Case and Research Letters
Treatment of Livedoid Vasculopathy With Rivaroxaban: A Potential Use of New Oral Anticoagulants for Dermatologists
Vasculopatía livedoide tratada con rivaroxabán. Potenciales usos de los nuevos anticoagulantes orales para el dermatólogo
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Potenciales usos de los nuevos anticoagulantes orales para el dermatólogo" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "278" "paginaFinal" => "281" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Treatment of Livedoid Vasculopathy With Rivaroxaban: A Potential Use of New Oral Anticoagulants for Dermatologists" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 649 "Ancho" => 1733 "Tamanyo" => 188263 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">a) Úlcera cutánea en cara medial del pie izquierdo sobre un fondo de <span class="elsevierStyleItalic">livedo racemosa</span> y púrpura retiforme. b) Atrofia blanca secundaria a la cicatrización tras el uso de rivaroxabán oral.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "D. 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Jiménez-Gallo, I. Villegas-Romero, M.E. Rodríguez-Mateos, M. Linares-Barrios" "autores" => array:4 [ 0 => array:4 [ "nombre" => "D." "apellidos" => "Jiménez-Gallo" "email" => array:1 [ 0 => "davidjimenezgallo@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "I." "apellidos" => "Villegas-Romero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "M.E." "apellidos" => "Rodríguez-Mateos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "M." "apellidos" => "Linares-Barrios" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Unidad de Gestión Clínica de Dermatología Médico-Quirúrgica y Venereología, Hospital Universitario Puerta del Mar, Cádiz, España" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Gestión Clínica de Farmacia Hospitalaria, Hospital Universitario Puerta del Mar, Cádiz, España" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Vasculopatía livedoide tratada con rivaroxabán. Potenciales usos de los nuevos anticoagulantes orales para el dermatólogo" ] ] "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" => 649 "Ancho" => 1733 "Tamanyo" => 188810 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Cutaneous ulcer on the medial aspect of the left foot against a background of livedo racemosa and retiform purpura. B, Atrophie blanche due to scarring following the use of oral rivaroxaban.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Livedoid vasculopathy (LV) is a noninflammatory thrombotic disease that affects the small blood vessels of the skin and is characterized by livedo racemosa and painful skin ulcers on the lower extremities.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> We report 2 cases of LV in which treatment with rivaroxaban achieved a full and sustained response. We also review novel oral anticoagulants with potential applications in dermatology.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Case Description 1</span><p id="par0010" class="elsevierStylePara elsevierViewall">A 53-year-old woman with no relevant past history presented with multiple skin ulcers on her feet. The ulcers were painful and had been present for 2 years. Physical examination revealed an ulcer measuring approximately 3<span class="elsevierStyleHsp" style=""></span>cm on the medial aspect of the left foot against a background of livedo racemosa and retiform purpura (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). The patient's medical history and exploratory tests ruled out hypercoagulability, systemic inflammatory disease, and infection. In the evaluation of peripheral arterial disease, no alterations were observed in the ankle-brachial index or in the Doppler ultrasound scan. Skin biopsy showed fibrin clots in the dermal vessels, extravasated red blood cells, hyalinization of the vessel walls, and neovascularization consistent with LV. Treatment was initiated with acetylsalicylic acid 300<span class="elsevierStyleHsp" style=""></span>mg/d, intravenous alprostadil 60<span class="elsevierStyleHsp" style=""></span>μg/d, and subcutaneous enoxaparin 1<span class="elsevierStyleHsp" style=""></span>mg/kg/d. These treatments resulted in a mild reduction of pain and had almost no effect on ulcer healing. The patient was subsequently started on rivaroxaban 10<span class="elsevierStyleHsp" style=""></span>mg/d, which resulted in full resolution of pain after a week and healing of the ulcer at 3 months (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). Twelve months after initiation of treatment with rivaroxaban, the patient was free of pain and ulcers, although there were no changes to the livedo racemosa.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Case Description 2</span><p id="par0015" class="elsevierStylePara elsevierViewall">A 55-year-old woman with no past history of interest presented with multiple painful cutaneous ulcers of 12 years’ duration on the lower legs. Physical examination revealed multiple ulcers, some measuring up to 10<span class="elsevierStyleHsp" style=""></span>cm, with a necrotic base and a livedo racemosa pattern extending up to the knees (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A). Based on the patient's medical history and tests, a secondary cause was ruled out. Skin biopsy findings were consistent with LV. The lesions were refractory to treatment with oral prednisone, hydroxychloroquine, acetylsalicylic acid, and pentoxifylline. Treatment with rivaroxaban 10<span class="elsevierStyleHsp" style=""></span>mg/d led to reversal of pain after 2 weeks and full resolution of ulcers by month 4 (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B-D). After 9 months of treatment with rivaroxaban, the patient remained pain free and ulcer free. Similarly to the first case described, there were no changes to the livedo racemosa.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">LV can occur as a primary idiopathic condition or secondary to hypercoagulability states, (e.g., presence of lupus anticoagulant, anticardiolipin, type I cryoglobulinemia, factor V Leiden mutation, protein C deficiency, hyperhomocysteinemia, and antithrombin III deficiency).<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> It can also occur in association with systemic inflammatory diseases, such as systemic lupus erythematosus and rheumatoid arthritis.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,3</span></a> The hallmark clinical findings in LV are livedo racemosa, skin necrosis, and on occasions, noninflammatory vascular thrombosis.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> The characteristic scarring pattern left by ulcers in LV is known as <span class="elsevierStyleItalic">atrophie blanche</span>, which appears as a porcelain-white scar with red dots (prominent capillaries).<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">There is evidence of reduced fibrinolytic and increased thrombin activity in the vessel walls in LV.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> This thrombotic microvascular state is a histopathologic feature of LV. A perivascular lymphocytic infiltrate may also be observed, but it is considered to be a secondary finding and does not cause vasculitis.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,4</span></a> The most novel, and effective, treatments for LV are thus anticoagulants rather than immunomodulatory drugs. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> provides a list of these anticoagulants together with a summary of their potential applications and doses.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,5</span></a> Thanks to these new anticoagulants, dermatologists are now better positioned to manage microcirculatory thrombotic disorders, essentially because they eliminate the need for hematologic control. Rivaroxaban is a novel factor X inhibitor that has proven effective in different clinical cases and a phase II multicenter clinical trial. The 10-mg dose has been found to achieve rapid relief of ischemic pain and complete remission of ulcers.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6–8</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">There have also been recent success stories with the use of dabigatran 220<span class="elsevierStyleHsp" style=""></span>mg/d<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> and apixaban 10<span class="elsevierStyleHsp" style=""></span>mg/d in patients<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> with LV refractory to vasodilators and/or antiplatelet agents. It should be noted that the doses used for LV tend to be lower than those established for the approved indications of these new anticoagulants. Formulations containing lower doses are also commercially available (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion, we have described 2 new cases of cutaneous ulcers due to LV that did not respond to treatment with vasodilators or antiplatelet agents but that were successfully treated with rivaroxaban. This anticoagulant resulted in rapid pain resolution and complete and lasting resolution of ulcers. Dermatologists should be familiar with the existence and use of these novel oral anticoagulants in view of their potential applications in thrombotic disorders of cutaneous microcirculation.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of Interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Case Description 1" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Case Description 2" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of Interest" ] 3 => array:2 [ "identificador" => "xack341079" "titulo" => "Acknowledgments" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as: Jiménez-Gallo D, Villegas-Romero I, Rodríguez-Mateos ME, Linares-Barrios M. Vasculopatía livedoide tratada con rivaroxabán. Potenciales usos de los nuevos anticoagulantes orales para el dermatólogo. Actas Dermosifiliogr. 2018;109:278–281.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 649 "Ancho" => 1733 "Tamanyo" => 188810 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Cutaneous ulcer on the medial aspect of the left foot against a background of livedo racemosa and retiform purpura. B, Atrophie blanche due to scarring following the use of oral rivaroxaban.</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" => 2309 "Ancho" => 1733 "Tamanyo" => 416315 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A, Cutaneous ulcers against a necrotic background on the legs. B-D, Progressive healing of ulcers after initiation of oral rivaroxaban.</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:2 [ "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">Novel Oral Anticoagulant \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">Mechanism of Action \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">Dose for Usual Indication<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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">Adjusted Dose<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \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">Commercial Dose \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">Dermatologic Condition Amenable to Anticoagulant Treatment<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rivaroxaban \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Factor Xa inhibitor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20<span class="elsevierStyleHsp" style=""></span>mg/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15<span class="elsevierStyleHsp" style=""></span>mg/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10<span class="elsevierStyleHsp" style=""></span>mg<br>15<span class="elsevierStyleHsp" style=""></span>mg<br>20<span class="elsevierStyleHsp" style=""></span>mg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- Livedoid vasculopathy<br>- Antiphospholipid syndrome<br>- Sneddon syndrome<br>- Systemic lupus erythematosus<br>- Rheumatoid arthritis<br>- Dysproteinemia (type I cryoglobulinemia) \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">Dabigatran \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Thrombin inhibitor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">150<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">110<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">75<span class="elsevierStyleHsp" style=""></span>mg<br>110<span class="elsevierStyleHsp" style=""></span>mg<br>150<span class="elsevierStyleHsp" style=""></span>mg \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">Apixaban \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Factor Xa inhibitor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.5<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.5 mg<br>5<span class="elsevierStyleHsp" style=""></span>mg \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">Edoxaban \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Factor Xa inhibitor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60<span class="elsevierStyleHsp" style=""></span>mg/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15<span class="elsevierStyleHsp" style=""></span>mg<br>30<span class="elsevierStyleHsp" style=""></span>mg<br>60<span class="elsevierStyleHsp" style=""></span>mg \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></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1712389.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Prevention of stroke and systemic embolism in adults with nonvalvular atrial fibrillation.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Moderate kidney failure (clearance ><span class="elsevierStyleHsp" style=""></span>30-49<span class="elsevierStyleHsp" style=""></span>mL/min or serum creatinine ≥<span class="elsevierStyleHsp" style=""></span>1.5); liver failure (apixaban, edoxaban); age ><span class="elsevierStyleHsp" style=""></span>80 years; weight <<span class="elsevierStyleHsp" style=""></span>60<span class="elsevierStyleHsp" style=""></span>kg; concomitant use of drugs, such as ciclosporin, azole antifungals, rifampicin, carbamazepine, phenytoin, erythromycin, ritonavir, verapamil (dabigatran).</p>" ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Cutaneous ulcers caused by noninflammatory thrombosis of small blood vessels of the skin that do not respond to treatment with vasodilators or antiplatelet agents.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Novel Oral Anticoagulants With Potential Therapeutic Applications in Dermatology.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Livedoid vasculopathy: An in-depth analysis using a modified Delphi approach" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. 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Shimizu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jdv.13691" "Revista" => array:6 [ "tituloSerie" => "J Eur Acad Dermatol Venereol" "fecha" => "2017" "volumen" => "31" "paginaInicial" => "e45" "paginaFinal" => "e46" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27166520" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack341079" "titulo" => "Acknowledgments" "texto" => "<p id="par0045" class="elsevierStylePara elsevierViewall">We thank Professor José María Báez Perea from the University of Cadiz, also a pathologist at Hospital Universitario Puerta del Mar, for his expert contribution to the histopathologic study of the cases presented.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010900000003/v1_201804020430/S1578219018300118/v1_201804020430/en/main.assets" "Apartado" => array:4 [ "identificador" => "6157" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Case and Research Letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010900000003/v1_201804020430/S1578219018300118/v1_201804020430/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219018300118?idApp=UINPBA000044" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 9 | 8 | 17 |
| 2024 October | 105 | 44 | 149 |
| 2024 September | 120 | 33 | 153 |
| 2024 August | 160 | 73 | 233 |
| 2024 July | 166 | 60 | 226 |
| 2024 June | 145 | 72 | 217 |
| 2024 May | 131 | 42 | 173 |
| 2024 April | 138 | 35 | 173 |
| 2024 March | 103 | 33 | 136 |
| 2024 February | 121 | 32 | 153 |
| 2024 January | 112 | 30 | 142 |
| 2023 December | 109 | 21 | 130 |
| 2023 November | 126 | 31 | 157 |
| 2023 October | 88 | 25 | 113 |
| 2023 September | 115 | 30 | 145 |
| 2023 August | 83 | 21 | 104 |
| 2023 July | 159 | 36 | 195 |
| 2023 June | 123 | 20 | 143 |
| 2023 May | 137 | 31 | 168 |
| 2023 April | 84 | 25 | 109 |
| 2023 March | 89 | 34 | 123 |
| 2023 February | 99 | 32 | 131 |
| 2023 January | 91 | 38 | 129 |
| 2022 December | 105 | 46 | 151 |
| 2022 November | 48 | 41 | 89 |
| 2022 October | 67 | 26 | 93 |
| 2022 September | 72 | 43 | 115 |
| 2022 August | 78 | 48 | 126 |
| 2022 July | 80 | 43 | 123 |
| 2022 June | 44 | 32 | 76 |
| 2022 May | 96 | 46 | 142 |
| 2022 April | 85 | 52 | 137 |
| 2022 March | 88 | 68 | 156 |
| 2022 February | 82 | 36 | 118 |
| 2022 January | 121 | 44 | 165 |
| 2021 December | 70 | 43 | 113 |
| 2021 November | 75 | 57 | 132 |
| 2021 October | 103 | 65 | 168 |
| 2021 September | 102 | 43 | 145 |
| 2021 August | 104 | 35 | 139 |
| 2021 July | 111 | 36 | 147 |
| 2021 June | 152 | 29 | 181 |
| 2021 May | 199 | 56 | 255 |
| 2021 April | 335 | 122 | 457 |
| 2021 March | 192 | 35 | 227 |
| 2021 February | 140 | 40 | 180 |
| 2021 January | 97 | 23 | 120 |
| 2020 December | 55 | 23 | 78 |
| 2020 November | 57 | 17 | 74 |
| 2020 October | 86 | 16 | 102 |
| 2020 September | 65 | 19 | 84 |
| 2020 August | 57 | 24 | 81 |
| 2020 July | 50 | 16 | 66 |
| 2020 June | 46 | 31 | 77 |
| 2020 May | 37 | 17 | 54 |
| 2020 April | 36 | 22 | 58 |
| 2020 March | 36 | 15 | 51 |
| 2020 February | 3 | 0 | 3 |
| 2020 January | 4 | 0 | 4 |
| 2019 December | 8 | 0 | 8 |
| 2019 November | 4 | 0 | 4 |
| 2019 September | 10 | 0 | 10 |
| 2019 August | 4 | 0 | 4 |
| 2019 July | 5 | 0 | 5 |
| 2019 June | 4 | 0 | 4 |
| 2019 May | 6 | 1 | 7 |
| 2019 April | 2 | 0 | 2 |
| 2019 March | 2 | 0 | 2 |
| 2019 February | 2 | 0 | 2 |
| 2018 December | 4 | 0 | 4 |
| 2018 November | 3 | 0 | 3 |
| 2018 October | 3 | 0 | 3 |
| 2018 September | 3 | 0 | 3 |
| 2018 April | 2 | 0 | 2 |
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