manifestations—but not skin lesions. At least one authority on the subject recommends that daily ingestion of calcium be restricted to 500 to 600 mg.27
Redundant skin folds can be treated with surgical excision.28 A case report describes the temporary treatment of chin folds with injectable collagen.29 Laser photocoagulation can prevent retinal hemorrhage, but recurrence is relatively common.30
How our patient’s case evolved
Once the patient’s presumptive diagnosis of pseudoxanthoma elasticum was confirmed by biopsy, we established the same diagnosis in her 18-year-old sister. The parents did not exhibit any clinical findings of pseudoxanthoma elasticum. We did refer the father to ophthalmology and to dermatology for skin biopsies of scars, but he never returned for follow-up.
To rule out cardiovascular involvement, we referred the patient to our cardiology colleagues. No abnormality was found on physical exam, and the EKG and echocardiography results were within normal limits. Results of myocardial perfusion testing were also within normal limits, and the patient achieved 92% of the maximum predicted heart rate.
Since the patient was not a smoker, we simply reinforced the importance of not smoking. We advised her to follow a diet low in fat and calcium, and to avoid platelet inhibitors and contact sports to prevent gastrointestinal bleeding and retinal hemorrhage, respectively. We also recommended that she have periodic funduscopic evaluations, as well as cardiovascular evaluations to monitor blood pressure and lipids.
Acknowledgments
The authors thank Rafael Doig, MD (Nuclear Medicine) and Jose Barriga, MD (Department of Ophthalmology) of British American Hospital, Lima, Peru, for their assistance in the preparation of this article.
Correspondence
Gustavo Vasquez, MD, Division of Infectious Diseases, Department of Medicine, Thomas Jefferson University, 834 Walnut Street, Suite 650, Philadelphia, PA 19107; Gustavo.Vasquez@jeffersonhospital.org
