-
Ophthalmology Science 2024We aimed to describe the epidemiology of angioid streaks (AS) and pseudoxanthoma elasticum (PXE), which are rare diseases, using a national claims database.
PURPOSE
We aimed to describe the epidemiology of angioid streaks (AS) and pseudoxanthoma elasticum (PXE), which are rare diseases, using a national claims database.
DESIGN
This was a population-based longitudinal cohort study.
PARTICIPANTS
A total of 126 million individuals were covered by the universal health coverage system in Japan.
METHODS
With permission from the Ministry of Health, Labor and Welfare, we accessed all data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan, which contains the nationwide health insurance claims data for 126 million Japanese. We identified individuals with AS and PXE between January 2011 and December 2020. The incidence rates, prevalence, overlap of AS and PXE, and mean age at death were calculated.
MAIN OUTCOME MEASURES
The incidence rates and prevalence of AS and PXE.
RESULTS
A total of 6598 cases of AS and 1020 cases of PXE were identified during the 10-year study period. The incidence rates of AS and PXE were 0.52 (95% confidence interval, 0.48-0.56) and 0.08 (95% confidence interval, 0.07-0.10) per 100 000 person-years, respectively. On October 1, 2020, the prevalence of AS and PXE was 6.5 (95% confidence interval, 6.38-6.66) and 0.83 (95% confidence interval, 0.78-0.89) per 100 000 persons, respectively. The overlap of AS and PXE was 363 patients. The mean age at death of individuals with AS and PXE was 79.3 ± 0.51 and 77.1 ± 2.68 years, respectively.
CONCLUSION
This is the first population-based study to elucidate the epidemiology of AS and PXE. The mean age of death of both AS and PXE patients was younger than the mean life expectancy of the general Japanese population, thus, appropriate diagnosis and management are important to avoid preventable death.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PubMed: 37868801
DOI: 10.1016/j.xops.2023.100370 -
Oral Surgery, Oral Medicine, Oral... Jan 2016Pseudoxanthoma elasticum (PXE), which is a genetic, multi-target disorder characterized by progressive calcification and fragmentation of elastic fibers, affects several... (Review)
Review
Pseudoxanthoma elasticum (PXE), which is a genetic, multi-target disorder characterized by progressive calcification and fragmentation of elastic fibers, affects several organs, including the eyes, skin, and cardiovascular system. Diagnosis of PXE is currently based on cutaneous and ocular signs, histopathologic findings, and a patient's family history. PXE-related oral mucosal lesions are rarely reported, possibly due to the potential for misdiagnosis as Fordyce spots; however, when such lesions are reported, they are primarily localized to the vestibular mucosa of the lower lip. Here, we report the case of a female with an intraoral presentation of PXE at the labial and palatal sites. PXE was previously suspected in this patient because of the presence of cardiovascular, ocular, and cutaneous signs; however, a cutaneous biopsy showed findings not consistent with PXE. Incisional biopsy of the palatal lesion confirmed the PXE diagnosis, leading to proper management of the disorder to prevent ophthalmologic and cardiovascular complications.
Topics: Biopsy; Diagnosis, Differential; Female; Humans; Middle Aged; Palate; Pseudoxanthoma Elasticum
PubMed: 26679366
DOI: 10.1016/j.oooo.2015.09.010 -
Scientific Reports Feb 2021ABCC6 deficiency promotes ectopic calcification; however, circumstantial evidence suggested that ABCC6 may also influence atherosclerosis. The present study addressed...
ABCC6 deficiency promotes ectopic calcification; however, circumstantial evidence suggested that ABCC6 may also influence atherosclerosis. The present study addressed the role of ABCC6 in atherosclerosis using Ldlr mice and pseudoxanthoma elasticum (PXE) patients. Mice lacking the Abcc6 and Ldlr genes were fed an atherogenic diet for 16 weeks before intimal calcification, aortic plaque formation and lipoprotein profile were evaluated. Cholesterol efflux and the expression of several inflammation, atherosclerosis and cholesterol homeostasis-related genes were also determined in murine liver and bone marrow-derived macrophages. Furthermore, we examined plasma lipoproteins, vascular calcification, carotid intima-media thickness and atherosclerosis in a cohort of PXE patients with ABCC6 mutations and compared results to dysmetabolic subjects with increased cardiovascular risk. We found that ABCC6 deficiency causes changes in lipoproteins, with decreased HDL cholesterol in both mice and humans, and induces atherosclerosis. However, we found that the absence of ABCC6 does not influence overall vascular mineralization induced with atherosclerosis. Decreased cholesterol efflux from macrophage cells and other molecular changes such as increased pro-inflammation seen in both humans and mice are likely contributors for the phenotype. However, it is likely that other cellular and/or molecular mechanisms are involved. Our study showed a novel physiological role for ABCC6, influencing plasma lipoproteins and atherosclerosis in a haploinsufficient manner, with significant penetrance.
Topics: Animals; Atherosclerosis; Bile Acids and Salts; Dyslipidemias; Female; Humans; Macrophages; Male; Mice, Inbred C57BL; Multidrug Resistance-Associated Proteins; Pseudoxanthoma Elasticum; Retrospective Studies; Mice
PubMed: 33594095
DOI: 10.1038/s41598-021-82966-y -
SAGE Open Medical Case Reports 2020We report a unique case of a patient presenting with histologically confirmed pseudoxanthoma elasticum-like phenotype and cutaneous polyarteritis nodosa. Cardiac,...
We report a unique case of a patient presenting with histologically confirmed pseudoxanthoma elasticum-like phenotype and cutaneous polyarteritis nodosa. Cardiac, gastroenterological, and ophthalmologic evaluations were within normal limits. Genetic evaluation was pertinent for absent ABCC6, ENPP1, and GGCX mutations and a normal array comparative genomic hybridization. Extensive workup revealed skin-limited cutaneous polyarteritis nodosa, and further genetic testing for ADA2 deficiency was negative. The cutaneous polyarteritis nodosa lesions had an excellent response to hydroxychloroquine and methotrexate. Pseudoxanthoma elasticum and polyarteritis nodosa are relatively uncommon, and our patient is among the first reported cases presenting with both pseudoxanthoma elasticum-like and polyarteritis nodosa. Furthermore, this case emphasizes the importance of a thorough cutaneous exam, as the patient had the lesions consistent with pseudoxanthoma elasticum-like since childhood and had previously gone undiagnosed.
PubMed: 35154765
DOI: 10.1177/2050313X20953110 -
International Journal of Molecular... Sep 2017Pseudoxanthoma elasticum (PXE) is an inherited metabolic disease with autosomal recessive inheritance caused by mutations in the gene. Since the first description of... (Review)
Review
Pseudoxanthoma elasticum (PXE) is an inherited metabolic disease with autosomal recessive inheritance caused by mutations in the gene. Since the first description of the disease in 1896, alleging a disease involving the elastic fibers, the concept evolved with the further discoveries of the pivotal role of ectopic mineralization that is preponderant in the elastin-rich tissues of the skin, eyes and blood vessel walls. After discovery of the causative gene of the disease in 2000, the function of the ABCC6 protein remains elusive. More than 300 mutations have been now reported and the concept of a dermal disease has progressively evolved toward a metabolic disorder resulting from the remote effects caused by lack of a circulating anti-mineralization factor. Very recently, evidence has accumulated that this anti-mineralizing factor is inorganic pyrophosphate (PPi). This leads to decreased PPi/Pi (inorganic phosphate) ratio that results from the lack of extracellular ATP release by hepatocytes and probably renal cells harboring the mutant ABCC6 protein. However, the mechanism by which ABCC6 dysfunction causes diminished ATP release remains an enigma. Studies of other ABC transporters, such as ABCC7 or ABCC1 could help our understanding of what ABCC6 exact function is. Data and a hypothesis on the possible roles of ABCC6 in acquired metabolic diseases are also discussed.
Topics: Animals; Humans; Multidrug Resistance-Associated Proteins; Mutation; Phosphates; Pseudoxanthoma Elasticum; Vascular Calcification
PubMed: 28891970
DOI: 10.3390/ijms18091941 -
Journal of Family Medicine and Primary... Dec 2022Increased laxity of the skin can be caused by aging, significant weight loss, or defects in the elastic tissue. A 38-year-old female presented with increased laxity of...
Increased laxity of the skin can be caused by aging, significant weight loss, or defects in the elastic tissue. A 38-year-old female presented with increased laxity of the skin over the neck, thighs, and abdomen for 6 years, associated with headache and blurring of vision for a week. On cutaneous examination, prominent skin folds, laxity, and wrinkles were noted over the neck, abdomen, thighs, and groin, with yellowish papules along the neck creases. Ocular examination revealed features suggestive of angioid streaks. Skin biopsy showed fragmented elastic fibers and intervening calcium deposits on Verhoeff Van Gieson and Von Kossa stains. Based on these findings, a diagnosis of pseudoxanthoma elasticum (PXE) was made. The patient was started on oral and topical sunscreens and eye protection and advised regular follow-up. Diagnosing the condition early based on skin findings can help prevent further multi-system manifestations by taking appropriate preventive measures as this condition is progressive and has no cure.
PubMed: 36994043
DOI: 10.4103/jfmpc.jfmpc_2337_21 -
Journal of Ophthalmic & Vision Research 2020To present a case of gigantic idiopathic angioid streaks.
PURPOSE
To present a case of gigantic idiopathic angioid streaks.
CASE REPORT
A young male presented with macular choroidal neovascular membrane (CNVM) and peripheral retinal hemorrhages secondary to angioid streaks. Swept source optical coherence tomography (SSOCT) and ultrawide field imaging were performed. The latter revealed extension of the angioid streaks up to the equator in both eyes. SSOCT showed breaks in the retinal pigment epithelium-Bruch's membrane complex in the area of peripheral retinal hemorrhages. The patient was extensively worked up for systemic associations, and the only significant finding was a long history of steroid abuse in the past.
CONCLUSION
Advanced imaging techniques helped to diagnose angioid streaks in this patient. The possible role of steroid abuse in accentuating the presentation of angioid streaks may be explored further.
PubMed: 32308959
DOI: 10.18502/jovr.v15i2.6742 -
FEBS Letters Dec 2020ATP-binding cassette subfamily C member 6 gene/protein (ABCC6) is an ATP-dependent transmembrane transporter predominantly expressed in the liver and the kidney. ABCC6... (Review)
Review
ATP-binding cassette subfamily C member 6 gene/protein (ABCC6) is an ATP-dependent transmembrane transporter predominantly expressed in the liver and the kidney. ABCC6 first came to attention in human medicine when it was discovered in 2000 that mutations in its encoding gene, ABCC6, caused the autosomal recessive multisystemic mineralization disease pseudoxanthoma elasticum (PXE). Since then, the physiological and pathological roles of ABCC6 have been the subject of intense research. In the last 20 years, significant findings have clarified ABCC6 structure as well as its physiological role in mineralization homeostasis in humans and animal models. Yet, several facets of ABCC6 biology remain currently incompletely understood, ranging from the precise nature of its substrate(s) to the increasingly complex molecular genetics. Nonetheless, advances in our understanding of pathophysiological mechanisms causing mineralization lead to several treatment options being suggested or already tested in pilot clinical trials for ABCC6 deficiency. This review highlights current knowledge of ABCC6 and the challenges ahead, particularly the attempts to translate basic science into clinical practice.
Topics: Animals; Cardiovascular Diseases; Cerebrovascular Disorders; Clinical Trials as Topic; Evolution, Molecular; Humans; Multidrug Resistance-Associated Proteins; Neoplasms; Pseudoxanthoma Elasticum; Vascular Calcification
PubMed: 33131056
DOI: 10.1002/1873-3468.13981 -
Scientifica 2012Among ectopic mineralization disorders, pseudoxanthoma elasticum (PXE)-a rare genodermatosis associated with ocular and cardiovascular manifestations-is considered a... (Review)
Review
Among ectopic mineralization disorders, pseudoxanthoma elasticum (PXE)-a rare genodermatosis associated with ocular and cardiovascular manifestations-is considered a paradigm disease. The symptoms of PXE are the result of mineralization and fragmentation of elastic fibers, the exact pathophysiology of which is incompletely understood. Though molecular analysis of the causal gene, ABCC6, has a high mutation uptake, a skin biopsy has until now been considered the golden standard to confirm the clinical diagnosis. Although the histological hallmarks of PXE are rather specific, several other diseases-particularly those affecting the skin-can present with clinical and/or histological characteristics identical to or highly resemblant of PXE. In this paper, we will summarize the histopathological features of PXE together with those of disorders that are most frequently considered in the differential diagnosis of PXE.
PubMed: 24278718
DOI: 10.6064/2012/598262 -
JTCVS Techniques Oct 2021
PubMed: 34647054
DOI: 10.1016/j.xjtc.2021.07.022