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Dermatology Reports Sep 2022Late-onset focal dermal elastosis is a rare cutaneous condition classified as an increased dermal elastic tissue disorder. It is distinguished clinically by multiple...
Late-onset focal dermal elastosis is a rare cutaneous condition classified as an increased dermal elastic tissue disorder. It is distinguished clinically by multiple papules with a preference for the neck and other flexures, as well as histologically by focally increased elastic fibers in the reticular dermis. Several elastic tissue disorders in the skin have a similar clinical presentation. The distinction between late-onset focal dermal elastosis and other pseudoxanthoma elasticum mimickers is critical because they are not associated with systemic lesions. We present a case of late-onset focal dermal elastosis and conduct a literature review on this unusual condition.
PubMed: 36199904
DOI: 10.4081/dr.2022.9337 -
Journal of Cardiology Cases Oct 2022Pseudoxanthoma elasticum (PXE) is a rare hereditary disorder that causes elastic tissue degeneration in the skin, eyes, and cardiovascular system. Gastrointestinal...
UNLABELLED
Pseudoxanthoma elasticum (PXE) is a rare hereditary disorder that causes elastic tissue degeneration in the skin, eyes, and cardiovascular system. Gastrointestinal bleeding and fundus hemorrhage are serious complications associated with PXE prognosis as well as cardiovascular involvement. This is a rare case of acute coronary syndrome in a PXE patient with high bleeding risk.
LEARNING OBJECTIVE
Pseudoxanthoma elasticum (PXE) resulting in acute coronary syndrome (ACS) is rare. Given PXE patients are generally at very high bleeding risk, antithrombotic therapy as secondary prevention after ACS onset should be taken into full consideration.
PubMed: 36187305
DOI: 10.1016/j.jccase.2022.06.004 -
International Medical Case Reports... 2022To describe a case of hypotony maculopathy following anti-VEGF intravitreal injection (IVI) in a patient with pseudoxanthoma elasticum (PE).
PURPOSE
To describe a case of hypotony maculopathy following anti-VEGF intravitreal injection (IVI) in a patient with pseudoxanthoma elasticum (PE).
METHODS
Clinical case report.
RESULTS
A 52-year-old male complained of right eye (OD) vision loss 2 days after an uncomplicated anti-VEGF IVI for the treatment of choroidal neovascularization secondary to angioid streaks. Relevant medical history included PE, pathologic myopia, and a previous pars plana vitrectomy (PPV) due to a retinal detachment. OD best-corrected visual acuity (BCVA) dropped from 6/12 to 6/18 after the IVI. Intraocular pressure (IOP) was 3 mmHg and chorioretinal folds were evident in the posterior pole. Topical dexamethasone and atropine were prescribed, and full recovery was noticed after 3 days. Four months later, the patient developed a new episode of vision loss after another IVI. His BCVA was counting fingers, IOP was 2mmHg, and more noticeable chorioretinal folds were found. This time, an open scleral wound at the injection site was evident and a scleral suture was necessary. Once again, the patient recovered well.
CONCLUSION
Hypotony maculopathy following intravitreal injection is a rare condition. However, the described patient presented several conditions which could be related with poor scleral wound closure: intrinsic scleral fragility due to myopia and pseudoxanthoma elasticum; repeated IVI procedures; and absence of vitreous in the posterior segment due to prior vitrectomy. Despite the good outcome, hypotony maculopathy may be a sight-threatening condition, and special attention is necessary for specific patients with risk factors.
PubMed: 36164320
DOI: 10.2147/IMCRJ.S382421 -
International Journal of Molecular... Aug 2022Mutations in ABCC6, an ATP-binding cassette transporter with a so far unknown substrate mainly expressed in the liver and kidney, cause pseudoxanthoma elasticum (PXE)....
Mutations in ABCC6, an ATP-binding cassette transporter with a so far unknown substrate mainly expressed in the liver and kidney, cause pseudoxanthoma elasticum (PXE). Symptoms of PXE in patients originate from the calcification of elastic fibers in the skin, eye, and vessels. Previous studies suggested an involvement of ABCC6 in cholesterol and lipid homeostasis. The intention of this study was to examine the influence of ABCC6 deficiency during adipogenic differentiation of human bone marrow-derived stem cells (hMSCs). Induction of adipogenic differentiation goes along with significantly elevated gene expression in mature adipocytes. We generated an -deficient cell culture model using clustered regulatory interspaced short palindromic repeat Cas9 (CRISPR-Cas9) system to clarify the role of ABCC6 in lipid homeostasis. The lack of ABCC6 in hMSCs does not influence gene expression of differentiation markers in adipogenesis but results in a decreased triglyceride content in cell culture medium. Protein and gene expression analysis of mature -deficient adipocytes showed diminished intra- and extra-cellular lipolysis, release of lipids, and fatty acid neogenesis. Therefore, our results demonstrate impaired lipid trafficking in adipocytes due to deficiency, highlighting adipose tissue and peripheral lipid metabolism as a relevant target for uncovering systemic PXE pathogenesis.
Topics: Adipocytes; Cholesterol; Homeostasis; Humans; Mesenchymal Stem Cells; Multidrug Resistance-Associated Proteins; Pseudoxanthoma Elasticum
PubMed: 36012482
DOI: 10.3390/ijms23169218 -
European Journal of Vascular and... Jan 2023Pseudoxanthoma elasticum (PXE) is an autosomal recessive metabolic disorder that may be associated with a high prevalence of peripheral artery disease (PAD) and related...
OBJECTIVE
Pseudoxanthoma elasticum (PXE) is an autosomal recessive metabolic disorder that may be associated with a high prevalence of peripheral artery disease (PAD) and related symptoms. However, the evidence supporting this association is weak, as only small cohort studies are available. Furthermore, limited data are available on the outcome of lower limb peripheral arterial interventions (PAI) in patients with PXE. It was the aim of this study to clarify the prevalence of PAD, and the occurrence and outcome of PAI in patients with PXE.
METHODS
This was a retrospective review of prospectively collected data from the Dutch Expertise Centre for PXE database. Clinical data of consecutive patients with a definitive diagnosis of PXE were examined. The primary endpoint was the prevalence of PAD (defined as an ankle brachial index of < 0.9). The secondary endpoint was to report an overview of PAI and target lesion revascularisations.
RESULTS
In 285 PXE patients (median age 58 years), 50.9% of patients (n = 145) met the criteria for PAD. Seventeen patients underwent a PAI, mostly for intermittent claudication, at a median age of 51 years. The incidence of PAI was 2.25 per 1 000 patient years in patients with PAD and PXE. A total of 58 interventions was recorded, of which 35 were target lesion revascularisations in nine patients. Twenty one revascularisations were performed within a year following the primary intervention, in 16 cases due to an acute occlusion.
CONCLUSION
Within a well phenotyped and large PXE cohort, the diagnosis of PAD was prevalent in one in two patients. The observed rate of peripheral interventions was low, while the re-intervention rate was unfavourable after endovascular or bypass surgical procedures, with over half of these re-interventions indicated within a year.
Topics: Humans; Middle Aged; Pseudoxanthoma Elasticum; Peripheral Arterial Disease; Retrospective Studies; Prevalence; Ankle Brachial Index
PubMed: 35977696
DOI: 10.1016/j.ejvs.2022.08.009 -
Frontiers in Endocrinology 2022Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) is a rare form of hereditary rickets, which is characterized by defective bone mineralization and renal... (Review)
Review
Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) is a rare form of hereditary rickets, which is characterized by defective bone mineralization and renal phosphate wasting due to a loss-of-function variant in the ectonucleotide pyrophosphatase/phosphodiesterase 1 () gene. Although pathogenic variant of has been known to manifest other phenotypes including arterial calcification, hearing loss, ossification of posterior longitudinal ligament, or pseudoxanthoma elasticum, there have been few reports including systematic examination in individuals diagnosed with ARHR2 to date. Herein, we report a case of ARHR2 with a bi-allelic pathogenic variant of , in which the patient presented with gait abnormalities with severe genu varum at 26 months of age. Targeted gene panel sequencing was performed to investigate the genetic cause of rickets, and a homozygous nonsense variant in , c.783C>G (p.Tyr261*), was identified. The patient was treated with oral phosphate and active vitamin D supplements and underwent corrective osteotomy for varus deformity. His phenotype was limited to rickets. A periodic systematic evaluation is needed to identify any comorbidities in ARHR2 patients since variants may present phenotypes other than rickets and symptoms may evolve or change over time.
Topics: Familial Hypophosphatemic Rickets; Humans; Mutation; Phosphates; Phosphoric Diester Hydrolases; Pyrophosphatases
PubMed: 35966073
DOI: 10.3389/fendo.2022.911672 -
Romanian Journal of Ophthalmology 2022To present a case of secondary type 2 choroidal neovascularization (CNV) and exudative maculopathy in a patient with Grönblad-Strandberg syndrome. A 37-year-old male...
To present a case of secondary type 2 choroidal neovascularization (CNV) and exudative maculopathy in a patient with Grönblad-Strandberg syndrome. A 37-year-old male was admitted with bilateral progressive painless visual acuity loss and metamorphopsias. A thorough ophthalmologic and clinical examination was performed. Best-corrected visual acuity (BCVA) on presentation was 20/ 200 OD (Oculus Dexter) and 20/ 60 OS (Oculus Sinister). Fundus examination revealed angioid streaks and subretinal hemorrhages on OU (Oculus Uterque), macular fibrosis on OD and "peau d'orange" pigmentary mottling on OS. Leakage areas on fundus fluorescein angiography (FFA) revealed active CNV on OU, which was confirmed by Optical Coherence Tomography (OCT). The presence of typical "plucked chicken" skin lesions in the latero-cervical area and their biopsy confirmed the diagnosis of Pseudoxanthoma elasticum (PXE). Consequently, the diagnosis of Grönblad-Strandberg syndrome was established. Every new diagnosis of angioid streaks entails not only a thorough ophthalmologic evaluation for secondary sight-threatening complications, but also a multidisciplinary evaluation due to the possibility of severe underlying systemic disease. BM = Bruch's membrane, RPE = Retinal Pigmented Epithelium, PXE = Pseudoxanthoma Elasticum, ABCC6 = ATP binding cassette subtype C number 6, CNV = Choroidal Neovascularization, BCVA = Best-Corrected Visual Acuity, OD = Oculus Dexter, OS = Oculus Sinister, OU = Oculus Uterque, FFA = Fundus Fluorescein Angiography, OCT = Optical Coherence Tomography, IPO = Intraocular Pressure, ECG = Electrocardiogram, anti-VEGF = anti-vascular endothelial growth factor.
Topics: Abnormalities, Multiple; Angioid Streaks; Choroidal Neovascularization; Darier Disease; Eyebrows; Fluorescein Angiography; Humans; Male; Pseudoxanthoma Elasticum; Tomography, Optical Coherence
PubMed: 35935090
DOI: 10.22336/rjo.2022.31 -
Eye (London, England) Jun 2023To assess systemic associations of angioid streaks (AS) using a large US healthcare database.
BACKGROUND/OBJECTIVES
To assess systemic associations of angioid streaks (AS) using a large US healthcare database.
SUBJECTS/METHODS
A retrospective cross-sectional study was conducted of patients diagnosed with AS in a large, national US insurer from 2000-2019. Cases were matched 1:5 to controls. The prevalence rates of established associated disease states and other systemic diseases were calculated and compared using logistic regression. Additionally, the rate of anti-VEGF treatment was assessed as a proxy for the incidence of choroidal neovascularization (CNV).
RESULTS
One thousand eight hundred fifty-two cases of AS and 9028 matched controls were included. The rates of association between AS and the well-characterized conditions included: Pseudoxanthoma elasticum (PXE)-228 patients (12.3%), Ehlers-Danlos syndrome-18 patients (1.0%), Paget's disease-6 patients (0.3%), hemoglobinopathies-30 patients (1.6%), and idiopathic-1573 patients (84.9%). There was a statistically higher prevalence of the following less classically associated diseases among patients with AS compared to controls: hereditary spherocytosis (1.7% vs. 0.6%, p < 0.001), connective tissue disease (1.0% vs 0.3%, p < 0.001) and non-exudative age-related macular degeneration (33.9% vs 10.6%, p < 0.001). Among 1442 eligible cases analyzed, 427 (29.6%) received at least 1 anti-VEGF injection with 338 (23.4%) patients having the injection after their AS diagnosis.
CONCLUSIONS
In the largest collection of AS patients to date, the classical teaching of systemic disease associations occur at rates far, far lower than previously reported. The association of AS with other less reported diseases highlights new potential associations and may contribute to the understanding of AS formation.
Topics: Humans; Angioid Streaks; Retrospective Studies; Cross-Sectional Studies; Pseudoxanthoma Elasticum; Choroidal Neovascularization; Delivery of Health Care; Fluorescein Angiography
PubMed: 35915234
DOI: 10.1038/s41433-022-02189-x -
Journal of Clinical Medicine Jun 2022Pseudoxanthoma elasticum (PXE) is a currently intractable genetic disorder characterized by progressive ectopic calcification in the skin, eyes and arteries. Therapeutic...
Pseudoxanthoma elasticum (PXE) is a currently intractable genetic disorder characterized by progressive ectopic calcification in the skin, eyes and arteries. Therapeutic trials in PXE are severely hampered by the lack of reliable biomarkers. Serum calcification propensity T50 is a blood test measuring the functional anticalcifying buffer capacity of serum. Here, we evaluated T50 in PXE patients aiming to investigate its determinants and suitability as a potential biomarker for disease severity. Fifty-seven PXE patients were included in this cross-sectional study, and demographic, clinical, imaging and biochemical data were collected from medical health records. PXE severity was assessed using Phenodex scores. T50 was measured using a validated, nephelometry-based assay. Multivariate models were then created to investigate T50 determinants and associations with disease severity. In short, the mean age of patients was 45.2 years, 68.4% was female and mean serum T50 was 347 min. Multivariate regression analysis identified serum fetuin-A (p < 0.001), phosphorus (p = 0.007) and magnesium levels (p = 0.034) as significant determinants of T50, while no correlations were identified with serum calcium, eGFR, plasma PPi levels or the ABCC6 genotype. After correction for covariates, T50 was found to be an independent determinant of ocular (p = 0.013), vascular (p = 0.013) and overall disease severity (p = 0.016) in PXE. To conclude, shorter serum T50—indicative of a higher calcification propensity—was associated with a more severe phenotype in PXE patients. This study indicates, for the first time, that serum T50 might be a clinically relevant biomarker in PXE and may thus be of importance to future therapeutic trials.
PubMed: 35807012
DOI: 10.3390/jcm11133727 -
Experimental Dermatology Oct 2022
Topics: Bone Diseases, Metabolic; Etidronic Acid; Humans; Multidrug Resistance-Associated Proteins; Mutation; Pseudoxanthoma Elasticum
PubMed: 35771123
DOI: 10.1111/exd.14636