Images in Dermatology
Scanning electron microscopy of panitumumab-induced eyelash and hair alterations – Pili canaliculi
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Among the skin adverse effects papulopustular eruptions are the most frequent,<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> in addition to pruritus, xerosis, periungual pyogenic granuloma, eyelash trichomegaly, hair thickening, and curling.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Panitumumab is a fully human anti-EGFR monoclonal antibody used primarily to treat metastatic colorectal cancer. However, in addition to its action on tumor cells, it also acts on other tissues that have EGFR expression, particularly on the keratinocytes in the basal layer of the epidermis and in the outer sheath of hair follicles, leading to skin toxicity in up to 90% of cases.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Although there have been reports describing the ultrastructural aspects of hair secondary to oral EGFR inhibitors, such as gefitinib<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and erlotinib,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> there are no reports of electron microscopy analysis of these effects on hair shafts with monoclonal antibodies that inhibit this receptor.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Case report</span><p id="par0020" class="elsevierStylePara elsevierViewall">This case report describes a 65-year-old male patient with a malignant colorectal neoplasm. Surgical treatment with hemicolectomy and adjuvant chemotherapy was performed. A year later, he started another chemotherapy regimen due to the appearance of liver metastases; however, this treatment was not effective, so treatment with panitumumab was initiated. After six months of treatment, the patient showed pyogenic periungual granulomas and eyelash alterations, which became elongated and straightened, requiring cutting for aesthetic reasons, his hair became slightly curly and rougher to the touch. Eyelash and hair fragments were collected by cutting them with scissors for <span class="elsevierStyleItalic">in natura</span> analysis using scanning electron microscopy.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The eyelash examination showed well-developed grooves at medium magnifications (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), high magnifications showed cuticle disorganization, in addition to the grooving, and some hair shafts had more than one groove (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Examination of head hairs also revealed grooves (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>) at small and medium magnifications, less evident than in the eyelashes. High magnifications showed slight cuticle disorganization (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Discussion</span><p id="par0030" class="elsevierStylePara elsevierViewall">The ultrastructural findings observed secondary to the use of panitumumab are similar to those previously described for erlotinib and gefitinib, in which grooving was described and classified as pili canaliculi. In the case of erlotinib, eyelash trichomegaly and curly hairs, were seen, ultrastructurally grooves and hair twisting were observed. In the reported case of gefitinib use, the alterations were subclinical with discrete grooving. The case investigated here had important eyelash trichomegaly, with more discreet alterations of head hairs, both clinically and on ultrastructural examination. Panitumumab prolongs the anagen phase, hence the occurrence of trichomegaly, with more evident effects on the eyelashes.</p><p id="par0035" class="elsevierStylePara elsevierViewall">These findings demonstrate that the ultrastructural aspects of hair follicle changes by EGF inhibition are independent of the inhibition pathway. Both intracellular tyrosine kinase inhibition by oral small molecules and competitive inhibition of the EGFR binding site on the cell surface with monoclonal antibodies, produce similar ultrastructural alterations.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Financial support</span><p id="par0040" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Authors' contributions</span><p id="par0045" class="elsevierStylePara elsevierViewall">Debora Sarzi Sartori: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Antônia Larangeira de Almeida: Approval of the final version of the manuscript; drafting and editing of the manuscript; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Gabriel Santana Pereira de Oliveira: Approval of the final version of the manuscript; drafting and editing of the manuscript; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Hiram de Almeida Jr: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:3 [ "identificador" => "xres1688464" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1497322" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Case report" ] 3 => array:2 [ "identificador" => "sec0010" "titulo" => "Discussion" ] 4 => array:2 [ "identificador" => "sec0015" "titulo" => "Financial support" ] 5 => array:2 [ "identificador" => "sec0020" "titulo" => "Authors' contributions" ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of interest" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-03-09" "fechaAceptado" => "2021-03-21" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1497322" "palabras" => array:3 [ 0 => "Microscopy, electron" 1 => "Panitumumab" 2 => "Scalp dermatoses" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Panitumumab is a monoclonal antibody against the epidermal growth factor receptor used in metastatic colorectal cancer; in addition to tumor cells, it acts on epidermal keratinocytes and on the outer root sheath and presents skin toxicity in up to 90% of cases. A scanning electron microscope was used to examine the eyelashes and hairs of a 65-year-old patient with eyelash trichomegaly, curly hair, and paronychia undergoing treatment with panitumumab. Grooving in the hair shafts were identified, which were more evident in the eyelashes. Similar to oral epidermal growth factor inhibitors (erlotinib and gefitinib), panitumumab can cause acquired pili canaliculi.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Study conducted at the Pós-Graduação em Saúde e Comportamento, Universidade Católica de Pelotas and Liga de Dermatologia da Universidade Federal de Pelotas, Pelotas, RS, Brazil.</p>" ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1735 "Ancho" => 1667 "Tamanyo" => 457441 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Scanning electron microscopy - Eyelash examination - small (A) and medium magnification (B), showing grooves in the hair shaft (×180, ×330).</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" => 2429 "Ancho" => 1667 "Tamanyo" => 734001 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Scanning Electron Microscopy – Eyelash examination – (A), high magnification, showing grooving in the hair shaft and cuticle irregularity (×450). (B), High magnification, showing two grooves in the hair shaft – arrows (×700).</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" => 1710 "Ancho" => 1667 "Tamanyo" => 396565 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Scanning electron microscopy - Hair examination - small (A) and medium magnification (B), showing grooves in the hair shaft (×45, ×250).</p>" ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1192 "Ancho" => 1667 "Tamanyo" => 307338 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Scanning electron microscopy - Hair examination - large magnification showing slight cuticle disorganization (×900).</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" => "Mechanisms underlying skin disorders induced by EGFR inhibitors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. 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