弾性線維性仮性黄色腫

OBJECTIVE: To investigate the prevalence, number, size, and distribution of rotator cuff calcifications in pseudoxanthoma elasticum (PXE) patients, relative to a comparison cohort, using computed tomography (CT). MATERIALS AND METHODS: This single-center retrospective study included adult PXE patients with available low-dose full-body CT scans, compared with a cohort of adult patients undergoing full-body 18F-fluordeoxyglucose-positron emission tomography/CT (FDG-PET/CT) scans. A blinded musculoskeletal radiologist assessed the presence, number, size, and location of rotator cuff calcifications on thin-slice axial CT images (1-2 mm), with multiplanar reconstruction. The association between disease status and calcifications were analysed using age- and sex-adjusted multivariable logistic and negative binomial regression, and mixed-effects models for anatomical locations. RESULTS: Two hundred sixty-nine PXE patients (51 ± 14 years, 64% female) and 124 non-PXE patients (55 ± 16 years, 50% female) were included. A total of 138 calcifications in 82 PXE patients (prevalence, 30%; median largest calcification length, 6.0 mm; IQR 3.0-8.0) and 48 calcifications in 30 non-PXE patients (prevalence, 24%; median largest calcification length, 4.5 mm; IQR 3.0-7.0) were detected. No significant association between PXE and the presence (adjusted OR 1.54, 95% CI 0.92-2.63) or number of calcifications (adjusted RR 1.37, 95% CI 0.89-2.09) was found. However, PXE patients had an increased odds of intratendinous calcifications (adjusted OR 2.56, 95% CI 1.09-6.03) and a higher number of calcifications at this site (adjusted RR 2.31, 95% CI 1.18-4.52). CONCLUSION: PXE was not significantly associated with the overall presence or burden of rotator cuff calcifications, but showed an increased odds of intratendinous involvement.

Inorganic pyrophosphate (PPi) is a key inhibitor of ectopic calcification, yet transcriptional regulation of genes controlling its systemic production and degradation (ABCC6, ALPL, ANKH, and ENPP1) remains poorly understood. We hypothesized that PPi homeostasis is regulated by an evolutionarily conserved transcription factor (TF) network. Promoter motif analysis combined with ATAC-seq revealed conserved enrichment of TF binding sites, including FOXA1, HNF4A, and SREBF1, across mouse and human orthologues. Bulk and single-cell RNA-seq together with RT-qPCR analyses in wild-type and Abcc6-/- mice showed hepatocytes as major cell type expressing the most relevant genes maintaining PPi homeostasis. Further inference analysis identifies a conserved transcriptional program that regulates systemic PPi balance across mice and humans. Functionally, mice showed an age-dependent inverse correlation between plasma PPi and serum alkaline phosphatase (AP) activity, strongest during early life. Abcc6-/- mice displayed persistently reduced but gradually increasing PPi levels and altered Pi/PPi ratios during aging. In humans, plasma PPi correlated inversely with AP activity and positively with Pi in both controls and ABCC6-deficient pseudoxanthoma elasticum patients. Together, these findings support a conserved TF-associated regulatory program linking PPi homeostasis gene expression with circulating mineralization-related factors across physiological and pathological states.

PURPOSE: To characterize fundus findings and the presence of pseudoxanthoma elasticum (PXE) in Japanese patients with angioid streaks (AS). STUDY DESIGN: Retrospective, single-center observational study. METHODS: This retrospective study included 33 patients (66 eyes) diagnosed with AS who underwent color fundus photography, optical coherence tomography, and fundus autofluorescence. The presence of PXE, peau d'orange, choroidal neovascularization (CNV), macular atrophy, comet tail lesions, pattern dystrophy-like changes, subretinal drusenoid deposits (SDD), outer retinal tubulation (ORT), and optic nerve head drusen were evaluated. RESULTS: PXE was diagnosed in 15 of 33 patients (45.5%), whereas peau d'orange was observed in 36 eyes (54.5%). There were no significant differences in the prevalence of peau d'orange (P=1.00) or comet tail lesions (P=0.70) between patients with and without clinical PXE diagnosis. CNV and macular atrophy were each present in 31 eyes (47.0%). Comet tail lesions, pattern dystrophy-like changes, SDD, and ORT were found in 17 (25.8%), 21 (31.8%), 6 (9.1%), and 13 (19.7%) eyes, respectively; optic nerve head drusen were not detected. Most pattern dystrophy-like changes (81.0%), SDD (83.3%), and ORT (92.3%) were associated with CNV. CONCLUSION: Japanese patients with AS showed a high frequency of CNV, which is often accompanied by macular atrophy and photoreceptor-related structural changes. Furthermore, the prevalence of peau d'orange was higher than of clinically diagnosed PXE, suggesting possible underdiagnosis of PXE in this cohort.