LAUSR

Mönckeberg medial calcific sclerosis (MCS) refers to a calcification of the medial arterial layer that is most found in the muscular arteries of the extremities and occasionally in visceral arteries [1]. We describe the case of a 50-year-old woman hospitalized because of acute ischemic lesions, involving her left lower limb, that developed over a few days. She had no conventional risk factors for atherosclerosis, and laboratory tests revealed severe renal insufficiency (serum creatinine 12.8 mg/dl), hyperparathyroidism (serum parathyroid hormone, PTH, 1559 ng/l, normal 10–60), and an elevated calcium–phosphate product (Ca 9.2 mg/dl, P 12.4 mg/dl). All common causes of renal failure were ruled out as well as paraneoplastic syndromes and autoimmune diseases. Ca–P metabolism was normalized using calcimimetics and calcium-free phosphate binders. Imaging studies, with X-ray, computed tomography (CT) and angiography, showed widespread vascular calcifications involving vertebral, renal, ovarian, hepatic, splenic, visceral, and peripheral arteries of the upper and lower limbs without overt organ or soft tissue calcifications (Fig. 1a–c). Because of the rapid progression of ischemic lesions, multiple amputations involving both lower limbs and hands became necessary. The histological examination of surgical specimens showed smallto-medium-sized muscular arteries displaying dystrophic medial calcifications that were focal or circumferential in the affected tunica media, causing luminal narrowing or sub-occlusion (Fig. 1d–f). There were no signs of atherosclerosis, and a diagnosis of MCS was made. Parathyroid ultrasound and scintigraphy revealed diffuse enlargement and hypermetabolism of the four glands. Total parathyroidectomy was performed, and histological examination of the excised glands showed diffuse hyperplasia. After parathyroidectomy, no new lesions appeared. There was a progressive healing at the sites of amputation. Chronic kidney disease (CKD) is known to be associated with bone and mineral disorders that present with laboratory alterations in Ca–P metabolism and with vascular calcifications. Vascular calcifications are not simply due to Ca–P precipitation, but result from an active, highly regulated process in which vascular smooth muscle cells (VSMCs) undergo apoptosis and are transformed into osteoblastlike cells involved in the mineralization process [1, 2]. The prevalence of vascular calcification of the media (VCm) of MCS type is estimated to be ~ 0.5% in adults, with the highest prevalence in type 2 diabetes patients. ESRD (end-stage renal disease) patients with VCm have less conventional risk factors for atherosclerosis, greater prevalence of Ca–P disorders, and a longer time on hemodialysis [3]. MCS is commonly observed in muscle-type conduit arteries, and is usually revealed in the arteries of the extremities, whereas a systemic distribution with involvement of visceral arteries appears uncommon [1]. Four stages of lesion progression are recognized in MCS. In stage 1, calcifications appear as irregular deposits within the media, they are both intracellular and extracellular: the first located in VSMCs, the second associated with damaged and fractured elastic fibers in the extracellular matrix. Then, calcifications may progress to involve up to three quadrants of the cross section (stage 2) or the entire vascular circumference (stage 3), distorting the architecture of the media. In stage 4, foci of bone formation may be found within the arterial media until they undergo osseous metaplasia giving rise to true bony trabeculae [3]. In our patient, MCS had a unique course because of the widespread distribution of vascular calcifications and the absence of classical risk factors for this complication, except for ESRD. The literature reports usually describe the involvement of arteries of the limbs; when other kinds of arteries are Domenico Corradi and Augusto Vaglio share senior authorship.