Hester Colboc1,2, Philippe Moguelet3, Dominique Bazin4, Priscille Carvalho5, Anne-Sophie Dillies6, Guillaume Chaby6, Hervé Maillard7, Diane Kottler8, Elisa Goujon9, Christine Jurus10, Marine Panaye10, Vincent Frochot11, Emmanuel Letavernier2,12, Michel Daudon11, Ivan Lucas13, Raphaël Weil14, Philippe Courville15, Jean-Benoit Monfort16, François Chasset16, Patricia Senet16. 1. Service Plaies et Cicatrisation, Sorbonne Université, Hôpital Rothschild, Paris, France. 2. Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) S 1155, Paris, France. 3. Anatomie et Cytologie Pathologiques, Sorbonne Université, Hôpital Tenon, Paris, France. 4. Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie Physique, Ba340, Université Paris XI, Orsay, France. 5. Service de Dermatologie, Centre Hospitalier Universitaire de Rouen, Rouen, France. 6. Service de Dermatologie, Centre Hospitalier Universitaire d'Amiens, Amiens, France. 7. Service de Dermatologie, Centre Hospitalier du Mans, Le Mans, France. 8. Service de Dermatologie, Hôpital Bichat, Paris, France. 9. Service de Dermatologie, Centre Hospitalier de Chalon-sur-Saône, Chalon-sur-Saône, France. 10. Service de Médecine Vasculaire, Clinique du Tonkin, Villeurbanne, France. 11. Service des Explorations Fonctionnelles Multidisciplinaires, Sorbonne Université, Hôpital Tenon, Paris, France. 12. Sorbonne Université, Hôpital Tenon, Service des Explorations Fonctionnelles Multidisciplinaires, Paris. 13. Sorbonne Universités, Unité Mixte de Recherche (UMR) 8235, Paris, France. 14. Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique des Solides, Ba510, Université Paris XI, Orsay, France. 15. Centre Hospitalier Universitaire de Rouen, Anatomie et Cytologie Pathologiques, Rouen, France. 16. Service de Dermatologie, Sorbonne Université, Hôpital Tenon, Paris, France.
Abstract
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-emission-scanning 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.
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-emission-scanning 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.
Authors: Sagar U Nigwekar; Donald B Bloch; Rosalynn M Nazarian; Cees Vermeer; Sarah L Booth; Dihua Xu; Ravi I Thadhani; Rajeev Malhotra Journal: J Am Soc Nephrol Date: 2017-01-03 Impact factor: 10.121
Authors: H Colboc; P Moguelet; D Bazin; C Bachmeyer; V Frochot; R Weil; E Letavernier; C Jouanneau; M Daudon; J F Bernaudin Journal: J Eur Acad Dermatol Venereol Date: 2018-07-31 Impact factor: 6.166
Authors: Eugenia Shmidt; Naveen S Murthy; John M Knudsen; Roger H Weenig; M Amanda Jacobs; Autumn M Starnes; Mark D P Davis Journal: J Am Acad Dermatol Date: 2012-07-28 Impact factor: 11.527
Authors: William R Lloyd; Shailesh Agarwal; Sagar U Nigwekar; Karen Esmonde-White; Shawn Loder; Shawn Fagan; Jeremy Goverman; Bjorn R Olsen; Dolrudee Jumlongras; Michael D Morris; Benjamin Levi Journal: J Biomed Opt Date: 2015-08 Impact factor: 3.170