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Goosebumps and angioid streaks in a patient with cerebrovascular disease.

      Keywords

      1. Case description

      A 55-year-old man was referred to the dermatology department for a long history of asymptomatic lesions on the skin of his neck and axillae. He had a remarkable history of recurrent ischemic strokes and cerebral small vessel disease with progressive cognitive decline during the last 10 years. He was also a regular smoker and he suffered from diabetes mellitus, hyperlipidemia, obesity, hypertension and hypertensive heart disease. Physical examination revealed small, yellowish papules looking like “goosebumps” in the lateral aspects of the neck (Fig. 1A) and a thickened and hanging skin in both axillae (Fig. 1B). Moreover, the patient presented prominent mental creases (Fig. 1C) and yellow papules on the mucosa of the lower lip (Fig. 1D). He reported that his brothers had similar cutaneous lesions. A punch biopsy from a cervical papule revealed abnormal fragmented and calcified elastic fibers of the middle-dermis. With a diagnostic suspicion, a dilated funduscopic examination was performed. It revealed the presence of angioid streaks in the left eye (Fig. 1E) accompanied by a choroidal neovascular membrane in the right eye (Fig. 1F). What is the diagnosis?
      Fig 1
      Fig. 1A: small and yellowish papules coalescing into large plaques in the left aspect of the neck. B: thickened, yellowish and hanging skin in the right axilla. C: prominent mental creases. D: yellow papules in the lower lip mucosa. E: angioid streaks (black arrows) in the left eye. F: angioid streaks (black arrows) and choroidal neovascular membrane (white asterisk) in the right eye.

      2. Diagnosis

      A genetic study showed a homozygous mutation in the ABCC6 gene that confirmed the diagnosis of pseudoxanthoma elasticum (PXE). PXE is caused by mutations in the gene that encodes the ABCC6 protein (a transmembrane ATP-binding efflux transporter) and is characterized by an ectopic mineralization of the elastic fiber-rich tissues, such as the dermis, the retina and the vascular wall. The characteristic small and yellowish papules are usually the earliest sign of PXE. They appear during the first or second decade of life, initially on the neck, and later in other flexural areas. The presence of prominent mental creases and yellowish papules in the oral mucosa may help to suspect the diagnosis. Angioid streaks occur due to ruptures of a calcified Bruck's membrane and predispose patients to neovascularization with subsequent risk of retinal hemorrhages and visual loss. The progressive calcification of medial layers of arteries leads to intermittent claudication, renovascular hypertension and premature atherosclerosis with myocardial infarcts and cerebrovascular accidents in young patients [
      • Roach ES
      • Islam MP
      Pseudoxanthoma elasticum.
      ]. Cerebrovascular complications appear in about 17% of individuals with PXE and derive from the progressive narrowing and occlusion of medium and small cerebral vessels, as well as from the rupture of intracranial aneurysms [
      • Kauw F
      • Kranenburg G
      • L Kappelle LJ
      • Hendrikse J
      • et al.
      Cerebral disease in a nationwide dutch pseudoxanthoma elasticum cohort with a systematic review of the literature.
      ]. In addition, the deficiency of the hepatic ABCC6 transporter predispose to hypertriglyceridemia and decreased HDL cholesterol levels [
      • Ibold B
      • Faust I
      • Tiemann J
      • Gorgels TGM
      • Bergen AAB
      • Knabbe C
      Abcc6 deficiency in mice leads to altered ABC transporter gene expression in metabolic active tissues.
      ]. Therefore, PXE may be understood as a systemic and metabolic disease, without an effective treatment. A strict and early control of cardiovascular risk factors should be carried out in order to avoid complications in young patients.

      3. Funding sources

      None.

      Declaration of Competing Interest

      The authors declare no conflicts of interest.

      References

        • Roach ES
        • Islam MP
        Pseudoxanthoma elasticum.
        Handb Clin Neurol. 2015; 132: 215-221
        • Kauw F
        • Kranenburg G
        • L Kappelle LJ
        • Hendrikse J
        • et al.
        Cerebral disease in a nationwide dutch pseudoxanthoma elasticum cohort with a systematic review of the literature.
        J Neurol Sci. 2017; 373 (Feb 15): 167-172
        • Ibold B
        • Faust I
        • Tiemann J
        • Gorgels TGM
        • Bergen AAB
        • Knabbe C
        Abcc6 deficiency in mice leads to altered ABC transporter gene expression in metabolic active tissues.
        Lipids Health Dis. 2019; 18 (Jan 5): 2