Pseudoxanthoma elasticum and Reflectance confocal microscopy: report of two affected young sisters

Introduction & Objectives: Pseudoxanthoma elasticum (PXE) is a rare inherited multisystem disorder that mainly affects skin, eyes and cardiovascular system. The associated clinical signs are due to progressive calcification of elastic fibres and blood vessels, although normal levels of calcium and phosphorus in blood and urine. The first clinical description of the disease was done in 1881 by Rigal, and in 1896 was named PXE by Darier. Transmission of the disease is autosomal recessive. PXE is caused by homozygous or compound heterozygous mutations in the ATP-binding cassette subfamily C member 6 (ABCC6) gene, which encodes a transmembrane transport ADP dependent protein (MRP6). The gene is expressed predominantly in the liver and kidney, and found in low level in the tissue involved by PXE. The clinical expression of PXE is heterogeneous with considerable variation in age of onset, progression and severity of the disease, even in individuals of the same family with identical mutations. We present the case of two young sisters of 13 and 14 years old affected by PXE and the correlation between the histopathology and the reflectance confocal microscopy (RCM). Material & Methods: In our two patients we made diagnosis of PXE using clinical assessment and RCM. RCM (Vivascope 1500®: Caliber I.D., Rochester, USA) is a novel technique, based on a laser light of 830 nm of wavelength (near-infrared), which allows the visualization of skin structures at a nearly histological resolution. A depth of 250  μm can be reached, enabling the examination of the skin up to the upper dermis or to the reticular dermis, in relation of the thickness of the epidermis. The clinical and instrumental diagnosis was also confirmed by histopathological examination. The parents and the brother of 20 years old are also investigated. Moreover, we performed genetic test and counseling to all the family. Results: At dermatological examination of both patients we observed that the skin in the cervical region appeared soft, lax, wrinkled and redundant hanging in folds, while in the axillae and cubital fossae there were coalescent yellowish papules forming plaques with a symmetrically distribution. Ophthalmoscopy identified the presence of angioid streaks in both eyes of the two sisters, confirmed by retinograpy and angiography. Cardiovascular evaluation didn’t show changes in the younger patient while mild mitral valve regurgitation was identified in the older patient. Histopathological examination revealed calcification and fragmentation of elastic fibers in the dermis that appeared distorted. The parents and the brother of 20 years old didn’t show signs and symptoms of the disorder. We found a mutation of the ABCC6 gene in the two sisters while parents and brother carried one copy of the mutated gene. We performed RCM on the skin surface of the neck of our two young patients and we observed curled and fragmented thick fibers of the connective tissue in reticular dermis on both patients, which correspond to the short and curled elastic fibers of the reticular dermis in histopathology. Conclusions: Dermatological, ophthalmological and cardiological evaluation and monitoring is essential for an early diagnosis of PXE, adequate handling and better management of the associated complications when these are present. We suggest that the use of RCM it may be usefool to detect PXE in an early stage.