Case and Research Letters
Cocaine/Levamisole-Associated Autoimmune Syndrome: A Case Report
Síndrome autoinmune cocaína-levamisol. Presentación de un caso
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Álvarez-Garrido, C. Horcajada-Reales, A. Hernández-Nuñez, J. Borbujo" "autores" => array:4 [ 0 => array:2 [ "nombre" => "H." "apellidos" => "Álvarez-Garrido" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Horcajada-Reales" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Hernández-Nuñez" ] 3 => array:2 [ "nombre" => "J." "apellidos" => "Borbujo" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219021002031?idApp=UINPBA000044" "url" => "/15782190/0000011200000008/v2_202110201006/S1578219021002031/v2_202110201006/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letters</span>" "titulo" => "Cocaine/Levamisole-Associated Autoimmune Syndrome: A Case Report" "tieneTextoCompleto" => true "saludo" => "To the Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "772" "paginaFinal" => "774" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "M.I. Cevallos Abad, A. Córdoba Iturriagagoitia, M. Larrea García" "autores" => array:3 [ 0 => array:4 [ "nombre" => "M.I." "apellidos" => "Cevallos Abad" "email" => array:1 [ 0 => "mcevalla@navarra.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "A." "apellidos" => "Córdoba Iturriagagoitia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "M." "apellidos" => "Larrea García" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Complejo Hospitalario de Navarra, Navarra, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Dermatología, Complejo Hospitalario de Navarra, Navarra, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome autoinmune cocaína-levamisol. Presentación de un caso" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 563 "Ancho" => 750 "Tamanyo" => 89620 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Purplish lesion on the outer ear.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A 55-year-old man visited the emergency department with clinical signs and symptoms that had appeared some days earlier, consisting of progressive dyspnea accompanied by fever of up to 39 °<span class="elsevierStyleSmallCaps">C</span>, productive cough, and flat, red-violaceous reticulated lesions with a purplish appearance on the left outer ear (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), left malar region, right nostril, and both arms. The patient was an ex-intravenous drug abuser and had a history of stage-2 infection with the human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, which was cured spontaneously, and presented chronic neutropenia. Laboratory tests showed leukopenia and thrombocytopenia, creatinine levels of 6 mg/dL, procalcitonin of 3.74, C-reactive protein (CRP) of 313, and a glomerular filtration rate of 9 mL/min. Antineutrophil cytoplasmic antibodies (ANCAs) and lupus anticoagulant were positive, whereas cryoglobulins were negative. A chest x-ray showed bilateral disperse alveolar-interstitial infiltrates and the patient was therefore diagnosed with lobar pneumonia and acute kidney failure.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">A punch biopsy of one of the skin lesions was performed and revealed massive occupation of the capillaries by mixed thrombi, with some trapped polymorphonuclear cells, without the characteristic abnormalities of leukocytoclastic vasculitis (<a class="elsevierStyleCrossRefs" href="#fig0010">Figs. 2 and 3</a>). The differential diagnosis included thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, cryoglobulinemia, and retiform purpura associated with cocaine use. The first 2 entities were ruled out clinically and the third was ruled out due to the absence of cryoglobulins. The patient subsequently admitted to using cocaine. The skin lesions remitted after administering treatment with methylprednisolone and the patient was referred to a mental-health center for cessation of cocaine use.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Levamisole is an anthelminthic drug that, due to its immunomodulatory effect, was used in the past to treat rheumatoid arthritis, collagenopathies, inflammatory bowel disease, pediatric nephrotic syndrome, and cancer. In 2000, the US Food and Drug Administration (FDA) withdrew the drug from the market due to its severe adverse effects, such as vasculitis and blood disorders (especially agranulocytosis)<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a>; the drug was, however, maintained for veterinary use.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">It has gained notoriety since 2008 through its use as an adulterant for cocaine due to its similar consistency, its availability, and its synergic activity.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> A syndrome has therefore been described in users of this drug that is characterized by retiform purpura,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a> pauci-immune crescentic glomerulonephritis, pulmonary hemorrhage with vasculitis, pulmonary hypertension,<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,5</span></a> and arthritis deformans, with variable frequency.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Serology reveals higher titers of perinuclear antineutrophilic antibodies than in idiopathic vasculitis. Its association with antinuclear antibodies (ANAs), anti-double stranded DNA (anti-dsDNA), and antiphospholipids such as lupus anticoagulant and anticardiolipin has also been reported.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> A study carried out in Spain in 2009 determined that 48% of cocaine samples studied contained levamisole.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The most notable symptom, and the one that causes patients to seek consultation, is the cutaneous symptom.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> It has also been found that 60% of these patients have blood disorders and between 95% and 100% have high ANCA titers.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> It usually manifests as retiform purpura involving the outer ear, zygomatic arches, and extremities, while sparing the torso. Typical histopathology findings include small-vessel leukocytoclastic vasculitis with fibrinoid necrosis of the vascular wall, extravasation of erythrocytes, karyorrhexis and angiocentric inflammation, and multiple fibrin thrombi in the vessels of the superficial and deep dermis.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3,5</span></a> These findings may present together or separately; microvascular thrombosis is the most consistent of these findings<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and was the only one found in our case.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Cascio and Jen<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> have suggested naming this constellation of abnormalities cocaine/levamisole-associated autoimmune syndrome (CLAAS). As well as the retiform purpura with the characteristic pattern, our patient presented a thrombotic vasculopathy, thrombocytopenia, neutropenia, lupus anticoagulant, and ANAs. Although the patient presented acute kidney failure, there is no clinical confirmation that this was due to the use of cocaine and levamisole.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The diagnosis of CLAAS is by exclusion. It should be considered in all patients with a history of cocaine use who present with purpura of the characteristics described above, joint pain, neutropenia, and high ANCA titers<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> in the absence of other apparent etiologies.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The basis of treatment is ceasing cocaine, and thus levamisole, use.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2,5</span></a> The literature shows treatment data similar to those for primary vasculitis: immunosuppression, anticoagulation, and antiaggregation.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In our patient, the dermal lesions remitted after treatment with methylprednisolone.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0040" class="elsevierStylePara elsevierViewall">This study has not received funding of any kind.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of Interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflicts of Interest" ] 2 => array:2 [ "identificador" => "xack562405" "titulo" => "Acknowledgments" ] 3 => 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: Cevallos-Abad MI, Córdoba-Iturriagagoitia A, Larrea-García M. Síndrome autoinmune cocaína-levamisol. Presentación de un caso. Actas Dermosifiliogr. 2021. <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.ad.2020.02.010">https://doi.org/10.1016/j.ad.2020.02.010</span></p>" ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 563 "Ancho" => 750 "Tamanyo" => 89620 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Purplish lesion on the outer ear.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 563 "Ancho" => 750 "Tamanyo" => 143043 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">(hematoxylin–eosin, x100) Massive occupation of dermal blood vessels by thrombi.</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 563 "Ancho" => 750 "Tamanyo" => 103498 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">(hematoxylin–eosin, x200 Higher-magnification image of a thrombosed blood vessel without leukocytoclastic vasculitis.</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" => "Levamisole-induced Vasculitis: A Characteristic Cutaneous Vasculitis Associated With Levamisole-Adulterated Cocaine" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.A. 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