Case and Research Letter
Alirocumab-Associated Lichenoid Reaction: A Case Report
Erupción liquenoide asociada al uso de alirocumab, presentación de un caso
R. Román Cheuque
, I. Navarro-Navarro, D. Jiménez-Gallo, M. Linares Barrios
Corresponding author
Unidad de Gestión Clínica de Dermatología y Venereología, Hospital Universitario Puerta del Mar, Cádiz, Spain
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Tinción hematoxilina-eosina, 9,6×. Paraqueratosis focal, dermatitis liquenoide en banda de predominio linfocitario, queratinocitos apoptóticos (cuerpos de Civatte) e imágenes de incontinencia pigmentaria. Ligera degeneración vacuolar de la interfase.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "R. Román Cheuque, I. Navarro-Navarro, D. Jiménez-Gallo, M. Linares Barrios" "autores" => array:4 [ 0 => array:2 [ "nombre" => "R." "apellidos" => "Román Cheuque" ] 1 => array:2 [ "nombre" => "I." "apellidos" => "Navarro-Navarro" ] 2 => array:2 [ "nombre" => "D." "apellidos" => "Jiménez-Gallo" ] 3 => array:2 [ "nombre" => "M." 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"apellidos" => "Linares Barrios" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731023008104?idApp=UINPBA000044" "url" => "/00017310/0000011500000005/v1_202405030647/S0001731023008104/v1_202405030647/es/main.assets" ] ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letter</span>" "titulo" => " Alirocumab-Associated Lichenoid Reaction: A Case Report" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">To the Editor,</span>" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "T522" "paginaFinal" => "T523" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "R. Román Cheuque, I. Navarro-Navarro, D. Jiménez-Gallo, M. Linares Barrios" "autores" => array:4 [ 0 => array:4 [ "nombre" => "R." "apellidos" => "Román Cheuque" "email" => array:1 [ 0 => "rroman.med@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "I." "apellidos" => "Navarro-Navarro" ] 2 => array:2 [ "nombre" => "D." "apellidos" => "Jiménez-Gallo" ] 3 => array:2 [ "nombre" => "M." "apellidos" => "Linares Barrios" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Unidad de Gestión Clínica de Dermatología 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" => "Erupción liquenoide asociada al uso de alirocumab, presentación de un caso" ] ] "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" => 976 "Tamanyo" => 43687 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical image. Multiple erythematous-violet, shiny, polygonal papules of up to 1cm in size located on both forearms.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Lichenoid eruptions (LE) pose a real diagnostic challenge due to their clinical and histopathological similarity to lichen planus. Inducers are varied being drug-induced lichenoid eruption (DILE) a common entity, particularly in an era characterized by the emergence of biologic or targeted therapies. This is the case of an alirocumab-induced lichenoid eruption, a proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitor used to treat dyslipidemia, a drug rarely associated with local skin adverse reactions and exceptionally with urticaria, or vasculitis.</p><p id="par0010" class="elsevierStylePara elsevierViewall">This is the case of a 61-year-old woman with a past medical history of mixed dyslipidemia and statin intolerance on an 18-month course of subcutaneous alirocumab, who presented with a 2-month history of highly pruritic eruption on her extremities. Examination revealed the presence of erythematous-violet, shiny, polygonal papules with Wickham striae on both her legs and forearms (<a class="elsevierStyleCrossRef" href="#fig0005">figure 1</a>). No lesions on mucous membranes were reported.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Blood tests results showed triglyceride levels at 358<span class="elsevierStyleHsp" style=""></span>mg/dL (< 150) and LDL at 215<span class="elsevierStyleHsp" style=""></span>mg/dL (< 130). The rest of the study, including a complete blood count, biochemistry, and autoantibodies was normal and tested negative for hepatotropic viruses. Dermatopathological examination revealed the presence of lichenoid interface dermatitis, a few necrotic keratinocytes, and vacuolar degeneration of the basal layer (<a class="elsevierStyleCrossRef" href="#fig0010">figure 2</a>). All these findings led to the diagnosis of alirocumab-related DILE.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">A 15-day systemic course of prednisone plus with topical betamethasone was started—without alirocumab discontinuation—which achieved complete remission at 3 weeks that was maintained at the 14-month follow-up.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Alirocumab is a monoclonal IgG1 antibody vs PCSK-9 that inhibits its binding to the LDL receptor, thus increasing the number of available receptors for LDL removal and reducing its plasma levels.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> Alirocumab has been authorized by the European Medicines Agency (EMA) to treat primary hypercholesterolemia and mixed dyslipidemia as a dietary supplement through subcutaneous injections. Recently, a correlation has been suggested among cutaneous/serum levels of PCSK-9, cardiovascular risk, and severity in diseases such as psoriasis and lupus, turning it into a potential therapeutic target.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> Adverse reactions such as erythema, or pain at the injection site have been reported, being nummular eczema, urticaria, and hypersensitivity vasculitis exceptionally rare.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">1,3</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">DILEs are skin reactions that typically appear weeks, or months after starting therapy. Uncertainty still surrounds their pathophysiology to this date. Clinically and histopathologically, DILEs are almost identical to lichen planus. Therefore, a suggestive medical history, physical examination, histopathology, and a plausible course of the disease are essential for diagnostic purposes.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> A few aspects of this case supporting the diagnosis of DILE include the absence of mucosal involvement, symmetric distribution in photo-exposed areas, and residual hyperpigmentation.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The list of drugs and vaccines associated with DILE is extensive and independent of the route of administration, including enalapril, amlodipine, beta-blockers, diuretics, antimalarials, imatinib, NSAIDs, and immunoglobulins. We should mention the existence of cases associated with simvastatin and biologic drugs such as infliximab, etanercept, pembrolizumab, and nivolumab.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">6,7</span></a> A search in Medline, Cochrane, and Epistemonikos databases using the keywords alirocumab, and lichenoid eruption, or lichen planus in both English and Spanish failed to reveal previously published cases.</p><p id="par0040" class="elsevierStylePara elsevierViewall">We used the Naranjo probability scale as a tool to assess the likelihood of an association between an adverse reaction and a drug,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">8</span></a> which showed a “probable” association between alirocumab and DILE.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The heterogeneity reported among the different pharmacological groups, doses, and routes of administration described as possible DILE triggers suggests the presence of likely immunomediated idiosyncratic reactions, which would explain the consistent response to corticosteroid therapy in this and other cases reported.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In conclusion, this was a case of a lichenoid eruption probably associated with the use of alirocumab, an association not described to this date.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">None declared.</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 "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" => 649 "Ancho" => 976 "Tamanyo" => 43687 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical image. Multiple erythematous-violet, shiny, polygonal papules of up to 1cm in size located on both forearms.</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" => 777 "Ancho" => 1456 "Tamanyo" => 444311 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Anatomopathological image. Hematoxylin-eosin staining, 9.6 ×. Presence of focal parakeratosis, lichenoid dermatitis with a predominance of lymphocytes, apoptotic keratinocytes (Civatte bodies), and images of pigmentary incontinence. Mild vacuolar degeneration of the interface.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0050" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of alirocumab in adults with homozygous familial hypercholesterolemia: The ODYSSEY HoFH Trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.J. Blom" 1 => "M. Harada-Shiba" 2 => "P. Rubba" 3 => "D. Gaudet" 4 => "J.J.P. Kastelein" 5 => "M.J. Charng" ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2020.05.027" "Revista" => array:6 [ "tituloSerie" => "J Am Coll Cardiol." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 14 | 16 | 30 |
| 2024 October | 151 | 84 | 235 |
| 2024 September | 144 | 47 | 191 |
| 2024 August | 157 | 85 | 242 |
| 2024 July | 113 | 74 | 187 |
| 2024 June | 158 | 63 | 221 |
| 2024 May | 251 | 72 | 323 |
| 2024 April | 174 | 50 | 224 |
| 2024 March | 128 | 48 | 176 |
