Case and Research Letters
Widespread Cutaneous Necrosis as the First Clinical Manifestation of Secondary Antiphospholipid Syndrome
Necrosis cutánea extensa como la primera manifestación clínica de un síndrome antifosfolípidico
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Perelló-Alzamora, J.C. Santos-Duran, A. Santos-Briz, P. Unamuno" "autores" => array:4 [ 0 => array:4 [ "nombre" => "M.R." "apellidos" => "Perelló-Alzamora" "email" => array:1 [ 0 => "mariarosaperello@yahoo.es" ] "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" => "J.C." "apellidos" => "Santos-Duran" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Santos-Briz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "P." "apellidos" => "Unamuno" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Dermatology, University Hospital of Salamanca, Salamanca, Spain" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Pathology, University Hospital of Salamanca, Salamanca, Spain" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Necrosis cutánea extensa como la primera manifestación clínica de un síndrome antifosfolípidico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1188 "Ancho" => 1585 "Tamanyo" => 305657 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Skin biopsy. Extensive epidermal basal vasculopathy, hemorrhage throughout the dermis with organized thrombi in many dermal vessels and no evidence of vasculitis.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Antiphospholipid syndrome (APS) is an acquired prothrombotic state characterized by recurrent thromboses, pregnancy loss, thrombocytopenia, and the presence of antiphospholipid antibodies, anticardiolipin antibodies, lupus anticoagulant and/or anti-β2-glycoprotein antibody.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a> The original clinical and laboratory criteria for APS, called the Sapporo criteria, were first published in 1999.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> These were replaced by the Sydney criteria in 2006,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> when patients were required to have at least 1 clinical criterion and 1 laboratory criterion for a diagnosis of APS to be made.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A wide variety of dermatologic manifestations have been described in patients with APS,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> including livedo reticularis, livedoid vasculitis, digital gangrene, erythematous macules,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> skin ulcerations, and, on rare occasions, extensive cutaneous necrosis.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> We report the case of a patient with widespread cutaneous necrosis as the initial manifestation of APS.</p><p id="par0015" class="elsevierStylePara elsevierViewall">A 48-year-old woman presented at the emergency room with a 2-week history of fever, arthralgia, malaise, and chest pain. On examination she was noted to have 3 bullous erythematous violaceous plaques on her right leg (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Her medical history was remarkable for hypothyroidism, systemic lupus erythematosus (SLE), and obsessive-compulsive disorder. Medications included thyroxine, olanzapine, risperidone, and sertraline. Laboratory tests revealed thrombocytopenia (platelet count 25,000) and normal prothrombin and partial thromboplastin times. Lupus anticoagulant was present and the antinuclear antibody titer was 1:320. C3 and C4 levels were normal.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The lesions deteriorated rapidly despite initiation of corticosteroid therapy with prednisolone at a dosage of 1<span class="elsevierStyleHsp" style=""></span>mg/kg/d. The dermatology service was called to evaluate the patient on day 7 of hospitalization. Examination revealed extensive cutaneous necrosis on the right leg (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Further laboratory data revealed an elevated anticardiolipin antibody immunoglobulin (Ig) G titer (30; normal <23). Anti-β2-glycoprotein antibody IgG levels were also elevated, but cryoglobulins and cryofibrinogens were normal. A 4-mm punch biopsy from the periphery of a lesion revealed hemorrhage throughout the dermis with organized thrombi in many dermal vessels, with no evidence of vasculitis (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). No further lesions developed after the addition of intravenous heparin. At discharge, the heparin was replaced by long-term oral anticoagulation therapy and prednisone was tapered over 8 weeks. At the 3-month follow-up, only residual scarring remained (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). There have been no new thrombotic events in 1 year of follow-up.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Only 23 cases of extensive cutaneous necrosis linked to APS have been reported in the literature.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,8</span></a> Most of the patients have been young women and the underlying diseases included SLE (9 cases), lupus-like disease (1 case), urinary tract infection (2 cases), acquired immunodeficiency syndrome (1 case), rheumatoid arthritis (1 case), mycosis fungoides (1 case), and mixed connective tissue disease (7 cases). Seven patients had no underlying disease. All of the patients developed thrombotic complications limited to skin, and, as in our patient, the lower limbs were the most commonly affected site. Skin biopsy revealed the presence of thrombi in dermal venules and capillaries, with no evidence of vasculitis.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The mechanisms of thrombosis associated with antiphospholipid antibodies remain unknown.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The main entities to take into consideration in the differential diagnosis are catastrophic antiphospholipid antibody syndrome and disseminated intravascular coagulation.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Our patient achieved complete healing with prednisolone at a dose of 1<span class="elsevierStyleHsp" style=""></span>mg/kg/d and heparin, which was replaced by oral anticoagulants at discharge. At the time of writing, after 1 year of follow-up, there have been no further thrombotic episodes.</p><p id="par0040" class="elsevierStylePara elsevierViewall">We conclude that widespread cutaneous necrosis is a rare initial manifestation of APS and should be considered a major thrombotic event.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> It is important to recognize these lesions because early diagnosis enables early treatment, and, possibly, better prognosis.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "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" => 1192 "Ancho" => 1585 "Tamanyo" => 117821 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cutaneous lesions on admission. Bullous erythematous violaceous plaques on the right leg.</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" => 1190 "Ancho" => 1585 "Tamanyo" => 176615 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Cutaneous lesions on day 7 of hospitalization. Extensive cutaneous necrosis on the right leg.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1188 "Ancho" => 1585 "Tamanyo" => 305657 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Skin biopsy. Extensive epidermal basal vasculopathy, hemorrhage throughout the dermis with organized thrombi in many dermal vessels and no evidence of vasculitis.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1190 "Ancho" => 1585 "Tamanyo" => 147979 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Cutaneous lesions after 3 months. Residual scarring visible on the leg.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Extensive cutaneous necrosis associated with anticardiolipin antibodies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S. Paira" 1 => "S. Roverano" 2 => "A. Zunino" 3 => "M.E. Oliva" 4 => "M.L. 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Piette" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/1529-0131(199907)42:7<1309::AID-ANR1>3.0.CO;2-F" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "1999" "volumen" => "42" "paginaInicial" => "1309" "paginaFinal" => "1311" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10403256" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Miyakis" 1 => "M.D. Lockshin" 2 => "D. Atsumi" 3 => "D.W. Branch" 4 => "R.L. Brey" 5 => "R. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 15 | 10 | 25 |
| 2024 October | 76 | 42 | 118 |
| 2024 September | 97 | 26 | 123 |
| 2024 August | 109 | 59 | 168 |
| 2024 July | 102 | 28 | 130 |
| 2024 June | 120 | 40 | 160 |
| 2024 May | 103 | 29 | 132 |
| 2024 April | 83 | 28 | 111 |
| 2024 March | 101 | 32 | 133 |
| 2024 February | 99 | 36 | 135 |
| 2024 January | 80 | 37 | 117 |
| 2023 December | 97 | 17 | 114 |
| 2023 November | 129 | 27 | 156 |
| 2023 October | 114 | 22 | 136 |
| 2023 September | 139 | 30 | 169 |
| 2023 August | 104 | 17 | 121 |
| 2023 July | 81 | 34 | 115 |
| 2023 June | 74 | 17 | 91 |
| 2023 May | 102 | 38 | 140 |
| 2023 April | 103 | 21 | 124 |
| 2023 March | 82 | 26 | 108 |
| 2023 February | 66 | 30 | 96 |
| 2023 January | 44 | 33 | 77 |
| 2022 December | 48 | 33 | 81 |
| 2022 November | 34 | 25 | 59 |
| 2022 October | 27 | 24 | 51 |
| 2022 September | 29 | 38 | 67 |
| 2022 August | 33 | 26 | 59 |
| 2022 July | 33 | 36 | 69 |
| 2022 June | 40 | 28 | 68 |
| 2022 May | 62 | 33 | 95 |
| 2022 April | 69 | 44 | 113 |
| 2022 March | 45 | 55 | 100 |
| 2022 February | 56 | 20 | 76 |
| 2022 January | 60 | 34 | 94 |
| 2021 December | 44 | 35 | 79 |
| 2021 November | 50 | 53 | 103 |
| 2021 October | 50 | 47 | 97 |
| 2021 September | 63 | 37 | 100 |
| 2021 August | 55 | 29 | 84 |
| 2021 July | 56 | 31 | 87 |
| 2021 June | 56 | 41 | 97 |
| 2021 May | 66 | 42 | 108 |
| 2021 April | 44 | 47 | 91 |
| 2021 March | 48 | 27 | 75 |
| 2021 February | 51 | 16 | 67 |
| 2021 January | 37 | 16 | 53 |
| 2020 December | 42 | 13 | 55 |
| 2020 November | 29 | 11 | 40 |
| 2020 October | 28 | 5 | 33 |
| 2020 September | 62 | 9 | 71 |
| 2020 August | 27 | 18 | 45 |
| 2020 July | 37 | 14 | 51 |
| 2020 June | 20 | 24 | 44 |
| 2020 May | 16 | 12 | 28 |
| 2020 April | 25 | 12 | 37 |
| 2020 March | 21 | 14 | 35 |
| 2020 February | 7 | 1 | 8 |
| 2020 January | 2 | 1 | 3 |
| 2019 December | 8 | 2 | 10 |
| 2019 November | 4 | 0 | 4 |
| 2019 September | 8 | 0 | 8 |
| 2019 August | 4 | 5 | 9 |
| 2019 July | 6 | 2 | 8 |
| 2019 June | 6 | 7 | 13 |
| 2019 May | 4 | 4 | 8 |
| 2019 April | 2 | 9 | 11 |
| 2019 March | 4 | 7 | 11 |
| 2019 February | 2 | 2 | 4 |
| 2019 January | 1 | 2 | 3 |
| 2018 December | 4 | 5 | 9 |
| 2018 November | 0 | 3 | 3 |
| 2018 October | 3 | 0 | 3 |
| 2018 September | 5 | 0 | 5 |
| 2018 June | 1 | 1 | 2 |
| 2018 March | 4 | 2 | 6 |
| 2018 February | 68 | 6 | 74 |
| 2018 January | 77 | 10 | 87 |
| 2017 December | 73 | 6 | 79 |
| 2017 November | 64 | 6 | 70 |
| 2017 October | 78 | 3 | 81 |
| 2017 September | 64 | 7 | 71 |
| 2017 August | 94 | 15 | 109 |
| 2017 July | 47 | 13 | 60 |
| 2017 June | 72 | 11 | 83 |
| 2017 May | 63 | 12 | 75 |
| 2017 April | 56 | 15 | 71 |
| 2017 March | 45 | 13 | 58 |
| 2017 February | 41 | 10 | 51 |
| 2017 January | 46 | 12 | 58 |
| 2016 December | 48 | 18 | 66 |
| 2016 November | 61 | 5 | 66 |
| 2016 October | 75 | 14 | 89 |
| 2016 September | 160 | 8 | 168 |
| 2016 August | 105 | 9 | 114 |
| 2016 July | 38 | 9 | 47 |
| 2016 June | 8 | 18 | 26 |
| 2016 May | 8 | 3 | 11 |
| 2016 April | 8 | 15 | 23 |
| 2016 March | 11 | 9 | 20 |
| 2016 February | 4 | 8 | 12 |
| 2016 January | 2 | 9 | 11 |
| 2015 December | 5 | 7 | 12 |
| 2015 November | 22 | 9 | 31 |
| 2015 October | 13 | 11 | 24 |
| 2015 September | 5 | 12 | 17 |
| 2015 August | 11 | 2 | 13 |
| 2015 July | 141 | 10 | 151 |
| 2015 June | 86 | 10 | 96 |
| 2015 May | 57 | 7 | 64 |
| 2015 April | 76 | 11 | 87 |
| 2015 March | 61 | 12 | 73 |
| 2015 February | 65 | 7 | 72 |
| 2015 January | 53 | 13 | 66 |
| 2014 December | 56 | 6 | 62 |
| 2014 November | 67 | 15 | 82 |
| 2014 October | 51 | 2 | 53 |
| 2014 September | 48 | 1 | 49 |
| 2014 August | 33 | 1 | 34 |
| 2014 July | 33 | 3 | 36 |
| 2014 June | 43 | 2 | 45 |
| 2014 May | 44 | 5 | 49 |
| 2014 April | 45 | 2 | 47 |
| 2014 March | 45 | 7 | 52 |
| 2014 February | 36 | 3 | 39 |
| 2014 January | 31 | 6 | 37 |
| 2013 December | 46 | 2 | 48 |
| 2013 November | 37 | 10 | 47 |
| 2013 October | 30 | 0 | 30 |
| 2013 September | 4 | 5 | 9 |
| 2013 August | 6 | 5 | 11 |
| 2013 July | 6 | 8 | 14 |
| 2013 June | 6 | 7 | 13 |
| 2013 May | 9 | 12 | 21 |
| 2013 April | 5 | 4 | 9 |
| 2013 March | 12 | 6 | 18 |
| 2013 February | 25 | 4 | 29 |
| 2013 January | 32 | 5 | 37 |
| 2012 December | 28 | 6 | 34 |
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