The extent of pseudoxanthoma elasticum skin changes is related to cardiovascular complications and visual loss: a cross‐sectional study

Navasiolava, Nastassia; Gnanou, M; Douillard, M; Saulnier, Patrick; Arányi, Tamàs; Ebran, Jean‐Marc; Henni, Samir; Humeau, H.; Lefthériotis, Georges; Martin, Ludovic

doi:10.1111/bjd.17094

Cited by 9 publications

(10 citation statements)

References 7 publications

(6 reference statements)

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“…The unexpected results of this study have not only provided a fresh insight into how the immediate environment affects the progression of this rare disease in an animal model, but also furthers the prospect of dietary intervention as a possible treatment for PXE. Importantly, the collective findings that PPi treatment does not reverse established calcification (Dedinszki et al, 2017;Pomozi et al, 2017b) and that the extent of skin lesions correlate with severe cardiovascular and/or ophthalmologic complications in PXE (Navasiolava et al, 2018) suggest that any PPi-based intervention should be initiated as early as possible, at diagnosis or soon thereafter.…”

Section: Animal Diet As An Important Variable In Laboratory Animal Rementioning

confidence: 99%

Dietary Pyrophosphate Modulates Calcification in a Mouse Model of Pseudoxanthoma Elasticum: Implication for Treatment of Patients

Pomozi

Julian

Zoll

et al. 2019

Journal of Investigative Dermatology

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Pseudoxanthoma elasticum is a heritable disease caused by ABCC6 deficiency. Patients develop ectopic calcification in skin, eyes, and vascular tissues. ABCC6, primarily found in liver and kidneys, mediates the cellular efflux of ATP, which is rapidly converted into inorganic pyrophosphate (PPi), a potent inhibitor of calcification. Pseudoxanthoma elasticum patients and Abcc6 e/e mice display reduced PPi levels in plasma and peripheral tissues. Pseudoxanthoma elasticum is currently incurable, although some palliative treatments exist. In recent years, we have successfully developed therapeutic methodologies to compensate the PPi deficit in animal models and humans. Here, we inadvertently discovered that modulating dietary PPi can also be an effective approach to reducing calcification in Abcc6 e/e mice. Our findings were prompted by a change in institutional rodent diet. The new chow was enriched in PPi, which increased plasma PPi, and significantly reduced mineralization in Abcc6 e/e mice. We also found that dietary PPi is readily absorbed in humans. Our results suggest that the consumption of food naturally or artificially enriched in PPi represents a possible intervention to mitigate calcification progression in pseudoxanthoma elasticum, that dietary preferences of patients may explain pseudoxanthoma elasticum heterogeneous manifestations, and that animal chow has the potential to influence data reproducibility.

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Section: Animal Diet As An Important Variable In Laboratory Animal Rementioning

confidence: 99%

Dietary Pyrophosphate Modulates Calcification in a Mouse Model of Pseudoxanthoma Elasticum: Implication for Treatment of Patients

Pomozi

Julian

Zoll

et al. 2019

Journal of Investigative Dermatology

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“…In this work, in addition to DS, we performed quantitative AF imaging and successfully distinguished PXE-affected skin from uninvolved skin areas using intensity descriptors with the aim to objectify the degree of skin involvement. A recent retrospective clinical study of 125 PXE patients found a significant correlation between the number of the PXE-affected skin sites of and the occurrence of severe cardiovascular events and/or ophthalmological complications [46]. In addition, in a smaller cohort of 14 patients, similar results were reported regarding the cardiovascular involvement [47].…”

Section: Discussionmentioning

confidence: 63%

Autofluorescence Imaging of the Skin Is an Objective Non-Invasive Technique for Diagnosing Pseudoxanthoma Elasticum

et al. 2021

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Pseudoxanthoma elasticum (PXE) is a rare multisystemic autosomal recessive connective tissue disease. In most cases, skin manifestations of PXE are the first to develop, followed later by severe ocular and cardiovascular complications. In our present study, in addition to dermoscopy, we introduced novel techniques, autofluorescence (AF) and diffuse reflectance (DR) imaging for the assessment of affected skin sites of five PXE patients. PXE-affected skin areas in most skin sites showed a previously observed pattern upon dermoscopic examination. With the novel imaging, PXE-affected skin lesions displayed high AF intensity. During our measurements, significantly higher mean, minimum and maximum AF intensity values were found in areas of PXE-affected skin when compared to uninvolved skin. Conversely, images acquired with the use of 660 and 940 nm illumination showed no mentionable difference. Our results demonstrate that AF imaging may be used in the in vivo diagnostics and quantification of the severity of the skin lesions of PXE patients. In addition, it is a safe, fast and cost-effective diagnostic method. AF imaging may be also used to objectively monitor the efficacy of the possible novel therapeutic approaches of PXE in the future.

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“…However, in an analysis of genotype-phenotype correlations in 289 patients with PXE, biallelic truncating variants were associated with more severe arterial and ophthalmological phenotypes than those of patients with mixed genotypes of one truncating and one non-truncating variant [3]. Additionally, severe skin phenotypes are correlated with cardiovascular and ophthalmic phenotypes [25,26].…”

Section: Discussionmentioning

confidence: 98%

Clinical Characterization of Korean Patients with Pseudoxanthoma Elasticum and Angioid Streaks

Jin

Joo

Woo

2021

Genes

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This study aimed to characterize Korean patients with pseudoxanthoma elasticum (PXE) presenting with angioid streaks. Retinal phenotypes were longitudinally evaluated by multimodal ophthalmic imaging, and targeted gene panel sequencing for inherited retinal diseases was conducted. Seven subjects from unrelated families (median age, 51.2 years) were enrolled and followed for a median of 3.2 years. Four asymptomatic patients were significantly younger than three symptomatic patients with decreased visual acuity at presentation (mean age; 38.1 vs. 61.5 years, p = 0.020). The asymptomatic patients maintained good vision (20/32 or better) and had no choroidal neovascularization (CNV) over the observation period. The symptomatic patients showed additional reduction in visual acuity and bilateral CNV occurrence during the longitudinal follow-up. Pathogenic ABCC6 variants were identified in all patients, leading to a diagnosis of PXE. Heterozygous monoallelic variants were identified in four patients and compound heterozygous variants were detected in three patients. Nine ABCC6 variants were identified, including one novel variant, c.2035G>T [p.Glu679Ter]. This is the first genetic study of Korean patients with PXE.

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The extent of pseudoxanthoma elasticum skin changes is related to cardiovascular complications and visual loss: a cross‐sectional study

Cited by 9 publications

References 7 publications

Dietary Pyrophosphate Modulates Calcification in a Mouse Model of Pseudoxanthoma Elasticum: Implication for Treatment of Patients

Dietary Pyrophosphate Modulates Calcification in a Mouse Model of Pseudoxanthoma Elasticum: Implication for Treatment of Patients

Autofluorescence Imaging of the Skin Is an Objective Non-Invasive Technique for Diagnosing Pseudoxanthoma Elasticum

Clinical Characterization of Korean Patients with Pseudoxanthoma Elasticum and Angioid Streaks

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