Case and Research Letters
Atypical Calciphylaxis Secondary to Treatment With Acenocoumarol
Calcifilaxia atípica secundaria al tratamiento con acenocumarol
A. Álvarez-Pérez
, E. Gutiérrez-González, D. Sánchez-Aguilar, J. Toribio
Corresponding author
Departamento de Dermatología, Complejo Hospitalario Universitario, Facultad de Medicina, Santiago de Compostela, Spain
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Álvarez-Pérez, E. Gutiérrez-González, D. Sánchez-Aguilar, J. Toribio" "autores" => array:4 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Álvarez-Pérez" "email" => array:1 [ 0 => "adriana_alpe@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "E." "apellidos" => "Gutiérrez-González" ] 2 => array:2 [ "nombre" => "D." "apellidos" => "Sánchez-Aguilar" ] 3 => array:2 [ "nombre" => "J." "apellidos" => "Toribio" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Departamento de Dermatología, Complejo Hospitalario Universitario, Facultad de Medicina, Santiago de Compostela, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Calcifilaxia atípica secundaria al tratamiento con acenocumarol" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 749 "Ancho" => 499 "Tamanyo" => 59202 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Ulcer with necrotic eschar surrounded by a reticular purpuric plaque on the back of the left leg.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Calciphylaxis is a rare disease characterized by cutaneous ischemia and necrosis caused by mural calcification of small and medium-sized blood vessels.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> This condition leads to cutaneous ulceration and eschar formation. It generally affects patients with end-stage renal failure and secondary hyperparathyroidism,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a> and is associated with a poor prognosis, high morbidity, and high mortality rates.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–4</span></a> In recent years, cases have been reported of calciphylaxis in patients with normal kidney function and calcium–phosphate metabolism.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4–7</span></a> When seen in patients without abnormalities of this sort—a rather rare occurrence—the condition is called atypical calciphylaxis.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> It has occasionally been reported in patients receiving oral anticoagulant therapy with coumarin derivatives, such as warfarin and phenprocoumon.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4,6,7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of an 80-year-old woman who came to our hospital with purpuric skin lesions in a livedoid pattern that had appeared 2 months earlier on the back of the right leg. The lesions were associated with induration and intense local pain. Several weeks after the onset of the first symptoms, the patient noticed the appearance of an ulcer, which was quickly covered by necrotic eschar. Similar intensely painful skin lesions began to appear on the left leg at the same time.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Relevant aspects of her medical history included diabetes mellitus, bronchial asthma, arterial hypertension, and atrial fibrillation. Current medication included acenocoumarol (which she had been taking for 1 year), acetaminophen, omeprazole, diltiazem, metformin, tiotropium bromide, and a formoterol–budesonide combination.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Dermatological examination revealed a well-defined and extremely painful ulcer on the back of the patient's left leg (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The lesion was covered with eschar and surrounded by a racemose erythematous-violaceous plaque. Livedo reticularis was observed on the back of both legs. The skin lesions and the underlying area were indurated on palpation. The patient's right leg had similar lesions, but without necrotic eschar. The physical examination was otherwise normal.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Testing revealed normal levels of urea, creatinine, parathyroid hormone, calcium, serum phosphate, protein C, and protein S. The patient tested negative for cryoglobulins and for antinuclear and anticardiolipin antibodies. Radiographs of both legs showed marked vascular calcification.</p><p id="par0030" class="elsevierStylePara elsevierViewall">A skin biopsy of the affected area revealed superficial ulceration with necrosis of the superficial dermal collagen, as well as extensive calcification and intimal proliferation in multiple arteries and arterioles (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The calcium deposits in the blood vessel walls were more visible with Von Kossa staining. As there were no extravascular calcium deposits or fat necrosis, the diagnosis of calciphylaxis was confirmed. Because the patient had normal levels of protein C, protein S, parathyroid hormone, calcium, and serum phosphate, a diagnosis of atypical calciphylaxis was established.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">In this case the condition was associated with treatment with coumarin derivatives, a phenomenon that has recently been described in the literature. Acenocoumarol was withdrawn and the patient was prescribed enoxaparin anticoagulant therapy at a dose of 1<span class="elsevierStyleHsp" style=""></span>mg/kg every 12<span class="elsevierStyleHsp" style=""></span>h, which led to rapid improvement in both the lesion and local pain. Moreover, the ulcer gradually healed and the livedo rash resolved.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Calciphylaxis is considered atypical when it occurs in patients who do not have renal failure or impaired calcium–phosphate metabolism.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In such cases, we must consider that the disease may be the result of the interaction between various risk factors, including obesity, liver disease, systemic corticosteroid therapy, elevated erythrocyte sedimentation rate, white race, female sex, warfarin therapy, vitamin D supplementation, protein C or protein S deficiency, and diabetes mellitus.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Our patient's kidney and parathyroid function were normal, but other risk factors were present; she was white, she had diabetes mellitus, and she was receiving acenocoumarol, a coumarin-derived oral anticoagulant. Since the anticoagulant treatment was the only risk factor that could be modified, it was withdrawn and replaced with low-molecular-weight heparin, the recommended anticoagulant for patients of these characteristics.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Atypical calciphylaxis has occasionally been described in association with oral coumarin-derived anticoagulants, which interact with the calcification inhibitor matrix gla protein.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The differential diagnosis should consider warfarin-induced skin necrosis, which normally appears 3–10 days after start of treatment and is caused by an imbalance between procoagulant and anticoagulant factors. Histopathology of this condition reveals thrombotic occlusion of dermal and subcutaneous venules and veins, surrounded by diffuse fat necrosis and bleeding,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> but no calcification of the blood vessel walls, unlike the case of our patient.</p><p id="par0055" class="elsevierStylePara elsevierViewall">None of the authors in the literature reviewed indicated an association between atypical calciphylaxis and acenocoumarol anticoagulant therapy. Risk factor modification should be considered whenever possible. In our case, the cessation of acenocoumarol was decisive in the favorable evolution of the disease.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Álvarez-Pérez A, Gutiérrez-González E, Sánchez-Aguilar D, Toribio J. Calcifilaxia atípica secundaria al tratamiento con acenocumarol. Actas Dermosifiliogr. 2012;103:79–81.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 749 "Ancho" => 499 "Tamanyo" => 59202 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Ulcer with necrotic eschar surrounded by a reticular purpuric plaque on the back of the left leg.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 628 "Ancho" => 948 "Tamanyo" => 174422 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Skin biopsy showing intramural calcification and intimal hyperplasia in an arteriole of the subcutaneous tissue (hematoxylin–eosin, original magnification ×400).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Calciphylaxis—a topical overview" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. 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Lahey" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/1076029609355588" "Revista" => array:6 [ "tituloSerie" => "Clin Appl Thromb Hemost" "fecha" => "2010" "volumen" => "16" "paginaInicial" => "345" "paginaFinal" => "350" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20019019" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Calciphylaxis in a diabetic patient provoked by warfarin therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "N. Asobie" 1 => "E. Wong" 2 => "M.G. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 5 | 11 |
| 2024 October | 68 | 54 | 122 |
| 2024 September | 82 | 36 | 118 |
| 2024 August | 109 | 61 | 170 |
| 2024 July | 88 | 48 | 136 |
| 2024 June | 91 | 54 | 145 |
| 2024 May | 94 | 68 | 162 |
| 2024 April | 71 | 32 | 103 |
| 2024 March | 87 | 40 | 127 |
| 2024 February | 66 | 36 | 102 |
| 2024 January | 47 | 35 | 82 |
| 2023 December | 55 | 16 | 71 |
| 2023 November | 54 | 39 | 93 |
| 2023 October | 50 | 23 | 73 |
| 2023 September | 72 | 34 | 106 |
| 2023 August | 41 | 29 | 70 |
| 2023 July | 63 | 34 | 97 |
| 2023 June | 53 | 25 | 78 |
| 2023 May | 45 | 25 | 70 |
| 2023 April | 40 | 21 | 61 |
| 2023 March | 36 | 26 | 62 |
| 2023 February | 35 | 22 | 57 |
| 2023 January | 39 | 32 | 71 |
| 2022 December | 55 | 35 | 90 |
| 2022 November | 21 | 20 | 41 |
| 2022 October | 29 | 20 | 49 |
| 2022 September | 21 | 35 | 56 |
| 2022 August | 16 | 35 | 51 |
| 2022 July | 30 | 31 | 61 |
| 2022 June | 45 | 27 | 72 |
| 2022 May | 45 | 33 | 78 |
| 2022 April | 84 | 32 | 116 |
| 2022 March | 53 | 54 | 107 |
| 2022 February | 43 | 29 | 72 |
| 2022 January | 38 | 41 | 79 |
| 2021 December | 37 | 31 | 68 |
| 2021 November | 45 | 55 | 100 |
| 2021 October | 46 | 59 | 105 |
| 2021 September | 32 | 42 | 74 |
| 2021 August | 37 | 30 | 67 |
| 2021 July | 47 | 35 | 82 |
| 2021 June | 33 | 39 | 72 |
| 2021 May | 41 | 41 | 82 |
| 2021 April | 78 | 39 | 117 |
| 2021 March | 83 | 23 | 106 |
| 2021 February | 59 | 28 | 87 |
| 2021 January | 50 | 17 | 67 |
| 2020 December | 27 | 16 | 43 |
| 2020 November | 31 | 15 | 46 |
| 2020 October | 21 | 15 | 36 |
| 2020 September | 32 | 27 | 59 |
| 2020 August | 33 | 14 | 47 |
| 2020 July | 29 | 14 | 43 |
| 2020 June | 42 | 26 | 68 |
| 2020 May | 34 | 12 | 46 |
| 2020 April | 35 | 16 | 51 |
| 2020 March | 27 | 25 | 52 |
| 2020 February | 5 | 1 | 6 |
| 2020 January | 6 | 3 | 9 |
| 2019 December | 4 | 3 | 7 |
| 2019 November | 4 | 1 | 5 |
| 2019 October | 0 | 5 | 5 |
| 2019 September | 0 | 2 | 2 |
| 2019 August | 4 | 1 | 5 |
| 2019 July | 4 | 6 | 10 |
| 2019 June | 4 | 36 | 40 |
| 2019 May | 7 | 29 | 36 |
| 2019 April | 2 | 27 | 29 |
| 2019 March | 2 | 7 | 9 |
| 2019 February | 0 | 3 | 3 |
| 2019 January | 3 | 0 | 3 |
| 2018 November | 1 | 0 | 1 |
| 2018 October | 2 | 0 | 2 |
| 2018 September | 3 | 2 | 5 |
| 2018 August | 1 | 7 | 8 |
| 2018 July | 0 | 4 | 4 |
| 2018 June | 0 | 1 | 1 |
| 2018 May | 0 | 3 | 3 |
| 2018 March | 0 | 5 | 5 |
| 2018 February | 50 | 5 | 55 |
| 2018 January | 75 | 9 | 84 |
| 2017 December | 73 | 11 | 84 |
| 2017 November | 65 | 12 | 77 |
| 2017 October | 46 | 12 | 58 |
| 2017 September | 52 | 8 | 60 |
| 2017 August | 76 | 10 | 86 |
| 2017 July | 64 | 6 | 70 |
| 2017 June | 75 | 15 | 90 |
| 2017 May | 76 | 17 | 93 |
| 2017 April | 66 | 9 | 75 |
| 2017 March | 60 | 16 | 76 |
| 2017 February | 54 | 15 | 69 |
| 2017 January | 48 | 15 | 63 |
| 2016 December | 65 | 19 | 84 |
| 2016 November | 89 | 21 | 110 |
| 2016 October | 124 | 26 | 150 |
| 2016 September | 205 | 14 | 219 |
| 2016 August | 128 | 27 | 155 |
| 2016 July | 59 | 82 | 141 |
| 2016 June | 14 | 21 | 35 |
| 2016 May | 10 | 9 | 19 |
| 2016 April | 9 | 3 | 12 |
| 2016 March | 7 | 3 | 10 |
| 2016 February | 14 | 11 | 25 |
| 2016 January | 11 | 2 | 13 |
| 2015 December | 8 | 1 | 9 |
| 2015 November | 26 | 10 | 36 |
| 2015 October | 41 | 13 | 54 |
| 2015 September | 18 | 7 | 25 |
| 2015 August | 20 | 1 | 21 |
| 2015 July | 122 | 9 | 131 |
| 2015 June | 97 | 28 | 125 |
| 2015 May | 132 | 27 | 159 |
| 2015 April | 126 | 16 | 142 |
| 2015 March | 85 | 12 | 97 |
| 2015 February | 72 | 11 | 83 |
| 2015 January | 90 | 10 | 100 |
| 2014 December | 85 | 17 | 102 |
| 2014 November | 52 | 8 | 60 |
| 2014 October | 77 | 16 | 93 |
| 2014 September | 62 | 15 | 77 |
| 2014 August | 57 | 14 | 71 |
| 2014 July | 93 | 19 | 112 |
| 2014 June | 103 | 12 | 115 |
| 2014 May | 136 | 14 | 150 |
| 2014 April | 70 | 15 | 85 |
| 2014 March | 79 | 17 | 96 |
| 2014 February | 67 | 21 | 88 |
| 2014 January | 55 | 12 | 67 |
| 2013 December | 34 | 10 | 44 |
| 2013 November | 17 | 12 | 29 |
| 2013 October | 13 | 10 | 23 |
| 2013 September | 12 | 8 | 20 |
| 2013 August | 16 | 23 | 39 |
| 2013 July | 20 | 14 | 34 |
| 2013 June | 14 | 28 | 42 |
| 2013 May | 15 | 20 | 35 |
| 2013 April | 9 | 8 | 17 |
| 2013 March | 16 | 6 | 22 |
| 2013 February | 21 | 4 | 25 |
| 2013 January | 72 | 9 | 81 |
| 2012 December | 16 | 5 | 21 |
| 2012 November | 0 | 2 | 2 |
| 2012 October | 2 | 4 | 6 |
| 2012 September | 0 | 9 | 9 |
| 2012 August | 1 | 0 | 1 |
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