Intermittent Claudication in a 28-Year-Old Man With Pseudoxanthoma Elasticum
A 28-year-old man was transferred to our outpatient clinic for further vascular studies and evaluation. Two weeks earlier, a standard x-ray had been performed after minor injury of the left knee during a soccer game (Figure 1). A bone fracture was excluded, but the x-ray revealed severe calcification of the left popliteal artery.
When we tried to ascertain the presence of claudication, the patient reported burning pain in both calves during ongoing and strenuous physical exercise, such as rapid walking for more than 1000 meters, with immediate relief at rest. He first noticed these symptoms when he was about 16 years old, and since then the symptoms have remained constant. He denied the presence of chest pain at rest or on exertion and reported no abdominal symptoms. He started to smoke few cigarettes a day 4 years before presentation. He denied the presence of arterial hypertension, hyperlipidemia, and diabetes. Because of acne-like skin lesion on the neck, a skin biopsy had been performed 14 years earlier. His parents, 4 siblings, wife, and 2 children (2 and 4 years of age) were to his knowledge devoid of any major disease. Physical examination revealed nonpalpable popliteal, posterior tibial, and dorsalis pedis pulses on both sides. Radial and femoral pulses were palpable. No trophic skin changes of the lower limbs were observed. The presence of acne-like yellowish skin lesions on the neck was confirmed (Figure 2).
The ankle-brachial indexes at rest were markedly reduced, at 0.65 on the right and 0.46 on the left. Duplex ultrasound with color imaging showed normal femoral arteries with triphasic Doppler signals and occlusion of both popliteal arteries. Subsequently, magnetic resonance angiography was performed and it showed severe peripheral artery disease with occlusion of both superficial femoral and popliteal arteries, as well as infrapopliteal occlusive disease (Figure 3). The patient was asked to bring all available medical records to the next visit, which was scheduled to discuss the results of magnetic resonance angiography. The records showed that the histology of the skin biopsy performed 14 years earlier indicated the presence of pseudoxanthoma elasticum (PXE) in this patient.
Additional studies were performed. Ophthalmologic examination revealed angioid streaks and peau d’orange on funduscopy (Figure 4). The patient’s vision was not impaired. Resting ECG and exercise electrocardiography were normal. A transthoracic echocardiography showed normal function of both ventricles and the heart valves, as well as normal size of all heart chambers. We recommended that the patient stop smoking and playing soccer and that he avoid other contact sports with the possibility of head trauma. A follow-up visit was scheduled for 12 months later.
PXE is a systemic disease with recessive inheritance of connective tissue primarily affecting the skin, retina, and cardiovascular system.1 It is characterized histologically by elastic fiber mineralization and fragmentation and clinically by a high heterogeneity in age of onset and extent and severity of organ system involvement. The disease is strongly associated with the occurrence of mutations in the ABCC6 (ATP binding cassette family C member 6) gene, which encodes MRP6 (multidrug resistance-associated protein 6).1–3 PXE is an important and possibly underdiagnosed cause of premature cardiovascular disease.1 Early identification of the disease and increased surveillance for its sequelae might improve the quality and length of life of those affected.3
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Pfendner EG, Vanakker OM, Terry SF, Vourthis S, McAndrew PE, McClain MR, Fratta S, Marais AS, Hariri S, Coucke PJ, Ramsay M, Viljoen D, Terry PF, De Paepe A, Uitto J, Bercovitch LG. Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a large international case series affected by pseudoxanthoma elasticum. J Med Genet. 2007; 44: 621–628.