Case and Research Letters
Intralesional Sodium Thiosulfate to Treat Calciphylaxis
Calcifilaxis tratada con tiosulfato sódico intralesional
L. Ossorio-García
, D. Jiménez-Gallo, C. Arjona-Aguilera, M. Linares-Barrios
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Unidad de Gestión Clínica de Dermatología Médico-Quirúrgica y Venereología, Hospital Universitario Puerta del Mar, Cádiz, Spain
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Ossorio-García, D. Jiménez-Gallo, C. Arjona-Aguilera, M. Linares-Barrios" "autores" => array:4 [ 0 => array:4 [ "nombre" => "L." "apellidos" => "Ossorio-García" "email" => array:2 [ 0 => "lidia.osga@gmail.com" 1 => "lidia.ossoriogarcia@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "D." "apellidos" => "Jiménez-Gallo" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Arjona-Aguilera" ] 3 => array:2 [ "nombre" => "M." "apellidos" => "Linares-Barrios" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Unidad de Gestión Clínica de Dermatología Médico-Quirúrgica y Venereología, Hospital Universitario Puerta del Mar, Cádiz, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Calcifilaxis tratada con tiosulfato sódico intralesional" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1350 "Ancho" => 1800 "Tamanyo" => 718083 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A and B, Skin ulcers with necrotic slough on a background of livedo racemosa and retiform purpura secondary to calciphylaxis. C and D, Healing of the calciphylaxis-induced ulcers after treatment with intralesional sodium thiosulfate.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Calciphylaxis or calcifying uremic arteriopathy is characterized by calcification of the media of the small arteries and arterioles of the skin, provoking cutaneous ischemia.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A 45-year-old woman with end-stage renal disease (ESRD) secondary to glomerulonephritis and on hemodialysis since 2008, consulted for a 10-month history of multiple, intensely painful ulcers on both lower limbs; the pain was resistant to opioids. She had previously undergone kidney transplant with subsequent rejection. Physical examination of the lower limbs revealed multiple skin ulcers, some with necrotic slough, on a background of livedo racemosa and retiform purpura. The largest ulcer measured approximately 6<span class="elsevierStyleHsp" style=""></span>cm in diameter (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>, A and B). Important findings on the blood tests were secondary hyperparathyroidism with parathormone levels of 911<span class="elsevierStyleHsp" style=""></span>pg/mL, calcium 10.1<span class="elsevierStyleHsp" style=""></span>mg/dL (normal range, 8.2-10.3<span class="elsevierStyleHsp" style=""></span>mg/dL), and phosphorus, 7.7<span class="elsevierStyleHsp" style=""></span>mg/dL (normal range, 2.7-4.5<span class="elsevierStyleHsp" style=""></span>mg/dL). Other additional tests, including complete blood count, general biochemistry, coagulation, serology for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus, hypercoagulability study, autoimmunity, microbiology culture, and echocardiography were normal or negative. Skin biopsy was compatible with calciphylaxis (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">After signing the informed consent, the patient started off-label treatment with intralesional sodium thiosulfate 1/6<span class="elsevierStyleHsp" style=""></span>molar, injecting 10<span class="elsevierStyleHsp" style=""></span>mL of the solution around the borders of the ulcers. The only adverse effect was pain during the injection; this improved when oral transmucosal fentanyl was administered prior to the injections. After the first treatment, the patient reported rapid pain relief that enabled the opioids to be withdrawn. The treatment was repeated each month for 6 months, achieving complete remission of all the skin ulcers (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C and D). Maintenance therapy was then administered with an intravenous sodium thiosulfate regimen after each hemodialysis session. At 6 months the patient returned to outpatients with new lesions. A further 3 monthly injections of sodium thiosulfate were therefore administered, and remission of the lesions was once again achieved. The patient now receives injections intermittently, whenever new symptoms develop, and overall control of the disease is good.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Calciphylaxis is characterized by the appearance of very painful skin ulcers and necrosis, mainly affecting patients with ESRD on hemodialysis, with an estimated prevalence between 1% and 4% in these patients.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1–3</span></a> Mortality is high and is most commonly due to sepsis.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> Cases of ischemia of internal organs have been reported.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Risk factors for the onset of calciphylaxis in patients with ESRD are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> Calciphylaxis has been described in patients without uremia. These cases are associated with primary hyperparathyroidism, malignancy, alcoholic liver disease, and connective tissue diseases, and are grouped under the name calcific nonuremic arteriolopathy.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Clinically, calciphylaxis manifests as a livedo racemosa syndrome that progresses to retiform purpura and skin necrosis with the formation of very painful ulcers.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">6–8</span></a> In <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> we describe the differential diagnosis and workup of this syndrome.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Diagnosis is mainly clinical. Skin biopsy is the gold-standard test for the diagnosis of calciphylaxis, although systematically performing biopsies when this disease is suspected is not recommended because of the risk of infection or poor wound healing. Histopathology findings include calcification of the media of small arteries and arterioles, intimal proliferation, small-vessel thrombosis and endovascular fibrosis, necrosis of the subcutaneous cellular tissue, and panniculitis.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> No laboratory alterations specific to this disease have been detected. However, the presence of an elevated calcium-phosphate product increases the sensitivity for its detection.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Among the imaging studies, ultrasound may show hyperechoic foci with a posterior acoustic shadow suggestive of calcifications. Modified mammography can facilitate early diagnosis of calciphylaxis. A bone scan can be useful to detect calcium deposits in the subcutaneous cellular tissue and thus help to define the extent of the disease and evaluate the response to treatment.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Treatment protocols have not been standardized. Treatment is based mainly on the use of bisphosphonates and intravenous sodium thiosulfate. Sodium thiosulfate acts as an antioxidant and vasodilator, producing rapid pain relief, and as an intravascular and intraparenchymal chelator of calcium salts.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> Intravenous sodium thiosulfate is used at a dose of 25<span class="elsevierStyleHsp" style=""></span>mg immediately after each hemodialysis session. This treatment is considered innocuous and is inexpensive. The most common side effects are nausea and vomiting, rhinorrhea, and headache. The most serious adverse effect is metabolic acidosis.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In the scientific literature, only Strazzula et al.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a> have described the use of intralesional sodium thiosulfate in 4 patients with calciphylaxis.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Although further studies are necessary to evaluate the therapeutic effect of intralesional sodium thiosulfate, we would like to draw attention to certain aspects. Intralesional treatment was very successful and led to rapid relief of the ischemic pain caused by calciphylaxis. In our patient, this intralesional treatment led to complete healing of the calciphylaxis-induced skin lesions, an objective not achieved with intravenous administration. We therefore consider that for cases that do not respond to standard intravenous treatment, the adjuvant role of intralesional sodium thiosulfate should be evaluated. The tolerance of the combined treatments was good, and although pain was the main limitation, it could be reduced by the previous administration of analgesia.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of Interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Ossorio-García L, Jiménez-Gallo D, Arjona-Aguilera C, Linares-Barrios M. Calcifilaxis tratada con tiosulfato sódico intralesional. Actas Dermosifiliogr. 2016;107:360–363.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1350 "Ancho" => 1800 "Tamanyo" => 718083 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A and B, Skin ulcers with necrotic slough on a background of livedo racemosa and retiform purpura secondary to calciphylaxis. C and D, Healing of the calciphylaxis-induced ulcers after treatment with intralesional sodium thiosulfate.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 727 "Ancho" => 995 "Tamanyo" => 146156 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Biopsy showing calcification of the media of blood vessels in the subcutaneous cellular tissue. Hematoxylin and eosin, original magnification ×200).</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hyperparathyroidism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Calcium-phosphate product<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>70 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vitamin D treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diabetes mellitus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systemic hypertension \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Obesity \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Treatment with warfarin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Protein S or C deficiency \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Immunosuppression \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Liver disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypoalbuminemia/weight loss/malnutrition \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Congestive heart failure \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Arteriovenous fistula \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1036596.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Risk Factors for the Onset of Calciphylaxis in Patients With End-Stage Renal Disease.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: ANA, antinuclear antibodies; ANCA, antineutrophil cytoplasmic antibodies; ENA, extractable nuclear antigen; MPA, microscopic polyangiitis; PAN, polyarteritis nodosum; SLE, systemic lupus erythematosus.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Disease \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Additional Tests \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Comment \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Antiphospholipid syndrome</td><td class="td" title="table-entry " align="left" valign="top">IgG and/or IgM phospholipid antibodies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Arterial or venous thrombosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IgG and/or IgM β2 glycoprotein <span class="elsevierStyleSmallCaps">i</span>antibodies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recurrent abortions \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lupus anticoagulant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Type <span class="elsevierStyleSmallCaps">i</span> cryoglobulinemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monoclonal peak and/or markedly elevated cryoglobulins in serum \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B-cell lymphoproliferative disease. Predominant manifestations are of occlusive vascular disease (livedo racemosa/retiform purpura) vs vasculitis (palpable purpura) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="4" align="left" valign="top">Autoimmune diseases with vasculitis (PAN, MPA, SLE, rheumatoid arthritis, Churg-Strauss syndrome, Wegener granulomatosis).</td><td class="td" title="table-entry " align="left" valign="top">ANA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Diagnostic criteria of the autoimmune disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anti-DNA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anti-ENA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ANCA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Thrombophilias \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Thrombophilia studies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Past personal or family history of thrombotic phenomena \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="4" align="left" valign="top">Disseminated intravascular coagulation</td><td class="td" title="table-entry " align="left" valign="top">Thrombocytopenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Purpura fulminans usually secondary to sepsis. May also be associated with trauma or obstetric complications \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prolonged coagulation times \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Peripheral blood smear (schistocytes) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Elevation of fibrinogen degradation products and D-dimer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Atrial myxoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Echocardiography \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Benign tumor arising in the endothelial cells and frequently localized in the left atrium \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pharmacological (propylthiouracil, cocaine, levamisole) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Detection of atypical ANCA in the standard ANCA assay \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Medical history. Consumption of cocaine adulterated with levamisole is associated with the presence of purpura especially in the earlobes and elastase-type atypical ANCA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sickle cell anemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Peripheral blood smear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Homozygous S hemoglobinopathy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Coumarin-induced skin necrosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Protein S and C deficiency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Warfarin consumption in the previous 3 to 10 days. Predominance in obese women in body areas with more subcutaneous cellular tissue \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Livedoid vascular disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Skin biopsy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hyalinization on histology \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Predominantly affects the malleolar area. Atrophic scars with telangiectasias and marginal pigmentation (white atrophy) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sneddon syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Skin biopsy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Neurologic disturbances, livedo reticularis, and thrombotic phenomena \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Cholesterol emboli</td><td class="td" title="table-entry " align="left" valign="top">Skin biopsy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cholesterol crystals on histology \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">History of catheterization, angioplasty, or angioradiology, or after starting anticoagulant or thrombolytic treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Primary hyperoxaluria</td><td class="td" title="table-entry " align="left" valign="top">Skin biopsy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Birefringent crystals on histology \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Autosomal recessive hereditary disease that produces an increase in the body concentration of calcium oxalate, with the consequent precipitation of calcium oxalate crystals in the joints, kidneys (nephrolithiasis), heart, eyes, and skin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lucio phenomenon \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Suspected leprosy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reactive form of untreated diffuse lepromatous leprosy \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1036597.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Investigation and Differential Diagnosis of Patients With Suspected Calciphylaxis.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Calcific uremic arteriolopathy in end stage renal disease: Pathophysiology and management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 4 | 4 | 8 |
| 2024 Octubre | 82 | 39 | 121 |
| 2024 Septiembre | 104 | 33 | 137 |
| 2024 Agosto | 129 | 61 | 190 |
| 2024 Julio | 97 | 29 | 126 |
| 2024 Junio | 94 | 27 | 121 |
| 2024 Mayo | 94 | 34 | 128 |
| 2024 Abril | 83 | 21 | 104 |
| 2024 Marzo | 89 | 30 | 119 |
| 2024 Febrero | 76 | 36 | 112 |
| 2024 Enero | 63 | 34 | 97 |
| 2023 Diciembre | 80 | 26 | 106 |
| 2023 Noviembre | 103 | 31 | 134 |
| 2023 Octubre | 103 | 34 | 137 |
| 2023 Septiembre | 89 | 31 | 120 |
| 2023 Agosto | 59 | 21 | 80 |
| 2023 Julio | 92 | 36 | 128 |
| 2023 Junio | 90 | 22 | 112 |
| 2023 Mayo | 91 | 17 | 108 |
| 2023 Abril | 62 | 20 | 82 |
| 2023 Marzo | 73 | 27 | 100 |
| 2023 Febrero | 71 | 23 | 94 |
| 2023 Enero | 45 | 35 | 80 |
| 2022 Diciembre | 50 | 41 | 91 |
| 2022 Noviembre | 43 | 25 | 68 |
| 2022 Octubre | 34 | 23 | 57 |
| 2022 Septiembre | 32 | 40 | 72 |
| 2022 Agosto | 26 | 25 | 51 |
| 2022 Julio | 28 | 36 | 64 |
| 2022 Junio | 35 | 24 | 59 |
| 2022 Mayo | 45 | 32 | 77 |
| 2022 Abril | 48 | 28 | 76 |
| 2022 Marzo | 56 | 40 | 96 |
| 2022 Febrero | 38 | 25 | 63 |
| 2022 Enero | 51 | 34 | 85 |
| 2021 Diciembre | 37 | 38 | 75 |
| 2021 Noviembre | 40 | 50 | 90 |
| 2021 Octubre | 50 | 42 | 92 |
| 2021 Septiembre | 52 | 44 | 96 |
| 2021 Agosto | 47 | 30 | 77 |
| 2021 Julio | 45 | 32 | 77 |
| 2021 Junio | 54 | 33 | 87 |
| 2021 Mayo | 53 | 41 | 94 |
| 2021 Abril | 135 | 60 | 195 |
| 2021 Marzo | 128 | 38 | 166 |
| 2021 Febrero | 83 | 27 | 110 |
| 2021 Enero | 61 | 21 | 82 |
| 2020 Diciembre | 59 | 22 | 81 |
| 2020 Noviembre | 33 | 27 | 60 |
| 2020 Octubre | 29 | 11 | 40 |
| 2020 Septiembre | 46 | 19 | 65 |
| 2020 Agosto | 34 | 16 | 50 |
| 2020 Julio | 36 | 18 | 54 |
| 2020 Junio | 26 | 31 | 57 |
| 2020 Mayo | 31 | 13 | 44 |
| 2020 Abril | 27 | 21 | 48 |
| 2020 Marzo | 18 | 22 | 40 |
| 2020 Febrero | 4 | 1 | 5 |
| 2020 Enero | 4 | 0 | 4 |
| 2019 Diciembre | 4 | 0 | 4 |
| 2019 Noviembre | 4 | 0 | 4 |
| 2019 Octubre | 1 | 2 | 3 |
| 2019 Agosto | 4 | 0 | 4 |
| 2019 Julio | 4 | 0 | 4 |
| 2019 Junio | 4 | 0 | 4 |
| 2019 Mayo | 4 | 0 | 4 |
| 2019 Abril | 2 | 1 | 3 |
| 2019 Marzo | 2 | 3 | 5 |
| 2019 Febrero | 6 | 0 | 6 |
| 2019 Enero | 4 | 0 | 4 |
| 2018 Diciembre | 1 | 0 | 1 |
| 2018 Noviembre | 2 | 0 | 2 |
| 2018 Octubre | 3 | 0 | 3 |
| 2018 Septiembre | 4 | 0 | 4 |
| 2018 Febrero | 19 | 2 | 21 |
| 2018 Enero | 39 | 8 | 47 |
| 2017 Diciembre | 41 | 5 | 46 |
| 2017 Noviembre | 31 | 6 | 37 |
| 2017 Octubre | 32 | 7 | 39 |
| 2017 Septiembre | 24 | 10 | 34 |
| 2017 Agosto | 32 | 3 | 35 |
| 2017 Julio | 22 | 13 | 35 |
| 2017 Junio | 37 | 7 | 44 |
| 2017 Mayo | 38 | 6 | 44 |
| 2017 Abril | 22 | 8 | 30 |
| 2017 Marzo | 18 | 24 | 42 |
| 2017 Febrero | 26 | 16 | 42 |
| 2017 Enero | 31 | 10 | 41 |
| 2016 Diciembre | 29 | 24 | 53 |
| 2016 Noviembre | 37 | 17 | 54 |
| 2016 Octubre | 30 | 14 | 44 |
| 2016 Julio | 2 | 12 | 14 |
| 2016 Mayo | 0 | 10 | 10 |
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