Case and Research Letter
Cutaneous Lymphocytic Vasculitis Due to Ibrutinib Therapy
Vasculitis cutánea linfocítica secundaria a tratamiento con ibrutinib
a Servicio de Dermatología, Complejo Asistencial Universitario de Salamanca, Spain
b Servicio de Hematología, Complejo Asistencial Universitario de Salamanca, Spain
c Instituto Biosanitario de Salamanca (IBSAL), Spain
d Servicio de Anatomía Patológica, Complejo Asistencial Universitario de Salamanca, Salamanca, Spain
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Un estudio transversal usando la herramienta Mentimeter" "tienePdf" => "es" "tieneTextoCompleto" => "es" "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "How do Medical Students Actually See Dermatology? A Cross-Sectional Study Using the Mentimeter App" ] ] "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" => 695 "Ancho" => 2508 "Tamanyo" => 227459 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Percepción de los estudiantes de medicina al inicio del curso sobre A) aspectos positivos de la especialidad y B) aspectos negativos de la especialidad.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "T. Montero-Vilchez, A. Molina-Leyva, A. Buendía-Eisman, S. Arias-Santiago" "autores" => array:4 [ 0 => array:2 [ "nombre" => "T." "apellidos" => "Montero-Vilchez" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Molina-Leyva" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Buendía-Eisman" ] 3 => array:2 [ "nombre" => "S." 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Note the improvement of the lesions after 6 months of treatment with apremilast 30<span class="elsevierStyleHsp" style=""></span>mg twice a day (C and D).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Mansilla-Polo, C. Abril-Pérez, M.Á. Navarro-Mira, R. Botella-Estrada" "autores" => array:4 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Mansilla-Polo" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Abril-Pérez" ] 2 => array:2 [ "nombre" => "M.Á." "apellidos" => "Navarro-Mira" ] 3 => array:2 [ "nombre" => "R." "apellidos" => "Botella-Estrada" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731023004908?idApp=UINPBA000044" "url" => "/00017310/unassign/S0001731023004908/v1_202307180913/en/main.assets" ] "asociados" => array:1 [ 0 => array:17 [ "pii" => "S0001731024008032" "issn" => "00017310" "doi" => "10.1016/j.ad.2024.10.029" "estado" => "S100" "fechaPublicacion" => "2024-10-25" "aid" => "4120" "copyright" => "AEDV" "documento" => "simple-article" "crossmark" => 0 "subdocumento" => "crp" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta científico-clínica</span>" "titulo" => "[Artículo Traducido] Vasculitis cutánea linfocítica secundaria a tratamiento con ibrutinib" "tienePdf" => "es" "tieneTextoCompleto" => "es" "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Cutaneous Lymphocytic Vasculitis Due to Ibrutinib Therapy" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 890 "Ancho" => 930 "Tamanyo" => 375455 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La biopsia reveló la presencia de infiltrado inflamatorio denso en la dermis superficial y media, compuesto principalmente de linfocitos (A, B). Se observaron imágenes de vasculitis linfocítica, con tumefacción endotelial, oclusión trombótica luminal, depósito de fibrina y extravasación de glóbulos rojos (C, D).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "D. Rodriguez-Baeza, E. Pérez-López, C. Román-Curto, A. Santos-Briz" "autores" => array:4 [ 0 => array:2 [ "nombre" => "D." "apellidos" => "Rodriguez-Baeza" ] 1 => array:2 [ "nombre" => "E." "apellidos" => "Pérez-López" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Román-Curto" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Santos-Briz" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731024008032?idApp=UINPBA000044" "url" => "/00017310/unassign/S0001731024008032/v1_202410250439/es/main.assets" ] ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letter</span>" "titulo" => "Cutaneous Lymphocytic Vasculitis Due to Ibrutinib Therapy" "tieneTextoCompleto" => true "saludo" => "To the Editor:" "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "D. Rodriguez-Baeza, E. Pérez-López, C. Román-Curto, A. Santos-Briz" "autores" => array:4 [ 0 => array:3 [ "nombre" => "D." "apellidos" => "Rodriguez-Baeza" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "E." "apellidos" => "Pérez-López" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "C." "apellidos" => "Román-Curto" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:4 [ "nombre" => "A." "apellidos" => "Santos-Briz" "email" => array:1 [ 0 => "santosbriz@usal.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Complejo Asistencial Universitario de Salamanca, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Hematología, Complejo Asistencial Universitario de Salamanca, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Instituto Biosanitario de Salamanca (IBSAL), Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Complejo Asistencial Universitario de Salamanca, Salamanca, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Vasculitis cutánea linfocítica secundaria a tratamiento con ibrutinib" ] ] "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" => 890 "Ancho" => 930 "Tamanyo" => 375455 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The biopsy revealed the presence of a dense inflammatory infiltrate on the superficial and mid dermis composed mainly of lymphocytes (A, B). Images of lymphocytic vasculitis were seen, with endothelial tumefaction, luminal thrombotic occlusion, fibrin deposition, and red blood cell extravasation (C, D).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Ibrutinib is a Bruton tyrosine kinase (BTK) inhibitor approved for the management of relapsed or refractory mantle-cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL). Ibrutinib is also being studied as a potential therapy for various dermatological conditions including graft-versus-host disease, chronic spontaneous urticaria, pemphigus, and systemic lupus erythematosus, with promising preliminary results in some cases.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Although cutaneous adverse events are a common finding in patients on ibrutinib,<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,5</span></a> no cases of lymphocytic vasculitis (LyV) have been reported in the medical literature to this date.</p><p id="par0015" class="elsevierStylePara elsevierViewall">A 57-year-old man was admitted to the dermatology department. He had a significant past medical history of stage IV blastic MCL, and had been treated with first-line chemotherapy with R-CHOP/R-DHAP (rituximab, cyclophosplamide, doxorubicin, vincristine and prednisone/rituximab dexamethasone, cytarabine, cisplatin), autologous stem cell transplantation, and rituximab, with progressive disease. He was also treated with second-line chemotherapy with ibrutinib (560<span class="elsevierStyleHsp" style=""></span>mg/day) with progressive disease, and third-line chemotherapy with autologous CAR-T19 achieving complete remission.</p><p id="par0020" class="elsevierStylePara elsevierViewall">While on ibrutinib, he had a 3-week history of multiple erythematous papular lesions on legs and arms (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). He reported previous episodes of similar lesions that remained unexamined by the dermatologist, with the concomitant administration of ibrutinib, and spontaneous resolution. No systemic symptoms, previous history of cutaneous, autoimmune disease, or drug reactions were reported. ANCA and serologic testing for multiple infections all tested negative including the RT-PCR assay for SARS-CoV-2. Eight days later the lesions resolved spontaneously, without need for treatment discontinuation.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">One of the lesions was biopsized revealing the presence of a dense infiltrate of lymphocytes, monocytes, and scattered eosinophils around small and medium sized vessels on the superficial and deep dermis. Images of LyV were seen, with cells reaching the vessel walls, which showed marked endothelial tumefaction, luminal thrombotic occlusion, fibrin deposition and red blood cell extravasation (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The epidermis showed slight spongiosis with irregular acanthosis. Immunohistochemical staining showed a reactive CD3+ T cell infiltrate with a mixture of CD4+ and CD8+ lymphocytes and scattered CD20+ B lymphocytes. CD5, SOX11, and cyclin D1 confirmed the absence of MCL.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Cutaneous toxicity has been reported as one of the most common non-hematological side effects of ibrutinib. Some authors have reported ibrutinib-related skin rashes in 13–27% of the patients with CLL and MZL.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,5</span></a> The rashes can range from asymptomatic ecchymosis, nonpalpable petechial rash, to leukocytoclastic vasculitis-like palpable purpura.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,5</span></a> Pileri et al.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> reviewed the cutaneous adverse events of patients treated with ibrutinib at their center. Paronychia of the nail fold was described in 7 out of 50 patients on ibrutinib, in some cases along with pyogenic granuloma, while 9 patients experienced eczematous reactions. Other findings include 1 case of angular cheilitis and acute glossitis, fungal infection, and perinasal impetigo.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Our patient showed LyV. To date 5 patients on ibrutinib have been identified with leucocytoclastic vasculitis (LCV) but none with LyV.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Other ibrutinib-related skin reactions include neutrophilic dermatosis,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> panniculitis with or without vasculitis, and bilateral, purpuric, painful cutaneous nodules consisting of a mixed lymphocytic, neutrophilic and granulomatous inflammation.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Cutaneous lymphocytic vasculitis is an inflammation of blood vessels with the potential to damage the skin and other organs of the body. The etiopathogenesis of cutaneous lymphocytic vasculitis is not fully understood, but it is believed to be an autoimmune response triggered by various factors, being infections, drugs, and connective tissue diseases the main ones.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In our case, the main dermatopathological differential diagnosis is leukemic vasculitis,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> a specific form of vasculitis, mediated by leukemic blast cells rather than reactive inflammatory cells. In our patient, both the immunohistochemical studies and the benign course of the lesions ruled out this possibility.</p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion, we report the first case of ibrutinib-related lymphocytic vasculitis with spontaneous resolution, which did not require treatment discontinuation. The origin of this disorder is still unclear, but could be associated with an abnormal drug-induced inflammatory response.</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0070" class="elsevierStylePara elsevierViewall">This study received no funding.</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interests</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interests" ] 2 => 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" => 666 "Ancho" => 930 "Tamanyo" => 101290 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Three-week history of erythematous papular lesions on legs and arms.</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" => 890 "Ancho" => 930 "Tamanyo" => 375455 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The biopsy revealed the presence of a dense inflammatory infiltrate on the superficial and mid dermis composed mainly of lymphocytes (A, B). Images of lymphocytic vasculitis were seen, with endothelial tumefaction, luminal thrombotic occlusion, fibrin deposition, and red blood cell extravasation (C, D).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cutaneous lymphocytic vasculitis after administration of the second dose of AZD1222 (Oxford–AstraZeneca) severe acute respiratory syndrome coronavirus 2 vaccination: casuality or causality?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.D.M. Ungari" 1 => "M.D.E. 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| Year/Month | Html | Total | |
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| 2024 November | 21 | 12 | 33 |
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