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Cureus Oct 2023Pseudoxanthoma elasticum (PXE) is a rare multisystem disease characterized by progressive calcification and disintegration of elastic fibers. The disorder is attributed...
Pseudoxanthoma elasticum (PXE) is a rare multisystem disease characterized by progressive calcification and disintegration of elastic fibers. The disorder is attributed to a genetic mutation occurring in the ABCC6 gene, which encodes for the ATP-binding cassette transporter C6. This gene is located on chromosome 16. Patients commonly present with cutaneous, ophthalmic, and cardiovascular manifestations. However, there is a significant degree of phenotypic diversity. The diagnosis is determined by clinical manifestations, histological analysis of the lesions, and genetic analysis. The present study includes a case report of a 12-year-old female patient who presented with a chief complaint of painless, mildly pruritic yellow papules located on her neck for a period of one year. These papules were accompanied by comedones.
PubMed: 38022106
DOI: 10.7759/cureus.47041 -
International Journal of Molecular... Oct 2023Pseudoxanthoma elasticum (PXE) is a heritable multisystem ectopic calcification disorder. The gene responsible for PXE, , encodes ABCC6, a hepatic efflux transporter...
Pseudoxanthoma elasticum (PXE) is a heritable multisystem ectopic calcification disorder. The gene responsible for PXE, , encodes ABCC6, a hepatic efflux transporter regulating extracellular inorganic pyrophosphate (PPi), a potent endogenous calcification inhibitor. Recent studies demonstrated that in addition to the deficiency of plasma PPi, the activated DDR/PARP signaling in calcified tissues provides an additional possible mechanism of ectopic calcification in PXE. This study examined the effects of etidronate (ETD), a stable PPi analog, and its combination with minocycline (Mino), a potent inhibitor of DDR/PARP, on ectopic calcification in an mouse model of PXE. mice, at 4 weeks of age, before the development of ectopic calcification, were treated with ETD, Mino, or both for 18 weeks. Micro-computed tomography, histopathologic examination, and quantification of the calcium content in mice treated with both ETD and Mino revealed further reduced calcification than either treatment alone. The effects were associated with reduced serum alkaline phosphatase activity without changes in plasma PPi concentrations. These results suggest that ETD and Mino combination therapy might provide an effective therapeutic approach for PXE, a currently intractable disease.
Topics: Mice; Animals; Pseudoxanthoma Elasticum; Poly(ADP-ribose) Polymerase Inhibitors; X-Ray Microtomography; Multidrug Resistance-Associated Proteins; Calcinosis; Disease Models, Animal; Etidronic Acid
PubMed: 37894722
DOI: 10.3390/ijms242015041 -
Biomedicines Oct 2023(1) Background: Genodermatoses are a clinically and genetically heterogenous group of inherited skin disorders. Diagnosing inherited skin diseases is a challenging task... (Review)
Review
(1) Background: Genodermatoses are a clinically and genetically heterogenous group of inherited skin disorders. Diagnosing inherited skin diseases is a challenging task due to their rarity and diversity. Dermoscopy is a non-invasive, easily accessible, and rapid tool used in dermatology not only for diagnostic processes but also for monitoring therapeutic responses. Standardized terminologies have been published for its proper use, reproducibility, and comparability of dermoscopic terms. (2) Methods: Here, we aimed to investigate dermoscopic features in various genodermatoses by conducting a systematic review and comparing its results to our own findings, data of patients diagnosed with genodermatoses at the Department of Dermatology, Venereology and Dermatooncology, Semmelweis University. (3) Results: Our systematic search provided a total of 471 articles, of which 83 reported both descriptive and metaphoric dermoscopic terminologies of 14 genodermatoses. The literature data were then compared to the data of 119 patients with 14 genodermatoses diagnosed in our department. (4) Conclusion: Dermoscopy is a valuable tool in the diagnosis of genodermatoses, especially when symptoms are mild. To enable the use of dermoscopy as an auxiliary diagnostic method, existing standardized terminologies should be extended to more genodermatoses.
PubMed: 37893091
DOI: 10.3390/biomedicines11102717 -
Biomedicines Sep 2023Previous studies revealed a link between inflammation and overactivation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling in...
Previous studies revealed a link between inflammation and overactivation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling in syndromes associated with aging. Pseudoxanthoma elasticum (PXE), a rare autosomal-recessive disorder, arises from mutations in (). On a molecular level, PXE shares similarities with Hutchinson-Gilford progeria syndrome, such as increased activity of senescence-associated- beta-galactosidase or high expression of inflammatory factors. Thus, this study's aim was the evaluation of activated STAT3 and the influence of JAK1/2-inhibitor baricitinib (BA) on inflammatory processes such as the complement system in PXE. Analysis of activation of STAT3 was performed by immunofluorescence and Western blot, while inflammatory processes and complement system factors were determined based on mRNA expression and protein level. Our results assume overactivation of JAK/STAT3 signaling, increased expression levels of several complement factors and high C3 protein concentration in the sera of PXE patients. Supplementation with BA reduces JAK/STAT3 activation and partly reduces inflammation as well as the gene expression of complement factors belonging to the C1 complex and C3 convertase in PXE fibroblasts. Our results indicate a link between JAK/STAT3 signaling and complement activation contributing to the proinflammatory phenotype in PXE fibroblasts.
PubMed: 37893046
DOI: 10.3390/biomedicines11102673 -
Annual Review of Pathology Jan 2024The enzyme ectonucleotide pyrophosphatase/phosphodiesterase 1 () codes for a type 2 transmembrane glycoprotein that hydrolyzes extracellular ATP to generate... (Review)
Review
The enzyme ectonucleotide pyrophosphatase/phosphodiesterase 1 () codes for a type 2 transmembrane glycoprotein that hydrolyzes extracellular ATP to generate pyrophosphate (PP) and adenosine monophosphate, thereby contributing to downstream purinergic signaling pathways. The clinical phenotypes induced by ENPP1 deficiency are seemingly contradictory and include early-onset osteoporosis in middle-aged adults and life-threatening vascular calcifications in the large arteries of infants with generalized arterial calcification of infancy. The progressive overmineralization of soft tissue and concurrent undermineralization of skeleton also occur in the general medical population, where it is referred to as paradoxical mineralization to highlight the confusing pathophysiology. This review summarizes the clinical presentation and pathophysiology of paradoxical mineralization unveiled by ENPP1 deficiency and the bench-to-bedside development of a novel ENPP1 biologics designed to treat mineralization disorders in the rare disease and general medical population.
Topics: Adult; Humans; Middle Aged; Phosphoric Diester Hydrolases; Vascular Calcification; Pyrophosphatases
PubMed: 37871131
DOI: 10.1146/annurev-pathmechdis-051222-121126 -
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 -
BMJ (Clinical Research Ed.) Oct 2023
Topics: Humans; Pseudoxanthoma Elasticum
PubMed: 37857417
DOI: 10.1136/bmj-2023-075323 -
Clinical and Experimental Nephrology Jan 2024Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by diminished inorganic plasma pyrophosphate (PPi), a strong calcification inhibitor. In...
BACKGROUND
Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by diminished inorganic plasma pyrophosphate (PPi), a strong calcification inhibitor. In addition to more typical calcification of skin, retina and arterial wall a diminished plasma PPi could lead to other ectopic calcification, such as formation of kidney stones.
OBJECTIVE
To compare the prevalence of kidney stones between PXE patients and hospital controls on computed tomography (CT).
METHOD
Low-dose CT images of PXE patients and controls were assessed by one radiologist, who was blinded for the diagnosis PXE. The number of kidney stones, and the size of the largest stone was recorded. Odds ratios (ORs) for having kidney stone were calculated using multivariable adjusted logistic regression.
RESULTS
Our study comprised 273 PXE patients and 125 controls. The mean age of PXE patients was 51.5 ± 15.9 years compared to 54.9 ± 14.2 in the control group (p = 0.04) and PXE patients more often were women (63 vs. 50%, p = 0.013). The prevalence of kidney stones on CT was similar: 6.9% in PXE patients, compared to 5.6% in controls (p = 0.6). In the multivariate analysis adjusting for age and sex, there was no significantly higher odds for PXE patients on having stones, compared to controls: OR 1.48 (95% CI 0.62-3.96).
CONCLUSION
There is no significant difference in the prevalence of incidental kidney stones on CT in PXE patients versus controls.
Topics: Humans; Female; Adult; Middle Aged; Aged; Male; Pseudoxanthoma Elasticum; Prevalence; Skin; Tomography, X-Ray Computed; Kidney Calculi
PubMed: 37837579
DOI: 10.1007/s10157-023-02405-2 -
Retina (Philadelphia, Pa.) Nov 2023
Topics: Humans; Pseudoxanthoma Elasticum; Ophthalmoscopy; Angioid Streaks; Multimodal Imaging; Lasers
PubMed: 37683255
DOI: 10.1097/IAE.0000000000003933 -
European Journal of Dermatology : EJD Jun 2023
Topics: Humans; Pseudoxanthoma Elasticum; Anemia, Hemolytic, Congenital Nonspherocytic; Pyruvate Metabolism, Inborn Errors; Iron Overload
PubMed: 37594352
DOI: 10.1684/ejd.2023.4501