Pregnancy and obstetrical outcomes in pseudoxanthoma elasticum

Characterization of dermal myofibroblast differentiation in pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE) is a rare genetic disorder caused by loss-of-function mutations in the ABCC6 gene. While PXE is characterized by ectopic mineralization of connective tissues clinically affecting the skin, eyes, and cardiovascular system, kidney stones were reported in some individuals with PXE. The aim of this study is to determine whether kidney stones are an incidental finding or a frequent manifestation of PXE. We investigated the genetic basis of two siblings diagnosed with PXE. The younger patient presented with recurrent kidney stones since age 8. To address whether kidney stones are associated with PXE, the prevalence of kidney stones in a survey cohort of 563 respondents with PXE was compared to that of a general U.S. population survey, NHANES (National Health and Nutrition Examination Survey), with 28,629 participants. Genetic analysis in both patients identified compound heterozygous mutations in ABCC6, c.2787+1G>T and c.3774_3775insC. The analysis of participants aged 20 and older revealed that 23.4% of PXE patients had previously had a kidney stone, a significant increase compared to 9.2% in the general population. In addition, 17.8% of PXE patients reported their first kidney stone episode before age 18. PXE correlates with an increased risk of developing kidney stones with considerable morbidity and health-care cost.

Pseudoxanthoma elasticum (PXE) is a rare, genetic,multisystem connective tissue disorder primarily affectingthe skin, eyes, and the cardiovascular system (CVS) [1, 2].PXE is characterized by progressive pathologic calcificationand fragmentation of the elastic tissue in the affected organs.PXEappears to bepresent inall overthe world’s populations.In different reports, the prevalence is given to range between1:25,000 and 1:100,000 [3]. Due to lack of adequate knowl-edge among patients and physicians, delay in diagnosis, andgenetic heterogeneity, the exact prevalence of PXE might beunderestimated. Although autosomal recessive inheritancepatterns have mainly been reported, some families show au-tosomal dominant inheritance and some cases are sporadicwithout family history [4]. In most cases, the skin is the firstorgan system affected. Skin changes are usually detected inthe second or third decade [5].Theaffectedskineventuallybecomeslax,redundant,andinelastic.PXEalsoaffectsocularfundusduetopathologicchangesinBruch’smembrane.Earlyocular findings are pigment irregularities of the temporalfundus called “Peau d’ orange”, angioid streaks due to breaksof Bruch’s membrane and later choroidal neovascularisationand disciform scars [1]. CVS manifestations of PXE includearterial hypertension, peripheral arterial disease, anginapectoris, restrictive cardiomyopathy, mitral valve prolapse,and sudden cardiac death [3, 6].A 61-year-old female patient was referred to our derma-tology outpatient clinic by the ophthalmology clinic becauseof angioid streaks detected on fundus examination. Patientdid not have any subjective complaints. She had had historyof diabetes for 11 years and coronary artery disease for10 years. On dermatologic examination, we detected yellowcobblestone like lesions with lax, redundant, and inelasticskin over the anterior and lateral parts of the neck and axilla(Fig. 1). She had not consulted any dermatologist beforebecause of these lesions.Patient had applied to the ophthalmology outpatient clin-ic because of visual impairment. Best corrected visual acu-itieswere0.2/0.2andintraocularpressureswere15/15mmHgrespectively for the right and left eyes. Anterior segmentswere normal. Fundoscopy revealed bilateral angioid streaksoriginating from the optic disk, radiating outwards especiallyunder the macula as grayish–brownish irregular lines (Figs. 2and 3). Optical coherence tomography examination re-vealed increased reflectivity at the level of retinal pig-ment epithelium–Bruch’smembrane–choroid complex.Biopsy taken from the affected skin showed calcifiedand fragmented elastic fibers in the middle and lowerdermis and confirmed the diagnosis.PXE is a rare connective tissue disorder leading to abroad range of complications including mainly the skin,eyes, and CVS [1]. Clinical findings are due to pathologiccalcificationandfragmentation ofelastic tissue inthe dermisof the skin, Bruch’s membrane of the retina, and intima ofthe vascular arteries [5]. These pathologic changes result incharacteristic skin lesions, visual problems, various CVScomplications, and rare problems such as gastrointestinalsystem bleeding [7].Clinical manifestations of PXE are rarely present at birth.The skin is the first organ affected in most cases and the

Pseudoxanthoma elasticum with abnormal nailfold microcirculatory findings.

A case of a patient with an early and severe visual impairment is described. Due to the occurrence of skin papules a suspect of pseudoxanthoma elasticum (PXE) was posed. PXE is a rare autosomal recessive disease clinically characterized by skin, cardiovascular and ocular manifestations, these last being those that most severely affect patients’ quality of life. A whole exome sequencing approach focusing on 340 genes related to the calcification process and/or to inherited retinal diseases (IRDs) was performed. Rare monoallelic sequence variants in ABCA4, ABCC6, IMPG1, POC1B and RAX2 were found. The presence of calcified elastic fibers was assessed by ultrastructural analysis on a skin biopsy. Diagnosis of PXE was based on clinical, biomolecular and morphological results, although the additional involvement of several IRD genes is important to explain the unexpectedly severe ophthalmological phenotype of the patient also in prognostic and therapeutic perspectives. Data indicate that genetic screening using a wide-spectrum analysis approach is essential to assist ophthalmologists in improving patient counseling.

Staining of elastic fibres with antilysozyme antibodies has been noted previously. In this study, we examined the staining pattern of dermal elastic fibres in aging, solar elastosis, and lesional skin of pseudoxanthoma elasticum (PXE) using an antibody to lysozyme and the indirect-peroxidase technique. To assess the effects of aging, sun-protected skin (buttock) from a younger and an older group of patients was used. Sun damage was studied in skin specimens from varying sun-exposed body regions (trunk; head and neck). No staining was seen in sun-protected skin from younger individuals, whereas sun-protected skin from older persons had scattered positive fibres. Solar elastotic material was intensely positive and the number of positive fibres appeared to correlate with the amount of sun damage. Abnormal elastic fibres in PXE also stained positively, but less intensely, than fibres in solar elastosis. This study shows that changes in the elastic fibres due to degenerative processes or genetic factors results in altered antigenic expression of the fibres. This may be an epiphenomenon secondary to changes in proteoglycans, which are known to occur with solar elastosis and PXE, or may represent an adaptive phenomenon to maintain the elastic properties of the altered fibres or to decrease their antigenicity.

Pseudoxanthoma elasticum (PXE) is a disorder of connective tissue in which abnormalities of elastic tissue and collagen are found. The purpose of this study was to examine the ultrastructure and distribution of connective tissue components in lesional and non-lesional skin of patients by means of indirect immunofluorescence, electron microscopy and indirect immunoelectron microscopy. Prominent abnormalities of elastic tissue were seen on electron microscopy and confirmed by immunoelectron microscopy. Abnormal elastic fibers containing electron-dense bodies and holes were seen even in non-lesional skin. In addition, the normal pattern of collagen bundles was disrupted in lesional skin, but not in non-lesional skin of patients with PXE. The majority of individual collagen fibrils appeared normal by electron microscopy. The distribution of type IV collagen and laminin was normal in small blood vessels. Finally, abnormalities in the distribution of fibronectin were seen. The finding of atypical elastic fibers in non-lesional skin supports an early role for elastic tissue components in the pathogenesis of PXE. Interactions between elastin, collagen and other matrix substances may explain some of the abnormalities seen.

EDITOR-Pseudoxanthoma elasticum (PXE, MIM 264800) is an inherited disorder of connective tissue in which the elastic fibres of the skin, eyes, and cardiovascular system slowly become calcified, causing a spectrum...

Co-existence of mutations in the FBN1 gene and the ABCC6 gene in a patient with Marfan syndrome associated with pseudoxanthoma elasticum

Alteration of Extracellular Nucleotide Metabolism in Pseudoxanthoma Elasticum

We describe an 11-year-old girl with severe renin-dependent hypertension. She had characteristic cutaneous, ocular, and vascular signs of pseudoxanthoma elasticum (PXE), and the diagnosis was confirmed histologically. Because PXE is a heterogeneous heritable disorder, the family was evaluated for this condition. Since the patient's mother and brother showed some manifestations of PXE, autosomal dominant inheritance is the most likely inheritance pattern in this family.

Can APOE and MTHFR polymorphisms have an influence on the severity of cardiovascular manifestations in Italian Pseudoxanthoma elasticum affected patients?

Introduction/Objective Pseudoxanthoma elasticum (PXE) is a rare genetic disorder caused by mutations in the ABCC6 gene, leading to progressive calcification and fragmentation of elastic fibers, primarily affecting the skin, eyes, and vascular system. Although systemic involvement is recognized, fatal pulmonary complications remain exceptionally rare and poorly characterized in the literature. We present the autopsy findings of an 80-year-old woman with a prolonged clinical history suggestive of PXE, including yellow papules and plaques over flexural surfaces and documented vascular calcifications. Although prior genetic testing was negative for known ABCC6 mutations, the diagnosis was supported postmortem by characteristic histopathologic features. Strikingly, there was diffuse pulmonary calcification and widespread vascular calcifications in the brain, heart, liver, spleen, kidneys, and pancreas.The cause of death was right-sided congestive heart failure due to severe pulmonary hypertension secondary to diffuse alveolar and vascular calcification. Methods/Case Report Case report Results NA Conclusion This case highlights a rare but critical manifestation of PXE and emphasizes the diagnostic value of clinicopathologic correlation when genetic findings are inconclusive, and highlights the often underrecognized potential for PXE to cause fatal cardiopulmonary disease.

Quality Antenatal Care (ANC) services can prevent complications during pregnancy, but during the Covid-19 pandemic, there is a policy for mothers to postpone ANC visits. The purpose of the study was to find out how the influence of ANC services during the Covid-19 pandemic on the incidence of complications in pregnant women. The research method used is an analytical survey with a Cross-Sectional approach. The number of samples is 110 pregnant women respondents. The statistical test used is the Chi-Square test. The results showed that the age of pregnant women was 92.1% of healthy reproductive age, high school education level was 90.4%, some pregnancies experienced by mothers 2 were 66.7%, work as housewives were 67%. The biggest complication that occurs in pregnant women is anemia (40%). The provision of quality ANC services with 10T has a positive influence on the incidence of complications in pregnancy during the pandemic (p-value <0.05), as well as understanding of the Maternal and Child Health (MCH) book (p-value <0.05) and the anxiety felt by the mother (p-value <0.05) influences the occurrence of complications. The conclusions obtained were the effect of providing quality ANC services with 10 T, understanding of the MCH handbook on the incidence of complications during the covid-19 pandemic.

Calciphylaxis is a rare condition of widespread calcification of tissues and blood vessels with accompanying vascular thrombosis and ischemic necrosis. Most cases develop in association with hyperparathyroidism in patients with chronic renal failure. Pseudoxanthoma elasticum (PXE) is a hereditary condition of abnormal elastic tissue structure that leads to widespread abnormalities of the skin, retina, and visceral organs. Histologic changes of PXE have been observed as coincidental findings in several conditions such as following trauma to the skin manifest as isolated plaques often in scars. We observed histologic findings of PXE in a patient with chronic renal failure who developed fatal calciphylaxis. Complete evaluation failed to reveal evidence of systemic findings of PXE. Histologic changes of PXE may be seen in patients with calciphylaxis as a coincidental finding. Rapidly developing soft tissue calcification may lead to the expression of the characteristic histopathologic findings of PXE without evidence of classic clinical manifestations of PXE. Calciphylaxis should be added to the list of disorders that may lead to microscopic PXE-like changes.