弹性假黄瘤的脉络膜新生血管和血管样条纹症

目的:报告1例表现为双眼视力模糊的48岁女子患弹性假黄瘤病(pseudoxanthoma elasticum,PXE)的病例。方法:病例报告。结果:患者,女,48岁,双眼视力模糊,右眼视物变形。10a前因左眼患血管样条纹症接受激光手术,残余视力较差。右眼视力为20/60,左眼6英尺数指。眼底检查可见视网膜下出血和右侧黄斑增厚及左侧椭圆形黄斑瘢痕伴病灶萎缩性色素上皮病变。双眼有血管样条纹和橙色视网膜色素图案。外部检查发现颈部侧面和后面有几处黄色皮肤丘疹和斑块,以及明显的颏皱褶。皮肤切片病理检查证实了PXE的诊断,显示有网状真皮层深层的钙沉积和成碎片的成丛的弹性纤维。患者对玻璃体内注射贝伐单抗反应良好,右眼视力提高到20/25。强调预防保健的重要性,建议患者求助于心脏病学、胃肠病学和人类遗传学咨询服务。结论:PXE是一个累及多系统的疾病,它影响着皮肤、眼和心血管系统。在固有的皮肤变化和明显的颏皱褶的存在下,血管样条纹症和脉络膜新生血管的眼科发现能提高PXE的评估。     

Visual Impairment in Pseudoxanthoma Elasticum: A Survey of 40 Patients

Background: Pseudoxanthoma elasticum is an inherited disorder of connective tissue characterized, among other symptoms, by impaired vision.

Objective: To evaluate the nature and age of onset of ophthalmologic manifestations in pseudoxanthoma elasticum.

Patients and Methods: Forty consecutive patients affected with pseudoxanthoma elasticum underwent measurements of their refractive error and visual acuity, together with slit-lamp examination.

Results: The mean age of the patients (8 M, 32 F) was 43.35 years. Fifty-seven eyes (33 patients, mean age: 40.75 years) had a BCVA >20/50 whereas 23 eyes in 16 patients (mean age: 53.31 years) had ≤20/50. Seven patients (17.50%), all but one over 52 years old, were visually disabled. BCVA ≤20/50 in at least one eye was observed in 73.33% of patients of 52 years old or older and in 20.00% of patients younger than 52, respectively. Angioid streaks were observed in 75 eyes (93.75%) and extended toward the macula in 51 eyes from 29 patients. Macular involvement was observed for the first time at a mean age of 44.28 years. Neovascularization was observed in 28 eyes (17 patients; mean age: 51.70 years), all with poor BCVA.

Conclusion: Macular choroidal neovascularization is frequent in pseudoxanthoma elasticum, and accounts for the poor ophthalmologic natural history of the disease. Patients should be advised to self-monitor their visual acuity using the Amsler grid. The frequency of choroidal neovascularization appears age-dependent, suggesting that bi-yearly fundus examination is appropriate in young patients whereas patients older than 40 should be examined twice a year.     

Pseudoxanthoma elasticum: a clinical,histopathological, and molecular update

Pseudoxanthoma elasticum is an autosomally inherited disorder that is associated with the accumulation of mineralized and fragmented elastic fibers in the skin, Bruch's membrane in the retina, and vessel walls. The ophthalmic and dermatologic expression of pseudoxanthoma elasticum and its vascular complications are heterogeneous, with considerable variation in phenotype, progression, and mode of inheritance. Using linkage analysis and mutation detection techniques, mutations in the ABCC6 gene were recently implicated in the etiology of pseudoxanthoma elasticum. ABCC6 encodes the sixth member of the ATP-binding cassette transporter and multidrug resistance protein family (MRP6). In humans, this transmembrane protein is highly expressed in the liver and kidney. Lower expression was found in tissues affected by pseudoxanthoma elasticum, including skin, retina, and vessel walls. So far, the substrates transported by the ABCC6 protein and its physiological role in the etiology of pseudoxanthoma elasticum are not known. A functional transport study of rat MRP6 suggests that small peptides such as the endothelin receptor antagonist BQ123 are transported by MRP6. Similar molecules transported by ABCC6 in humans may be essential for extracellular matrix deposition or turnover of connective tissue at specific sites in the body. One of these sites is Bruch's membrane. This review is an update on etiology of pseudoxanthoma elasticum, including its clinical and genetic features, pathogenesis, and biomolecular basis.