PXE is a systemic disease characterised by elastic fibre degeneration and calcification in multiple organ systems. The present study combines radiological and histological findings in two PXE patients to investigate which alterations can and which cannot be seen using CT. The study has two important results. First, most of the abnormalities seen on histological slides were not seen on the CT, except for the intradermal skin alterations and part of the vascular calcifications. Second, this study adds to the existing knowledge regarding the abnormalities that can be seen in PXE patients. Degenerated and calcified elastic fibres were not only found in the skin, arteries, heart and pleura, where they have been described before, but also in the fibrous bands in between the subcutaneous fat tissue and around the oesophagus.
Besides the histological skin alterations typical for PXE, we also found histological alterations in macroscopically unaltered skin, most abundantly located in the subcutaneous fat. The presence of some abnormal elastic fibres in non-lesional skin has been described before . However, the presence of subcutaneous lesions at these locations has not been described before. A possible explanation could be that most knowledge about histological skin alterations is obtained by studies in skin biopsies, with only small amounts of subcutaneous fat.
In the heart degenerated and calcified elastic fibres were present subendocardially and in the interstitium between the cardiomyocytes. The presence of these altered elastic fibres in the cardiac tissue has been described before and has been suggested as a cause of restrictive cardiomyopathy and congestive heart failure [9, 14].
The vascular system showed the presence of both atherosclerotic intimal lesions with calcifications and calcifications present in the medial layer and/or around the internal and external elastic lamina of the vascular wall. In case of extensive calcification of the medial layer or elastic lamina, on CT scans a more or less circumferential pattern over a longer segment of the vessel was seen. This pattern is comparable to the pattern of medial calcification seen on X-rays described in the scarce literature . Our findings of vascular calcifications and the combination of both atherosclerosis and medial calcification are consistent with previous findings .
Central nervous system
In both patients, a lacunar infarction was found. The combination of PXE and lacunar infarctions of the brain has been described before as a complication of small vessel disease . Also the white matter lesions, as seen in one of our patients, have been described before in association with PXE [11, 17, 18]. The combination of lacunar infarctions and white matter lesions have been described in association with cognitive deterioration, although reports also mention extensive white matter lesions in a patient with normal baseline cognitive status . On CT scans nonspecific abnormalities could be found in the white matter area. For diagnostic purposes and further research, MRI probably is a better imaging technique.
A kidney stone was found in one of the patients. A possible relation between PXE and nephrolithiasis has been suggested before . However, in most of the patients described phosphocalcic abnormalities were present, which was not the case in our patient. Since nephrolithiasis is not a rare condition, it is not unlikely that this is a coincidental finding. In the same patient, also gallstones and a calcified adrenal gland were found. It is unknown to which extent this can be related to PXE. Furthermore, in the other patient some calcified fibres were found in the pleura and around the oesophagus. To our knowledge, degenerated and calcified elastic fibres have not been described in these locations before.
An important limitation of this study is the limited number of bodies studied, which can be explained by the low incidence of the disease and low autopsy rate in The Netherlands. Due to this small number of patients, it is possible that by chance we selected two patients in which many abnormalities were not seen on CT scans, while in larger series of patients this would not have been the case. Therefore, our findings need confirmation in a larger series of patients. Nevertheless, the findings in our patients during autopsy are comparable to those described in the literature. Furthermore, we did not study the eyes of the patients. However, most of the ocular findings in PXE (peau d’orange, angioid streaks, chorioretinal atrophies) can already be diagnosed in living patients using a variety of diagnostic techniques . It is doubtful whether CT, with a relatively low resolution for a small organ such as the eye, can contribute to these diagnoses.
In conclusion, autopsy of two PXE patients revealed degenerated and calcified elastic fibres and calcifications in skin, heart and arteries, but also in between the subcutaneous fat tissue, in the pleura and around the oesophagus, locations where they have not been described before. Only the intradermal and vascular calcifications were seen on CT. Our results indicate that CT can be used to study vascular calcifications in this patient population. However, while doing so, one should keep in mind that small calcifications are not visible using this technique.