Letter to the Editor
Hand ulcers and cutaneous leucocytoclastic vasculitis secondary to cabozantinib treatment for renal cell carcinoma
Lesiones ulcerosas en manos y vasculitis leucocitoclástica secundarias al tratamiento con cabozantinib por carcinoma renal
Francisco Javier Melgosa Ramos
, Andrea Estebánez Corrales, Almudena Mateu Puchades
Corresponding author
Department of Dermatology, University Hospital Doctor Peset of Valencia, Spain
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(B) Cabozantinib induced ulcers on the hands associated with palmar erythrodysestesia.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Cabozantinib is a small molecule approved for the treatment of metastatic/advanced renal cell carcinoma and medullary thyroid carcinoma. It is a multikinase inhibitor targeting VEGF 2 receptor, mesenchymal–epithelial transition receptor, and a receptor tyrosine kinase.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> However, cabozantinib, is associated with diverse toxicities that may affect patient's quality of life. The most frequent adverse events are diarrhea, asthenia, hypertension, weight loss and stomatitis but also cutaneous reactions (in over 70% of patients in some series). On this topic we present the case of a 77-year-old male treated with cabozantinib 60<span class="elsevierStyleHsp" style=""></span>mg daily because of metastatic kidney cancer who presented 15 days after cabozantinib prescription bilateral, symmetric non desquamative annular macules over his both lower legs suggesting vasculitis or pigmented purpuric dermatosis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). He also referred symmetric ulcers on the hands from the beginning of the treatment, associated with palmar erythrodysestesia (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). A skin biopsy of the leg with direct immunoflurescence was taken confirming the diagnosis of leukocytoclastic vasculitis. After discussing the patient with the oncologist, we decided to stop cabozantinib temporarily with cutaneous improvement in two weeks.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Hand–foot skin reaction is an important and very well-known dose-limiting dermatological adverse event caused by cabozantinib are characterized by bilateral, painful, localized calluslike hyperkeratosis with surrounding edema and erythema primarily affecting palmoplantar surfaces).<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">2,3</span></a> Patients receiving this drug can also develop other cutaneous toxic effects as partial hair despigmentation, pigment dilution of the skin (commonly reversible), bullae, hyperkeratosis and erythema of plantar or palmar surfaces, xerosis, scrotal erythema/ulceration, nail splinter hemorrhages or vasculitis as our patient. Most reactions usually take place in the first two months, and commonly require cabozantanib dose reduction and in some cases, treatment discontinuation.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">4,5</span></a> The mechanism that induces cabozantinib leukocytoclastic vasculitis is unknown, but may be dose-dependent. Some authors have considered different mechanism as direct effect of vascular endothelial growth factor inhibition, immune complex deposition, or also a paraneoplastic phenomenon resulting from antigen exposure from the tumor. To conclude, it is important for oncologist and dermatologist to know the most common cutaneous toxicities derived from novel therapies (TKIs, checkpoint inhibitors etc) in order to anticipate severe reactions and achieve a correct management.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Informed consent</span><p id="par0015" class="elsevierStylePara elsevierViewall">All informed consents are available.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Data availability</span><p id="par0020" class="elsevierStylePara elsevierViewall">All data are available.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Funding</span><p id="par0025" class="elsevierStylePara elsevierViewall">This research received no specific grant from any funding agency in the public or private sector.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Author's contribution</span><p id="par0030" class="elsevierStylePara elsevierViewall">All authors have contributed to this research</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflict of interest</span><p id="par0035" class="elsevierStylePara elsevierViewall">None.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Informed consent" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Data availability" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Funding" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Author's contribution" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interest" ] 5 => array:2 [ "identificador" => "xack613375" "titulo" => "Acknowledgements" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1022 "Ancho" => 950 "Tamanyo" => 99929 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Cabozantinib induced leukocytoclastic vasculitis. (B) Cabozantinib induced ulcers on the hands associated with palmar erythrodysestesia.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of adverse events associated with cabozantinib therapy in renal cell carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. Schmidinger" 1 => "R. Danesi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1634/theoncologist.2017-0335" "Revista" => array:6 [ "tituloSerie" => "Oncologist" "fecha" => "2018" "volumen" => "23" "paginaInicial" => "306" "paginaFinal" => "315" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29146618" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence and risk of hand–foot skin reaction with cabozantinib, a novel multikinase inhibitor: a meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "V.R. Belum" 1 => "C. Serna-Tamayo" 2 => "S. Wu" 3 => "M.E. Lacouture" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/ced.12694" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Dermatol" "fecha" => "2016" "volumen" => "41" "paginaInicial" => "8" "paginaFinal" => "15" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26009777" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The hand–foot-syndrome associated with medical tumortherapy—classification and management" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Degen" 1 => "M. Alter" 2 => "F. Schenck" 3 => "I. Satzger" 4 => "B. Völker" 5 => "A. 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Nanda" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jamadermatol.2014.2734" "Revista" => array:6 [ "tituloSerie" => "JAMA Dermatol" "fecha" => "2015" "volumen" => "151" "paginaInicial" => "170" "paginaFinal" => "177" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25427282" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cutaneous leucocytoclastic vasculitis secondary to cabozantinib therapy for renal cell carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "G.S. Coltart" 1 => "J.E. Sutton" 2 => "H.J. Roche" 3 => "M.P. Sommerlad" 4 => "S.J. Crabb" 5 => "E. Healy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/ced.14541" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Dermatol" "fecha" => "2021" "volumen" => "46" "paginaInicial" => "739" "paginaFinal" => "740" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33332666" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack613375" "titulo" => "Acknowledgements" "texto" => "<p id="par0040" class="elsevierStylePara elsevierViewall">Thanks for doctor Héctor Gegúndez Hernández, to be present during the diagnosis.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015800000011/v1_202206190623/S2387020622002534/v1_202206190623/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015800000011/v1_202206190623/S2387020622002534/v1_202206190623/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020622002534?idApp=UINPBA00004N" ]
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