The amount of calcifications in pseudoxanthoma elasticum patients is underestimated in computed tomographic imaging; a post-mortem correlation of histological and computed tomographic findings in two cases

Abstract

ObjectivesPseudoxanthoma elasticum (PXE) is a rare genetic disorder, characterised by elastic fibre degeneration and calcifications in multiple organ systems. Computed tomography (CT) imaging is a potential method to monitor disease progression in PXE patients; however, this method has not been validated. The aim of this study was to correlate histological and computed tomographic findings in PXE patients to investigate the ability of CT scanning to detect these alterations.MethodsPost mortem total body CT scans were obtained from two PXE patients (a 69-year-old male and 77-year-old female). Autopsy was performed, and 38 tissue samples of the first and 45 tissue samples of the second patient were extensively investigated histologically. The findings were compared with the CT scans.ResultsDegenerated and calcified elastic fibres and calcifications were histologically found in the skin, subcutaneous fat, heart, arteries and pleura and around the oesophagus. On CT imaging only the intradermal alterations of the skin and the larger vascular calcifications were detected. The smaller PXE-related abnormalities were not visible on CT.ConclusionsWith CT imaging vascular calcifications and skin alterations can be monitored in PXE patients. However, many of the subtle PXE-related abnormalities found in other organ systems during the autopsy were not visualised by CT scans. Furthermore, we extended the current knowledge on the disease location of PXE with subcutaneous, oesophageal and pleural lesions.Teaching Points • CT can be used to monitor gross vascular calcifications in PXE patients. • Many subtle PXE-related abnormalities are not visualised by CT scans. • PXE-related alterations can also be found in oesophagus, pleura and subcutaneous fat. Electronic supplementary materialThe online version of this article (10.1007/s13244-018-0621-6) contains supplementary material, which is available to authorized users.

Etidronate halts systemic arterial calcification in pseudoxanthoma elasticum

“…PPi is one of the strongest inhibitors of ectopic calcification and therefore PXE results in extensive calcification of the elastic fibers in the skin, the Bruch's membrane of the eyes, and the peripheral arteries [7]. The arterial phenotype involves medial arterial calcification of predominantly the intracranial arteries and the arteries of the legs, but other arteries, including the carotid arteries, aorta and iliac arteries are also affected by vascular calcifications [8,9]. PXE can therefore be used as a model disease to investigate the role of relatively isolated medial arterial calcification on vascular physiology and function and the effect of arterial stiffness on end organ damage [10].…”

Genetic deletion of Abcc6 disturbs cholesterol homeostasis in mice

“…Studies of human and mice found an increased carotid intima media thickness [22][23][24] due to ABCC6 deficiency, which correlates with higher risk for cardiovascular complications 25 . In current case reports it has been noticed that PXE patients suffer from degenerated and calcified elastic fibers in heart tissue as well stenosis in coronary arteries 26,27 . Furthermore, in a cardiac ischemia-reperfusion injury mice model could be demonstrated that the infarct size in heart tissue was increased in Abcc6 −/− mice 28 .…”

Pseudoxanthoma elasticum – also a microvascular disease

“…According to Gheduzzi et al the lung was more severely affected than digestive system or kidneys. Vos and Krankenburg et al found degenerated elastic fibers in the pleura of two patients with PXE [22]. Lately, these reports were the subject of a study by Pingel et al who interpreted reduced levels of DLCO % as a lead on restrictive lung disease.…”