Localization, Morphologic Features, and Chemical Composition of Calciphylaxis-Related Skin Deposits in Patients With Calcific Uremic Arteriolopathy

Abstract

; for the Groupe Angio-Dermatologie of the French Society of Dermatology IMPORTANCE Calcific uremic arteriolopathy (CUA), a rare, potentially fatal, disease with calcium deposits in skin, mostly affects patients with end-stage renal disease who are receiving dialysis. Chemical composition and structure of CUA calcifications have been poorly described. OBJECTIVES To describe the localization and morphologic features and determine the precise chemical composition of CUA-related calcium deposits in skin, and identify any mortality-associated factors. DESIGN, SETTING, AND PARTICIPANTS A retrospective, multicenter cohort study was conducted at 7 French hospitals including consecutive adults diagnosed with CUA between January 1, 2006, and January 1, 2017, confirmed according to Hayashi clinical and histologic criteria. Patients with normal renal function were excluded. For comparison, 5 skin samples from patients with arteriolosclerosis and 5 others from the negative margins of skin-carcinoma resection specimens were also analyzed. MAIN OUTCOMES AND MEASURES Localization and morphologic features of the CUA-related cutaneous calcium deposits were assessed with optical microscopy and field-emissionscanning electron microscopy, and the chemical compositions of those deposits were evaluated with μ Fourier transform infrared spectroscopy, Raman spectroscopy, and energy dispersive radiographs. RESULTS Thirty-six patients (median [range] age, 64 [33-89] years; 26 [72%] female) were included, and 29 cutaneous biopsies were analyzed. Calcific uremic arteriolopathy and arteriolosclerosis skin calcifications were composed of pure calcium-phosphate apatite. Calcific uremic arteriolopathy vascular calcifications were always circumferential, found in small to medium-sized vessels, with interstitial deposits in 22 (76%) of the samples. A thrombosis, most often in noncalcified capillary lumens in the superficial dermis, was seen in 5 samples from patients with CUA. Except for calcium deposits, the vessel structure of patients with CUA appeared normal, unlike thickened arteriolosclerotic vessel walls. Twelve (33%) patients died of CUA. CONCLUSIONS AND RELEVANCE Calcific uremic arteriolopathy-related skin calcifications were exclusively composed of pure calcium-phosphate apatite, localized circumferentially in small to medium-sized vessels and often associated with interstitial deposits, suggesting its pathogenesis differs from that of arteriolosclerosis. Although the chemical compositions of CUA and arteriolosclerosis calcifications were similar, the vessels' appearances and deposit localizations differed, suggesting different pathogenetic mechanisms.

Crystalline pathologies in the human body: first steps of pathogenesis

“…Les figures 7A et 7B montrent une colocalisation de l'ADN mise en évidence par une coloration DAPI et la calcification mise en évidence par une coloration avec le « von Kossa ». Dans le cas de l'artériolosclérose (figures 7C et 7D), la coloration au « von Kossa » montre clairement que la calcification suit les fibres présentes dans la paroi de l'artère [33]. Dans le cas de la calciphylaxie (figures 7E et 7F), la localisation des calcifications peut être complètement différente puisque celle-ci se situe dans la lumière du vaisseau [33].…”

“…Dans le cas de l'artériolosclérose (figures 7C et 7D), la coloration au « von Kossa » montre clairement que la calcification suit les fibres présentes dans la paroi de l'artère [33]. Dans le cas de la calciphylaxie (figures 7E et 7F), la localisation des calcifications peut être complètement différente puisque celle-ci se situe dans la lumière du vaisseau [33]. Cette distinction sur la localisation des calcifications n'est pas sans rappeler ce que l'on observe pour les calcifications ectopiques présentes dans une biopsie rénale [34].…”

Scanning electron microscopy—a powerful imaging technique for the clinician

“…Scanning and transmission mode electron microscopy of biopsies has been performed for several decades [118][119][120][121][122]. In our investigations, we have used FE-SEM on human biopsy tissue coming from various organs namely kidney [123][124][125][126], pancreas [127], skin [128][129][130][131], hairs [132], breast [26], thyroid [133,134], or arterial wall [135], but of course we must stress that such opportunities exist for cells and mice as well [136][137][138][139][140].…”

Calcifilaxis. Comunicación de un caso

“…La tinción con Von Kossa demuestra la presencia de calcificación en los vasos sanguíneos. 9 La tomografía computarizada SPECT-CT muestra los sitios de calcificación vascular. Tiene sensibilidad de 87% y especificidad de 97%.…”