Case and Research Letters
Embolia Cutis Medicamentosa (Nicolau Syndrome) After Glatiramer Acetate Injection
Embolia cutis medicamentosa (síndrome de Nicolau) tras inyección de acetato de glatirámero
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"apellidos" => "Borbujo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Universitario de Fuenlabrada, Madrid, Spain" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario de Fuenlabrada, Madrid, 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" => "Embolia cutis medicamentosa (síndrome de Nicolau) tras inyección de acetato de glatirámero" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 762 "Ancho" => 952 "Tamanyo" => 217323 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Epidermal necrosis corresponding clinically to the area of the scab, degeneration of dermal collagen, and fibrin clots in the lumen of the vessels of the superficial dermis (hematoxylin–eosin, original magnification x100).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Injection-site reactions are some of the most common complications in subcutaneously administered treatments.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 31-year-old woman with no known drug allergies, a history of asthma and hidradenitis suppurativa, neither of which was being treated, and relapsing-remitting multiple sclerosis. For four-and-a-half years, the patient had been receiving treatment with daily subcutaneous injections of 20<span class="elsevierStyleHsp" style=""></span>mg of glatiramer acetate (GA, Copolymer-1, Copaxone, Sanofi-Aventis, Barcelona, Spain).</p><p id="par0015" class="elsevierStylePara elsevierViewall">She visited the emergency department due to acute pain in the left buttock after an injection of glatiramer acetate; the patient had not experienced the pain with previous injections. There was a whitish plaque at the injection site that became erythematous and necrotic over the following 5 days.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Physical examination (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) showed a reddish-gray, livedoid plaque on the left buttock, measuring approximately 3<span class="elsevierStyleHsp" style=""></span>cm, with geographic borders, a necrotic center, and a more intensely erythematous-violaceous border. On the caudal part of the lesion there was a deep, round, adherent scab measuring approximately 8<span class="elsevierStyleHsp" style=""></span>mm in diameter.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Questioning of the patient revealed that she complied with the injection protocol: the same injection site was not used in less than a week, the drug was left at room temperature 20<span class="elsevierStyleHsp" style=""></span>minutes before use, and the needle was placed in the correct position. Furthermore, the patient had continued to inject the treatment in the thighs and abdomen in the following days and no lesions had appeared at those sites. She reported a similar event in the same buttock a year earlier that had resolved without treatment and left an area of residual hypopigmentation.</p><p id="par0030" class="elsevierStylePara elsevierViewall">A biopsy was performed of the peripheral area of the skin lesion on the buttock and showed a partially necrotic epidermis with coagulative necrosis of the dermal collagen, fat necrosis, and some fibrin clots in the small blood vessels (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Analyses, including a complete blood count, biochemistry with liver and kidney function tests, immunoglobulins, complement, antibodies to extractable nuclear antigens, antinuclear and anticardiolipin antibodies, and coagulation studies showed no relevant abnormalities.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">These data led to a diagnosis of Nicolau syndrome. Topical treatment was instated with fusidic acid and betamethasone twice daily for 10 days; the lesion improved slowly and resolved within a month later, leaving a slightly depressed scar.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Glatiramer acetate is a mixture of synthetic polypeptides that is used to treat relapsing-remitting multiple sclerosis and has been shown to reduce the number of relapses of the disease and patient disability.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The most common adverse event is a reaction at the injection site, producing pain, inflammation, and induration; this occurs in 60% of patients and resolves within hours or days, leaving no residual lesion.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The rapid resolution of this event differentiates it from panniculitis at the injection site, which is less common, but nonetheless characteristic of glatiramer acetate. This is predominantly lobular panniculitis, which presents clinically as subcutaneous nodular erythematous lesions that resolve in 2 to 3 months and leave residual lipoatrophy in all cases.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Nicolau syndrome, also known as livedoid vasculopathy or embolia cutis medicamentosa, was first described in 1924 by Freudenthal and then, in 1925, by Nicolau.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Gay-Prieto<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> reported a similar case in 1930. Nicolau syndrome after subcutaneous injection of glatiramer acetate was first reported by Gaudez<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> in 2003, and few similar cases have been published since then.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6–8</span></a> The pathogenic mechanism is not clearly understood, but accidental perivascular or intravascular injection of the drug appears to cause vasospasm and intravascular thrombosis, which gives rise to local skin necrosis due to ischemia.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">This is an unforeseeable but inevitable reaction, in which the injection technique plays a determining role; we also believe that it bears some relation to the drug administered, either due to its molecular weight or to the pH of the excipient used.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Because this reaction is mainly due to the injection technique and not to the drug itself, it should not contraindicate continuation of treatment.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Because the drug is administered daily, when the patient visited our department she had already administered 4 further injections after the appearance of the skin lesion and it was therefore logical to assume that this was not a reaction caused by an immune or allergic mechanism, as in this case the lesion would have recurred in the following days.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Because the patient is right-handed, the left buttock is the most inconvenient and inaccessible site for injecting the drug; the angle of injection or depth of administration of the drug may therefore have been incorrect.</p><p id="par0070" class="elsevierStylePara elsevierViewall">After symptoms resolved and the patient had been advised not to inject in the buttocks, she continued with the same administration regimen and no new lesions had appeared at the injection sites a year after her visit to our department.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as. Martínez-Morán C, et al. Embolia cutis medicamentosa (síndrome de Nicolau) tras inyección de acetado de glatirámero.Actas Dermosifiliogr.2011;102:742-744.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 568 "Ancho" => 851 "Tamanyo" => 59042 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Violaceous livedoid plaque, with erythematous borders and a central scab located on the left buttock.</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" => 762 "Ancho" => 952 "Tamanyo" => 217323 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Epidermal necrosis corresponding clinically to the area of the scab, degeneration of dermal collagen, and fibrin clots in the lumen of the vessels of the superficial dermis (hematoxylin–eosin, original magnification x100).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.P. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 21 | 12 | 33 |
| 2024 Octubre | 96 | 57 | 153 |
| 2024 Septiembre | 133 | 27 | 160 |
| 2024 Agosto | 148 | 68 | 216 |
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| 2024 Mayo | 114 | 44 | 158 |
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| 2024 Marzo | 102 | 40 | 142 |
| 2024 Febrero | 82 | 34 | 116 |
| 2024 Enero | 64 | 42 | 106 |
| 2023 Diciembre | 77 | 20 | 97 |
| 2023 Noviembre | 111 | 31 | 142 |
| 2023 Octubre | 94 | 23 | 117 |
| 2023 Septiembre | 85 | 43 | 128 |
| 2023 Agosto | 59 | 33 | 92 |
| 2023 Julio | 91 | 50 | 141 |
| 2023 Junio | 80 | 40 | 120 |
| 2023 Mayo | 94 | 31 | 125 |
| 2023 Abril | 82 | 21 | 103 |
| 2023 Marzo | 90 | 26 | 116 |
| 2023 Febrero | 88 | 29 | 117 |
| 2023 Enero | 56 | 36 | 92 |
| 2022 Diciembre | 67 | 44 | 111 |
| 2022 Noviembre | 41 | 28 | 69 |
| 2022 Octubre | 36 | 30 | 66 |
| 2022 Septiembre | 33 | 35 | 68 |
| 2022 Agosto | 27 | 33 | 60 |
| 2022 Julio | 28 | 32 | 60 |
| 2022 Junio | 28 | 18 | 46 |
| 2022 Mayo | 61 | 29 | 90 |
| 2022 Abril | 60 | 47 | 107 |
| 2022 Marzo | 69 | 51 | 120 |
| 2022 Febrero | 64 | 35 | 99 |
| 2022 Enero | 90 | 63 | 153 |
| 2021 Diciembre | 66 | 53 | 119 |
| 2021 Noviembre | 47 | 60 | 107 |
| 2021 Octubre | 59 | 54 | 113 |
| 2021 Septiembre | 72 | 44 | 116 |
| 2021 Agosto | 46 | 93 | 139 |
| 2021 Julio | 52 | 48 | 100 |
| 2021 Junio | 76 | 35 | 111 |
| 2021 Mayo | 75 | 37 | 112 |
| 2021 Abril | 97 | 77 | 174 |
| 2021 Marzo | 65 | 29 | 94 |
| 2021 Febrero | 82 | 38 | 120 |
| 2021 Enero | 39 | 18 | 57 |
| 2020 Diciembre | 59 | 19 | 78 |
| 2020 Noviembre | 48 | 16 | 64 |
| 2020 Octubre | 32 | 20 | 52 |
| 2020 Septiembre | 39 | 15 | 54 |
| 2020 Agosto | 55 | 17 | 72 |
| 2020 Julio | 24 | 19 | 43 |
| 2020 Junio | 46 | 23 | 69 |
| 2020 Mayo | 27 | 20 | 47 |
| 2020 Abril | 29 | 15 | 44 |
| 2020 Marzo | 30 | 26 | 56 |
| 2020 Febrero | 3 | 0 | 3 |
| 2019 Diciembre | 4 | 0 | 4 |
| 2019 Noviembre | 0 | 2 | 2 |
| 2019 Octubre | 0 | 3 | 3 |
| 2019 Septiembre | 4 | 6 | 10 |
| 2019 Agosto | 0 | 15 | 15 |
| 2019 Julio | 0 | 13 | 13 |
| 2019 Junio | 0 | 15 | 15 |
| 2019 Mayo | 2 | 16 | 18 |
| 2019 Abril | 0 | 25 | 25 |
| 2019 Marzo | 2 | 10 | 12 |
| 2019 Febrero | 0 | 5 | 5 |
| 2019 Enero | 1 | 0 | 1 |
| 2018 Diciembre | 3 | 0 | 3 |
| 2018 Noviembre | 2 | 0 | 2 |
| 2018 Octubre | 3 | 0 | 3 |
| 2018 Septiembre | 2 | 0 | 2 |
| 2018 Junio | 0 | 1 | 1 |
| 2018 Mayo | 0 | 8 | 8 |
| 2018 Marzo | 0 | 2 | 2 |
| 2018 Febrero | 69 | 7 | 76 |
| 2018 Enero | 93 | 10 | 103 |
| 2017 Diciembre | 110 | 12 | 122 |
| 2017 Noviembre | 112 | 14 | 126 |
| 2017 Octubre | 74 | 10 | 84 |
| 2017 Septiembre | 98 | 19 | 117 |
| 2017 Agosto | 132 | 22 | 154 |
| 2017 Julio | 124 | 15 | 139 |
| 2017 Junio | 124 | 31 | 155 |
| 2017 Mayo | 138 | 11 | 149 |
| 2017 Abril | 87 | 23 | 110 |
| 2017 Marzo | 56 | 44 | 100 |
| 2017 Febrero | 82 | 22 | 104 |
| 2017 Enero | 82 | 20 | 102 |
| 2016 Diciembre | 94 | 21 | 115 |
| 2016 Noviembre | 156 | 17 | 173 |
| 2016 Octubre | 159 | 20 | 179 |
| 2016 Septiembre | 233 | 14 | 247 |
| 2016 Agosto | 201 | 16 | 217 |
| 2016 Julio | 89 | 11 | 100 |
| 2016 Junio | 12 | 12 | 24 |
| 2016 Mayo | 12 | 12 | 24 |
| 2016 Abril | 3 | 1 | 4 |
| 2016 Marzo | 7 | 9 | 16 |
| 2016 Febrero | 7 | 17 | 24 |
| 2016 Enero | 2 | 11 | 13 |
| 2015 Diciembre | 8 | 7 | 15 |
| 2015 Noviembre | 18 | 10 | 28 |
| 2015 Octubre | 24 | 1 | 25 |
| 2015 Septiembre | 13 | 10 | 23 |
| 2015 Agosto | 15 | 10 | 25 |
| 2015 Julio | 98 | 2 | 100 |
| 2015 Junio | 64 | 8 | 72 |
| 2015 Mayo | 101 | 27 | 128 |
| 2015 Abril | 100 | 22 | 122 |
| 2015 Marzo | 61 | 32 | 93 |
| 2015 Febrero | 67 | 12 | 79 |
| 2015 Enero | 57 | 29 | 86 |
| 2014 Diciembre | 67 | 26 | 93 |
| 2014 Noviembre | 51 | 14 | 65 |
| 2014 Octubre | 75 | 20 | 95 |
| 2014 Septiembre | 71 | 18 | 89 |
| 2014 Agosto | 78 | 17 | 95 |
| 2014 Julio | 79 | 16 | 95 |
| 2014 Junio | 105 | 20 | 125 |
| 2014 Mayo | 106 | 17 | 123 |
| 2014 Abril | 73 | 10 | 83 |
| 2014 Marzo | 114 | 24 | 138 |
| 2014 Febrero | 73 | 19 | 92 |
| 2014 Enero | 85 | 24 | 109 |
| 2013 Diciembre | 71 | 14 | 85 |
| 2013 Noviembre | 50 | 14 | 64 |
| 2013 Octubre | 23 | 16 | 39 |
| 2013 Septiembre | 33 | 24 | 57 |
| 2013 Agosto | 31 | 27 | 58 |
| 2013 Julio | 14 | 33 | 47 |
| 2013 Junio | 14 | 15 | 29 |
| 2013 Mayo | 14 | 7 | 21 |
| 2013 Abril | 9 | 16 | 25 |
| 2013 Marzo | 19 | 15 | 34 |
| 2013 Febrero | 33 | 15 | 48 |
| 2013 Enero | 35 | 7 | 42 |
| 2012 Diciembre | 16 | 4 | 20 |
| 2012 Noviembre | 0 | 1 | 1 |
| 2012 Octubre | 1 | 5 | 6 |
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