Calciphylaxis
By:
Sagar U. NigwekarDivision of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

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  • 1.

    Nigwekar SU, Thadhani R, Brandenburg VM: Calciphylaxis. N Engl J Med 378: 17041714, 2018 PubMed

  • 2.

    Nigwekar SU, Kroshinsky D, Nazarian RM, Goverman J, Malhotra R, Jackson VA, et al.: Calciphylaxis: risk factors, diagnosis, and treatment. Am J Kidney Dis 66: 133146, 2015 10.1053/j.ajkd.2015.01.034 PubMed

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  • 3.

    Polizzotto MN, Bryan T, Ashby MA, Martin P: Symptomatic management of calciphylaxis: a case series and review of the literature. J Pain Symptom Manage 32: 186190, 2006 10.1016/j.jpainsymman.2006.03.009 PubMed

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  • 4.

    Riemer CA, El-Azhary RA, Wu KL, Strand JJ, Lehman JS: Underreported use of palliative care and patient-reported outcome measures to address reduced quality of life in patients with calciphylaxis: a systematic review. Br J Dermatol 177: 15101518, 2017 10.1111/bjd.15702 PubMed

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  • 5.

    Dutta P, Chaudet KM, Nazarian RM, Kroshinsky D, Nigwekar SU: Correlation between clinical and pathological features of cutaneous calciphylaxis. PLoS One 14: e0218155, 2019 PubMed

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  • 6.

    Ghosh T, Winchester DS, Davis MDP, El-Azhary R, Comfere NI: Early clinical presentations and progression of calciphylaxis. Int J Dermatol 56: 856861, 2017 10.1111/ijd.13622 PubMed

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  • 7.

    Selye H, Gentile G, Prioreschi P: Cutaneous molt induced by calciphylaxis in the rat. Science 134: 18761877, 1961 PubMed

  • 8.

    O’Neill WC: Sodium thiosulfate: mythical treatment for a mysterious disease? Clin J Am Soc Nephrol 8: 10681069, 2013 10.2215/CJN.04990513 PubMed

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  • 9.

    Kramann R, Brandenburg VM, Schurgers LJ, Ketteler M, Westphal S, Leisten I, et al.: Novel insights into osteogenesis and matrix remodelling associated with calcific uraemic arteriolopathy. Nephrol Dial Transplant 28: 856868, 2013 10.1093/ndt/gfs466 PubMed

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  • 10.

    Weenig RH: Pathogenesis of calciphylaxis: Hans Selye to nuclear factor kappa-B. J Am Acad Dermatol 58: 458471, 2008 10.1016/j.jaad.2007.12.006 PubMed

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  • 11.

    Jeong HS, Dominguez AR: Calciphylaxis: Controversies in pathogenesis, diagnosis and treatment. Am J Med Sci 351: 217227, 2016 10.1016/j.amjms.2015.11.015 PubMed

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  • 12.

    Brandenburg VM, Kramann R, Rothe H, Kaesler N, Korbiel J, Specht P, et al.: Calcific uraemic arteriolopathy (calciphylaxis): Data from a large nationwide registry. Nephrol Dial Transplant 32: 126132, 2017 PubMed

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  • 13.

    Nigwekar SU, Zhao S, Wenger J, et al. A Nationally Representative Study of Calcific Uremic Arteriolopathy Risk Factors JASN 27: 3421–3429, 2016 DOI: ASN.2015091065 [pii]

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  • 14.

    Weenig RH, Sewell LD, Davis MD, McCarthy JT, Pittelkow MR: Calciphylaxis: natural history, risk factor analysis, and outcome. J Am Acad Dermatol 56: 569579, 2007 PubMed

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  • 15.

    McCarthy JT, El-Azhary RA, Patzelt MT, Weaver AL, Albright RC, Bridges AD, et al.: Survival, risk factors, and effect of treatment in 101 patients with calciphylaxis. Mayo Clin Proc 91: 13841394, 2016 10.1016/j.mayocp.2016.06.025 PubMed

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  • 16.

    Bajaj R, Courbebaisse M, Kroshinsky D, Thadhani RI, Nigwekar SU: Calciphylaxis in patients with normal renal function: A case series and systematic review. Mayo Clin Proc 93: 12021212, 2018 10.1016/j.mayocp.2018.06.001 PubMed

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  • 17.

    Nigwekar SU, Wolf M, Sterns RH, Hix JK: Calciphylaxis from nonuremic causes: A systematic review. Clin J Am Soc Nephrol 3: 11391143, 2008 10.2215/CJN.00530108 [doi] PubMed

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  • 18.

    Yu WY-H, Bhutani T, Kornik R, Pincus LB, Mauro T, Rosenblum MD, et al.: Warfarin-associated nonuremic calciphylaxis. JAMA Dermatol 153: 309314, 2017 PubMed

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  • 19.

    Nigwekar SU: An unusual case of nonhealing leg ulcer in a diabetic patient. South Med J 100: 851852, 2007 10.1097/SMJ.0b013e3180f6100c PubMed

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  • 20.

    Anderson DC, Stewart WK, Piercy DM: Calcifying panniculitis with fat and skin necrosis in a case of uraemia with autonomous hyperparathyroidism. Lancet 2: 323325, 1968 PubMed

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  • 21.

    Coates T, Kirkland GS, Dymock RB, Murphy BF, Brealey JK, Mathew TH, et al.: Cutaneous necrosis from calcific uremic arteriolopathy. Am J Kidney Dis 32: 384391, 1998 10.1053/ajkd.1998.v32.pm9740153 PubMed

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  • 22.

    Nigwekar SU, Solid CA, Ankers E, Malhotra R, Eggert W, Turchin A, et al.: Quantifying a rare disease in administrative data: The example of calciphylaxis. J Gen Intern Med 29[Suppl 3]: S724S731, 2014 10.1007/s11606-014-2910-1 PubMed

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  • 23.

    Sowers KM, Hayden MR: Calcific uremic arteriolopathy: Pathophysiology, reactive oxygen species and therapeutic approaches. Oxid Med Cell Longev 3: 109121, 2010 10.4161/oxim.3.2.11354 PubMed

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  • 24.

    Nigwekar SU, Bhan I, Turchin A, Skentzos SC, Hajhosseiny R, Steele D, et al.: Statin use and calcific uremic arteriolopathy: A matched case-control study. Am J Nephrol 37: 325332, 2013 10.1159/000348806 PubMed

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  • 25.

    Nigwekar SU, Nazarian RM: Cutaneous calcification in patients with kidney disease is not always calciphylaxis. Kidney Int 94: 244246, 2018 10.1016/j.kint.2018.04.019 PubMed

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  • 26.

    Hayashi M: Calciphylaxis: diagnosis and clinical features. Clin Exp Nephrol 17: 498503, 2013 10.1007/s10157-013-0782-z PubMed

  • 27.

    Zhang Y, Corapi KM, Luongo M, Thadhani R, Nigwekar SU: Calciphylaxis in peritoneal dialysis patients: A single center cohort study. Int J Nephrol Renovasc Dis 9: 235241, 2016 10.2147/IJNRD.S115701 PubMed

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  • 28.

    Ahmed S, O’Neill KD, Hood AF, Evan AP, Moe SM: Calciphylaxis is associated with hyperphosphatemia and increased osteopontin expression by vascular smooth muscle cells. Am J Kidney Dis 37: 12671276, 2001 10.1053/ajkd.2001.24533 PubMed

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  • 29.

    Gaisne R, Péré M, Menoyo V, Hourmant M, Larmet-Burgeot D: Calciphylaxis epidemiology, risk factors, treatment and survival among French chronic kidney disease patients: A case-control study. BMC Nephrol 21: 63, 2020 10.1186/s12882-020-01722-y PubMed

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  • 30.

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    Gabel C, Chakrala T, Shah R, Danesh MJ, Dobry AS, Garza-Mayers AC, et al.: Penile calciphylaxis: A retrospective case-control study. [published online ahead of print May 15, 2020] J Am Acad Dermatol 10.1016/j.jaad.2020.05.042 PubMed

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  • 32.

    Moe SM, Chen NX: Calciphylaxis and vascular calcification: A continuum of extra-skeletal osteogenesis. Pediatr Nephrol 18: 969975, 2003 10.1007/s00467-003-1276-0 PubMed

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  • 33.

    Tan RYP, Juneja R, Gunawardane DN, Milton CA: Isolated mesenteric calciphylaxis with ischemic colitis in a hemodialysis patient without active cutaneous calciphylaxis: A case report of calcific uremic arteriolopathy. Kidney Med 2: 209212, 2020 10.1016/j.xkme.2019.12.005 PubMed

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  • 34.

    Nigwekar SU: Calciphylaxis. Curr Opin Nephrol Hypertens 26: 276281, 2017 10.1097/MNH.0000000000000328 PubMed

  • 35.

    Aouizerate J, Valleyrie-Allanore L, Limal N, Ayache SS, Gherardi RK, Audard V, et al.: Ischemic myopathy revealing systemic calciphylaxis. Muscle Nerve 56: 529533, 2017 10.1002/mus.25505 PubMed

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  • 36.

    Farooqui S, Chan A, Cullen JF, Milea D: Too young to undergo temporal artery biopsy? Calciphylaxis-related anterior ischemic optic neuropathy. Neuroophthalmology 43: 252255, 2018 10.1080/01658107.2018.1493739 PubMed

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  • 37.

    Lin B, Srikanth P, Castle AC, Nigwekar S, Malhotra R, Galloway JL, et al.: Modulating cell fate as a therapeutic strategy. Cell Stem Cell 23: 329341, 2018 10.1016/j.stem.2018.05.009 PubMed

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  • 38.

    Chen NX, O’Neill K, Akl NK, Moe SM: Adipocyte induced arterial calcification is prevented with sodium thiosulfate. Biochem Biophys Res Commun 449: 151156, 2014 10.1016/j.bbrc.2014.05.005 PubMed

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  • 39.

    Dominguez AR: New debates surrounding the histopathological findings of calciphylaxis: Do these give us new insights into pathogenesis of the disease? JAMA Dermatol 155: 773775, 2019 10.1001/jamadermatol.2019.0051 PubMed

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  • 40.

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  • 41.

    Colboc H, Moguelet P, Bazin D, Carvalho P, Dillies AS, Chaby G, et al..; Groupe Angio-Dermatologie of the French Society of Dermatology: Localization, morphologic features, and chemical composition of calciphylaxis-related skin deposits in patients with calcific uremic arteriolopathy. JAMA Dermatol 155: 789796, 2019 10.1001/jamadermatol.2019.0381 PubMed

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  • 42.

    Nigwekar SU, Bloch DB, Nazarian RM, Vermeer C, Booth SL, Xu D, et al.: Vitamin K-dependent carboxylation of matrix gla protein influences the risk of calciphylaxis. J Am Soc Nephrol 28: 17171722, 2017 10.1681/ASN.2016060651 [doi] PubMed

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  • 43.

    Nigwekar SU, Thadhani R: Long-term anticoagulation for patients receiving dialysis. Circulation 138: 15301533, 2018 10.1161/CIRCULATIONAHA.118.037091 PubMed

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  • 44.

    Cozzolino M, Mangano M, Galassi A, Ciceri P, Messa P, Nigwekar S: Vitamin K in chronic kidney disease. Nutrients 11: E168, 2019 10.3390/nu11010168 PubMed

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  • 45.

    Portales-Castillo I, Kroshinsky D, Malhotra CK, Culber-Costley R, Cozzolino MG, Karparis S, et al.: Calciphylaxis as a drug induced adverse event. Expert Opin Drug Saf 18: 2935, 2019 10.1080/14740338.2019.1559813 PubMed

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  • 46.

    Galloway PA, El-Damanawi R, Bardsley V, Pritchard NR, Fry AC, Ojha SK, et al.: Vitamin K antagonists predispose to calciphylaxis in patients with end-stage renal disease. Nephron 129: 197201, 2015 10.1159/000371449 [doi] PubMed

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  • 47.

    Nigwekar SU, Jiramongkolchai P, Wunderer F, Bloch E, Ichinose R, Nazarian RM, et al.: Increased bone morphogenetic protein signaling in the cutaneous vasculature of patients with calciphylaxis. Am J Nephrol 46: 429438, 2017 10.1159/000484418 PubMed

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  • 48.

    Mochel MC, Arakaki RY, Wang G, Kroshinsky D, Hoang MP: Cutaneous calciphylaxis: A retrospective histopathologic evaluation. Am J Dermatopathol 35: 582586, 2013 10.1097/DAD.0b013e31827c7f5d PubMed

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  • 49.

    Au S, Crawford RI: Three-dimensional analysis of a calciphylaxis plaque: Clues to pathogenesis. J Am Acad Dermatol 47: 5357, 2002 PubMed

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  • 50.

    Hayden MR, Kolb LG, Khanna R: Calciphylaxis and the cardiometabolic syndrome. J Cardiometab Syndr 1: 7679, 2006 PubMed

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    Janigan DT, Hirsch DJ, Klassen GA, MacDonald AS: Calcified subcutaneous arterioles with infarcts of the subcutis and skin (“calciphylaxis”) in chronic renal failure. Am J Kid Dis 35: 588597, 2000

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  • 52.

    El-Azhary RA, Patzelt MT, McBane RD, Weaver AL, Albright RC, Bridges AD, et al.: Calciphylaxis: A disease of pannicular thrombosis. Mayo Clin Proc 91: 13951402, 2016 10.1016/j.mayocp.2016.06.026 PubMed

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  • 53.

    Dobry AS, Ko LN, St John J, Sloan JM, Nigwekar S, Kroshinsky D: Association between hypercoagulable conditions and calciphylaxis in patients with renal disease: A case-control study. JAMA Dermatol 154: 182187, 2018 PubMed

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  • 54.

    Ruderman I, Toussaint ND, Hawley CM, Krishnasamy R, Pedagogos E, Lioufas N, et al.: The Australian Calciphylaxis Registry: Reporting clinical features and outcomes of patients with calciphylaxis. [published online ahead of print December 19, 2019]. Nephrol Dial Transplant 10.1093/ndt/gfz256 PubMed

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  • 55.

    Brandenburg VM, Sinha S: Calciphylaxis: Another piece of the puzzle. Am J Nephrol 46: 427428, 2017 10.1159/000484545 PubMed

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    Nigwekar SU, Brunelli SM, Meade D, Wang W, Hymes J, Lacson E Jr: Sodium thiosulfate therapy for calcific uremic arteriolopathy. Clin J Am Soc Nephrol 8: 11621170, 2013 10.2215/CJN.09880912 PubMed

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  • 57.

    Fine A, Zacharias J: Calciphylaxis is usually non-ulcerating: Risk factors, outcome and therapy. Kidney Int 61: 22102217, 2002 10.1046/j.1523-1755.2002.00375.x PubMed

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  • 59.

    Li JY, Yong TY, Choudhry M, Rao N, Milton C, Juneja R, et al.: Successful treatment of calcific uremic arteriolopathy with sodium thiosulfate in a renal transplant recipient. Ren Fail 34: 645648, 2012 10.3109/0886022X.2012.656560 PubMed

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  • 60.

    Adapa S, Naramala S, Gayam V, Koduri NM, Daggubati SR, Patel P, et al.: Calciphylaxis in a patient on home hemodialysis. J Investig Med High Impact Case Rep 8: 2324709620922718, 2020 10.1177/2324709620922718 PubMed

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  • 61.

    Kale G, Jeloka T, Shrividya S, Mulay A, Deshmukh M, Krishnan S, et al.: Calciphylaxis in a renal transplant recipient with normal graft function: A case report and review of literature. Saudi J Kidney Dis Transpl 30: 215220, 2019 PubMed

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  • 62.

    Floege J, Kubo Y, Floege A, Chertow GM, Parfrey PS: The Effect of Cinacalcet on Calcific Uremic Arteriolopathy Events in Patients Receiving Hemodialysis: The EVOLVE trial. Clin J Am Soc Nephrol 10: 800807, 2015 10.2215/CJN.10221014 PubMed

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  • 63.

    Hayashi M, Takamatsu I, Kanno Y, Yoshida T, Abe T, Sato Y; Japanese Calciphylaxis Study Group: A case-control study of calciphylaxis in Japanese end-stage renal disease patients. Nephrol Dial Transplant 27: 15801584, 2012 10.1093/ndt/gfr658 PubMed

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  • 64.

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  • 66.

    Allegretti AS, Nazarian RM, Goverman J, Nigwekar SU: Calciphylaxis: A rare but fatal delayed complication of Roux-en-Y gastric bypass surgery. Am J Kidney Dis 64: 274277, 2014 10.1053/j.ajkd.2014.02.029 PubMed

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  • 67.

    Liebman TN, Tamez R, Daly JA: Calciphylaxis in association with alcoholic cirrhosis and hepatorenal syndrome. Skinmed 18: 4649, 2020 PubMed

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    Harris RJ, Cropley TG: Possible role of hypercoagulability in calciphylaxis: Review of the literature. J Am Acad Dermatol 64: 405412, 2011 10.1016/j.jaad.2009.12.007 PubMed

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    Zechlinski JJ, Angel JR: Calciphylaxis in the absence of renal disease: Secondary hyperparathyroidism and systemic lupus erythematosus. J Rheumatol 36: 23702371, 2009 10.3899/jrheum.090252 PubMed

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  • 72.

    Malabu UH, Roberts LJ, Sangla KS: Calciphylaxis in a morbidly obese woman with rheumatoid arthritis presenting with severe weight loss and vitamin D deficiency. Endocr Pract 17: e104e108, 2011 10.4158/EP11099.CR PubMed

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    Chaudet KM, Dutta P, Nigwekar SU, Nazarian RM: Calciphylaxis-associated cutaneous vascular calcification in noncalciphylaxis patients. Am J Dermatopathol 42: 557563, 2020 10.1097/DAD.0000000000001519 PubMed

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    Ellis CL, O’Neill WC: Questionable specificity of histologic findings in calcific uremic arteriolopathy. Kidney Int 94: 390395, 2018 10.1016/j.kint.2018.03.016 PubMed

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    Musso CG, Enz PA, Kowalczuk A, Cozzolino M, Brandenburg V, Nigwekar S: Differential diagnosis of calciphylaxis in chronic dialysis patients. Int Urol Nephrol 52: 595597, 2020 PubMed

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  • 83.

    Bahrani E, Perkins IU, North JP: Diagnosing calciphylaxis: A review with emphasis on histopathology. Am J Dermatopathol 42: 471480, 2020 10.1097/DAD.0000000000001526 PubMed

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    McMullen ER, Harms PW, Lowe L, Fullen DR, Chan MP: Clinicopathologic features and calcium deposition patterns in calciphylaxis: Comparison with gangrene, peripheral artery disease, chronic stasis, and thrombotic vasculopathy. Am J Surg Pathol 43: 12731281, 2019 PubMed

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    Williams EA, Moy AP, Cipriani NA, Nigwekar SU, Nazarian RM: Factors associated with false-negative pathologic diagnosis of calciphylaxis. J Cutan Pathol 46: 1625, 2019 10.1111/cup.13364 PubMed

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    Bonchak JG, Park KK, Vethanayagamony T, Sheikh MM, Winterfield LS: Calciphylaxis: A case series and the role of radiology in diagnosis. Int J Dermatol 55: e275e279, 2016 10.1111/ijd.13043 PubMed

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  • 88.

    Paul S, Rabito CA, Vedak P, Nigwekar SU, Kroshinsky D: The role of bone scintigraphy in the diagnosis of calciphylaxis. JAMA Dermatol 153: 101103, 2017 10.1001/jamadermatol.2015.4591 PubMed

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  • 89.

    Shmidt E, Murthy NS, Knudsen JM, Weenig RH, Jacobs MA, Starnes AM, et al.: Net-like pattern of calcification on plain soft-tissue radiographs in patients with calciphylaxis. J Am Acad Dermatol 67: 12961301, 2012 10.1016/j.jaad.2012.05.037 PubMed

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  • 90.

    Alniemi DT, Kanner C, Stowman AM, Knapp M, McGevna L, Seward DJ, et al.: Diagnosing calciphylaxis: A series of cases with both imaging and tissue biopsy. [published online ahead of print June 8, 2020]. J Am Acad Dermatol 10.1016/j.jaad.2020.05.111 PubMed

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  • 91.

    Lloyd WR, Agarwal S, Nigwekar SU, Esmonde-White K, Loder S, Fagan S, et al.: Raman spectroscopy for label-free identification of calciphylaxis. J Biomed Opt 20: 80501, 2015 10.1117/1.JBO.20.8.080501 PubMed

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  • 93.

    Hafner J: Calciphylaxis and Martorell hypertensive ischemic leg ulcer: Same pattern - one pathophysiology. Dermatology 232: 523533, 2016 10.1159/000448245 PubMed

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    Nazarian RM, Van Cott EM, Zembowicz A, Duncan LM: Warfarin-induced skin necrosis. J Am Acad Dermatol 61: 325332, 2009 10.1016/j.jaad.2008.12.039 PubMed

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